期刊：
FRONTIERS IN PSYCHIATRY,2024年15:1304916 ISSN：1664-0640
通讯作者：
Li, JS;Chen, M
作者机构：
[Lyu, Kaifeng; Chen, Min] Macau Univ Sci & Technol, Fac Chinese Med, Macau, Peoples R China.;[Li, Wu; Feng, Xiang; Li, Jiangshan; Zhang, Yuxing] Hunan Univ Tradit Chinese Med, Coll Acupuncture Moxibust Massage & Rehabil, Changsha, Peoples R China.;[Chen, Min] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.;[Zhang, Wei] Heilongjiang Univ Tradit Chinese Med, Affiliated Hosp 1, Pediat 1, Harbin, Peoples R China.;[Hu, Meichao] Chifeng Obstet & Gynecol Hosp, Chifeng Obstet & Gynecol Hospitalal, Chifeng, Peoples R China.
通讯机构：
[Li, JS ] H;[Chen, M ] M;Hunan Univ Tradit Chinese Med, Coll Acupuncture Moxibust Massage & Rehabil, Changsha, Peoples R China.;Macau Univ Sci & Technol, Fac Chinese Med, Macau, Peoples R China.;Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.
摘要：
BACKGROUND: This study employs bibliometric methods to comprehensively understand the fundamental structure of research about Autism Spectrum Disorder (ASD) Signaling Pathways by examining key indicators such as nations, institutions, journals, authors, and keywords. METHODOLOGY: We utilized the WoScc database to retrieve literature relevant to ASD Signaling Pathways published between 2013 and 2023. Through visual analysis and tools like CiteSpace and VosViewer, we explored nations, institutions, journals, authors, and keywords, thereby constructing relevant networks. RESULTS: 26 The study encompasses 1,396 articles, revealing a consistent increase in publications. The United States, China, and Germany are leading nations in this literature. Regarding research institutions, the University of California system and Eric Klann have garnered significant attention due to their substantial contributions to the field of ASD Signaling Pathways. Most relevant research is published in the journal "Molecular Autism." Research interests are concentrated across various themes, including "elevating neuronal β-catenin levels," "Tunisian children," "Fmr1 knockout (KO) mice," "de novo mutations," "autistic children," "local translation," "propionic acid-induced mouse models," "neurosystems," "glucose metabolism," and "neuronal migration." Future research may emphasize exploring aspects such as gut microbiota, genes, stress, maternal immune activation, memory, and neurodevelopmental disorders of ASD. CONCLUSION: This study, through bibliometric analysis of key indicators such as nations, institutions, journals, authors, and keywords, provides a comprehensive overview of the current state of research on ASD Signaling Pathways. These investigations predominantly focus on molecular mechanisms, animal model studies, population-based research, and the structure and function of neurosystems. Future research directions are also clearly proposed. First, in-depth research on the genes and neurodevelopmental disorders associated with ASD will continue to reveal the genetic basis and provide support for precise treatments. At the same time, attention to the gut microbiota will help explore its association with ASD, which may provide clues for new treatments. In addition, the relationship between stress and ASD will become the focus of research to understand better the emotional and behavioral characteristics of ASD patients in stressful situations. Maternal immune activation will also be further studied to explore how environmental factors influence the risk and development of ASD. Finally, a deeper understanding of the cognitive functions of patients with ASD, especially memory and learning, will help develop individualized treatment strategies to improve patients' quality of life. These directions will work together and are expected to provide a more comprehensive understanding of Signaling Pathways research in ASD and provide new ideas and opportunities for future intervention and treatment.
摘要：
Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and alpha-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.
期刊：
European Journal of Pharmacology,2024年963:176264 ISSN：0014-2999
通讯作者：
Yang, Yantao;Chen, Naihong;Liu, F;Chen, NH
作者机构：
[Ai, Qidi; Peng, Caiwang; Sun, Yang; Zhao, Fengyan; Tang, Keyan; Yang, Yantao; Chen, Naihong; Li, Hengli; Liu, Fang] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.;[Ai, Qidi; Peng, Caiwang; Sun, Yang; Yang, YT; Liu, Fang; Zhao, Fengyan; Chen, NH; Tang, Keyan; Yang, Yantao; Chen, Naihong; Li, Hengli] Ctr Standardizat & Funct Engn Tradit Chinese Med H, Changsha 410208, Peoples R China.;[Peng, Caiwang; Zhao, Fengyan; Tang, Keyan; Li, Hengli; Liu, Fang] Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410208, Peoples R China.;[Chen, NH; Chen, Naihong] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China.;[Liu, Fang] Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
通讯机构：
[Yang, YT; Liu, F ; Chen, NH ; Chen, NH] C;Ctr Standardizat & Funct Engn Tradit Chinese Med H, Changsha 410208, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
摘要：
AIMS: Ischemic stroke is a severe cerebrovascular disease in which neuronal death continually occurs through multiple forms, including apoptosis, autophagy, pyroptosis and ferroptosis. Quercetin (QRC), as a natural flavonoid compound, has been reported to have pharmacological effects on ischemic injury accompanied by unclear anti-ferroptotic mechanisms. This study is designed to investigate the therapeutic effects of QRC against ferroptosis in ischemic stroke. MATERIALS AND METHODS: In vivo, the model of MCAO rats were used to assess the protective effect of QRC on cerebral ischemic. Additionally, we constructed oxidative stressed and ferroptotic cell models to explore the effects and mechanisms of QRC on ferroptosis. The related proteins were analysed by western blotting, immunohistochemical and immunofluorescence techniques. RESULTS: The experiments demonstrated that QRC improves neurological deficits, infarct volume, and pathological features in MCAO rats, also increased the viability of HT-22cells exposed to H(2)O(2) and erastin. These results, including MDA, SOD, GSH, ROS levels and iron accumulation, indicated that QRC suppresses the generation of lipid peroxides and may involve in the regulatory of ferroptosis. Both in vitro and in vivo, QRC was found to inhibit ferroptosis by up-regulating GPX4 and FTH1, as well as down-regulating ACSL4. Furthermore, we observed that QRC enhances the nuclear translocation of Nrf2 and activates the downstream antioxidative proteins. Importantly, the effect of QRC on ferroptosis can be reversed by the Nrf2 inhibitor ML385. CONCLUSIONS: This study provides evidence that QRC has a neuroprotective effect by inhibiting ferroptosis, demonstrating the therapeutic potential for cerebral ischemic stroke.
