Vitamin D deficiency associates with susceptibility to tuberculosis in Pakistan, but polymorphisms in VDR, DBP and CYP2R1 do not

Background: Single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and the vitamin D binding protein (DBP) have been reported to modify the influence of vitamin D deficiency on susceptibility to active tuberculosis (TB) in the UK, but this phenomenon has not been investigated in settings with a high TB burden. SNPs in CYP2R1, which encodes a vitamin D 25-hydroxylase enzyme, are known to influence vitamin D status, but their potential role in determining susceptibility to TB has not previously been investigated in any setting. Method: We conducted a case–control study in 260 pulmonary TB patients and 112 controls recruited in Lahore, Pakistan. Analyses were conducted to test for main effects of vitamin D status and SNPs in VDR (rs731236, rs2228570 and rs1544410), DBP (rs7041 and rs4588) and CYP2R1 (rs2060793, rs10500804 and rs10766197) on susceptibility to TB, and to investigate whether these SNPs modify the association between vitamin D status and disease susceptibility. Results: Profound vitamin D deficiency (serum 25-hydroxyvitamin D concentration ≤ 20 nmol/L) was common among TB patients (118/260, 45 %), and was independently associated with susceptibility to TB (adjusted odds ratio 1.87, 95 % CI 1.15 to 3.04, P = 0.01). However, none of the SNPs investigated associated with susceptibility to TB, either in main effects analysis, or in interaction with vitamin D status. Conclusion: Profound vitamin D deficiency was common among TB patients in this high-burden setting, and was independently associated with disease susceptibility. However, no statistically significant associations between SNPs in the vitamin D pathway and disease susceptibility was demonstrated.Higher Education Commission of Pakistan grant number BM7-139

Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense

Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host’s signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies

High prevalence of vitamin D deficiency among women of child-bearing age in Lahore Pakistan, associating with lack of sun exposure and illiteracy

BACKGROUND: Vitamin D status is a key determinant of maternal and neonatal health. Deficiency has been reported to be common in Pakistani women, but information regarding environmental and genetic determinants of vitamin D status is lacking in this population. METHODS: We conducted a cross-sectional study among three groups of healthy women living in Lahore, Pakistan: university students, students or employees of Medrasas or Islamic Institutes, and employees working in office, hospital or domestic settings. Multivariate analysis was performed to identify environmental and genetic determinants of vitamin D status: polymorphisms in genes encoding the vitamin D receptor, vitamin D 25-hydroxylase enzyme CYP2R1 and vitamin D binding protein [DBP] were investigated. We also conducted analyses to identify determinants of body ache and bone pain in this population, and to determine the sensitivity and specificity of testing for hypocalcaemia and raised serum alkaline phosphatase to screen for vitamin D deficiency. RESULTS: Of 215 participants, 156 (73 %) were vitamin D deficient (serum 25[OH]D <50 nmol/L). Risk of vitamin D deficiency was independently associated with illiteracy (adjusted OR 4.0, 95 % CI 1.03–15.52, P = 0.04), <30 min sun exposure per day (adjusted OR 2.13, 95 % CI 1.08–4.19, P = 0.02), sampling in January to March (adjusted OR 2.38, 95 % CI 1.20–4.70), P = 0.01) and lack of regular intake of multivitamins (adjusted OR 2.61, 95 % CI 1.32–5.16, p = 0.005). Participants with the GG genotype of the rs4588 polymorphism in the gene encoding vitamin D binding protein tended to have lower 25(OH)D concentrations than those with GT/TT genotypes (95 % CI for difference 22.7 to −0.13 nmol/L, P = 0.053). Vitamin D deficiency was independently associated with increased risk of body ache or bone pain (adjusted OR 4.43, 95 % CI 2.07 to 9.49, P = 0.001). Hypocalcaemia (serum calcium concentration ≤9.5 mg/dL) and raised alkaline phosphatase concentration (≥280 IU/L) had low sensitivity and very low specificity for identification of vitamin D deficiency. CONCLUSION: Vitamin D deficiency is common among healthy women of child-bearing age in Lahore, Pakistan: illiteracy, decreased sun exposure and lack of multivitamin intake are risk factors

Heavy Metal Tolerance Trend in Extended-Spectrum β-Lactamase Encoding Strains Recovered from Food Samples

