摘要：
In response to the limitations of traditional cancer synergistic photothermal–chemodynamic therapy (PTT‐CDT), MoS2–Cu2O–PEG@QE/Znpp IX (MCPQZ) can pre‐weaken tumor multiple resistance and induce severe cell apoptosis by ·OH‐induced lysosomal membrane penetration under near‐infrared light in the second region laser irradiation, thereby achieving high‐efficient synergistic therapeutic effects. Abstract The fast conversion of hydrogen peroxide (H2O2) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near‐infrared light in the second region (NIR‐II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high‐density copper‐based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high–density cuprous (Cu2O) supported molybdenum disulfide (MoS2) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR‐II light irradiation, the ROS intensity and maximum reaction velocity (Vmax) produced by MC NFs are 21.6 and 33.8 times that of the non–irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre–weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS‐based cancer therapy.
期刊：
BMC Complementary Medicine and Therapies,2023年23(1):1-19 ISSN：2662-7671
通讯作者：
Wang, YH;Ge, JW
作者机构：
[Meng, Pan; Xie, Ming-xia; Luo, Yan; Wang, Yu-hong; Liu, Tong-tong; Zhong, Zi-yan] Hunan Univ Chinese Med, 300 Xueshi Rd, Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.;[Zhang, Xi; Guo, Dong-wei] Second Peoples Hosp Hunan Prov, Changsha, Hunan, Peoples R China.;[Yang, Hui; Liu, Jian] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China.;[Fang, Rui; Ge, Jin-Wen] Hunan Acad Chinese Med, 58 Lushan Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Wang, YH ; Ge, JW ] H;Hunan Univ Chinese Med, 300 Xueshi Rd, Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.;Hunan Acad Chinese Med, 58 Lushan Rd, Changsha, Hunan, Peoples R China.
关键词：
Xiaoyaosan;Depression;Whole transcriptomic analysis;Synapse loss;BDNF/trkB/PI3K signal axis
摘要：
BACKGROUND: Depression is a neuropsychiatric disease resulting from deteriorations of molecular networks and synaptic injury induced by stress. Traditional Chinese formula Xiaoyaosan (XYS) exert antidepressant effect, which was demonstrated by a great many of clinicalandbasicinvestigation. However, the exact mechanism of XYS has not yet been fully elucidated. METHODS: In this study, chronic unpredictable mild stress (CUMS) rats were used as a model of depression. Behavioral test and HE staining were used to detect the anti-depressant effects of XYS. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. The biological functions and potential mechanisms of XYS for depression were gathered from the GO and KEGG pathway. Then, constructed the competing endogenous RNA (ceRNA) networks to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Additionally, longest dendrite length, total length of dendrites, number of intersections, and density of dendritic spines were detected by Golgi staining. MAP2, PSD-95, SYN were detected by immunofluorescence respectively. BDNF, TrkB, p-TrkB, PI3K, Akt, p-Akt were measured by Western Blotting. RESULTS: The results showed that XYS could increase the locomotor activity and sugar preference, decreased swimming immobility time as well as attenuate hippocampal pathological damage. A total of 753 differentially expressed lncRNAs (DElncRNAs), 28 circRNAs (DEcircRNAs), 101 miRNAs (DEmiRNAs), and 477 mRNAs (DEmRNAs) were identified after the treatment of XYS in whole transcriptome sequencing analysis. Enrichment results revealed that XYS could regulate multiple aspects of depression through different synapse or synaptic associated signal, such as neurotrophin signaling and PI3K/Akt signaling pathways. Then, vivo experiments indicated that XYS could promote length, density, intersections of synapses and also increase the expression of MAP2 in hippocampal CA1, CA3 regions. Meanwhile, XYS could increase the expression of PSD-95, SYN in the CA1, CA3 regions of hippocampal by regulating the BDNF/trkB/PI3K signal axis. CONCLUSION: The possible mechanism on synapse of XYS in depression was successfully predicted. BDNF/trkB/PI3K signal axis were the potential mechanism of XYS on synapse loss for its antidepressant. Collectively, our results provided novel information about the molecular basis of XYS in treating depression.
