A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

Impact of Brain derived Neurotrophic factor gene polymorphism on its peripheral levels in schizophrenic patients.

Objectives: To determine serum levels of brain-derived neurotrophic factor and its polymorphism rs12291063 in schizophrenic patients. METHODS: The case-control study was conducted from January1, 2020, to May 15, 2021, at Dr Abdul Qadeer Khan Institute of Behavioural Sciences, Dow University of Health Sciences, Karachi, and comprised schizophrenia cases aged 14-60 years who were diagnosed using Diagnostic and Statistical Manual of Mental Disorders-V criteria, and healthy controls without any psychiatric illness. Positive and negative syndrome scale score was used to assess disease severity. The genomic deoxyribonucleic acid of the subjects was isolated from peripheral blood, followed by polymerase chain reaction, gel electrophoresis and sequencing of the amplicons. The sequences were analysed using MEGA X software for genotyping. Serum brain-derived neurotrophic factor levels were assessed using enzyme-linked immunosorbent assay. Data was analysed using SPSS 21. RESULTS: Of the 100 subjects, 50(50%) were cases; 36(72%) males and 14(28%) females (p<0.05) with mean age 34.34±10.32 years. There were 50(50%) controls; 32(64%) males and 18(36%) females (p=0.391) with mean age 30.886±8.88 years. Among the cases, the mean age at schizophrenia diagnosis was 25.14±9.54 years, and there was a significant association with positive family history for psychiatric disorders (p<0.05). Sequencing revealed no T>C substitution. Serum brain-derived neurotrophic factor levels were significantly higher in cases compared to controls (p<0.001). There was a weak negative correlation between brain-derived neurotrophic factor levels and positive and negative syndrome scale score (p<0.05). CONCLUSIONS: Higher brain-derived neurotrophic factor levels were found to be associated with schizophrenia, while no association of rs12291063 T>C was found with schizophrenia.

Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN.

Objectives: To investigate the anticancer potential of a novel synthetic derivative of a naturally occurring diterpenoid against glioblastoma. METHODS: The in vitro study was conducted at the Ojha Campus of Dow University of Health Sciences, Karachi, from February to December 2021, and comprised U87 cells. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the growth inhibitory effect of 16(R and S) - phenylamino-cleroda3, 13(14) Zdiene- 15, 16 olide and standard drug temozolomide against glioblastoma cells, and half-maximal inhibitory concentration was calculated. Microscopy and immunocytochemistry were used to investigate apoptotic morphology and active caspase-3 and B-cell lymphoma 2 (Bcl-2) expression. Quantitative real time polymerase chain reaction was used to investigate the expression of proliferation markers. Data was analysed using SPSS 21. RESULTS: Both the synthetic derivative and the standard drug significantly inhibited growth of U87 cells (p<0.001) with half-maximal inhibitory concentration of 19µM and 185µM, respectively. Apoptotic morphology and upregulation of active caspase-3 protein expression was observed in cells treated with half-maximal inhibitory concentration doses of both the synthetic derivative (p<0.05) and the standard drug (p<0.001), and Bcl-2 was downregulated in both the synthetic derivative (p<0.01) and the standard drug (p=0.05). However, no significant difference was observed in the expression of proliferation markers (p>0.05). CONCLUSIONS: The synthetic diterpene derivative PGEA-AN showed growth inhibitory actiity against glioblastoma.

Etiologies Associated With Elevated Liver Enzymes After Renal Transplant.

