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.
期刊：
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,2024年83(1):86-92 ISSN：0160-2446
通讯作者：
Liu, XL;Ye, HH
作者机构：
[Ma, Lili; Zhou, Hua; Zhang, Yuyu; Huang, Yun; Fang, Chongbo; Rong, Weibo] Ningbo Univ, Li Huili Hosp, Ningbo Med Ctr, Dept Pharm, Ningbo, Zhijiang, Peoples R China.;[Liu, Xiaoli] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Caie North Rd 233, Changsha, Hunan, Peoples R China.;[Ye, Honghua] Ningbo Univ, Li Huili Hosp, Ningbo Med Ctr, Dept Cardiol, Xingning Rd 57, Ningbo 315040, Zhijiang, Peoples R China.;[Liu, Xiaoli] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Caie North Rd 233, Changsha 410119, Hunan, Peoples R China.
通讯机构：
[Liu, XL ] H;[Ye, HH ] N;Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Caie North Rd 233, Changsha, Hunan, Peoples R China.;Ningbo Univ, Li Huili Hosp, Ningbo Med Ctr, Dept Cardiol, Xingning Rd 57, Ningbo 315040, Zhijiang, Peoples R China.;Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Caie North Rd 233, Changsha 410119, Hunan, Peoples R China.
关键词：
SGLT2 inhibitors, heart failure, cost-effectiveness, China
摘要：
Supplemental Digital Content is Available in the Text. This study aimed to compare the cost-effectiveness of the new quadruple therapy regimen of adding sodium-glucose-linked transporter 2 (SGLT2) inhibitors, with standard treatment for patients with heart failure (HF) in China. From the payer's perspective, the dates of cardiovascular event recurrences were extracted from a meta-analysis including 6 trials, combined with the treatment cost for patients with HF in China to construct a Markov model. The outcomes included per capita medical costs and incremental cost-effectiveness ratio, using quality-adjusted life years (QALYs) data. Single-factor, probability sensitivity analysis, and scenario analysis were used to explore the potential uncertainties of the model. The per capita costs of the new quadruple therapy regimen and standard treatment were $87441.26 and $87087.54, respectively. The new regimen was associated with a mean of 21.44 QALYs gained, compared with 18.60 QALYs gained with the standard treatment. The incremental cost-effectiveness ratio was $124.03 per QALY gained. The sensitivity analysis revealed that changes in the parameters within the set range did not affect the model results. In China, compared with standard treatment, the new quadruple therapy regimen with SGLT2 inhibitors reduce the frequency of cardiovascular events among patients with HF, and it has economic advantages.
摘要：
BACKGROUND: Studies are ongoing to examine the versatile functions of circular RNAs (circRNAs) in human diseases. This research investigates the effects of hsa_circ_0000644 (circ_644) and its related molecules on the malignant behavior of bladder cancer (BCa) cells. METHODS: Abundant bioinformatics analyses were performed to screen the key circRNA and its related molecules in BCa. Tumor tissues and the para-tumorous tissues were collected from 58 patients with BCa. Expression of RUNX family transcription factor 3 (RUNX3), circ_644, microRNA-143-3p (miR-143-3p), and musashi RNA binding protein 2 (MSI2) in BCa tissues or cells was determined. Molecular interactions were confirmed by chromatin immunoprecipitation, RNA pull-down, and luciferase assays. Gain and loss-of function assays were performed using two BCa cell lines (T24 and HT1376). RESULTS: Circ_644 was highly expressed whereas RUNX3, which could suppress circ_644 transcription, was lowly expressed in BCa tissues and cells. Upregulation of RUNX3 suppressed proliferation, colony formation, migration and invasion, and tumorigenicity of BCa cells and induced cell cycle arrest. However, the tumor-suppressive effects of RUNX3 were blocked by circ_644 upregulation. Circ_644 served as a sponge for miR-143-3p, and miR-143-3p bound to MSI2 mRNA. The rescue experiments showed that miR-143-3p inhibition or MSI2 overexpression restored the malignant behaviors of BCa cells induced by circ_644 knockdown or RUNX3 overexpression. CONCLUSION: This study demonstrates that transcriptional activation of circ_644 upon RUNX3 downregulation drives the malignant development of BCa through the miR-143-3p/MSI2 axis. RUNX3 restoration or specific inhibition of circ_644 or MSI2 may help block BCa progression.
