Background The understanding of the pathogenesis of osteoarthritis (OA) is often fragmented, with studies focusing on individual tissues. A holistic view integrating multi-tissue molecular changes with systemic metabolic shifts is urgently needed. Glutamine metabolism, a central bioenergetic and biosynthetic hub, represents a critical but largely unexplored nexus in this disease network. This study leverages a multi-omics, multi-tissue approach to deconstruct the role of glutamine metabolism in OA and identify a robust, blood-based signature for potential diagnostic use. Methods We conducted a comprehensive bioinformatic investigation by integrating multiple GEO transcriptomic datasets from cartilage, synovium, subchondral bone, and peripheral blood. A machine learning pipeline, incorporating weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression, was employed to identify a signature of glutamine metabolism-related genes (GMRGs). The signature’s clinical relevance was then validated in an independent cohort of 62 subjects (31 OA patients vs. 31 healthy controls) using RT-qPCR on peripheral blood samples and plasma metabolomics. Furthermore, we computationally explored its potential regulatory mechanisms and predicted candidate therapeutic compounds. Results Our multi-layered analysis identified a core three-gene signature (F13A1, IRS2, RELA). Functional analysis linked this signature to pathways essential for OA pathogenesis, including mechanical stress, metabolic regulation, and inflammatory responses. Clinical validation in an independent cohort confirmed significant downregulation of all three genes in OA peripheral blood (P < 0.001) and revealed distinct regulatory patterns, including disease-specific activation of RELA and a metabolic regulatory reversal of IRS2, as well as negative correlations with disease severity and alterations in circulating glutamine-related metabolites. The resulting diagnostic model showed strong discriminatory performance across both training and validation datasets. Plasma creatine emerged as an independent predictor of disease severity. Finally, exploratory analyses suggested potential epigenetic regulation and identified several candidate drugs capable of modulating the signature. Conclusions This study identifies a blood-based, multi-omics-derived gene signature that links localized joint pathology with systemic metabolic dysfunction in osteoarthritis. The signature offers a robust non-invasive diagnostic marker and reveals new opportunities for patient stratification and therapeutic development.

Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This study evaluates YQJSD’s effectiveness in ameliorating RIF and explores the underlying molecular mechanisms using the unilateral ureteral obstruction (UUO) model. YQJSD has been shown to effectively reduce serum creatinine and blood urea nitrogen levels, decrease extracellular matrix deposition, and down-regulate the expression of α-SMA, COL4α1, Fibronectin (FN). Mechanistically, YQJSD exerts its effects by modulating multiple pathways: it inhibits the NF-κB signaling pathway, inhibiting the expression of pro-inflammatory cytokines like NF-κB1, IL-1β, TNF-α, and CCR1. Simultaneously, YQJSD suppresses the epithelial-mesenchymal transition (EMT) by downregulating the expression of Snail1, Vimentin, Twist1, and FSP1, while increasing E-cadherin expression. Moreover, YQJSD can regulate the PI3K/AKT signaling pathway by decreasing the expression of LOXL2 and PIK3R1, along with p-AKT1/2/3. This modulation of the LOXL2/PI3K/AKT pathway contributes to the inhibition of both EMT and inflammation, highlighting a critical role in the therapeutic intervention against RIF. These findings suggest that YQJSD may serve as a promising therapeutic management of RIF in CKD patients.