摘要：
BACKGROUND: Post-stroke spasticity (PSS) is the most common complication of stroke. Acupuncture is widely used in clinical practice for the treatment of PSS, and is therefore considered a common complementary treatment. Several systematic reviews (SRs) and meta-analyses (MAs) have demonstrated the efficacy and safety of acupuncture in the treatment of PSS; however, the quality of evidence of these studies has not been adequately assessed. OBJECTIVE: To evaluate and summarize the SRs/MAs and inform future research and clinical practice on the efficacy and safety of acupuncture for PSS. DATA SOURCES AND EXTRACION: The following databases were searched from their dates of inception to March 26, 2023: PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, SinoMed, and Chinese Science and Technology Periodical Database (VIP), and grey literature were manually searched. Two reviewers independently completed literature retrieval, screening, and data extraction. REVIEW APPRAISAL: Systematic evaluation tools to Assess Systematic Reviews (AMSTAR) 2, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020 Checklist), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to systematically evaluate the methodological, reporting, and evidence quality of the SRs/MAs. RESULTS: Overall, 226 papers were examined, and after careful consideration, 10 SRs/MAs were deemed eligible for inclusion. The AMSTAR 2 assessment revealed that one SR/MA had medium, one study had low, and the remaining eight studies had critically low methodological qualities. Additionally, four SRs/MAs completed more than 60 % of the PRISMA 2020 checklist. The GRADE system indicated that six outcomes were medium, 26 outcomes were low, and 24 outcomes were critically low. CONCLUSION: Based on the evidence, acupuncture may be a promising complementary treatment to improve post-stroke spasticity and quality of life. Further high-quality RCTs are needed in future studies to support the broader application of acupuncture for the treatment of PSS.
摘要：
OBJECTIVES: Statistics on the rate of unconventional lymph node metastases (ULNM) at the time of one-stage radical surgery in tongue cancer patients. To assess whether an extended neck dissection group with additional removal of ULNs has a lower rate of neck recurrence compared to the traditional neck dissection group. MATERIALS AND METHODS: A total of 336 patients with TSCC who underwent radical surgery were recruited and underwent traditional or extended neck dissection. Compared to traditional neck dissection, the aim of extended neck dissection is designed to additional resect ULNs. RESULTS: In total, 180 patients underwent extended neck dissection, while 156 underwent traditional neck dissection. The incidence of ULNM was 11.67% (21/180) in patients treated with extended neck dissection. The incidence of ipsilateral neck recurrence was 9.49% and 0.56% in patients who underwent traditional and extended neck dissection, respectively (p = 0.0001). CONCLUSIONS: Extended neck dissection is effective for preventing neck recurrence in TSCC patients with ULNs. CLINICAL RELEVANCE: ULNM may be the main cause of neck recurrence after neck dissection in patients with tongue cancer. A better prognosis may be achieved by additional resection of ULNs on the basis of traditional neck dissection.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Huzhang-Guizhi herb pair (HGHP), composed of Polygonum cuspidatum (Huzhang [HZ] in Chinese, the root of Polygonum cuspidatum Sieb. & Zucc.) and Ramulus Cinnamomi (Guizhi [GZ] in Chinese, the dried twig of Cinnamomum cassia Presl.), is a popular herb pair commonly used to treat arthritis and involved in many Chinese prescriptions. In order to reveal the influence of GZ on HZ on bioavailability, the pharmacokinetic behaviors and tissue distribution variations of the three analytes from HZ were detected between oral administration of HZ and HGHP extracts to rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to two groups for pharmacokinetics study and eight groups for tissues distribution research with the equivalent dose of 18g crude HZ/kg. Assays for analytes from HZ (polydatin, resveratrol, emodin) were developed and validated using high performance liquid chromatography with ultraviolet detection (HPLC-UV). RESULTS: Part pharmacokinetic parameters including area under the concentration-time curve (AUC), the maximum plasma concentration (C(max)), biological half-life (t(1/2)), mean residence time (MRT), time to peak concentration (T(max)), clearance rate/bioavailability (CL/F) and volume of distribution/bioavailability (Vd/F) showed significant difference (P<0.05) after oral administration of HGHP, as compared to those of HZ. The three analytes could be detected in heart, liver, spleen, lung, kidney and brain. Compared with the HZ group, AUC(0-t) of polydatin in heart, liver and kidney increased significantly (p<0.05) while that in spleen decreased significantly (p<0.05); AUC(0-t) of resveratrol in all detected tissues increased conspicuously (p<0.05) in the HGHP group; AUC(0-t) of emodin in heart, liver, spleen, lung, and kidney increased conspicuously (p<0.05), and decreased obviously (p<0.05) in brain in the HGHP group. CONCLUSIONS: GZ could strongly influence the pharmacokinetic parameters and tissue distribution characteristics of polydatin, resveratrol and emodin in rats when administrated with HZ or HGHP extracts. It might provide a reference for further explanation of the compatibility mechanism and the clinical application of HGHP.
