Association between APOA5 polymorphisms and susceptibility to metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: The association between Apolipoprotein A5 (APOA5) genetic polymorphisms and susceptibility to metabolic syndrome (MetS) has been established by many studies, but there have been conflicting results from the literature. We performed a meta-analysis of observational studies to evaluate the association between APOA5 gene polymorphisms and the prevalence of MetS. METHODS: PubMed, Web of Science, Embase, and Scopus were searched up to April 2024. The random effects model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) of the association between APOA5 gene polymorphisms and the prevalence of MetS development. The potential sources of heterogeneity were evaluated by subgroup analyses and sensitivity analyses. RESULTS: A total of 30 studies with 54,986 subjects (25,341 MetS cases and 29,645 healthy controls) were included. The presence of rs662799 and rs651821 polymorphisms is associated with an approximately 1.5-fold higher likelihood of MetS prevalence (OR = 1.42, 95% CI: 1.32, 1.53, p < 0.001; I2 = 67.1%; P-heterogeneity < 0.001; and OR = 1.50, 95% CI: 1.36-1.65, p < 0.001), respectively. MetS is also more prevalent in individuals with the genetic variants rs3135506 and rs2075291. There was no evidence of a connection with rs126317. CONCLUSION: The present findings suggest that polymorphisms located in the promoter and coding regions of the APOA5 gene are associated with an increased prevalence of MetS in the adult population. Identifying individuals with these genetic variations could lead to early disease detection and the implementation of preventive strategies to reduce the risk of MetS and its related health issues. However, because the sample size was small and there was evidence of significant heterogeneity for some APOA5 gene polymorphisms, these results need to be confirmed by more large-scale and well-designed studies.

Production of IgY polyclonal antibody against diphtheria toxin and evaluation of its neutralization effect by Vero cell assay.

BACKGROUND: Diphtheria is a bacterial disease which is caused by Corynebacterium diphtheriae. The symptoms are due to the diphtheria toxin produced by the bacteria. Antibiotic therapy and the use of diphtheria antitoxin is a recommended strategy to control diphtheria. Although mammalian antibodies are used to treat patients, IgY antibody has advantages over mammalian ones, including cost-effectiveness and production through non-invasive means. Moreover, in contrast to mammalian antibodies, IgY does not bind to the rheumatoid factor and does not activate the complement system. The objective of this study was to evaluate the in vitro neutralizing effect of IgY against diphtheria toxin. RESULTS: Anti-DT IgY was produced by immunization of the laying white leghorn chickens. Indirect enzyme-linked immunosorbent assay revealed successful immunization of the animals, and the IgY was purified with a purity of 93% via polyethylene glycol precipitation method. The neutralizing activity of the purified IgY was evaluated by Vero cell viability assay. This assay confirmed that 1.95 µg (8.6 µg/ml of culture medium) of anti-DT IgY would neutralize 10 fold of cytotoxic dose 99% of DT, which was 0.3 ng (1.33 ng/ml of culture medium). CONCLUSION: This anti-DT IgY may be applicable for diphtheria treatment and quality controls in vaccine production.

In vitro evaluation of cross-strain inhibitory effects of IgY polyclonal antibody against H. pylori.

The present study aimed to evaluate in vitro cross-strain inhibitory effects of IgY polyclonal antibody on both growth and urease enzyme of four local strains of H. pylori. Leghorn chickens were immunized with whole cells of four different strains of H. pylori, separately. Rising of specific IgY was detected by ELISA. The IgY purified using polyethylene glycol method and the purity was evaluated by SDS-PAGE and Western blotting. Each strain was treated with its own-specific and also other strain-specific IgYs. The strain-specific IgY could inhibit the growth of specific strains by 49-72% and also other different strains of H. pylori by 29-86%. Our findings revealed that strain-specific IgY could inhibit urease activity of its own by 64-72% and other different strains by 49-79%. These findings confirmed strain-specific and also cross-strain inhibitory effects of the IgY polyclonal antibody on both growth and urease activity of H. pylori.

Co-delivery of doxorubicin and paclitaxel via noisome nanocarriers attenuates cancerous phenotypes in gastric cancer cells.

