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.
作者机构：
[Zhou, Hao] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Urol, Changsha 410001, Hunan, Peoples R China.;[Wang, Fang] Changsha Social Work Coll, Med Coll, Changsha 410004, Hunan, Peoples R China.;[Wang, F; Wang, Fang] Changsha Social Work Coll, Med Coll, 22 XiangZhang Rd, Changsha 410004, Hunan, Peoples R China.
通讯机构：
[Wang, F ] C;Changsha Social Work Coll, Med Coll, 22 XiangZhang Rd, Changsha 410004, Hunan, Peoples R China.
摘要：
Hepatic leukemia factor (HLF), a transcription factor, is dysregulated in many cancers. This study investigates the function of HLF in prostate cancer (PCa) and its relation to tensin 1 (TNS1). Clinical tissues were collected from 24 PCa patients. Duke University 145 (DU145) and PC3 cells overexpressing HLF were established. HLF signaling was downregulated in PCa tissues compared to adjacent tissues and in DU145 and PC3 cells compared to prostate epithelial cells RWPE-1 or prostate stromal cells (WPMY-1). PCa cell lines with overexpression of HLF had reduced proliferative, migratory, and invasive activity, increased apoptosis, and cell mitosis mostly in the G0/G1 phase. HLF induced the TNS1 transcription to activate the p53 pathway. Depletion of TNS1 reversed the anti-tumor effects of HLF on PCa cells and tumor growth and metastasis in vivo. In summary, our findings suggest that HLF suppressed PCa progression by upregulating TNS1 expression and inducing the p53 pathway activation, which might provide insights into novel strategies for combating PCa.
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.
期刊：
REVISTA INTERNACIONAL DE MEDICINA Y CIENCIAS DE LA ACTIVIDAD FISICA Y DEL DEPORTE,2023年22(88):1-11 ISSN：1577-0354
通讯作者：
Liu, YH
作者机构：
[Li, Wenjuan; Qin, Zuoai; Liu, Nian; Fu, Zhongying; Yan, Jie; Ye, Haimin; Guo, Xiajun; Liu, Yehui; Wang, Xiaoyi; Zhou, Liu] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, 233 Caie North Rd, Changsha 410000, Hunan, Peoples R China.
通讯机构：
[Liu, YH ] H;Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, 233 Caie North Rd, Changsha 410000, Hunan, Peoples R China.
关键词：
Neck acupuncture;Scalp acupuncture;Stroke;Cognitive impairment;Quality of life;Therapeutic effect
摘要：
Objective: To explore the intervention value of needle acupuncture and scalp acupuncture in improving cognitive impairment and life in stroke patients; Methods: A total of 62 stroke patients who were healed in our hospital from August 2019 to October 2021 were retrospectively selected as the research objects, and were divided into a combined healing cluster (Combined healing cluster, CTG, n=31, The patients received conventional healing combined with acupuncture and acupuncture) and the general healing cluster (GTG, n=31). The healing effects of the two clusters were contrast, and the National Institutes of Health Stroke Scale (NIHSS), neurological deficit score before and after healing Table (NDS) and Barthel Index (BI) score changes, the follow-up outcomes of the two clusters of patients were calculated and contrast between the two clusters; Results: (1) The total effective rate of patients in CTG cluster was 96.77%, and the total effective rate of patients in GTG cluster was 80.65%, and the variation in effective rate between the two clusters was notable (P<0.05). The NIHSS and NDS marks of the CTG cluster were notably bottom than those of the GTG cluster, and the variation between the clusters was notable (P<0.05). (3) On the 7th, 15th and 30th days of healing, the BI marks of the CTG cluster were notably upper than those in the GTG cluster, and the variation between the clusters was notable (P<0.05). (4) There were a total of 3 recurrences in the CTG cluster after 6 months of follow-up, with a recurrence rate of 10.00%, and a total of 9 recurrences in the GTG cluster. The recurrence rate of patients in the CTG cluster was notably bottom than that in the GTG cluster (P<0.05); Conclusion: The combined use of acupuncture and scalp acupuncture for stroke patients can help to enhance the healing effect and life of patients, enhance the neurological function of patients, and reduce the recurrence rate of stroke in patients in the short-term. It is recommended to popularize and apply it.