RESEARCH PURPOSE:This investigation explored the therapeutic effects and mechanisms of Skullcapflavone II in hepatic fibrosis (HF). MATERIALS AND METHODS:The optimal concentration of Skullcapflavone II for LX2 hepatic stellate cells was determined using the CCK8 assay. EdU staining and flow cytometry were utilised to assess cell proliferation and G2/M phase arrest. Mice with carbon tetrachloride-triggered HF were administered Skullcapflavone II at low (15 mg/day), medium (30 mg/day), and high (60 mg/day) doses. Subsequently, hepatic damage and fibrosis were assessed via body weight, liver index, biochemical markers, and histopathological staining. Immunohistochemistry for Collagen I and α-SMA were utilised to examine hepatic stellate cell (HSC) activation. RNA sequencing was utilised to ascertain differentially expressed genes. Molecular docking simulated interactions among Skullcapflavone II and target proteins as well as outcomes were validated by implementing western blotting, immunohistochemistry, and RT-qPCR. RESULTS:Skullcapflavone II inhibited LX2 cell proliferation and triggered G2/M phase arrest. Its optimal intervention concentration was 160 μM. In vivo, it ameliorated hepatic function, diminished serum indicators of fibrosis, and suppressed HSC activation. Diminished collagen sediment was validated utilising histopathological examination, whereas immunohistochemistry indicated decreased expression of Collagen I and α-SMA. Additionally, molecular docking showed strong binding of Skullcapflavone II to DNA replication-related proteins. Western blotting and RT-qPCR implied that Skullcapflavone II disrupted DNA replication, which triggered G2/M arrest and hindered HSCs activation and proliferation. CONCLUSION:The abovementioned mechanisms of action of Skullcapflavone II substantiate its prospective clinical application against HF.

Background: Hepatic fibrosis is a major global health issue without an optimal drug treatment, highlighting the urgent need to find effective therapies. This study aimed to clarify the role and mechanism of micheliolide in treating hepatic fibrosis. Methods: The efficacy of MCL was evaluated in a mouse model of CCl4-induced hepatic fibrosis. LX-2 cells were subjected to MCL treatment, and subsequent changes in fibrosis markers, autophagy, and the MEK/ERK pathway were analyzed using transcriptomics and Western blotting. The interaction between MCL and TrxR1 or TrxR2 were validated using cellular thermal shift assays (CETSA) and drug affinity responsive target stability (DARTS) assays. Results: Our findings indicated that MCL significantly alleviated CCl4-induced hepatic fibrosis, improved liver function, and downregulated the expression of fibrosis markers. Additionally, MCL significantly inhibited LX-2 cell activation by suppressing cell proliferation, extracellular matrix (ECM) production, and autophagy, while activating the MEK/ERK pathway. Moreover, MCL elevated intracellular and mitochondrial reactive oxygen species (ROS) levels, reduced mitochondrial membrane potential, and altered mitochondrial morphology. The ROS scavenger N-acetylcysteine (NAC) attenuated MCL-induced MEK/ERK pathway activation and increased collagen type I alpha 1 (COL1A1) and fibronectin (FN) expression. Further analysis confirmed that MCL directly interacts with TrxR1 and TrxR2, leading to the inhibition of their enzymatic activities and the induction of ROS generation. Ultimately, MCL attenuated the fibrotic process and autophagic flux in LX-2 cells. Conclusions: The findings of our study confirmed that MCL has the potential to alleviate hepatic fibrosis, thereby introducing a novel candidate drug and therapeutic strategy for management of this condition.

ETHNOPHARMACOLOGICAL RELEVANCE:The limitations of modern medicine in mitigating the pathological process of diabetic kidney disease (DKD) necessitate novel, precise, and effective prevention and treatment methods. Huangqi, the root of Astragalus membranaceus Fisch. ex Bunge has been used in traditional Chinese medicine for various kidney ailments. Astragaloside IV (AS-IV), the primary pharmacologically active compound in A. membranaceus, is involved in lipid metabolism regulation; however, its potential in ameliorating renal damage in DKD remains unexplored. AIM OF THE STUDY:To elucidate the specific mechanism by which AS-IV moderates DKD progression. MATERIALS AND METHODS:A murine model of DKD and high glucose-induced HK-2 cells were treated with AS-IV. Furthermore, multiomics analysis, molecular docking, and molecular dynamics simulations were performed to elucidate the mechanism of action of AS-IV in DKD, which was validated using molecular biological methods. RESULTS:AS-IV regulated glucose and lipid metabolism in DKD, thereby mitigating lipid deposition in the kidneys. Proteomic analysis identified 12 proteins associated with lipid metabolism regulated by AS-IV in the DKD renal tissue. Additionally, lipid metabolomic analysis revealed that AS-IV upregulated and downregulated 4 beneficial and 79 harmful lipid metabolites, respectively. Multiomics analysis further indicated a positive correlation between the top-ranked differential protein heme oxygenase (HMOX)1 and the levels of various harmful lipid metabolites and a negative correlation with the levels of beneficial lipid metabolites. Furthermore, enrichment of both ferroptosis and hypoxia-inducible factor (HIF)-1 signaling pathways during the AS-IV treatment of DKD was observed using proteomic analysis. Validation results showed that AS-IV effectively reduced ferroptosis in DKD-affected renal tubular epithelial cells by inhibiting HIF-1α/HMOX1 pathway activity, upregulating glutathione peroxidase-4 and ferritin heavy chain-1 expression, and downregulating acyl-CoA synthetase long-chain family member-4 and transferrin receptor-1 expression. Our findings demonstrate the potential of AS-IV in mitigating DKD pathology by downregulating the HIF-1α/HMOX1 signaling pathway, thereby averting ferroptosis in renal tubular epithelial cells. CONCLUSIONS:AS-IV is a promising treatment strategy for DKD via the inhibition of ferroptosis in renal tubular epithelial cells. The findings of this study may help facilitate the development of novel therapeutic strategies.

