Introduction Sorafenib remains the only approved treatment for advanced hepatocellular carcinoma (HCC), yet its clinical use is hindered by toxicity and the emergence of drug resistance. Sorafenib's anticancer effects are largely attributed to its inhibition of multiple kinases, including c-Raf, a key player in the Ras-Raf-MEK-ERK signalling cascade that promotes cell growth and survival. Given the critical role of c-Raf in tumor progression, targeting this kinase offers a promising strategy for improving therapeutic outcomes. Developing new analogues with stronger c-Raf inhibition, better pharmacokinetics, and reduced side effects could help address the current limitations of sorafenib. Objectives This study aimed to design novel sorafenib analogues with enhanced binding affinity and favourable pharmacokinetic profiles, specifically targeting the c-Raf kinase to increase therapeutic efficacy against HCC. By using a fragment replacement approach combined with computational methods, the goal was to identify candidates capable of forming stronger, more stable interactions with c-Raf, potentially overcoming resistance linked to sorafenib treatment. Methods A total of 84 sorafenib analogues (A1-A84) were generated by modifying key functional groups, including the 2-picolinamide and substituted phenyl moieties known to influence kinase binding and anticancer activity. These analogues were evaluated through chemoinformatics and pharmacokinetic screening to assess their drug-likeness and safety. Molecular docking was performed to estimate their binding affinity toward c-Raf. Six top-performing analogues (A2, A6, A9, A20, A22, A63) were selected for further analysis. To evaluate their dynamic behaviour, 100 ns all-atom molecular dynamics simulations were conducted, followed by MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) calculations to determine binding free energies. Principal component analysis (PCA) was carried out to explore key motion patterns within the protein-ligand complexes. Results Molecular docking showed that the selected analogues exhibited stronger binding affinities (-11.6 to -10.9 kcal/mol) compared to sorafenib (-9.3 kcal/mol) and regorafenib (-9.5 kcal/mol). Molecular dynamics simulations substantiated the docking results. MM-PBSA results revealed that at 100 ns, the binding free energy for the c-Raf-sorafenib complex was 86.751 kJ/mol, while the c-Raf complexes with A2, A6, A9, A20, A22, and A63 demonstrated significantly lower free energies of -129.114, -135.637, -136.242, -127.178, -94.25, and -123.176 kJ/mol, respectively, indicating stronger and more stable binding. PCA further confirmed the stability and favourable dynamic profiles of these analogues trajectory with c-Raf. Discussion The improved binding affinities and lower free energies of the top analogues indicate that specific structural changes to sorafenib can enhance its effectiveness against c-Raf. Molecular dynamics and MM-PBSA results suggest the stability and strength of these interactions, particularly for A2, A6, and A9. Conclusion This study identified six promising sorafenib analogues with improved binding affinity, favourable pharmacokinetic characteristics, and stable interactions with c-Raf. By focusing on c-Raf inhibition, the combined use of computational modelling, molecular simulations and mmPBSA analysis provided valuable insights for drug design. Among the candidates, A2, A6, and A9 emerged as promising drug candidates for further development, supporting the potential of targeting c-Raf to enhance therapeutic strategies against hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a leading cause of death worldwide, is primarily caused by uncontrolled cellular proliferation, invasion and metastasis leading to tumor development in the liver. miR-195 regulates G1 to S phase transition in the cell cycle by targeting CDK6. In the current study, expression of miR-195 was significantly reduced while that of CDK6 was upregulated in HCC patients. The results of expression analysis were supported by the Pearson correlation coefficient indicating a moderate negative (r = -0.459, p = 0.02) relation between miR-195 and CDK6. However, the association of miR-195 and CDK6 with age and sex was not statistically significant. The predicted secondary and tertiary structures of miR-195 showed the presence of loops, stems, and flanking regions. Further, in silico analysis identified potential amino acid residues in CDK6, CDK4 and Cyclin D1 proteins interacting with the miR-195. We designed a mimic RNA of miR-195 by mutagenesis at 4 points. The mimic RNA_3 of miR-195 presented a well-defined stable structure showing strong binding interactions with CDK4 and Cyclin D1 and comparable interactions with CDK6. In conclusion, our study has demonstrated the potential of using miR-195 mimic RNA as a therapeutic strategy to target the CDK6 gene in HCC with reduced miR-195 expression.