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：
Objective: Exosomes in the central nervous system (CNS) have become an attractive area of research with great value. However, few bibliometric analysis has been conducted. The study aimed to visualize the scientific trends and research hotspots of exosomes in the CNS by bibliometric analysis.Methods: All potential articles and reviews on exosomes in the CNS published in English from 2001 to 2021 were extracted from the Web of Science Core Collection. The visualization knowledge maps of critical indicators, including countries/regions, institutions, authors, journals, references, and keywords, were generated by CiteSpace and VOSviewer software. Besides, each domain's quantitative and qualitative analysis was also considered.Results: A total of 2,629 papers were included. The number of exosomes-related publications and citations regarding CNS increased yearly. These publications came from 2,813 institutions in 77 countries/regions, led by the United States and China. Harvard University was the most influential institution, while the National Institutes of Health was the most critical funding source. We identified 14,468 authors, among which Kapogiannis D had the most significant number of articles and the highest H-index, while Thery C was the most frequently co-cited. The cluster analysis of keywords generated 13 clusters. In summary, the topic of biogenesis, biomarker, and drug delivery will serve as hotspots in future research.Conclusion: Exosomes-related CNS research has gained considerable attention in the past 20 years. The sources and biological functions of exosomes and their promising role in diagnosing and treating CNS diseases are considered hotspots in this field. The clinical translation of the results from exosomes-related CNS research will be of great importance in the future.
摘要：
MicroRNAs (miRNAs) play vital roles in the post-transcriptional regulation of gene expression. Previous studies have shown that miR-150 is a crucial regulator of B cell proliferation, differentiation, metabolism, and apoptosis. miR-150 regulates the immune homeostasis during the development of obesity and is aberrantly expressed in multiple B-cell-related malignant tumors. Additionally, the altered expression of MIR-150 is a diagnostic biomarker of various autoimmune diseases. Furthermore, exosome-derived miR-150 is considered as prognostic tool in B cell lymphoma, autoimmune diseases and immune-mediated disorders, suggesting miR-150 plays a vital role in disease onset and progression. In this review, we summarized the miR-150-dependent regulation of B cell function in B cell-related immune diseases.
期刊：
Open Life Sciences,2023年18(1):20220597 ISSN：2391-5412
通讯作者：
Zhang, XP
作者机构：
[Zhang, Hui; Long, Ting; Peng, Lu; Zhang, Hong-Mei; Zhang, Xian-Ping; Tang, Shi-Huan] Univ South China, Loudi Affiliated Hosp, Hengyang Med Sch, Dept Reprod Med Ctr, Loudi 417000, Peoples R China.;[He, Xiao-Juan; Zhu, Fei-Yue] Univ South China, Loudi Affiliated Hosp, Hengyang Med Sch, Dept Hematol, Loudi 417000, Peoples R China.;[Zou, Zong-Zhi] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Nephropathy Endocrinol, Changsha 410000, Peoples R China.;[Xiong, Zhu] China Med Univ, Shenzhen Childrens Hosp, Dept Pediat Orthoped, Shenzhen 518034, Guangdong, Peoples R China.
通讯机构：
[Zhang, XP ] U;Univ South China, Loudi Affiliated Hosp, Hengyang Med Sch, Dept Reprod Med Ctr, Loudi 417000, Peoples R China.