In China, the Astragalus membranaceus root is used to treat chronic kidney disease. Astragaloside IV (AS-IV), the primary bioactive compound, exhibits anti-inflammatory and antioxidative properties; however, its renoprotective mechanism in diabetic kidney disease (DKD) remains unclear. The study aimed to investigate the protective effects of AS-IV on DKD revealing the underlying mechanisms. We established an early diabetic rat model by feeding a high-fat diet and administering low-dose streptozotocin. Twelve weeks post-treatment, renal function was evaluated using functional assays, histological analyses, immunohistochemistry, western blotting, and transmission electron microscopy. HK-2 cells exposed to high glucose conditions were used to examine the effect of AS-IV on oxidative stress, iron levels, reactive oxygen species (ROS), and lipid peroxidation. Network pharmacology, proteomics, molecular docking, and molecular dynamics simulation techniques were employed to elucidate the role of AS-IV in DKD. The results revealed that AS-IV effectively enhanced renal function and mitigated disease pathology, oxidative stress, and ferroptosis markers in DKD rats. In HK-2 cells, AS-IV lowered the levels of lipid peroxides, Fe2+, and glutathione, indicating the repair of ferroptosis-related mitochondrial damage. AS-IV reduced mitochondrial ROS while enhancing mitochondrial membrane potential and ATP production, indicating its role in combating mitochondrial dysfunction. Overall, in silico analyses revealed that AS-IV interacts with HMOX1, FTH1, and TFR1 proteins, supporting its efficacy in alleviating renal injury by targeting mitochondrial dysfunction and ferroptosis. AS-IV may play a renoprotective role by regulating mitochondrial dysfunction and inhibiting. HMOX1/FTH1/TFR1-induced ferroptosis. Accordingly, AS-IV could be developed for the clinical treatment of DKD-related renal injury.

ETHNOPHARMACOLOGICAL RELEVANCE:Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown.AIM OF THE STUDY:By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action.MATERIALS AND METHODS:The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis.RESULT:Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization.CONCLUSIONS:QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD.

Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.

Numerous studies have demonstrated the involvement of messenger RNAs (mRNAs) and non-coding RNAs, including long non-coding RNAs (lncRNA), circular RNAs (circRNAs) and microRNA (miRNAs), in gouty arthritis onset; however, the regulatory mechanism has not yet been elucidated. Here, we applied whole-transcriptome sequencing to identify the differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs between the gout patients and normal people, and constructed co-regulated networks of circRNAs and lncRNAs according to the competitive endogenous RNA (ceRNA) theory for gouty arthritis onset to improve our understanding of the pathogenesis of this disease. The most significant finding of this study is the co-regulated ceRNA network of circRNAs and lncRNAs in gouty arthritis. The circRNA novel_circ_0030384 and the lncRNAs AAMP, TRIM16, PKN1, XLOC_184579 and XLOC_189826 were upstream genes in the co-regulated network. These upstream genes upregulated miR550a-5p and miR550a-3-5p, which downregulated PSME1 and FERMT3 expression. These mRNAs participated in proteasome dynamics, antigen processing and presentation, and platelet activation, which are associated with inflammation in gouty arthritis. In addition, the circRNA and lncRNAs upregulated miR550a-5p, which downregulated GRK2 and OS9 expression. Also, it proved that the down-regulated of PSME1, FERMT3, GRK2 and OS9 can aggravate gouty arthritis in vitro. In summary, these genes mediate inflammation in gouty arthritis through chemokine signaling to regulate neutrophil function.