期刊：
Journal of Functional Foods,2023年103:105485 ISSN：1756-4646
作者机构：
[Gui, Rui; Zhang, Wei; Wu, Jian-Ping; Wang, Yi-Kun; Wei, Xi -Fan; Wang, Wen-Xuan; Xu, Kang-Ping] Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Peoples R China.;[Zhu, Gang-Zhi; He, Xiao-Ai] Cent South Univ, Xiangya Sch Med, Dept Pharm, Affiliated HaiKou Hosp, Haikou 570100, Peoples R China.;[Wang, Yi-Kun] Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Peoples R China.;[Ren, Wei-Qiong; Deng, Gui-Ming; Long, Hong-Ping; Xu, Kang-Ping] Hunan Univ Chinese Med, Hosp 1, Changsha 410208, Peoples R China.;[Cheng, Fei; Zeng, Hong-Liang] Hunan Acad Chinese Med, Inst Chinese Mat Med, Changsha 410013, Peoples R China.
关键词：
Cyclocarya paliurus;Hyperuricemic nephropathy;Modulation of purine metabolism;Antiinflammation;Antifibrosis
摘要：
Cyclocarya paliurus, as an important edible and medicinal plant, its effects and mechanisms on hyperuricemic nephropathy remain unclear. Herein, we investigated the hypouricemic and nephroprotective effects of the water extracts of C. paliurus leaves (CPE) in a hyperuricemic nephropathy rat model induced by adenine and ethambutol. The results showed that CPE could significantly decrease plasma uric acid (PUA) and urea nitrogen (PUN), as well as reduce renal fibrosis in the hyperuricemic nephropathy rat model. Plasma metabolomics indicated that CPE improved the disordered arachidonic acid metabolism. Meanwhile, CPE reduced renal inflammation via inhibition of COX--2. Moreover, CPE could improve disturbed purine metabolism by inhibiting the hepatic xanthine oxidase (XOD), reversing the renal urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1). Collectively, this study demonstrated that CPE could exhibit hypouricemic effect by improving purine metabolism, and attenuate kidney injury by improving arachidonic acid metabolism and alleviating kidney inflammation.
摘要：
Disturbed structure and dysfunction of the retinal pigment epithelium (RPE) lead to degenerative diseases of the retina. Excessive accumulation of reactive oxygen species (ROS) in the RPE is thought to play an important role in RPE dysfunction and degeneration. Autophagy is a generally low-activity degradation process of cellular components that increases significantly when high levels of oxidative stress are present. Agents with antioxidant properties may decrease autophagy and provide protection against RPE dysfunction and damage caused by ROS. Lycium barbarum polysaccharide (LBP) has been widely studied as an antioxidant and cell-protective agent. Therefore, we designed this study to investigate the effects of LBP, which inhibits miR-181, on autophagy in retinal pigment epithelium (RPE) with oxidative stress in vitro and in vivo. In the current study, we found that the highly expressed miR-181 downregulated the expression of Bcl-2 in hydrogen peroxide- (H2O2-) induced ARPE-19 cells, resulting in an increase in ROS, apoptosis, and autophagy flux. LBP inhibited the expression of miR-181, decreased the levels of ROS, apoptosis, and autophagy flux, and increased cell viability in H2O2-induced ARPE-19 cells, suggesting that LBP provides protection against oxidative damage in ARPE-19 cells. We also found that LBP decreased RPE atrophy and autophagy flux in rd10 mice. Taken together, the results showed that LBP has a protective effect for RPE under oxidative stress by inhibiting miR-181 and affecting the Bcl-2/Beclin1 autophagy signaling pathway.
作者机构：
[Shen, Hongrong; Wang, Jinling; Gao, Hui; Li, Ping; Zhou, Shuwei; Li, Jianyu; Zhong, Zeya; You, Tian; Hu, Xiaoli; Luo, Muqing; Yan, Luyou; Zhang, Kun; He, Yewen] Hunan Univ Chinese Med, Hosp 1, Dept Radiol, 95 Shaoshan Middle Rd, Changsha 410007, Peoples R China.;[Wang, Jinling; Zhou, Shuwei; Zhang, Kun] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Peoples R China.;[Chen, Suping] GE Healthcare Shanghai Co Ltd, Shanghai 201203, Peoples R China.
