043365   MANASWINI Y H, ULOOPI KS , VINAY C , CHANDRASEKHAR R , RAMYA K S R (Pedodontics and Preventive Dentistry Dep, Vishnu Dental Coll, Bhimavaram, Andhra Pradesh, Email: rojachowdary28@gmail.com) : Impact of calcium glycerophosphate-supplemented carbonated beverages in reducing mineral loss from the enamel surface. Int J Clin Pediatr Dent 2020, 13(1), 1-5.

The aim of this study was to evaluate the surface microhardness and mineral loss from enamel exposed to carbonated beverages supplemented with and without calcium glycerophosphate (CaGP). Forty enamel blocks were prepared from 20 extracted premolars, and their initial surface microhardness was measured using the Knoop microhardness testing machine. The samples were divided into four groups based on the concentration of CaGP added to the beverage: group I: beverage without CaGP (control group), group II: beverage with 2 mM CaGP, group III: beverage with 5 mM CaGP, and group IV: beverage with 10 mM CaGP. The samples were subjected to four cycles of exposure to plain and CaGP-supplemented carbonated beverage with an intermittent buffering in artificial saliva, after which the final surface microhardness was measured. The mineral loss from enamel blocks was estimated spectrophotometrically. The obtained data were analyzed using paired t test and analysis of variance. A highly significant (p < 0.01) reduction in surface microhardness was observed in group I (beverage without CaGP). The reduction in surface microhardness in group III (beverage + 5 mM CaGP) and group IV (beverage + 10 mM CaGP) was not significantly different from that of sound enamel. A highly significant difference in calcium loss was observed between the groups (p = 0.00). Calcium loss reduced as the CaGP concentration increased in the groups. A similar trend was observed when phosphate loss was analyzed. Addition of CaGP to the carbonated beverages significantly prevented the reduction in surface microhardness of enamel and mineral loss. As the concentration of CaGP in carbonated beverages increased from 2 mM to 10 mM, the mineral loss is decreased. Consumption of carbonated beverages has been increasing among the children and adolescents, leading to a higher incidence of dental erosion and caries. Hence, supplementation of these acidic beverages with buffering agents such as CaGP may help in preventing such dental problems among vulnerable populations.

1 illus, 3 tables, 22 ref

046618   SNEHA S, SARATHI S, KUMAR P S, RAJESH R, JAGDISH KAMAL CHANDER U (Forensic Medicine & Toxicology Dep, Sri Ramachandra Medical Coll & Research Institute, Chennai- 600 116) : Perspective on the immorality of honor killings – A review article. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194296.

The killing of a family member, when the offenders believe that the victim’s activities have resulted in immense dishonor to the family or community is called honor killing or shame killing. The absence of systematic data collection in most countries has resulted in lack of clarity on the judicial approach and its consequences, with many of the killings being reported falsely as suicides or accidental deaths by the families. Honor killings are prevalent all over the world, with the majority of them happening in the Asian countries, closely followed by the Middle East and South Asia regions. This review article attempts to analyze the present legal status of honor killing in the country of India, predominantly in the southern states. The sensational killing of a Dalit youth, Gokulraj in 2015 found in the company of a girl belonging to the Gounder community at a temple in Tiruchengode , sent shock waves across the state. Another prominent case occurred in the state of Tamil Nadu, where the marriage of Ilavarasan – a Dalit youth from Dharmapuri to a Vanniyar girl from Sellangottai, evoked deep conflicts in 2013, that lead to the former’s body lying on a railway track. With the ideals of ‘honor’ and ‘disgrace’ being deeply rooted in the Indian mindset, the laws alone will not suffice to curb such forms of violence and it has to be addressed as a sociological issue.

15 ref

041551   SREEHARSHA N, HIREMATH J G, AL-DHUBIAB B E, MERAVANIGE G, KARNATI R K, ATTIMARAD M, NAIR A B, VENUGOPAL K N, MORSY M A, POTTATHIL S ET AL (Pharmaceutical Sciences Dep, King Faisal Univ, Al-Ahsa-31982, Saudi Arabia, Email: sharsha@kfu.edu.sa) : Fabrication of poly (sebacic acid-co-ricinoleic-ester anhydride) with β-cyclodextrin-loaded doxorubicin implants and in vitro characterization. Indian J Pharm Edu Res 2020, 54(3), 826-34.

Doxorubicin is an excellent molecule for the formation of biodegradable implants using the poly (sebacic acid-co-ricinoleic-ester anhydride) 70:30 w/w (poly[SARA] 70:30 w/w PSRA 7/3) polymer. The cylindrical implants were successfully produced by means of hot melt extrusion. We used differential scanning calorimetric (DSC) and X-ray diffraction (XRD) methods to identify the melting state and crystal type of blank and drug-loaded implants. A study was conducted on PSRA 7/3 w/w blank and drug-loaded implants for in vitro hydrolytic degradation. The drug present in the remaining sample was estimated. The hydrolytic degradation rate of the 10 % w/w (F2)-loaded implant was relatively low when compared with the 20 % w/w (F3) implant. In vitro drug release studies illustrated that the drug-release rate was faster in association with increasing amounts of doxorubicin in the implant.

5 illus, 1 table, 31 ref

041550   SALIMATH G S, GANACHARI M S, GUDHOOR M (Pharmacy Practice Dep, KLE Coll of Pharmacy, Belagavi - 590 010, Karnataka, Email: geetanjalisalimath@gmail.com) : Paediatric focused triggering tool (PFTT) to assess the harm and its utilization to minimize the levels of harm among children at a tertiary care hospital. Indian J Pharm Edu Res 2020, 54(3), 819-25.

Very few paediatric trigger tools have been developed to assess harm in children. Hence, a Paediatric-focused trigger tool has been developed, assess its utility to measure the levels of harm, categorize and minimize them further. The final 40 trigger tool developed by modifying IHI-GTT adult care, was prospectively tested for structural review of records (n=520) of paediatric population of a tertiary care hospital for incidence of adverse events (AE’s) with associated harm and categorized using modified NCCMERP (National Coordinating Council for Medication Error Reporting and Prevention) index from E-I. Among 292 male and 228 female children, the incidence of AEs was 35 %, more in the category of 1-5 years of age with harm assessment events. Out of 182 AEs identified, 107(58.80 %) were found to be of E-category, 43(23.62 %) were of category F, 22(12.08 %) with category G, 9(4.95 %) with category H and 1(0.55%) was category I. Two third of the paediatric population of category E and F (82.4 %) had temporary harm and remaining (17.6 %) were of nonpreventable harm, category G-I. One example of AE identified with harm was, decrease in 25 % in Haemoglobin or Haematocrit and number of blood transfusions. Further action was taken to strictly monitor and minimize further harm. The present study highlights on the harm assessment among the paediatric population with the help of developed Paediatric-Focused Trigger Tool (PFTT) modified by using IHI-GTT adult trigger tool. This helps paediatric set ups to assess its usefulness and further develop strategies to mitigate the harm.

1 illus, 4 tables, 22 ref

041549   RAMASAMY R, MOHANTA G P, HIREMATH S R R, RAMNARAYANAN C, DANG R, GHARAT M S (Pharmacy Practice Dep, Krupanidhi Coll of Pharmacy, Bengaluru - 560 035, Karnataka, Email: rajeswari.vidula@gmail.com) : Dynamic method for liaison of community pharmacists with national programme for tuberculosis control: Efforts to harness untapped opportunities. Indian J Pharm Edu Res 2020, 54(3), 809-18.

Revised National Tuberculosis Control Program (RNTCP) - Directly Observed Treatment-Short course (DOTS) strategy to involve Community Pharmacist (CPs), was conceived and implemented in India, with the objective of improving accessibility of Tuberculosis free medicines. Though the RNTCP personnel in the study area had tried to create liaison with CPs; and to train them in DOTS provision roles, it was not successful as CPs were not forthcoming to be a part RNTCP - DOTS paradigm. Hence this study was ideated and executed to develop a liaison model between CP and RNTCP personnel, to support the delivery of DOTS treatment under RNTCP programme. This article discusses the liaison method followed by the researchers to integrate the CPs with RNTCP’S TB centres in Bangalore City. To establish liaison between community pharmacists and RNTCP personnel to strengthen Public Private Mix (PPM) Partnership for providing TB care role in Bengaluru City, India. An educational interventional study involving CPs in Bengaluru City was conducted with the regulatory support from Drugs Control department, Karnataka.Awareness and Training was given on the basis of the RNTCP training module for Community Pharmacist. The change in the level of awareness on existence of PPM RNTCP strategy among community pharmacist; and the percentage of pharmacists showing interest for TB care role after the program was measured. Out of 125 CPs representations, 93 CPs enrolled them as Private DOTS providers immediately after programme. The change in the Level of Awareness on the existence of TB-DOTS provider role was found to be 100 % in this study. This result clearly points to the fact that CPs needs to be sensitized. The policy level changes in the ease of enrolling CPs to be a DOTS provider under the aegis of drugs control department, needs to be revisited and rethought in RNTCP’s national strategy for pharmacists.

8 illus, 2 tables, 10 ref

041548   ROMPICHERLA N C, PAUL E, GANESH A, NARAYANAN V A (Pharmaceutics Dep, NGSM Institute of Pharmaceutical Sciences, Mangalore - 575 018, Karnataka, Email: anoopvn84@gmail.com) : The significance of quality metrics in a pharmaceutical quality management system – a case based study. Indian J Pharm Edu Res 2020, 54(3), 798-808.