Chronic obstructive pulmonary disease (COPD) is exacerbated by inflammatory reactions triggered by cigarette smoke, air pollutants, dusts, and chemical products. In order to have a better understanding of the disease, its effect on the function of lung specific genes formaldehyde induced COPD mice model were developed. Mice were administered different doses of formaldehyde intraperitoneally, and expression of SFTPD and GSTα4 genes were determined. Some in silico approaches were also adopted to evaluate the diagnostic significance of the SFTPD and GSTα4 genes. Histopathological examination showed significant lung tissue damage indicative of COPD pathology in formaldehyde administered mice groups. The expression of SFTPD and GSTα4 genes were significantly downregulated in the lung tissues of FA administered mice in a dose dependent manner. ADMET analysis indicated that formaldehyde has favorable water solubility and high intestinal absorption, but is linked to skin sensitization and hepatotoxicity. Docking results depicted that formaldehyde’s interaction with SFTPD and GSTα4 may lead to decreased expression of these genes and may impair lung function. Overall, the study has provided an insight into the toxic and deteriorating effects of formaldehyde on the respiratory system and underscores the promise of SFTPD and GSTα4 as diagnostic and prognostic biomarkers for COPD.

Hepatocellular carcinoma (HCC), commonly linked to chronic Hepatitis C virus (HCV) infection, remains a significant global health challenge. One promising treatment approach involves targeting the internal ribosome entry site (IRES) located in the highly conserved 5 ' untranslated region of the HCV genome. The JIIIabc domain of the IRES is particularly important because of its role in recruiting the ribosome and initiating translation. In this study, a drug repurposing strategy was used to identify small-molecule inhibitors that could effectively bind to and stabilize this RNA region. The crystal structure of HCV-IRES (PDB ID: 6U8K) was prepared using UCSF Chimera, and its secondary and tertiary structures were modeled with mfold, trRosettaRNA and RNAComposer. The RNA-binding pocket was identified using DogSite3. A library of 435 clinically trialed kinase inhibitors from the PKIDB database was processed with Open Babel and screened via molecular docking with AutoDock Vina. Rocbrutinib, Fenebrutinib and Bemcentinib emerged as top candidates based on binding affinity. These were further assessed through 500 ns molecular dynamics simulations in GROMACS. Rocbrutinib demonstrated strong and stable interaction with the IRES, maintaining a compact structure and consistent root mean square deviation (RMSD) values, while Bemcentinib showed noticeable instability. Overall, Rocbrutinib exhibited the most favorable binding behavior, indicating its potential as a repurposed therapeutic agent targeting HCV-IRES. These promising results provide a solid foundation for further laboratory studies to evaluate its effectiveness in treating HCV-related HCC.

Rheumatoid arthritis (RA), a chronic autoimmune condition that causes joint inflammation due to altered genetic expression in synovial tissue, affects 1

Introduction: Tuberculosis (TB) is a chronic infectious disease that continues to cause significant morbidity and mortality in developing nations. The emergence of Drug Resistant Tuberculosis (DR-TB) has further aggravated the problem. The treatment of DR-TB is challenging due to poor compliance, stemming from drug toxicity and the long duration of treatment. Bedaquiline (BDQ), a novel drug, has shown promising results in terms of safety and efficacy for the treatment of Multidrug Resistant TB (MDR-TB). Aim: To evaluate the safety and efficacy of BDQ in patients with DR-TB. Materials and Methods: This was a prospective, observational, hospital-based study carried out in the Department of Respiratory Medicine at JNMC, Aligarh, Uttar Pradesh, India, over a period of two years from December 2020 to November 2022. A total of 303 patients were enrolled. BDQ treatment was initiated after satisfying the inclusion criteria and patients were monitored for Adverse Events (AE). The study evaluated outcomes in terms of sputum conversion and clinical improvement. A follow-up was conducted for six months after the completion of therapy. Data entry was performed on Microsoft Excel and the final analysis was conducted thereafter. Results: Out of 303 patients, successful outcomes with BDQ were observed in 272 (89.77%) patients who were cured. Sixteen patients died (5.28%), 10 (3.30%) cases were lost to follow-up and in 5 (1.65%) patients, BDQ was discontinued due to adverse effects. Clinical improvement, in terms of an increase in body weight, improvement in symptoms and radiological improvement, was observed in 265 (97.43%) patients. Conclusion: The study concludes that BDQ demonstrates promising safety and efficacy, establishing itself as a valuable option for the treatment of DR-TB.

