MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2022
·
IF 4.369
Dandan Wang,Yixin Zhang,Liangyi Cui,Qing Yang,Jiao Wang
Endometriosis , defined as the abnormal growth of functional endometrium outside the uterus , is characterized by the abnormal phenotype of endometrial cells. This study aimed to investigate the role of latent transforming growth factor beta binding protein 2 (LTBP2), an extracellular matrix protein , in the occurrence and development of endometriosis. Elevated LTBP2 expression levels were observed in endometrial tissues and serum of endometriosis patients and their area under the ROC curve (AUC) values for distinguishing endometriosis were 0.9044 and 0.9534, respectively. Overexpressing-LTBP2 could promote proliferation, migration, and invasion, whereas suppressing apoptosis of endometrial stromal cells (ESCs). Moreover, LTBP2 downregulation induced the opposite effect. The supernatant from ESCs overexpressing LTBP2 promoted the tube formation of human umbilical vein endothelial cells (HUVECs), thus indicating an angiogenic effect. Furthermore, overexpression of LTBP2 facilitated the inflammation and might promote endometriosis progression through the NF- k B signaling pathway . Conclusively, LTBP2 might be a potential target in the diagnosis and treatment of endometriosis.
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ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Min Tang,Daixiu Yuan,Peng Liao
The aim of this study was to evaluate the effect of berberine (BBR) on the intestinal health of piglets exposed to deoxynivalenol (DON). A total of 180 weaned piglets were randomly allotted to 1 of 3 treatment groups with 10 replication pens per treatment and 6 piglets per pen. The treatments were basal diet, basal diet +4 mg/kg DON, and basal diet +4 mg/kg DON +40 mg/kg BBR. The experiment lasted for 21 d. BBR improved the growth performance of DON-challenged piglets. BBR could inhibit DON-induced intestinal injury by increasing the expression of serum antioxidant enzymes and T cell surface antigens and reducing the release of proinflammatory cytokines in the small intestine. BBR significantly increased the protein expression levels of zonula occludens 1 (ZO-1), Occludin and Claudin-1 in the ileal and jejunal mucosa and increased the morphological parameters of the jejunum. Moreover, we found that BBR significantly reduced the DON-induced gene and protein expression levels of ERK, JNK, and NF- κ B in the jejunum and ileum. In conclusion, BBR can regulate DON-induced intestinal injury, immunosuppression and oxidative stress by regulating the NF- κ B and MAPK signaling pathways and ultimately maintain the intestinal health of piglets.
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高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4815
·
IF 3.267
Minmin Sun,Yaoting Ji,Zhen Li,Rourong Chen,Shuhui Zhou,Chang Liu,Minquan Du
Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 onPorphyromonas gingivalisLPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 amelioratedPorphyromonas gingivalisLPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.Keywords:anti-inflammatory agents;chronic periodontitis;ginsenoside;lipopolysaccharides
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DRUG DEVELOPMENT RESEARCH
·
2020
·Vol. 82
·期 3
·404-411
·
IF 1.902
Xiaolong Sun,Xu Wang,Zhenyu Zhao,Jing Chen,Cheng Li,Gang Zhao
Diabetic foot ulcer (DFU) is an invariably common complication of diabetes, characterized by delayed wound healing process and increased inflammation. Evidence has indicated that paeoniflorin exerts an anti-inflammatory effect in diabetic retinopathy. The current work was aimed to investigate the effect of paeoniflorin on inflammation and wound healing in DFU. DFU rat models by streptozotocin and skin biopsy punch, as well as high glucose-treated human immortalized keratinocytes (HaCaT) were established. Levels of blood glucose, wound contraction and proinflammatory cytokine were detected after paeoniflorin administration. Several essential targets associated with the NF-κB and Nod-like receptor protein-3 (NLRP3) signaling pathways were examined. Results showed markedly down-regulation of interleukin (IL)-1β, IL-18 and tumor necrosis factor-alpha in paeoniflorin-treated DFU rats. Paeoniflorin decreased the expression levels of chemokine receptor CXCR2, nuclear NF-κB and p-IκB (Ser36), as well as increased IκB level. Histological analysis and immunostaining showed lower inflammatory cells with decreased NLRP3 and cleaved caspase-1 levels following paeoniflorin treatment. Further in vitro evidence confirmed that paeoniflorin efficiently inhibited NLRP3 and NF-κB-mediated inflammation in DFU by inhibiting CXCR2. These findings are suggestive of greatly attenuated wound inflammation and better wound healing in paeoniflorin-treated DFU rats. Our study demonstrates that paeoniflorin is a potential therapeutic agent for DFU.
