Hypolipidemic effect of brown seaweed (Sargassum crassifolium) extract in vivo (Study of histopathology, mRNA expression, and immunohistochemistry (IHC) with VCAM-1, ICAM-1, and MCP-1 parameters).

The purpose of this study was to obtain natural drugs from brown seaweed (Sargassum crassifolium) as antiatherosclerosis candidates through the study of hypolipidemic mechanisms of action. Modeling of dyslipidemia rats was carried out by feeding high-fat (HFF) and doses of crude fucoidan 100. 200. 400mg / KgBB. in both treatments measured blood lipid profile levels taken from the orbital sinuses. HE's histopathology. mRNA expression. immunohistochemistry (IHC) with parameters VCAM-1. ICAM-1. and MCP-1 were performed on adipose tissue. as well as liver. Total cholesterol values 51.07-225.2. triglycerides 30.43-115.73. HDL 13.1-24.86 mg/dl and LDL 20.22-189.68 mg/dl. In the treatment of crude fucoidan obtained the result of p value < α (0.05. Histopathological features of adipose tissue after administration of HFF for 60 days resulted in an increase in adipose cell size. and the liver experienced structural damage and inflammation. but after 21 days of treatment the morphological picture of adipose tissue was similar to normal morphology and the liver also decreased in severity and inflammation. The results of histochemical staining after treatment showed a positive staining part on MCP-1. The result of p value < α (0.05) of mRNA expression for administration of 3 treatment doses. A dyslipidemic mouse model with HFF administration for 60 days succeeded in becoming a dyslipidemic rat. and crude fucoidan had hypolipidemic activity. Doses of 100. 200. and 400 mg/KgBB crude fucoidan showed improvement in adipose and liver morphological features of severity and inflammation of dyslipidemic rats and decreased mRNA expression.

Upregulated IL-32 Expression And Reduced Gut Short Chain Fatty Acid Caproic Acid in People Living With HIV With Subclinical Atherosclerosis.

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, ß, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1ß and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1ß in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH.

Upregulation of IL-32 Isoforms in Virologically Suppressed HIV-Infected Individuals: Potential Role in Persistent Inflammation and Transcription From Stable HIV-1 Reservoirs.

BACKGROUND: Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4 T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory. SETTING AND METHODS: Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4 T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4 T-cells from HIV-1cART individuals by qRT-PCR. RESULTS: All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV individuals with IL-32ß representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4 T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32ß showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32ß, induced HIV-1 production in latently infected CD4 T-cells isolated from combined antiretroviral therapy-treated individuals. CONCLUSIONS: Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.

Popular Mobile Phone Apps for Diet and Weight Loss: A Content Analysis.

BACKGROUND: A review of the literature has revealed that the rates of overweight and obesity have been increasing in Australia over the last two decades and that wellness mobile phone apps play a significant role in monitoring and managing individuals' weight. Although mobile phone app markets (iTunes and Google Play) list thousands of mobile phone health apps, it is not always clear whether those apps are supported by credible sources. Likewise, despite the prevailing use of mobile phone apps to aid with weight management, the usability features of these apps are not well characterized. OBJECTIVE: The research explored how usability taxonomy could inform the popularity of downloaded, socially focused wellness mobile phone apps, in particular weight loss and diet apps. The aim of the study was to investigate the Australian mobile phone app stores (iTunes and Google Play) in order to examine the usability features of the most popular (ie, most downloaded) wellness apps. METHODS: The design of this study comprises 3 main stages: stage 1, identifying apps; stage 2, development of weight loss and diet evaluation framework; and stage 3, application of the evaluation framework. Each stage includes specific data collection, analysis tools, and techniques. RESULTS: The study has resulted in the development of a justified evaluation framework for weight loss and diet mobile phone apps. Applying the evaluation framework to the identified apps has shown that the most downloaded iTunes and Google Play apps are not necessarily the most usable or effective. In addition, the research found that search algorithms for iTunes and Google Play are biased toward apps' titles and keywords that do not accurately define the real functionality of the app. Moreover, the study has also analyzed the apps' user reviews, which served as justification for the developed evaluation framework. CONCLUSIONS: The analysis has shown that ease of use, reminder, bar code scanning, motivation, usable for all, and synchronization are significant attributes that should be included in weight loss and diet mobile phone apps and ultimately in potential weight loss and diet evaluation frameworks.