👤 Reyhaneh Maleki

Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes mellitus and a leading cause of end-stage renal disease worldwide. Although hyperglycemia and hypertension are well-established drivers of DKD, accumulating evidence suggests that additional factors, such as lipoprotein(a) [Lp(a)], may contribute to its pathogenesis. Lp(a) is a genetically determined lipoprotein with pro-atherogenic, pro-inflammatory, and pro-thrombotic properties, and elevated circulating levels have been associated with increased cardiovascular and renal risk in diabetic individuals. In this review, we summarize the current understanding of the relationship between Lp(a) and DKD, with a focus on the proposed molecular mechanisms. These include activation of TGF-β/Smad signaling leading to fibrosis, induction of oxidative stress, chronic inflammation, endothelial dysfunction, impaired fibrinolysis, and direct injury to podocytes resulting in proteinuria. While several clinical and experimental studies support the involvement of Lp(a) in these pathways, the precise molecular mediators remain largely undefined. Understanding these mechanisms may offer novel insights into the pathophysiology of DKD and identify new therapeutic targets. This article aims to provide a comprehensive overview of the potential role of Lp(a) in DKD and to highlight areas requiring further investigation. Show less

Encapsulation of Lactiplantibacillus plantarum (L. plantarum) ZGP-Lpl.19 in alginate-pectin-chitosan microcapsules significantly improved its survival under simulated gastrointestinal conditions and attenuated Shigella flexneri (S. flexneri) growth and pathogenicity through downregulation of the mdoH and IcsA virulence genes. Microencapsulation was achieved via extrusion using a polysaccharide blend, yielding an encapsulation efficiency of 98.44%. Structural integrity of the microcapsules was confirmed by scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Encapsulation markedly enhanced probiotic survivability, with viable counts of 5.37 log CFU/mL after 60 min in gastric fluid and 120 min in intestinal fluid, compared with 2.25 log CFU/mL for free cells. Both encapsulated and free L. plantarum ZGP-Lpl.19 demonstrated potent antimicrobial activity against S. flexneri ATCC 12022, with comparable antimicrobial metabolite production. The minimum inhibitory concentration (MIC) of cell-free supernatants from both forms was 1/8 of the original concentration. Importantly, real-time PCR analysis confirmed that both encapsulated and free cells significantly downregulated mdoH and IcsA expression. Overall, these findings demonstrate that alginate-pectin-chitosan microencapsulation provides effective protection for L. plantarum and enhances its functional delivery, positioning encapsulated L. plantarum as a promising therapeutic strategy to mitigate S. flexneri infections. Show less

IL-27 is structurally an immune-enhancing and pleiotropic two-chain cytokine associated with IL-12 and IL-6 families. IL-27 contains two subunits, namely IL-27p28 and EBI3. A heterodimer receptor of IL-27, composed of IL27Rα (WSX1) and IL6ST (gp130) chains, mediates the IL-27 function following the activation of STAT1 and STAT3 signaling pathways. Specifically, IL-27 is identified as augmenting cytokine of immune responses, including Th1 cell differentiation, TCd4 + cell proliferation, and IFN-γ production with the help of IL-12. According to several published studies, due to the pro-inflammatory or anti-inflammatory functions of cytokine related to the biological context in various disorders and diseases, IL-27 has been considered a complex regulator of the immune system. Surprisingly, the dual role of IL-27, the same as the double-edged sword, has also been evidenced in clinical models of various hematological or solid tumors. Predominantly, Il-27 applies anti-tumor functions by inducing the responses of a cytotoxic T lymphocyte (CTL) and Th1 and suppressing the growth, proliferation, angiogenesis, invasiveness, metastasis, and survival of tumor cells. On the other hand, IL-27 may also play a protumor role in cancers and induce tumor progression. The current update study aimed to summarize the protumor anti-tumor and biological functions of IL-27 in different hematological malignancies and solid tumors. Show less

MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM. Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein. Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients. Show less