Background. Diabetic microvascular complications are the main causes of organ dysfunction and even death in diabetic patients. Our previous studies confirmed the beneficial effects of Yiqi Jiedu Huayu Decoction (YJHD) on diabetic cardiomyopathy and diabetic nephropathy. It is not clear whether YJHD can treat multiple diabetic microvascular complications including diabetic retinopathy, diabetic cardiomyopathy, and diabetic nephropathy through some common mechanisms. Methods. TCMSP, SymMap, STITCH, Swiss Target Prediction, and SEA databases were used to collect and analyze the components and targets of YJHD. GeneCards, DrugBank, DisGeNET, OMIM, and GEO databases were used to obtain target genes for diabetic retinopathy, diabetic cardiomyopathy, and diabetic nephropathy. The GO and KEGG enrichment analyses were performed on the DAVID and STRING platforms. Molecular docking was used to evaluate the binding sites and affinities of compounds and target proteins. Animal experiments were designed to validate the network pharmacology results. Results. Through network pharmacological analysis, oxidative stress, inflammatory response, and apoptosis were identified as key pathological phenotypes for the treatment of diabetic microvascular complications with YJHD. In addition, JNK, p38, and ERK1/2 were predicted as key targets of YJHD in regulating the abovementioned pathological phenotypes. The results of animal experiments showed that YJHD could ameliorate retinal pathological changes of diabetes rats. YJHD can inhibit oxidative stress and inflammation in heart and kidney of diabetic rats. Molecular docking showed strong binding between compounds and JNK, p38, and ERK1/2. Berlambine may play a key role in the treatment process and is considered as a promising regulator of MAPK protein family. The regulatory effects of YJHD on JNK, p38, and ERK1/2 were demonstrated in animal experiments. Conclusions. YJHD may play a therapeutic role in diabetic microvascular complications by regulating oxidative stress, inflammatory response, and apoptosis. The regulation of JNK, p38, and ERK1/2 phosphorylation may be the key to its therapeutic effect.

Purpose:Our study aims to reveal the pharmacological mechanism of Astragaloside IV in the treatment of pulmonary fibrosis(PF) through network pharmacology and experimental validation.Methods:We first determined the in vivo anti-pulmonary fibrosis effect of Astragaloside IV by HE, MASSON staining, and lung coefficients, then used network pharmacology to predict the signaling pathways and molecularly docked key pathway proteins, and finally validated the results by in vivo and in vitro experiments.Results:In in vivo experiments, we found that Astragaloside IV improved body weight (P < 0.05), increased lung coefficients (P < 0.05), and reduced lung inflammation and collagen deposition in mice with pulmonary fibrosis. The network pharmacology results showed that Astragaloside IV had 104 cross-targets with idiopathic pulmonary fibrosis, and the results of KEGG enrichment analysis indicated that cellular senescence could be an important pathway for Astragaloside IV in the treatment of pulmonary fibrosis. Astragaloside IV also bound well to senescence-associated proteins, according to molecular docking results. The results of both in vivo and in vitro experiments showed that Astragaloside IV significantly inhibited senescence protein markers such as P53, P21, and P16 and delayed cellular senescence (P < 0.05). In in vivo experiments, we also found that Astragaloside IV reduced the production of SASPs (P < 0.05), and in in vitro experiments, Astragaloside IV also reduced the production of ROS. In addition, by detecting epithelial-mesenchymal transition(EMT)-related marker protein expression, we also found that Astragaloside IV significantly inhibited the development of EMT in both in vivo and in vitro experiments (P < 0.05).Conclusion:Our research found that Astragaloside IV could alleviate bleomycin-induced PF by preventing cellular senescence and EMT.

慢性阻塞性肺疾病(简称慢阻肺)是临床最常见的疾病之一,虽然现代医学对发病机制、治疗手段较过去取得了一定的进展,但因其病因复杂,发病机制至今尚不十分清楚,疗效亦不尽如人意.临床医师致力于寻找其他的治疗手段,而中医的肺肠同治理论已被现代医学研究的"肺肠轴"学说证实,十枣汤作为肺肠同治的代表方,成为未来治疗慢阻肺的新思路.

