摘要：
It targets to explore the expression of Th17/Treg in oral submucous fibrosis (OSF) carcinogenesis and its significance in the development of mucosal lesions. In this research, 100 patients with OSF who visited our hospital for surgical treatment from March 2020 to April 2022 were selected. Based on pathological examination results, the patients were divided into 27 patients with oral leukoplakia (OK) group, 14 patients with oral lichen planus (OLP) group, 9 patients with oral squamous cell carcinoma (OSCC) group, and 50 patients with OSF group. It adopted flow cytometry (FC) to calculate the ratio of peripheral blood Th17 cells and Treg cells in four groups, and the Th17/Treg ratio was calculated; The area of oral mucosal lesions (OML) from patients was collected. It needs to compare the differences in Th17/Treg ratio and OML area among four groups and determine the correlation between indicators. ROC curve was used to analyze the diagnostic threshold of the Th17/Treg ratio for carcinogenesis. Except for the OK and OLP, it had statistical significance differences in Th17, Treg cells, and Th17/Treg ratio (P<0.001); The area of OML in the OK, OLP, and OSCC was higher than that in the simple OSF, with statistical significance (P<0.001); Th17 (%), Treg (%), and Th17/Treg all had direct ratio with the area of OML; The area of OML has directed ratio with the development of mucosal lesions (r>0, P<0.05); The areas under the ROC curve for patients with OSF combined with OK, OLP, or OSCC with Th17 (%), Treg (%), Th17/Treg, and OML area were 0.560, 0.986, 0.936, and 0.466, respectively. The expression of Th17/Treg is elevated in oral submucosal fibrosis and carcinogenesis. When mucosal lesions progress or become cancerous, the Th17/Treg ratio increases accordingly, and it has more clinical value than the increase in the OML area.
摘要：
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI), a subsequent injury caused by thrombolytic reperfusion post ischemic stroke (IS). Naotaifang (NTF) formula, a novel traditional Chinese medicine (TCM) remedy against IS, was shown to exert beneficial effects in inhibiting inflammation and inhibiting lipid peroxide synthesis in our previous research. PURPOSE: This study aimed to further explore the role of NTF in attenuating oxygen-glucose deprivation//reoxygenation (OGD/R)-induced inflammation and ferroptosis by regulating microglial M1/M2 polarization through the bone morphogenetic protein 6（BMP6）/SMADs signaling pathway. METHODS: BV2 microglia were used to establish an OGD/R model. The effects of NTF on inflammation and ferroptosis in OGD/R-injured BV2 cells were separately detected by immunofluorescence assay, fluorescent probe, DCFH-DA flow cytometry, enzyme-linked immunosorbent assay, and western-blot. RESULTS: The present results revealed that the M1 phenotype of microglia promoted the secretion of pro-inflammatory cytokines and aggravated ferroptosis and brain damage following OGD/R. However, an inhibitor of BMP6, LND-193189, reversed the aforementioned effects. Similarly, NTF promoted the shift of microglia from M1 to M2. Besides, NTF treatment effectively inhibited the expression of hepcidin, BMP6, SMADs and promoted the expression of ferroportin (FPN, SLC40A1) and γ-L-glutamyl-L-cysteinylglycine (glutathione or GSH) peroxidase 4 (GPX4). CONCLUSION: Microglial M1/M2 polarization plays a pivotal role in inflammation and ferroptosis during OGD/R. The BMP6/SMADs signaling pathway is a potential therapeutical target of inflammation and ferroptosis induced by the transformation of microglia. Moreover, NTF could alleviate inflammation and ferroptosis through the BMP6/SMADs signaling pathway in OGD/R-injured microglia.