This study evaluates bacteriological profiles in ready-to-eat (RTE) foods and assesses antibiotic resistance, extended-spectrum β-lactamase (ESBL) production by gram-negative bacteria, and heavy metal tolerance. In total, 436 retail food samples were collected and cultured. The isolates were screened for ESBL production and molecular detection of ESBL-encoding genes. Furthermore, all isolates were evaluated for heavy metal tolerance. From 352 culture-positive samples, 406 g-negative bacteria were identified. Raw food samples were more often contaminated than refined food (84.71% vs. 76.32%). The predominant isolates were Klebsiella pneumoniae (n = 76), Enterobacter cloacae (n = 58), and Escherichia coli (n = 56). Overall, the percentage of ESBL producers was higher in raw food samples, although higher occurrences of ESBL-producing E. coli (p = 0.01) and Pseudomonas aeruginosa (p = 0.02) were observed in processed food samples. However, the prevalence of ESBL-producing Citrobacter freundii in raw food samples was high (p = 0.03). Among the isolates, 55% were blaCTX-M, 26% were blaSHV, and 19% were blaTEM. Notably, heavy metal resistance was highly prevalent in ESBL producers. These findings demonstrate that retail food samples are exposed to contaminants including antibiotics and heavy metals, endangering consumers

Impact of vitamin D on infectious disease-tuberculosis-a review

Summary: Vitamin D, a fat soluble vitamin, is well known for calcium homeostasis. In recent years, many researchers have suggested that vitamin D performs multiple functions extending far beyond mineral homeostasis. The vitamin D synthesis machinery and related receptor have been reported in multiple tissues, where they play a key role in immune system modulation. Deficiency of vitamin D is not linked only with rickets or osteomalacia but with many other infectious and metabolic disorders. Emerging evidences suggest the relation of vitamin D deficiency in establishing tuberculosis. High prevalence of vitamin D deficiency in pulmonary TB patients indicates that vitamin D is a risk factor for the development of active tuberculosis. Therefore, maintaining vitamin D status in TB patients might be helpful to control tuberculosis. The level of vitamin can be maintained in reference limit by changing life style and use of multivitamin supplements. This review outlines the role of vitamin D in infectious diseases like tuberculosis and also effect of supplementation on treatment of TB; however, more studies are needed due to the clinical changes observed in patients with tuberculosis after vitamin D supplementation. Keywords: Vitamin D, Vitamin D 25-hydroxylase, Hypovitaminosis D, Infectious diseases, Tuberculosi

Performance Analysis of Artificial Neural Network Based Land Cover Classification

Landcover classification using automated classification techniques, while employing remotely sensed multi-spectral imagery, is one of the promising areas of research. Different land conditions at different time are captured through satellite and monitored by applying different classification algorithms in specific environment. In this paper, a SPOT-5 image provided by SUPARCO has been studied and classified in Environment for Visual Interpretation (ENVI), a tool widely used in remote sensing. Then, Artificial Neural Network (ANN) classification technique is used to detect the land cover changes in Abbottabad district. Obtained results are compared with a pixel based Distance classifier. The results show that ANN gives the better overall accuracy of 99.20% and Kappa coefficient value of 0.98 over the Mahalanobis Distance Classifier

Exploring the virulence potential of immune evasion cluster genes in methicillin-resistant Staphylococcus aureus from cancer patients

Methicillin-resistant Staphylococcus aureus (MRSA) is accountable for a plethora of infections, ranging from minor cutaneous manifestations to grave metastatic conditions. The dissemination of MRSA among cancer patients poses a substantial public health hazard on a global scale. This study explores the association between MRSA and bacteriophage-encoded immune evasion cluster (IEC) genes. This investigation employed a total of 168 pathogenic MRSA collected from 38 cancer and 130 non-cancer patients. A cefoxitin disc diffusion method followed by PCR analysis was used to identify the mecA gene. In this study, we employed singleplex and multiplexed PCR techniques to detect specific IEC genes. No association (p = 0.98) was observed between the sex and age of patients and MRSA isolates. However, MRSA isolates demonstrated a notable association (p = 0.01) with pus samples in non-cancer patients and skin swabs in cancer patients. The resistance profiles of MRSA strains from cancer and non-cancer patients did not show significant differences (p > 0.05). Notably, the sea gene was found to be more prevalent in MRSA isolates from cancer patients, displaying a significant association (p = 0.03). Additionally, this study identified two novel and distinct combinations of IEC types, namely V1 (sea, chp, scn) and V2 (sea, scn). Cancer patients had higher multidrug resistance and toxin gene abundance than non-cancer patients. The identification of two novel IEC patterns underscores the urgent need to control MRSA dissemination in hospitals and monitor emerging clones

