BACKGROUND:Ischemic stroke (IS), the predominant clinical stroke subtype, is increasingly linked to dysregulation of the gut-brain axis (GBA)-a bidirectional neuroendocrine-immune interface connecting intestinal homeostasis with cerebrovascular pathophysiology. Xinqingning Tablet (XQNT) demonstrates neuroprotective potential in IS complicated by gut dysbiosis (GD), yet its mechanisms of GBA modulation remain unclear. METHODS:A dual-hit IS-GD mouse model was established via fecal slurry transplantation and permanent middle cerebral artery occlusion (pMCAO) surgery. Gut function was evaluated by constipation indices and histopathological changes, while the neuroprotective efficacy of XQNT (0.36, 0.48, and 0.61 g kg⁻¹) was assessed via TTC staining, neurological deficit scores, cerebral water content, and Evans blue (EB) extravasation assays. Additionally, Western blot was employed to quantify blood-brain barrier (BBB) and inflammation-associated proteins. microRNA sequencing was used to screen the differentially expressed miRNAs. miR-126 expression levels were measured by RT-qPCR, while concentrations of LPS, IL-6 and IL-10 were determined by ELISA. Finally, mechanistic validation employed intravenous miR-126 agonism/antagonism coupled with phenotypic rescue experiments. RESULTS:XQNT conferred robust survival benefits, while concurrently ameliorating intestinal dysfunction and neurovascular injury. Mechanistically, XQNT elevated miR-126 expression, suppressing NF-κB-driven neuroinflammation. Additionally, miR-126 agonism phenocopied XQNT efficacy, whereas miR-126 inhibition abrogated therapeutic benefits. CONCLUSIONS:This study provides early evidence that XQNT functions as a dual-target GBA modulator that alleviates IS with GD via regulation of the miR-126/NF-κB axis. By simultaneously promoting barrier restoration and inflammatory resolution, XQNT offers a promising therapeutic approach that links regulation of the gastrointestinal system with cerebrovascular protection.

Long-stranded noncoding RNAs (lncRNAs) are a group of RNAs that are longer than 200 nucleotides and without protein-coding ability. Current researches indicated that the dysregulated expression of lncRNAs not only impaired normal cell growth and development, but also interfered with the cell cycle and cellular metabolism, thereby causing the development of various diseases. LncRNA ADAMTS9-AS1 is an antisense lncRNA produced by reversing transcription of ADAMTS9-AS1. LncRNA ADAMTS9-AS1 is closely related to different types of diseases. In addition to its own aberrant expression, it could also act as a miRNA sponge and competitively bind to miRNAs to participate in the process of disease occurrence through complex pathways and interactions with other genes and proteins. Therefore, this paper reviews the specific mechanism of lncRNA ADAMTS9-AS1 in different diseases, which promises to be a new biomarker and therapeutic target for a variety of diseases.