The pharmaceutical quality management system is a concept of management function that design and implement the “Quality policy”. The pharmaceutical manufacturing industries all over the world have just begun to apply the United States Food and Drug Administration (USFDA) guidelines in the 21^st century. The study tries to identify the quality metrics based on Quality Indicators for a pharmaceutical industry and to investigate the utilization of quality KPIs. The work experience from a successfully working pharmaceutical organization related to Research and and Development (R&D) of pharmaceutical products are discussed here. Important areas were identified and analysed based on the data collected from the deviation reports of selected organization and other resources. The R&D centre uses a software system for Quality management system including, Deviation management, Change management, Laboratory investigation, Incident management and Corrective Action and Preventive Action (CAPA). The primarily considered Quality indicator (QI) was the pharmaceutical deviation. A Among the deviations reported in the year of 2017-18, 214 cases were selected as sample. In this 171 were permanent deviations and 43 is temporary deviations. Secondarily, Pharmaceutical incidents are selected for the study as the QI in which 70 % of the root cause is due to human related issues. Failure to meet acceptance criteria comes first with 48 % and failure to follow procedure with 28 %. A good quality metrics system supports both industries’ profitability, GMP compliance and precludes overproduction of metrics; only measure what adds value to quality in the most efficient way.

6 illus, 3 tables, 18 ref

046616   PATHI R, PENUMATSHA S V, NEERUKONDA L K, KRISHNA P R (Rayalaseema Univ, Andhra Pradesh- 518 002) : Querying the dataset from the developed ontology for swineflu disease. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194294.

Ontology design and querying the data set to obtain accurate results has been a topic of research. The aim of the paper is to represent ontological knowledge in the field of Medical Information Systems to store the knowledge about Swine flu disease and thereby querying the data and formalize the knowledge base development. The developed knowledge from RDF is converted to rules and then querying is done through different methods and performance analysis has been done on the retrieved query. The results predicted determine the suitability of the method where querying gives the accurate result for swine flu disease ontology.

6 illus, 13 ref

046615   SEQUEIRA S, D’SILVA P (Father Muller Coll of Nursing, Karnataka- 575 002) : Client satisfaction and preferences towards nonverbal communication(NVC) of health care providers in a therapeutic setting, Mangaluru. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194293.

Non verbal communication refers to the communication and interpretation of information by any means other than language. Non verbal communication is used to express and communicate thoughts, feelings and emotions to establish and maintain relationships and to influence others. In health care setting it is very important to maintain a healthy provider- client relationship. The present study studies the non verbal behaviors between doctors and nurses and ranks the client preference during interaction. The results revealed that there is no significant difference in the non verbal behaviours used by doctors and nurses. Henry Garret ranking was used to rank the preferences rated by Clients. Hence it is concluded that NVC are very much essential in health care.

5 tables, 8 ref

043356   YADAV A R , MOHITE S K (Pharmaceutical Chemistry Dep, Rajarambapu Coll of Pharmacy, Sangli, Maharashtra) : In-Silico ADME Analysis of 1, 3, 4-oxadiazole derivatives as CDK9 Inhibitors. Int J Chem Sci 2020, 4(2), 01-4.

Many drug targets have been identified in fighting against different types of cancer. Inhibition of cell cycle is strategy used in anti-cancer research. Cyclin dependent kinases were found to be promising drug targets. The goal is to find a molecule to inhibit CDK which are involved in cell cycle progression. Many drugs molecules fail during clinical trials as for streamlining study and ADME analysis is one of the crucial step. The ADME properties including blood brain barrier, GI absorption, aqueous solubility and skin permeabilitywere evaluated for these molecules. A various in-silico methods share the aim of ADME prediction from molecular structure. Swiss ADME is tool focus on specific property and it is most relevant computational methodsprovides pharmacokinetics properties of small molecules. ADME screening was carried out to know efficacy of molecules before proceeding to in-vivo or in-vitro assays.

4 tables, 28 ref

046614   YADAV P K, CHOUDHURY R, VERMA A K, SINGH M, RUPANI R, KUMARI S, SINGH R R (Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, Email: drrajiv01@gmail.com) : A study on the cause of death due to burn cases and histopathological changes in north Indian setting-a cross sectional study. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194292.

Fatal burns and related injuries are major cause of death and disability. There are certain pathological changes such as lungs shows necrotizing pneumonia, congestion of alveolar walls, capillary proliferation, intra alveolar oedema, giant epithelial cells. To study on the cause of death due to burn cases and histopathological changes in north Indian setting. This was a cross-sectional study. All autopsies with history of burn injury were studied to find out the significant histopathological change in lung. Cases was thoroughly studied using specially designed proforma that included demographic profile of deceased, history from relatives, police & hospital records, autopsy findings. The most common cause of death due to burn injury was found to be Sepsis (48.2 %) and neurogenic shock (29.5 %). On histopathological examination, Congestion in trachea was present in majority 434 (78.9 %) cases while Tracheal soot particles were present in only 40 (7.3 %) cases. Specimens of 375 cases were available for histopathology out of which 52 (13.9 %) specimens were autolyzed. Changes suggestive of Pneumonia (50.1 %), Congestion (83.7 %), alveolar and interstitial haemorrhage (63.2 %) were present in majority of the cases while changes suggestive of alveolar interstitial edema (64.3 %), alveolar wall disruption (66.1 %), inflammatory cells (55.5 %), hyaline membrane (79.7 %) and Fibrin strands (79.7) were absent in majority of cases. Capillary dilatation was present in 39.2 %. In the present study, an important observation in burn deaths is the Sepsis and Neurogenic shock. Congestion in trachea was most common on histopathological change.

2 tables, 14 ref

046613   AGARWAL P K, KUMAR P, SINGH H (Forensic Medicine Dep, Muzaffarnagar Medical Coll, Muzaffarnagar- 251 203, Email: docpranav3@gmail.com) : Toxicological trends of poisoning in a tertiary care center of western Uttar Pradesh. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194291.

Poisoning is a significant global public health problem which leads to nearly a million deaths per year. Incidence of poisoning is high in India. This study was carried out on poisoning cases reported to casualty department of Muzaffarnagar Medical College, Muzaffaranagar from 1st January 2016 to 31st December 2016.The main objectives of the study were to analyze pattern and demographic variables of poisoning cases. Data were collected and analyzed. A total of 72 cases (male: 46, female: 26) were included in the study. Maximum cases were of age group 21-30 years (30.5 %). More cases from rural area (75 %) were reported. Summer months saw maximum number of cases (37.5 %). Poisoning by Organophosphorus was seen in maximum cases (31.9 %) followed by Aluminium phosphide (29.1 %)and in maximum cases reason for poisoning was Intentional (52.7 %) and route of exposure was by oral ingestion (84.7 %).The study concludes that the burden of poisoning demands strategies for identification, prevention and its rational management.

6 tables, 14 ref

046612   AGARWAL P K, KUMAR P, SINGH H (Muzaffarnagar Medical Coll, Muzaffarnagar, Uttar Pradesh, Email: docpranav3@gmail.com ) : Causes and factors in road traffic accidents at a tertiary care center of western Uttar Pradesh. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194290.

Road Traffic Accidents are one of the leading causes of morbidity and mortality in the world. The etiological factors may be classified into human and environmental out of which human factors are much more responsible for number of accidents. This study was carried out on Road Traffic Accidents cases reported to casualty department of Muzaffarnagar Medical College, Muzaffarnagar (U.P) from 1st July 2016 to 30th June 2017. The main objectives of the study were to know the causes and factors responsible for the accidents. Data were collected and analyzed. A Total of 416 cases were included in the study. Human error is responsible for accidents in 78 % of cases in which drivers were at fault in 57.0 % of cases followed by the pedestrians and passengers of vehicles who were responsible for 18 % and 3.0 % cases respectively. Faults in vehicles and poor weather accounted for accidents 8.0 % & 7.8 % of total cases respectively. Bad roads were responsible for accidents in 4.0 % of total cases. None of the driver or passengers of the vehicles was wearing helmets or seat belts which are a very alarming trend. The important human factors responsible for accidents were over speeding, rash driving, violation of traffic rules, carelessness, wrong crossing, playing on roads, alcohol intake, fatigue or sleepiness.

6 tables, 14 ref

043341   PERERA B T , RAJAPAKSHA RMH , ARACHCHIGE RCW , KOTTEGODA IRM (Industrial Technology Institute, Colombo 07, Sri Lanka) : Cost-effective and non-toxic method to modify clay to increase the hardness adsorption capacity of clay. Int J Chem Sci 2020, 4(1), 22-7.

Hardness of the drinking water has been considered as one of the major causes of Chronic Kidney Disease of unknown etiology (CKDu) in the Northern part of Sri Lanka. The present study was ultimately aimed at removing the water hardness using clay as a cheap renewable adsorbent. The hardness adsorption capacity of raw clay was increased by treating clay with NaCl_(aq). The present methodology was proposed due to low toxicity, low cost, and high commercial availability of clay and NaCl. Clay samples were collected from Deniyaya Sri Lanka. The particle size reduction of clay was achieved by treating raw clay with NaCl_(aq) at different durations at 303K temperature. During the study, adsorption of Ca²⁺ and Mg²⁺ (the water hardness) was analyzed using EDTA titration following the standard APHA method protocols. The highest adsorption was observed at 33 hours of treatment. XRD spectrum of raw clay showed a sharp strong diffraction peak of the sample at 2θ = 22.45 ° which is a characteristic peak of Kaolinite-2M with 97.1 % abundance. XRD spectrum of treated clay showed considerable changes that the clay consisted of kaolinite (44 %) and Orthoclase (56 %). It was noted that with the increasing of treating time, although the particle size decreased, after some point small clay particles tend to aggregate again reducing cation adsorption capacity. Treated clay enabled to reduce the total hardness by 96 % of the tested water obtained from CKDu prevalent area.

10 illus, 20 ref

043340   BARIYAA W T , SUNDAY I P (Rivers State Coll Of Health Science and Management Technology Port Harcourt, PMB 5039 Nigeria) : The effect of biodeterioration due to microbial growth in diesel, control using optimization of sulphur and consequences on Nigeria economy. Int J Chem Sci 2020, 4(1), 17-21.

