In Silico Analysis of Differentially Expressed Genes in Colorectal Carcinoma

Background: Colorectal carcinoma (CRC) is a primary cause of morbidity and mortality worldwide. Resistance to therapy contributes to poor patient prognosis. The aim of our study is to identify the key proteins and interaction networks implicated in CRC which may serve as possible therapeutic targets and help in overcoming therapy resistance.Methods: The microarray dataset of 58 cases and 62 controls was used to identify Differentially Expressed Genes (DEGs).After constructing protein-protein interaction networks , Cytoscape analysis was done to identify the hub proteins. Based on sub graph centrality, between-ness and degree (≥10), hub proteins were selected for further literature search and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.Results: A total of 85 up-regulated genes and 95 down-regulated genes of CRC patients were selected based on criteria of P>0.05 and fold change>2.0. The PPI analysis revealed STAT3, HNRNPA2B1, RBM8A, RBM25, ATM, HIST1H2BK, SRSF5 and HNRNPDLas hub proteins. On the basis of criteria set for cytoscape analysis, STAT3 and HNRNPA2B1 were identified as key hub proteins. KEGG pathway analysis revealed vital role of STAT3 in carcinogenesis.Conclusion: In addition of HNRNPA2B1 activation by STAT3, cross talk of STAT3 with other oncogenic signaling pathways signifies its role in colorectal carcinogenesis. Our study highlights thatSTAT3may be a possible therapeutic target which may help in overcoming the dilemma of resistance to drug treatment in advanced cases.Keywords: STAT3, drug resistance, targeted therapy, bioinformatics    

Celiac Disease and its Association with Socio-Demographic Parameters in Patients with Diabetes Mellitus Type-1

Objective: To determine the frequency of Celiac disease in patients with Type-1 Diabetes Mellitus (DM) and its association with socio-demographic parameters. Study Design: Cross-sectional study. Place and Duration: Medical Departments of Dr Ruth K. M. Pfau, Civil Hospital, Karachi Pakistan, from Apr to Sep 2019. Methodology: Patients diagnosed with type-1 DM were enrolled in the study. Patients underwent blood testing for Celiac Serology. IgA level greater than 10U/m1 was taken as positive for celiac disease. If IgA levels were low, then Anti-tTG IgG was tested. Results: One hundred seventy-seven patients diagnosed with type-1 diabetes mellitus were included in this study. The average age of patients was 36.39±6.81 years. There were 109(61.58%) males and 68(38.2%) females. The frequency of celiac disease in patients with type-1 DM was observed at 8.47%. The frequency of celiac disease was not statistically significant among different age groups (p=0.644), gender and disease duration (p>0.05). However, celiac disease was more frequent in patients with a family history, but it was not statistically significant (25% vs 7.7%; p=0.086). Conclusion: This study showed a higher frequency of celiac disease in patients with T1DM than in the general population in our country, and the data lend support to recommend regular screening for Celiac disease in all patients with Type-1 DM

A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)

<p>Abstract</p> <p>Background</p> <p>Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.</p> <p>Methods</p> <p>We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].</p> <p>Results</p> <p>Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.</p> <p>Conclusions</p> <p>The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.</p

Life-time tobacco consumption and oral cancer among citizens of Karachi: one of the world’s highest reported incidence areas for oral squamous cell carcinoma

Objective: To analyze dose-response relationship between the common risk factor of tobacco consumption and oral lesions like squamous cell carcinoma and pre-cancerous lesions. Methods: The study comprises of 150 histologically confirmed OSCC cases, 100 cases of clinically diagnosed oral pre-cancerous lesions and 108 habit-matched controls. Life-time tobacco-exposures were calculated as tobacco indices, i.e., chewing index and smoking index, for comparison between cases and controls. Results: The age of OSCC cases ranged from 20-78 years and pre-cancerous cases from 16-78 years, mean 47.1 ± 12.22 and 34.17 ± 13.78, respectively. Of all OSCC patients 125 (83.33%) and 96 (96%) of PCL patients gave a positive history of tobacco use. 68.8% of all 250 cases were exclusive tobacco chewers which turned out to be the most prevalent tobacco habit. Exclusive smoking was seen in 11 (4.4%) cases, 38 (15.2%) patients had a mixed tobacco habit of chewing plus smoking while 29 (11.6%) were tobacco free. Tobacco indices (median values) in exclusive chewer’s category were found to be lower in cancers (150) as compared to matched controls (210) but were nearer to pre-cancers (144). In pre-cancers we found lower median values of tobacco indices for all chewers, exclusive chewers and all-smokers categories in comparison to controls, i.e., 144/200, 144/210, 10/21 respectively.  Conclusion: Life-time tobacco exposure indices were either comparable or lower in studied patients as compared to controls pointing towards the role of other etiological factors in addition to tobacco for malignant transformation of oral mucosa. Continuous..