摘要：
Cerebral ischemia-reperfusion (CIR) is a serious complication often associated with cerebral ischemia. The pur-pose of this study was to explore the therapeutic effect of nourishing qi, activating blood circulation, and inducing resuscitation (Borneol with astragaloside IV and Panax notoginseng total saponins, BAP) on CIR. Neurological function score system was used to determine the neurological function. The survival of nerve cells was detected by Nissl staining. The levels of IL-1(3, IL-18, IL-4, and IL-10 were detected by ELISA. The expression of GSDMD, GSDMD-N, Nrf2, and HO-1 proteins in hippocampus tissues was measured by immunohistochemistry (IHC). Western blot, RT-qPCR, or immunofluorescence (IF) were used to detect the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), pro-Caspase-1, Caspase-1, Nrf2, and HO-1 expression. Lactate dehy-drogenase (LDH) level was analyzed by LDH release assay. Cell viability was determined by cell counting kit-8 (CCK8). Apoptosis was detected by flow cytometry. BAP significantly promoted the recovery of nerve function, the activity of nerve cells, and the expression of Nrf2, HO-1, IL-4, and IL-10 in rat hippocampus tissues after CIR. BAP has an obvious inhibitory effect on the expression of NLRP3, pro-Caspase-1, and Caspase-1 proteins, the release of IL-1(3 and IL-18 factors, and neuronal pyroptosis in hippocampal tissues. BAP also promoted IL-4 and IL-10 levels, and the activity of SH-SY5Y cells. The IL-1(3, IL-18, NLRP3, pro-Caspase-1, Caspase-1, GSDMD, and GSDMD-N expressions were significantly inhibited by BAP in vitro, which was reversed by Nrf2 knockdown. This study confirmed that BAP alleviated rat CIR and inhibited the pyroptosis of SH-SY5Y cells by regulating the Nrf2/ HO-1 signaling pathway. This study provided new directions and ideas for the treatment of CIR.
期刊：
Journal of Clinical Gastroenterology,2023年57(8):782-788 ISSN：0192-0790
通讯作者：
Tian, XF
作者机构：
[Huang, Caizhi; Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;[Huang, Caizhi] Hunan Childrens Hosp, Dept Lab Med, Changsha, Peoples R China.;[Mei, Si] Hunan Univ Chinese Med, Dept Physiol, Changsha, Peoples R China.;[Zhang, Xue] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Tian, XF ] H;Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
关键词：
gut microbiota, hepatocellular carcinoma, inflammation, dysbiosis
摘要：
Hepatocellular carcinoma (HCC) is an invasive primary liver cancer caused by multiple pathogenic factors and is a significant global health concern. With few effective therapeutic options, HCC is a heterogeneous carcinoma that typically arises in an inflammatory environment. Recent studies have suggested that dysbiotic gut microbiota is involved in hepatocarcinogenesis via multiple mechanisms. In this review, we discuss the effects of gut microbiota, microbial components, and microbiota-derived metabolites on the promotion and progression of HCC by feeding a persistent inflammatory milieu. In addition, we discuss the potential therapeutic modalities for HCC targeting the inflammatory status induced by gut microbiota. A better understanding of the correlation between the inflammatory milieu and gut microbiota in HCC may be beneficial for developing new therapeutic strategies and managing the disease.
摘要：
Evidence is mounting that abnormal vascular remodeling leads to many cardiovascular diseases (CVDs). This suggests that vascular remodeling can be a crucial target for the prevention and treatment of CVDs. Recently, celastrol, an active ingredient of the broadly used Chinese herb Tripterygium wilfordii Hook F, has attracted extensive interest for its proven potential to improve vascular remodeling. Substantial evidence has shown that celastrol improves vascular remodeling by ameliorating inflammation, hyperproliferation, and migration of vascular smooth muscle cells, vascular calcification, endothelial dysfunction, extracellular matrix remodeling, and angiogenesis. Moreover, numerous reports have proven the positive effects of celastrol and its therapeutic promise in treating vascular remodeling diseases such as hypertension, atherosclerosis, and pulmonary artery hypertension. The present review summarizes and discusses the molecular mechanism of celastrol regulating vascular remodeling and provides preclinical proof for future clinical applications of celastrol.
关键词：
Endotoxin-induced uveitis;traditional Chinese medicine;network pharmacology;Astragalus membranaceus;total flavonoids of Astragalus
摘要：
Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com). Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat's iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-gamma and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.