Previous studies show that astragaloside IV (ASIV) has anti-renal fibrosis effects. However, its mechanism remains elusive. In this study, we investigated the anti-fibrosis mechanisms of ASIV on chronic kidney disease (CKD) in vivo and in vitro. A CKD model was induced in rats with adenine (200 mg/kg/d, i.g.), and an in vitro renal fibrosis model was induced in human kidney-2 (HK-2) cells treated with TGF-β1. We revealed that ASIV significantly alleviated renal fibrosis by suppressing the expressions of epithelial–mesenchymal transition (EMT)-related proteins, including fibronectin, vimentin, and alpha-smooth muscle actin (α-SMA), and G2/M arrest-related proteins, including phosphorylated p53 (p-p53), p21, phosphorylated histone H3 (p-H3), and Ki67 in both of the in vivo and in vitro models. Transcriptomic analysis and subsequent validation showed that ASIV rescued ALDH2 expression and inhibited AKT/mTOR-mediated autophagy. Furthermore, in ALDH2-knockdown HK-2 cells, ASIV failed to inhibit AKT/mTOR-mediated autophagy and could not blunt EMT and G2/M arrest. In addition, we further demonstrated that rapamycin, an autophagy inducer, reversed the treatment of ASIV by promoting autophagy in TGF-β1-treated HK-2 cells. A dual-luciferase report assay indicated that ASIV enhanced the transcriptional activity of the ALDH2 promoter. In addition, a further molecular docking analysis showed the potential interaction of ALDH2 and ASIV. Collectively, our data indicate that ALDH2-mediated autophagy may be a novel target in treating renal fibrosis in CKD models, and ASIV may be an effective targeted drug for ALDH2, which illuminate a new insight into the treatment of renal fibrosis and provide new evidence of pharmacology to elucidate the anti-fibrosis mechanism of ASIV in treating renal fibrosis.

程序主任中医师为重庆市垫江中医院呼吸与危重症医学科学术带头人,从事临床医疗及教学工作30余年,临床经验丰富.擅长古方结合现代中药药理研究防治呼吸科疾病.在临床治疗中程序应用玄麦甘桔汤治疗燥咳疗效甚好.现将其经验总结如下. 1燥咳病因病机 程序认为外燥虽为秋令主气,但非独秋有.重庆夏日暑湿较重,气候炎热,导致市民长时间在空调房休息或作业,长时间吹空调,致室内空气凉燥,如不注意防护,亦会感受风燥邪气,肺失濡润,宣降失职,出现燥咳.且暑热本属阳邪,易致津液耗伤,再加之重庆人喜食辛辣,辛热之品易助阳耗阴,致素体阴虚热重.感邪后同气相求可致内外合燥.可见燥邪致病是与地理环境、时令气候、生活习惯、体质等因素相关.

Background: Gut microbiota is closely related to cardiac fibrosis (CF). Regulating the gut microbiota provides new insights into complex pathogenesis of CF and offers novel therapeutic targets. Puerarin, an isoflavone glycoside isolated from the Chinese herb Pueraria lobata, has exhibited potential anti-fibrosis effects, but its mechanism against CF remains unclear.PurposeThis study aimed to elucidate whether puerarin could alleviate CF by modulating intestinal microbiota, increasing short-chain fatty acids (SCFAs), and protecting intestinal integrity.Methods: Mice received a subcutaneous injection of isoproterenol (ISO, 10mg/kg/d) and concurrently received intragastric administration with puerarin (100mg/kg/d) for 14 days. The heart gross appearance, cardiac weight index (CWI), and heart weight/tibia length (HW/TL) were investigated to assess the effects of puerarin against ISO-induced cardiac fibrosis. Transthoracic echocardiography was performed to investigate cardiac function. Myocardial enzymes were detected to assess the myocardial injury. Histopathology and collagen deposition in heart tissues of mice were detected by HE, Masson, and immunohistochemistry staining. ZO-1, Occludin, and lipopolysaccharide were measured to evaluate intestinal integrity. Intestinal microbiota composition was detected by 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was used to analyze fecal SCFAs.Results: Puerarin treatment effectively improved heart histopathological changes, prevented cardiac dysfunction, and alleviated myocardial injury, inflammation, and cardiac fibrosis induced by ISO. Moreover, puerarin maintained intestinal integrity. 16S rRNA analysis discovered that puerarin effectively ameliorated ISO-induced gut microbiota dysbiosis, especially of Lactobacillus. GC-MS analysis revealed that puerarin could promote SCFA production.Conclusions: This study demonstrates that puerarin attenuates ISO-trigged cardiac fibrosis by inhibiting inflammation, modulating gut microbiota, increasing short-chain fatty acids production, and protecting intestinal integrity.