Parkinson’s disease (PD) is a progressive neurological disorder with an increasing prevalence in aging populations. Identifying effective therapeutic targets and treatments remains a critical challenge. This study aimed to discover potential therapeutic targets and design novel compounds for PD treatment. Gene expression analysis was conducted using diverse datasets, including microarray, mRNA sequencing, and miRNA sequencing. While no common genes were identified across all datasets, the RNA-seq dataset GSE-135036 was prioritized. The investigation focused on downregulated miRNAs targeting upregulated mRNAs, revealing that hsa-mir-5585 regulates Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) within the Shigellosis pathway. Given RIPK1’s role in cell death and inflammation, it emerged as a promising therapeutic target for PD. To identify RIPK1 inhibitors, 67 compounds were screened via molecular docking, with CHEMBL-3109201 exhibiting the highest binding affinity. A structurally similar compound, CHEMBL-76328382, also demonstrated strong interactions. A fragment-based drug design approach generated two novel compounds, BI-1215 and BI-146, which, along with RIPK1-IN-4 and CHEMBL-70909876, were shortlisted based on docking scores and ADME profiles. Molecular dynamics simulations confirmed the stability of CHEMBL-70909876 and BI-1215, with RMSD fluctuations between 0.005 and 0.2 nm. MM-PBSA analysis further validated their superior thermodynamic stability and binding affinity compared to other candidates. This study offers novel insights into PD pathogenesis and potential therapeutic interventions, marking a significant step toward effective treatment strategies for this debilitating disorder.

B and T-lymphoid cancers usually originate from lymphoid progenitor cells. T-cell ALL, a subtype of acute lymphoblastic leukemia (ALL), arises due to unlimited and abnormal growth of blast cells. KPT-330, also known as Selinexor, prevents the transport of mRNAs and proteins from the nucleus to the cytoplasm by inhibiting the XPO1 transporter protein. The study aims to explore the NOTCH1 gene as a novel therapeutic target of KPT-330 in T-cell ALL by targeting the XPO1 protein. mRNA expression of the NOTCH1 gene was significantly elevated in T-cell ALL patients. The IC50 value of KPT330 for the Jurkat cells was determined by cell viability assay. The effect of KPT-330 on NOTCH1 gene expression in Jurkat cells was evaluated after 24, 48, and 72 h intervals. KPT-330 significantly downregulated the NOTCH1 gene expression at all time points in a dose-dependent manner. The molecular docking results revealed a binding affinity of -8.8 kcal/mol and identified GLU-140, LEU-141, and SER-144 as the potential amino acids of XPO1 forming a hydrogen bond with KPT-330. In silico analysis suggested the interaction of KPT-330 with the RNA-based NES_1 (UGUAUUAUU), NES_2 (UGUAUUUUU), and NES_3 (UUGUA) motifs in the 3 ' UTR of NOTCH1 mRNA resulting in NOTCH1 inhibition. Based on the results of in vitro and in silico studies, it was suggested that KPT-330 could be an ideal candidate drug for treating T-cell ALL patients with NOTCH1 overexpression.