This study aims to investigate the anti-arthritis effects and mechanisms of total triterpenoids from the fruits of Chaenomeles speciosa(TCS) on MH7A cells treated with lipopolysaccharide(LPS) and adenosine triphosphate(ATP) as well as the rat model of adjuvant arthritis(AA) induced by Freund's complete adjuvant(CFA). In the cell experiment, the MTT assay and Transwell assay were employed to test cell viability and migration, respectively; the colorimetric method and ELISA were employed to determine the levels of lactate dehydrogenase(LDH), cyclooxygenase(COX)-1, COX-2, interleukin(IL)-4, IL-1β, IL-6, IL-10, IL-18, prostaglandin E2(PGE2), and tumor necrosis factor-α(TNF-α) in the cell supernatant; immunofluorescence was utilized to detect the co-localization of NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a CARD(ASC), and cysteinyl aspartate-specific proteinase-1(caspase-1). In the animal experiment, the degree of paw swelling and arthritis index in AA rats were tested; hematoxylin-eosin staining was used to observe the morphological changes in the ankle joint tissue, and the joint histological score was calculated; the colorimetric method and ELISA were utilized to assess the levels of LDH, COX-1, COX-2, IL-4, IL-1β, IL-6, IL-10, IL-18, PGE2, and TNF-α in the synovial tissue of ankle joints in AA rats. Real-time PCR was used to determine the mRNA levels of ASC, caspase-1, COX-1, COX-2, myeloid differentiation factor 88(MyD88), NLRP3, PGE2, and Toll-like receptor 4(TLR4) in MH7A cells and ankle synovial tissue. Western blot was utilized to assess the protein expression levels of ASC, caspase-1, cytosolic NF-κB p65, MyD88, NLRP3, nuclear NF-κB p65, pro-caspase-1, pro-IL-18, pro-IL-1β and TLR4 in MH7A cells and ankle synovial tissues. The results manifested that TCS prominently depressed LPS-and ATP-induced migration of MH7A cells, reduced paw swelling degree and joint index in AA rats, alleviated synovial edema and inflammatory cell infiltration, lessened bone erosion, cartilage destruction, and vascular opacity formation, and lowered joint histological scores of joint inflammation, vascular opacities, and cartilage and bone injury. Moreover, TCS prominently reduced the levels of COX-2, IL-6, IL-18, IL-1β, LDH, PGE2, and TNF-α while heightening the levels of COX-1, IL-4, and IL-10 in the supernatant of MH7A cells and the synovial tissue. It dramatically down-regulated the mRNA levels of ASC, caspase-1, COX-2, MyD88, NLRP3, PGE2, and TLR4, as well as the protein levels of ASC, caspase-1, MyD88, NLRP3, nuclear NF-κB p65, pro-caspase-1, pro-IL-18, pro-IL-1β, and TLR4 in the MH7A cells treated with LPS and ATP and the ankle synovial tissue of AA rats, restrained co-localization of NLRP3, ASC, and caspase-1 in the MH7A cells treated with LPS and ATP, and up-regulated the mRNA level of COX-1 and the protein level of cytosolic NF-κB p65 in the MH7A cells treated with LPS and ATP and the ankle synovial tissue of AA rats. These aforementioned results manifest that TCS has a good anti-rheumatoid arthritis effect on MH7A cells treated with LPS and ATP and the rat model of CFA-induced AA by repressing TLR4/NF-κB/NLRP3 pathway activation and reducing inflammatory responses.

Fetal growth restriction (FGR), a common obstetric complication, significantly increases the risks of fetal intrauterine death and neonatal death, and fetuses with growth restriction are prone to cognitive retardation and various diseases in adulthood. The early determination of FGR risk is contentious in clinical research, and few indicators are available for the early prediction and diagnosis of FGR. This review focuses on the prediction and diagnosis of FGR, as well as the significance of biomarkers for FGR, such as those related to gene regulation, apoptosis, mitochondrial function, and inflammation. Although many of these biomarkers are still in the early stages of research, they are good predictors of the threats to fetal health and safety, and they provide new insights for the treatment of FGR.

Total triterpenoids from the fruits of Chaenomeles speciosa(TCS) are active components in the prevention and treatment of gastric mucosal damage, which have potential anti-aging effects. However, it is still unclear whether TCS can improve gastric aging, especially its molecular mechanism against gastric aging. On this basis, this study explored the effect and mechanism of TCS on senescent GES-1 cells induced by D-galactose(D-gal) to provide scientific data for the clinical use of TCS to prevent gastric aging. GES-1 cells cultured in vitro and those transfected with overexpression GLS1(GLS1-OE) plasmid of glutaminase 1(GLS1) were induced to aging by D-gal, and then TCS and or GLS1 inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide(BPTES) were given. Cell survival rate, positive rate of β-galactosidase(SA-β-gal) staining, mitochondrial membrane potential(MMP), and apoptosis were investigated. GLS1 activity, levels of glutamine(Gln), glutamate(Glu), α-ketoglutarate(α-KG), urea, and ammonia in supernatant and cells were detected by enzyme-linked immunosorbent assay(ELISA) and colorimetric methods. The mRNA and protein expressions of GLS1 and the related genes of the mitochondrial apoptosis signaling pathway were measured by real-time fluorescence quantitative PCR and Western blot. The results manifested that compared with the D-gal model group and GLS1-OE D-gal model group, TCS significantly decreased the SA-β-gal staining positive cell rate and MMP of D-gal-induced senescent GES-1 cells and GLS1-OE senescent GES-1 cells, inhibited the survival of senescent cells, and promoted their apoptosis(P<0.01). It decreased the activity of GLS1 and the content of Gln, Glu, α-KG, urea, and ammonia in supernatant and cell(P<0.01), reduced the concentration of cytochrome C(Cyto C) in mitochondria and the mRNA and protein expressions of GLS1 and proliferating nuclear antigen in cells(P<0.01). The mRNA expression of Bcl-2 and Bcl-xl, the protein expression of pro-caspase-9 and pro-caspase-3, and the ratio of Bcl-2/Bax and Bcl-xl/Bad in cells were decreased(P<0.01). Cyto C concentration in the cytoplasm, the mRNA expressions of Bax, Bad, apoptosis protease activating factor 1(Apaf-1), and protein expressions of cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 were increased(P<0.01). The aforementioned results indicate that TCS can counteract the senescent GES-1 cells induced by D-gal, and its mechanism may be closely related to suppressing the Gln/GLS1/α-KG metabolic axis, activating the mitochondrial apoptosis pathway, and thereby accelerating the apoptosis of the senescent cells and eliminating senescent cells.