关键词：
DNA fragmentation index;apoptosis;clinical pregnancy;in vitro fertilization and embryo transfer/intracytoplasmic sperm injection;reactive oxygen species
摘要：
We investigated the influence of DNA fragmentation index (DFI) on in vitro fertilization (IVF), embryo transfer (ET), and intracytoplasmic sperm injection (ICSI). We analyzed the semen parameters of 61 cycles in infertile couples undergoing IVF-ET and ICSI and determined DFI by sperm chromatin dispersion testing. Based on DFI, the patients were differentiated into a control group (DFI < 25%, n = 35) and a test group (DFI ≥ 25%, n = 26). Flow cytometry and immunofluorescence were used to investigate the extent of sperm reactive oxygen species (ROS) and apoptosis. We also investigated the effect of DFI on pregnancy outcomes of IVF-ET/ICSI. DFI was negatively related to sperm motility and positively correlated with ROS and apoptosis (P < 0.05). Abnormally elevated DFI reduced the rate of transplantable, high-quality embryos, implantation, clinical pregnancy, delivery, and live birth after IVF-ET, and increased the chance of early abortion per transfer cycle (P < 0.05). However, there was no significant correlation between DFI and fertilization rate, cleavage rate, transplantable rate, high-quality embryo rate, implantation rate, clinical pregnancy rate, early abortion rate, delivery rate and live birth rate when assisted by ICSI (P > 0.05). Sperm DNA integrity is crucial for fertilization and the development of healthy offspring. ROS may increase the level of DFI by inducing apoptosis in sperm.
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.
关键词：
N 6-Methyladenosine (m6a) RNA modification;ALKBH5;Re-epithelialization;PELI2;RNA stability
摘要：
Impaired wound re-epithelialization contributes to cutaneous barrier reconstruction dysfunction. Recently, N6-methyladenosine (m6A) RNA modification has been shown to participate in the determination of RNA fate, and its aberration triggers the pathogenesis of numerous diseases. Howbeit, the function of m6A in wound re-epithelialization remains enigmatic. Alkbh5‒/‒ mouse was constructed to study the rate of wound re-epithelialization after ALKBH5 ablation. Integrated high-throughput analysis combining methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq was used to identify the downstream target of ALKBH5. In vitro and in vivo rescue experiments were conducted to verify the role of the downstream target on the functional phenotype of ALKBH5-deficient cells or animals. Furthermore, the interacting reader protein and regulatory mechanisms were determined through RIP-qPCR, RNA pull–down, and RNA stability assays. ALKBH5 was specifically upregulated in the wound edge epidermis. Ablation of ALKBH5 suppressed keratinocyte migration and resulted in delayed wound re-epithelialization in Alkbh5‒/‒ mouse. Integrated high-throughput analysis revealed that PELI2, an E3 ubiquitin protein ligase, serves as the downstream target of ALKBH5. Concordantly, exogenous PELI2 supplementation partially rescued keratinocyte migration and accelerated re-epithelialization in ALKBH5-deficient cells, both in vitro and in vivo. In terms of its mechanism, ALKBH5 promoted PELI2 expression by removing the m6A modification from PELI2 mRNA and enhancing its stability in a YTHDF2-dependent manner. This study identifies ALKBH5 as an endogenous accelerator of wound re-epithelialization, thereby benefiting the development of a reprogrammed m6A targeted therapy for refractory wounds.
摘要：
Objective: To explore the effects of Compound Qinbo Decoction (CQD) on the intestinal mucosa of ulcerative colitis (UC) through the Notch signaling pathway.Methods: The UC rat model, established using 2,4,6- Trinitrobenzene sulfonic acid (TNBS)/ethanol, was divided into the UC group, mesalazine (MS) group and CQD group. Normal rats were set as the normal group (n = 10). The pathological changes, messager RNA (mRNA) levels and protein expressions of Notch 1 and hairy and enhancer of split 1 (Hes1), epithelial cell proliferation in colon tissues were detected. Primary rat colon epithelial NCM460 cells were added with Tumor Necrosis Factor-a (TNF-a) to establish the UC model, then treated with different drug-contained serum. The cell proliferation and protein expressions of Notch 1 and Hes1 were measured.Results: In vivo, the UC rat model was established with obvious pathological changes in colon tissues, which were greatly relieved by MS or CQD. After MS or CQD treatment, mRNA and protein levels of Notch 1 and Hes1 in the UC rat model were increased (p < 0.05). The epithelial cell proliferation was listed from high to low: MS group, CQD group, normal group and UC group (p < 0.05). In vitro, UC in NCM460 cells was established with TNF-a of 50 ng/mL for 6 h, and the cell proliferation level was decreased, which was then increased with MS-containing serum or CQD-containing serum (p < 0.05). The protein expressions of Notch 1 and Hes1 were decreased with TNF-a treatment, which was increased with MS-containing serum or CQD-containing serum (p < 0.05). The effect of CQD-containing serum was suppressed by the Notch signaling pathway inhibitor (p < 0.05).Conclusions: CQD has a good therapeutic effect on the intestinal mucosa of UC through the Notch signaling pathway, and the underlying mechanism needs to be explored in the future.