Extended storage of petroleum product such as diesel enhances microbial growth resulting in sludge formation, diesel loss and corrosion in storage tanks. The use of biocides have been confirmed inappropriate due to high resistance to biodeteriorating agents, as well, high concentration of biocides have been confirmed to be hazardous to man. The research is targeted at the optimization of sulphur content in diesel in other to prevent biodeterioration due to microbial proliferation in storage tanks and pipes. The following concentrations of: 350, 400, 450 and 500 ppm of sulphur content were prepared to determine the corrosion frequencies and the degree of growth of Hormoconis resinae in each sample by measuring the deterioration effects in the diesel. Graphs are plotted to show the growth and corrosion in terms of losses due to sulphur. Suphur content optimizations were reach in other to struck a balance between the degree of corrosion to inhibition of Hormoconis resinae. The optimized sulphur content came to be between 380-400 ppm after analysis. Results shows that; the higher the sulphur concentration, the higher the corrosion rates of storage tanks and pipes. Also the higher the concentration of suphur the lower the proliferation of biodeteriorative agent Hormonis resinae. This implies that the increase in sulphur concentration prevents the growth of Hormoconis resinae which cause deterioration of diesel but increases corrosion. While the lower the concentration of suphur the lower the corrosion rate of storage tanks and pipes but high microbial growth rate in the diesel. The total loss of diesel due to microbial deterioration, the cost of purchasing sulphur and cost of replacing storage tanks and pipelines is a sort of economic lost to Nigeria thereby depreciating its gross domestic product (GDP).

4 illus, 7 tables, 7 ref

043337   REN R, WANG Z, WU M, WANG H (Oncology Dep, First Affiliated Hospital of Anhui Medical Univ, Hefei 230022, Anhui, China, Email: wanghua@ahmu.edu.cn) : Emerging roles of SIRT1 in alcoholic liver disease. Int J Biol Sci 2020, 16(16), 3174-83.

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide with a wide spectrum of liver pathologies ranging from simple steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. It has been demonstrated that ALD is mediated in whole or in part by a central signaling molecule sirtuin 1 (SIRT1), a conserved class III histone deacetylase.SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, inhibiting hepatic inflammation, controlling hepatic fibrosis and mediating hepatocellular carcinoma in ALD. However, underlying molecular mechanisms are complex and remain incompletely understood. The aim of this review was to highlight the latest advances in understanding of SIRT1 regulatory mechanisms in ALD and discuss their unique potential role as novel therapeutic target for ALD treatment.

3 illus, 107 ref

043336   ZHENG Y, PEI Y, YANG L, ZENG Z, WANG J, XIE G, WANG L, YUAN J (Sun Yat-sen Univ, Guangdong 510080, China, Email: yuanjie@mail.sysu.edu.cn) : Upregulated GRB7 promotes proliferation and tumorigenesis of bladder cancer via phospho-AKT pathway. Int J Biol Sci 2020, 16(16), 3221-30.

Growth factor receptor-bound protein 7 (GRB7) has been found closely related to the occurrence and development of various tumors, but its function in bladder cancer has not yet been elucidated. The study is aiming at investigating the expression and function of GRB7 in bladder cancer. The Cancer Genome Atlas (TCGA) database was selected to analyze mRNA levels of GRB7 in bladder cancer. RT-qPCR and Western blot were conducted to detect the expression of GRB7 in normal bladder epithelial cells, seven bladder cancer cell lines and eight pairs of malignant/nonmalignant bladder tissues. The role of GRB7 in tumor proliferation and tumorigenesis was explored by establishing stable cells, in vitro cell experiments and in vivo xenograft models. The molecular regulation mechanism of GRB7 in bladder cancer was investigated by treatment with AKT inhibitor. GRB7 mRNA was upregulated in bladder cancer samples compared with that in normal tissue samples. Overexpressing GRB7 significantly promoted the proliferation and tumorigenesis of bladder cancer. However, silencing GRB7 played the retarding part. GRB7 promoted G1/S transition by activating the AKT pathway. Our results indicate that GRB7 plays an important role in promoting proliferation and tumorigenesis of bladder cancer.

6 illus, 35 ref

041540   DUYU T, KHANAL P, KHATIB N A, PATIL B M (Pharmacology and Toxicology Dep, KLE Coll of Pharmacy, Belagavi - 590 010, Karnataka, Email: pukarkhanal58@gmail.com) : Mimosa pudica modulates neuroactive ligandreceptor interaction in parkinson’s disease. Indian J Pharm Edu Res 2020, 54(3), 732-9.

Mimosa pudica is scientifically reported for the enhancement of memory in multiple animal models including Parkinson’s disease (PD); however, the probable molecular mechanism for this effect has not been explained yet. The present study demonstrates the probable molecular mechanism to improve memory via in silico techniques. Phytoconstituents present in M. pudica and their targets involved in Parkinson’s disease were identified using open-source databases and published literature. Enrichment analysis of targeted proteins was identified using STRING, druglikeness of compounds was assessed using MolSoft and docking was carried using autodock4. Out of twenty-seven phytoconstituents, seventeen modulated the proteins involved in the pathogenesis of PD. Norepinephrine was predicted to have the highest druglikeness score. The ADMET profiles revealed all phytoconstituents to be safe and are suitable for human consumption. Similarly, network analysis identified ADORA1 to be primarily targeted by phytoconstituents and luteolin was predicted to interact with maximum proteins. A docking study predicted quercetin and luteolin to possess the highest binding affinity with highly modulated protein ADORA1. M. pudica could primarily modulate neuroactive ligand receptor interaction followed by dopamine and serotonin synapses by regulating multiple proteins in PD.

3 illus, 3 tables, 36 ref

043334   ZHANG J, DENG M, TONG H, XUE W, GUO Y, WANG J, CHEN L, WANG S (Radiology Dep, Army Medical Univ, Chongqing 400042, China, Email: wangshunan@tmmu.edu.cn) : A novel miR-7156-3p-HOXD13 axis modulates glioma progression by regulating tumor cell stemness. Int J Biol Sci 2020, 16(16), 3200-9.

Malignant glioma is the most common brain tumor in adults. Despite the great advances in anti-glioma treatments which have led to significant improvement in clinical outcomes, tumor recurrence remains the major cause of mortality. Increased cancer cell stemness and invasiveness are correlated with glioma progression. By searching the Cancer Genome Atlas, we showed that the expression of miR-7156-3p is significantly decreased in glioma tissues compared to the normal brain, and the decreased level of miR-7156-3p is closely correlated with glioma grade and patient survival. Clinical study consistently confirmed that miR-7156-3p is negatively correlated with glioma grade. Cell culture and animal experiments revealed that inhibition of miR-7156-3p effectively stimulates glioma cell stemness, invasion, and growth. In contrast, the augmentation of miR-7156-3p inhibits these phenotypes. Using Next-generation sequencing combined with target prediction approach, Homeobox D13 (HOXD13) is identified as the target gene of miR-7156-3p and further validated by luciferase reporter assay and cell transfection experiments. Additional in vitro and animal experiments demonstrated that miR-7156-3p regulates glioma cell stemness, invasion, and growth by mediating HOXD13. In conclusion, our findings provide new insight into the regulation of glioma stemness and invasiveness and may propose a potential strategy for anti-glioma treatment. Moreover, miR-7156-3p may serve as a candidate biomarker for predicting glioma progression in clinical practice.

7 illus, 1 table, 27 ref

041538   JOSHI T A, TATKE P (SNDT Women’s Univ, Mumbai, Maharashtra, Email: drpratimatatke@gmail.com) : Neuroprotective effects of licorice extracts in tibial and sural transection induced neuropathic pain in rats. Indian J Pharm Edu Res 2020, 54(3), 741-23.

Neuropathic pain (NP) is the worst of tortures, a nerve wound may experience as a result of nerve damage or complication of diabetes/HIV /cancer. There are no defined guidelines for treatment. Available treatments have various side effects. Glycyrrhiza glabra (Licorice) has not been explored scientifically with respect to NP. Hence there is a dire need to develop treatment for NP which will be safe, effective and can be taken for prolonged time. The present study is to evaluate effects of licorice extracts in Tibial and Sural Transection (TST) induced neuropathic pain in rats. Extracts prepared from crude drug were tested for antioxidant activity. NP was induced by TST surgery method. After induction of NP, it leads to chemical and heat evoked hyperalgesia, cold and mechanical allodynia. Rats were divided into eight groups, Control (Treated with Na-CMC), Standard (Treated with Pregabalin), Test (Treated with three licorice extracts), Sham operated and Normal (Without surgery). Rats were treated with extracts and standard for 21 days. At the end of 21 days’ rats were sacrificed and tested for biochemical parameters. At the end of study biochemical parameters; superoxide generation, malondialdehyde (MDA) and TNF-α were evaluated. Rats treated with licorice extracts showed improvement all the pain related symptoms and tibial functional index. Treated rats also showed significant improvement in superoxide ions and MDA supporting their antinociceptive and antioxidant activities. Licorice extracts have shown significant decrease in pain symptoms in TST induced NP in rats. This effect may be attributed to anti-inflammatory, antioxidant and neuroprotective properties of licorice. Hence licorice extracts can be potential candidates for treatment of NP.

7 illus, 4 tables, 46 ref

043333   BUYANDELGER B, BAR E E, HUNG K-S, CHEN R-M, CHIANG Y-H, LIOU J-P, HUANG H-M, WANG J-Y (Taipei Medical Univ, 110 Taipei, Taiwan, Email: jywang2010@tmu.edu.tw) : Histone deacetylase inhibitor mpt0b291 suppresses glioma growth in vitro and in vivo partially through acetylation of p53. Int J Biol Sci 2020, 16(16), 3184-99.

Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocytes. We also demonstrated that MPT0B291 suppressed proliferation by inducing G1 phase cell cycle arrest and increased apoptosis in human and rat glioma cell lines by flow cytometry and immunocytochemistry. We further investigated the anti-tumor effects of MPT0B291 in xenograft (mouse) and allograft (rat) models. The IVIS200 images and histological analysis indicated MPT0B291 (25 mg/kg, p. o.) reduced tumor volume. Mechanistically, MPT0B291 increased phosphorylation and acetylation/activation of p53 and increased mRNA levels of the apoptosis related genes PUMA, Bax, and Apaf1 as well as increased protein level of PUMA, Apaf1 in C6 cell line. The expression of cell cycle related gene p21 was also increased and Cdk2, Cdk4 were decreased by MPT0B291. Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth.