作者机构：
[Hu, Fan; Li, Mei; Wang, Wei; Xu, Chongsi; Xiao, You] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anorectal 5, Changsha, Peoples R China.;[He, Yuanyuan] Hunan Univ, Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Wang, Zhenquan] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anorectal 3, Changsha 410005, Peoples R China.;[Cao, Yi] Univ South China, Hengyang Med Sch, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.
通讯机构：
[Zhenquan Wang] T;Third Department of Anorectal, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China
关键词：
3D Caco-2 spheroids;Kruppel-like factor 4 (KLF4);MoS2 nanosheets (NSs);Oral exposure;RNA-sequencing
摘要：
MoS(2) nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS(2) NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS(2) NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS(2) NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS(2) materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.
摘要：
Background Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB response.Methods NSCLC patients from the OAK and POPLAR clinical trials were used as the training cohorts for algorithm development. Survival analyses with overall survival (OS) and progression-free survival (PFS) as endpoints were performed to assess clinical response. The predictive value of bITH was subsequently validated with an independent cohort of 42 NSCLC patients treated with PD-1 blockade.Findings bITH was significantly associated with the differential OS and PFS elicited by atezolizumab vs. docetaxel in both univariable and multivariable analyses in the OAK patients, suggesting bITH as an independent predictor for response to ICB. Moreover, compared with blood tumor mutation burden (bTMB), bITH enabled greater OS segregation and comparable PFS segregation, and obtained a predictive role regardless of bTMB status. Moreover, the association between bITH and PFS was validated with an independent cohort. Interpretation Patients with low blood-based ITH metric manifest significant OS and PFS benefit from immunotherapy versus chemotherapy. Future research is awaited to corroborate our findings and to enrich the clinical utility of ITH.Funding This study was supported by the National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepre-neurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).Copyright (c) 2023 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
摘要：
OBJECTIVE: To explore the therapeutic effect of naringin on colorectal cancer (CRC) and the related mechanism. METHODS: Cell counting kit-8 (CCK-8) assay and annexin V-FITC/PI assay were used to detect the effect of naringin (50-400 µg/mL) on cell proliferation and apoptosis of CRC cells, respectively. The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration. Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model. Naringin was injected intraperitoneally at 50 mg/(kg·d), with solvent and 5-fluorouracil treatment as control. The width and length of the tumors were measured and recorded every 6 days, and tumor tissues were photographed and weighed on the last day of the 24-d observation period. Immunohistochemical staining for caspase-3, proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues. The body weight, food and water intake of mice were recorded, and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis. Meanwhile, the routine blood indicators were recorded. RESULTS: CCK-8 and annexin V-FITC/PI results confirmed that naringin (100, 200, and 400 µg/mL) could inhibit proliferation and promote apoptosis. The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration. In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility. CONCLUSION: Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells.
作者机构：
[Dong, Kefang; Zhang, Shenyao; Wang, Fan; Zeng, Xiangjing] Hunan Univ Chinese Med, Orthoped Dept, Affiliated Hosp 2, Changsha, Peoples R China.;[Lu, Min] Hunan Univ Chinese Med, Orthoped Dept, Affiliated Hosp 1, Changsha, Peoples R China.
通讯机构：
[Lu, M ] H;Hunan Univ Chinese Med, Orthoped Dept, Affiliated Hosp 1, Changsha, Peoples R China.
关键词：
Astragalus polysaccharide;miR-200b-3p;SP1;Steroid-induced osteonecrosis of the femoral head;Wnt/β-catenin
摘要：
Steroid-induced osteonecrosis of the femoral head (SONFH) is the necrosis of the femur bone caused by prolonged and massive use of corticosteroids. The present study probed into the significance of Astragalus polysaccharide (APS) in SONFH progression. SONFH cell model was constructed using murine long bone osteocyte Y4 (MLO-Y4) cells and then treated with APS. mRNA microarray analysis selected differentially expressed genes between control group and SONFH group. RT-qPCR determined SP1 and miR-200b-3p expression. Levels of SP1, β-catenin, autophagy-related proteins (LC3II/LC3I, Beclin1, p62) and apoptosis-related proteins (Bax, C-caspase3, C-caspase9, Bcl-2) were tested by Western blot. ChIP and luciferase reporter assays confirmed relationship between SP1 and miR-200b-3p. Fluorescence intensity of LC3 in cells was detected by immunofluorescence. Flow cytometry assessed cell apoptosis. Osteonecrosis tissues from SONFH mice were examined by HE and TRAP staining. APS induced autophagy and suppressed apoptosis in SONFH cell model. APS inhibited SP1 expression and SP1 overexpression reversed effects of APS on SONFH cell model. Mechanistically, SP1 targeted miR-200b-3p to inhibit Wnt/β-catenin pathway. MiR-200b-3p depletion rescued the promoting effect of SP1 on SONFH cell model by activating Wnt/β-catenin pathway. HE staining showed that APS treatment reduced the empty lacunae and alleviated inflammation in trabecular bone of SONFH mice. TRAP staining revealed decreased osteoclasts number in SONFH mice after APS treatment. APS regulated osteocyte autophagy and apoptosis via SP1/miR-200b-3p axis and activated Wnt/β-catenin signaling, thereby alleviating SONFH, shedding new insights for therapy of SONFH. APS induced autophagy and reduced apoptosis in SONFH cell model. APS suppressed SP1 level in SONFH cell model. SP1 reversed the effects of APS on SONFH cell model. SP1 targeted miR-200b-3p and inhibited Wnt/β-catenin signaling pathway. MiR-200b-3p depletion overturned effects of overexpressed SP1 via Wnt/β-catenin.