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PHARMACEUTICAL BIOLOGY
·
2020
·
IF 2.971
Xiaoman Zhang,Jie Feng,Shaofeng Su,Lei Huang
Context Camellia nitidissima Chi (Theaceae) is an evergreen shrub, the leaves of which are used in many medicinal applications.Objective To characterize the chemical composition of a 10% aqueous ethanol extract of C. nitidissima leaves (CNE), and to explore the protective effect of the extract against acute liver injury (ALI) in rats.Materials and methods Male Sprague-Dawley rats were divided into six groups (n = 10): control and negative (0.5% CMC-Na, 5 mL/kg/d), thiopronin (20 mg/kg/d) and CNE (40, 80 and 160 mg/kg/d). All groups were treated for seven consecutive days, and then, except for the control, carbon tetrachloride was administered intraperitoneally. The biochemical parameters, mRNAs, and proteins were analyzed using enzyme-linked immunoassays kits, quantitative polymerase chain reaction and western blot. Chemical components were identified using mass spectroscopy, and the phenol and flavonoid content determined by ultraviolet spectrophotometry.Results Pre-treatment with CNE (160 mg/kg) attenuated the pathological changes in liver tissues and decreased alanine transaminase (62 and 60%), aspartate transaminase (49 and 53%) and malondialdehyde (35 and 42%) levels in serum and liver tissues. Moreover, CNE reduced the concentrations of reactive oxygen species (55%), tumour necrosis factor-α (26%), interleukin-1β (19%) and IL-6 (19%) and blocked the nuclear translocation of p65. Pre-treatment with CNE increased anti-heme oxygenase-1 (40%), superoxide dismutase (108%) and glutathione (97%) levels through upregulating nuclear factor erythroid-2-related factor 2. Twelve compounds were detected; the content of phenols and flavonoids was determined as 34.474 ± 1.026 and 15.228 ± 0.422 mg/g crude drug in CNE, respectively.Discussion and conclusions These results suggested that CNE is a promising agent for functional food and hepatoprotective drug against ALI.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Yaojian Rao,Junjie Li,Ruofei Qiao,Jinxin Luo,Yan Liu
Background Both Tetramethylpyrazine (TMPZ) and Astragaloside IV (AGS-IV) can ameliorate neuronal apoptosis and neuroinflammation in CNS diseases. This study revolves around the underlying mechanism of TMPZ and AGS-IV in spinal cord injury (SCI)-associated neuropathic pain (NP). Materials and methods An in-vivo NP model was constructed in Sprague-Dawley (SD) rats via SCI. qRT-PCR was employed to detect OIP5-AS1 and miR-34a. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of the rats were evaluated. Neuronal apoptosis in the spinal cord of rats was examined by Nissl staining and TUNEL staining. The interactions between OIP5-AS1 and miR-34a as well as miR-34a and Sirt1 were investigated through dual luciferase assay and RIP assay. The protein expressions of Bad, Bax, Caspase-3, iNOS, COX2, NF-κB, and Sirt1 were examined by western blot. Results TMPZ and AGS-IV combination relieved behavioral symptoms of neuropathic pain in the SCI rat model, enhanced the levels of OIP5-AS1 and Sirt1, and lowered the profile of miR-34a. OIP5-AS1 downregulation weakened the neuroprotective function of TMPZ and AGS-IV in SCI rats and reversed their anti-inflammatory and anti-apoptotic effects on LPS-elicited primary spinal cord neurons. miR-34a was identified as a target of OIP5-AS1. Upregulated miR-34a partly abated the protective functions of TMPZ and AGS-IV in primary spinal cord neurons. Additionally, miR-34a targeted and repressed Sirt1, thus activating the NF-κB pathway and inflammatory reactions. Sirt1 inhibition reduced the protective effects mediated by OIP5-AS1. Conclusion TMPZ and AGS-IV ameliorate SCI-elicited NP via the OIP5-AS1/miR-34a/Sirt1/NF-κB pathway.
