Statistical Bioinformatics to Uncover the Underlying Biological Mechanisms That Linked Smoking with Type 2 Diabetes Patients Using Transcritpomic and GWAS Analysis.

Type 2 diabetes (T2D) is a chronic metabolic disease defined by insulin insensitivity corresponding to impaired insulin sensitivity, decreased insulin production, and eventually failure of beta cells in the pancreas. There is a 30-40 percent higher risk of developing T2D in active smokers. Moreover, T2D patients with active smoking may gradually develop many complications. However, there is still no significant research conducted to solve the issue. Hence, we have proposed a highthroughput network-based quantitative pipeline employing statistical methods. Transcriptomic and GWAS data were analysed and obtained from type 2 diabetes patients and active smokers. Differentially Expressed Genes (DEGs) resulted by comparing T2D patients' and smokers' tissue samples to those of healthy controls of gene expression transcriptomic datasets. We have found 55 dysregulated genes shared in people with type 2 diabetes and those who smoked, 27 of which were upregulated and 28 of which were downregulated. These identified DEGs were functionally annotated to reveal the involvement of cell-associated molecular pathways and GO terms. Moreover, protein-protein interaction analysis was conducted to discover hub proteins in the pathways. We have also identified transcriptional and post-transcriptional regulators associated with T2D and smoking. Moreover, we have analysed GWAS data and found 57 common biomarker genes between T2D and smokers. Then, Transcriptomic and GWAS analyses are compared for more robust outcomes and identified 1 significant common gene, 19 shared significant pathways and 12 shared significant GOs. Finally, we have discovered protein-drug interactions for our identified biomarkers.

Antioxidants activities of phytochemicals perspective modulation of autophagy and apoptosis to treating cancer.

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field.

Recent Advances in Cellular Signaling Interplay between Redox Metabolism and Autophagy Modulation in Cancer: An Overview of Molecular Mechanisms and Therapeutic Interventions.

Autophagy is a fundamental homeostatic process in which certain cellular components are ingested by double-membrane autophagosomes and then degraded to create energy or to maintain cellular homeostasis and survival. It is typically observed in nutrient-deprived cells as a survival mechanism. However, it has also been identified as a crucial process in maintaining cellular homeostasis and disease progression. Normal cellular metabolism produces reactive oxygen (ROS) and nitrogen species at low levels. However, increased production causes oxidative stress, which can lead to diabetes, cardiovascular diseases, neurological disorders, and cancer. It was recently shown that maintaining redox equilibrium via autophagy is critical for cellular responses to oxidative stress. However, little is understood about the molecular cancer processes that connect to the control of autophagy. In cancer cells, oncogenic mutations, carcinogens, and metabolic reprogramming cause increased ROS generation and oxidative stress. Recent studies have suggested that increased ROS generation activates survival pathways that promote cancer development and metastasis. Moreover, the relationship between metabolic programming and ROS in cancer cells is involved in redox homeostasis and the malignant phenotype. Currently, while the signaling events governing autophagy and how redox homeostasis affects signaling cascades are well understood, very little is known about molecular events related to autophagy. In this review, we focus on current knowledge about autophagy modulation and the role of redox metabolism to further the knowledge of oxidative stress and disease progression in cancer regulation. Therefore, this review focuses on understanding how oxidation/reduction events fine-tune autophagy to help understand how oxidative stress and autophagy govern cancer, either as processes leading to cell death or as survival strategies for maintaining redox homeostasis in cancer.

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management.

Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy's dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.

Bioinformatics Strategies to Identify Shared Molecular Biomarkers That Link Ischemic Stroke and Moyamoya Disease with Glioblastoma.

Expanding data suggest that glioblastoma is accountable for the growing prevalence of various forms of stroke formation, such as ischemic stroke and moyamoya disease. However, the underlying deterministic details are still unspecified. Bioinformatics approaches are designed to investigate the relationships between two pathogens as well as fill this study void. Glioblastoma is a form of cancer that typically occurs in the brain or spinal cord and is highly destructive. A stroke occurs when a brain region starts to lose blood circulation and prevents functioning. Moyamoya disorder is a recurrent and recurring arterial disorder of the brain. To begin, adequate gene expression datasets on glioblastoma, ischemic stroke, and moyamoya disease were gathered from various repositories. Then, the association between glioblastoma, ischemic stroke, and moyamoya was established using the existing pipelines. The framework was developed as a generalized workflow to allow for the aggregation of transcriptomic gene expression across specific tissue; Gene Ontology (GO) and biological pathway, as well as the validation of such data, are carried out using enrichment studies such as protein-protein interaction and gold benchmark databases. The results contribute to a more profound knowledge of the disease mechanisms and unveil the projected correlations among the diseases.

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases.

Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

Potential Therapeutic Action of Autophagy in Gastric Cancer Managements: Novel Treatment Strategies and Pharmacological Interventions.

