Fisetin Attenuates Arsenic-Induced Hepatic Damage by Improving Biochemical, Inflammatory, Apoptotic, and Histological Profile: In Vivo and In Silico Approach.

Arsenic (As) is a toxic metalloid and human carcinogen that may cause hepatotoxicity. Fisetin (3, 3', 4', 7-tetrahydroxyflavone) is a phytoflavonoid, which shows diverse therapeutic activities. This study aimed to examine the remedial potential of fisetin against As-instigated hepatotoxicity in adult male rats. To accomplish this aim, albino rats (N = 48) were evenly classified into 4 groups: control group, As (10 mg/kg) group, fisetin (2.5 mg/kg) + As (10 mg/kg) group, and fisetin (2.5 mg/kg) group. After one month of treatment, biochemical assay, total protein content (TPC), hepatic serum enzymes, inflammatory as well as pro- or anti-apoptotic markers, and histopathological profile of hepatic tissues were estimated. As administration disordered the biochemical profile by decreasing activities of antioxidant enzymes i.e., catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS), and thiobarbituric acid reactive substances (TBARS). TPC was also considerably reduced after exposure to As. Furthermore, As markedly raised the levels of liver serum enzymes such as aspartate transaminase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) as well as the levels of inflammatory markers, i.e., nuclear factor- κB (NF-κB), tumor necrosis- α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclo-oxygenase-2 (COX-2) activity. Besides, it lowered the level of antiapoptotic markers (Bcl-2) and upregulated the levels of proapoptotic markers (Bax, Caspase-3, and Caspase-9). Additionally, As exposure led to histopathological damage in hepatic tissues. However, fisetin administration remarkably alleviated all the depicted hepatic damages. For further verification, the screening of several dock complexes was performed by using the GOLD 5.3.0 version. Based on docking fitness and GOLD score, the ranking order of receptor proteins with fisetin compound is superoxide dismutase, interleukin, aspartate aminotransferase, alkaline phosphatase, TNF-alpha, alanine transaminase, cyclo-oxygenase 2, antiapoptotic, and glutathione reductase. Out of these three receptor proteins superoxide dismutase, interleukin, and aspartate aminotransferase showed the best interaction with the fisetin compound. In vivo and in silico outcomes of the current study demonstrated that fisetin could potentially ameliorate As-instigated hepatotoxicity.

The occurrence of multidrug-resistant Mycobacterium tuberculosis from patients of pulmonary tuberculosis.

INTRODUCTION: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is one of the leading causes of death in the world. The resource constraints make it difficult to diagnose and monitor the cases of MDR-TB. GeneXpert is a recognized tool used to diagnose the patients of pulmonary tuberculosis in clinical settings across the globe. METHODOLOGY: The present one-year cross-sectional study was conducted to estimate the occurrence of MDR-TB in patients with pulmonary TB. A total of 1000 patients suspected of pulmonary tuberculosis were included in this study. A random convenient sampling technique was done to collect the sputum samples (twice) from the patients. Samples were processed for the detection of Mycobacterium tuberculosis using conventional detection methods like the Ziehl Nelson staining method and fluorescent microscopy. Additionally, Cepheid GeneXpert was used for molecular detection of MDR-TB in smear-positive samples of pulmonary tuberculosis by amplifying the rifampicin resistance determining region (RRDR; rpoB gene). All the tests were performed in the biosafety level III lab of District Headquarters Hospital Nankana Sahib. RESULTS: It was observed that 103 (10.3%) individuals were diagnosed as positive for tuberculosis among 1000 patients. Among these 103 TB positive cases, there were 11 (10.7%) patients diagnosed with rifampicin resistance gene (RR-Gene) of Mycobacterium tuberculosis. CONCLUSIONS: Overall findings of the study showed that MDR-TB is prevalent in pulmonary TB patients and GeneXpert is the most sensitive technique for early diagnosis of the disease, which may be very helpful in the treatment and control of this public health menace in low and middle-income countries.

Isolation and molecular characterization of the indigenous Staphylococcus aureus strain K1 with the ability to reduce hexavalent chromium for its application in bioremediation of metal-contaminated sites.

BACKGROUND: Urbanization and industrialization are the main anthropogenic activities that are adding toxic heavy metals to the environment. Among these, chromium (in hexavalent: Cr+6 and/or trivalent Cr+3) is being released abundantly in wastewater due to its uses in different industrial processes. It becomes highly mutagenic and carcinogenic once it enters the cell through sulfate uptake pathways after interacting with cellular proteins and nucleic acids. However, Cr+6 can be bio-converted into more stable, less toxic and insoluble trivalent chromium using microbes. Hence in this study, we have made efforts to utilize chromium tolerant bacteria for bio-reduction of Cr+6 to Cr+3. METHODS: Bacterial isolate, K1, from metal contaminated industrial effluent from Kala Shah Kaku-Lahore Pakistan, which tolerated up to 22 mM of Cr6+ was evaluated for chromate reduction. It was further characterized biochemically and molecularly by VITEK®2 system and 16S rRNA gene sequencing respectively. Other factors affecting the reduction of chromium such as initial chromate ion concentration, pH, temperature, contact-time were also investigated. The role of cellular surface in sorption of Cr6+ ion was analyzed by FTIR spectroscopy. RESULTS: Both biochemical and phylogenetic analyses confirmed that strain K1 was Staphylococcusaureus that could reduce 99% of Cr6+ in 24 hours at 35 °C (pH = 8.0; initial Cr6+ concentration = 100 mg/L). FTIR results assumed that carboxyl, amino and phosphate groups of cell wall were involved in complexation with chromium. Our results suggested that Staphylococcusaureus K1 could be a promising gram-positive bacterium that might be utilized to remove chromium from metal polluted environments.

Secreted frizzled-related protein 4 and its implication in obesity and type-2 diabetes.

Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to ß-cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic ß-cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesity-induced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro-inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1-ß (IL1-ß). This review highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D.

Cross-sectional epidemiological investigations of Giardia lamblia in children in Pakistan

ABSTRACT BACKGROUND: The prevalence of Giardia lamblia in Pakistani children is currently unknown. The aim here was to evaluate the prevalence and risk factors of Giardia lamblia in children exhibiting diarrhea. DESIGN AND SETTING: Cross-sectional study at different district healthcare hospitals in Pakistan. METHODS: A total of 800 samples were collected from children aged 0-10 years. Information regarding personal data, demographic data and supposed risk factors was collected through a structured questionnaire. Giardia lamblia was detected through direct microscopy and antigens through the enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of Giardia lamblia was 2.75% through direct microscopy and inflated to 9.5% through ELISA. The demographic factors positively associated with occurrences of giardiasis were age (P = 0.035; odds ratio, OR = 1.96; 95% confidence interval, CI = 1.094-3.533), mother's educational level (P = 0.031; OR = 2.67; 95% CI = 1.186-6.045) and father's educational level (P = 0.004; OR = 3.56; 95% CI = 1.612-7.899). Similarly, among the supposed risk factors, rural residency (P = 0.032; OR = 1.76; 95% CI = 1.098- 2.851), absence of proper sewerage system (P = 0.000; OR = 6.60; 95% CI = 4.029-10.841) and unavailability of safe drinking water (P = 0.000; OR = 4.08; 95% CI = 2.207-7.547) were the factors strongly connected with giardiasis. Abdominal discomfort was a prominent clinical sign with 46% frequency. CONCLUSION: Various risk factors were associated with occurrences of Giardia, thus emphasizing the importance of parents' education, safe drinking water and proper sewerage systems for Pakistani children's health.