摘要：
We describe a graphene oxide (GO)-based bioassay for the fluorometric determination of norA gene transcription (mRNA) in methicillin-resistant Staphylococcus aureus (MRSA). This approach is based on Nb.BbvCI-assisted target recycling (NATR) and T7 exonuclease (T7 Exo)-triggered cascade dual-recycling signal amplification (TTCDRSA). The system included GO, a capture probe (CP), an assistant probe (AP), two carboxyfluorescein (FAM)-labeled hairpins (HP1 and HP2), endonuclease Nb.BbvcI, and exonuclease T7. In the presence of a target, AP, together with the target RNA, can hybridise with CP via partial complementarity to one another and open its hairpin structure to form a triple complex that is recognised by Nb.BbvCI. Once the CP is cleaved, the released AP and target RNA can walk on the carboxylated graphene oxide (CGO) surface to bind with another CP which induces the next round of cleavage, accumulating many trigger probes (TPs). The TPs then activate TTCDRSA with the assistance of T7 Exo, HP1, and HP2 to produce large amounts of free FAMs. These free FAMs are repelled by GO and exhibit enhanced fluorescence signals at excitation/emission wavelengths of 480/514 nm. The limit of detection (LOD) of the bioassay was calculated to be 0.37 fM, and the linear range of the method ranged from 1 fM to 1 nM. More importantly, the bioassay also exhibited high sensitivity and selectivity for target RNA detection in real samples, which may open a new promising avenue for monitoring drug efflux and studying the mechanisms of drug actions.
作者机构：
[Zhang, Hongning; Zhang, Jian; Chen, Wen; Hu, Xiang; Yuan, Changyue; Hu, X; Huang, Shulan; Su, Na] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;[Chen, Wen] Hunan Univ Chinese Med, Med Sch, Key Lab Vasc Biol & Translat Med, Changsha 410208, Peoples R China.;[Xiang, Shuanglin; Su, Na] Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
通讯机构：
[Xiang, SL ; Hu, X ] H;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
摘要：
TNF α-induced protein 1 (TNFAIP1) was first identified in human umbilical vein endothelial cells and can be induced by tumor necrosis factor α (TNFα). Early studies have found that TNFAIP1 is involved in the development of many tumors and is closely associated with the neurological disorder Alzheimer’s disease. However, little is known about the expression pattern of TNFAIP1 under physiological conditions and its function during embryonic development. In this study, we used zebrafish as a model to illustrate the early developmental expression pattern of tnfaip1 and its role in early development. First, we examined the expression pattern of tnfaip1 during early zebrafish development using quantitative real-time PCR and whole mount in situ hybridization and found that tnfaip1 was highly expressed in early embryonic development and, subsequently, expression became localized to anterior embryonic structures. To investigate the function of tnfaip1 during early development, we constructed a model of a stably inherited tnfaip1 mutant using the CRISPR/Cas9 system. Tnfaip1 mutant embryos showed significant developmental delays as well as microcephaly and microphthalmia. At the same time, we found decreased expression of the neuronal marker genes tuba1b, neurod1, and ccnd1 in tnfaip1 mutants. Analysis of transcriptome sequencing data revealed altered expression of the embryonic development related genes dhx40, hspa13, tnfrsf19, nppa, lrp2b, hspb9, clul1, zbtb47a, cryba1a, and adgrg4a in the tnfaip1 mutants. These findings suggest an important role for tnfaip1 in the early development of zebrafish.
摘要：
Objectives: The nuclear factor-kappa B (NF-kappa B) signaling pathway plays an important role in regulating tubular epithelial-mesenchymal transition (EMT), an indispensable cellular programme for driving organ fibrosis and tumor progression. Liuwei Dihuang Decoction (LWD) is an effective Chinese formula for treating chronic renal failure. Methods: First, by using morphological examination, immunofluorescence staining assay, RT-qPCR, and Western blot analysis, in vitro experiments were designed to analyze NF-kappa B and EMT markers (including Snail, alpha-SMA, and E-cadherin) in transforming growth factor-beta 1 (TGF-beta 1) induced renal tubular epithelial cells (HK-2) and to detect the expression levels of LWD-CS co-treatment. Then, the recombinant lentiviral vector was overexpressed and knocked down by NF kappa B and transfected into HK-2 cells. Cells were treated with TGF-beta 1 (10 ng/ml) with blank serum or LWD-containing serum, respectively, and the expression of these molecules in the NF-kappa B/Snail signaling pathway was further evaluated. Results: Our results confirmed that TGF-beta 1 could induce EMT, nuclear translocation of NF-kappa B p65, and activate the NF-kappa B/Snail signaling pathway in HK-2 cells. Furthermore, NF-kappa B knocked-down dramatically increases the TGF-beta 1-induced mRNA and protein expression level of E-cadherin and reduces the level of Snail and alpha-SMA; this is reversed by NF-kappa B overexpression. LWD can decrease the EMT levels through the NF-kappa B/Snail signaling activation in TGF-beta 1-induced EMT of HK-2 cells. Conclusion: The present study provides evidence suggesting a novel mechanism that LWD exerts anti-fibrosis effects through inhibiting activation of the NF-kappa B/Snail signaling pathway and consequently downregulating the TGF-beta 1-induced EMT in renal tubular epithelial cells.