化疗后手足综合征是恶性肿瘤患者化疗后出现的一组临床综合征,主要表现为手足皮肤麻木、疼痛、脱屑、皲裂、渗液等症状的.中医辨病属"痹证"范畴,临床辨证分型主要分为为营卫不和、筋脉失养、络脉瘀阻等证.化疗后HFS虽不会直接导致病情进展,但症状严重者生活质量下降,更有甚者生活不能自理,导致患者依从性降低,严重者影响化疗进程延误病情,所以找到规避化疗后HFS发生以及缓解化疗后HFS的方法有着重要的临床意义.

尿酸的产生与代谢、饮食、生活方式息息相关,在社会发展和生活方式改变的影响下,高尿酸血症和痛风的发病率亦逐年升高.近年研究结果显示中国高尿酸血症的总体患病率为13.3％,痛风患病率为1.1％[1].在日常饮食情况下,非同日2次空腹血尿酸水平＞420 μmol/L即可诊断高尿酸血症[2].

Hepatic fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) which is mainly secreted by activated hepatic stellate cells (HSCs). Lamiophlomis rotata (L. rotata) was recorded to treat jaundice in the traditional Tibetan medical system with the potential of hepatoprotection. However, the bioactivities and the possible mechanism of L. rotata on hepatic fibrosis is still largely unknown.To investigate the anti-hepatic fibrosis effects of bioactivities in L. rotata and the probable mechanism of action.Herein, total polyphenolic glycosides of L. rotata (TPLR) was purified with the selectivity adsorption resin and was analyzed by ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q/TOF/MSn). The anti-hepatic fibrosis effect of TPLR was evaluated by carbon tetrachloride (CCl4)-induced liver fibrosis, and was evaluated with the apoptosis of activated HSCs.In total, sixteen compounds, including nine phenylpropanoids and six flavonoids, were identified in the UPLC-TOF-MSn profile of the extracts. TPLR significantly ameliorated hepatic fibrosis in CCl4-induced mice and inhibited HSCs proliferation, Moreover, TPLR notably increased the apoptosis of activated HSCs along with up-regulated caspase-3, -8, -9, and -10. Furthermore, TPLR inhibited TGF-β/Smad pathway ameliorating hepatic fibrosis though downregulation the expression of Smad2/3, Smad4, and upregulation the expression of Smad7 in vivo and in vitro. Simultaneously, the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and Collagen I (Col1α1) were decreased in tissues and in cells with TPLR administration.These results initially demonstrated that TPLR has the potential to ameliorate hepatic fibrosis through an apoptosis mechanism via TGF-β/Smad signaling pathway.

慢性咳嗽指病程超过8周,咳嗽是唯一或主要症状,而胸部影像学检查并未见特殊异常[1].目前临床上经常应用抗生素、支气管解痉、镇咳祛痰等药物治疗慢性咳嗽,但这有易复发、细菌耐药、副作用较多等弊端,而中医治疗慢性咳嗽效果显著,没有明显不良反应,对提高患者生存质量有重要意义[2].

脂溢性脱发(Seborrheic alopecia,SA)又称为雄激素性脱发,属中医"发蛀脱发"、"虫蛀脱发"、"蛀发癣"范畴[1].是好发于青春期及中年期的毛囊进行性微小化的慢性毛发疾病.既往以指南推荐西药治疗为主,但最新文献指出,西医治疗脂溢性脱发靶点单一,存在一定局限性[2],而中药因其多成分、多靶点、协同作用等阻断未知的疾病途径,达到较好的治疗效果,逐渐成为科研领域的研究热点[3].