Background: Alzheimer’s disease (AD) patients often display not only cognitive impairment but also cardiac malfunction, but the underlying factors remain elusive. Phosphorylation of Ser14 of RPN6 (p-S14-RPN6) is required for cAMP/protein kinase A (PKA) to activate 26S proteasomes. Proteasome priming is implicated in the protection by cAMP-PKA augmentation against AD, but this remains to be established. Hence, we conducted this study to address these critical gaps. Methods: The Rpn6 S14A knock-in mice recently created for genetic blockade of p-S14-Rpn6 were crossbred with the PS19 tauopathy model (Jackson Lab Stock # 008169). Littermate wild type (WT), PS19, and PS19::S14A mice were compared. Cardiac function was evaluated with echocardiography (Echo). Hippocampal and myocardial tissues were used for western blot analyses (WB) and histopathology. Results: Increases in hippocampal insoluble tau proteins and in total and K48-linked ubiquitin conjugates were markedly greater in PS19::S14A mice than PS19 and WT mice. WBs for PSD95, synaptotagmin, Neu N, GFAP, and IBA1 revealed exacerbated synaptic loss, neuronal loss, gliosis, and microglial activation in the hippocampus of PS19::S14A mice in comparison to PS19 and WT mice. A more significant decline in cognitive function indicated by object recognition index was found in PS19::S14A mice vs. PS19 mice at 6 months. More interestingly, as compared to PS19 and WT littermates, PS19::S14A mice showed greater increases in myocardial tau proteins, ubiquitin conjugates, and cleaved caspase 3 and displayed more cardiac fibrosis, as reflected by increased mRNA expression of collagen 1 and picrosirius red staining. Echo revealed that PS19::S14A had significantly reduced fractional shortening, ejection fraction, stroke volume, and cardiac output at 9 months. Conclusions: The findings of this study demonstrate that genetic blockade of p-S14-RPN6 exacerbates tauopathy pathology in both the brain and heart. This is the first to have established the role of p-S14-RPN6 and, by extension, the significance of PKA-mediated proteasome activation in AD/tauopathy. Proteasome activation via augmentation of cAMP/PKA signaling should be explored for the alleviation of AD-associated brain and cardiac pathologies.

ALL (acute lymphoblastic leukemia) is a type of hematological malignancy that involves developmental and differentiation arrest at the lymphoblast stage. BLACE, a gene specifically expressed in B-cell acute lymphoblastic leukemia shows little or no expression in mature B-lymphocytes. The current pilot study involves transcriptional analysis of BLACE in B-cell ALL patients. Expression of BLACE was high in both pediatric and adult ALL patients. Promoter analysis of the BLACE gene showed the presence of CAAT and TATA box promoters and G-rich sequences with a potential to form G-quadruplexes. Due to identification of TAL1 transcription factor binding sites within the BLACE promoter region, expression of TAL1 gene was measured and found to correlate with the BLACE expression. The presence of an overlapping G-rich sequence and TAL1 binding site at -1291 bps within BLACE promoter indicated a new target site for controlling BLACE expression. The docking studies performed between BLACE-TAL1 protein showed a binding score of -208.68 kcal/mol and identified 21 BLACE nucleotide TAL1 residues interacting at the docking interface. Together, our findings suggested that BLACE gene specifically expressed in B-cell ALL could serve as a new therapeutic target. Further investigations are required to get a comprehensive understanding of the BLACE gene mechanism.

Background: Jarcho Levin syndrome is a rare genetic disorder characterized by spine abnormalities and the absence of ribs. It is associated with various congenital malformations and carries significant morbidity and mortality. The simultaneous presentation of this syndrome with neural tube defects is seldom encountered. Case Presentation: We report a case of a 2-day-old male who presented with a lesion on his back since birth. Clinical and radiological examinations revealed thoracolumbar meningomyelocele with the absence of upper ribs on the right side and a patent foramen ovale. Subsequently, the patient underwent surgery for meningomyelocele, while the rib anomalies were managed conservatively. Conclusion: Jarcho Levin syndrome is a rare disorder, and its association with meningomyelocele is extremely uncommon. It should be considered in the evaluation of a patient with a neural tube defect and respiratory distress.