7 illus, 1 table, 64 ref

043332   HAO K, JIANG W, ZHOU M, LI H, CHEN D, JIANG F, HU Q (China Pharmaceutical Univ, Nanjing 210009, PR China, Email: huqh@cpu.edu.cn) : Targeting BRD4 prevents acute gouty arthritis by regulating pyroptosis. Int J Biol Sci 2020, 16(16), 3163-73.

Acute gouty arthritis is a common inflammatory arthropathy resulting from urate deposition in joints during persistent hyperuricemia. Nevertheless, effective therapeutic strategies are still unavailable. Here, we propose the crucial role of bromodomain-containing protein 4 (BRD4) in acute gouty arthritis. Therapeutic effect of BRD4 specific inhibitor JQ-1 on acute gouty arthritis was evaluated in vivo and in vitro. Pyroptosis was analyzed by Caspase-1/PI double staining and cleavage of gasdermin D (GSDMD). Expression of key factors involved in BRD4/NF-κB/NLRP3/GSDMD signaling pathway were measured by western blot, and colocalization of NLRP3 and ASC was detected using immunofluorescence. In addition, the role of BRD4 on monosodium uric acid crystals (MSU)-induced pyroptosis was verified in BRD4 siRNA-transfected THP-1 cells. Pretreatment of JQ1 and BRD4 siRNA significantly suppressed pyroptosis and inhibited activation of p65 NF-κB signaling as well as NLRP3 inflammasome in THP-1 cells exposed to MSU. In vivo, JQ-1 administration could effectively attenuate joint swelling and synovial inflammation in rats treated by intra-articular injection of MSU. More importantly, MSU led to macrophage pyroptosis and Brd4/NF-κB/NLRP3/GSDMD signaling induction in rat synoviums, which was improved by JQ-1. Our study identifies the role of BRD4 in MSU-induced pyroptosis through regulating NF-κB/NLRP3/GSDMD signaling pathways, which provides a potential target for treatment of acute gouty arthritis.

6 illus, 2 tables, 31 ref

043331   PAN X-W, ZHANG H, XU D, CHEN J-X, CHEN W-J, GAN S-S, QU F-J, CHU C-M, CAO J-W, FAN Y-H, et al. (Urology Dep, Gongli Hospital of Second Military Medical Univ, Shanghai 200135, China, Email: cuixingang@smmu.edu.cn) : Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis. Int J Biol Sci 2020, 16(16), 3149-62.

Cancer stem cells (CSCs) are biologically characterized by self-renewal, multi-directional differentiation and infinite proliferation, inducing anti-tumor drug resistance and metastasis. In the present study, we attempted to depict the baseline landscape of CSC-mediated biological properties, knowing that it is vital for tumor evolution, anti-tumor drug selection and drug resistance against fatal malignancy. We performed single-cell RNA sequencing (scRNA-seq) analysis in 15208 cells from a pair of primary and metastatic sites of collecting duct renal cell carcinoma (CDRCC). Cell subpopulations were identified and characterized by t-SNE, RNA velocity, monocle and other computational methods. Statistical analysis of all single-cell sequencing data was performed in R and Python. A CSC population of 1068 cells was identified and characterized, showing excellent differentiation and self-renewal properties. These CSCs positioned as a center of the differentiation process and transformed into CDRCC primary and metastatic cells in spatial and temporal order, and played a pivotal role in promoting the bone destruction process with a positive feedback loop in the bone metastasis microenvironment. In addition, CSC-specific marker genes BIRC5, PTTG1, CENPF and CDKN3 were observed to be correlated with poor prognosis of CDRCC. Finally, we pinpointed that PARP, PIGF, HDAC2, and FGFR inhibitors for effectively targeting CSCs may be the potential therapeutic strategies for CDRCC. The results of the present study may shed new light on the identification of CSCs, and help further understand the mechanism underlying drug resistance, differentiation and metastasis in human CDRCC.

4 illus, 62 ref

043330   HUANG Y, ZHANG K, JIANG M, NI J, CHEN J, LI L, DENG J, ZHU Y, MAO J, GAO X, et al. (First Teaching Hospital of Tianjin Univ of Traditional Chinese Medicine, Tianjin 300193, People’s Republic of China, Email: guanwei.fan@tjutcm.edu.cn) : Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure. Int J Biol Sci 2020, 16(16), 3133-48.

Cardiac metabolic remodeling is recognized as an important hallmark of heart failure (HF), while strategies that target energy metabolism have therapeutic potential in treating HF. Shen-Fu formula (S-F) is a standardized herbal preparation frequently used in clinical practice and is a promising combinatorial therapy for HF-related metabolic remodeling. Herein, we performed an untargeted multi-omics analysis using transcriptomics, proteomics, and metabolomics on HF mice induced by transverse aortic constriction (TAC). Integrated and pathway-driven analyses were used to reveal the therapeutic targets associated with S-F treatment. The cardioprotective effect and potential mechanism of S-F were verified by the results from echocardiography, hemodynamics, histopathology, and biochemical assays. As a result, S-F significantly alleviated myocardial fibrosis and hypertrophy, thus reducing the loss of heart function during adverse cardiac remodeling in TAC mice. Integrated omics analysis showed that S-F synergistically mediated the metabolic flexibility of fatty acids and glucose in cardiac energy metabolism. These effects of S-F were confirmed by the activation of AMP-activated protein kinase (AMPK) and its downstream targets in the failing heart. Collectively, our results demonstrated that S-F suppressed cardiac metabolic remodeling through activating AMPK-related pathways via energy-dependent mechanisms.

7 illus, 45 ref

043329   YIP H-K, LEE M S, LI Y-C, SHAO P-L, CHIANG J Y, SUNG P-H, YANG C-H, CHEN K-H (Anesthesiology Dep, Kaohsiung Chang Gung Memorial Hospital and Chang Gung Univ Coll of Medicine, Kaohsiung 83301, Taiwan, Email: amigofx35@gmail.com) : Dipeptidyl peptidase-4 deficiency effectively protects the brain and neurological function in rodent after acute hemorrhagic stroke. Int J Biol Sci 2020, 16(16), 3116-32.

This study tested the hypothesis that abrogated dipeptidyl peptidase-4 (DPP4) activity played a crucial role on reducing stroke volume and preserving neurological function in rodent after acute hemorrhagic stroke (AHS). Animals (n=6/each group) were categorized into group 1 (sham-control of F344 rat), group 2 (sham-control of DPP4-deficiency rat), group 3 [AHS by right cerebral injection of autologous blood (100 µL) in F344 rat], group 4 (AHS + sitagliptin/600 mg/kg 3 h prior to and at 3 h then once per day after AHS) and group 5 (AHS in DPP4-deficiency rat). The results of corner test showed the neurological function was significantly improved from days 3, 7, and 14 in groups 4 and 5 than in group 3 (all p<0.001). By days 1 and 14 after AHS procedure, the circulating levels of SDF-1α and GLP-1 were significantly increased from groups 1/2 to group 5 (all p<0.001), whereas circulating DPP4 activity was significantly increased in group 3 than other groups (all p<0.001). The brain ischemic area (BIA) was highest in group 3, lowest in groups 1/2 and significantly lower in group 5 than in group 4 (all p<0.0001). The protein expressions of oxidative-stress/inflammatory/apoptotic/cell-proliferation signaling, and the cellular expressions of inflammatory/DNA-damaged biomarkers exhibited a similar pattern to BIA among the groups (all p<0.01). In conclusion, deprivation of DPP4 activity protected the brain from AHS damage and preserved neurological function.

11 illus, 37 ref

046611   NAGRALE N, WANKHADE P, GATHE B, DONGRE A P (Forensic Medicine & Toxicology Dep, Chandulal Chandrakar Memorial Medical Coll, Durg, Chattisgarh, Email: drpawan9781@gmail.com) : Knowledge & perception of medical students towards the LGBT (lesbian, gay, bisexual & transgender) patients & their rights: a cross sectional study. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194289.

Diversity is a part of our everyday lives. Having good attitudes towards LGBT (lesbian, gay, bisexual & transgender) individuals is one of the ways of accepting and respecting human diversity. In this way, the quality of offered services will be same for all the people. Attitudes of medical professionals towards homosexuals can influence their willingness to provide these individuals with medical help. The study evaluates the medical students’ knowledge about homosexuality and their attitudes towards it. The sample consisted of 200 participants (104 from second year & 96 from first year) who anonymously completed the preformed questionnaire. The study showed that the second year students have more knowledge than the first year students. Degree of knowledge had significant predictive effect on attitudes in the analyzed predictive model & is important tool in shaping the attitudes towards LGBT patients and reducing stigmatization.

6 tables, 8 ref

041536   SAHOO C R, PAIDESETTY S K, PADHY R N (Siksha ‘O’ Anusandhan Univ, Bhubaneswar - 751 003, Odisha, Email: rnpadhy54@gmail.com) : Nostocine a derivatives as human DNA topoisomerase II-alpha inhibitor. Indian J Pharm Edu Res 2020, 54(3), 698-704.

Due to heavy morbidity and mortality from cancer, the designing of newer drugable molecules against breast cancer is the call of day. As, Schiff-base sulfonamides have been widely used in tumor treatments. Nostocine-sulfonamide (NS) Schiff-base molecules were designed with tools of bioinformatics against the target enzyme, human topoisomerase II-alpha (topo IIa) against breast cancer. The designed NS conjugates were assessed by RO5, ADMET and molecular docking. Herein, these analogues, NS-20b (Nostocine A-sulfaphenazole), 12a (Nostocine A-sulfisoxazole) and 16b (Nostocine A-sulfamethazineare) are N-heteroaryl substituted sulfonamide moieties linked with pyrazolo[4,3-e][1,2,4]triazine of Nostocine A. These derivatives would act as potent inhibitors of topo IIa for breast cancer.