作者机构：
[Huang, Pan; Li, Ying; Peng, Youhua; Zeng, Bijun; Zhang, Yujin; Wang, Haizhen; Yang, Zhibo; Luo, Meijunzi] Hunan Univ Chinese Med, Hosp 2, Dept Dermatol, Domest Class Discipline Construct Project Chinese, Changsha 410005, Hunan, Peoples R China.;[Tang, Qing; Gao, Jie] Hunan Univ Chinese Med, Grad Sch, Changsha 410005, Hunan, Peoples R China.;[Gao, Jie] Ninth Hosp Changsha, Dept Dermatol, Changsha 410004, Hunan, Peoples R China.
通讯机构：
[Bijun Zeng; Zhibo Yang] D;Department of Dermatology, The Second Hospital of Hunan University of Chinese Medicine, The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Department of Dermatology, The Second Hospital of Hunan University of Chinese Medicine, The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, China
摘要：
BACKGROUND: Androgenetic alopecia can affect up to 70% of males and 40% of females; however, certain therapeutic medications offer partial and transitory improvement but with major side effects. Dendrobium officinale polysaccharide (DOP) has been reported to improve androgen-related hair loss in mice, but the molecular mechanism remains unclear. OBJECTIVES: To explore the effects of DOP on androgenetic alopecia. METHODS: In this study, testosterone was subcutaneously administered to shave dorsa skin of mice to establish androgenetic alopecia; the effects of DOP in androgenetic alopecia were explored by DOP administration. RESULTS: Testosterone treatment extended the time of skin growing dark and hair growing, decreased the mean numbers of follicles in skin tissues, decreased β-catenin and cyclin D1 levels, and elevated testosterone, DHT (dihydrotestosterone), and 5α-reductase levels. In contrast, DOP administration shortened skin growing dark and hair growing times, promoted follicle cell proliferation, increased follicle numbers, increased β-catenin and cyclin D1 levels, and decreased testosterone, DHT, and 5α-reductase levels. CONCLUSION: DOP application significantly improved testosterone-induced hair follicle miniaturization and hair loss, possibly through affecting the Wnt signaling and hair follicle stem cell functions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
期刊：
Journal of Ethnopharmacology,2023年307:116203 ISSN：0378-8741
通讯作者：
Xiaolong Lu
作者机构：
[Lu, Xiaolong] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Orthoped, Changsha 410005, Hunan, Peoples R China.;[Lu, Xuedi; Li, Wei; Li, Juan; Ouyang, Jian] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Orthoped, Changsha 410005, Hunan, Peoples R China.;[Zhou, Biao] Chinese Acad Chinese Med Sci, Wangjing Hosp, Dept Orthoped, Beijing 100102, Peoples R China.;[Zhou, Biao] Univ South China, Xiangtan Hosp, Dept Orthoped, Xiangtan 411101, Hunan, Peoples R China.;[Lu, Xiaolong] 233 Cai E Bei Rd, Changsha 410005, Hunan, Peoples R China.