The interleukin-10 family: Major regulators of the immune response against Plasmodium falciparum infections

Malaria caused by the Plasmodium falciparum strain is more severe because of this protozoan’s ability to disrupt the physiology of host cells during the blood stages of development by initiating the production of the interleukin-10 (IL-10) family of cytokines. P. falciparum feeds on hemoglobin and causes host cells to adhere to the walls of blood vessels by remodeling their composition. IL-10 is produced by CD4+ T cells that inhibits antigen-presenting cells’ activity to prevent inflammation. This cytokine and its family members are crucial in promoting malarial infection by inhibiting the host’s protective immune response, thus initiating Plasmodium parasitemia. IL-10 is also responsible for preventing severe pathology during Plasmodium infection and initiates several signaling pathways to alter the physiology of host cells during malarial infection. This review summarizes the critical aspects of P. falciparum infection, including its role in signaling pathways for cytokine exudation, its effect on microRNA, the human immune response in malaria, and the role played by the liver hormone hepcidin. Moreover, future aspects of vaccine development and therapeutic strategies to combat P. falciparum infections are also discussed in detail

Integrative analysis of RNA expression data unveils distinct cancer types through machine learning techniques

Cancer is a highly complex and heterogeneous disease. Traditional methods of cancer classification based on histopathology have limitations in guiding personalized prognosis and therapy. Gene expression profiling provides a powerful approach to unraveling molecular intricacies and better-stratifying cancer subtypes. In this study, we performed an integrative analysis of RNA sequencing data from five cancer types - BRCA, KIRC, COAD, LUAD, and PRAD. A machine learning workflow consisting of dataset identification, normalization, feature selection, dimensionality reduction, clustering, and classification was implemented. The k-means algorithm was applied to categorize samples into distinct clusters based solely on gene expression patterns. Five unique clusters emerged from the unsupervised machine learning based analysis, significantly correlating with the known cancer types. BRCA aligned predominantly with one cluster, while COAD spanned three clusters. KIRC was represented within two main clusters. LUAD is associated strongly with a single cluster and PRAD with another cluster. This demonstrates the ability of machine learning approaches to unravel complex signatures within transcriptomic profiles that can delineate cancer subtypes. The proposed study highlights the potential of integrative analytics to derive meaningful biological insights from high-dimensional omics datasets. Molecular subtyping through machine learning clustering enhances our understanding of the intrinsic heterogeneities and pathways dysregulated in different cancers. Overall, this study exemplifies a powerful computational framework to classify gene expressions of patients having different types of cancers and guide personalized therapeutic decisions. Finally, Wide Neural Network demonstrates a significantly higher accuracy, achieving 99.834% on the validation set and an even more impressive 99.995% on the test set

Detection of antibacterial activities of Miswak, Kalonji and Aloe vera against oral pathogens & anti-proliferative activity against cancer cell line

Abstract Background Emerging drug resistance and hindrance of treatment is provoking scientists to search new, less expensive medicinally active compounds. Dental diseases caused by oral pathogens are very frequent chronic infections around the world. The medical potentials of a lot of Pakistani local herbs and herbal combinations is relatively unknown, hence attempted to explore. A study was designed to investigate potential role of local medicinal herbs for example Miswak, Kalonji & Aloe vera as antimicrobial, antioxidant and anti-proliferative agents against oral pathogens and cancer cell line. Methods Medicinal extracts were prepared in solvents of different polarities. Their antimicrobial activity was determined alone and in combination against oral pathogens. Antioxidant activity was evaluated through Catalase and Superoxide dismutase assay and anti-proliferative activity was evaluated through 3-(4, 5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Results Plant extracts alone and in combinations were found significantly effective as antimicrobial agent against standard ATCC strains of C. albicans and S. aureus (P ˂0.001). Especially Miwak extract was found highly significant against fungus. Extracts of Kalonji were found significant in inhibiting growth of HeLa cell lines. Miswak and Kalonji showed significant levels of antioxidant activity. Conclusion Medicinal herbs Miswak and Kalonji have potential to be used for therapeutic purposes. Results suggested that herbal medicinal composition can be prepared using these extracts after applying scientific standardization methods