作者机构：
[Huang, Jiawang; Ma, Xinyue; Li, Ling; Liao, Zexuan; Liu, Zhuolin] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;[Feng, Zhiying; Wang, Kangyu] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410208, Peoples R China.;[Ning, Yi; Lu, Fangguo] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.;[Li, Ling; Liu, Zhuolin] Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
通讯机构：
[Li, L ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
摘要：
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1 alpha (HIF-1 alpha), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
摘要：
Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking β-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/β-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.
期刊：
Journal of Pharmacy and Pharmacology,2023年75(5):666-676 ISSN：0022-3573
通讯作者：
Biao Tang
作者机构：
[Wang, Linlin; Xiao, Lan; Kang, Zhineng; Xiao, Qian; Tang, Biao] Hunan Univ Chinese Med, Basic Res Ctr Integrated Chinese & Western Med Pre, Changsha, Peoples R China.;[Tang, Biao] Hunan Univ Chinese Med, Med Sch, Xiangzui Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Biao Tang] B;Basic Research Center of Integrated Chinese & Western Medicine for Prevention & Treatment of Vascular Diseases, Hunan University of Chinese Medicine , Changsha , China
摘要：
OBJECTIVES: This study aimed to observe the effect of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischaemia-reperfusion injury (CIRI) and explore the specific mechanism of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated combination of AST IV and PNS against CIRI based on ferroptosis and inflammatory response. METHODS: The therapeutic effect and mechanism of AST IV and PNS were evaluated by constructing a Sprague-Dawley rat middle cerebral artery ischaemia-occlusion-reperfusion model. The specific mechanism of the combination of AST IV and PNS against CIRI was revealed through the combined intervention of the Nrf2-specific inhibitor brusatol. KEY FINDINGS: After AST IV and PNS treatment, the cerebral infarction area of the rats was reduced; behavioural performance was improved; Fe2+, malondialdehyde, lipid peroxidation, interleukin-6, interleukin-1β, tumour necrosis factor-α and myeloperoxidase levels were reduced; and glutathione and glutathione peroxidase 4 levels were increased. In addition, the expression of Nrf2 was significantly increased, the combined treatment was more effective than the single treatment, and the Nrf2 inhibitor brusatol could reverse the effects of the combined intervention of AST IV and PNS. CONCLUSIONS: The findings of this study suggest that combining AST IV and PNS attenuates CIRI by activating Nrf2 to inhibit ferroptosis and inflammatory responses.
期刊：
Frontiers in Cardiovascular Medicine,2023年10 ISSN：2297-055X
通讯作者：
Zhong, Yancheng;Tuo, Q
作者机构：
[Zhong, Yancheng; Tuo, Qinhui; Chen, Wen; Zhong, YC; Hu, Bo] Hunan Univ Chinese Med, Med Sch, Hunan Key Lab Vasc Biol & Translat Med, Changsha, Peoples R China.
通讯机构：
[Tuo, Q ; Zhong, YC] H;Hunan Univ Chinese Med, Med Sch, Hunan Key Lab Vasc Biol & Translat Med, Changsha, Peoples R China.
关键词：
Cardiovascular disease (CVD);LncRNA - long noncoding RNA;gasdermins (GSDMs);pyroptosis;Inflammatory
摘要：
Cardiovascular disease (CVD) is the leading cause of death worldwide. Pyroptosis is a unique kind of programmed cell death that varies from apoptosis and necrosis morphologically, mechanistically, and pathophysiologically. Long non-coding RNAs (LncRNAs) are thought to be promising biomarkers and therapeutic targets for the diagnosis and treatment of a variety of diseases, including cardiovascular disease. Recent research has demonstrated that lncRNA-mediated pyroptosis has significance in CVD and that pyroptosis-related lncRNAs may be potential targets for the prevention and treatment of specific CVDs such as diabetic cardiomyopathy (DCM), atherosclerosis (AS), and myocardial infarction (MI). In this paper, we collected previous research on lncRNA-mediated pyroptosis and investigated its pathophysiological significance in several cardiovascular illnesses. Interestingly, certain cardiovascular disease models and therapeutic medications are also under the control of lncRNa-mediated pyroptosis regulation, which may aid in the identification of new diagnostic and therapy targets. The discovery of pyroptosis-related lncRNAs is critical for understanding the etiology of CVD and may lead to novel targets and strategies for prevention and therapy.