2 illus, 1 table, 12 ref

043328   DING M, BU X, LI Z, XU H, FENG L, HU J, WEI X, GAO J, TAO Y, CAI B, et al. (Biochemistry and Molecular Biology Dep, Fourth Military Medical Univ, Shaanxi, Xi’an 710032, China, Email: bioliangshen@fmmu.edu.cn) : NDRG2 ablation reprograms metastatic cancer cells towards glutamine dependence via the induction of ASCT2. Int J Biol Sci 2020, 16(15), 3100-15.

Metastasis is the most common cause of lethal outcome in various types of cancers. Although the cell proliferation related metabolism rewiring has been well characterized, less is known about the association of metabolic changes with tumor metastasis. Herein, we demonstrate that metastatic tumor obtained a mesenchymal phenotype, which is obtained by the loss of tumor suppressor NDRG2 triggered metabolic switch to glutamine metabolism. mRNA-seq and gene expression profile analysis were performed to define the differential gene expressions in primary MEC1 and metastatic MC3 cells and the downstream pathways of NDRG2. NDRG2 regulation of Fbw7-dependent c-Myc stability were determined by immunoprecipitation and protein half-life assay. Luciferase reporter and ChIP assays were used to determine the roles of Akt and c-Myc in mediating NDRG2-dependent regulation of ASCT2 in in both tumor and NDRG2-knockout MEF cells. Finally, the effect of the NDRG2/Akt/c-Myc/ASCT2 signaling on glutaminolysis and tumor metastasis were evaluated by functional experiments and clinical samples. Based on the gene expression profile analysis, we identified metastatic tumor cells acquired the mesenchymal-like characteristics and displayed the increased dependency on glutamine utilization. Further, the gain of NDRG2 function blocked epithelial-mesenchymal transition (EMT) and glutaminolysis, potentially through suppression of glutamine transporter ASCT2 expression. The ASCT2 restoration reversed NDRG2 inhibitory effect on EMT program and tumor metastasis. Mechanistic study indicates that NDRG2 promoted Fbw7-dependent c-Myc degradation by inhibiting Akt activation, and subsequently decreased c-Myc-mediated ASCT2 transcription, in both tumor and NDRG2-knockout MEF cells. Supporting the biological significance, the reciprocal relationship between NDRG2 and ASCT2 were observed in multiple types of tumor tissues, and associated with tumor malignancy. NDRG2-dependent repression of ASCT2 presumably is the predominant route by which NDRG2 rewires glutaminolysis and blocks metastatic tumor survival. Targeting glutaminolytic pathway may provide a new strategy for the treatment of metastatic tumors.

8 illus, 60 ref

041535   ROHILLA R, GOYAL A, VARSHNEY V, SEMWAL B C, YADAV H N (Pharmacology Dep, GLA Univ, Mathura - 281406, Uttar Pradesh, Email: richa.rohilla10@gmail.com) : Role of heme oxygenase- 1(HO-1) and endothelin-1 (ET-1) in modulation of cardioprotective effect of ischemic postconditioning in diabetic rat heart. Indian J Pharm Edu Res 2020, 54(3), 690-7.

We have recently reported that heme oxygenase-1 (HO-1) is involved in ischemic preconditioning-mediated cardioprotection by promoting nitric oxide (NO) release into diabetic rat heart (DRH). The upregulation of HO-1 decreases the endothelin-1 (ET-1) production, which is a negative regulator of NO. In diabetes, the level of HO-1 is reduced while the level of ET-1 gets elevated. Thus, the present analysis was aimed to explore the concept of HO-1 and ET-1 in the abrogated cardioprotective role of ischemic post conditioning (IPOC) in the DRH. To explore the concept, a selective HO-1 inducer hemin, 18 hrs prior and a selective ETA receptor antagonist BQ123, one week prior, were administered to DRH before isolation. DRH was removed and then mounted on Langendorff's apparatus, subjected to 10 min stabilization followed by 30 min ischemia. IPOC had been induced by four cycles of 5 min reperfusion along with 5 min ischemia followed by further 120 min of reperfusion. The extent of the infarct was measured and the coronary effluent was tested for the LDH, CK-MB and NO release. In DRH, cardioprotection mediated by the IPOC was significantly attenuated. Hemin and BQ-123 reinstated the impact of IPOC in DRH and also increased the release of NO. In BQ-123 pre-treated diabetic rat, the administration of hemin was unable to produce the additive cardioprotective effect of IPOC. Thus, it is suggested that hemin and BQ-123 restore the attenuated cardioprotective effect of IPOC in the DRH, which may be due to increased NO release.

6 illus, 45 ref

043327   ADAMI R, BOTTAI D (Milan Univ, San Paolo Hospital via A di Rudinì 8 20142, Milan Italy, Email: daniele.bottai@unimi.it) : S-adenosylmethionine tRNA modification: Unexpected/ unsuspected implications of former/new players. Int J Biol Sci 2020, 16(15), 3018-27.

S-adenosylmethionine supplies methyl groups to many acceptors, including lipids, proteins, RNA, DNA, and a wide range of small molecules. It acts as the precursor in the biosynthesis of metal ion chelating compounds, such as nicotianamine and phytosiderophores, of the polyamines spermidine and spermine and of some plant hormones. Finally, it is the source of catalytic 5′-deoxyadenosyl radicals. Radical S-adenosylmethionine (SAM) enzymes (RS) represent one of the most abundant groups (more than 100,000) of enzymes, exerting a plethora of biological functions, some of which are still unknown. In this work, we will focus on two RS: CDK5RAP1 and CDKAL1, both of which are involved in tRNA modifications that result in important tRNA folding and stability and in maintaining high translational fidelity. Based on this crucial role, their impairment can be important in the development of different human diseases.

4 illus, 75 ref

041534   WANG X, LI Y, SHEN Y, ZHANG D (Affiliated Hospital of Hebei Univ, Baoding-071000, Hebei, China, Email: zhangdongzi6688@sina.com) : Exploring the role and mechanism of imatinib in chronic unpredictable mild stress-induced depression model of rats. Indian J Pharm Edu Res 2020, 54(3), 682-9.

The study was planned to examine the potential effect of imatinib in chronic unpredictable mild stress (CUMS)-induced depression model of rats. Male rats were subjected to the 6-week CUMS with unpredictable stressors to induce depression and the imatinib was started from the 4^th week (for 21 days during 6 weeks of the protocol). CUMS significantly increased immobility time and decreased consumption of sucrose in the swimming and sucrose preference test respectively. Furthermore, a considerable reduction in the Brain-derived neurotrophic factor (BDNF) levels and an increase in phosphorylated NF-kB levels (p-NF-kB) were noticed in the prefrontal cortex (PFC). However, imatinib (25 and 50 mg/kg) significantly reversed sucrose consumption as well as reduced immobility times in CUMS-subjected rats, suggesting the antidepressant potential of imatinib. Moreover, imatinib treatment significantly increases in the levels of BDNF and a decrease in the p-NF-kB levels in the PFC of the brain of stress-subjected rats. The co-administration of tropomyosin receptor kinase B (TrkB) antagonist, ANA-12 (0.25 and 0.5 mg/kg) with imatinib (50 mg/kg) considerably attenuated imatinib-mediated antidepressant effects in sucrose preference behavior and immobility period in CUMS subjected rats. ANA-12 abolished imatinibinduced effects in stress-subjected rats. The antidepressant actions of imatinib may be attributed to an increase in the BDNF levels and a decrease in the p-NFkB levels in the stress-susceptible PFC region of the CUMS subjected rats.

4 illus, 47 ref

046609   KALKI M, PRIYA S M, THIVYA N (Chettinad Academy of Research and Education, Kanchipuram, Tamilnadu, Email: kalkimeshack03@gmail.com) : A study to assess the patients compliance to medications among hypertension patients at selected areas in Kanchipuram District Tamil Nadu. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194287.

Hypertension is the most prevalent cause for cardio vascular disease, affecting at least 600 million people worldwide and is an important contribute to cardiovascular mortality and mortality. Compliance to antihypertensive medication has been found to be a major concern. The study was conducted to assess the patient’s compliance to medications among hypertension patients at selected areas in Kanchipuram district Tamilnadu. The objectives of the study were to assess the patient’s compliance to medications among hypertensive patients and to associate patient’s compliance to medications with selected demographic variables. The research design selected for the study were Descriptive research design. The sampling technique used for the study were purposive sampling with the sample size of 60. Data collection was done by identifying the demographic variables and by using Morisky Medication Adherence scale, the patient’s compliance to hypertension medications was assessed. The results revealed that assessing patients compliance to medications, the study shows that 48(80 %) of hypertensive patients are following medium compliance of hypertension medication and 12(20 %), of the patients are having low compliance and none of the patients 0 % are following high compliance to medication. Regarding association with demographic variables, factors like sex and blood pressure are highly associated with compliance to medications and there is no significant association with the demographic variables like age, educational status, types of family, religion, socio economic status Hence community education is needed to improve the patient’s ability to cope up of medications and make informed decision regarding hypertensive medications and to motive the community people to introduce changes in diet and life style modification.

24 ref

043335   LIU F, GUO X, DONG W, ZHNAG W, WEI S, ZHANG S, ZHU X, ZHOU W, ZHANG J, LIU H (Hepatic Surgery Dep, Navy Medical Univ, Shanghai 200438, China, Email: liuhuigg@hotmail.com) : Postoperative adjuvant TACE-associated nomogram for predicting the prognosis of resectable hepatocellular carcinoma with portal vein tumor thrombus after liver resection. Int J Biol Sci 2020, 16(16), 3210-20.

