The key target for treating inflammatory osteolysis is osteoclasts. In an inflammatory environment, osteoclast differentiation increases, and bone resorption is enhanced. Periplogenin (Ppg) is a traditional Chinese medicine. It has anti-inflammatory and antitumor effects, but its impact on inflammatory osteolysis is unknown. This study found that Ppg prevented LPS-induced skull osteolysis by inhibiting the expression of inflammatory cytokines and osteoclast production. In vitro, Ppg blocked the RANKL-induced generation of osteoclasts, the development of pseudopodia bands, and bone resorption. Ppg also attenuated the expression of NFATc1, c-Fos, CTSK, and Atp6v0d2 proteins by inhibiting the NFATc1 signaling pathway. In addition, Ppg inhibited the expression of osteoclast-specific genes, including NFATc1, c-Fos, CTSK, Atp6v0d2, and Mmp9. Moreover, Ppg also inhibited NF-κB and MAPK pathways. In vivo, Ppg reduced the number of osteoclasts on the surface of the bone and suppressed LPS-induced osteolysis of the skull. These outcomes suggest that Ppg can serve as a new alternative therapy for treating inflammatory osteolysis by inhibiting inflammation and osteoclasts.

BACKGROUND Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP’s main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2 ) knockdown elucidated Andro’s molecular mechanisms. RESULTS XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2 /HO-1 pathway activation, with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects. CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models. As XP’s key component, Andro activates the Nrf2 /HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Background Liver cancer represents a most common and fatal cancer worldwide. Xianglian Pill (XLP) is an herbal formula holding great promise in clearing heat for treating diseases in an integrative and holistic way. However, due to the complex constituents and multiple targets, the exact molecular mechanisms of action of XLP are still unclear. Purpose This study is focused on hepatocellular carcinoma (HCC), the most common type of liver cancer. The aim of this study is to develop a fast and efficient model to investigate the anti-HCC effects of XLP, and its underlying mechanisms. Materials and methods HepG2, Hep3B, Mahlavu, HuH-7, or Li-7 cells were employed in the studies. The ingredients were analyzed using liquid chromatography tandem mass spectrometry (LC-MS). RNA sequencing combined with network pharmacology was used to elucidate the therapeutic mechanism of XLP in HCC via in silico and in vitro studies. An approach was constructed to improve the accuracy of prediction in network pharmacology by combining big data and omics. Results First, we identified 13 potential ingredients in the serum of XLP-administered rats using LC-MS. Then the network pharmacology was performed to predict that XLP demonstrates anti-HCC effects via targeting 94 genes involving in 13 components. Modifying the database thresholds might impact the accuracy of network pharmacology analysis based on RNA sequencing data. For instance, when the matching rate peak is 0.43, the correctness rate peak is 0.85. Moreover, 9 components of XLP and 6 relevant genes have been verified with CCK-8 and RT-qPCR assay, respectively. Conclusion Based on the crossing studies of RNA sequencing and network pharmacology, XLP was found to improve HCC through multiple targets and pathways. Additionally, the study provides a way to optimize network pharmacology analysis in herbal medicine research.

Periodontal disease and arthroplasty prosthesis loosening and destabilization are both associated with osteolysis, which is predominantly caused by abnormal bone resorption triggered by pro-inflammatory cytokines. Osteoclasts (OCs) are critical players in the process. Concerns regarding the long-term efficacy and side effects of current frontline therapies, however, remain. Alternative therapies are still required. The aim of this work was to investigate the involvement of Tenacissoside H (TDH) in RANKL-mediated OC differentiation, as well as inflammatory osteolysis and associated processes. In vitro, bone marrow-derived macrophages (BMMs) cultured with RANKL and M-CSF were used to detect TDH in the differentiation and function of OCs. Real-time quantitative PCR was used to measure the expression of specific genes and inflammatory factors in OCs. Western blot was used to identify NFATc1, IKK, NF-κB, MAPK pathway, and oxidative stress-related components. Finally, an LPS-mediated calvarial osteolysis mouse model was employed to explore TDH's role in inflammatory osteolysis. The results showed that in vivo TDH inhibited the differentiation and resorption functions of OCs and down-regulated the transcription of osteoclast-specific genes, as well as Il-1β, Il-6 and Tnf-α. In addition, TDH inhibited the IKK and NF-κB signalling pathways and down-regulated the level of ROS. In vivo studies revealed that TDH improves the bone loss caused by LPS. TDH may be a new candidate or treatment for osteoclast-associated inflammatory osteolytic disease.

Meloxicam (MLX) is one of the most effective NSAIDs, but its poor water solubility and low bioavailability limit its clinical application. In this study, we designed a thermosensitive in situ gel of the hydroxypropyl-β-cyclodextrin inclusion complex (MLX/HP-β-CD-ISG) for rectal delivery to improve bioavailability. The best method for preparing MLX/HP-β-CD was the saturated aqueous solution method. The optimal inclusion prescription was optimized using an orthogonal test, and the inclusion complex was evaluated via PXRD, SEM, FTIR and DSC. Then, MLX/HP-β-CD-ISG was characterized regarding the gel properties, release in vitro, and pharmacokinetics in vivo. The inclusion rate of the inclusion complex obtained via the optimal preparation process was 90.32 ± 3.81%. The above four detection methods show that MLX is completely embedded in the HP-β-CD cavity. The developed MLX/HP-β-CD-ISG formulation has a suitable gelation temperature of 33.40 ± 0.17 °C, a gelation time of 57.33 ± 5.13 s, pH of 7.12 ± 0.05, good gelling ability and meets the requirements of rectal preparations. More importantly, MLX/HP-β-CD-ISG significantly improved the absorption and bioavailability of MLX in rats, prolonging the rectal residence time without causing rectal irritation. This study suggests that the MLX/HP-β-CD-ISG can have a wide application prospect with superior therapeutic benefits.

BACKGROUND:Activated osteoclasts cause excessive bone resorption, and disrupt bone homeostasis, leading to osteoporosis. The extracellular signal-regulated kinase (ERK) signaling is the classical pathway related to osteoclast differentiation, and mitochondrial reactive oxygen species are closely associated with the differentiation of osteoclasts. Myrislignan (MRL), a natural product derived from nutmeg, has multiple pharmacological activities; however, its therapeutic effect on osteoporosis is unclear. Here, we investigated whether MRL could inhibit osteoclastogenesis and bone mass loss in an ovariectomy mouse model by suppressing mitochondrial function and ERK signaling.METHODS:Tartrate-resistant and phosphatase (TRAP) and bone resorption assays were performed to observe the effect of MRL on osteoclastogenesis of bone marrow macrophages. MitoSOX RED and tetramethyl rhodamine methyl ester (TMRM) staining was performed to evaluate the inhibitory effect of MRL on mitochondria. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was performed to detect whether MRL suppressed the expression of osteoclast-specific genes. The impact of MRL on the protein involved in the mitogen-activated protein kinase (MAPK) and nuclear factor-κB pathways was evaluated using western blotting. In addition, a specific ERK agonist LM22B-10, was used to revalidate the inhibitory effect of MRL on ERK. Finally, we established an ovariectomy mouse model to assess the therapeutic effect of MRL on osteoporosis in vivo.RESULTS:MRL inhibited osteoclast differentiation and the associated bone resorption, by significantly decreasing osteoclastic gene expression. Mechanistically, MRL inhibited the phosphorylation of ERK by suppressing the mitochondrial function, thereby downregulating the nuclear factor of activated T cells 1 (NFATc1) signaling. LM22B-10 treatment further verified the targeted inhibition effect of MRL on ERK. Microscopic computed tomographic and histologic analyses of the tibial tissue sections indicated that ovariectomized mice had lower bone mass and higher expression of ERK compared with normal controls. However, MRL treatment significantly reversed these effects, indicating the anti-osteoporosis effect of MRL.CONCLUSION:We report for the first time that MRL inhibits ERK signaling by suppressing mitochondrial function, thereby ameliorating ovariectomy-induced osteoporosis. Our findings can provide a basis for the development of a novel therapeutic strategy for osteoporosis.

Background: Many studies have shown that Shensong Yangxin capsule (SSYX)–metoprolol combination has efficacy in treating cardiac arrhythmia. However, it is still lacking large randomized controlled trials and comprehensive and rigorous systematic evaluations. Purpose: A meta-analysis was conducted to evaluate the efficacy and safety of Shensong Yangxin capsule (SSYX) combined with metoprolol for treating cardiac arrhythmia. Methods: The following databases were searched from inception to October 2022 for randomized controlled trials evaluating the effect of SSYX combined with metoprolol for treating cardiac arrhythmia: Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journal Database. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool. Subgroup and sensitivity analyses were conducted to explore possible sources of heterogeneity across eligible studies. Results: A total of 107 publications and 9550 participants were included. Compared with metoprolol alone, SSYX combined with metoprolol significantly improved the total electrocardiographic efficacy (risk ratio [RR]: 1.26, 95% confidence interval [CI]: 1.24–1.28) and the total clinical efficacy on the symptoms (RR: 1.26, 95% CI: 1.24–1.29) and significantly reduced the number of premature ventricular contractions (weighted mean difference: −923.55, 95% CI: −1337.15 – −509.95). In addition, the incidence of adverse reactions was significantly lower with the SSYX–metoprolol combination than with metoprolol alone (RR: 0.65, 95% CI: 0.55–0.78). Subgroup analysis revealed that the efficacy was higher when the SSYX dose was 1.6 g. Conclusions: The combination of SSYX and metoprolol exhibited higher electrocardiographic and clinical efficacy and fewer adverse effects than metoprolol alone for treating cardiac arrhythmia.

Abstract Triptolide (TP) is a toxic component of Tripterygium wilfordii Hook. f. that exhibits liver and gastrointestinal toxicity. However, TP-induced liver injury varies between individuals via an unknown mechanism, which limits the safe clinical application of TP. Herein, we aimed to study the mechanism underlying the regulation of TP-induced liver injury via the gut-liver axis using a multi-omics technique. C57BL/6 mice were administered with TP at 800 µg/kg. We also constructed a mouse model based on the male C57BL/6 gut microbiota with quadruple antibiotics. 16S rRNA gene sequencing, hematoxylin and eosin staining, and biochemical analyses were used to analyze the intestinal microbiota composition in stool samples and TP-induced hepatotoxicity and enterotoxicity. Proteomics and targeted metabonomics were performed to analyze key proteins related to intestinal injury and differential liver metabolic markers. Gut microbiota Lactobacillus and Bacteroides were related to TP hepatotoxicity, while the Lactobacillus rhamnosus or Bacteroides fragilis colonization alleviated TP-induced liver and ileum damage after gut microbiota disorder. Multi-omics analyses showed that the TP caused changes in genes related to intestinal and liver immune responses. Gut microbiota disorder amplified related immune responses, causing changes in intestinal immune barrier-related proteins REG3B and REG3G and changes to liver metabolites via the gut-liver axis. Thus, the gut microbiota (via the gut–liver axis) plays an important role in liver injury induced by TP, allowing a better interpretation of TP-induced hepatotoxicity.

Capparis spinosa L. (C. spinosa) is an edible plant with health-promoting benefits. C. spinosa possesses various biological activities, including antioxidant, antidiabetic, anticancer, hepatoprotective, neuroprotective, anti-inflammatory, anti-arthritic, antibacterial, and insecticidal effects. The active compounds associated with these effects mainly include flavonoids, phenolic acids, alkaloids, volatile oils, fatty acids, and polysaccharides. Moreover, C. spinosa has considerable nutritional value. Apart from being a food condiment, it belongs to a class of functional ingredients that act as preservatives and antioxidants in food products. C. spinosa has also shown good potential applications in novel food packaging materials. In this article, in addition to systematically reviewing the botanical characteristics, traditional edible uses, phytochemical composition, bioactivities and safety of C. spinosa, we highlight for the first time its potential applications in the foods. The findings will provide critical information for the future development of C. spinosa into a multifunctional food product with essential roles in health benefits.

周华教授诊治心律失常过程中,注重现代医学诊治与中医辨证论治结合,以辨主病,辨病势,辨证候为主线,注重防变,取得较好的疗效.

目的 探讨鹿红方抑制心肌梗死后心力衰竭大鼠心肌细胞凋亡的作用机制.方法 60只Wistar大鼠随机分为假手术组、模型组、鹿红方组和培哚普利组,每组15只.除假手术组外,采用结扎左冠状动脉前降支制备心力衰竭大鼠模型,分别给予相应干预8周.采用超声心动图检测大鼠左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左室舒张末期内径(LVIDd)和左室收缩末期内径(LVIDs);HE染色和Masson染色观察心肌组织病理改变及纤维化情况;ELISA检测血清B型利钠肽(BNP)含量;TUNEL法观察心肌细胞凋亡情况;Western blot检测心肌组织PI3K、AKT、p-AKT及凋亡相关蛋白Bcl-2、Bax表达.结果 与假手术组比较,模型组大鼠LVEF、LVFS明显降低,LVIDd、LVIDs明显升高,血清BNP含量增加,心肌组织病理损伤明显,纤维化面积增大,心肌细胞凋亡率明显升高,PI3K、p-AKT及Bax蛋白表达升高,Bcl-2蛋白表达降低,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,鹿红方组和培哚普利组大鼠心功能明显改善,LVEF、LVFS明显升高,LVIDd、LVIDs明显降低,血清BNP含量减少,心肌纤维化面积缩小,心肌细胞凋亡率明显降低,PI3K、p-AKT及Bax蛋白表达降低,Bcl-2蛋白表达升高,差异均有统计学意义(P<0.05,P<0.01).结论 鹿红方能有效抑制心力衰竭大鼠心肌细胞凋亡,缩小心肌纤维化面积,改善心功能,其机制可能与抑制PI3K/AKT/Bax信号通路活化有关.

目的 利用住院病案首页信息,分析急性心肌梗死流行病学特点,为制定急性心肌梗死防治策略提供重要依据.方法 筛选2012年1月1日—2016年12月31日在上海市某三级甲等医院出院诊断为急性心肌梗死(ICD-10编码为I21.9)的病人,提取住院号、年龄、性别、入院途径、治疗方式、介入治疗、治疗费用、治疗结果等数据,使用SAS软件进行统计分析.结果 男性病人的中位年龄小于女性病人,差异有统计学意义(P<0.001),女性病人的死亡风险是男性病人的2.54倍,急诊入院途径与门诊入院途径的病人在年龄、住院费用和病死率方面比较差异无统计学意义(P>0.05);死亡病人中仅有53.66％接受过介入治疗,低于未死亡病人;70岁及以上病人死亡风险是70岁以下病人的8.39倍.结论 急性心肌梗死防治要重点关注中老年病人,绝经女性也不容忽视,提倡介入治疗等积极的治疗方式.

目的 观察清脂化瘀方对常规他汀类药物治疗后血脂仍未达标的冠心病痰瘀互结证病人血脂、血液流变学及炎性因子的影响.方法 选取2018年5月—2019年12月上海某三级甲等医院心血管内科门诊及住院治疗的冠心病痰瘀互结证病人72例,均经常规他汀类药物治疗后血脂仍未达标.按照随机数字表法分为对照组和治疗组,各36例,对照组给予西药常规治疗(阿托伐他汀及其他冠心病二级预防药物)加用安慰剂,治疗组给予西药常规治疗(阿托伐他汀及其他冠心病二级预防药物)及清脂化瘀方治疗.观察两组治疗前后血脂[小而密低密度脂蛋白胆固醇(sdLDL-C)、血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)]、血液流变学[全血黏度(高切、低切)、纤维蛋白原(FIB)及红细胞比容]、炎性因子[白介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)]的变化,比较两组中医证候疗效.结果 治疗组中医证候疗效总有效率高于对照组(88.9％与63.9％,P<0.05).治疗后,治疗组sdLDL-C、TC、LDL-C、FIB、红细胞比容、TNF-α、IL-6均低于对照组(P<0.05);两组治疗后TG、HDL-C、全血高切黏度、全血低切黏度比较差异均无统计学意义(P>0.05).结论 对于常规他汀类药物治疗后血脂仍未达标的冠心病痰瘀互结证病人,加用清脂化瘀方可进一步降低血清sdLDL-C、TC、LDL-C、FIB、红细胞比容、TNF-α、IL-6水平,改善中医证候.

综述国内外关于中药单体及复方制剂对肠道菌群干预心力衰竭的研究,揭示中药可以通过恢复肠道稳态、调节菌群的种类及代谢物水平起到治疗心力衰竭的作用,以期为心力衰竭的防治提供新的方向.心力衰竭与肠道菌群的相关性是当今医学研究的热点,肠道菌群的失衡与心力衰竭的发生、发展密切相关,中医药在调节肠道微生物方面发挥着重要作用,并广泛应用于心力衰竭的预防与治疗中.

自噬与心血管疾病的发生发展密切相关,同时中药单体及复方通过多靶点、多途径干预自噬,延缓心力衰竭发展.现综述中药调控自噬防治心力衰竭的研究进展,以期为研发具有心肌细胞保护作用的活性成分提供参考.

冠心病是一种严重危害人类健康的流行性疾病,血脂代谢异常是主要发病机制.其中,小而密低密度脂蛋白(sdLDL-C)是冠心病的独立危险因素,目前治疗sdLDL-C不达标的方法主要为他汀类药物.现从sdLDL-C在冠心病中西医治疗中的研究进展进行综述,为冠心病的防治提供新思路.

中医认为冠心病合并高脂血症与脾的生理功能存在密切联系,"脾失健运,痰瘀互结"是其发生的重要病机.近年来通过分析冠心病合并高脂血症与肠道菌群之间关系,发现肠道菌群失调使脂质吸收、炎症反应及代谢产物增加,诱导冠心病及高脂血症的发生.另外,中医"脾"与肠道菌群间存在密切联系,中医认为"脾为生痰之源""心气受气于脾",从脾论治冠心病合并高脂血症是对整个机体病理网络的调控.因此,基于肠道菌群,从中医脾生理出发,探讨通过健脾益气、降脂化浊,改善肠道菌群治疗冠心病合并高脂血症的可行性.

Liver is the main place of drug metabolism. Mitochondria of hepatocytes are important targets of drug-induced liver injury. Mitochondrial autophagy could maintain the healthy operation of mitochondria in cells and the stable proliferation of cells. Therefore, the use of mitochondrial autophagy to remove damaged mitochondria is an important strategy of anti-drug-induced liver injury. Active ingredients that could enhance mitochondrial autophagy are contained in many traditional Chinese medicines, which could regulate the mitochondrial autophagy to alleviate relevant diseases. However, there are only a few reports on how to accurately and efficiently identify and evaluate such components targeting mitochondria from traditional Chinese medicine. Liquid chromatography-mass spectro-metry(LC-MS) combined with serum pharmacology in vivo can be used to accurately and efficiently find active ingredients of traditional Chinese medicine acting on mitochondrial targets. This paper reviewed the research ideas and methods of traditional Chinese medicine ingredients for increasing the hepatotoxicity of mitochondrial autophagy, in order to provide new ideas and methods for the study of active ingredients of traditional Chinese medicine targeting mitochondria.

目的:研究刺山柑果实提取物对四氯化碳(CCl4)诱导的小鼠肝纤维化的保护作用及可能机制.方法:45只C57BL小鼠随机分为正常组、模型组、扶正化瘀方组(FZHY组,4 g/kg)、刺山柑低剂量组(0.93 g/kg)和高剂量组(2.80 g/kg),每组9只.除正常组外,其余各组小鼠腹腔注射10％CCl4,每次2 ml/kg,每周3次,连续8周,诱导小鼠实验性肝纤维化模型.造模第5周起,各药物组灌胃给予相应剂量的药液,连续4周.末次给药后,采集血清和肝脏样本.试剂盒检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)活性以及总胆红素(TBIL)、白蛋白(ALB)、总蛋白(TP)水平.HE染色和天狼猩红染色后,光镜下观察肝组织形态学变化.试剂盒检测肝组织羟脯氨酸(Hyp)水平以及超氧化物歧化酶(SOD)、丙二醛(MDA)活性.Western blot检测肝组织自噬相关蛋白LC3-I和LC3-Ⅱ的表达水平.结果:①与模型组相比,FZHY组和刺山柑低、高剂量组小鼠的ALT、AST、ALP、TBIL水平显著降低(P＜0.05,P＜0.01),TP和ALB水平显著升高(P＜0.01);且刺山柑高剂量组小鼠的ALT和AST水平明显低于低剂量组(P＜0.05.P＜0.01).②HE染色和天狼猩红染色观察显示,模型组小鼠肝细胞可见大面积出血性坏死,纤维组织广泛增生形成间隔,并将肝组织包围形成假小叶;与模型组相比,FZHY组及刺山柑低、高剂量组小鼠的肝组织形态均有不同程度改善,肝细胞坏死明显减少,同时纤维增生有所减轻,假小叶逐渐消失;且刺山柑高剂量组的改善作用优于低剂量组.半定量分析结果表明,FZHY组和刺山柑高剂量组的胶原阳性染色面积占比较模型组显著降低(P＜0.05).③与模型组相比,FZHY组及刺山柑低、高剂量组小鼠肝组织Hyp含量显著降低(P＜0.01),SOD水平显著升高(P＜0.01),MDA水平显著降低(P＜0.05,P＜0.01).④Western blot结果显示,刺山柑低、高剂量组小鼠肝组织LC3-Ⅱ蛋白表达较模型组显著上调(P＜0.01),但LC3-Ⅰ蛋白表达无明显变化.结论:刺山柑果实提取物可有效减轻CCl4诱导的小鼠肝纤维化,明显改善模型小鼠的肝功能及病理损伤,其作用机制与抑制肝脏胶原纤维生成、清除氧自由基和促进线粒体自噬有关.