摘要：
Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking. Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted. Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C(17)H(18)N(2)O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk. Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.
摘要：
The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.
作者机构：
[Gu, Wenping; Zheng, Lan; Huang, Qianyi; Sun, Xinyu; Gu, WP; Song, Mingyu] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Gu, Wenping; Yi, Fang; Gu, WP; Song, Mingyu] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Gu, Wenping; Gu, WP; Song, Mingyu] Cent South Univ, Clin Res Ctr Cerebrovasc Dis Hunan Prov, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.;[Wang, Hong; Yi, Fang] Cent South Univ, Xiangya Hosp, Dept Geriatr Neurol, Changsha 410008, Hunan, Peoples R China.;[Zeng, Feiyue] Cent South Univ, Xiangya Hosp, Dept Radiol, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Gu, WP ] C;Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Clin Res Ctr Cerebrovasc Dis Hunan Prov, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.
关键词：
Ischemic stroke;Mitophagy;USP18;FTO;SIRT6
摘要：
Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Delta psi m), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1 alpha/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1 alpha/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1 alpha/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.
摘要：
BACKGROUND: Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis. METHODS: A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described. RESULTS: Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = -2.08, 95% CI (-2.96, -1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups. CONCLUSION: The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.
关键词：
Nonspecific orbital inflammation (NSOI);Gln-Metabolism genes (GlnMgs);Lasso regression;SVM-RFE;Bioinformatics
摘要：
Nonspecific orbital inflammation (NSOI) is an idiopathic, persistent, and proliferative inflammatory condition affecting the orbit, characterized by polymorphous lymphoid infiltration. Its pathogenesis and progression have been linked to imbalances in tumor metabolic pathways, with glutamine (Gln) metabolism emerging as a critical aspect in cancer. Metabolic reprogramming is known to influence clinical outcomes in various malignancies. However, comprehensive research on glutamine metabolism's significance in NSOI is lacking. This study conducted a bioinformatics analysis to identify and validate potential glutamine-related molecules (GlnMgs) associated with NSOI. The discovery of GlnMgs involved the intersection of differential expression analysis with a set of 42 candidate GlnMgs. The biological functions and pathways of the identified GlnMgs were analyzed using GSEA and GSVA. Lasso regression and SVM-RFE methods identified hub genes and assessed the diagnostic efficacy of fourteen GlnMgs in NSOI. The correlation between hub GlnMgs and clinical characteristics was also examined. The expression levels of the fourteen GlnMgs were validated using datasets GSE58331 and GSE105149. Fourteen GlnMgs related to NSOI were identified, including FTCD, CPS1, CTPS1, NAGS, DDAH2, PHGDH, GGT1, GCLM, GLUD1, ART4, AADAT, ASNSD1, SLC38A1, and GFPT2. Biological function analysis indicated their involvement in responses to extracellular stimulus, mitochondrial matrix, and lipid transport. The diagnostic performance of these GlnMgs in distinguishing NSOI showed promising results. This study successfully identified fourteen GlnMgs associated with NSOI, providing insights into potential novel biomarkers for NSOI and avenues for monitoring disease progression.
关键词：
Geriatric nursing;Postgraduate;Respite care;Volunteer service;Qualitative research
摘要：
As China’s population ages, the demand for care for the disabled elderly is increasing, and family caregivers find it challenging to meet the comprehensive care needs of the disabled elderly. Through home respite services, families of the disabled elderly can receive help and support from specialized nursing professionals to ease the burden on family caregivers and provide high-quality services. This study explores the willingness and influencing factors of Master of Geriatric Nursing Specialist postgraduates in China to volunteer to provide home respite services for disabled elderly individuals. A qualitative study based on Grounded Theory used Strauss and Corbin’s programmatic version. A purposive sampling method was employed to conduct semi-structured interviews with 12 Master of Geriatric Nursing Specialist postgraduates from a tertiary hospital in Changsha, Hunan Province, China. The willingness of Master of Geriatric Nursing Specialist postgraduates to volunteer to provide home respite services for the disabled elderly was established as a core category, which was influenced by three main categories: personal factors, service object factors, and social factors, and nine categories formed from 39 initial concepts were included under the main category. Influenced by China’s traditional cultural background, Master of Geriatric Nursing Specialist postgraduates in China have shown high motivation in volunteering to provide home respite services for the families of the disabled elderly but have been challenged by several challenges from China’s healthcare environment and education system. Relevant departments need to adopt a series of policies and measures to increase volunteers’ willingness to participate in respite care and promote its development.
作者机构：
[Luo, Min; Luo, M; Luo, Shu; Chen, Yanjie] Hunan Univ Tradit Chinese Med, Affiliated Changde Hosp 2, Changsha, Peoples R China.
通讯机构：
[Luo, M ] H;Hunan Univ Tradit Chinese Med, Affiliated Changde Hosp 2, Changsha, Peoples R China.