通讯机构：
[Kun Zhang] D;Department of Radiology, The First Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China<&wdkj&>College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
摘要：
With the aging population of society, the incidence rate of osteoporosis is increasing year by year. Early diagnosis of osteoporosis plays a significant role in the progress of disease prevention. As newly developed technology, computed tomography (CT) radiomics could discover radiomic features difficult to recognize visually, providing convenient, comprehensive and accurate osteoporosis diagnosis. This study aimed to develop and validate a clinical-radiomics model based on the monochromatic imaging of single source dual-energy CT for osteoporosis prediction. One hundred sixty-four participants who underwent both single source dual-energy CT and quantitative computed tomography (QCT) lumbar-spine examination were enrolled in a study cohort including training datasets (n = 114 [30 osteoporosis and 84 non-osteoporosis]) and validation datasets (n = 50 [12 osteoporosis and 38 non-osteoporosis]). One hundred seven radiomics features were extracted from 70-keV monochromatic CT images. With QCT as the reference standard, a radiomics signature was built by using least absolute shrinkage and selection operator (LASSO) regression on the basis of reproducible features. A clinical-radiomics model was constructed by incorporating the radiomics signature and a significant clinical predictor (age) using multivariate logistic regression analysis. Model performance was assessed by its calibration, discrimination and clinical usefulness. The radiomics signature comprised 14 selected features and showed good calibration and discrimination in both training and validation cohorts. The clinical-radiomics model, which incorporated the radiomics signature and a significant clinical predictor (age), also showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.938 (95% confidence interval, 0.903–0.952) in the training cohort and an AUC of 0.988 (95% confidence interval, 0.967–0.998) in the validation cohort, and good calibration. The clinical-radiomics model stratified participants into groups with osteoporosis and non-osteoporosis with an accuracy of 94.0% in the validation cohort. Decision curve analysis (DCA) demonstrated that the radiomics signature and the clinical-radiomics model were clinically useful. The clinical-radiomics model incorporating the radiomics signature and a clinical parameter had a good ability to predict osteoporosis based on dual-energy CT monoenergetic imaging.
作者机构：
[Xiao, Yanni] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Xiao, Yanni; Tang, Chuwen; Luo, Zhihong; Xiao, Pengfei; Zeng, Xianxiang] Brain Hosp Hunan Prov, Changsha, Hunan, Peoples R China.;[Yu, Yu] Yale Sch Med, Dept Psychiat, Div Prevent & Community Res, New Haven, CT USA.;[Tang, Chuwen; Zhou, Ziqi] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[Zhou, Ziqi] Hunan Univ Chinese Med, Hosp 1, Dept Obstet & Gynecol, Changsha, Hunan, Peoples R China.
通讯机构：
[Shen, MX ; Luo, ZH; Zeng, XX] C;Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Changsha, Hunan, Peoples R China.;Furong Lab, Changsha, Hunan, Peoples R China.
关键词：
Mental disorder;Schizophrenia;Hospitalization;Spending;Length of hospital stay
摘要：
Objectives: To describe hospital spending and length of stay for mental disorders in Hunan, China.Methods: We extracted hospital care data for Hunan province from the Chinese National Health Statistics Network Reporting System. Patients with mental disorders (ICD-10 codes: F00 to F99) as the principal diagnosis and hospitalized between January 1, 2017 and December 31, 2019 were included. We retrieved information on age, sex, number of comorbidities, diagnosis, level of hospital, hospital costs, date of admission and discharge, length of stay (LOS), and method of payment of eligible participants. Spending at the provincial level, and spending and LOS at the individual level were described. Quantile regression and linear regression were conducted to investigate factors for hospital cost and LOS for major mental disorders.Results: The 2019 annual spending on mental disorders in Hunan province was 160 million US dollars, and 71.7% was paid by insurance. The annual spending on schizophrenia was 84 million dollars, contributing to a primary burden of mental disorders. The median spending for mental disorders was $1,085 per patient, and the median hospital stay was 22 days. The study identified several significant factors associated with hospital cost and LOS, including age, sex, comorbidity, and level of the hospital. In particular, a higher level of the hospital was associated with a higher hospital spending but a shorter LOS. Women with schizophrenia had a comparable hospital spending but a significantly shorter LOS than men with schizophrenia.Conclusion: Hospitalization spending for patients with mental disorders is substantial. Schizo- phrenia is the major burden of hospitalization for mental disorders. While patients treated at a higher level of hospital had higher spending, they stayed shorter in these hospitals.