摘要：
Context. Infertility is a common disease among women of childbearing age and seriously endangers the reproductive health of human beings. Aims. We aimed to study the active effect and mechanism of betulonic acid (BTA) on tubal inflammatory infertility. Methods. An inflammatory model was established in isolated rat oviduct epithelial cells. Immunofluorescence of cytokeratin 18 was performed in cells. The therapeutic effect of BTA on cells was observed. Subsequently, we added JAK/STAT inhibitor AG490 and MAPK inhibitor U0126 and measured the levels of inflammatory factors via enzyme-linked immunosorbent assay and qRT-PCR. CCK-8 assay was applied to test cell proliferation, whereas flow cytometry was used to measure apoptosis. The levels of TLR4, I kappa B alpha, JAK1, JAK2, JAK3, Tyk2, STAT3, p38, ERK and the phosphorylation of p65 were determined by Western blotting. Key results. Betulonic acid inhibited the activation of TLR4 and NF-kappa B signalling pathways, and significantly downregulated IL-1 beta, IL-6, and TNF-alpha, with high doses being the most effective. Furthermore, high-dose BTA promoted the proliferation of oviduct epithelial cells and inhibited apoptosis. In addition, BTA inhibited the activation of JAK/STAT signalling pathway to perform effectively in oviduct epithelial cells inflammation. The addition of AG490 led to the inhibition of the JAK/STAT signalling pathway. BTA also inhibited the activation of MAPK signalling pathway in oviduct epithelial cells inflammation. Under U0126 treatment, the inhibition of proteins in MAPK pathway by BTA was weakened. Conclusions. Therefore, BTA inhibited the TLR, JAK/STAT and MAPK signalling pathways. Implications. Our study provided a new therapeutic strategy for infertility caused by oviduct inflammation.
期刊：
Frontiers in Cellular Neuroscience,2023年17:1191629 ISSN：1662-5102
通讯作者：
Ge, Jinwen;Mei, ZG;Ge, JW
作者机构：
[She, Ruining; Ge, Jinwen; Mei, Zhigang; Wang, Guozuo] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.;[Liu, Danhong; Liao, Jun] Hunan Univ Chinese Med, Med Sch, Changsha, Hunan, Peoples R China.;[Ge, Jinwen] Hunan Acad Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Mei, Zhigang] China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med Approved Sta, Yichang, Hubei, Peoples R China.
通讯机构：
[Ge, JW; Mei, ZG ; Ge, JW ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.;Hunan Acad Tradit Chinese Med, Changsha, Hunan, Peoples R China.;China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med Approved Sta, Yichang, Hubei, Peoples R China.
摘要：
Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca2+ overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS.
摘要：
The correlation between chemical structure and antibacterial activity of a series of heterocyclic organobismuth (III) complexes based on bidentate C,O‐coordinating ligands against various pathogenic bacterial stains was explored. A series of heterocyclic organobismuth (III) complexes based on bidentate C,O‐coordinating ligands were designed and synthesized as antimicrobials. Antibacterial assays showed that complexes of this type are more effective for Gram‐positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis) than Gram‐negative ones (Escherichia coli and Pseudomonas aeruginosa). Their activities are especially relevant to the synergism of lipophilicity, geometry, and stability, which depends on both the identity of coordinating ligands and the coordination number at the bismuth center. By comparison, the hypervalent 14‐Bi‐6 species diarylbismuth nitrate (8) was found to exhibit the most potent inhibitory effect, together with a high degree of selectivity, which gives an IC50(LO2)/MIC(Staphylococcus aureus) ratio of up to 23.08. Time–kill analysis demonstrated that complex 8 is bacteriostatic at low concentrations while displaying significant bactericidal activity at high doses. The results of drug resistance experiments suggested that complex 8 can inhibit the formation of bacterial biofilm and consequently delay or prevent the development of drug resistance. Furthermore, complex 8 also showed high inhibition efficiency against several drug‐resistant Staphylococcus aureus, and the MIC values are within the range of 0.39–1.56 μM, thus indicating the lack of cross‐resistance between this organometallic compound and commonly used antibiotics.