通讯机构：
[Xiaolong Lu] D;Department of Orthopedics, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is a conventional traditional Chinese prescription aiming at promoting blood circulation and alleviating blood stasis. It is widely prescribed in instances of ischemic strokes, cardiovascular diseases, osteoporosis and bone fracture. However, its molecular functions in bone formation remain uncharacterized. AIM OF STUDY: This study aims to explore the potential effects of THSWD treatment on human bone marrow mesenchymal stem cells (BMSCs) proliferation, osteogenic differentiation, and migration. MATERIALS AND METHODS: BMSCs undergo osteogenic, adipogenic, and chondrogenic differentiation to determine cell stemness. BMSCs were treated with low dose (200μg/ml), medium dose (400μg/ml) and high dose (600μg/ml) THSWD. The cell viability was determined by CCK-8 assays, the osteogenic differentiation ability was determined by alizarin red staining and ALP staining, and cell migration was determined by wound healing and transwell assays. The effect of THSWD on the vascular endothelial growth factor (VEGF)/focal adhesion kinase (FAK) pathway was determined by immunoblotting. RESULTS: THSWD time-dependently and dose-dependently promoted BMSC viability. Moreover, THSWD also promoted BMSC osteogenic differentiation and migration. As opposed to THSWD, VEGF receptor inhibitor Bevacizumab suppressed BMSC osteogenic differentiation and migration. In BMSCs that have been co-treated with THSWD and Bevacizumab, THSWD effects on BMSC functions were partially eliminated by Bevacizumab. Moreover, THSWD treatment boosted VEGF content in the supernatant and was conducive to the phosphorylation of FAK and Src, whereas Bevacizumab exerted opposite effects; similarly, Bevacizumab partially abolished THSWD effects on VEGF and FAK (Tyr397) and Src (Tyr418) phosphorylation. CONCLUSION: THSWD enhances the capacities of BMSCs to proliferate, differentiate, and migrate, possibly through VEGF and the FAK-Src, thereby improving fracture healing.
作者机构：
[李恋秋; 张鹏; 陈壮志; 林佩怡; 许慧; 康贞] Department of Acupuncture-Moxibustion, Tuina and Rehabilitation, Second Affiliated Hospital of Hunan University of CM, Changsha 410005, China;[方灵莨; 叶海敏] Neurological Department, Second Affiliated Hospital of Hunan University of CM, Changsha 410005, China
摘要：
Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/β-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/β-catenin axis to repress CRC cell stemness.
摘要：
Atopic dermatitis (AD) is a common inflammatory skin disease. Matrine is the main component of the traditional Chinese medicine Sophora flavescens, and it poses good therapeutic effects on inflammatory diseases. This study aimed to explore the pharmacological effects of matrine on AD and its underlying mechanism. An AD mouse model and inflamed human epidermal keratinocyte cells (HaCaT) cells were established. Histopathological aspects were examined using hematoxylin and eosin staining, toluidine blue staining, and immunohistochemistry. The mRNA and protein expressions were assessed using quantitative real-time polymerase chain reaction and Western blot, respectively. The secretions of cytokines and chemokines were examined by enzyme-linked immunosorbent assay. Flow cytometry was carried out to analyze the proportions of T-helper (Th) 1 and Th2 cells. Herein, our results displayed that matrine diminished AD symptoms and decreased heat shock protein 90 (Hsp90) expression. Matrine decreased the Th2 cytokine levels in the ear tissues and serum, and it also significantly repressed inflammatory cytokines (thymus activation regulated chemokine and interleukin-6) secretions by repressing the Hsp90/NF-κB signaling axis in inflamed HaCaT cells. Furthermore, matrine inhibited Th2 differentiation of CD4(+) T cells when co-cultured with inflamed HaCaT cells. Matrine can regulate the Th1/Th2 inflammatory response by inhibiting the Hsp90/NF-κB signaling axis to alleviate AD. Therefore, it may be a candidate for AD treatment.
摘要：
A chalcone-flavonone type biflavonoid, trichocladabiflavone A (1), along with eight known biflavonoids (2–9) were isolated from the 70% EtOH extract of Selaginella trichoclada. Their structures were elucidated by extensive spectroscopic analyses. Compound 1 was the first chalcone-flavonone type biflavonoid reported in the genus Selaginella. Moreover, compound 1 exhibited moderate cytotoxicity against DU145, MCF-7 and PC3 human cancer cell lines.
作者：
Wang Yan-fang;Deng Yan;Zhang Su-ying;Liu Dong;Luo Bin;...