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JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Rongjia Xu,Jiajia Zhang,Xingge Hu,Penghao Xu,Shiqi Huang,Shiyan Cui,Yuxin Guo,Hongtao Yang,Xiangmei Chen,Chen Jiang
Ethnopharmacological relevance Controversy persists regarding the treatment of immunoglobulin A nephropathy (IgAN), thereby highlighting the demand for safer more effective therapeutic drugs. Although supplementary treatment using Yi-Shen-Hua-Shi (YSHS) granules has distinct advantages with respect to improving renal function in IgAN, a lack of clarity regarding the underlying mechanisms limits their clinical application. Aim of the study In this study, we aimed to elucidate the therapeutic mechanisms underlying the efficacy of YSHS granules in the treatment of IgAN. Materials and methods A rat model of IgAN was established based on lipopolysaccharide, carbon tetrachloride, and bovine serum albumin induction. In order to evaluate the effects of YSHS granules, we performed a range of techniques, including immunofluorescence assays, hematoxylin and eosin staining, and flow cytometry, to assess inflammation, immunity, and other relevant factors. Direct data-independent acquisition–mass spectrometry (DIA-MS) analysis and parallel reaction monitoring (PRM) were used for functional characterization and quantitative validation of differentially expressed proteins (DEPs), and Western blot analysis is used to identify downstream proteins associated with DEPs. Results Compared with the model group, the levels of proteinuria, urine red blood cells, serum creatinine, blood urea nitrogen, low-density lipoprotein-cholesterol, triglycerides, and pathological kidney damage were reduced in the YSHS group. A high dose of YSHS granules was found to raise the levels of CD8 T cells and reduce the CD4/CD8 ratio in the peripheral serum. To examine the mechanisms underlying the therapeutic effects YSHS granules, we performed direct DIA-MS analysis to identify proteins that were differentially expressed among the model, YSHS, and control groups. A total of 29 proteins were identified as being commonly expressed in all three groups. Further KEGG and protein–protein interaction (PPI) network analysis revealed that YSHS granules can contribute to the regulation of N -glycosylation-associated proteins, such as ALG3 and STT3A, in rats with IgAN. Detected changes in the expression of ALG3 and STT3A were consistent with the PRM results. We also established that the administration of YSHS granules can contribute to regulation of the ALG3-associated PPAR-γ/NF-κB signaling pathway. Conclusions Our findings in this study provide evidence to indicate the efficacy of YSHS granules in the treatment of IgAN, the putative underlying mechanisms of which involve the modulation of N-glycosylation, mediated via the PPAR-γ/NF-κB pathway.
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International Journal of Biological Sciences
·
2023
·Vol. 19
·期 12
·3678-3693
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IF 9.2
Cao Mingbo,Ren Yupeng,Li Yuxuan,Deng Junfeng,Su Xiaorui,Tang Yongchang,Yuan Feng,Deng Haixia,Yang Gaoyuan,He Zhiwei,Liu Bo,Yao Zhicheng,Deng Meihai
Long non-coding RNAs have been reported to play a crucial role in tumor progression in hepatocellular carcinoma (HCC). Lnc-ZEB2-19 has been validated to be deficiently expressed in HCC. However, the capabilities and underlying mechanisms of lnc-ZEB2-19 remain uncertain. In this study, we verified that the downregulation of lnc-ZEB2-19 was prevalent in HCC and significantly correlated with the unfavorable prognosis. Further in vitro and in vivo verified that lnc-ZEB2-19 notably inhibited the proliferation, metastasis, stemness, and lenvatinib resistance (LR) of HCC cells. Mechanistically, lnc-ZEB2-19 inhibited HCC progression and LR by specifically binding to transformer 2α (TRA2A) and promoting its degradation, which resulted in the instability of RSPH14 mRNA, leading to the downregulation of Rela(p65) and p-Rela(p-p65). Furthermore, rescue assays showed that silencing RSPH14 partially restrained the effect of knockdown expression of lnc-ZEB2-19 on HCC cell metastatic ability and stemness. The findings describe a novel regulatory axis, lnc-ZEB2-19/TRA2A/RSPH14, downregulating the nuclear factor kappa B to inhibit HCC progression and LR.
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BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-11
·
IF 3.9
Yi Zhirong,Jia Qingling,Wang Yujiao,Zhang Yuqin,Xie Tianyi,Ling Jianghong
Background Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.Methods The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue.Results Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC.Conclusion sThe results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.