关键词：
acupoint application;Buzhongyiqi decoction;functional constipation in elderly people;meta-analysis;systematic review
摘要：
Purpose:This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people.(1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software.Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research.Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.Functional constipation belongs to 1 of the 4 subtypes of chronic constipation classified by the Rome IV standard, which is distinguished from constipation caused by organic pathology, with the main clinical manifestations of hard or lumpy stools, straining to defecate or a sense of incomplete evacuation, and a prolonged defecation cycle.[1] The prevalence of constipation in the general population is approximately 20%; however, the prevalence of functional constipation is much higher than that in young people.[2] Its etiology may be related to diet, drugs, endocrine disorders, metabolic abnormalities and other factors.[3] Currently, the first-line clinical treatment for functional constipation is usually an over-the-counter osmotic laxative, with the main second-line options being secretion promoters or 5-HT drugs.[4] However, long-term use in elderly patients can be difficult to tolerate and susceptible to a number of adverse effects.[5] Therefore, there is an urgent need to apply more safer, more effective and sustainable clinical protocols for the treatment of functional constipation in this elder population.Chinese Medicine (CM) considers that an imbalance of qi, blood, yin, and yang can lead to constipation.[6] Decline in body function and weakening of gastrointestinal power are significant causes of constipation in elderly people.[7] CM diagnosis in elderly patients with constipation mostly belongs to the pattern of spleen and stomach qi deficiencies. [8] Buzhongyiqi decoction tonifies the spleen and stomach, elevates the Yang qi and promotes the movement of the intestinal tract.[9] Clinical research and web-based pharmacological analysis showed that Buzhongyiqi decoction could efficacy alleviate constipation by regulating gastrointestinal hormone levels or exerting anti-inflammatory and antioxidant effects on patients.[10,11] Acupoint application can treat constipation by means of acupoint stimulation, and its adverse effects are only manifested in topical application on the skin.[12] Therefore, this research will apply evidence-based medicine to objectively evaluate the clinical efficacy of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people and provide evidence-based evidence for clinical application.Purpose:This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people.(1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software.Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research.Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.Functional constipation belongs to 1 of the 4 subtypes of chronic constipation classified by the Rome IV standard, which is distinguished from constipation caused by organic pathology, with the main clinical manifestations of hard or lumpy stools, straining to defecate or a sense of incomplete evacuation, and a prolonged defecation cycle.[1] The prevalence of constipation in the general population is approximately 20%; however, the prevalence of functional constipation is much higher than that in young people.[2] Its etiology may be related to diet, drugs, endocrine disorders, metabolic abnormalities and other factors. [3] Currently, the first-line clinical treatment for functional constipation is usually an over-the-counter osmotic laxative, with the main second-line options being secretion promoters or 5-HT drugs.[4] However, long-term use in elderly patients can be difficult to tolerate and susceptible to a number of adverse effects.[5] Therefore, there is an urgent need to apply more safer, more effective and sustainable clinical protocols for the treatment of functional constipation in this elder population.Chinese Medicine (CM) considers that an imbalance of qi, blood, yin, and yang can lead to constipation.[6] Decline in body function and weakening of gastrointestinal power are significant causes of constipation in elderly people.[7] CM diagnosis in elderly patients with constipation mostly belongs to the pattern of spleen and stomach qi deficiencies.[8] Buzhongyiqi decoction tonifies the spleen and stomach, elevates the Yang qi and promotes the movement of the intestinal tract.[9] Clinical research and web-based pharmacological analysis showed that Buzhongyiqi decoction could efficacy alleviate constipation by regulating gastrointestinal hormone levels or exerting anti-inflammatory and antioxidant effects on patients.[10,11] Acupoint application can treat constipation by means of acupoint stimulation, and its adverse effects are only manifested in topical application on the skin.[12] Therefore, this research will apply evidence-based medicine to objectively evaluate the clinical efficacy of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people and provide evidence-based evidence for clinical application.Purpose:This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people.(1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software.Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research. Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.Functional constipation belongs to 1 of the 4 subtypes of chronic constipation classified by the Rome IV standard, which is distinguished from constipation caused by organic pathology, with the main clinical manifestations of hard or lumpy stools, straining to defecate or a sense of incomplete evacuation, and a prolonged defecation cycle.[1] The prevalence of constipation in the general population is approximately 20%; however, the prevalence of functional constipation is much higher than that in young people.[2] Its etiology may be related to diet, drugs, endocrine disorders, metabolic abnormalities and other factors.[3] Currently, the first-line clinical treatment for functional constipation is usually an over-the-counter osmotic laxative, with the main second-line options being secretion promoters or 5-HT drugs.[4] However, long-term use in elderly patients can be difficult to tolerate and susceptible to a number of adverse effects.[5] Therefore, there is an urgent need to apply more safer, more effective and sustainable clinical protocols for the treatment of functional constipation in this elder population.Chinese Medicine (CM) considers that an imbalance of qi, blood, yin, and yang can lead to constipation.[6] Decline in body function and weakening of gastrointestinal power are significant causes of constipation in elderly people.[7] CM diagnosis in elderly patients with constipation mostly belongs to the pattern of spleen and stomach qi deficiencies.[8] Buzhongyiqi decoction tonifies the spleen and stomach, elevates the Yang qi and promotes the movement of the intestinal tract.[9] Clinical research and web-based pharmacological analysis showed that Buzhongyiqi decoction could efficacy alleviate constipation by regulating gastrointestinal hormone levels or exerting anti-inflammatory and antioxidant effects on patients.[10,11] Acupoint application can treat constipation by means of acupoint stimulation, and its adverse effects are only manifested in topical application on the skin.[12] Therefore, this research will apply evidence-based medicine to objectively evaluate the clinical efficacy of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people and provide evidence-based evidence for clinical application.Purpose:This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people.