OBJECTIVES: One of the most important causes of morbidity and mortality in renal transplant recipients is liver disease. Liver dysfunction is shown in 7% to 67% of kidney transplant recipients. Liver insufficiency accounts for death in up to 28% of kidney transplant recipients. We stratified various etiological factors responsible for elevated liver enzymes in kidney transplant recipients. MATERIALS AND METHODS: We enrolled all patients who fulfilled inclusion criteria. The principal investigator obtained and recorded demographic and clinical information via a standardized form. We reviewed clinical records of kidney recipients with hepatotoxicity during the course of illness, and we analyzed data with SPSS statistical software (version 22). Descriptive statistics were used for continuous and categorical variables. RESULTS: All recipients of living related renal transplants from January 2015 to December 2016 were included in the study (n = 496). We excluded 64 patients with positive serology for hepatitis B or hepatitis C before transplant. Of the remaining 432 patients, 74 (17.1%) had deranged liver enzymes. Forty-one patients (55.4%) had deranged liver enzymes 3 to 4 years after transplant, whereas 23 patients (31.1%) had deranged liver enzymes 4 years after transplant. Liver parenchymal biopsy was performed in 17 patients (23%) to evaluate the etiology. The most common cause of deranged liver enzymes was sepsis, which was seen in 21 patients (28.4%), followed by viral hepatitis, ie, cytomegalovirus hepatitis in 7 (9.5%) and hepatitis C in 6 (8.1%) patients. Other causes included antituberculosis treatment-induced liver injury, autoimmune hepatitis, sinusoidal obstruction syndrome, and nonalcoholic steatohepatitis, observed in 4 patients each (5.4%). CONCLUSION: The most common cause of deranged liver enzymes in patients who received living related renal transplants in our population was sepsis, which can have a substantial effect on graft survival.

Recurrence Rate of Early Hepatitis C Virus Infection After Renal Transplantation Following Successful Treatment of Patients on Dialysis With Direct-Acting Antiviral Agents.

OBJECTIVES: Recurrence of hepatitis C virus after organ transplant has dreadful complications. An excellent response has been shown with direct-acting antiviral agents in transplant recipients. Although a sustained virological response is considered as the virological cure, it requires patients to be on dialysis for 3 months more before undergoing renal transplant, thus increasing the risk of hepatitis C virus reinfection and associated complications. We aimed to determine hepatitis C virus recurrence in renal transplant recipients who had achieved endof-treatment response before transplant. MATERIALS AND METHODS: Per our institutional dialysis protocol, patients who do not achieve rapid virological response are treated with 6 months of direct-acting antiviral agents. All patients who achieve end-of-treatment response are then referred for renal transplant. Our study included kidney transplant recipients who were treated with directacting antiviral agents and had a hepatitis C virus polymerase chain reaction test 3 months after renal transplant. We obtained demographic and clinical data of patients and used SPSS version 20.0 for statistical analyses. RESULTS: Our study included 48 transplant recipients; most were males (81.1%) with mean age of 28.7 ± 9.4 years. All patients received sofosbuvir, daclatasvir, and ribavirin combination before transplant. Most patients (70%) received treatment for 3 months. The polymerase chain reaction test for hepatitis C virus was conducted after a mean of 8.3 ± 3.3 months posttransplant. Laboratory parameters showed total bilirubin of 3.6 ± 17.5 mg/day, alanine aminotransferase of 51.5 ± 80.2 IU/L, and gammaglutamyltransferase of 133.9 ± 220 IU/L. Two recipients (4.2%) had posttransplant recurrence of hepatitis C virus infection. CONCLUSIONS: To our knowledge, this study is the first to document excellent response of direct-acting antivirals in renal transplant recipients who had been referred early for transplant. Thus, dialysis patients can undergo transplant after achieving end-oftreatment response.

Management of Tacrolimus-Induced Toxicity With Normal Serum Levels After Liver Transplant.

Drug-induced liver injury after liver transplant occurs in 1.7% of patients. Tacrolimus is an effective immunosuppressant that is used to treat acute rejection. Although rare, it can cause toxicity, which is demonstrated by cholestatic liver injury. Here, we present a case of a young male patient who was diagnosed with Wilson disease, had penicillaminechelating therapy, and underwent living related liver transplant. Within 1 month posttransplant, he developed deranged, predominantly cholestatic pattern liver function tests. Laboratory parameters showed total bilirubin of 1.12 mg/ dL, alanine aminotransferase of 553 IU/L, gammaglutamyltransferase of 624 IU/L, and tacrolimus level of 10.2 ng/mL. After thorough evaluation, a liver biopsy was performed. Liver biopsy showed hepatocellular necrosis with centrilobular cholestasis without any evidence of graft rejection. However, with normal level of tacrolimus, the biopsy was suggestive of drug-induced liver injury. Thus, tacrolimus dose was reduced, resulting in improved liver function tests and patient discharge from the hospital. Tacrolimus is an effective immunosuppressant after liver transplant and has the ability to treat early acute rejection. The patient's liver biopsy showed hepatocellular necrosis with centrilobular cholestasis without any evidence of graft rejection. Cholestatic liver injury after tacrolimus usually resolves after dose reduction or by switching to another agent. With demonstrated tacrolimus-induced toxicity in liver transplant recipients, despite normal serum levels, transplant physicians should keep high index of suspicion regarding toxicity in the posttransplant setting.

Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population.

Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson's correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.

1st International Conference on Biomedical Sciences, Dow University of Health Sciences, Karachi Pakistan.

Institute of Biomedical Sciences (IBMS) at Dow University of Health Sciences (DUHS), organised a two day's conference on Biomedical Sciences. IBMS being the part of one of the largest public sector health universities of Pakistan, is now transforming the research trends to be effectively translated at the community level. Currently with a strong PhD faculty line in basic and clinical sciences, DUHS has a significant contribution in research output of the country. The scientific data however represents a small population per scientific study and the generalization of results may not be inferred. It must be extended through translational research for effectiveness. The conference was planned with a theme to bridge the gap between basic and translational research. The two day's conference conducted in second week of March 2023 at Dow International Medical College Ojha Campus DUHS was able to attract more than 300 participants. The scientific sessions encompassed a vast variety of health issues and their proposed solutions including neurosciences, virtual biopsies, metabolomics, medical writings and incorporation of engineering and artificial intelligence to facilitate detection and prognosis of disease. The conference was able to conclude that the multidisciplinary research studies with collaboration of two or more institutes/organizations are the need of time. Young researchers need an effective platform to showcase their research and make collaborations. Moreover, the incorporation of artificial intelligence would enhance patient care within health systems.

miR-3174 Is a New Tumor Suppressor MicroRNA That Inhibits Several Tumor-Promoting Genes in Glioblastoma.

microRNAs (miRNAs) play an important role in the pathology of glioblastoma (GBM), which is the most malignant and most common primary malignant brain tumor. miRNAs can target multiple genes simultaneously and are considered as potential therapeutic agents or targets. This study aimed to determine the role of miR-3174 in the pathobiology of GBM using both in vitro and in vivo approaches. This is the first study deciphering the role of miR-3174 in GBM. We studied the expression of miR-3174 and found it to be downregulated in a panel of GBM cell lines, GSCs and tissues relative to astrocytes and normal brain tissue. This finding led us to hypothesize that miR-3174 has a tumor-suppressive role in GBM. Exogenous expression of miR-3174 inhibited GBM cell growth and invasion, and hampered the neurosphere formation ability of GSCs. miR-3174 downregulated the expression of multiple tumor-promoting genes including CD44, MDM2, RHOA, PLAU and CDK6. Further, overexpression of miR-3174 reduced tumor volume in nude mice with intracranial xenografts. Immuno-histochemical study of brain sections with intracranial tumor xenografts revealed the pro-apoptotic and anti-proliferative activity of miR-3174. In conclusion, we demonstrated that miR-3174 has a tumor-suppressive role in GBM and could be exploited for therapeutic purposes.

Hepatic manifestations of coronavirus disease 2019 infection: Clinical and laboratory perspective.

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has become a global challenge of unprecedented nature since December 2019. Although most patients with COVID-19 exhibit mild clinical manifestations and upper respiratory tract involvement, in approximately 5%-10% of patients, the disease is severe and involves multiple organs, leading to multi-organ dysfunction and failure. The liver and gastrointestinal tract are also frequently involved in COVID-19. In the context of liver involvement in patients with COVID-19, many key aspects need to be addressed in both native and transplanted organs. This review focuses on the clinical presentations and laboratory abnormalities of liver function tests in patients with COVID-19 with no prior liver disease, patients with pre-existing liver diseases and liver transplant recipients. A brief overview of the history of COVID-19 and etiopathogenesis of the liver injury will also be described as a prelude to better understanding the above aspects.

A Tertiary Care Center's Experience with Clinicopathological Characteristics of Gallbladder Carcinoma in Our Population.

