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.
期刊：
Journal of International Medical Research,2023年51(2) ISSN：0300-0605
通讯作者：
Shunhua Cheng
作者机构：
[Wang, Yinhuai; Cheng, Xu; Cheng, Shunhua] Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China;[Xiong, Qi] Department of Urology, The Second Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan Province, China
通讯机构：
[Shunhua Cheng] D;Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
关键词：
Radical prostatectomy;dorsal vascular complex;blood loss;positive margin;urinary control
摘要：
Radical prostatectomy has undergone a development from open to laparoscopic surgery to a surgical robotic approach. With improved surgical equipment and the continuous development of surgical techniques, various surgical strategies for controlling the dorsal vascular complex (DVC) during RP have been investigated, which affect intraoperative blood loss, postoperative tumour control and postoperative urinary and sexual function. The present narrative review summarizes the latest anatomical information about the prostatic apex and DVC and then describes the three types of DVC control. More detailed anatomy of the DVC is required and the optimal DVC control under different situations needs further research.
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.