(1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software. Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research.Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.Functional constipation belongs to 1 of the 4 subtypes of chronic constipation classified by the Rome IV standard, which is distinguished from constipation caused by organic pathology, with the main clinical manifestations of hard or lumpy stools, straining to defecate or a sense of incomplete evacuation, and a prolonged defecation cycle.[1] The prevalence of constipation in the general population is approximately 20%; however, the prevalence of functional constipation is much higher than that in young people.[2] Its etiology may be related to diet, drugs, endocrine disorders, metabolic abnormalities and other factors.[3] Currently, the first-line clinical treatment for functional constipation is usually an over-the-counter osmotic laxative, with the main second-line options being secretion promoters or 5-HT drugs.[4] However, long-term use in elderly patients can be difficult to tolerate and susceptible to a number of adverse effects.[5] Therefore, there is an urgent need to apply more safer, more effective and sustainable clinical protocols for the treatment of functional constipation in this elder population.Chinese Medicine (CM) considers that an imbalance of qi, blood, yin, and yang can lead to constipation.[6] Decline in body function and weakening of gastrointestinal power are significant causes of constipation in elderly people.[7] CM diagnosis in elderly patients with constipation mostly belongs to the pattern of spleen and stomach qi deficiencies.[8] Buzhongyiqi decoction tonifies the spleen and stomach, elevates the Yang qi and promotes the movement of the intestinal tract.[9] Clinical research and web-based pharmacological analysis showed that Buzhongyiqi decoction could efficacy alleviate constipation by regulating gastrointestinal hormone levels or exerting anti-inflammatory and antioxidant effects on patients.[10,11] Acupoint application can treat constipation by means of acupoint stimulation, and its adverse effects are only manifested in topical application on the skin.[12] Therefore, this research will apply evidence-based medicine to objectively evaluate the clinical efficacy of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people and provide evidence-based evidence for clinical application.Purpose:This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people. (1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software.Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research.Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.Functional constipation belongs to 1 of the 4 subtypes of chronic constipation classified by the Rome IV standard, which is distinguished from constipation caused by organic pathology, with the main clinical manifestations of hard or lumpy stools, straining to defecate or a sense of incomplete evacuation, and a prolonged defecation cycle.[1] The prevalence of constipation in the general population is approximately 20%; however, the prevalence of functional constipation is much higher than that in young people.[2] Its etiology may be related to diet, drugs, endocrine disorders, metabolic abnormalities and other factors.[3] Currently, the first-line clinical treatment for functional constipation is usually an over-the-counter osmotic laxative, with the main second-line options being secretion promoters or 5-HT drugs.[4] However, long-term use in elderly patients can be difficult to tolerate and susceptible to a number of adverse effects.[5] Therefore, there is an urgent need to apply more safer, more effective and sustainable clinical protocols for the treatment of functional constipation in this elder population.Chinese Medicine (CM) considers that an imbalance of qi, blood, yin, and yang can lead to constipation.[6] Decline in body function and weakening of gastrointestinal power are significant causes of constipation in elderly people.[7] CM diagnosis in elderly patients with constipation mostly belongs to the pattern of spleen and stomach qi deficiencies.[8] Buzhongyiqi decoction tonifies the spleen and stomach, elevates the Yang qi and promotes the movement of the intestinal tract. [9] Clinical research and web-based pharmacological analysis showed that Buzhongyiqi decoction could efficacy alleviate constipation by regulating gastrointestinal hormone levels or exerting anti-inflammatory and antioxidant effects on patients.[10,11] Acupoint application can treat constipation by means of acupoint stimulation, and its adverse effects are only manifested in topical application on the skin.[12] Therefore, this research will apply evidence-based medicine to objectively evaluate the clinical efficacy of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people and provide evidence-based evidence for clinical application.Purpose:This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people.(1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software.Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research.Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.Functional constipation belongs to 1 of the 4 subtypes of chronic constipation classified by the Rome IV standard, which is distinguished from constipation caused by organic pathology, with the main clinical manifestations of hard or lumpy stools, straining to defecate or a sense of incomplete evacuation, and a prolonged defecation cycle.[1] The prevalence of constipation in the general population is approximately 20%; however, the prevalence of functional constipation is much higher than that in young people.[2] Its etiology may be related to diet, drugs, endocrine disorders, metabolic abnormalities and other factors.[3] Currently, the first-line clinical treatment for functional constipation is usually an over-the-counter osmotic laxative, with the main second-line options being secretion promoters or 5-HT drugs. [4] However, long-term use in elderly patients can be difficult to tolerate and susceptible to a number of adverse effects.[5] Therefore, there is an urgent need to apply more safer, more effective and sustainable clinical protocols for the treatment of functional constipation in this elder population.Chinese Medicine (CM) considers that an imbalance of qi, blood, yin, and yang can lead to constipation.[6] Decline in body function and weakening of gastrointestinal power are significant causes of constipation in elderly people.[7] CM diagnosis in elderly patients with constipation mostly belongs to the pattern of spleen and stomach qi deficiencies.[8] Buzhongyiqi decoction tonifies the spleen and stomach, elevates the Yang qi and promotes the movement of the intestinal tract.[9] Clinical research and web-based pharmacological analysis showed that Buzhongyiqi decoction could efficacy alleviate constipation by regulating gastrointestinal hormone levels or exerting anti-inflammatory and antioxidant effects on patients.[10,11] Acupoint application can treat constipation by means of acupoint stimulation, and its adverse effects are only manifested in topical application on the skin.[12] Therefore, this research will apply evidence-based medicine to objectively evaluate the clinical efficacy of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people and provide evidence-based evidence for clinical application.