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JOURNAL OF MEMBRANE SCIENCE
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2023
·
IF 9.5
Haojie Zeng,Feiyun Sun,Jianjun Zhang,Ying Wang,Songwen Yang,Dingyu Xing
Polyvinyl alcohol (PVA) has been employed and crosslinked as the selective layer of NF membranes with enhanced hydrophilicity. However, the influences of different crosslinking methods and agents on the reaction mechanism and membrane performance still need to be comprehensively studied. In this study, NF membranes were prepared by coating crosslinking (CC-membrane) and gradient crosslinking (GC-membrane) methods. Compared with CC-membrane, the GC-membrane possessed a 65% higher flux with Na 2 SO 4 rejection around 90%, under the optimal preparation conditions with PVA content of 0.10%, curing at 80 °C for 10 min. Crosslinking agents including 1,3,5-benzenetricarboxylic acid (TMA), 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and pyromellitic dianhydride (PMDA) with different spatial structure were used to optimize the GC-membrane. As confirmed by SEM, XPS, FTIR and contact angle tests, the 6FDA-GC membrane showed a thinner, smoother and more hydrophilic selective layer, and kept an excellent balance between the water flux (88.6 L/m 2 h) and Na 2 SO 4 rejection (88.7%). This is because the 6FDA with a large molecule and flexible spatial structure could form a more integrated crosslinking structure compared to PMDA. Meanwhile, the 6FDA-GC membrane showed rejections of over 80% towards the endocrine-disrupting compound 17α-Ethinylestradiol and exhibited stable antifouling ability and durability. Overall, this work studied systematically the influences of various crosslinking agents on the GC-membrane, and verified the potential of hydrophilic PVA membranes for nanofiltration.
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DESALINATION
·
2023
·
IF 9.9
Qingyi Wang,Yongping Dong,Junmei Ma,Huimin Wang,Xuping Xue,Chaojie Bai,Mingjie Lin,Lingping Luo,Congjie Gao,Lixin Xue
Polyamide/polyethylene thin film composite (PA/PE-TFC) NF membranes were prepared from reverse-phase interface polymerization (RIP) for improved Mg(II)/Li(I) separation. RIP processes between 1,3,5-benzenetricarbonyl chloride (TMC) in bottom organic phase and piperazine (PIP) in upper aqueous phase were developed to form continuous and intact surface PA separation layers on PE porous substrates thinner than traditional polysulfone (PSF) based substrates. After activation with isopropyl alcohol (IPA), PA/PE-TFC-IPA NF membranes were formed, whose NF performance could be tuned by adjusting the preparation conditions. When TMC concentration was kept at 0.15 % w/v, RIP with low PIP concentration (0.025 wt%) yield PA/PE-TFC-IPA NF membranes with negatively charged surfaces , high Na 2 SO 4 rejection rate (95 % ± 3 %) and water permeance (13–19 L·m −2 ·h −1 ·bar −1 ). RIP with high PIP concentration (0.3 wt%) formed PA/PE-TFC-IPA NF membranes with less negative surfaces, high MgCl 2 rejection rate (94.3 ± 0.7 %), low water permeance (4.8 ± 0.3 L·m −2 ·h −1 ·bar −1 ), and high Mg(II)/Li(I) separation coefficient S Li/Mg (18 ± 1) for 1000 ppm LiCl and MgCl 2 mixed solution. PA/PE-TFC-IPA NF membranes also showed good long-term stability and improved anti-fouling performance for positively charged pollutants, bearing high potential for applications in the lithium extraction processes.
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JOURNAL OF INVESTIGATIVE DERMATOLOGY
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2023
·
IF 6.5
Qinqin Meng,Mei Bai,Meiliang Guo,Zhengxiao Li,Wanwen Liu,Xiaojing Fan,Rui Sun,Xinrong Yang,Dingfen Yuan,Yuling Shi,Hui Deng
Although the anti-inflammatory effect of serum- and glucocorticoid-regulated protein kinase 1 (SGK1) has been established in other diseases, the possible regulatory role of SGK1 in psoriasis and the underlying molecular mechanisms remain largely unknown. In this study, we found that SGK1 expression was decreased in macrophages from patients with psoriasis. Moreover, a specific pharmacological SGK1 inhibitor, EMD638683, significantly enhanced imiquimod-mediated toll-like receptor 7/8 activity and proinflammatory cytokine production in RAW264.7 cells, and this result was confirmed by Sgk1 small interfering RNA . Further mechanistic data showed that SGK1 inhibition increased the phosphorylation of Bruton’s agammaglobulinemia tyrosine kinase ; moreover, Bruton’s agammaglobulinemia tyrosine kinase inhibition abrogated the proinflammatory effects of the SGK1 inhibitor on toll-like receptor 7/8 activation, thereby validating that SGK1 inhibition enhances the toll-like receptor 7/8 pathway by increasing Bruton’s agammaglobulinemia tyrosine kinase phosphorylation. In addition, our in vivo results showed that SGK1 inhibition significantly increased the secretion of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the infiltration of T helper 17 cells in an imiquimod-induced psoriasis mouse model. Altogether, these results show that SGK1 plays a critical role in the pathogenesis of psoriasis by modulating inflammatory responses in skin lesions , indicating that SGK1‒Bruton’s agammaglobulinemia tyrosine kinase signaling could be a novel therapeutic target for the control of psoriasis.
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