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The result of improper treatment has led to the rise of Multidrug-resistant (MDR) strains. This concern still exists in Pakistan. In order to save energy, time and resources an early detection of resistant cases is imperative. Thus, a treated group of 100 isolates and a control group of 56 untreated isolates were studied. PCR and gene sequencing showed mutations at codon 531 and 513 in the rpoB gene. 12% of cases showed a double mutation in the rpoB gene. katG gene showed mutations at codon 315 and 299. 28.6% of the control group cases were positive for MDR whereas 100% of the treated group were positive for MDR. This study explores the significantly increasing ratio of MDR-TB among Pakistani population. This study provides prevalent MDR mutations among Pakistanis and suggests developing such molecular assays that are time and cost effective. Importance: Pakistan is a developing country and has fourth highest incidence rate of MDR-TB. The treatment of MDR-TB is the use of second line drugs that has severe side effects as well as it requires long time span. One of the strategies to control the spread of MDR-TB is to decipher the aberrations at molecular level in order to formulate potent drugs that can treat the patients within short span of time. Determining the mutation profile of MDR in Pakistani populations will open new horizons for the improvement of drug treatment regimens to make it more effective or for the development of novel potent drugs and vaccines to better treat the drug-resistant TB. Moreover, this study will be help in disease control program.

Oxidative stress is the process by which reactive molecules and free radicals are formed in cells. In this study, we report the blood-based gene expression profile of oxidative stress and antioxidant genes for identifying surrogate markers of liver tissue in chronic hepatitis C (CHC) patients by using real-time PCR. A total of 144 untreated patients diagnosed with CHC having genotype 3a and 20 healthy controls were selected for the present study. Liver biopsy staging and grading of CHC patients were performed using the METAVIR score. Total RNA was extracted from liver tissue and blood samples, followed by cDNA synthesis and real-time PCR. The relative expression of genes was calculated using the ΔΔCt method. The expression profile of 84 genes associated with oxidative stress and antioxidants was determined in liver tissue and blood samples. In liver tissue, 46 differentially expressed genes (upregulated, 27; downregulated, 19) were identified in CHC patients compared to normal samples. In blood, 61 genes (upregulated, 51; downregulated; 10) were significantly expressed in CHC patients. A comparison of gene expression in liver and whole blood showed that 20 genes were expressed in a similar manner in the liver and blood. The expression levels of commonly expressed liver and blood-based genes were also correlated with clinical factors in CHC patients. A receiver operating curve (ROC) analysis of oxidative stress genes (ALB, CAT, DHCR24, GPX7, PRDX5, and MBL2) showed that infections in patients with CHC can be distinguished from healthy controls. In conclusion, blood-based gene expression can reflect the behavior of oxidative stress genes in liver tissue, and this blood-based gene expression study in CHC patients explores new blood-based non-invasive biomarkers that represent liver damage.

Background Since the first reported outbreak of dengue hemorrhagic fever in Pakistan, several mini outbreaks have erupted in the region. Dengue virus serotype 3 (DEN-3) was first documented in 2005 outbreak in Karachi. Reports show that serotype 3 is prevalent in Lahore since 2008. Serotype 2 (DEN-2) is the major circulating serotype in Pakistan as it is documented since 1994. We have conducted a detailed study of three outbreaks of dengue virus infection that occurred in years 2007, 2008 and 2009 in Lahore by using molecular techniques such as PCR and nucleotide sequencing of the C-prM gene junction of Dengue virus. Results Through the analysis of 114 serum samples collected over the period of three years (2007-2009), total 20 patients were found to be infected with dengue virus. In year 2007, four were positive for serotype 2 and one sample was positive for serotype DEN-3. In 2008, five samples had concurrent infection with serotypes DEN-2 and DEN-3 while three samples were infected only with serotype DEN-2. In year 2009, one sample had concurrent infection with serotypes DEN-2 and DEN-3 while six were positive for serotype DEN-2 only. Conclusions Our study showed that serotype DEN-2 was dominant in positive samples of dengue virus infection collected during the period of three years (2007-2009). The other serotype present was serotype DEN-3. Genotypes of serotype DEN-2 and serotype DEN-3 were subtype IV and subtype III, respectively.