Gastric cancer (GC), second most leading cause of cancer-associated mortality globally, is the cancer of gastrointestinal tract in which malignant cells form in lining of the stomach, resulting in indigestion, pain, and stomach discomfort. Autophagy is an intracellular system in which misfolded, aggregated, and damaged proteins, as well as organelles, are degraded by the lysosomal pathway, and avoiding abnormal accumulation of huge quantities of harmful cellular constituents. However, the exact molecular mechanism of autophagy-mediated GC management has not been clearly elucidated. Here, we emphasized the role of autophagy in the modulation and development of GC transformation in addition to underlying the molecular mechanisms of autophagy-mediated regulation of GC. Accumulating evidences have revealed that targeting autophagy by small molecule activators or inhibitors has become one of the greatest auspicious approaches for GC managements. Particularly, it has been verified that phytochemicals play an important role in treatment as well as prevention of GC. However, use of combination therapies of autophagy modulators in order to overcome the drug resistance through GC treatment will provide novel opportunities to develop promising GC therapeutic approaches. In addition, investigations of the pathophysiological mechanism of GC with potential challenges are urgently needed, as well as limitations of the modulation of autophagy-mediated therapeutic strategies. Therefore, in this review, we would like to deliver an existing standard molecular treatment strategy focusing on the relationship between chemotherapeutic drugs and autophagy, which will help to improve the current treatments of GC patients.

Mycoremediation of reactive red HE7B dye by Aspergillus salinarus isolated from textile effluents.

Reactive dyes are widely utilized in the textile industry due to their advantageous properties of vivid color, water-fastness, and simple application procedures with minimal energy usage. The toxicity of most azo dyes is a significant environmental concern, as effluents from dye processing and manufacturing sectors are known to be carcinogenic and mutagenic to numerous species. These issues are more grievous in Bangladesh, one of the largest exporters of apparel. This study aimed to isolate and identify potential fungal strains from textile effluent that are capable of degrading Reactive Red HE7B dye (a sulphonated reactive azo dye), a widely used dye in local thread dyeing industries. Dye degradation assay was performed in potato dextrose broth supplemented with 50 mg/l Reactive Red HE7B and the degradation rate was measured by a UV spectrophotometer. DNA extraction, quantification, PCR, internal transcribed spacer (ITS) sequencing, and phylogenetic analysis were performed to identify the selected fungi. Among the isolates, the three best performing strains TEF -3, TEF -4, and TEF -5 showed 97.41%, 93.12%, and 82.89% dye degrading efficacy after 96 h of incubation, respectively. All three strains, TEF-3, TEF-4, and TEF-5 showed similarity with Aspergillus salinarus (accession no. NR_157473.1) and the similarity percentages were 97.02, 96.95, and 95.28 respectively. Interestingly, this study probably the very first indication of textile dye degradation by Aspergillus salinarus strains. Thus, these fungal strains possess the prospectiveness to be utilized in the textile wastewater treatment plants, since the isolates demonstrated the substantial capacity (>80%) to degrade Reactive Red dye after 96 h of incubation.

Comparative proteomic analysis to annotate the structural and functional association of the hypothetical proteins of S. maltophilia k279a and predict potential T and B cell targets for vaccination.

Stenotrophomonas maltophilia is a multidrug-resistant bacterium with no precise clinical treatment. This bacterium can be a vital cause for death and different organ failures in immune-compromised, immune-competent, and long-time hospitalized patients. Extensive quorum sensing capability has become a challenge to develop new drugs against this pathogen. Moreover, the organism possesses about 789 proteins which function, structure, and pathogenesis remain obscured. In this piece of work, we tried to enlighten the aforementioned sectors using highly reliable bioinformatics tools validated by the scientific community. At first, the whole proteome sequence of the organism was retrieved and stored. Then we separated the hypothetical proteins and searched for the conserved domain with a high confidence level and multi-server validation, which resulted in 24 such proteins. Furthermore, all of their physical and chemical characterizations were performed, such as theoretical isoelectric point, molecular weight, GRAVY value, and many more. Besides, the subcellular localization, protein-protein interactions, functional motifs, 3D structures, antigenicity, and virulence factors were also evaluated. As an extension of this work, 'RTFAMSSER' and 'PAAPQPSAS' were predicted as potential T and B cell epitopes, respectively. We hope our findings will help in better understating the pathogenesis and smoothen the way to the cure.

Community-acquired pneumonia: aetiology, antibiotic resistance and prospects of phage therapy.

Bacteria are the most common aetiological agents of community-acquired pneumonia (CAP) and use a variety of mechanisms to evade the host immune system. With the emerging antibiotic resistance, CAP-causing bacteria have now become resistant to most antibiotics. Consequently, significant morbimortality is attributed to CAP despite their varying rates depending on the clinical setting in which the patients being treated. Therefore, there is a pressing need for a safe and effective alternative or supplement to conventional antibiotics. Bacteriophages could be a ray of hope as they are specific in killing their host bacteria. Several bacteriophages had been identified that can efficiently parasitize bacteria related to CAP infection and have shown a promising protective effect. Thus, bacteriophages have shown immense possibilities against CAP inflicted by multidrug-resistant bacteria. This review provides an overview of common antibiotic-resistant CAP bacteria with a comprehensive summarization of the promising bacteriophage candidates for prospective phage therapy.