Niaodukang mixture inhibits micro-inflammation in CKD rats by enhancing MiR-146a levels in enterogenous exosomes.

ETHNOPHARMACOLOGICAL RELEVANCE: The Niaodukang mixture (NDK) is a preparation known for its ability to lower serum creatine levels in individuals with chronic kidney disease (CKD) and is commonly administered at medical facilities like the Zhongshan Hospital of Traditional Chinese Medicine. The initial use of NDK was mainly to treat CKD. Our hospital frequently utilizes NDK, which consists of Rheum officinaleBaill., Salvia miltiorrhiza Bunge., Astragalus aaronii (Eig) Zohary., Carthamus tinctorius L., and Sanguisorba officinalis L., for treating patients with CKD-MBD. It has the effects of eliminating dampness and turbidity and dredging kidney collaterals. However, The impact and process of NDK in chronic kidney disease remain unknown. AIM OF THE STUDY: To determine whether microRNA-146a (miR-146a) is associated with CKD micro-inflammationand whether NDK protects against CKD micro-inflammation by modulating the miR-146a/nuclear factor kappa-B (NF-κB) signaling pathway. MATERIALS AND METHODS: (1) An adenine-induced rat model of chronic kidney disease was created through the use of materials and methods. The levels of miR-146a in exosomes from plasma and ileum were determined by RT-PCR. (2) Human cloned colon adenocarcinoma (Caco-2)cellswere stimulated with lipopolysaccharide (LPS)and transfected with miR-146a mimic and inhibitor. Following that, the Western blot and RT-PCR techniques were used to measure the protein and mRNA quantities of Toll-like receptor 4 (TLR4), NF-κB, and TNF receptor-associated factor 6 (TRAF6). (3) Enzyme-linked immunosorbent assay (ELISA) was used to identify serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). (4) Plasma exosomes were extracted, and the exosomes in intestinal tissues were extracted via ultrahigh-speed centrifugation.Negative staining electron microscopy was used to analyze the morphology of exosomes and the ultrastructure of intestinal tissue and exosomes. The particle size of the exosomes was measured using nanoparticle tracking analysis. RESULTS: The pathological characteristics of CKD rats included those associated with systemic micro-inflammation, which may be associated with the release of exosomes in intestinal tissue. NDK suppressed the inflammatory response in Caco-2 cells and decreased the levels of IL-1ß, IL-6, and TNF-α in rats with CKD. The expression of miR-146a, which regulates inflammation, differed between plasma-derived and enterogenous exosomes in CKD rats, which may be due to stimulation of ileal exosome release into the blood. NDK effectively reduced the levels of TRAF6, NF-κB, and TLR4 in the ileum tissue of CKD rats. CONCLUSION: NDK can effectively improve micro-inflammation in CKD ratsby enhancing the release of enterogenous exosomes, thereby enhancing the release of exosome-associated miR-146a and inhibiting micro-inflammation.

Autophagy, Pyroptosis and Ferroptosis are Rising Stars in the Pathogenesis of Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes and can potentially develop into end-stage renal disease. Its pathogenesis is complex and not fully understood. Podocytes, glomerular endothelial cells (GECs), glomerular mesangial cells (GMCs) and renal tubular epithelial cells (TECs) play important roles in the normal function of glomerulus and renal tubules, and their injury is involved in the progression of DN. Although our understanding of the mechanisms leading to DN has substantially improved, we still need to find more effective therapeutic targets. Autophagy, pyroptosis and ferroptosis are programmed cell death processes that are associated with inflammation and are closely related to a variety of diseases. Recently, a growing number of studies have reported that autophagy, pyroptosis and ferroptosis regulate the function of podocytes, GECs, GMCs and TECs. This review highlights the contributions of autophagy, pyroptosis, and ferroptosis to DN injury in these cells, offering potential therapeutic targets for DN treatment.

The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy.

Osteoarthritis (OA) is a worldwide chronic disease that can cause severe inflammation to damage the surrounding tissue and cartilage. There are many different factors that can lead to osteoarthritis, but abnormally progressed programmed cell death is one of the most important risk factors that can induce osteoarthritis. Prior studies have demonstrated that programmed cell death, including apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and cuproptosis, has a great connection with osteoarthritis. In this paper, we review the role of different types of programmed cell death in the generation and development of OA and how the different signal pathways modulate the different cell death to regulate the development of OA. Additionally, this review provides new insights into the radical treatment of osteoarthritis rather than conservative treatment, such as anti-inflammation drugs or surgical operation.

Preliminary analysis of spatial-temporal homogeneity and heterogeneity of TCR ß chain CDR3 repertoires in BALB/c mice.

The T-cell response and tolerance in non-lymph tissues differs from those in lymph tissues such as the spleen and thymus. The distribution and composition of the TCR repertoires in non-lymph tissues and how they differ and associate with their counterparts in lymph tissue remain unclear. Thus, we studied the thymus, spleen, blood, liver and small intestine of BALB/c mice at the ages of one, three and five months to carry out a preliminary analysis of the spatial-temporal homogeneity and heterogeneity of the total TCR ß chain CDR3 repertoire using high-throughput sequencing technology and immune bioinformatics approaches. The data show that the diversity of the CDR3 repertoires was decreased as the mouse age increased, except in the small intestine. The number of low-expanded clones in the CDR3 repertoires was greatest in the thymus, followed by the spleen, blood, liver and small intestine, and highly expanded clones had an opposite trend in the different mice ages. The thymus and the spleen showed the greatest overlap of CDR3 sequences with the other tissues across the different mice ages. The distribution of the CDR3 repertoire length was normal, with a median of 14 aa in all the mouse tissues, except the small intestine of the one-month-old mice had a median of 12 aa. In summary, the composition and characteristics of the CDR3 repertoires in the thymus were similar to those in the spleen, and repertoires in the blood were similar to those in the liver; only the small intestine showed a unique composition. These results offer a novel method to explore the source, differentiation, proliferation and response of distinct T cells in different tissues at different mice ages.

Quorum Sensing Involved in the Spoilage Process of the Skin and Flesh of Vacuum-Packaged Farmed Turbot (Scophthalmus maximus) Stored at 4 °C.

Fish skin has both positive and negative effects on the shelf-life of the fish. This study aimed to investigate the spoilage process of the skin and flesh of refrigerated farmed turbot (Scophthalmus maximus) with vacuum packaging. Microbial community changes were analyzed by combining culture-dependent and culture-independent methods. The results indicated that the shelf-life of vacuum-packaged refrigerated turbot was 16 d; skin mucus was the interference factor of turbot quality. The culture-dependent analysis demonstrated that the total viable counts and the population of H2 S-producing bacteria, Pseudomonas spp., Enterobacteriaceae spp., and lactic acid bacteria in skin had a range of 0.45 to 1.40 log (CFU/g) higher than the microbial numbers in flesh after 16 d in storage. 16S high throughout sequencing results demonstrated that the compositions of spoilage microbes were similar in skin and flesh. Shewanella spp., followed by Carnobacterium spp., was the dominant spoilage organism at day 16. Quorum sensing (QS) signaling activity increased during the storage. Exogenous N-butanoyl-L-homoserinelactone(C4-HSL) and N-hexanoyl-Lhomoserine lactone (C6-HSL) significantly accelerated the spoilage process of refrigerated turbot, while the addition of 4, 5-Dihydroxypentane-2, 3-dione (DPD) prolonged the lag phase duration. Therefore, QS may be involved in the spoilage process of refrigerated turbot.