Naringin: Cardioprotective properties and safety profile in diabetes treatment.

Flavonoids derived from plants offer a broad spectrum of therapeutic potential for addressing metabolic syndrome, particularly diabetes mellitus (DM), a prevalent non-communicable disease. Hyperglycemia in DM is a known risk factor for cardiovascular diseases (CVDs), which substantially impact global mortality rates. This review examines the potential effects of naringin, a citrus flavonoid, on both DM and its associated cardiovascular complications, including conditions like diabetic cardiomyopathy. The safety profile of naringin is summarized based on various pre-clinical studies. The data for this review was gathered from diverse electronic databases, including Medline, PubMed, ScienceDirect, SpringerLink, Google Scholar, and Emerald Insight. Multiple pre-clinical studies have demonstrated that naringin exerts hypoglycemic and cardioprotective effects by targeting various vascular mechanisms. Specifically, research indicates that naringin down-regulates the renin-angiotensin and oxidative stress systems while concurrently upregulating ß-cell and immune system functions. Clinical trial outcomes also support the therapeutic potential of naringin in managing hyperglycemic states and associated cardiovascular issues. Moreover, toxicity studies have confirmed the safety of naringin in animal models, suggesting its potential for safe administration in humans. In conclusion, naringin emerges as a promising natural candidate for both antidiabetic and cardioprotective purposes, offering potential improvements in health outcomes. While naringin presents a new avenue for therapies targeting DM and CVDs, additional controlled and long-term clinical trials are necessary to validate its efficacy and safety for human use.

PD1 is transcriptionally regulated by LEF1 in mature T cells.

The role of programmed cell death 1 (PD1) in cancer immune evasion is of considerable importance, prompting the development of monoclonal antibodies that specifically target PD-1 to enhance the immune system for cancer therapy. Nevertheless, the efficacy of PD1/programmed cell death-Ligand 1 (PD-L1) blocking antibodies is limited to certain patients or tumor types. Although researchers have demonstrated the influence of PD-1 on the positive selection of T cells, its effect on the T-cell repertoire remains uncertain. Lymphoid enhancer binding factor 1 (LEF1) has been known to play a critical role as a transcription factor in the development and maturation of T cells. Despite the greater focus on the study of its homologous protein, T cell factor 1 (TCF1), we discovered that LEF1 had a positive regulatory effect on the transcription of PD1 in mature T cells, including CD4+ T cells, CD8+ T cells, and Treg cells. This finding was observed in LEF1 knockout and LEF1-stimulated mice models. Additionally, we confirmed the direct regulation of PD1 by LEF1 in tumor-infiltrating lymphocytes through tumor-implantation experiments. The direct regulation of PD1 by LEF1 was further validated in the LEF1 knockout cell line. The results of our study provide novel perspectives on the regulation of PD1 in immune responses and investigate potential approaches for clinical anti-PD1 therapy.

The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes.

Transcription factors directly regulate gene expression by recognizing and binding to specific DNA sequences, involving the dynamic alterations of chromatin structure and the formation of a complex with different kinds of cofactors, like DNA/histone modifying-enzymes, chromatin remodeling factors, and cell cycle factors. Despite the significance of transcription factors, it remains unclear to determine how these cofactors are regulated to cooperate with transcription factors, especially DNA/histone modifying-enzymes. It has been known that DNA/histone modifying-enzymes are regulated by post-translational modifications. And the most common and important modification is phosphorylation. Even though various DNA/histone modifying-enzymes have been classified and partly explained how phosphorylated sites of these enzymes function characteristically in recent studies. It still needs to find out the relationship between phosphorylation of these enzymes and the diseases-associated transcriptional regulation. Here this review describes how phosphorylation affects the transcription activity of these enzymes and other functions, including protein stability, subcellular localization, binding to chromatin, and interaction with other proteins.

Epigenetic Mechanisms Involved in HCV-Induced Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths, which is largely caused by virus infection. About 80% of the virus-infected people develop a chronic infection that eventually leads to liver cirrhosis and hepatocellular carcinoma (HCC). With approximately 71 million HCV chronic infected patients worldwide, they still have a high risk of HCC in the near future. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches. Hepatitis C virus (HCV) infection largely causes hepatocellular carcinoma (HCC) worldwide with 3 to 4 million newly infected cases diagnosed each year. It is urgent to explore its underlying molecular mechanisms for therapeutic treatment and biomarker discovery. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches.

Ultrasensitive Detection of Exosome Using Biofunctionalized Gold Nanorods on a Silver-Island Film.

Exosomes are often a promising source of biomarkers for cancer diagnosis in the early stages. Therefore, it is important to develop a sensitive and low-cost detection method. Here, we introduce a new substrate using gold nanorods (GNRs) on a silver-island film that produces a 360-fold AF647 molecule fluorescence enhancement compared to glass. The amplified fluorescence was proven theoretically by using finite difference time-domain simulation (FDTD). Utilizing the enhanced fluorescence from the substrate, GNRs attached with the biomolecules and created a sandwich immunoassay that can significantly detect human CD63 antigen on the exosome. By applying the method, the detection limit of mouse IgG goes down to 0.3 ng/mL, which is considerably better than the existing methods. Moreover, the sensitivity and accuracy for clinical plasma from six patients confirm its diagnostic feasibility. The proposed substrate can be uniformly extended to the identification of other biomarkers by modifying the antibodies on the surfaces of the GNRs.

Isolation and functional characterization of exopolysaccharide produced by Lactobacillus plantarum S123 isolated from traditional Chinese cheese.

During the past few years, there are growing interests in the potential use of exopolysaccharide (EPS) in the food industry as an efficient biopolymer because of its exceptional biological features. Therefore, the aim of the present study is EPS production by Lactobacillus Plantarum S123 (S123 EPS), its partial structural and biopotential characterization. The results from this study suggested that the major portion of S123 EPS has an amorphous sponge-like structure with partial crystalline nature. The FTIR and NMR results suggested that the S123 EPS consists of carbonyl and hydroxyl groups, respectively. Furthermore, the results of technological as well as biotechnological characterization suggested that the S123 EPS was exhibited excellent antibacterial activity against Gram-positive (7.2 mm) and Gram-negative bacteria (11.5 mm), DPPH radical scavenging activity (> 65%), water holding capacity (326.6 ± 0.5%), oil holding capacity (995.3 ± 0.2%), flocculation (89.5 ± 0.6%), and emulsifying (80.1 ± 1.1%) activities. Overall, the present results suggested that due to the highly porous structure and efficient biotechnological potential, S123 EPS from Lactobacillus plantarum S123 (L. plantarum S123) can be used in the functional food product.