作者机构：
[Liu, Hao; Liu, H; Xie, Jing; Xie, Zhen-ni; Jin, Jian; Liu, Xiao-liu; Jin, J; Zhang, Shui-han; Zhong, Can] Hunan Acad Chinese Med, Inst Chinese Med Resources, Changsha 410013, Peoples R China.;[Xie, Jing; Xie, Zhen-ni; Liu, Xiao-liu; Zhang, Shui-han] Hunan Univ Tradit Chinese Med, Hunan Acad Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Liu, H; Jin, J ] H;Hunan Acad Chinese Med, Inst Chinese Med Resources, Changsha 410013, Peoples R China.
关键词：
Poria cocos;Squalene epoxidase;CRISPR/Cas9 system;Triterpenoids;Gene function
摘要：
Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids. In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. The sgRNA were designed based on the active site residues. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. The results showed that deletion of PcSE inhibited triterpene synthesis. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach. The findings from this study provide a foundation for further studies on heterologous biosynthesis of P. cocos secondary metabolites.
作者机构：
[Yang, Renyi; Zeng, Puhua; Jian, Huiying; Xue, Peisen; Li, Kexiong; Li, KX; Yu, Xiaopeng; Peng, Wei; Peng, W] Hunan Acad Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Canc Res Inst, Hunan Acad Tradit Chinese Med, Changsha 410006, Hunan, Peoples R China.;[Gao, Wenhui; Peng, Lian] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Wang, Zhibing] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Li, KX; Zeng, PH ; Peng, W] H;Hunan Acad Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Canc Res Inst, Hunan Acad Tradit Chinese Med, Changsha 410006, Hunan, Peoples R China.
关键词：
Ferroptosis;Hepatocellular carcinoma;Mitochondrial dysfunction;Nrf2/HO-1/GPX4 axis;Polyphyllin I
摘要：
BACKGROUND: Ferroptosis is an emerging iron-dependent programmed cell death mode characterized by lipid peroxidation and iron accumulation, closely associated with Hepatocellular Carcinoma (HCC) progression. Although the impact of Polyphyllin I (PPI), a prominent bioactive constituent derived from Paris polyphylla, on diverse malignancies has been established, the specific role and potential mechanistic pathways through which PPI modulates ferroptosis in HCC remain elusive. PURPOSE: This study aimed to elucidate the anti-cancer properties and potential mechanisms of PPI in inducing ferroptosis and triggering mitochondrial injury in HCC. METHODS: Cell viability was assessed using CCK-8 assays. EdU proliferation and colony formation assays were employed to evaluate cell proliferation. A wound-healing assay was performed to assess cell migration. Transwell assay was utilized to evaluate cell invasion. Ferroptosis was evaluated through the utilization of a FerroOrange fluorescent probe, malondialdehyde (MDA) and reduced glutathione (GSH) assay kits, DCFH-DA fluorescent probe, western blotting, and transmission electron microscopy (TEM) analysis. Molecular docking, immunofluorescence, and western blotting were employed to predict and validate the binding and interaction of PPI with Nrf2, HO-1, xCT, and GPX4. Mitochondrial structure and membrane potential changes were evaluated using JC-1 and Mito Tracker Green fluorescent probes. A nude mice xenograft model was constructed to determine the inhibitory effects and the levels of ferroptosis of PPI on HCC through hematoxylin and eosin (H&E), Prussian blue reaction, immunofluorescence staining, immunohistochemistry, and western blotting analysis, in vivo. RESULTS: PPI exhibited dose-dependent inhibitory effects on the proliferation, invasion, and metastasis of HCC cells mediated by increasing reactive oxygen species (ROS) and MDA levels, promoting Fe(2+) accumulation, depleting GSH, and suppressing the expression of xCT and GPX4, thereby inducing ferroptosis in HCC. The induction of ferroptosis by PPI was associated with the binding of PPI to Nrf2, HO-1, and GPX4 proteins, modulating the Nrf2/HO-1/GPX4 antioxidant axis. PPI also induced mitochondrial structural damage and decreased mitochondrial membrane potential (MMP). Inhibition of ferroptosis by ferrostatin-1 (Fer-1) mitigated the mitochondrial disruption induced by PPI. In vivo, PPI inhibited Nrf2/HO-1/GPX4 axis-induced ferroptosis, impeding HCC growth similar to the effects of sorafenib. CONCLUSION: These results demonstrated that PPI intervention can suppress the proliferation, invasion, and metastasis of HCC cells by enhancing mitochondrial disruption and inducing ferroptosis via the Nrf2/HO-1/GPX4 axis. Consequently, our research advances the frontiers of pharmacodynamics and deepens our comprehension of the intricate mechanisms underpinning PPI. Furthermore, it has yielded an innovative treatment stratagem rooted in the tenets of Traditional Chinese Medicine (TCM), thereby furnishing a novel therapeutic avenue for addressing HCC.