摘要：
Pyroptosis is a novel pro-inflammatory cell programmed death dependent on Gasdermin (GSMD) family-mediated membrane pore formation and subsequent cell lysis, accompanied by the release of inflammatory factors and expanding inflammation in multiple tissues. All of these processes have impacts on a variety of metabolic disorders. Dysregulation of lipid metabolism is one of the most prominent metabolic alterations in many diseases, including the liver, cardiovascular system, and autoimmune diseases. Lipid metabolism produces many bioactive lipid molecules, which are important triggers and endogenous regulators of pyroptosis. Bioactive lipid molecules promote pyroptosis through intrinsic pathways involving reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lysosomal disruption, and the expression of related molecules. Pyroptosis can also be regulated during the processes of lipid metabolism, including lipid uptake and transport, de novo synthesis, lipid storage, and lipid peroxidation. Taken together, understanding the correlation between lipid molecules such as cholesterol and fatty acids and pyroptosis during metabolic processes can help to gain insight into the pathogenesis of many diseases and develop effective strategies from the perspective of pyroptosis.
作者机构：
[Liu, Zhao; Lin, Qing-xia; Yi, Zi-yang; Xie, Jing; Zhang, Shui-han; Yu, Rong; Hui, Bo-ping; Huang, Jian-hua; Zhao, Di] Hunan Univ Chinese Med, Hunan Acad Chinese Med, Changsha 410013, Hunan, Peoples R China.;[Peng, Ya-Jun] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Liu, Xiu; Yu, Rong; Huang, Jian-hua; Peng, Ya-Jun] Hunan Univ Chinese Med, Hunan Key Lab TCM Prescript & Syndromes Translat M, Changsha 410208, Hunan, Peoples R China.;[Wang, Yan] Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
关键词：
Gut microbiota;HK-2;NLRP3 signaling;Pyroptosis;Trimethylamine N-oxide
摘要：
BACKGROUND: Nowadays, diabetic kidney disease (DKD) has become one of the most threatening to the end-stage renal diseases, and the early prevention of DKD is inevitable for Diabetes Mellitus (DM) patients. AIMS: Pyroptosis, a programmed cell death that mediates renal inflammation induced early renal injury. The trimethylamine n-oxide (TMAO) was also an independent risk factor for renal injury. Here, the associations between TMAO-induced pyroptosis and pathogenesis of DKD were studied, and the potential mechanism of Zuogui-Jiangtang-Yishen (ZGJTYS) decoction to prevent DKD was further investigated. METHOD: Using Goto-Kakizaki (GK) rats to establish the early DKD models. The 16S-ribosomal RNA (16S rRNA) sequencing, fecal fermentation and UPLC-MS targeted metabolism techniques were combined to explore the changes of gut-derived TMAO level under the background of DKD and the effects of ZGJTYS. The proximal convoluted tubule epithelium of human renal cortex (HK-2) cells was adopted to explore the influence of pyroptosis regulated by TMAO. RESULTS: It was demonstrated that ZGJTYS could prevent the progression of DKD by regulating glucolipid metabolism disorder, improving renal function and delaying renal pathological changes. In addition, we illustrated that gut-derived TMAO could promote DKD by activating the mROS-NLRP3 axis to induce pyroptosis. Furthermore, besides interfering with the generation of TMAO through gut microbiota, ZGJTYS inhibited TMAO-induced pyroptosis with a high-glucose environment and the underlying mechanism was related to the regulation of mROS-NLRP3 axis. CONCLUSION: Our results suggested that ZGJTYS inhibited the activation of pyroptosis by gut-derived TMAO via the mROS-NLRP3 axis to prevent DKD.
作者机构：
[Zhu, Ying; Zhu, Y; Sun, Hao-xian] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Gastroenterol, Changsha 410007, Peoples R China.;[Sun, Hao-xian] Hunan Univ Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Zhu, Y ] H;Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Gastroenterol, Changsha 410007, Peoples R China.
关键词：
NLRP3 inflammasome;ulcerative colitis;Chinese medicine;mechanism of action;review
摘要：
Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.
