Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS

Oxidative phosphorylation (OXPHOS) is a vital pathway provides ATP for intracellular activities. Here, we found that Hantaan virus (HTNV) exploited mitochondria OXPHOS to assist its replication in host cells and Protein Kinase B/AKT played a major function in this process. Inhibiting AKT activation by BEZ treatment can inhibit HTNV replication and prevent the increase of OXPHOS level caused by HTNV infection. We also found that HTNV infection can promote AKT translocation to mitochondria, where AKT phosphorylates Polynucleotide phosphorylase (PNPT). Taken together, our research demonstrates that HTNV replication exploits OXPHOS in host cells and it increases OXPHOS function by AKT-PNPT interaction in mitochondria.

Specialized protrusions coordinate migratory border cell cluster cohesion via Scribble, Cdep, and Rac

Apicobasal polarity is a defining characteristic of epithelial cells and its disruption is a cancer hallmark. Distinct apical and basolateral protein modules antagonize each other to establish separate membrane domains. These modules interact with dozens of potential effector proteins. Here we describe polarity protein localization and function within a migrating epithelial cell cluster and identify a functionally significant effector protein. In Drosophila egg chambers, border cells delaminate from the follicular epithelium and migrate collectively. We report that the basolateral protein Scribble is required for border cell cluster cohesion and migration. The basolateral module localizes the Rac guanine nucleotide exchange factor Cdep to membranes, and Cdep knockdown phenocopies Scribble cluster cohesion defects. Remarkably, membrane targeting of Cdep is sufficient to partially suppress multiple Scribble phenotypes. We describe specialized basolateral protrusions that promote cluster cohesion. Scribble restricts these protrusions from encroaching onto the apical domain. Thus, a major function of the basolateral module is to localize Cdep, promoting specialized protrusions, cluster cohesion, and collective migration.

Scavenger receptors in host defense: from functional aspects to mode of action

Scavenger receptors belong to a superfamily of proteins that are structurally heterogeneous and encompass the miscellaneous group of transmembrane proteins and soluble secretory extracellular domain. They are functionally diverse as they are involved in various disorders and biological pathways and their major function in innate immunity and homeostasis. Numerous scavenger receptors have been discovered so far and are apportioned in various classes (A-L). Scavenger receptors are documented as pattern recognition receptors and known to act in coordination with other co-receptors such as Toll-like receptors in generating the immune responses against a repertoire of ligands such as microbial pathogens, non-self, intracellular and modified self-molecules through various diverse mechanisms like adhesion, endocytosis and phagocytosis etc. Unlike, most of the scavenger receptors discussed below have both membrane and soluble forms that participate in scavenging; the role of a potential scavenging receptor Angiotensin-Converting Enzyme-2 has also been discussed whereby only its soluble form might participate in preventing the pathogen entry and replication, unlike its membrane-bound form. This review majorly gives an insight on the functional aspect of scavenger receptors in host defence and describes their mode of action extensively in various immune pathways involved with each receptor type.

Formulation and evaluation of dexlansoprazole extended-release tablet

Dexlansoprazole (DSP) is a proton pump inhibitor, it used to treat GERD and ulcer colitis. DSP works by decreasing the volume of acid in the stomach. DSP is an acid-labile medication that may be destroyed in the stomach's acidic pH. A coating technique was used to postpone drug release in the stomach, which can extend pharmacological activity. Shellac can be used to develop the sustain release tablet of dexlansoprazole as retardation of the drug (dexlansoprazole) was observed in the acidic pH of the stomach, and hence a sustain coated dexlansoprazole tablet was prepared and evaluated. The coating's primary function is to allow for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits faster degradation in the acidic pH of the stomach, therefore increasing pharmacological action. DSP coating with different polymers inhibits fast degradation in the stomach's acidic pH, enhancing pharmacological action. The major function of the coating is to enable for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits fast breakdown in the stomach's acidic pH, enhancing pharmacological action.

Channels and Transporters of the Pulmonary Lamellar Body in Health and Disease

The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific surfactant proteins. The major function of surfactant in the lung is the reduction of surface tension and stabilization of alveoli during respiration. Its lack or deficiency may cause various forms of respiratory distress syndrome (RDS). Surfactant is also part of the innate immune system in the lung, defending the organism against air-borne pathogens. The limiting (organelle) membrane that encloses the LB contains various transporters that are in part responsible for translocating lipids and other organic material into the LB. On the other hand, this membrane contains ion transporters and channels that maintain a specific internal ion composition including the acidic pH of about 5. Furthermore, P2X4 receptors, ligand gated ion channels of the danger signal ATP, are expressed in the limiting LB membrane. They play a role in boosting surfactant secretion and fluid clearance. In this review, we discuss the functions of these transporting pathways of the LB, including possible roles in disease and as therapeutic targets, including viral infections such as SARS-CoV-2.

Production and Analysis of Lip Balm using Herbal Resources

Lip care products are an integral part of a day-to-day lifestyle. These impart the colour and protect the lips from the external environment. The major function of lip balm is to protect and moisturize the lips. A variety of lip care products are available in the market. The main concern with this product is that these contain synthetic colourant and flavouring agents that may have adverse effects such as darkening of lips. Besides, these may contain heavy metals that adversely affect various body organs. The current research work deals with preparation lip balm by using maximum possible natural ingredients and evaluation of the formulation. Various natural ingredients used were beetroot extract, Cocoa powder, Almond oil and Vitamin E. The physicochemical properties such as colour, odour, consistency, spreadability, melting point, pH and stability were studied. It was found that the formulation possesses red colour due to the addition of beetroot pigments, it had a typical flavour of cocoa powder, uniform in consistency and good spreadability. The melting point and pH of formulation were found to be 58-60°C ± 0.62 and 6.9 ± 0.25 respectively. The stability study indicated that formulation is stable at room temperature and refrigeration temperature. It can be concluded that lip balm formulation was successfully prepared by using these natural additives and better alternatives to synthetic excipients.