Ineffectiveness of conventional antibiotics due to antimicrobial resistance and microbial adaptations has led to the exploration of alternative or complementary therapeutics. In the present study, surface engineered nano systems (SENS) were developed by conjugation of chitosan with rhamnolipids (RL) through amide linkage. Subsequently, FTIR and NMR analyses affirmed covalent immobilization of RL. SENS exhibited an increase in the particle size and reduction in zeta potential as compared to chitosan nanosystems (CNS). In parallel, first-line antibiotic (ciprofloxacin) was encapsulated in SENS and CNS for augmenting their antimicrobial potential against drug-resistant Salmonella enterica subsp. enterica serotype Typhi. Drug entrapment efficiency for AB-SENS (64 +/- 2 %) was higher than AB-CNS. Furthermore, bacterial growth kinetics assay along with colony forming unit (CFU) assay revealed that AB-SENS inhibited the growth of Salmonella sp. even at 1/2 MIC with restoration of the antibiotic activity. Due to enhanced biofilm penetration ability, the diffusion of entrapped drug from AB-SENS resulted in an effective biofilm disruption to control drug-resistant Salmonella sp. Release kinetics study demonstrated a pH dependent drug release from AB-SENS in simulated gastric fluid (14.2 +/- 2 %) and simulated intestinal fluid (28.4 +/- 3 %). Hence, our findings suggest that void or drug-loaded SENS can be a versatile synergistic tool to revive the conventional antibiotics for improved treatment outcomes against resistant pathogens.

Hepatitis C virus is a single-stranded RNA based virus which can cause chronic HCV and hepatocellular carcinoma. HCV genotype 3a has relatively higher rate of fibrosis progression, prevalence of steatosis and incidence of HCC. Despite HCVs variation in genomic sequence, the 5' untranslated region containing internal ribosome entry site (IRES) is highly conserved among all genotypes. It is responsible for translation and initiation of the viral protein. In present study, IRES was targeted by designing variants of reported antigen binding fragment (Fab) through affinity maturation approach. Affinity maturation strategy allowed the rational antibody designing with better biophysical properties and antibody-antigen binding interactions. Complementarity determining regions of reported Fab (wild type) were assessed and docked with IRES. Best generated model of Fab was selected and subjected to alanine scanning Three sets of insilico mutations for variants (V) designing were selected; single (1-71), double (a-j) and triple (I-X). Redocking of IRES-Fab variants consequently enabled the discovery of three variants exhibiting better docking score as compared to the wild type Fab. V1, V39 and V4 exhibited docking scores of -446.51, -446.52 and-446.29 kcal/mol respectively which is better as compared to the wild type Fab that exhibited the docking score of -351.23 kcal/mol. Variants exhibiting better docking score were screened for aggregation propensity by assessing the aggregation prone regions in Fab structure. Total A3D scores of wild type Fab, V1, V4 and V39 were predicted as -315.325, -312.727, -316.967 and -317.545 respectively. It is manifested that solubility of V4 and V39 is comparable to wild type Fab. In future, development and invitro assessment of these promising Fab HCV3 variants is aimed.