Introduction: Gallbladder cancer (GBC) is the most common malignant biliary tract tumor with the shortest survival from the time of diagnosis. This poor prognosis is due to the destructive biologic behavior of GBC, lack of sensitive screening tests for early detection, and vague nature of first presentation. Here in this study, we will evaluate the baseline characteristics of the patients presenting with gallbladder carcinoma in our population. Materials and methods: This retrospective study was conducted in the Department of Gastroenterology at Sindh Institute of Urology and Transplantation (SIUT), Karachi. Patient data were compiled and composed from the in-patient health records, radiology, and operational records. Those patients with suspicion of GBC, but negative at histology, or patients having inconclusive radiologic findings, were excluded. Baseline characteristics were recorded. Results were presented as means ± SD for quantitative data or as numbers with percentages for qualitative data. Continuous variables were analyzed using the Student's t-test, while categorical variables were analyzed using the Chi-square test. A p-value of <0.05 was considered statistically significant. Results: A total of 162 patients were included in our study. Among them, 101 (62.3%) were females. Hypertension was the most common comorbid illness noted in 29 (17.9%) patients while 91 (56.2%) patients had no concurrent comorbidities. Most common risk factor for carcinoma of gallbladder was gallstones seen in 106 (65.1%) patients. The most common presenting complaint was combination of obstructive jaundice, weight loss with right hypochondrial pain seen in 66 (40.7%) patients. On CT abdomen, direct liver infiltration without lymphovascular invasion was noted in 77 (47.5%) patients followed by liver infiltration along with lymphovascular invasion in 26 (16%) patients and distant metastasis in 24 (14.8%) patients. On gallbladder (GB) mass biopsy, 58 (35.8%) patients had well-differentiated, 46 (28.4%) had moderately differentiated, while 33 (20.4%) had poorly differentiated adenocarcinoma. Of 162 patients, 103 (63.6%) patients underwent endoscopic retrograde cholangiopancreatography (ERCP). The most common finding on ERCP was proximal common bile duct (CBD) stricture with intrahepatic biliary system dilatation which was noted in 95 (58.6%) patients. Percutaneous transhepatic cholangiography (PTC) was performed only in 9 (5.6%) patients. Seventeen (10.5%) patients were managed by simple cholecystectomy, 39 (24.1%) patients underwent extended cholecystectomy, 14 (8.6%) patients underwent chemotherapy, while 102 (56.8%) patients were given palliative management. When followed for 1 year, 101 (62.3%) patients died within 6 months. Conclusion: The baseline characteristics, biopsy findings, modes of treatment, and rates of 1 year mortality were studied in patients with gallbladder carcinoma in our population. Advanced age, high white blood cell counts, and serum bilirubin at presentation with low lymphocyte count and presence of comorbid illnesses were the factors independently associated with increased mortality in patients with gallbladder carcinoma. However, further studies with large sample size and stratification with respect to age, gender, and different variables can be done in terms of mortality in patients with gallbladder carcinoma. How to cite this article: Akbar N, Yaseen T, Muhammad A, et al. A Tertiary Care Center's Experience with Clinicopathological Characteristics of Gallbladder Carcinoma in Our Population. Euroasian J Hepato-Gastroenterol 2022;12(1):35-39.

Role of "HinCh Score" as a Non-invasive Predictor of Post-endoscopic Retrograde Cholangiopancreatography Cholangitis.