摘要：
Resistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMβ, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases.
摘要：
Inflammation and immunity play a major role in the development of hypertension, and a potential correlation between host mucosal immunity and inflammatory response regulation. We explored the changes of intestinal mucosal microbiota in hypertensive rats induced by high-salt diet and the potential link between the intestinal mucosal microbiota and inflammation in rats. Therefore, we used PacBio (Pacific Bioscience) SMRT sequencing technology to determine the structure of intestinal mucosal microbiota, used enzyme-linked immunosorbent assay (ELISA) to determined the proinflammatory cytokines and hormones associated with hypertension in serum, and used histopathology methods to observe the kidney and vascular structure. We performed a potential association analysis between intestinal mucosal characteristic bacteria and significantly different blood cytokines in hypertensive rats induced by high-salt. The results showed that the kidney and vascular structures of hypertensive rats induced by high salt were damaged, the serum concentration of necrosis factor-alpha (TNF-alpha), angiotensin II (AngII), interleukin-6 (IL-6), and interleukin-8 (IL-8) were significantly increased (p < 0.05), and the coefficient of immune organ spleen was significantly changed (p < 0.05), but there was no significant change in serum lipids (p > 0.05). From the perspective of gut microbiota, high-salt diet leads to significant changes in intestinal mucosal microbiota. Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were the dominant differential bacteria in intestinal mucosal, with the AUC (area under curve) value of Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were 1 and 0.875 according to ROC (receiver operating characteristic) analysis. Correlation analysis showed that Bifidobacterium animalis subsp. was correlated with IL-6, IL-8, TNF-alpha, and Ang II. Based on our results, we can speculated that high salt diet mediated chronic low-grade inflammation through inhibited the growth of Bifidobacterium animalis subsp. in intestinal mucosa and caused end-organ damage, which leads to hypertension.
通讯作者：
Liming Zhu<&wdkj&>Yongliang Jiang<&wdkj&>Aiguo Dai
作者机构：
[Li, Guang; Peng, Yanping; Zhu, Liming; Dai, Aiguo; Jiang, Yongliang; Meng, Fang; Li, San; Zhu, Hao; Zhang, Shaoze; Li, Cheng; Gu, Jing] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Resp & Crit Care Med, Changsha, Hunan, Peoples R China.;[Liu, Pingping] Hunan Childrens Hosp, Dept Emergency, Key Lab Pediat Emergency Med Hunan Prov, Changsha, Hunan, Peoples R China.;[Yao, Huiling] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Gen Med, Changsha, Hunan, Peoples R China.;[Dai, Aiguo] Hunan Univ Chinese Med, Med Sch, Dept Resp Dis, Changsha, Hunan, Peoples R China.;[Dai, Aiguo] Hunan Prov Key Lab Vasc Biol & Translat Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Liming Zhu; Yongliang Jiang; Aiguo Dai] D;Department of Respiratory and Critical Care Medicine, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P.R. China<&wdkj&>Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, P.R. China<&wdkj&>Hunan Province Key Laboratory of Vascular Biology and Translational Medicine, Changsha, Hunan, P.R. China<&wdkj&>Department of Respiratory and Critical Care Medicine, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P.R. China
关键词：
Tfh/Tfr;hypoxia;pulmonary hypertension;regulatory B cells
摘要：
Chronic hypoxia promoted Breg cells differentiation in the early stage of HPH, which significantly decreased in the late stage. Insufficient Breg cells exacerbated pulmonary vascular remodelling and dysregulated Tfh/Tfr cells in HPH. Adoptive transfer of Breg cells ameliorated pulmonary vascular remodelling and dysregulated Tfh/Tfr cells in HPH. Abstract Hypoxia‐induced pulmonary hypertension (HPH) is a progressive and lethal disease characterized by the uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) and obstructive vascular remodelling. Previous research demonstrated that Breg cells were involved in the pathogenesis of pulmonary hypertension. This work aimed to evaluate the regulatory function of Breg cells in HPH. HPH mice model were established and induced by exposing to chronic hypoxia for 21 