To explore the effects of postoperative adjuvant transarterial chemoembolization (PA-TACE) on the prognosis of HCC patients with Portal Vein Tumor Thrombus (PVTT) undergoing resection, and to develop a PA-TACE-related nomogram for predicting survival individually. Two hundred and ninety-three consecutive HCC patients with PVTT under R0 hepatectomy were recruited. Forty-seven cases had recurrence within one month after surgery. The remaining 246 cases consisted of 90 PA-TACE and 156 non-PA-TACE cases. COX regression analysis was performed for overall survival (OS) or recurrence-free survival (RFS) of these 246 cases, allowing the derivation of independent factors that were integrated into the nomogram. C-index, calibration curves, and risk stratification were performed to evaluate the performance and discriminative power of the nomograms. In 246 patients without recurrence within one month after surgery, the OS and RFS for the PA-TACE group were significantly better than those for the non-PA-TACE group (P<0.0001, P<0.0001, respectively). After Cox regression analysis of OS or RFS, PA-TACE-related nomogram models were constructed. The C-index of the PA-TACE-related nomogram for OS and RFS was 0.72 and 0.73, respectively. Calibration curves revealed a good agreement between predictions and observations for the nomograms. Based on the nomogram-related risk stratification, Kaplan-Meier curves showed powerful discriminative ability. PA-TACE therapy improved the survival of HCC patients with PVTT undergoing hepatectomy. Accurate nomogram models were developed for predicting the individual survival and recurrence of these patients.

5 illus, 3 tables, 40 ref

043326   TAN W, ZOU J, YOSHIDA S, JIANG B, ZHOU Y (Ophthalmology Dep, Central South Univ, Changsha, Hunan 410011, China, Email: zhouyedi@csu.edu.cn) : The role of inflammation in age-related macular degeneration. Int J Biol Sci 2020, 16(15), 2989-3001.

Age-related macular degeneration (AMD) is a blinding eye disease which incidence gradually increases with age. Inflammation participates in AMD pathogenesis, including choroidal neovascularization and geographic atrophy. It is also a kind of self-protective regulation from injury for the eyes. In this review, we described inflammation in AMD pathogenesis, summarized the roles played by inflammation-related cytokines, including pro-inflammatory and anti-inflammatory cytokines, as well as leukocytes (macrophages, dendritic cells, neutrophils, T lymphocytes and B lymphocytes) in the innate or adaptive immunity in AMD. Possible clinical applications such as potential diagnostic biomarkers and anti-inflammatory therapies were also discussed. This review overviews the inflammation as a target of novel effective therapies in treating AMD.

2 illus, 2 tables, 168 ref

041533   PRABHAKAR O (Pharmacology Dep, GITAM Institute of Pharmacy, Visakhapatnam - 530 045, Andhra Pradesh, Email: prabhakar.orsu@gitam.edu) : Naringin attenuates aluminum induced cognitive deficits in rats. Indian J Pharm Edu Res 2020, 54(3), 674-81.

The exposure of aluminum for longer period in brain can lead to impaired cognition and behavioral changes. The present study was aimed to investigate the aluminum induced cognitive deficits and possible protective outcomes of naringin. Aluminum chloride in a dose of 100 mg/kg i.p was employed for 60 days to induce cognitive deficits in Westar rats. The animals were divided into groups each group contain six animals, as normal, aluminum treated, naringin treated (25, 50, 100 mg/kg). These animals were used to estimate behavioral characters such as Open field, eight arm radial maze, Morris water maze and Rota-rod tests and also used to assess the biochemical parameters such as acetylcholine esterase activity, malondialdehyde, superoxide dismutase and catalase. Aluminum intoxicated rats showed significantly reduced exploratory and spontaneous locomotors activities in open field test and significant impairment in working and learning memory assessed by Morris water maze and radial arm maze tests. It also significantly increased acetylcholine esterase activity and malondialdehyde. The superoxide dismutase and catalase were also decreased significantly. Naringin was given (25, 50 and 100 mg/kg PO) to the aluminum intoxicated rats for a period of 30 days. The naringin treatment has shown significant improvements in spontaneous locomotors and exploratory activities and memory performance tasks of rats. The oxidative stress (reduced lipid peroxidation, restored reduced superoxide dismutase and catalase) and acetylcholine esterase activity were significantly decreased in the naringin group. Thus, these findings supported that naringin has showed potential neuroprotection against aluminum induced oxidative stress and cognitive deficit.

3 illus, 4 tables, 41 ref

043325   TIZAOUMI K, ZIDI I, LEE K H, GHAYDA R A, HONG S H, LI H, SMITH L, KOYANAGI A, JACOB L, KRONBICHLER A, et al. (Pediatrics Dep, Yonsei Univ Coll of Medicine, Seoul 03722, Republic of Korea, Email: shinji@yuhs.ac) : Update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (COVID-19). Int J Biol Sci 2020, 16(15), 2906-23.

In December 2019, an acute respiratory disease caused by novel species of coronavirus (SARS-CoV-2), emerged in China and has spread throughout the world. On 11th March 2020, the World Health Organization (WHO) officially declared coronavirus disease 19 (COVID-19) a pandemic, severe coronavirus-mediated human disease. Based on genomic and phylogenetic studies, SARS-CoV-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. However, the exact origin or the host intermediate remains unknown. Genetically, SARS-CoV-2 is similar to several existing coronaviruses, particularly SARS-CoV, but differs by silent and non-silent mutations. The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious. COVID-19 shares both the main clinical features and excessive/dysregulated cell responses with the two previous Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronavirus (SARS) epidemics. In this review, we provide an update of the current knowledge on the COVID-19 pandemic. Gaining a deeper understanding of SARS-CoV-2 structure, transmission routes, and molecular responses, will assist in the prevention and control of COVID-19 outbreaks in the future.

3 illus, 1 table, 214 ref

041532   GUO Z, XING Y, WANG W, LAI J (Endocrinology and Metabolism Dep, Xijing Hospital Affiliated to Air Force Military Medical Univ, Xi’an-710032, Shaanxi, China, Email: jblaixian@sina.cn) : Apigetrin inhibits thyroid cancer cell growth and proliferation through down-regualtion of hif1α and vegf expression. Indian J Pharm Edu Res 2020, 54(3), 668-73.

Thyroid cancer is a commonly detected endocrine malignant tumour which accounts for 1 % of the total human cancers. The present study was aimed to investigate the effect of apigetrin on anaplastic thyroid cancer cell viability and understand the mechanism involved. Fluorescent microscopy using diamidino-2- phenylindole (DAPI)staining was used to examine the nuclear fragmentation. Changes in protein expression were analysed by Western blot analysis and migration potential using wound healing assay. Treatment with apigetrin exhibited inhibitory effect on anaplastic thyroid cancer cell viability in dose based manner. The cleavage of PARP and activation of caspase-3/-9 was promoted in anaplastic thyroid cancer cells on treatment with apigetrin. A significant reduction in hypoxiainducible factor1α (HIF1α) and vascular endothelial growth factor (VEGF) expression was caused by apigetrin in anaplastic thyroid cancer cells. The count of Terminal deoxynucleotidyltransferase-mediated nick end labeling (TUNEL)-positive cells was increased significantly (p<0.05) in the cell cultures on treatment with apigetrin. The cell migration was also suppressed by apigetrin in dose based manner. Moreover, treatment of mice with apigetrin inhibited the tumor growth and development markedly in comparison to the untreated group. The present study demonstrates that apigetrin plays an important role in the inhibition of thyroid cancer. Therefore, apigetrin needs to be investigated further as therapeutic agent for thyroid cancer treatment. 

6 illus, 19 ref

046608   AGARWAL H K, SINGHAL A, YADAV A K (Ophthalmology Dep, MAMC, Agroha, Haryana, Email: ahasai1413@gmail.com) : Crossword puzzle: an innovative assessment tool to improve learning of students in forensic medicine. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194286.

As per Medical Council of India (MCI) for setting teaching learning standards according to need of society, now has focus shift from traditional teaching methods to adopting teaching learning method that is been termed as competency-based learning. Faculty training programme by MCI are also providing the right platform for learning the new methodology in medical education. To prepare an interesting and effective tool in assessing the knowledge of Forensic medicine among the medical undergraduate students to produce competent and confident Indian Medical Undergraduates. : Crossword puzzle exercise was given to 2nd year students, who were in 5th semester. 38 students participated in this study. A questionnaire was given to the participants to evaluate the response consisting of 15 questions; responses were obtained on Likert scale 5 to 0. Out of 38 students 92 % of students found the puzzle interesting. 76.4 % students found this puzzle as a useful tool to learn forensic medicine. 73 % students agreed it to be a useful tool for the assessment of their knowledge. 81 % students were in favour to use such puzzle in competitive exams. In terms of retaining the knowledge of topics, 84 % students found this puzzle useful. : Crossword puzzle improves memory power, performance and critical thinking of students with fun. This can be tried as a question in periodic internal examination for internal assessment as well as well as for the purpose of structured viva examination in university examination.

3 illus, 20 ref

043325   HAN D, LI R, HAN Y, ZHANG R, LI J (National Center for Clinical Laboratories, Beijing 100730, People’s Republic of China, Email: jmli@nccl.org.cn) : COVID-19: Insight into the asymptomatic SARS-COV-2 infection and transmission. Int J Biol Sci 2020, 16(15), 2803-11.

The existence of a substantial but unclear number of asymptomatic SARS-COV-2 patients worldwide has raised concerns among global public health authorities. In this review, according to the published literature, we provided the evidence that asymptomatic infections can result in person-to-person transmission. Four studies suggested that the virus can be transmitted by asymptomatic patients for at least two consecutive generations, indicating its strong infectivity. Asymptomatic infection tends to be, but is not only, identified among young people (<20 years old). The majority of asymptomatic patients appear to have a milder clinical course during hospitalization, but the severity of the symptoms of the secondary patients infected by SARS-COV-2 from asymptomatic patients varies with their physical constitution. The proportion of asymptomatic individuals among all confirmed cases widely differed (from 1.95 % to 87.9 %) according to the study setting and the populations studied. The increasing large-scale tests are expected to give more information about the true number of asymptomatic infections in the population. In China and other countries, various guidelines for management of asymptomatic cases have been issued. Importantly, early detection, early reporting, early isolation and early treatment of asymptomatic patients require the joint efforts of policy makers, clinicians, technicians, epidemiologists, virologists and patients.

1 illus, 1 table, 77 ref

041530   ZEESHAN F, LIN P Y, SHESHALA R (Pharmaceutics Dep, Teknologi MARA Selangor Univ, Kuala Selangor, Malaysia, Email: ravisheshala@uitm.edu.my) : Application of similarity factor (f₂) and time required to drug release (t_%) indicators for dissolution profiles comparison of paracetamol tablets. Indian J Pharm Edu Res 2020, 54(3), 647-53.