期刊：
Journal of Ethnopharmacology,2024年319(Pt 3):117343 ISSN：0378-8741
通讯作者：
Wang, Xianwen;He, YC
作者机构：
[Wang, Xianwen; He, Yingchun; Liu, Liu; Zhou, Fangliang; Tang, Le; Wang, Wen; Xu, Runshi; Lin, Ting] Hunan Univ Chinese Med, Changsha 410208, Peoples R China.;[Zhou, Fangliang; Tang, Le; Wang, Wen; He, Yingchun; He, Lan] Hunan Univ Chinese Med, Hunan Prov Engn & Technol Res Ctr Prevent & Treatm, Changsha 410208, Peoples R China.;[Lin, Ting] Hunan Univ Chinese Med, Hunan Prov Key Lab Prevent & Treatment Ophthalmol, Changsha 410208, Peoples R China.;[Wang, Wen; He, Lan] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Peoples R China.
通讯机构：
[Wang, XW; He, YC ] H;Hunan Univ Chinese Med, Changsha 410208, Peoples R China.
关键词：
Nasopharyngeal carcinoma;Network pharmacology;Non-targeted-metabolomics;Traditional Chinese medicine;Yiqi Jiedu formula
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Yiqi Jiedu formula (YQJDF), rooted in the traditional Chinese medicinal principle of "tonifying qi and detoxifying", is remarkably efficacious in the clinical treatment of nasopharyngeal carcinoma (NPC). Previous studies have shed light on some of its anti-NPC effects and mechanisms, but the responsible pharmacological substances and their precise mechanisms of action remain unclear. AIM OF THE STUDY: The purpose of this study was to identify components of YQJDF that entered the bloodstream and to investigate their mechanisms of action against NPC through network pharmacology and serum metabolomics. MATERIAL AND METHODS: Components of YQJDF in serum were identified using liquid chromatography-tandem mass spectrometry. With these serum species as the focus of our research, network pharmacology analysis was used to identify active compounds and target genes that might mediate the efficacy of YQJDF in the treatment of NPC. Following establishment of an NPC xenograft model in nude mice, a non-targeted metabolomics approach was adopted to identify significant serum metabolites and metabolic pathways influenced by YQJDF. RESULTS: Thirty-six components of YQJDF were identified, primarily consisting of alkaloids, phenylpropanoids, and flavonoids. Notably, pathways such as PI3K/AKT, factors associated with Epstein-Barr virus infection, IL-17 signaling, and lipid metabolism, were highlighted as potential therapeutic targets of YQJDF during NPC treatment. Additionally, our findings suggested that YQJDF modified the metabolism of arginine and proline in the serum of mice bearing nasopharyngeal tumor grafts. CONCLUSIONS: This study identified the primary active components of YQJDF, highlighting its holistic role in the treatment of NPC through multiple targets and pathways. Furthermore, our findings provided a roadmap for future research into the mechanism of YQJDF in the therapy of NPC, setting the stage for its clinical application.
摘要：
Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue-light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti-inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age-related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.
作者机构：
[Liang, Xuejuan; Wan, Dan] Hunan Acad Chinese Med, Inst Innovat Tradit Chinese Medicat, Changsha 410013, Peoples R China.;[Tan, Lei] Cili Meteorol Bureau, Zhangjiajie 410013, Peoples R China.;[Liu, Hao; Liu, H] Hunan Acad Chinese Med, Inst Tradit Chinese Med Resources, Changsha 410013, Peoples R China.;[Liu, Hao; Wan, Dan; Liu, H] 142 Yuehua Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Liu, H ] H;Hunan Acad Chinese Med, Inst Tradit Chinese Med Resources, Changsha 410013, Peoples R China.;142 Yuehua Rd, Changsha, Hunan, Peoples R China.
摘要：
The bark and leaves of the Eucommia ulmoides Oliv. (E. ulmoides) have good medicinal value. Studies show endophytes play important roles in host medicinal plant secondary metabolite synthesis, with season being a key influencing factor. Therefore, we used 16 S rRNA to detect endophytic bacteria (EB) in E. ulmoides bark and leaves collected in winter, spring, summer, and autumn, and analyzed the contents of major active components respectively. The results showed that the species diversity and richness of EB of the E. ulmoides bark were higher than those of leaves in all seasons except fall. Among them, the higher species diversity and richness were found in the E. ulmoides bark in winter and spring. EB community structure differed significantly between medicinal tissues and seasons. Concurrently, the bark and leaves of E. ulmoides showed abundant characteristic EB across seasons. For active components, geniposidic acid showed a significant positive correlation with EB diversity and richness, while the opposite was true for aucubin. Additionally, some dominant EB exhibited close correlations with the accumulation of active components. Delftia, enriched in autumn, correlated significantly positively with aucubin. Notably, the impact of the same EB genera on active components differed across medicinal tissues. For example, Sphingomonas, enriched in summer, correlated significantly positively with pinoresinol diglucoside (PDG) in the bark, but with aucubin in the leaves. In summary, EB of E. ulmoides was demonstrated high seasonal dynamics and tissue specificity, with seasonal characteristic EB like Delftia and Sphingomonas correlating with the accumulation of active components in medicinal tissues.