Metformin Inhibits Mitochondrial Complex I To Promote Health

The major function of mitochondria in cellular homeostasis has been the generation of ATP through oxidative phosphorylation. However, we have previously demonstrated that mitochondria can serve as signaling organelles by releasing low levels of reactive oxygen species (ROS) and TCA cycle metabolites that are essential for hypoxic activation of HIF, antigen activation of T cells, cellular differentiation and proliferation of cancer cells. The anti-diabetic drug metformin has been proposed to inhibit mitochondrial complex I. We will present data indicating that metformin inhibits mitochondrial complex I to exert it’s biological effects through controlling ROS, ATP, and NAD+.

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease

Gaucher disease is a lysosomal storage disease, which happens due to mutations in GBA1/Gba1 that encodes the enzyme termed as lysosomal acid β-glucosidase. The major function of this enzyme is to catalyze glucosylceramide (GC) into glucose and ceramide. The deficiency of this enzyme and resultant abnormal accumulation of GC cause altered function of several of the innate and adaptive immune cells. For example, augmented infiltration of T cells contributes to the increased production of pro-inflammatory cytokines, (e.g., IFNγ, TNFα, IL6, IL12p40, IL12p70, IL23, and IL17A/F). This leads to tissue damage in a genetic mouse model (Gba19V/−) of Gaucher disease. The cellular mechanism(s) by which increased tissue infiltration of T cells occurs in this disease is not fully understood. Here, we delineate role of the CXCR3 receptor and its exogenous C-X-C motif chemokine ligand 9 (CXCL9) in induction of increased tissue recruitment of CD4+ T and CD8+ T cells in Gaucher disease. Intracellular FACS staining of macrophages (Mϕs) and dendritic cells (DCs) from Gba19V/− mice showed elevated production of CXCL9. Purified CD4+ T cells and the CD8+ T cells from Gba19V/− mice showed increased expression of CXCR3. Ex vivo and in vivo chemotaxis experiments showed CXCL9 involvement in the recruitment of Gba19V/− T cells. Furthermore, antibody blockade of the CXCL9 receptor (CXCR3) on T cells caused marked reduction in CXCL9- mediated chemotaxis of T cells in Gba19V/− mice. These data implicate abnormalities of the CXCL9-CXCR3 axis leading to enhanced tissue recruitment of T cells in Gaucher disease. Such results provide a rationale for blockade of the CXCL9/CXCR3 axis as potential new therapeutic targets for the treatment of inflammation in Gaucher disease.

Analysis of the prognostic biomarkers associated with cancer stem cell characteristics and immune infiltration of Helicobacter pylori-induced gastric cancer

BackgroundChina is a country with a high incidence of gastric cancer, accounting for about half of the new cases in the world every year. The development of Gastric cancer (GC) is closely related to Helicobacter pylori (H. pylori) infection. Cancer stem cells (CSCs) play important roles in the survival, proliferation, metastasis and recurrence of tumors. However, the mechanism of CSCs and H. pylori-induced GC remains unclear.At the same time, the effect of tumor microenvironment on tumor stem cells and GC with H. pylori infection is also worth exploring. On the basis of the existing research on GC, it is still of great significance to further understand and explore the pathogenesis of GC through bioinformatics analysis.ResultsThere was higher mRNA expression-based stemness index (mRNAsi) in H. pylori (+) GC tumor tissue than in normal tissue. The clinical features of stage T and N were highly correlated with mRNAsi. The purple module was the most significant modules related to the mRNAsi by WGCNA and its key genes played played a major function related to tumor immunity, mainly involved in regulating the Jak-STAT signal pathway, Th17 cell differentiation pathway, and so on. These key genes were correlated with the high level of immune infiltration of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in GC via Tumor Immune Estimation Resource (TIMER). 28 genes were found to be closely related to the characteristics of gastric CSCs (GCSCs) associated with H. pylori infection. 13 genes were associated with lymph node metastasis in GC, which may lead to poor prognosis in patients.ConclusionThe characteristics of GCSCs were related to the interleukins signaling, cytokine signaling, Jak-STAT signaling pathway, which provides a new idea for screening therapeutic targets to inhibit the characteristics of GCSCs and a basis for the eradication of H. pylori and the prevention of GC.

Enhancer analysis of the Drosophila zinc finger transcription factor Earmuff by gene targeting

Background Many transcription factors are involved in the formation of the brain during the development of Drosophila melanogaster. The transcription factor Earmuff (Erm), a member of the forebrain embryonic zinc finger family (Fezf), is one of these important factors for brain development. One major function of Earmuff is the regulation of proliferation within type II neuroblast lineages in the brain; here, Earmuff is expressed in intermediate neural progenitor cells (INPs) and balances neuronal differentiation versus stem cell maintenance. Erm expression during development is regulated by several enhancers. Results In this work we show a functional analysis of erm and some of its enhancers. We generated a new erm mutant allele by gene targeting and reintegrated Gal4 to make an erm enhancer trap strain that could also be used on an erm mutant background. The deletion of three of the previously analysed enhancers showing the most prominent expression patterns of erm by gene targeting resulted in specific temporal and spatial defects in defined brain structures. These defects were already known but here could be assigned to specific enhancer regions. Conclusion This analysis is to our knowledge the first systematic analysis of several large enhancer deletions of a Drosophila gene by gene targeting and will enable deeper analysis of erm enhancer functions in the future.