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 .
摘要：
Thirteen robustaflavones (1-13) were isolated from the 70% EtOH extract of Selaginella trichoclada Alston herbs for the first time. The structures of these compounds were identified on the basis of extensive spectroscopic data including UV-vis, 1D and 2D NMR, and mass spectra. The molecular docking results indicate that the robustaflavone derivates may play a role as a NEDD4 protein inhibitor.
摘要：
Immune-mediated inflammatory diseases (IMIDs) consist of a common and clinically diverse group of diseases. Despite remarkable progress in the past two decades, no remission is observed in a large number of patients, and no effective treatments have been developed to prevent organ and tissue damage. Brain-derived neurotrophic factor precursor (proBDNF) and receptors, such as p75 neurotrophin receptor (p75(NTR)) and sortilin, have been proposed to mediate intracellular metabolism and mitochondrial function to regulate the progression of several IMIDs. Here, the regulatory role of proBDNF and its receptors in seven typical IMIDs, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, allergic asthma, type I diabetes, vasculitis, and inflammatory bowel diseases, was investigated.
期刊：
Skin Research and Technology,2023年29(9) ISSN：0909-752X
通讯作者：
Li, X
作者机构：
[Li, Xiaosha; Wang, Haizhen] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Dermatol, Changsha, Peoples R China.;[Tang, Shiyang] Hunan Univ Chinese Med, Sch Chinese Med, Changsha, Peoples R China.;[Li, Xin] Hunan Univ Chinese Med, Hunan Prov Key Lab Diagnost Chinese Med, 300 Xueshi Rd, Hanpu Sci & Educ Pk, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Li, X ] H;Hunan Univ Chinese Med, Hunan Prov Key Lab Diagnost Chinese Med, 300 Xueshi Rd, Hanpu Sci & Educ Pk, Changsha 410208, Hunan, Peoples R China.
关键词：
NLRP3;pyroptosis;ROS;tanshinoneIIA;vitiligo
摘要：
Abstract Background Pyroptosis has been implicated in the development of human diseases, including vitiligo. TanshinoneIIA has been confirmed to play anti‐vitiligo role. However, whether tanshinoneIIA inhibits vitiligo progression via regulating cell pyroptosis remains unclear. Methods Hydrogen peroxide (H2O2)‐induced melanocytes were used to mimic vitiligo cell model in vitro. Cell viability was assessed by cell counting kit 8 assay, and reactive oxygen species (ROS) production was detected by DCFH‐DA staining. Nod‐like receptor protein 3 (NLRP3) expression was detected by quantitative real‐time PCR, western blot and immunofluorescence staining. Cell pyroptosis was measured using flow cytometry, and the contents of interleukin‐1β and interleukin‐18 were determined by ELISA. Besides, the protein levels of apoptosis‐associated speck‐like protein containing CARD (ASC) and cleaved‐Caspase‐1 were examined by western blot analysis. Results H2O2 could induce ROS production, NLRP3 expression and pyroptosis in melanocytes. TanshinoneIIA inhibited ROS production, pyroptosis, and the expression of NLRP3, ASC and cleaved‐caspase‐1 in H2O2‐induced melanocytes. Compared with the function of ROS inhibitor (NAC), tanshinoneIIA acted as a ROS scavenger to relieve melanocyte pyroptosis. In addition, NLRP3 inhibitor (MCC950) also could aggravate the inhibition effect of tanshinoneIIA on melanocyte pyroptosis. Conclusion TanshinoneIIA suppressed melanocyte pyroptosis probably through modulating the ROS/NLRP3 signaling axis, which provides the evidence for therapeutic effect in vitiligo.
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.