Breast cancer is a complex disease that is characterized by altered functions of many genes. In this study, we aim to establish long non-coding RNAs as prognostic biomarkers as they play vital roles in their prognosis and progression. For this purpose, we retrieved four datasets (GSE10810, GSE42568, GSE65194, and GSE45827) from NCBI Gene Expression Omnibus. Using R studio, we identified differentially expressed genes followed by functional enrichment analysis with the help of DAVID software. DEGs were used to construct a protein–protein interaction map which we later used to identify highly correlated genes with the help of sub-network identification and centrality analysis in cytoscape software. Next, lncRNAs-mRNA coexpression analysis was performed to determine the potential role of lncRNAs. Later on, we assessed their role in survival with the help of Kaplein Meir’s plot. The results of these analyses establish long noncoding RNAs i.e. EPB41L4A-AS1, LINC00667, MAGI2-AS3, and MALAT1 as prognostic biomarkers. This study provides a blueprint for identifying mRNA-lncRNA networks in any cancer, facilitating the use of lncRNAs as prognostic biomarkers and aiding in the identification of therapeutic targets. Future research may focus on validating this research biologically to further substantiate the role of lncRNAs as prognostic biomarkers in breast cancer.

Numerous benefits of nanotechnology are available in many scientific domains. In this sense, nanoparticles serve as the fundamental foundation of nanotechnology. Recent developments in nanotechnology have demonstrated that nanoparticles have enormous promise for use in almost every field of life sciences. Nanoscience and nanotechnology use the distinctive characteristics of tiny nanoparticles (NPs) for various purposes in electronics, fabrics, cosmetics, biopharmaceutical industries, and medicines. The exclusive physical, chemical, and biological characteristics of nanoparticles prompt different immune responses in the body. Nanoparticles are believed to have strong potential for the development of advanced adjuvants, cytokines, vaccines, drugs, immunotherapies, and theranostic applications for the treatment of targeted bacterial, fungal, viral, and allergic diseases and removal of the tumor with minimal toxicity as compared to macro and microstructures. This review highlights the medical and non-medical applications with a detailed discussion on enhanced and targeted natural and acquired immunity against pathogens provoked by nanoparticles. The immunological aspects of the nanotechnology field are beyond the scope of this Review. However, we provide updated data that will explore novel theragnostic immunological applications of nanotechnology for better and immediate treatment.

Tuberculosis (TB) is the largest infectious disease with 10 million new active-TB patients and1.7 million deaths per year. Active-TB is an inflammatory disease and is increasingly viewed as an imbalance of immune responses to M . tb . infection. The mechanisms of a switch from latent infection to active disease is not well worked out but a shift in the immune responses is thought to be responsible. Increasingly, the role of gut microbiota has been described as a major influencer of the immune system. And because the gut is the largest immune organ, we aimed to analyze the gut microbiome in active-TB patients in a TB-endemic country, Pakistan. The study revealed that Ruminococcacea , Enetrobactericeae , Erysipelotrichaceae , Bifidobacterium , etc. were the major genera associated with active-TB, also associated with chronic inflammatory disease. Plasma antibody profiles against several M . tb . antigens, as specific biomarkers for active-TB, correlated closely with the patient gut microbial profiles. Besides, bcoA gene copy number, indicative of the level of butyrate production by the gut microbiome was five-fold lower in TB patients compared to healthy individuals. These findings suggest that gut health in TB patients is compromised, with implications for disease morbidity (e.g., severe weight loss) as well as immune impairment.

In cancer, DJ-1/PARK7 acts as an oncogene that drives Akt-mediated cell survival. Although amplification of DJ-1 has been described in several types of tumors, the mechanistic basis of DJ-1's oncogenic effect remains incompletely understood. A tumor's ability to adapt to hypoxia is absolutely critical for its survival and progression, and this adaptation is largely mediated by the transcription factor HIF1. The stabilization of HIF1 subunits during hypoxia is at least partly dependent on the PI3K/Akt/mTOR pathway. We hypothesized that DJ-1, a positive regulator of Akt when over-expressed, might be involved in regulating HIF1 transcriptional activity under hypoxic conditions. Our results show that loss of DJ-1 in human cell lines and transformed mouse fibroblasts decreases the transcription of a variety of HIF1-responsive genes during hypoxia. Moreover, DJ-1 expression is critical for the Akt and mTOR activities that sustain HIF1 stability. Surprisingly, DJ-1 also regulates the activity of the metabolic sensor AMPK, especially during hypoxia. Finally, DJ-1 appears to protect cells against hypoxia-induced cell death and is required for their adaptation to severe hypoxic stress. Our work positions DJ-1 as an upstream activator of HIF1 function in cancer cells and establishes that DJ-1's oncogenic activity stems from its ability to increase a cell's resistance to hypoxic stress through DJ-1's regulatory effects on mTOR and AMPK. The discovery of these functions of DJ-1 strengthens the case for the development of therapeutics that target DJ-1 activity in cancer cells.