Introduction: Post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) is associated with increased morbidity and mortality in patients ERCP. The aim of the present study was to analyze the predictors of PEC and to formulate a predictive model for early diagnosis and management. Materials and methods: It was a cross-sectional study that was carried out at the Sindh Institute of Urology and Transplantation from September 2019 to June 2021. All patients aged between 18 and 75 years and undergoing ERCP due to obstructive jaundice were included. Patients with altered biliary anatomy, history of hepatobiliary surgery, and concurrent sepsis were excluded. Endoscopic retrograde cholangiopancreatography intervention was performed by an expert gastroenterologist. Laboratory parameters (total leukocyte count, total bilirubin, alanine transaminase) and patient temperature were checked on admission, at 12 hours, 24 hours, and 36 hours after ERCP to document PEC. Results: A total of 349 patients were included in the study. Among them, 176 (50.4%) patients were males. Common bile duct (CBD) stricture was the most common indication of ERCP seen in 148 (42.4%) patients followed by CBD stone and cholangiocarcinoma in 108 (30.9%) and 48 (13.8%) patients, respectively. The most common presenting complaint was jaundice noted in 300 (86%) patients followed by right hypochondrial pain in 280 (80.2%) and weight loss in 194 (55.6%) patients, respectively. Post-ERCP cholangitis developed in 251 (71.9%) patients. On univariate analysis, age >50 years, female gender, right hypochondrial pain, fever, bilirubin >5 mg/dL on admission, CBD stricture on ERCP, TLC of >10,000 cells/L at 12 hours, 24 hours, and 36 hours post-ERCP and rise in ALT >50 IU 24 and 48 hours post-ERCP were significantly associated with PEC. While on multivariate analysis, female gender, bilirubin >5 mg/dL on admission, CBD stricture on ERCP, post-ERCP fever, and rise in TLC of >10000 cells/L at 24 hours post-ERCP were independently associated with PEC. HinCh score was formulated and was found to be significantly associated with the presence of cholangitis. Area under the receiver operating characteristics (AUROC) of HinCh score was 0.74 and at cutoff of ≥4, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HinCh were 81.67%, 59.18%, 83.67%, and 55.71%, respectively with a diagnostic accuracy of 75.36%. Conclusion: The performance of HinCh score in predicting PEC was accurate in 86% of the patients. However, further studies are needed to validate the score. How to cite this article: Ismail H, Yaseen RT, Danish M, et al. Role of "HinCh Score" as a Non-invasive Predictor of Post-endoscopic Retrograde Cholangiopancreatography Cholangitis. Euroasian J Hepato-Gastroenterol 2022;12(1):19-23.

Revolution in the diagnosis and management of hepatitis C virus infection in current era.

Chronic hepatitis C virus (HCV) infection is a major global public health problem, particularly in developing part of the world. Significant advances have been made in the early diagnosis and treatment of the disease. Its management has been particularly revolutionized during the past two decades. In this review, we summarize the major advances in the diagnostic and management armamentarium for chronic HCV infection. The focus of the present review is on the newer directly acting anti-viral agents, which have revolutionized the management of chronic HCV infection. Management of uncomplicated chronic HCV infection and of specific complications and special at-risk populations of patients will be covered in detail. Despite the advent and approval of highly effective and well tolerable oral agents, still many challenges remain, particularly the affordability, the equitable distribution and access to later drugs. The World Health Organization aims to eliminate viral hepatitis including HCV by 2030 since its poses a major public health threat. There is an urgent need to ensure uniform and early access to diagnostic and therapeutic facilities throughout the world if the later goal has to be realized.

Transcribed Ultraconserved Regions in Cancer.

Transcribed ultraconserved regions are putative lncRNA molecules that are transcribed from DNA that is 100% conserved in human, mouse, and rat genomes. This is notable, as lncRNAs are typically poorly conserved. TUCRs remain very understudied in many diseases, including cancer. In this review, we summarize the current literature on TUCRs in cancer with respect to expression deregulation, functional roles, mechanisms of action, and clinical perspectives.

Refactory Coeliac disease-a case series from Pakistan.

Coeliac disease or gluten intolerance is a frequent cause of chronic diarrhoea leading to malabsorptive symptoms. Refractory coeliac disease is a rare entity, which is not only harder to diagnose but managing it can be challenging. We hereby present three such cases.

Clinical Characteristics and Comparison of Different Prognostic Scores in Wilson's Disease.