作者机构：
[Lu, Huiling; Xiao, Yifei; Li, Ya; Du, Lixin] Hunan Univ Chinese Med, Coll Pharm, Changsha, Peoples R China.;[Guo, Zhihua] Hunan Univ Chinese Med, Coll Chinese Med, Changsha, Peoples R China.;[Li, Y; Li, Ya] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Li, Y ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
关键词：
Chuantieling gel patch;fingerprint;HPLC;network pharmacology;Q-markers
摘要：
The Chuantieling gel patch (CGP), a traditional Chinese medicine compound, is an external treatment for asthma. It has shown remarkable effectiveness in alleviating asthma-related airway hyperresponsiveness and inflammation. Nevertheless, there is currently no information available regarding the analysis of quality markers for CGP, and there is a need for further improvement in quality control research. In this study, we developed an HPLC fingerprinting method for CGP and conducted a comprehensive methodological investigation. We assessed the similarity among 10 batches of CGP, identified common peaks, and quantified the content of seven major quality markers. Furthermore, we built a network pharmacology-based 'active ingredients-targets-pathways-diseases' network to forecast the potential mechanisms of action for the primary active components in asthma treatment. Our findings demonstrated that the developed CGP fingerprinting and content determination methods were consistent and trustworthy. We verified the existence of 25 shared peaks and successfully identified 7 chromatographic peaks, including sinigrin thiocyanate, ephedrine hydrochloride, methyleugenol, imperatorin, cinnamaldehyde, emodin, and 6-gingerol, using reference standards. The network pharmacology analysis suggested that these seven active components may target proteins such as STAT3 (signal transducer and activator of transcription 3), MAPK3 (mitogen-activated protein kinase 3), and TP53 (tumor protein P53) and influence various diseases through pathways including cancer pathways, hepatitis B, and PI3K-Akt (phosphoinositide 3-kinase-protein kinase B) signaling. This study provides insight into the complex multicomponent composition of CGP, and the predictive analysis through network pharmacology sets the stage for uncovering the mechanisms responsible for the therapeutic effects of CGP.
期刊：
Journal of Ethnopharmacology,2024年323:117682 ISSN：0378-8741
通讯作者：
Liu, JJ;Wang, W
作者机构：
[Shi, Huan; Jiang, Lihong; Liu, Jianjun; Liao, Xiaolin; Zhao, Hongqing; Peng, Wangxia; Liu, JJ; Lu, Huaguan] Hunan Univ Tradit Chinese Med, Innovat Base Hunan State Key Lab Innovat Med & Tra, Sci & Technol Innovat Ctr, Changsha 410208, Peoples R China.;[Yang, Yupei; Wang, Wei] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
通讯机构：
[Wang, W ; Liu, JJ ] H;Hunan Univ Tradit Chinese Med, Innovat Base Hunan State Key Lab Innovat Med & Tra, Sci & Technol Innovat Ctr, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: The Kadsura coccinea (Lem.) A. C. Smith is known as "Heilaohu" of the Tujia ethnomedicine in China. It has anti-tumor, anti-oxidation, anti-HIV, anti-inflammatory and liver protective effects, used to treat diseases such as rheumatoid arthritis, cancer, gastritis and hepatitis. In this research, we investigated the anti-fibrotic effect and possible mechanisms of acetylbinankadsurin A (ACBA) in vitro and in vivo, which is a natural compound derived from roots of K. coccinea. AIM OF THE STUDY: We try to evaluate the efficacy of ACBA in the treatment of liver fibrosis and to explore the underlying mechanisms of ACBA by network pharmacology, machine learning, molecular docking, molecular dynamics simulations, and experimental assessment. MATERIALS AND METHODS: ACBA was isolated from the CH(2)Cl(2) layer of the roots of K. coccinea through column chromatographic techniques. The structure of ACBA was determined by using 1D and 2D NMR. CCl(4)-induced C57BL/6 mouse liver fibrosis models were established to evaluate the anti-fibrosis effects of ACBA in vivo. The molecular targets of ACBA and liver fibrosis were obtained from various databases, then constructed a protein-protein interaction (PPI) networks through the STRING database. Gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were applied using the "clusterProfiler" R package. Furthermore, the key genes for ACBA treatment of liver fibrosis were identified by the least absolute shrinkage and selection operator (LASSO). Molecular docking and molecular dynamics simulations were also carried out. Finally, the target and pathway of ACBA were verified by immunofluorescence staining, RT-PCR and Western blot. RESULT: First, ACBA attenuated CCl(4)-induced liver injury and fibrosis in vivo. These findings were accompanied by decreased expression of α-SMA and collagen I. Second, ACBA significantly decreased serum levels of ALT, AST, TNF-α and IL-6. Then, we identified 133 potential targets of ACBA and 7987 targets of liver fibrosis. KEGG analysis showed that ACBA could regulate the drug metabolism - cytochrome P450, fructose and mannose metabolism, IL-17 and NF-κB signaling pathways. Next, six core targets was screened by LASSO analysis including AKR1B1, PFKFB3, EPHA3, CDK1, CCR1 and CYP3A4. Molecular docking showed that ACBA has a good binding affinity for CCR1. Furthermore, compared with CCR1 inhibitor BX-471, The results of molecular simulation dynamics showed that ACBA was stable in binding with CCR1. Consistently, ACBA remarkably downregulated the expression of CCR1, p-NF-κBp65, p-IκBα, p-STAT1 and TNF-α proteins, which were upregulated in CCl(4)-induced hepatic fibrosis and LPS-THP-1cells. CONCLUSION: Our results suggest that ACBA significantly attenuated CCl(4)-induced liver fibrosis in histopathological and in serum level. This effect may be mediated by CCR1, NF-κB and STAT1 signalling.