摘要：
The aim of this study is to explore the active components and potential molecular mechanism of action of Rubia cordifolia L. against nasopharyngeal carcinoma (NPC). We used network pharmacology, molecular docking, and bioinformatics analysis to identify the active components and their role against NPC. The experimental verification was detected by MTT, AnnexinV-FITC/PI double fluorescence staining and Western blotting method. Network pharmacology identified that mollugin is one of the most effective components inRubia cordifolia L. Important NPC targets included HSP90AA1, CDK1, EGFR, PIK3CA, MAPK14, and CDK2. Molecular docking revealed considerable binding activity of mollugin with either of the 6 important NPC targets. Bioinformatics analysis showed that these 6 important targets were mutated in NPC, and the expression of HSP90AA1, PIK3CA, and CDK2 in cancer tissues was significantly different from that in normal tissues. MTT detection and AnnexinV-FITC/PI double fluorescence staining showed that mollugin inhibited the proliferation and induced apoptosis of NPC cells. Western blotting indicated that the molecular mechanism of mollugin against NPC was related to the regulation of the expression of Survivin and XIAP. This study predicted and partially verified the pharmacological and molecular mechanism of action of Rubia cordifolia L. against NPC. Mollugin was identified as a potential active ingredient against NPC. These results prove the reliability of network pharmacology approaches and provide a basis for further research and application of Rubia cordifolia L. against NPC.
摘要：
The proliferation of extravillous trophoblasts (EVT) and their further migration, invasion, and differentiation into the decidual and myometrial vasculature are vital for spiral artery remodeling. These physiological functions of EVT are also essential steps in the implantation of the human embryo and the formation of the placenta and are closely related to pregnancy maintenance and the occurrence of abortion. Hyperin is a flavonoid with anti-inflammatory, pro-proliferative, and anti-apoptotic properties. Consequently, we investigated the previously unexplored effects of hyperin on the proliferation, migration, and invasion of HTR-8/SVneo cells. Human extravillous trophoblast-derived HTR-8/SVneo cells were incubated with different concentrations of hyperin (0, 5, 10, 25, 50, and 100 mu M) to observe the changes in cell proliferation, migration, invasive capacity, and pathway activation. Proliferation, migration, and invasion were promoted by activating the JAK1/STAT3 pathway in HTR-8/SVneo cells treated with hyperin. In addition, brepocitinib (PF-06700841) significantly inhibited the proliferation, migration, and invasion effects of hyperin on HTR-8/SVneo cells. In vivo experiments confirmed that hyperin reduces the embryo loss rate in recurrent spontaneous abortion (RSA) model mice. Furthermore, our study revealed that hyperin promoted the proliferation, migration, and invasion of HTR-8/SVneo cells via activation of the JAK1/STAT3 pathway, further improving pregnancy outcomes in RSA.
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：
[He, Chao -ping; Li, Zhen-xian; Tuo, QH; Quan, Wen-juan; Liao, Duan-fang; Lin, Li-mei; Tuo, Qin-hui; Li, Ya-mei; Liao, DF] Hunan Univ Chinese Med, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha, Hunan, Peoples R China.;[Zhou, Hong-yan; Liu, Bin] Hunan Univ, Coll Biol, Changsha, Hunan, Peoples R China.;[Liao, Duan-fang; Tuo, Qin-hui] Hunan Univ Chinese Med, Hosp 1, Changsha, Peoples R China.;[You, Pei-dong; Zeng, Ya-ling] Ningxia Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Yinchuan 750004, Peoples R China.;[Tuo, Qin-hui] Hunan Univ Chinese Med, Lab Vasc Biol & Translat Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Tuo, QH ; Liao, DF] H;Hunan Univ Chinese Med, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha, Hunan, Peoples R China.