Aim: Wilson's disease (WD) is a rare autosomal recessive disease, that can involve any organ of the body, the main ones being the liver and the brain. These patients can have varied presentations, ranging from having no symptoms to having neurological manifestations to features of chronic liver disease (CLD). Those patients that end up having CLD are prognosticated via the Child-Turcotte-Pugh (CTP) score and the Model for End-stage Liver Disease (MELD) score. However, two specific scores exist for prognostication in patients having WD, namely, the Nazar score and the Dhawan score. However, these are yet to be validated nor has their use been implemented in clinical practice. Materials and methods: Our study involved 65 patients with WD, comprising both the pediatric and the adult population. We aimed at evaluating the clinical manifestations the lab parameters and the management of these patients. Furthermore, we tried validating the Nazar and the Dhawan score and later compared them with the CTP and the MELD score, which are well-known prognostic tools in CLD. Results: Our patients were subdivided into the pediatric (more than 50%) and the adult group. The most common presenting complaint noted in both groups was abdominal distension. Values of the urine copper and serum ceruloplasmin did not defer between the pediatric and adult patients. Hepatic involvement is frequently seen in the pediatric age-group. Also, CTP class C was chiefly seen in pediatrics 17/33 (51.5%), while CTP class B was in adults 13/32 (40.6%). The mean Nazar score was 3 ± 3, while the mean Dhawan score was 5 ± 4. The main treatment offered for both groups was zinc along with penicillamine. Conclusion: Our study showed the Dhawan score was comparable to the CTP and the MELD score in terms of predicting the disease severity of WD in our patient population. How to cite this article: Majid Z, Abrar G, Laeeq SM, et al. Clinical Characteristics and Comparison of Different Prognostic Scores in Wilson's Disease. Euroasian J Hepato-Gastroenterol 2022;12(2):69-72.

The Use of Albumin-to-bilirubin Score in Predicting Variceal Bleed: A Pilot Study from Pakistan.

Variceal hemorrhage is a serious consequence of patients having chronic liver disease (CLD). Various scores exist that predict the outcome for non-variceal bleed. However, only a few scores evaluate patients with variceal bleed. We, in our study, evaluated 48 cirrhotics who presented with variceal gastrointestinal (GI) bleed over a period of 3 months. Majority of these were males and the most common etiology was hepatitis C infection. The main presenting complaints were hematemesis seen in 39.6% followed by hematemesis and melena in 31.25%. Most bleeding episodes were secured via banding in 62.5% followed by injection of histoacryl in 12.5%. Finally, Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), albumin-to-bilirubin (ALBI), and the ABC score were applied and none correlated with the presence of esophageal varices. However, the ALBI score did correlate with the presence of tachycardia in our study, a pertinent sign of upper GI bleed. How to cite this article: Majid Z, Khan SA, Akbar N, et al. The Use of Albumin-to-bilirubin Score in Predicting Variceal Bleed: A Pilot Study from Pakistan. Euroasian J Hepato-Gastroenterol 2022;12(2):77-80.

Opuntiol Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells by Upregulating Active Caspase 3 Expression.

BACKGROUND: Glioblastoma Multiforme (GBM) is a deadly tumor with poor prognosis. Resistance to apoptosis considered as an important factor in treatment failure. Therefore, identification of new compounds that facilitates apoptosis is crucial. Natural Anti-inflammatory compounds have emerged as potential anti-cancer agents and should be explored for their apoptotic activity against GBM. Therefore, the present study aims to evaluate growth inhibitory and apoptotic activity of a natural anti-inflammatory compound "Opuntiol" against GBM cell line U87. METHODS: MTT assay was performed to determine the effect of Temozolomide and Opuntiol on growth inhibition of U87 cell. While, TUNEL assay was used to assess their apoptotic activity. To further assess apoptosis, nuclear condensation and nuclear area factor (NAF) was evaluated through DAPI staining. Whereas, active caspase-3 protein expression determined using immunocytochemistry. RESULTS: Significant growth inhibition was observed in U87 cells treated with Temozolomide (IC50 380 µM) and Opuntiol (IC50 357 µM). Temozolomide (p<0.001) and Opuntiol (p<0.001) significantly improved rate of apoptosis when compared to control group. A significant decrease in NAF was also observed in Temozolomide (p < 0.05) and Opuntiol (p < 0.05) treated cells. There was a significant increase in active caspase-3 expression when observed in Temozolomide (p<0.001) and Opuntiol (p<0.05) treated groups as compared to control. CONCLUSION: In conclusion our findings suggests, Opuntiol repress cell viability and possess strong apoptotic activity against GBM cell line U-87. However, further mechanistic studies will be required to confirm whether it can be develop as a potential drug against GBM.