BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H O ), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H O . After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na /K -ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na /K -ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes