摘要：
Seco-triterpenoids are a unique class of triterpenoids possessing distinct structural features. Based on the differences in their parent nucleus, they can be divided into two categories: tetracyclic triterpenes and pentacyclic triterpenes, which are widely distributed across various plant species. Previous studies indicate that natural seco-triterpenoids have diverse chemical structures and exhibit extensive biological activities, including anti-tumor, anti-inflammatory, hypoglycemic, and neuroprotective effects. This review comprehensively summarizes recent research (2020–2023) on seco-triterpenoids and derived saponins, encompassing their chemical structures, plant distributions, pharmacological activities, structure–activity relationships, and future development trends. Furthermore, we utilized the latest bibliometric tool, VOSviewer, to conduct a keyword cluster analysis, enabling us to identify current research hotspots and patterns. Besides, we have cataloged and analyzed 351 compounds, inclusive of 298 tetracyclic triterpenoids and 53 pentacyclic triterpenoids, in order to provide valuable references for activity mining and structural modification of seco-triterpenoids, facilitating further clinical applications and developments. Collectively, seco-triterpenoids represent an important class of natural products with significant potential for pharmacological use. By summarizing recent research achievements, this review provides a beneficial resource for scientists in the field, promoting the exploration and development of seco-triterpenoid-based drugs.
关键词：
Chinese herbal compound;Large intestine cancer;AOM/DSS-Induced colorectal cancer mice;16S rRNA;Inflammation
摘要：
This study was conducted to observe the effect of Chinese herbal compound on the treatment of colon cancer using AOM/DSS-induced C57BL/6J colon cancer mice and to validate potential influence on intestinal flora of mice. A colorectal cancer (CRC) mouse model was built with a total of 50 C57BL/6J mice that were induced by administrating AOM/DSS. These experimental animals were split up into 5 groups, a control group, a model group, and low-, medium- and high-dose Chinese herbal compound groups. All mice were given Chinese herbal compound treatment, and the colon tissues of each group were harvested with the length measured and the number of colon polyps accounted. The Ki-67 expression in the colon tissues was detected via immuno-histochemistry. Relative quantification of the expression of genes and proteins was determined through qPCR and WB assays. Contents of IL-6, TNF-α, IFN-γ, and IL-10 in serum and colon tissues of mice were determined by ELISA. An additional 16S rRNA sequencing analysis was implemented for the identification of mouse intestinal flora. The results suggested that all low-, medium- or high-dose Chinese herbal compound could markedly inhibit the shortening of colon length and significant number reduction of colon polyps in the model group. The relative expression of genes and proteins (PCNA, Muc16, and MMP-9) associated with proliferation in mouse colon tissues were inhibited. In addition, compared with the model group, the contents of IL-6, TNF-α, and IFN-γ in serum and colon tissues were substantially decreased in the high-dose Chinese herbal compound group, thereby reducing the structure damage in colon tissues and the infiltration degree of inflammatory cells. Besides, the expression of TLR4/MyD88/NF-κB protein was markedly decreased. The 16S rRNA sequencing analysis demonstrated that mice in the model group had decreased intestinal flora diversity, and there were significant changes in flora abundance and amino acid metabolism between the control group and the model group. Taken together, the treatment of Chinese herbal compound against CRC in this study might be regulated by the TLR4/MyD88/NF-κB signaling pathway, and the imbalance in intestinal flora was also closely related to CRC occurrence.
期刊：
TISSUE ENGINEERING AND REGENERATIVE MEDICINE,2024年21(1):185-197 ISSN：1738-2696
通讯作者：
Zhang, Ying;Cao, XY
作者机构：
[Zhang, Leilei; Cao, XY; Zhang, Ying; Cao, Xiangyang] Luoyang Orthoped Traumatol Hosp, Orthoped Hosp Henan Prov, Med Ctr Hip, 82 Qiming South Rd, Luoyang 471002, Henan, Peoples R China.;[Li, Chuan] 920Th Hosp Joint Logist Support Force, Dept Oncol, Kunming 650032, Yunnan, Peoples R China.;[Wei, Qiushi; He, Wei] Guangzhou Univ Tradit Chinese Med, Inst Orthopaed, Guangzhou 510240, Peoples R China.;[Wei, Qiushi; He, Wei] Guangzhou Univ Tradit Chinese Med, Affiliated Hosp 3, Guangzhou 510240, Peoples R China.;[Jing, Zhenhao; Yuan, Qiang; Dong, Yiping] Henan Univ Tradit Chinese Med, Zhengzhou 450046, Henan, Peoples R China.
通讯机构：
[Cao, XY ; Zhang, Y] L;Luoyang Orthoped Traumatol Hosp, Orthoped Hosp Henan Prov, Med Ctr Hip, 82 Qiming South Rd, Luoyang 471002, Henan, Peoples R China.
关键词：
Osteonecrosis of the femoral head;Sustained release system;PEG-PLGA-PLL nanoparticle;MiR-320a;Bone regeneration
摘要：
BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin-eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.
作者机构：
[Zheng, Yu; Zheng, Huizhen] Hunan Univ Chinese Med, Clin Coll Chinese Med 1, Changsha 410007, Peoples R China.;[Zheng, Yu; Zheng, Huizhen; Guo, Zhihua] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Guo, ZH ] H;Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.
关键词：
Bayesian model;Clinical efficacy;Heart failure with (mildly) reduced ejection fraction;Network meta-analysis;Traditional Chinese medicine injection
摘要：
BACKGROUND: More than half of all heart failure (HF) patients have heart failure with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF). The combination of traditional Chinese medicine injections (TCMIs) with Western medicine treatment (WMT) has been reported to have better efficacy than using WMT alone. However, the positive effects of TCMIs combined with WMT on HFrEF and HFmrEF require more comprehensive and systematic evidence and warrant further investigation. METHODS: The NMA searched eight databases, including four English and four Chinese, from database creation to November 10, 2022. We used the Cochrane Risk of Bias tool (ROB 2) to assess the selected studies' quality. OpenBUGS and STATA 17.0 were used for network meta-analysis. RESULTS: The 101 RCTs were included in the systematic review. Studies have shown that when combined with any of the five TCMIs, WMT was more efficient than WMT alone. Shenmai injection (SMI)+WMT may be the best treatment for clinical effectiveness rate (CER) improvement and b-type natriuretic peptide (BNP) reduction. Huangqi injection (HQI)+WMT was the best treatment for improving left ventricular ejection fraction (LVEF). Danhong injection (DHI)+WMT may be the best treatment for lowering left ventricular end-diastolic dimension (LVEDD). Xinmailong injection (XMLI)+WMT was likely the best treatment for increasing the 6-min walking test (6MWT). In addition, XMLI had the lowest incidence of adverse reactions (3.38%). CONCLUSIONS: Shenfu injection (SFI), SMI, DHI, XMLI, and HQI combined with WMT have stronger efficiency in treating HFrEF and HFmrEF. However, as all studies were conducted in China, this review is limited by the inevitable selection bias, and further high-quality multicenter randomized controlled trials (RCTs) are required.
期刊：
Supportive Care in Cancer,2024年32(2):136 ISSN：0941-4355
通讯作者：
So, WKW
作者机构：
[Xu, Binbin] Hunan Univ Chinese Med, Sch Nursing, Changsha, Peoples R China.;[So, Winnie K. W.; Choi, Kai Chow; Xu, Binbin; So, WKW] Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Peoples R China.
通讯机构：
[So, WKW ] C;Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Peoples R China.
关键词：
COmprehensive Score for financial Toxicity;Cut-off score;Cost-related treatment nonadherence;Health-related quality of life;Cancer;Chinese
摘要：
PURPOSE: This study aimed to determine a cut-off for the simplified Chinese version of the COmprehensive Score for financial Toxicity (COST) that could identify cost-related treatment nonadherence among Chinese patients with cancer. The study also sought to validate this cut-off score by using it to assess impaired health-related quality of life (HRQoL) in the same population. METHODS: A secondary analysis was conducted using data from a cross-sectional survey of 1208 Chinese patients with cancer who were recruited from 12 hospitals in six cities across three provinces of the Chinese mainland. Sociodemographic information and data on financial toxicity (FT), cost-related treatment nonadherence, and HRQoL were used in the analysis. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off for the simplified Chinese version of the COST. RESULTS: The ROC analysis identified a COST cut-off of 18.5 for identifying cost-related treatment nonadherence, yielding a sensitivity of 76.5% and specificity of 71.4%. In the validation study, this cut-off score yielded a sensitivity of 64.2% and a specificity of 67.1% for identifying impaired HRQoL. CONCLUSION: Early and dynamic assessment of cancer-related FT in routine clinical practice may play a crucial role in the early identification and management of FT. Accordingly, a COST cut-off of 18.5 was identified to indicate cost-related treatment nonadherence and impaired HRQoL in a population of patients with cancer from the Chinese mainland. This finding may facilitate the implementation of universal FT screening among patients with cancer in specific settings such as the Chinese mainland.
摘要：
INTRODUCTION: Innate and acquired chemoresistance in colorectal cancer (CRC) often results in 5-fluorouracil (5-FU) treatment failure. This study aimed to investigate the potential of Jianpi Jiedu (JPJD) decoction to reverse 5-FU resistance in CRC and clarify its potential mechanism of action. METHODS: The CCK-8 assay was employed to assess cell activity. Flow cytometry was employed to assess various parameters including cell apoptosis, cell cycle distribution, P-glycoprotein (P-gp) activity, reactive oxygen species levels, and lipid peroxidation. Metabolomics analysis was conducted to identify differentially expressed metabolites. Western blotting was utilized for protein expression analysis. RESULTS: In this study, we demonstrated that the combined JPJD and 5-FU treatment reversed 5-FU resistance in HCT8/5-FU cells, inducing cell apoptosis, causing G2/M-phase cell cycle arrest, and reducing P-gp protein expression and activity. Metabolomics analysis revealed ferroptosis as a key pathway in the development of 5-FU resistance. Furthermore, the combination treatment reversed drug resistance primarily by impacting ferroptosis and triggering critical ferroptosis events through the suppression of the cystine/glutamate transporter (xCT)/glutathione (GSH)/glutathione peroxidase (GPX4) axis. CONCLUSION: JPJD decoction primarily suppressed the xCT/GSH/GPX4 axis to trigger ferroptosis, thereby effectively reversing 5-FU resistance in colorectal cancer (CRC).
通讯机构：
[Peng, QH ; Yao, XL] H;Hunan Univ Tradit Chinese Med, Changsha, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha, Hunan, Peoples R China.
关键词：
nonspecific orbital inflammation (NSOI);purine metabolism genes (PMGs);LASSO regression;SVM-RFE;bioinformatics
摘要：
Background Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by a heterogeneous lymphoid infiltration within the orbital region. This condition, marked by the aberrant metabolic activities of its cellular constituents, starkly contrasts with the metabolic equilibrium found in healthy cells. Among the myriad pathways integral to cellular metabolism, purine metabolism emerges as a critical player, providing the building blocks for nucleic acid synthesis, such as DNA and RNA. Despite its significance, the contribution of Purine Metabolism Genes (PMGs) to the pathophysiological landscape of NSOI remains a mystery, highlighting a critical gap in our understanding of the disease's molecular underpinnings.Methods To bridge this knowledge gap, our study embarked on an exploratory journey to identify and validate PMGs implicated in NSOI, employing a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 92 known PMGs, we aimed to pinpoint those with potential roles in NSOI. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), facilitated a deep dive into the biological functions and pathways associated with these PMGs. Further refinement through Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) enabled the identification of key hub genes and the evaluation of their diagnostic prowess for NSOI. Additionally, the relationship between these hub PMGs and relevant clinical parameters was thoroughly investigated. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the seven PMGs identified as potentially crucial to NSOI pathology.Results Our investigation unveiled seven PMGs (ENTPD1, POLR2K, NPR2, PDE6D, PDE6H, PDE4B, and ALLC) as intimately connected to NSOI. Functional analyses shed light on their involvement in processes such as peroxisome targeting sequence binding, seminiferous tubule development, and ciliary transition zone organization. Importantly, the diagnostic capabilities of these PMGs demonstrated promising efficacy in distinguishing NSOI from non-affected states.Conclusions Through rigorous bioinformatics analyses, this study unveils seven PMGs as novel biomarker candidates for NSOI, elucidating their potential roles in the disease's pathogenesis. These discoveries not only enhance our understanding of NSOI at the molecular level but also pave the way for innovative approaches to monitor and study its progression, offering a beacon of hope for individuals afflicted by this enigmatic condition.
作者机构：
[Ma, YM; Ma, Yanmei; Zhang, Yan] Changzhi Med Coll, Heji Hosp, Dept Hematol, Changzhi 046000, Shanxi, Peoples R China.;[Li, Jie] Hunan Univ Chinese Med, Liuyang Hosp Tradit Chinese Med, Dept Oncol & Hematol, Changsha 410300, Hunan, Peoples R China.;[Li, Xi] Changzhi Med Coll, Heping Hosp, Dept Nephrol, Changzhi 046000, Shanxi, Peoples R China.;[Wei, Mingxia; Wei, MX; Xie, Yuqin; Zhang, Guoxiang; Geng, Qianshuang] Changzhi Med Coll, Heping Hosp, Dept Hematol, Changzhi 046000, Shanxi, Peoples R China.
通讯机构：
[Wei, MX ; Ma, YM ] C;Changzhi Med Coll, Heji Hosp, Dept Hematol, Changzhi 046000, Shanxi, Peoples R China.;Changzhi Med Coll, Heping Hosp, Dept Hematol, Changzhi 046000, Shanxi, Peoples R China.
摘要：
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA. We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis. A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58–2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60–2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75–1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83–4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08–3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85–2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15–2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93–2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46–1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics. EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events. This paper aims to perform a meta-analysis analyzing the efficacy and safety of eltrombopag for severe aplastic anemia. Our study suggests that EPAG added to IST is beneficial for patients with SAA.
摘要：
AIMS: This work aims to analyse the current state of the professional identity of Chinese nurses; examine the relationship amongst regulatory focus, organizational silence and professional identity and determine how regulatory focus affects the relationship between professional identity and organizational silence. DESIGN: This study conducted a cross-sectional survey. METHODS: From June to August 2023, 420 nurses from six hospitals in Hunan Province, China, were selected through convenience sampling and surveyed by using a general information questionnaire, the regulatory focus scale, the organizational silence scale and the professional identity scale. The relationship amongst the regulatory focus, organizational silence and professional identity of nurses was examined by utilizing SPSS 25.0 and the mediating role of regulatory focus between organizational silence and nurses' professional identity was examined by applying AMOS 24.0. RESULTS: Nurses had a moderate level of professional identity. Professional identity was positively correlated with regulatory focus and negatively correlated with organizational silence. Regulatory focus was negatively correlated with organizational silence. Mediation effect studies revealed that organizational silence and professional identity were partially mediated by regulatory focus. CONCLUSION: In accordance with research showing that nurses' organizational silence can indirectly affect professional identity via regulatory focus, clinical nursing managers should concentrate on the interaction amongst these three variables to strengthen professional identity. IMPACT: The results of this study serve as a reminder to nurses to select a preventive or promotive focus based on their career objectives and to effectively express their views to enhance their professional identity. This also reminds nursing managers assess nurse-led regulatory focus, identify their underlying qualities and understand their professional aspirations and career orientation, create a good atmosphere for advice and encourage nurses to express their views, so as to improve nurses 'professional identity. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
作者：
Shah, Muhammad Raza;Fatima, Samreen;Khan, Sehrosh Naz;Azam, Zahid;Shaikh, Hafeezullah;...
期刊：
Frontiers in Pharmacology,2024年15:1293272 ISSN：1663-9812
通讯作者：
Shah, MR
作者机构：
[Shah, MR; Fatima, Samreen; Shah, Muhammad Raza; Khan, Sehrosh Naz] Univ Karachi, Ctr Bioequivalence Studies & Clin Res, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi, Pakistan.;[Shaikh, Hafeezullah; Azam, Zahid] Dow Univ Hlth Sci, Natl Inst Liver & GI Dis NILGID, Karachi, Sindh, Pakistan.;[Majid, Shahid] Indus Hosp Karachi, Karachi, Sindh, Pakistan.;[Zhou, Daijun; He, Chengdong] Hunan Xinhui Pharmaceut Co Ltd, Changsha, Hunan, Peoples R China.;[Wang, Wei] Hunan Univ Chinese Med, Sch Pharm, TCM & Ethnomed Innovat & Dev Int Lab, Changsha, Peoples R China.
通讯机构：
[Shah, MR ] U;Univ Karachi, Ctr Bioequivalence Studies & Clin Res, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi, Pakistan.
关键词：
Houtou Jianweiling tablet (HTJWT);clinical trial;omeperazole;randomization;traditional Chinese medicine (TCM)
摘要：
Background: Common symptoms of Chronic Non-atrophic Gastritis (CNAG) include nausea, stomach distension, and abdominal pain. The Houtou Jianweiling Tablet (HTJWT) is a chinese patent medicine (CN1368229A) and it has been used clinically for more than 20years with proven clinical efficacy in treating CNAG, prompted us to establish the clinical efficacy and safety of HTJWT on patients with mild to moderate CNAG symptoms in Pakistani population. Methods: This phase II, double-blind, randomized, parallel-controlled trial was conducted in a single center between November 2022 and February 2023 in Pakistan. In a ratio of 1:1, total 240 CNAG patients with erosion identified by pathological biopsy and gastroscopy were randomly assigned to control (Omeprazole) group (n = 120) and the treatment (HTJWT) group (n = 120). Patients in the treatment group received orally four HTJWT (0.38g/tablet), three times a day and one placebo of Omeprazole enteric-coated tablet prior to breakfast, daily. On the other hand, patients in the control group received one Omeprazole enteric-coated tablet (20 mg/tablet) prior to breakfast and four placebo of HTJWT, thrice a day. The patients consumed the investigated drugs (i.e., treatment and control) treatment regimen was followed for a duration of 28days. The safety of the patients were evaluated through adverse events, serious adverse events and laboratory tests such as blood biochemistry, urine analysis, liver and renal function tests. Vital signs like; blood pressure, pulse rate, body temperature, respiratory rate for all the patients were recorded. The cardiac status of the patients were assessed through electrocardiogram (ECG). The primary efficacy indicators were the improvement rate of gastric distention and gastralgia as the main clinical symptoms. Secondary indicators were visual analogue score (VAS); improvement rate of secondary clinical symptoms and signs; improvement rate of total clinical signs and symptoms; the disappearance/remission rate of Gastric pain and, remission/disappearance time of gastric distension; and the negative conversion rate of Helicobacter pylori (H. pylori). The outcomes among each group were compared using the chi-square test. Results: Patients in both groups had good drug compliance (80%-120%), and there was no statistically significant difference in the patients' baseline characteristics. The clinical improvement rate was found to be 91.1% in the treatment group and 91.0% in the control group with negligible variation among the two groups (p = 0.9824; 95% confidence interval: -0.0781-0.0798). Similarly, hardly no difference was found in the negative conversion rate of H. pylori between the treatment group and the control group (i.e., 70.1% and 71.8% respectively, p = 0.8125). There were no significant differences in respiratory rate, vital signs, blood pressure, laboratory results for blood biochemistry, urine analysis, liver and renal function tests between the two groups. The ECG assessment carried out for the treatment and control group revealed no considerable difference. Margin variation in the disappearance time of gastric pain (p = 0.1860) and remission rate (p = 0.5784) between the two groups were observed. The control group exhibited a faster remission period for gastrointestinal discomfort indications as compared to treatment group (p = 0.0430). Only one patient in the control group experienced mild to moderate adverse events, namely,; epigastric pain and dyspepsia. The results were consistent with the intention-to-treat and per-protocol analysis that included patients who were 100% compliant to the assigned therapy. Conclusion: The lower limit of confidence interval (CI, 95%) for the differences in the effective rate between the treatment and the control groups was found to be -0.0781 which is greater than -0.15, hence the treatment group is non-inferior to the control group. The therapeutic dosage used in the trial and treatment period did not cause any significant adverse event, and there were no obvious changes in the ECG profile, vital signs and biochemistry of the patients. Based on the clinical efficacy evaluation and reported adverse events, it can be concluded that the HTJWT is a safe and effective traditional chinese medicine for the treatment of patients suffering from chronic non-atrophic gastritis with mild to moderate symptoms. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [NCT04672018].
作者机构：
[Wang, Zhu; Hu, Jinyang; Wang, Z; Niu, Junjie] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Med Oncol, 58 Lushan Rd, Changsha 410000, Hunan, Peoples R China.
通讯机构：
[Wang, Z ] H;Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Med Oncol, 58 Lushan Rd, Changsha 410000, Hunan, Peoples R China.
关键词：
triple negative breast cancer;RhoA;ROCK1;Ezrin;scutellaria barbata D.Don extract
摘要：
BACKGROUND: Triple-negative breast cancer (TNBC) lacks effective therapeutic targets. Scutellaria barbata D.Don (SB) has been revealed to have anti-breast cancer (BC) effect, but the effect of SB extract in TNBC is still unclear. Herein, this research delves into the underlying mechanism. METHODS: SB was extracted by solvent extraction, and the main components were identified using an Agilent 6,520 HPLC-Chip/Q-TOF (Chip/Q-TOF) MS system. In vitro cell experiments were conducted. The effects of SB extract alone, SB extract plus EGF, GSK alone, GSK plus Ezrin overexpression, or SB extract plus Ezrin overexpression on cell viability, invasion, migration, and apoptosis were examined by cell function experiments. The apoptosis- and RhoA/ROCK1 pathway-related protein levels were analyzed by western blot assay. RESULTS: Mass spectrometry analysis exhibited that SB extract mainly contains long-chain fatty acids and ursolic acid. SB extract mitigated TNBC cell biological phenotypes, apoptosis- and RhoA/ROCK1 pathway-related marker expressions, which were reversed by EGF. The further results found that GSK obviously weakens TNBC cell biological behaviors, apoptosis- and RhoA/ROCK1 signaling-related protein levels, while oe-Ezrin treatment reverses the effect of GSK on TNBC cells. Moreover, SB extract regulated Ezrin-mediated function of TNBC cells by impeding the RhoA/ROCK1 pathway. CONCLUSION: Our findings demonstrated that SB extract regulated Ezrin-mediated proliferation, migration, invasion, and apoptosis of TNBC cells via suppressing the RhoA /ROCK1 signaling. Our results offer the experimental foundation for further investigation of the anti-cancer role of SB in TNBC cells. HIGHLIGHTS: SB extract inhibits the biological phenotypes of TNBC cells.SB extract inhibits the biological behaviors of TNBC cells through the RhoA/ROCK1 pathway.SB extract modulates Ezrin-mediated TNBC cell proliferation, migration, invasion, and apoptosis via restraining the RhoA/ROCK1 signaling.
通讯机构：
[Tan, Y; Pei, G ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410000, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410000, Peoples R China.
关键词：
H3K18la;LDHA;histone lactylation;liver injury;macrophages;salvianolic acid B
摘要：
Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B's effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl(4)-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear. AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment. METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors. RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines. CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.
关键词：
Acute toxicity;Behavioral analysis;Danggui Shaoyao San;Danio rerio;Histopathological alteration index
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. AIM OF THE STUDY: To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. MATERIALS AND METHODS: The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. RESULTS: Compared with the control group, 25, 50 and 100mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio, only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. CONCLUSION: A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation.
作者机构：
[Li, Hua; Chen, Xinhao; Li, H] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Peoples R China.
通讯机构：
[Li, H ] H;Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Peoples R China.
摘要：
BACKGROUND: Breast cancer is one of the most common female malignancies. This study explored the underlying mechanism through which the two plant compounds (Brucaine D and Narclasine) inhibited the proliferation of breast cancer cells. OBJECTIVE: The purpose of this study was to explore the effect of Brucaine D and Narclasine on breast cancer development and their potential drug targets. METHODS: GSE85871 dataset containing 212 samples and the hallmark gene set "h.all.v2023.1.Hs.symbols.gmt" were downloaded from the Gene Expression Omnibus (GEO) database and the Molecular Signatures Database (MSigDB) database, respectively. Principal component analysis (PCA) was applied to classify clusters showing similar gene expression pattern. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the hallmark score for different drug treatment groups. The expressions of genes related to angiogenesis, glycolysis and cell cycle were detected. Protein-protein interaction (PPI) network analysis was performed to study the interaction of the hub genes. Then, HERB database was employed to identify potential target genes for Narclasine and Bruceine D. Finally, in vitro experiments were conducted to validate partial drug-target pair. RESULTS: PCA analysis showed that the significant changes in gene expression patterns took place in 6 drugs treatment groups (Narciclasine, Bruceine D, Japonicone A, 1beta-hydroxyalatolactone, Britanin, and four mixture drugs) in comparison to the remaining drug treatment groups. The ssGSEA pathway enrichment analysis demonstrated that Narciclasine and Bruceine treatments had similar enriched pathways, for instance, suppressed pathways related to angiogenesis, Glycolysis, and cell cycle, etc.. Further gene expression analysis confirmed that Narciclasine and Bruceine had a strong ability to inhibit these cell cycle genes, and that MYC, CHEK2, MELK, CDK4 and EZH2 were closely interacted with each other in the PPI analysis. Drug target prediction revealed that Androgen Receptor (AR) and Estrogen Receptor 1 (ESR1) were the targets for Bruceine D, and Cytochrome P450 3A4 enzyme (CYP3A4) was the target for Narciclasine. Cell experiments also confirmed the connections between Narciclasine and CYP3A4. CONCLUSION: The present study uncovered that Narciclasine and Bruceine D could inhibit the growth of breast cancer and also predicted the potential targets for these two drugs, providing a new therapeutic direction for breast cancer patients.
期刊：
BALKAN MEDICAL JOURNAL,2024年41(2):130-138 ISSN：2146-3123
通讯作者：
Peng, Wei;Zeng, PH
作者机构：
[Yang, Renyi; Zeng, Puhua; Chen, Hongyao; Li, Kexiong; Yu, Xiaopeng; Peng, Wei; Peng, W] Hunan Acad Chinese Med, Hunan Acad Tradit Chinese Med, Canc Res Inst, Hunan Prov Hosp Integrated Tradit Chinese & Weste, Changsha, Hunan, Peoples R China.;[Yang, Renyi; Chen, Hongyao; Xue, Peisen] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Zeng, PH ; Peng, W] H;Hunan Acad Chinese Med, Hunan Acad Tradit Chinese Med, Canc Res Inst, Hunan Prov Hosp Integrated Tradit Chinese & Weste, Changsha, Hunan, Peoples R China.
摘要：
BACKGROUND: The changes in risk scores of inflammatory markers among patients diagnosed with hepatocellular carcinoma (HCC) remain unknown. AIMS: To investigate the relationship between the inflammation risk score and other contributing factors and the prognostic outcomes in patients with moderate and advanced hepatitis B virus (HBV)-related HCC. STUDY DESIGN: A retrospective cohort study. METHODS: A total of 174 patients with moderate and advanced HBV related HCC were recruited to investigate the impact of stratified inflammatory risk scores and other associated risk factors on disease prognosis. Based on the optimal cut-off values calculated by the Youden index, the patients were divided into high-risk and low-risk groups based on their inflammation risk scores. RESULTS: The study found a significant difference in median survival time between the low-risk and high-risk groups based on the inflammation risk score. Furthermore, the inflammation risk score, alpha-fetoprotein levels, transarterial chemoembolization treatment, and Barcelona Clinic Liver Cancer stage were identified as independent prognostic factors. The four variables were used to construct a prognostic nomogram for HCC. Subsequent evaluations using time-dependent receiver operating characteristic analysis and calibration curve tests revealed the nomogram's commendable discriminatory ability. As a result, the nomogram proved to be an effective tool for predicting survival at 2- to 4-years. CONCLUSION: The inflammation risk score has been identified as a significant prognostic factor for HBV-related HCC. The development of nomogram models has provided a practical and effective tool for determining the prognosis of patients affected by HBV-related HCC.
摘要：
BACKGROUND: Rosacea, a common chronic inflammatory skin disease worldwide, is currently incurable with complex pathogenesis. Dendrobium polysaccharide (DOP) may exert therapeutic effects on rosacea via acting on the NF-κB-related inflammatory and oxidative processes. MATERIALS AND METHODS: In this study, an LL-37-induced rosacea-like mouse model was established. HE staining was used to assess the skin lesions, erythema severity scores, pathological symptoms, and inflammatory cell numbers of mice in each group. The inflammation level was quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of TLR4 and p-NF-κB were finally detected. RESULTS: DOP improved skin pathological symptoms of rosacea mice. DOP also alleviated the inflammation of rosacea mice. Moreover, the TLR4/NF-κB pathway was observed to be inhibited in the skin of mice after DOP application. These findings evidenced the anti-inflammatory effects of DOP on the LL-37-induced rosacea mouse model. DOP could inhibit NF-κB activation, suppress neutrophil infiltration, and reduce pro-inflammatory cytokines production, which may be the reason for DOP protecting against rosacea. CONCLUSION: This study may propose an active candidate with great potential for rosacea drug development and lay a solid experimental foundation for promoting DOP application in rosacea therapy.
摘要：
The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.
期刊：
Life Sciences in Space Research,2024年40:35-43 ISSN：2214-5524
通讯作者：
Liu, XM
作者机构：
[Liu, Xinmin; Zhang, Yiwen; Jiang, Ning; Yao, Caihong] Chinese Acad Med Sci & Peking Union Med Coll, Res Ctr Pharmacol & Toxicol, Inst Med Plant Dev IMPLAD, Beijing 100193, Peoples R China.;[Chen, Fang; Liu, Xinmin; Chen, Yuzhen; Liu, Yupei] Hunan Univ Chinese Med, Changsha 410000, Hunan, Peoples R China.;[Choudhary, Muhammad Iqbal; Wang, Yan] Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
通讯机构：
[Liu, XM ] C;Chinese Acad Med Sci & Peking Union Med Coll, Res Ctr Pharmacol & Toxicol, Inst Med Plant Dev IMPLAD, Beijing 100193, Peoples R China.;Hunan Univ Chinese Med, Changsha 410000, Hunan, Peoples R China.
摘要：
Sleep deprivation (SD) is common during spaceflight. SD is known to cause cognitive deficits and depression, requiring treatment and prevention. Hemerocallis citrina Baroni (Liliaceae) is a perennial herb with antidepressant, antioxidant, antitumor, anti-inflammatory, and neuroprotective effects.The aim of our study was to investigate the effects of H. citrina extract (HCE) on SD-induced cognitive decline and depression-like behavior and possible neuroinflammation-related mechanisms. HCE (2g/kg/day, i.g.) or vortioxetine (10mg/kg/day, i.g.) were given to mice by oral gavage for a total of 28 days during the SD process. HCE treatment was found to ameliorate SD-induced impairment of short- and long-term spatial and nonspatial memory, measured using Y-maze, object recognition, and Morris water maze tests, as well as mitigating SD-induced depression-like behaviors, measured by tail suspension and forced swimming tests. HCE also reduced the levels of inflammatory cytokines (IL-1β, IL-18, and IL-6) in the serum and hippocampus. Furthermore, HCE suppressed SD-induced microglial activation in the prefrontal cortex (PFC) and the CA1 and dentate gyrus (DG) regions of the hippocampus. HCE also inhibited the expression of phosphorylated NF-κB and activation of the NLRP3 inflammasome. In summary, our findings indicated that HCE attenuated SD-induced cognitive impairment and depression-like behavior and that this effect may be mediated by the inhibition of inflammatory progression and microglial activation in the hippocampus, as well as the down-regulation of NF-κB and NLRP3 signaling. The findings of these studies showingTthese results indicate that HCE exerts neuroprotective effects and are consistent with the findings of previous studies, suggesting that HCE is beneficial for the prevention and treatment of cognitive decline and depression in SD.
摘要：
The human intestinal tract constitutes a complex ecosystem, made up of countless gut microbiota, metabolites, and immune cells, with hypoxia being a fundamental environmental characteristic of this ecology. Under normal physiological conditions, a delicate balance exists among these complex "residents", with disruptions potentially leading to inflammatory bowel disease (IBD). The core pathology of IBD features a disrupted intestinal epithelial barrier, alongside evident immune and microecological disturbances. Central to these interconnected networks is hypoxia-inducible factor-1 alpha (HIF-1 alpha), which is a key regulator in gut cells for adapting to hypoxic conditions and maintaining gut homeostasis. Short-chain fatty acids (SCFAs), as pivotal gut metabolites, serve as vital mediators between the host and microbiota, and significantly influence intestinal ecosystem. Recent years have seen a surge in research on the roles and therapeutic potential of HIF-1 alpha and SCFAs in IBD independently, yet reviews on HIF-1 alpha-mediated SCFAs regulation of IBD under hypoxic conditions are scarce. This article summarizes evidence of the interplay and regulatory relationship between SCFAs and HIF-1 alpha in IBD, pivotal for elucidating the disease's pathogenesis and offering promising therapeutic strategies.