Hepatocellular carcinoma (HCC) remains the third leading cause of cancer-related mortality worldwide, with limited treatment efficacy and poor prognosis, particularly in advanced-stage disease. Despite progress in diagnostic imaging and systemic therapies, early detection and effective targeted interventions remain major clinical challenges. Long non-coding RNAs (lncRNAs), a class of regulatory RNA molecules exceeding 200 nucleotides in length, have emerged as essential regulators of oncogenic signaling, metabolism, and tumor microenvironment in HCC. This review provides a comprehensive overview of the molecular mechanisms, biological functions, and clinical relevance of key lncRNAs involved in HCC progression. We summarize the dual roles of lncRNAs as oncogenic drivers and tumor suppressors, with particular emphasis on oncogenic lncRNAs including CYTOR, UCA1, MALAT1, SPRY4-IT1, uc001ncr, AF085935, HULC, and HOTAIR. Their regulatory functions are discussed within major cancer-associated signaling networks, including the PI3K/AKT/mTOR, Wnt/β-catenin, TGF-β/NF-κB, and EMT-associated pathways. Furthermore, each lncRNA is discussed in the context of its expression pattern, endogenous RNA (ceRNA) interactions, molecular partners, and functional contributions to cellular proliferation, invasion, metastasis, angiogenesis, immune modulation, and therapeutic resistance. In addition, we explore the emerging potential of lncRNAs as minimally invasive diagnostic and prognostic biomarkers, owing to their stability and detectability in tissue and circulating biofluids. We also discuss recent advances in RNA- targeted therapeutic strategies, including RNA interference, siRNA-mediated silencing, antisense oligonucleotides, and CRISPR-based genome editing approaches. Collectively, this review highlights the importance of integrating lncRNA expression signatures into personalized HCC management and the promising role of lncRNA-based diagnostics and therapeutics in transforming the future landscape of liver cancer detection, prognosis, and treatment.

Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs with high rates of virological clearance. The reduction in cirrhosis-related consequences, particularly HCC, is the long-term objective of DAAs therapy for HCV. Although the risk of developing HCC is decreased in HCV patients who achieve a disease-sustaining virological response, these patients are nevertheless at risk, especially those with severe fibrosis and cirrhosis. Previous studies have shown that HCV induce several mechanisms of hepatocarcinogenesis in the host’s hepatic micro- and macro-environment, which leads to HCC progression. In an HCV-altered environment, compensatory liver regeneration favors chromosomal instability and irreversible alterations, which encourage hepatocyte neoplastic transformation and the development of malignant clones. These mechanisms involve a series of genetic and epigenetic modifications including host genetic factors, dysregulation of several signaling pathways, histone, and DNA modifications including methylation and acetylation. This review highlights the genetic and epigenetic factors that lead to the development of HCC in chronic HCV-infected individuals and can be targeted for earlier HCC diagnosis and prevention.

Background & objectives: Dengue virus (DENV) is an RNA virus that infects approximately 2.5 billion people around the world. The incidence of dengue fever has rapidly increased at an alarming rate in the last few years and has affected thousands of people in Pakistan. This review explores the prevalence, serotypes and pathogenesis of dengue virus circulating in Pakistan. Methods: A systematic review of observational studies published between 1994 and December 2019 was performed. All records of the confirmed outbreak of dengue fever in Pakistan were reviewed and articles containing no primary data were excluded. Results: Four identified serotypes of dengue virus (DENV 1-4) circulate in different regions of the world causing epidemics. The most prevalent serotype, which is still epidemic and dominant in Pakistan, is DENV-2. Many factors like over-population, rapid urbanization, travelling, lack of vector control in dengue endemic areas and inadequate health-care are responsible of dynamic and huge raise of dengue in Pakistan. Interpretation & conclusion: Currently there is no specific treatment for prevention of dengue virus. Recently some antiviral compounds were being tested to eradicate this disease. There is a need to develop an efficient and safe vaccine for all four serotypes to combat dengue viral infection globally and particularly in Pakistan.