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1β, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) is a single species of Cyclocarya paliurus in Juglandaceae. It is a unique rare medicinal plant resource in China that is mainly distributed in the south of China. The leaves of C. paliurus, as a new food ingredient, are processed into tea products in daily life. Triterpenoids are the main active ingredient in C. paliurus. So far, 164 triterpenoid compounds have been isolated and identified from C. paliurus, which are included 3,4-seco-dammaranes, dammaranes, oleanane, ursane, lupinanes, taraxeranes, and norceanothanes. Modern pharmacological studies manifested that these ingredients have a wide range of pharmacological activities both in vitro and in vivo, such as reducing blood sugar, lowering blood lipids, and anti-tumor, anti-inflammatory, anti-oxidant, and other activities. In addition, current results indicate that the pharmacological mechanisms of triterpenoids were closely related to their chemical structure, molecular signaling pathways, and the expression of related proteins. In order to further study C. paliurus based on the current research situation, this review summarizes the prospect and systematic summary of the triterpenes of C. paliurus from the aspects of structural characteristics, quality control, biological activity, and the structure-activity relationship, which provide a reference for further research and application of the triterpenoids from C. paliurus in the field of functional food and medicine.

CONTEXT:Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE:To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS:TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS:TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS:TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.

Polylactic-co-glycolic acid（PLGA） has the characteristics of biocompatibility, biodegradability, modifiability, and slow release, which has attracted extensive attention in the treatment of gynecological diseases. This paper summarizes the relevant literature reports at home and abroad in recent years, expounds the research situation of PLGA nanoparticles as drug carriers in gynecological diseases such as ovarian cancer, breast cancer,cervical cancer and endometriosis, and looks forward to its great potential in clinical application in gynecological diseases, providing guidance for its prevention and treatment in gynecological diseases.

An understanding of the transport of silica nanoparticles (NPs) across the placental barrier is important in perinatal medicine. The cytotoxicity of silica NPs was investigated in this study. In uptake assays, we examined the size of NPs, as well as the effects of various inhibitors, on the internalization of silica NPs in BeWo b30 cells. The levels of PI3K, AKT, and GSK3β were assessed after the cells were treated with silica NPs and/or the PI3K/AKT signaling pathway inhibitor LY294002. The integrity of the cell monolayer was assessed by culturing cells on Transwell inserts and measuring the transepithelial electrical resistance, assessing fluorescein sodium transport, and staining the tight junction protein zonula occludens-1. Silica NPs were spherical in shape, and concentrations <300 μg/mL were not cytotoxic. The internalization of silica NPs with a diameter of 50 nm was greater than that of silica NPs with a diameter of 20 nm. CPZ showed the most pronounced inhibitory effects, with inhibition rates of 20-nm, 50-nm, and 100-nm silica NPs reaching 57.5%, 49.6%, and 46.9%, respectively, indicating that silica NPs were internalized through clathrin- and caveolae-mediated endocytosis. Furthermore, LY294002 affected the uptake of 50-nm silica NPs dose-dependently. The treatment of cells with silica NPs also increased the levels of P-PI3K/PI3K, P-AKT/AKT, and P-GSK3β/GSK3β, while LY294002 inhibited the levels of these proteins, indicating that the internalization of silica NPs is regulated by the PI3K/AKT/GSK3β signaling pathway. Taken collectively, these results provide new insights on the transplacental transport of NPs in perinatal medicine.