The comparison of in vitro dissolution profiles is an integral step during the development of any generic product. However, using merely similarity factor (f₂) as a dissolution parameter may not be adequate. The present study was conducted to explore whether f₂ alone suffices to adequately compare the dissolution profiles of tablets or both f₂ and time required to percentage drug release (t_%) generate closely similar results. The reference (R) and two generic paracetamol test products (T1 and T2), each containing 500 mg drug were subjected to dissolution studies under different pH conditions namely 1.2, 4.5 and 6.8. The amount of drug released was quantified using validated UV-Visible spectrophotometric method and results were analysed using bootstrap similarity factor approach and the time required to release 25 % (t_{25 %}), 50 % (t_{50 %}) and 75 % (t_{75 %}) of drug. The data were evaluated statistically using one-way multivariate analysis of variance (MANOVA) followed by post hoc Tukey’s test. T1 tablets demonstrated similarity in the drug release with R product at pH 1.2. Although T2 product did not show any similarity with R at all pH values used yet it depicted rapid release profiles pivotal for an immediate-release product. Both f₂ and t_% exhibited closely similar results for all sets of data. Application of similarity factor alone may provide reliable results for comparison of dissolution profile. Nevertheless, the time required to release t_{25 %}, t_{50 %} and t_{75 %} may be used along with similarity factor for better interpretation of in vitro dissolution results particularly for potent drugs.

1 illus, 5 tables, 24 ref

043324   LI S, GHOSH C, ZING Y, SUN Y (Virginia Commonwealth Univ, Richmond, VA 23298, USA, Email: ysun4@vcu.edu) : Phosphatidylinositol 4,5-bisphosphate in the control of membrane trafficking. Int J Biol Sci 2020, 16(15), 2761-74.

Phosphoinositides are membrane lipids generated by phosphorylation on the inositol head group of phosphatidylinositol. By specifically distributed to distinct subcellular membrane locations, different phosphoinositide species play diverse roles in modulating membrane trafficking. Among the seven known phosphoinositide species, phosphatidylinositol 4,5-bisphosphate (PI4,5P₂) is the one species most abundant at the plasma membrane. Thus, the PI4,5P₂ function in membrane trafficking is first identified in controlling plasma membrane dynamic-related events including endocytosis and exocytosis. However, recent studies indicate that PI4,5P₂ is also critical in many other membrane trafficking events such as endosomal trafficking, hydrolases sorting to lysosomes, autophagy initiation, and autophagic lysosome reformation. These findings suggest that the role of PI4,5P₂ in membrane trafficking is far beyond just plasma membrane. This review will provide a concise synopsis of how PI4,5P₂ functions in multiple membrane trafficking events. PI4,5P₂, the enzymes responsible for PI4,5P₂ production at specific subcellular locations, and distinct PI4,5P₂ effector proteins compose a regulation network to control the specific membrane trafficking events.

6 illus, 155 ref

043323   FU W, YUE Y, MIAO K, XI G, ZHANG C, WANG W, AN L, TIAN J (China Agricultural Univ, No.2 Yuanmingyuan West Road, Beijing 100193, P. R. China, Email: tianjh@cau.edu.cn) : Repression of FGF signaling is responsible for dnmt3b inhibition and impaired de novo DNA methylation during early development of in vitro fertilized embryos. Int J Biol Sci 2020, 16(15), 3085-99.

Well-orchestrated epigenetic modifications during early development are essential for embryonic survival and postnatal growth. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various shortor long-term consequences. Among these, DNA methylation defects are of great concern. Despite the critical role of DNA methylation in determining embryonic development potential, the mechanisms underlying IVF-associated DNA methylation defects, however, remains largely elusive. We reported herein that repression of fibroblast growth factor (FGF) signaling as the main reason for IVF-associated DNA methylation defects. Comparative methylome analysis by postimplantation stage suggested that IVF mouse embryos undergo impaired de novo DNA methylation during implantation stage. Further analyses indicated that Dnmt3b, the main de novo DNA methyltransferase, was consistently inhibited during the transition from the blastocyst to postimplantation stage (Embryonic day 7.5, E7.5). Using blastocysts and embryonic stem cells (ESCs) as the model, we showed repression of FGF signaling is responsible for Dnmt3b inhibition and global hypomethylation during early development, and MEK/ERK-SP1 pathway plays an essential mediating role in FGF signaling-induced transcriptional activation of Dnmt3b. Supplementation of FGF2, which was exclusively produced in the maternal oviduct, into embryo culture medium significantly rescued Dnmt3b inhibition. Our study, using mouse embryos as the model, not only identifies FGF signaling as the main target for correcting IVF-associated epigenetic errors, but also highlights the importance of oviductal paracrine factors in supporting early embryonic development and improving in vitro culture system.

7 illus, 66 ref

046606   MAZUMDER A, NAGRALE N (Shri Shankaracharya Institute of Medical Sciences, Bhilai, Chattisgarh) : Age estimation from radiological evaluation of epiphyseal union of related bones around elbow joint: A cross sectional study from Central India (Chhattisgarh). Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194284.

Radiological evaluation of the skeletal age represents an important tool for the estimation of the chronological age in the living. The aim of our study was to evaluate the relationship between the chronological age and degree of epiphyseal fusion around elbow joint in population of Chhattisgarh (Central India) and to compare our results with the results of similar studies. The study was carried out in 100 healthy subjects (40 girls and 60 boys) aging from 13 to 20 years. The obtained results from the radiographs revealed that the complete fusion of epiphysis of elbow joint is seen at 16-20 years. Females were consistently developing epiphyseal union at a younger age than their male counterparts. Results also suggest that the age of epiphyseal union is found to vary greatly all over the world indicating the need for separate standards of age of epiphyseal union for separate regions.

6 tables, 17 ref

043322   JIANG C, LIU J, GUO M, GAO X, WU X, BAI N, GUO W, LI N, YI F, CHENG R, et al. (China Medical Univ, Shenyang, 110042, Liaoning, China, Email: lcao@cmu.edu.cn) : The NAD-dependent deacetylase SIRT2 regulates T cell differentiation involved in tumor immune response. Int J Biol Sci 2020, 16(15), 3075-84.

Sirtuin 2 (SIRT2), an NAD⁺-dependent deacetylase, regulates multiple biologic and pathologic processes including mitosis, genomic integrity, cell homeostasis and tumorigenesis. However, the role of SIRT2 in the immune response to cancer remains largely elusive. In this study, we found significantly lower expression of SIRT2 in peripheral T lymphocytes from breast cancer patients when compared to normal individuals. Moreover, SIRT2 levels positively correlated with CD8⁺ effector memory T (TEM) cells in breast cancer patients. In keeping with these findings, altered T cells differentiation manifested as decreased T_EM cells and increased naive T cells were observed in Sirt2 deficient mice. The upregulation of CD8⁺ T_EM by SIRT2 might attribute to the activation of aerobic oxidation as well as the inhibition of GSK3β acetylation in CD8⁺ T cells. Taken together, these results suggest that SIRT2 participate in tumor immune response by regulating T cell differentiation, which may provide novel insight for tumor prevention and immune therapy.

6 illus, 1 table, 45 ref

043321   ZHANG P, THE E, NEDUMARAN B, AO L, JARRET M J, XU D, FULLERTON D A, MENG X (Surgery Dep, Colorado Denver Univ, 12700 E 19th Avenue, Box C-320, Aurora, CO 80045, Email: x.meng@cuanschutz.edu) : Monocytes enhance the inflammatory response to TLR2 stimulation in aortic valve interstitial cells through paracrine up-regulation of TLR2 level. Int J Biol Sci 2020, 16(15), 3062-74.

Chronic valvular inflammation associated with monocyte infiltration promotes calcific aortic valve disease (CAVD) progression. Further, innate immunity in aortic valve interstitial cells (AVICs), mediated by Toll-like receptors (TLRs), up-regulates cellular inflammatory, fibrogenic and osteogenic activities. Currently, the pro-inflammatory communication between monocytes and AVICs and the underlying mechanism are unclear. We hypothesized that monocytes up-regulate AVIC inflammatory activity. This study sought to characterize the interaction between monocytes and AVICs and to elucidate the mechanism underlying cell-to-cell communication. AVICs, monocytes and co-cultures were exposed to a low concentration of TLR2 activator Pam3CSK4 (0.03 µg/ml). The TLR2 activator at this dose induced a marked increase in AVIC production of ICAM-1 and VCAM-1 only when co-cultured with monocytes. Adding conditioned medium from Pam3CSK4-treated monocytes (Pam3 CM, containing 0.1 µg/ml of Pam3CSK4) to AVIC culture (30% vol/vol; diluting Pam3CSK4 to 0.03 µg/ml) greatly increased the expression of adhesion molecules while adding conditioned medium from untreated monocytes (control CM) had no effect. Inhibition or knockdown of TLR2 in AVICs markedly reduced ICAM-1 and VCAM-1 expression induced by Pam3 CM. Further, Pam3 CM increased TLR2 levels in AVICs. Multiplex-ELISA analysis of Pam3 CM identified greater levels of TNF-α. Neutralization of TNF-α abolished the effect of Pam3 CM on AVIC TLR2 levels, resulting in marked attenuation of its potency in the induction of adhesion molecule expression. This study demonstrates that activated monocytes use paracrine signaling to sensitize AVICs for inflammatory responses to a low level of TLR2 activator. The mechanism of sensitization involves up-regulation of AVIC TLR2 levels by TNF-α from monocytes. Infiltrated monocytes in aortic valve tissue may exacerbate valvular inflammation by rendering AVICs hypersensitive to TLR2 activators.

6 illus, 1 table, 46 ref

046605   MADDILETI G B, RAJ A D I, KUMAR R, MAHESH G, YAMINI K (Forensic Medicine Dep, Trichy SRM Medical Coll Hospital and Research Centre, Irungalur, Trichy, Email: dodombbs@gmail.com. ) : An autopsy study of cranio-cerebral injuries due to road traffic accidents. Med Legal Update 2020, 20(1), 10.37506/v20/i1/2020/mlu/194282.

