Hydroxychloroquine ameliorates immune functionality and intestinal flora disorders of IgA nephropathy by inhibition of C1GALT1/Cosmc pathway.

BACKGROUND: Hydroxychloroquine (HCQ) has emerged as a potential and secure antiproteinuric agent in IgA nephropathy (IgAN). This study endeavored to explore the impact of HCQ on the immune functionality and intestinal flora disorders in IgAN rats, as well as to elucidate the underlying mechanisms through in vivo and in vitro experiments. METHODS: IgAN model was established in Sprague-Dawley rats through the administration of BSA, LPS, and CCl4, and the IgAN rats received a continuous 8-week treatment with HCQ. Moreover, the human glomerular mesangial cells (HMCs) were incubated with IgA1 to establish an in vitro cellular model of IgAN. At the end of experimental period, samples were collected for further analysis. RESULTS: HCQ ameliorated the elevated levels of 24hUTP, SCr, BUN, the number of urinary RBC, and the activation of inflammation-related proteins within the TLR4/NF-κB signaling pathway. In the IgAN rat group, there was a pronounced escalation in IgA deposition, mesangial matrix hyperplasia, and glomerular inflammatory cell infiltration, while the administration of HCQ effectively mitigated these pathological changes. In addition, the reduced production of CD4+CD25+Foxp3+ Treg in the IgAN group was effectively reversed by HCQ. Furthermore, HCQ has the capacity to restore the compromised state of the intestinal mucosal barrier induced by IgAN and mitigate the circumstances of intestinal permeability and disruption in the intestinal flora. CONCLUSION: HCQ diminishes IgA aberrant glycosylation levels, ameliorates renal and intestinal histopathological damage, and attenuates intestinal flora disorders and immune dysfunction in IgAN rats by means of activating the C1GALT1/Cosmc pathway.

Exploring the effect of microecological agents on postoperative immune function in patients undergoing liver cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Precision hepatectomy for primary liver cancer has been widely used in clinical practice. As an effective nutritional supplement to prevent endotoxemia and hepatic impairment, microecological agents have been used together with traditional enteral nutritional support substances in several clinical studies. METHODS: Chinese and English databases were searched using the terms "hepatocellular carcinoma", "hepatectomy", "microecological agents", and "microecological regulators". The search terms were "hepatocellular carcinoma", "liver resection", "microecological agents", and "microecological regulators". Meta-analysis was performed using Rev Man 5.3 and Stata 13 software provided by the Cochrane system. RESULTS: Eleven randomized controlled trials (RCTs) were included in this study. Of these, all 11 described the correct method of random assignment; 8 described in detail the concealment of the assignment scheme; and 9 used blinding methods in the research. Microecological agents significantly reduced total bilirubin (TBIL) levels [mean difference (MD)=-0.10, 95% confidence interval (CI): (-0.14, -0.06), P<0.00001] of patients after hepatectomy. The alanine transaminase (ALT) levels [MD =-3.65, 95% CI: (-14.65, 7.34), P=0.52], aspartate aminotransferase (AST) levels [MD =-0.64, 95% CI: (-6.87, 5.58), P=0.84], prothrombin level [MD=1, 95% CI: (-2.57, 4.57), P=0.58], and C-reactive protein (CRP) level [MD =-0.28, 95% CI: (-3.01, 2.45), P=0.84] among the included articles were statistically significant. However, probiotics could significantly reduce the risk of postoperative infection in patients with liver cancer (MD =0.23, 95% CI: (0.07, 0.79), P=0.02 <0.05), and did not significantly increase the risk of complications in patients with liver cancer [odds ratio (OR) =0.82, 95% CI: (0.38, 1.77), P=0.61]. DISCUSSION: This study used meta-analysis to confirm that microecological agents can significantly improve the immune function of patients with hepatocellular carcinoma, and have alleviating effects on endotoxemia and hyperbilirubinemia.

In vitro uptake and immune functionality of digested Rosemary extract delivered through food grade vehicles.