关键词：
atherosclerosis;curcumin nicotinate;Prussian Blue nanoparticles;macrophage;cholesterol efflux
摘要：
Reducing lipid uptake of macrophages and stimulating cholesterol efflux are two necessary steps for atherosclerotic plaque regression. In this study, a compound of curcumin nicotinate (CN) was synthesized from nicotinic acid which can raise raising high-density lipoprotein (HDL) and curcumin which can lower lipid. However, the shortcomings of CN, such as poor water solubility and low bioavailability, limit its clinical application. In this article, a CN loaded biomimetic nanosystem was constructed by using Prussian blue nanoparticles (PB NPs) to improve its solubility, thereby changing its administration route. In addition, hyaluronic acid (HA) modification on the biomimetic PB NPs was adopted to prolong circulation time and improve the accumulation of drugs in the plaque region. Mechanism studies have shown that the constructed nanosystem could exert anti-AS effects through the pathway of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) /Low-density lipoprotein receptor (LDL-R), ATP Binding Cassette Transporter A1(ABCA1) /Caveolin-1 /Liver X Receptor (LXR). These findings indicated that the designed nano-platform is expected to be used for prevention and targeted therapy of atherosclerosis. & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
作者机构：
[Zhou, Kang; Tan, Zhoujin; Peng, Xinxin; Yi, Xin; Peng, XX; Jiang, Ping; Deng, Na] Hunan Univ Chinese Med, Domest Class Discipline Construct Project Chinese, Changsha 410208, Peoples R China.;[Peng, Xinxin; Jiang, Ping; Peng, XX] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Peoples R China.
通讯机构：
[Peng, XX; Tan, ZJ ; Peng, XX ] H;Hunan Univ Chinese Med, Domest Class Discipline Construct Project Chinese, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Peoples R China.
关键词：
Diet and water intake;Folium sennae;Intestinal mucosal microbiota;Microbial diversity;Oxidative stress;Spleen deficiency constipation
摘要：
Intestinal microbiota disorder was associated with constipation. This study investigated the microbiota-gut-brain axis and oxidative stress mediated by intestinal mucosal microbiota in mice with spleen deficiency constipation. The Kunming mice were randomly divided into the control (MC) group and the constipation (MM) group. The spleen deficiency constipation model was established by gavage with Folium sennae decoction and controlled diet and water intake. The body weight, spleen and thymus index, 5-Hydroxytryptamine (5-HT) and Superoxide Dismutase (SOD) content were significantly lower in the MM group than the MC group, the content of vasoactive intestinal peptide (VIP) and malondialdehyde (MDA) content were significantly higher than the MC group. The Alpha diversity of intestinal mucosal bacteria was not changed but beta diversity was changed in mice with spleen deficiency constipation. Compared to the MC group, the relative abundance of Proteobacteria was an upward trend and the Firmicutes/Bacteroidota (F/B) value was a downward trend in the MM group. There was a significant difference in the characteristic microbiota between the two groups. In the MM group, Brevinema, Akkermansia, Parasutterella, Faecalibaculum, Aeromonas, Sphingobium, Actinobacillus, and other pathogenic bacteria were enriched. Meanwhile, there was a certain relationship between the microbiota and gastrointestinal neuropeptide and oxidative stress indicators. The community structure of intestinal mucosal bacteria in mice with spleen deficiency constipation was changed, which was characterized by the reduction of F/B value and enrichment of Proteobacteria. Microbiota-gut-brain axis may be important for spleen deficiency constipation.
关键词：
Argon-helium cryoablation;radiofrequency ablation;advanced lung cancer;immune function
摘要：
Objective: This study was designed to explore the clinical effect of cold and heat ablation on patients with advanced lung cancer (LC) and its influence on immune function. Methods: Data of 104 cases of advanced LC treated between July 2015 and April 2017 in the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed. Among them, 49 patients receiving argon helium cryoablation (AHC) were regarded as group A, and 55 patients receiving radiofrequency ablation (RFA) were regarded as group B. The short-term postoperative efficacy and local tumour control rate were compared between the two groups. The changes in im-munoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were compared between the two groups before and after treatment. After treatment, the changes in carcinoembryonic antigen (CEA) and cytokeratin 19 frag-ment (CYFRA21-1) were compared between the two groups. During the treatment, the complications and incidence of adverse reactions were compared between the two groups. Cox regression analysis was applied to analyze the factors influencing the prognosis of patients. Results: There was no statistical difference in IgA, IgG and IgM be-tween the two groups after treatment (P>0.05). There was no statistical difference in CEA and CYFRA21-1 between the two groups after treatment (P>0.05). There was no notable difference in disease control rate and response rate between the two groups at 3 and 6 months after operation (P>0.05). The incidence of pleural effusion in group A was obviously lower than that in group B (P<0.05). The incidence of intraoperative pain in group A was obviously higher than that in group B (P<0.05). Age, clinical stage, CEA and CYFRA21-1 were found to be independent prog-nostic factors impacting overall survival (P<0.05). Conclusion: AHC and RFA are minimally invasive procedures that lead to few complications in the treatment of advanced LC. Cold and heat ablation is a relatively safe and effective minimally invasive technique for tumour treatment, which is worthy of application and promotion in the clinical treatment of LC.