This study seeks to investigate the interaction profile of the L5 protein of oncolytic adenovirus with the overexpressed surface receptors of pancreatic cancer. This is an important area of research because pancreatic cancer is one of the most fatal malignancies with a very low patient survival rate. Multiple therapies to date to improve the survival rate are reported; however, they show a comparatively low success rate. Among them, oncolytic virus therapy is a type of immunotherapy that is currently under deliberation by researchers for multiple cancer types in various clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus approved by the US Food and Drug Administration (FDA) for melanoma. The oncolytic virus not only kills cancer cells but also activates the anticancer immune response. Therefore, it is preferred over others to deal with aggressive pancreatic cancer. The efficacy of therapy primarily depends on how effectively the oncolytic virus enters and infects the cancer cell. Cell surface receptors and their interactions with virus coat proteins are a crucial step for oncolytic virus entry and a pivotal determinant. The L5 proteins of the virus coat are the first to interact with host cell surface receptors. Therefore, the objective of this study is to analyze the interaction profile of the L5 protein of oncolytic adenovirus with overexpressed surface receptors of pancreatic cancer. The L5 proteins of three adenovirus serotypes HAdV2, HAdV5, and HAdV3 were utilized in this study. Overexpressed pancreatic cancer receptors include SLC2A1, MET, IL1RAP, NPR3, GABRP, SLC6A6, and TMPRSS4. The protein structures of viral and cancer cell protein were docked using the High Ambiguity Driven protein-protein DOCKing (HADDOCK) server. The binding affinity and interaction profile of viral proteins against all the receptors were analyzed. Results suggest that the HAdV3 L5 protein shows better interaction as compared to HAdV2 and HAdV5 by elucidating high binding affinity with 4 receptors (NPR3, GABRP, SLC6A6, and TMPRSS4). The current study proposed that HAdV5 or HAdV2 virus pseudotyped with the L5 protein of HAdV3 can be able to effectively infect pancreatic cancer cells. Moreover, the current study surmises that the affinity maturation of HAdV3 L5 can enhance virus attachment with all the receptors of cancer cells.

OBJECTIVE Environmental pollution has undoubtedly been established as a planetary, intergenerational, and existential threat to global human health and safety. Environmental pollution is adversely affecting the world, mainly the countries where human health is not a priority aspect, and this has been exacerbated due to the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and pandemic is known as "COVID pandemic". This study investigates the association of environmental pollutants, particulate matter (PM2.5), with SARS-CoV-2 daily cases and deaths in Karachi, Lahore, and Islamabad, Pakistan, presenting the perspectives from the Global South. MATERIALS AND METHODS The day-to-day PM2.5 levels were recorded from the metrological website, Real-Time Air Quality Index-AQI. The corresponding data on the COVID cases and deaths in Karachi, Lahore, and Islamabad were obtained from August 1, 2020, to September 30, 2021, from the Health Ministry and National Command Operations Centre Pakistan. RESULTS The mean values for PM2.5 in Karachi were 110.4±46.2; in Lahore 174.0±83.2; and in Islamabad 107.1±40.0. The COVID-19 mean daily cases in Karachi were 538.9±446.6; Lahore 398.3±403.1; and Islamabad 212.2±187.6; and mean daily deaths in Karachi were 9.2±8.3; Lahore 9.3±9.7; and Islamabad 1.8±1.8. The results further depicted that the SARS-CoV-2 cases were 2.86 times higher in Karachi and 1.4 times higher in Lahore than in Islamabad. Similarly, the SARS-CoV-2 deaths were 3.6 and 2.8 times higher in Karachi and Lahore, respectively, compared to Islamabad. CONCLUSIONS The findings claim that cases and deaths augmented significantly along with PM2.5 levels. These empirical estimates demonstrate an association between PM2.5 and SARS-CoV-2 daily cases and deaths in the cities of the Global South. These findings can contribute to policy-making decisions about addressing air pollutants and climate concerns in developing countries and create an urgency to develop a strategy for minimizing environmental pollution. This study can also steer the actions needed to address the environmental problems in developing countries to improve public health and safety.

With the apparent stagnation in the antibiotic discovery and the propagation of multidrug resistance, Helicobacter pylori associated gastric infections are hard to eradicate. In pursuance of alternative medicines, in this study, covalent modification of chitosan (CS) polymer with curcumin (Cur) was accomplished. Proton Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy elucidated the covalent interaction between Cur and CS with characteristic peak of imine functional group (C=N). Scanning Electron Microscopy provided visual proof for surface topology, while size and zeta potential values further affirmed the development of curcumin functionalized chitosan nanosystems (Cur-FCNS). The complexation efficiency of CS with Cur was found as 70 ± 3% at an optimal ratio of 5:1 for CS and Cur, respectively. Cur-FCNS developed with ionic gelation and ultrasonication method demonstrated synergistic anti-H. pylori activity in growth-kinetics and anti-biofilm assays, which was superior to free Cur and even chitosan nanosystems. Under simulated gastric conditions, Cur-FCNS revealed cumulative-release of only 16 ± 0.8% till 40 h, which indicated its improved stability to interact with H. pylori. In silico findings affirmed high binding affinity of Cur-FCNS with multiple bacterial virulence factors. Thus, our results affirmed the exceptional potential of Cur-FCNS as next-generation alternative-medicine to treat resistant H. pylori.