Inflammatory markers and COVID-19 disease progression

Background: The COVID-19 pandemic has resulted in a global humanitarian crisis. Despite ongoing research, transmission risks and many disease characteristics remained unclear. Most patients have displayed elevated levels of certain inflammatory markers, which we sought to investigate further in relation to disease severity. The aim of this study was to examine the correlation between inflammatory markers and the severity of COVID-19 among patients. Methods: We conducted a cross-sectional study from April to September 2020, involving 143 COVID-19 PCR-positive patients from Ziauddin Hospital. Electronic patient records provided data on demographics, clinical status, and laboratory results. Results: The majority of PCR-positive patients were elderly males with comorbidities such as diabetes and hypertension. Almost all patients exhibited increased levels of various inflammatory markers, with procalcitonin (97.2%) being the most common. Statistically significant differences were observed in the levels of TLC (p = 0.005), CRP (p = 0.001), LDH (p = 0.001), Ferritin (p = 0.001), D-dimer (p = 0.001), and procalcitonin (p = 0.028), in relation to COVID-19 severity. Conclusions: The data suggest a significant association between levels of inflammatory markers and COVID-19 severity. All markers, except procalcitonin, demonstrated a significant correlation with disease severity. These results could enhance our understanding of COVID-19 pathogenesis and help predict and manage severe cases

Additional file 2 of Angiotensin-converting enzyme 2 (ACE2) polymorphisms and susceptibility of severe SARS-CoV-2 in a subset of Pakistani population

Supplementary Table 1: ACE2 haplotypes, haplotype frequency and permutation test for all haplotypes organized in block 1 and block

Additional file 1 of Angiotensin-converting enzyme 2 (ACE2) polymorphisms and susceptibility of severe SARS-CoV-2 in a subset of Pakistani population

Supplementary Figure: 1 (a): Gel doc for ACE2 demonstrating the bands for PCR products

Synthesis of metal organic framework (MOF-5) embedded cryogel composite and its application for the extraction and determination of cholesterol from milk samples

Metal-organic frameworks (MOFs)/coordination polymers (CPs) are a new class of hybrid inorganic/organic porous material. Recently MOFs have attracted much attention due to their large surface area, tunable pore structure, and high thermal stability. MOF-5 is composed of zinc salt and 1,4 benzene dicarboxylic linker. In the current study, MOF-5/cryogel composite was applied to extract cholesterol selectively from milk samples. This extraction process was used to clean-up milk samples with MOF-5/cryogel composite followed by determination of cholesterol in milk using UV-Vis spectrophotometric technique. The parameters such as concentration of cholesterol, volume of cholesterol solution, adsorbent amount, adsorption and desorption time were studied to obtain good extraction of cholesterol. The amount of cholesterol adsorbed and desorbed was 84 and 80%, respectively, from milk samples using MOF-5 composite cryogel. The developed method was validated in terms of linearity, accuracy, precision, limit of detection, and quantification. The response was linear in the range of 5-200 µg/mL with a coefficient of determination (r2) of 0.990. Detection limit (0.15 µg/mL) and quantification (0.45 µg/mL) were obtained

Sex Determination Using Hand Morphometric Parameters in Individuals from Pakistani Descent

Objective: To identify the presence or absence of sexual dimorphism using hand measurements alone in people from Pakistan. Moreover, to identify the variable that can be better at predicting sex among the rest of hand measurements. Methods: The research involved 122 male and 182 female participants, ranging in age from 18 to 60 years, without any hand deformities or missing fingers. Each participant underwent a set of hand measurements, including hand breadth, which was measured in a linear line from the lateral-most end on the head of the second metacarpal to the medial end on the head of the fifth metacarpal in centimeters. Additionally, hand length measured to be as the direct distance from the midpoint of the distal wrist crease to the top most point of the middle finger in centimeters. Logistic regression was used to analyze six hand measurements on the likelihood of prediction of the male or female gender Results: The logistic regression model showed statistical significance, ÷2 = 19.502, p < .012. The model explained 58.0% (Nagelkerke R2) of the variance in gender and accurately identified 84.2% of cases. A statistically substantial disparity was evident in hand measurements and hand indices across genders. (P-value=.0001). Conclusion: Our study reveals the presence of sexual dimorphism in hand morphometric parameters among the population of Pakistan. Hand measurements prove to be a reliable indicator for predicting gender in the majority of cases. Nevertheless, relying on a single hand measurement may not yield accurate gender predictions. Instead, a combination of various hand measurements can enhance the overall reliability of gender prediction