通讯机构：
[Wang, YA ] H;[Peng, QH ; Wang, ZY ] C;[Li, J ] U;Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Ultrasound, Changsha, Peoples R China.;Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Dept Ultrasound, Changsha, Hunan, Peoples R China.
摘要：
We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system's diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.
摘要：
BACKGROUND: Atherosclerosis (AS) is a common vascular disease, and its main influencing factor is endothelial damage caused by oxidized low-density lipoprotein (ox-LDL). As one of the main active ingredients of ginseng, ginsenoside Rb3 has anti-inflammatory and anti-oxidative effects. However, the role of ginsenoside Rb3 in endothelial injury induced by ox-LDL is not clear. OBJECTIVES: This study aimed to evaluate the effect and potential mechanism of ginsenoside Rb3 action on ox-LDL-treated human aortic endothelial cells (HAECs). MATERIAL AND METHODS: The HAECs treated with ox-LDL were used to establish an in vitro AS model. The viability of the HAECs was analyzed with Cell Counting Kit-8 (CCK-8). Flow cytometry was performed to assess the apoptosis. Oxidative stress, inflammation and endothelial dysfunction were evaluated using enzyme-linked immunosorbent assay (ELISA) and western blotting. The levels of miR-513a-5p were assessed using quantitative real-time polymerase chain reaction (qPCR). A dual-luciferase assay was performed to analyze the relationship between miR-513a-5p and a zinc finger and BTB domain-containing protein (ZBTB20). RESULTS: Exposure of HAECs to ox-LDL (50 μg/mL) reduced cell viability, superoxide dismutase (SOD) activity and endothelial nitric oxide synthase (eNOS) expression, while increasing the levels of malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and soluble intercellular adhesion molecule-1 (sICAM-1). The pretreatment with Rb3 markedly enhanced cell viability and decreased ox-LDL-induced oxidative stress, inflammation and endothelial dysfunction in HAECs. The ox-LDL decreased the level of miR-513a-5p, which was reversed by Rb3 pretreatment. The ZBTB20 was a target of miR-513a-5p in HAECs, and ox-LDL upregulated ZBTB20 expression, which was reversed by Rb3 pretreatment. The protective effect of Rb3 on ox-LDL-induced HAECs was diminished by miR-513a-5p inhibition, which was reversed by ZBTB20 knockdown. CONCLUSIONS: Ginsenoside Rb3 reduces the effects of ox-LDL on HAECs by regulating the miR-513a-5p/ZBTB20 axis, which provides a theoretical basis for the treatment of AS.
摘要：
Inhibition of extensive osteoclastogenesis and bone resorption is considered a potential therapeutic target for the treatment of osteoporosis. Isobavachalcone (IBC) is derived from the traditional Chinese herb Psoralea corylifolia Linn. We showed that IBC dose-dependently suppressed receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis in bone marrow monocyte/macrophage (BMMs) and osteoclastic bone-resorption function without cytotoxicity at a dose of no more than 8 µmin vitro. Mechanistically, the results of western blot and quantitative real-time polymerase chain reaction (qRT-PCR) indicated that IBC inhibited the RANKL-induced degradation of IκBα and phosphorylation of nuclear factor kappa B (NF-κB) in BMMs, and subsequently downregulated the expression of osteoclastic-specific genes and osteoclastogenesis-related proteins. TRAP staining and qRT-PCR showed that IBC can inhibit osteoclast differentiation by down-regulating the expression of miR-193-3p on osteoclast differentiation. Overall, our findings suggest that IBC may serve as a promising compound for the treatment of osteoporosis and other metabolic bone diseases.
The signaling pathway of IBC inhibiting RANKL-induced osteoclast formation.