Cranio-cerebral injuries are a morbid state, resulting from gross structural changes to the scalp, skull and the contents of the cranium. In present scenario, accidents are now considered as one of major contributing factors of Non-Communicable Diseases which have become major health problems of developing countries like India. According to the national crime bureau statistics In India, over 1,46,133 people were killed in various road traffic accidents during 2015 and the count raised to 1,50,785 in 2016. Information on the contributing factors is mandatory to reduce this burden. A prospective study of all Road Traffic accidents coming for autopsy at Government Medical College, Anantapuram. Majority of victims were male in the age group between 31-40 years. Most of them had Linear fractures of the skull along with Sub dural haemorrhage. Two Wheeler riders were the most common victims. Most of the victims died due to CranioCerebral Injury. Most of the times, it is the negligence, which results in an accident. The negligence may be on the part of the victim or may be there on the part of other person who occupied the second vehicle. Sometimes innocent pedestrians are also victimized to these deaths. An accident for all practical purposes is preventable, provided if it is anticipated and proper precaution and preventive measures are adopted.

6 tables, 20 ref

041523   RAO R R, SHENOY P J, ULLAL S D, KAMATH A (Pharmacology Dep, Kasturba Medical Coll, Mangalore - 575 001, Karnataka, Email: preethi.pai@manipal.edu) : A learner centered approach of teaching and learning in pharmacology: A questionnaire based analysis of student cognizance and experiences. Indian J Pharm Edu Res 2020, 54(3), 580-8.

Innovative and flexible educational methods like Problem Based Learning (PBL) and integrated teaching practices were integrated into the Pharmacology course in a manner that they complement the didactic lectures or, completely replace the lecture classes with the aim to optimize the educational atmosphere for a better learner experience. The present study is an attempt to gather feedback on newer teaching learning methods and audiovisual aids employed during the didactic lectures and small group teaching sessions newly introduced into the curriculum. The study is a cross sectional questionnaire-based analysis. The questionnaires were distributed to the second-year medical students inviting them to share their opinion on usefulness of current teaching-learning methods. The data collected was analyzed by means of descriptive statistics. The students rated small group discussions and small testsassessment for learning to be more useful in understanding the subject as well as scoring more marks in the examinations (Likert score of 4.5 and 4.51 respectively). Didactic lectures were less useful with a Likert score of 3.71. Both problems based learning and integrated teaching scores were equivocal with more students favoring integrated teaching. Student feedback forms the backbone for continuing revisions of undergraduate curriculum with the aim of making the subject more learner-oriented and practically relevant. Constant review of our current methodology will reflect on success of newer teaching-learning methods introduced in encouraging learning. It would enable us to incorporate appropriate changes in curricula where and when necessary.

3 tables, 28 ref

041522   DYMEK J, KOWALSKI T, GO?DA A, POLAK W, SKOWRON A (Jagiellonian Univ, Krakow 30-699, Poland, Email: tomek.kowalski@doctoral.uj.edu.pl) : The first objective structured practical examination (OSPE) in pharmacy teaching in Poland: Designing, implementing and assessing the results. Indian J Pharm Edu Res 2020, 54(3), 572-9.

Education of pharmacy students in preparation for their profession is still changing. It is therefore important to improve students’ skills necessary to provide pharmaceutical services according to the professional standards. One of the elements of the pharmacy curriculum is to teach and improve student’s practical and interpersonal skills e.g. solving drug problems. OSPE (Objective Structured Practical Examination) is one of a broad family of structured and objectified examinations assessing practical, clinical, communication competencies. The aim of our study was to prepare a tool to assess the knowledge and skills of 5^th-year pharmacy students in the provision of pharmaceutical care services in pharmacies and to check whether the assumed learning outcomes were achieved during studies. OSPE was designed and implemented in accordance with the education standards for the field of pharmacy. OSPE performance scores of 5^th year pharmacy students at the Faculty of Pharmacy, Jagiellonian University Medical College in Poland were analyzed using descriptive statistics. OSPE consisted of six stations of which four stations with standardized patient. Standardized patient was used in stations: pharmaceutical interview, advice for selfmedication, education about medicines, medical device education, identification and resolution of drug-related problems. OSPE was implemented in January and February 2019 and lasted 6 days. The students of the Faculty of Pharmacy were assessed in blocks of 2-2.5 hr a total of ten examiners. Objective Structured Practical Examinations can assess practical competence and communication skills. Appropriately designed stations make it possible to perform professional activities that reflect the real situations in pharmacy. Implementation of OSPEs may be an effective tool to assess the objective outcomes pharmacy students. Results can be used as a tool for enhancing lessons and may be considered valuable for further development OSPE.

4 tables, 20 ref

043320   YE M, LU H, TANG W, JING T, CHEN S, WEI M, ZHANG J, WANG J, MA J, MA D, et al. (Pediatric Surgery Dep, Children’s Hospital of Fudan Univ, Shanghai, 201102, China, Email: kuirand@hotmail.com) : Downregulation of MEG3 promotes neuroblastoma development through FOXO1-mediated autophagy and mTOR-mediated epithelial-mesenchymal transition. Int J Biol Sci 2020, 16(14), 3050-61.

Our previous studies demonstrated that MEG3 was significantly downregulated in neuroblastoma (NB) and its expression was negatively associated with the INSS stage. Overexpression of MEG3 promoted apoptosis and inhibited proliferation in NB cells. In this study, we discovered more potential functions and molecular mechanisms of MEG3 in NB. According to the database, MEG3 positively correlated with the NB survival rate and was negatively associated with malignant clinical features. Moreover, we determined that MEG3 was mainly located in the nucleus by nuclear-cytoplasmic separation and RNA fish assays. Upregulation of MEG3 in stably transfected cell lines was accomplished, and CCK8, colony formation, and EDU assays were performed, which indicated that MEG3 significantly suppressed cell proliferation. Both wound healing and transwell experiments demonstrated that MEG3 decreased cell migration and invasion. CHIRP enrichments showed the anticancer effects of MEG3 were probably linked to autophagy and the mTOR signaling pathway. LC3 fluorescence dots and western blots showed that MEG3 attenuated autophagy by inhibiting FOXO1, but not the mTOR signaling pathway. Furthermore, MEG3 inhibited metastasis through epithelial-mesenchymal transition via the mTOR signaling pathway. Consistent with the above results, downregulation of MEG3 facilitated NB malignant phenotypes. Mechanistically, MEG3 and EZH2 regulated each other via a negative feedback loop and promoted NB progression together. In conclusion, our findings suggested that MEG3 was a tumor suppressor in NB and could be a potential target for NB treatment in the future.

7 illus, 47 ref

043319   JIA S, WU X, WU Y, CUI X, TAO B, ZHU Z, HU W (Institute of Hydrobiology, Wuhan 430072, China, Email: huwei@ihb.ac.cn) : Multiple developmental defects in sox11a mutant zebrafish with features of coffin-siris syndrome. Int J Biol Sci 2020, 16(14), 3039-49.

A previous study suggested that human Coffin-Siris syndrome is related to the mutation of SOX11. Since the homozygous SOX11 mutant mice died soon after birth, no suitable model was available for the study of the pathogenic mechanism of Coffin-Siris syndrome. To solve this problem, we generated two viable homozygous zebrafish mutants, sox11am/m and sox11bm/m. We found that the sox11a^m/m mutant possessed Coffin-Siris syndrome features. The sox11a^m/m mutants exhibited growth deficiency from 3.3 hpf embryos to adulthood. Furthermore, the sox11a^m/m mutant also displayed microcephaly, narrow pupillary distance, achondroplasia, and bone deformity in adults. Growth deficiency could be rescued by the injection of sox11a mRNA at the one-cell stage. In addition, the expression levels of genes related to cartilage and bone were downregulated in the sox11a^m/m mutant, indicating that sox11a mainly affected the growth and development of zebrafish by regulating the expression of genes related to skeletal development. Our results indicate that sox11a^m/m mutant zebrafish offered a potential model system to help with the search for pathogenic mechanisms of human Coffin-Siris syndrome.

6 illus, 25 ref

041521   ATIK N, TALITHA D, DWIWINA R G, BERBUDI A, SARI N M, DEWI P I C, RAHMANI N R (Biomedical Sciences Dep, Padjadjaran Univ, Bandung, West Java, Indonesia, Email: n.atik@unpad.ac.id) : Correlation between academic evaluation scores within the undergraduate medical education: A cross-sectional study. Indian J Pharm Edu Res 2020, 54(3), 565-71.

There are several evaluations to assess the medical students finishing the courses. Examinations could be multiple-choice questions that tend to evaluate the memorization rather than analytical ability. Another is oral examination tests that evaluate the ability in analysing the specific cases. However, though the oral examination assesses by two examiners, still the subjectivity of the examiner cannot be ignored. This study aims to provide insight on the correlation between test scores of multiple choice question and oral examination in the medical undergraduate program. The cross sectional study included test scores from first to fourth year medical undergraduate students at Faculty of Medicine, Padjadjaran University. Scores were collected from the Multiple Disciplinary Examination (MDE), a summative multiple choice exam; and Student’s Objective Oral Case Analysis (SOOCA), a summative case analysis oral exam. Test scores analysed were initial scores prior to remedial. Spearman’s correlation test was used to analyse correlation between scores. A total of 1031 corresponding sets of MDE and SOOCA test scores were collected. Spearman test showed a positive and significant correlation between MDE and SOOCA scores of all study courses throughout the year. The strongest correlation was found in the sixth semester within the Gastrointestinal System and Genitourinary System Block (rs=0.571 (p< 0.01). The weakest correlation was found in the first semester within the Fundamental Basic Science II Block (rs=0.197 (p< 0.01)). There is a positive correlation between test scores from multiple-choice question examinations and oral examination scores. Both tests complement each other in evaluating medical undergraduate education.

2 illus, 2 tables, 17 ref