Metabolic hypertension (MH) is characterized by elevated blood pressure accompanied by metabolic abnormalities, with the gut-derived lipopolysaccharide/toll like receptor 4 (LPS/TLR4) pathway an important triggering mechanism. The conventional Chinese plant Polygonatum sibiricum Red. is traditionally used as a medicinal and edible food source. Currently, several studies have examined its anti-obesity and anti-diabetic actions, with potential roles for MH treatment; however, specific P. sibiricum Red. roles in MH and associated mechanisms remain unclear. Our purpose was to identify the effects and mechanisms of P. sibiricum Red. superfine powder (PSP) in a MH rat model triggered by high sugar and high fat compounds in an excessive alcohol diet (ACHSFDs). A MH rat model was induced by ACHSFDs, and PSP was administered daily at 0.5 and 1.0 g/kg doses, respectively. Firstly, the effects of PSP on MH were assessed using blood pressure, serum lipid, and lipid deposition assays in the liver. Changes in intestinal flora were detected by high-throughput 16S rRNA sequencing, while metabolite short-chain fatty acids (SCFAs) and LPS levels were quantified by gas chromatography (GC) and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin & eosin (H&E) staining and transmission electron microscopy (TEM) were performed to evaluate histopathological changes in the rat colon. d-lactic acid (d-LA) levels and tight junction proteins (TJPs) expression were also measured to assess intestinal barrier function. Also, aortic endothelial microstructures, serum endothelin 1 (ET-1), and nitric oxide (NO) levels were investigated to determine vascular endothelial function. Finally, the TLR4/MyD88 signaling pathway in the aorta and gut was evaluated by western blotting, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR). Blood pressure and blood lipid metabolism disorders induced by ACHSFDs in MH rats were improved by PSP administration. Intestinal flora analyses revealed decreased SCFAs and LPS levels following PSP administration, which was accompanied by increased Streptococcus species levels and decreased Desulfobacter and Desulfovibrio species levels. PSP increased SCFAs levels, and the expression of SCFAs receptors GPCR41 and GPCR43 in the colon. Meanwhile, the expression of tight junction proteins (TJPs) such as Claudin-1, occludin were upregulated in the ileum and colon, while TLR4 and MyD88 were downregulated, thereby strengthening intestinal barrier integrity and reducing serum LPS levels. Additionally, PSP treatment improved vascular endothelial function by inhibiting the TLR4/MyD88 pathway in vessels, improving vascular endothelial cell shedding, and regulating the NO and ET-1 balance. We demonstrated the beneficial effects and potential mechanisms of PSP in our MH rat model. Based on gut microbiota structure modulation and intestinal barrier improvements, PSP inhibited LPS-induced vascular TLR4/MyD88 signaling activation to improve vascular endothelial function, which in turn reduced blood pressure. Our study provides valuable insights on PSP therapy for MH.

Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs). Generally, Tα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells. Moreover, TLR2 and TLR7 are also associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines, thereby enhancing the innate and adaptive immune responses. At present, there are many reports on the clinical application and pharmacological research of Tα1, but there is no systematic review to analyze its exact clinical efficacy in these viral infectious diseases via its modulation of immune function. This review offers an overview and discussion of the characteristics of Tα1, its immunomodulatory properties, the molecular mechanisms underlying its therapeutic effects, and its clinical applications in antiviral therapy.

The thymus is the most sensitive organ under various pathophysiological conditions, such as aging, starvation, and infection. As a key stromal cell for T cell development, it is well-known that thymic epithelial cells (TECs) play an important role in the thymus response to the external environment. Thymosin beta 15 (Tβ15) is a G-actin binding protein secreted by TECs, it plays an important role in maintaining the dynamic balance of actin, angiogenesis, axonal formation, and wound healing, but the relationship between Tβ15 and TECs is not clear yet. Here, we show the impact of Tβ15 on the TEC’s spatial development, as well as the T-cell differentiation and thymic output. As a result, TEC is the main effector cell of Tβ15 in the thymus. Tβ15 OX inhibits the chemotaxis of TECs to the medulla and subsequently blocks the positive selection of thymocytes from CD3⁺TCRβ⁺CD4⁺CD8⁺ double positive cells to CD3⁺TCRβ⁺CD4⁺CD8⁻ single-positive (CD4SP) cells. Tβ15-knockdown accelerates the reticular differentiation of astral TECs and medullary TECs. Importantly, mice implanted with Tβ15-knockdown iTECs show high thymic output but low peripheral T cell maturity and activity. In a word, our results explain the role of Tβ15 on the differentiation and function of TECs and provide a new perspective for understanding the process of thymus development and degeneration.

Background: The phenomenon of population aging presents a significant global challenge, with the aging population in China steadily increasing. As individuals progress in age, there is a gradual deterioration of human organs and systems, as well as a decline in the immune system, referred to as immunosenescence. Atractylodis macrocephalae rhizoma (BZ) has been historically used in China for its medicinal properties, including gastrointestinal improvement, immunomodulation, anti-aging, antioxidant effects, and anti-tumor effects. Nevertheless, there remains a gap in understanding the pharmacological and molecular mechanisms underlying its anti-immunosenescence effects.Methods: This study employed UPLC-ESI-MS and network pharmacology to create a network map of BZ ultrafine powder (BZU) and its aging targets. Enrichment analysis was then used to identify the primary mechanistic pathways underlying BZU’s anti-immunosenescence effects. The primary components of BZU were quantitatively analyzed using high-performance liquid chromatography (HPLC). Naturally aging rats were used to examine the effects of different oral doses (0.25, 0.5, and 1 g/kg) of BZU over 5 weeks on aging performance, peripheral blood immunophenotyping and cell count, and splenic lymphocyte proliferation rate. To validate the findings of network pharmacology, quantitative RT-PCR, Western blotting, and immunofluorescence analyses were conducted.Results: Our analyses demonstrated that BZU improved various indicators of aging in naturally aging rats, such as increasing the number of voluntary activities, enhance grip strength and fatigue resistance, increasing the microcirculatory blood flow and improving hematological levels. The BZU administration enhanced T and B lymphocyte proliferation and significantly improved the lymphocyte-to-T cell subpopulation ratio. It can elevate serum IL-2 and IL-4 levels while reducing IL-6, IFN-γ and TNF-α levels in naturally aging rats. Finally, it increased CD3 protein expression in the spleen while decreasing protein levels of PI3K, p-AKT, IKKα/β, and NF-κB. It also decreased the mRNA expression of Pik3cg, Akt1, Pdk1 and Nfκb1.Conclusion: These findings suggest that BZU may enhance lymphocyte proliferation by inhibiting the PI3K/Akt/NF-κB signaling pathway, correcting immune cell imbalances, reducing inflammatory responses, and ultimately enhancing immune function and potentially delaying aging.