Inflammatory bowel disease (IBD) is a chronic inflammatory condition of gastrointestinal (GI) tract with dysregulated mucosal immune functions and disturbed commensal ecosystem of the intestinal lumen. IBD is categorized into two major subsets: Crohn’s disease (CD) and ulcerative colitis (UC). Though advent of biologics has shifted the treatment with relatively longer remission compared to small molecule pharmaceuticals, patients still suffer from long-term complications. Since gut-microbiome is now accepted as another human organ holding potential for long-lasting human health, probiotics, and its engineering hold great promises to treat several previously untreatable chronic inflammatory conditions including IBD. Several emerging biological engineering tools have unlimited potential to manipulate probiotic bacterial system. These can produce useful therapeutic biologics with a goal to either ameliorate and/or treat previously untreatable chronic inflammatory conditions. As gut-microbiome is diverse and vary in different ethnic, geographic, and cultural human population, it will be important to develop vision for personalized probiotic treatment and develop the technology thereof to make personalized probiotic options a reality. The aim of this review paper is to present an overview of the current knowledge on both pharmacological and nonpharmacological IBD treatment modalities with a special emphasis on probiotic strains that are developed through the probiotic engineering. These engineered probiotics contain the most anti-inflammatory cytokines found within the human immune response and are currently being used to treat the intestinal inflammation in IBD for the IBD treatment.
Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER) resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs.Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Further, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Further, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage.We also present an overview of the pathogenic mechanisms with a brief focus on potential strategies for pharmacological interventions.
Janus kinases (Jaks) are a family of nonreceptor tyrosine kinase that include four different members, viz., Jak1, Jak2, Jak3, and Tyk2. Jaks play critical roles in immune cells functions; however, recent studies suggest they also play essential roles in nonimmune cell physiology. This review highlights the significance of epithelial Jaks in understanding the molecular basis of some of the diseases through regulation of epithelial-mesenchymal transition, cell survival, cell growth, development, and differentiation. Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. Among Jaks, Jak3 is widely expressed in both immune cells and in intestinal epithelial cells (IECs) of both humans and mice. Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 mutations lead to the development of hematologic and epithelial cancers. A selective Jak3 inhibitor CP-690550 (Xeljanz) approved by the FDA for certain chronic inflammatory conditions demonstrates immunosuppressive activity in rheumatoid arthritis, psoriasis, and organ transplant rejection. Here, we also focus on the consequences of Jak3-directed drugs on adverse effects in light of recent discoveries in mucosal epithelial functions of Jak3 with some information on other Jaks. Lastly, we brief on structural implications of Jak3 domains beyond the immune cells. As information about the roles of Jak3 in gastrointestinal functions and associated diseases are only just emerging, in the review, we summarize its implications in gastrointestinal wound repair, inflammatory bowel disease, obesity-associated metabolic syndrome, and epithelial cancers. Lastly, we shed lights on identifying potential novel targets in developing therapeutic interventions of diseases associated with dysfunctional IEC.
Background Alzheimer’s disease (AD), a neurodegenerative disease, is the most common form of dementia among older patients and is the 6th leading cause of death in the US. Almost 1 in 10 people over the age of 65 have AD and every 65 second someone in the US develop AD. Worldwide 30 million people have AD, and 5.8 million American are living with this disease where by 2050, it is projected to be 14 million. Problems in AD and other forms of dementia involve an irreversible brain tissue damage and destruction, leading to progressive cognitive impairment led difficulty of performing simple tasks. In 2019, AD and other dementia in US costed $290 billion. By 2050, these costs could rise as high as 1.1 trillion. Due to technological advancements in artificial intelligence, the computer can not only plan & predict the path or course for a robot, but for multiple proteins and their metabolites. Several digital models and simulations can determine the interactions and commonality between proteins of all sorts. The goal of this project is to identify biological markers by metabolomic meta‐analysis that correlate with the progression of AD and be integrated to a prototype biosensor capable of detecting the stable biomarker for an early detection of dementia. This project analyzes the commonalties in dementia related proteins through data mining and analysis of the cerebrospinal fluid and blood metabolome to see (when altered in Alzheimer disease) the metabolic reactions that could potentially relate to phenotypes detectable for an early onset Alzheimer's. Along with that, the project utilizes the novel findings to assemble a detection system via electrochemical analysis by observing the difference in the relative resistance between varying solution of key analyte changed in Alzheimer’s patient. Material and Methods Plastic straw, Hydrogel, Electrical resistant measuring machine and specialized Electrode. Protein sequences analysis: Information on the proteins that are associated with the Alzheimer diseases were obtained from PubMed; Amino acid sequences of these proteins (in FASTA format) were obtained through ExPASy. The amino acid sequences of proteins in FASTA format were obtained from the UniProt database in Expasy. Clastalw‐Multiple Alignment: The commonality in the protein sequences was deduced obtained by aligning multiple protein sequences through the Clustal‐W. Results and Conclusion Bioinformatics tools and computer algorithms shows three dimensional structures of Alzheimer’s disease associated proteins where majority of them were associated with the membrane. Mutational analysis indicated that most of them in AD fall into transmembrane regions of the protein which may be due to change in lipid composition of the cells. Metabolomics studies indicated that the relative abundance of lipid metabolites was relatively low in the blood of AD compared to healthy or MCI. In contrast, the cerebrospinal fluid levels of lipid metabolites were higher in AD/dementia patients compared to their healthy counterparts. Increased l...
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