The digestion, absorption, uptake and bioavailability of a rosemary supercritical fluid extract encapsulated in oil in water emulsion were studied. Two emulsions with opposite surface charge were prepared, containing 7% canola oil, and either 2% lactoferrin or whey protein isolate. When absorption and uptake of carnosic acid and carnosol were followed on Caco-2 cell monolayers, there were no differences with protein type. However, when co-cultures of HT-29 MTX were employed, the presence of mucus caused a higher retention of carnosic acid in the apical layer for lactoferrin emulsions. The immune activity of the bioavailable fractions collected from cell absorption experiments was tested ex vivo on murine splenocytes. Although transport through the intestinal barrier models was low, the bioavailable fractions showed a significant effect on splenocytes proliferation. These results demonstrated the potential of using rosemary supercritical extract through protein stabilized oil in water emulsions, as a food with immunomodulatory functionality.

Nanoparticle and polysaccharide conjugate: a potential candidate vaccine to improve immunological stimuli.

Active polysaccharides isolated from various fungal sources have been implicated to stimulate immune response against various pathogens as well as self anomalies such as cancer. Therefore, the nuanced approach presented in our work was to blend polysaccharides derived from Pleurotus ostreatus with biocompatible ferrite nanoparticles and thereafter investigate the enhanced immune functionality of the polysaccharide-nanoparticle composite. A Schiff base reductive amination reaction occurred between the aldehyde group of the polysaccharide and the amine group of the nanoparticles in the presence of a strong reducing agent such as sodium cyanoborohydride to form a stable amide bond between the two conjugating molecules. The multifaceted conjugate was characterized by physiochemical techniques such as electron microscopy, FTIR, VSM and DLS measurements. This particulate form of the polysaccharide showed a marked escalation in the production of free radicals such as reactive oxygen and nitrogen species in murine macrophages as compared to the soluble form. Animal based experiments demonstrated a reduction in tumor volume and augmentation in the proliferation of splenocytes in particulate or conjugated polysaccharide treated mice. Furthermore, molecular signaling studies showed a high upregulation in p-p38 and p-MEK molecules in particulate polysaccharide treated RAW264.7 cells suggesting a cellular downstream mechanistic regulation behind the immunostimulative response.

A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes.

Participants with CFS were grouped into viral and non-viral onset fatigue categories and assessed for differential immunological marker expression. Peripheral Blood Mononuclear Cells were assessed for differential phenotypic expression of surface adherence glycoproteins on circulating lymphocytes. The flow cytometric analysis employed fluorescent monoclonal antibody labeling. The viral in comparison to the non-viral group demonstrated significant elevations in several Th1 type subsets including: the percentage and number of CD4+ cells, the percentage and number of CD2+CD26+ cells, the percentage and number of CD2+CD4+CD26+ cells, the percentage and number of CD4+ CD26+ cells, and the percentage of Th2 naïve cells (CD4+ CD45RA+CD62L+). Of the remaining significant findings, the non viral group demonstrated significant elevations in comparison to the viral group for the following Th1 type subsets: the percentage of CD8+ cells, the percentage of T-cytotoxic suppressor cells (CD3+8+), and the percentage and number of Th1 memory cells (CD8+CD45RA-CD62L-). The viral group demonstrated a pattern of activation that differed from that of the group with a non-viral etiology, as evidenced by an elevated and out of range percentage and number of CD4+ cells, the percentage of CD2+CD26+, and the percentage of Th2 naïve cells (CD4+CD45RA+CD62L+). Both groups demonstrated reduced and out of range Natural Killer Cell Cytotoxicity and percentage of B-1 cells (CD5+CD19). In addition, both groups demonstrated an elevated and out of range percentage of CD2+CD8+CD26+, percentage of the Th1 memory subset (CD4+CD45RA-CD62L-), the percentage of Th1 memory and naïve cells (CD8+CD45RA-CD62L-, CD8+CD45RA+CD62L-), the percentage and number of Th2 memory cells (CD4+CD45RA-CD62L+), and the percentage of Th2 memory and naïve cells (CD8+CD45RA-CD62L+, CD8+CD45RA+CD62L+). These findings imply that the homeostatic mechanism responsible for the regulation of the Th1 (cell mediated) and Th2 (humoral) immune responses is disturbed in CFS. The implications of these findings are discussed.