Introduction: To identify whether there is an association between maternal socioeconomic status as in living style, and preeclampsia in women from Pakistan, and if so, to what extent it increases the risk of developing preeclampsia.Methods: This is a case-control study, consisting of 74 normal pregnant and 76 already diagnosed preeclamptic Pakistani females, recruited from various hospitals in Karachi. Their socioeconomic status was assessed through the standard of living index (SLI) using the National Family Health Surveys (NFHS) criteria, which considers different living facilities as an indicator of socioeconomic status. Odds ratios of preeclampsia were calculated for low, middle and high socioeconomic status and other maternal anthropometric parameters.Results: Based on their groups, it appeared that the highest percentage of preeclamptic females (n= 65; 43.3%) and the lowest of control patients (n=14; 9.3%) lie in lower socioeconomic groups and the results were highly significantly different. Study observed that having lower socioeconomic status (P<0.001) significantly increase risk of having preeclampsia by 9% and middle socioeconomic status has no role in prevalence of preeclampsia shown by 0.0 odds ratio. In addition, odds ratio of age and PreBMI for the preeclamptic females were found as 1.37 (P<0.001) and 1.55 (P<0.001) respectively, which shows that each year increase in age, increases risk of preeclampsia by 1.37 times and 1.55 times with each increased in BMI.Conclusion: Living facilities are indications of socioeconomic status and are strong risk factors of preeclampsia

Objective: The study was performed to investigate the association of hypertension in pregnancy with prostasin gene polymorphism in Pakistani females. Methods: This case-control study was performed at University of Karachi, Pakistan from April 2018 to May 2019. A total of 160 females, including 90 hypertensives and 70 healthy pregnant females, were recruited by purposive sampling after obtaining informed written consent. Genotyping was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: The frequencies of the TC and CC genotypes were higher in hypertensive pregnant females compared to healthy controls. A significant difference was evident for CC (P=0.012) genotype; however, no significant difference was observed for TC (P=0.49) and TT genotypes (P=0.06) between control and hypertensive groups. The adjusted odds ratio for CC genotype was 6.2 (P=0.025) and 1.48 (P=0.44) for TC genotype compared to the TT genotype. There was a significantly higher prevalence of the C allele of the prostasin gene at rs12597511 in the hypertensive group, suggesting that this allele is a risk factor for hypertension and cardiovascular diseases. Conclusion: C allele at rs12597511 of prostasin gene demonstrate as a risk factor for having hypertension in pregnancy.

Objectives: To investigate the relationship between a prostasin gene variations and the development of preeclampsia in a Pakistani female population. Methods: This was a case-control study carried out at University of Karachi, Karachi, Pakistan between May 2018 and 2019. A single nucleotide polymorphism (SNP) at rs12597511 locus was examined with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses in 76 preeclamptic and 74 normotensive expecting mothers. Results: We observed significantly increased risk of preeclampsia associated with the CC genotype of rs12597511 polymorphism as compared to TT (p<0.001, OR=8.08, 95% CI: 1.28-31.19) and TT/TC (p<0.001, OR=14.66 and 95% CI: 3.31-65.07) genotypes carriers. Calculation of the allelic distribution revealed a higher frequency of the T allele (82%) among controls; however, the C allele was more prevalent in the preeclamptic group (36%) significantly. Conclusion: The significantly higher C allele frequency in the prostasin gene at the rs12597511 locus in the preeclamptic group indicates that the distribution of the C allele of the prostasin gene is a potential risk factor contributing to the development of preeclampsia.