Gastric cancer (GC) is known as a deadly malignancy all over the world, yet none of the current therapeutic regimens have achieved efficacy. this current study has aimed to optimize and reduce treatment doses and overcome multidrug resistance in GC by developing optimum niosomal formulation for the delivery of doxorubicin (DXR), paclitaxel (PTX), and their co-delivery. The particles' size, polydispersity index (PDI), and entrapment efficacy (EE%) were optimized using statistical techniques, i.e., Box-Behnken and Central Composite Design. In contrast to soluble drug formulations, the release rate of medicines from nanoparticles were higher in physiological and acidic pH. Niosomes were more stable at 4 °C, compared to 25 °C. The MTT assay revealed that the IC50 of drug-loaded niosomes was the lowest among all developed formulations. The apoptosis-related genes (CASPASE-3, CASPASE-8, and CASPASE-9) and tumor suppressor genes (BAX, BCL2) were evaluated in cancer cells before and after treatment. In comparison to control cells and cells treated with soluble forms of DXR and PTX, while the expression of BCL2 decreased, the expression of BAX, CASPASE-3, CASPASE-8, and CASPASE-9 was enhanced in cells treated with drug-loaded niosomes. Drug-loaded niosomes inhibited colony formation capacity and increased apoptosis in human AGS gastric cancer cells. Our results indicate that co-delivery of DXR and PTX-loaded niosomes may be an effective and innovative therapeutic approach to gastric cancer.

Organoid and microfluidics-based platforms for drug screening in COVID-19.

Proposing efficient prophylactic and therapeutic strategies for coronavirus 2019 (COVID-19) requires precise knowledge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. An array of platforms, including organoids and microfluidic devices, have provided a basis for studies of SARS-CoV-2. Here, we summarize available models as well as novel drug screening approaches, from simple to more advanced platforms. Notably, organoids and microfluidic devices offer promising perspectives for the clinical translation of basic science, such as screening therapeutics candidates. Overall, modifying these advanced micro and macro 3D platforms for disease modeling and combining them with recent advances in drug screening has significant potential for the discovery of novel potent drugs against COVID-19.

Hepatic stellate cell activation by TGFß induces hedgehog signaling and endoplasmic reticulum stress simultaneously.

Activation of hepatic stellates (HSCs) is known as the major cause of initiation and progression of liver fibrosis. A wide array of events occurs during HSC activation including induction of hedgehog (Hh) signaling and endoplasmic reticulum (ER) stress. Targeting HSC activation may provide promising insights into liver fibrosis treatment. In this regard, establishing in vitro models which can mimic the molecular pathways of interest is very important. We aimed to activate HSC in which Hh signaling and ER stress are stimulated simultaneously. We used 5 ng/ml TGFß to activate LX-2 cells, HSC cell line. Gene expression analysis using qRT-PCR, immunostaining and immunoblotting were performed to show HSC activation associated markers. Furthermore, the migration capacity of the TGFß treated cells is evaluated. The results demonstrated that major fibrogenic markers including collagen1a, lysyl oxidase, and tissue inhibitor of matrix metalloproteinase 1 genes are up-regulated significantly. In addition, our immunofluorescence and immunoblotting results showed that protein levels of GLI-2 and XBP1, were enhanced. Moreover, we found that TGFß treatment reduced the migration of LX-2 cells. Our results are compatible with high throughput data analysis with respect to differentially expressed genes of activated HSC compared to the quiescent ones. Moreover, our findings suggest that quercetin can reduce fibrogenic markers of activated HSCs as well as osteopontin expression, a target gene of hedgehog signaling.

Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.

Background: A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers' attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2'-chloro-5'-nitrobenzenesulfonyl)-2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. Results: In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. Conclusion: CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition.

Metabolic hallmarks of liver regeneration.

Despite the crucial role of cell metabolism in biological processes, particularly cell division, metabolic aspects of liver regeneration are not well defined. Better understanding of the metabolic activity governing division of liver cells will provide powerful insights into mechanisms of physiological and pathological liver regeneration. Recent studies have provided evidence that metabolic response to liver failure might be a proximal signal to initiate cell proliferation in liver regeneration. In this review, we highlight how lipids, carbohydrates, and proteins dynamically change and orchestrate liver regeneration. In addition, we discuss translational studies in which metabolic intervention has been used to treat chronic liver diseases (CLDs).

The impact of sex on susceptibility to systemic lupus erythematosus and rheumatoid arthritis; a bioinformatics point of view.