期刊：
中国结合医学杂志,2022年28(12):1072-1080 ISSN：1672-0415
通讯作者：
Ai-jun Sun
作者机构：
[Ma Rui-lin; Wang Yan-fang; Deng Yan; Sun Ai-jun] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing 100730, Peoples R China.;[Zhang Su-ying] Hunan Univ Chinese Med, Dept Obstet & Gynecol, Affiliated Hosp 2, Changsha 410001, Peoples R China.;[Luo Bin; Liu Dong] Sichuan Univ, West China Hosp 2, Key Lab Birth Defects & Related Dis Women & Child, Minist Educ, Chengdu 610041, Peoples R China.;[Wang Xue; Deng Miao] Hangzhou Womens Hosp, Dept Obstet & Gynecol, Hangzhou Matern & Child Hlth Care Hosp, Hangzhou 310008, Peoples R China.
通讯机构：
[Ai-jun Sun] D;Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
关键词：
Chinese medicine;Buxue Yimu Pills;gynecological anemia;network pharmacology;multi-target mechanism
摘要：
OBJECTIVE: To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology. METHODS: A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP. RESULTS: Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified. CONCLUSION: BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).
摘要：
The malignant phenotype of the cells resulting from human liver cancer is driven by liver cancer stem-like cells (LCSLCs). Transient Receptor Potential Vanilloid-type 2 channel (TRPV2) contributes to the progression of different tumor types, including liver cancer. In the current study, the TRPV2 expression levels give rise to the effect on stemness in liver cancer cell lines. TRPV2 knockdown in HepG2 cells enhanced spheroid and colony formation, and expression levels of CD133, CD44 and ALDH1 whereas the opposite effects were observed in TRPV2 enforced expression in SMMC-7721 cells. Furthermore, TRPV2 overexpression restored inhibition of spheroid and colony formation, and stem cell markers expression in HepG2 cells with TRPV2 silencing. The addition of the TRPV2 agonist probenecid and the TRPV2 antagonist tranilast suppressed and/or increased in vitro spheroid and colony formation, and stem cell marker expression of LCSLCs and/or liver cancer cell lines, respectively. Notably, probenecid and tranilast significantly inhibited or promoted tumor growth of HepG2 xenografts in the severe combined immunodeficiency (SCID) mouse model, respectively. TRPV2 expression at protein levels revealed converse correlation with those of CD133 and CD44 in human hepatocellular carcinoma (HCC) tissue. Collectively, the data demonstrate that TRPV2 exert effects on stemness of liver cancer and is a potential target in the treatment of human liver cancer patients.
期刊：
Molecular Medicine Reports,2018年17(1):660-666 ISSN：1791-2997
通讯作者：
Tang, Siyuan;Su, Feng
作者机构：
[Zhu, Shilin] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Neurol, Changsha 410005, Hunan, Peoples R China.;[Tang, Siyuan] Cent S Univ, Xiang Ya Nursing Sch, 172 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;[Su, Feng] Cent S Univ, Xiang Ya Hosp, Dept Emergency, 87 Xiang Ya Rd, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Tang, Siyuan; Su, Feng] C;Cent S Univ, Xiang Ya Nursing Sch, 172 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;Cent S Univ, Xiang Ya Hosp, Dept Emergency, 87 Xiang Ya Rd, Changsha 410008, Hunan, Peoples R China.
摘要：
Diosgenin, as an essential natural steroidal saponin, can be extracted from numerous sources, primarily from fenugreek. It is an important raw material for the synthesis of steroid hormone drugs. It exhibits antitumor, antiinflammatory, antioxidation and several other significant pharmacologic actions, and is of high pharmaceutical value. In the present study, the activities and underlying mechanisms of dioscin in the inhibition of ischemic stroke in rats were investigated. Inflammatory responses wer analyzed using ELISA kits and caspase3 and caspase9 activity was analyzed using Caspase3 and caspase9 activity kits. Western blot analysis was used to measure Tolllike receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factorkappaB (NFkappaB), transforming growth factorbeta1 (TGFbeta1), highmobility group protein 1 (HMGB1), interleukin1 receptorassociated kinase 1 (IRAK1), and tumor necrosis factor receptorassociated factor 6 (TRAF6) protein expression. Dioscin inhibited infarct volume and neurological scores in the ischemic stroke rat model. The results demonstrated that dioscin reduced inflammatory responses, and suppressed the expression of TLR4, MyD88, NFkappaB, TGFbeta1, HMGB1, IRAK1, and TRAF6 in the rat ischemic stroke model. Taken together, these findings suggested that dioscin inhibited ischemic strokeinduced inflammation through inhibition of the TLR4/MyD88/NFkBinduced inflammation the rat model, which provided novel insights into the mechanisms underlying the effect of dioscin as an antiinflammatory candidate for the treatment of ischemic stroke in in the future.