days. Mice with HPH were treated with anti‐CD22 or adoptive transferred of Breg cells. The coculture systems of Breg cells with CD4+ T cells and Breg cells with PASMCs in vitro were constructed. Lung pathology was evaluated by HE staining and immunofluorescence staining. The frequencies of Breg cells, Tfh cells and Tfr cells were analysed by flow cytometry. Serum IL‐21 and IL‐10 levels were determined by ELISA. Protein levels of Blimp‐1, Bcl‐6 and CTLA‐4 were determined by western blot and RT‐PCR. Proliferation rate of PASMCs was measured by EdU. Compared to the control group, mean PAP, RV/(LV + S) ratio, WA% and WT% were significantly increased in the model group. Anti‐CD22 exacerbated abnormal hemodynamics, pulmonary vascular remodelling and right ventricle hypertrophy in HPH, which ameliorated by adoptive transfer of Breg cells into HPH mice. The proportion of Breg cells on day 7 induced by chronic hypoxia was significantly higher than control group, which significantly decreased on day 14 and day 21. The percentage of Tfh cells was significantly increased, while percentage of Tfr cells was significantly decreased in HPH than those of control group. Anti‐CD22 treatment increased the percentage of Tfh cells and decreased the percentage of Tfr cells in HPH mice. However, Breg cells restrained the Tfh cells differentiation and expanded Tfr cells differentiation in vivo and in vitro. Additionally, Breg cells inhibited the proliferation of PASMCs under hypoxic condition in vitro. Collectively, these findings suggested that Breg cells may be a new therapeutic target for modulating the Tfh/Tfr immune balance in HPH.
作者机构：
[Chen, Kaiqin; Chen, Chunjing; Lu, Fangguo; Ye, Chun; Hu, Jue; Wei, Ke; Gao, Zihan; Xiao, Rong] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.
通讯机构：
[Wei, Ke] M;Medical School, Hunan University of Chinese Medicine, Changsha 410208,China. Electronic address:
关键词：
Immune infiltration;GDF10;NCKAP5;RTKN2;Non-small cell lung cancer
摘要：
This study aimed to identify potential biomarkers for non-small cell lung cancer (NSCLC) and analyze the role of immune cell infiltration in NSCLC. R software was used to screen differentially expressed genes (DEGs) from NSCLC datasets obtained from the Gene Expression Omnibus (GEO) database, and functional correlation analysis was performed. The machine learning algorithms were used to screen the potential biomarkers of NSCLC. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. The protein and mRNA expression levels of potential biomarkers were verified based on the Human Protein Atlas (HPA) database and qRT-PCR. CIBERSORT was used to evaluate the infiltration of immune cells in NSCLC tissues, and the correlation between potential biomarkers and infiltrated immune cell was analyzed. Finally, specific siRNAs were utilized to reduce the GDF10, NCKAP5, and RTKN2 expression in A549 and H1975 cells. The proliferation ability of A549 and H1975 cells was detected by MTT assay. A total of 848 upregulated DEGs and 1308 downregulated DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the DEGs were mainly related to cell division. Disease ontology (DO) enrichment analysis showed that the diseases with these DEGs were mainly lung diseases, including NSCLC. In addition,three potential biomarkers were identified: GDF10, NCKAP5, and RTKN2. Immune cell infiltration analysis showed that resting NK cells, activated dendritic cells, and Tregs may be involved in the pathogenesis of NSCLC. Meanwhile, GDF10, NCKAP5, and RTKN2 were negatively correlated with Tregs and naïve B cells but were positively correlated with activated dendritic cells and resting NK cells. Immunohistochemical staining showed that the expression of GDF10, NCKAP5, and RTKN2 in the lung tissue of patients with NSCLC was lower than that of normal lung tissue. qRT-PCR also confirmed that the mRNA expression of three biomarkers in NSCLC cell lines A549 and H1975 were significantly lower than those in human normal lung epithelial cells BEAS-2B. An MTT assay showed that GDF10, NCKAP5, and RTKN2 knockdown significantly promoted the proliferation of A549 and H1975 cells. The in vitro experiments showed that GDF10, NCKAP5, and RTKN2 played the inhibitory effects on NSCLC cell lines proliferation. Hence, GDF10, NCKAP5, and RTKN2 can be used as diagnostic biomarkers for NSCLC.