The unknown etiology of systemic autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), with a remarkable predominance of female, have prompted many researchers for unveiling the precise molecular mechanisms involved in this gender bias. In fact, depending on hormones and transcribed genes from sex chromosomes, at least, the initial mechanisms involved in pathogenesis might differ largely. With the aim of elucidating the above mechanisms, we have tried to specify the differentially expressed genes (DEGs) extracted from microarray libraries from both female and male SLE and RA patients. Subsequently, the androgen and estrogen receptor elements (ARE and ERE) among differentially expressed transcription factors (TFs) and the DEGs located on X or Y chromosomes have been determined. Moreover, the pathways regarding the common DEGs in both sexes are enriched. Our data revealed several ARE and ERE-containing genes (LCN2, LTF, RPL31, RPL9, RPS17, RPS24, RPS27L, S100A8, ABCA1, HIST1H2BD, ISG15, MAFB, GNLY, EVL, and HDC) to be associated with the related autoimmune disease and sex. Also, two DEGs (KDM5D and RPS4Y1) in SLE patients were determined to be on Y chromosome with one had been proved to be associated with autoantigens in SLE. Altogether, our data showed a number of plausible pathways in both autoimmune conditions together with the relevance of several sex-related genes in the mentioned diseases pathogenesis.

Novel molecular targets in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related death worldwide. A high mortality rate and resistance to treatment protocols due to a heterogeneous molecular pathogenesis has made discovering the key etiologic molecular alterations of the utmost importance. The remarkable role played by epigenetic modifications in repressing or activating many cancer-related genes and forming new epigenetic signatures can affect cancer initiation and progression. Hence, targeting the key epigenetic drivers could potentially attenuate cancer progression. MLLs, ARID1A and EZH2 are among the major epigenetic players that are frequently mutated in GACs. In this paper, we have proposed the existence of a network between these proteins that, together with PCAF and KDM6A, control the 3D chromatin structure and regulate the expression of tumor suppressor genes (TSGs) and oncogenes in GAC. Therefore, we suggest that manipulating the expression of EZH2, PCAF, and KDM6A or their downstream targets may reduce the cancerous phenotype in GAC.

Therapeutic modalities and novel approaches in regenerative medicine for COVID-19.

The recent coronavirus disease 2019 outbreak around the world has had an enormous impact on the global health burden, threatening the lives of many individuals, and has had severe socio-economic consequences. Many pharmaceutical and biotechnology companies have commenced intensive research on different therapeutic strategies, from repurposed antiviral drugs to vaccines and monoclonal antibodies to prevent the spread of the disease and treat infected patients. Among the various strategies, advanced therapeutic approaches including cell- and gene-editing-based therapeutics are also being investigated, and initial results in in-vitro and early phase I studies have been promising. However, further assessments are required. This article reviews the underlying mechanisms for the pathogenesis of severe acute respiratory syndrome coronavirus-2, and discusses available therapeutic candidates and advanced modalities that are being evaluated in in-vitro/in-vivo models and are of note in clinical trials.

Optimization of rPDT fusion protein expression by Escherichia coli in pilot scale fermentation: a statistical experimental design approach.

High yield recombinant protein production is highly desirable for biotechnological purposes. In the design of recombinant expression conditions, a number of essential central elements such as expression strain, type of medium, bioprocess optimization, and mathematical modeling should be considered. Well-designed industrial scale production of one recombinant protein with optimized influential parameters and yield can address the cost and production reproducibility issues. In the present study, statistical experimental design methodology was used to investigate the effect of fermentation conditions (dissolved oxygen, IPTG, and temperature) on rPDT production by Escherichia coli. rPDT is a recombinant fusion protein consisting of three different protein domains including the N-terminal 179 amino acid fragment of the S1 subunit of pertussis toxin, the full-length genetically detoxified diphtheria toxin (CRM197), and the 50 kDa tetanus toxin fragment C. A 15 Box-Behnken design augmented with center points revealed that IPTG and DO at the center point and low temperature will result in high yield. The optimal condition for rPDT production were found to be 100 µM IPTG, DO 30% and temperature 20 °C.

Rapid fluorometric quantification of bacterial cells using Redsafe nucleic acid stain.

BACKGROUND AND OBJECTIVES: Numerous procedures in biology and medicine require the counting of cells. Direct enumeration of Colony Forming Units (CFUs) is time-consuming and dreary accurate cell counting on plates with high numbers of CFUs is error prone. In this study we report a new indirect cell counting method that was developed based on the use of Redsafe fluorometric assay. The usefulness of Redsafe, a nucleic acid stain, in liquid medium is based on the binding of the fluorescent dye to DNA. MATERIALS AND METHODS: Redsafe fluorometric assay was evaluated in comparison with MTT colorimetric assay as a colourimetric assay for enumeration of bacterial cells. RESULTS: Obtained results showed that fluorometric assay threshold for LB grown E. coli is 6×10(4) CFU/ml. Redsafe fluorescent assay can be used as a rapid and inexpensive method for bacterial enumeration and quantification with increased sensitivity. CONCLUSION: The sensitivity of the Redsafe fluorometric assay for detection and enumeration of bacterial cells was 2-log-unit more than that was observed for the MTT assay.