An understanding of the transport of silica nanoparticles (NPs) across the placental barrier is important in perinatal medicine. The cytotoxicity of silica NPs was investigated in this study. In uptake assays, we examined the size of NPs, as well as the effects of various inhibitors, on the internalization of silica NPs in BeWo b30 cells. The levels of PI3K, AKT, and GSK3β were assessed after the cells were treated with silica NPs and/or the PI3K/AKT signaling pathway inhibitor LY294002. The integrity of the cell monolayer was assessed by culturing cells on Transwell inserts and measuring the transepithelial electrical resistance, assessing fluorescein sodium transport, and staining the tight junction protein zonula occludens-1. Silica NPs were spherical in shape, and concentrations <300 μg/mL were not cytotoxic. The internalization of silica NPs with a diameter of 50 nm was greater than that of silica NPs with a diameter of 20 nm. CPZ showed the most pronounced inhibitory effects, with inhibition rates of 20-nm, 50-nm, and 100-nm silica NPs reaching 57.5%, 49.6%, and 46.9%, respectively, indicating that silica NPs were internalized through clathrinand caveolae-mediated endocytosis. Furthermore, LY294002 affected the uptake of 50-nm silica NPs dose-dependently. The treatment of cells with silica NPs

Abstract Our previous study demonstrated that pentacyclic triterpenoids from the fruits of Chaenomeles speciosa had prominent treatment functions on gastric damage patients and animals. However, little has been known about the pharmacological activity and mechanism of its each triterpene component (oleanolic acid, maslinic acid, betulinic acid, ursolic acid, 3-O-acetyl ursolic acid, 3-O-acetyl pomolic acid, tormentic acid (TA)). In current study, we found that TA possessed stronger cell protective effect and promoted proliferation activity on IND-damaged GES-1 cells than other triterpenoids from the fruits of Chaenomeles speciose by bioscreening. Therefore, we selected TA for further research. The results demonstrated that TA might ameliorate the gastric mucosal injury induced by IND, which was associated with accelerating the damaged GES-1 cell proliferation and migration, meliorating the injured rat GBF, ulcer inhibitor, ulcer area and pathologic changes of gastric mucous tissue, reducing the total acidity and volume of the gastric effluents, and raising the gastric pH; Further empirical research indicated that TA dramatically suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expressions, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expressions. these data demonstrated that TA avoided gastric mucosal injury by suppressing miR-139 expression and activating the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway, thereby boosting the epithelial cell proliferation and migration, and promoting the gastric damaged healing.

目的 评价七芪地黄丸对糖尿病肾病（DN）大鼠肾损伤的保护作用，并探讨其可能作用机制。方法 建立高脂饲料联合链脲佐菌素（STZ）诱导的DN大鼠模型，将DN模型制作成功大鼠随机分为模型组、厄贝沙坦组（39 mg/kg）和七芪地黄丸（生药9.36 g/kg）组，另取健康大鼠作为正常组，每组10只；治疗组各组大鼠分别给予相应的药物，每天1次。灌胃4周后，测量尿液中尿糖、尿微量白蛋白（mAlb）、Cr、硒结合蛋白（SBP-1）、M2型丙酮酸激酶（PKM2）、肾损伤分子（KIM-1）、中性粒细胞明胶相关脂蛋白（NGAL）含量，血液中Glu、TC、TG、LDL-C、HDL-C、BUN、SCr、TNF-α、IL-1β、IL-6、TGF-β1、IL-4、IL-10含量和肾组织中晚期糖基化终未产物（AGEs）、活性氧（ROS）、8-羟基酸脱氧写苷（8-OHdG）、羟脯氨酸（HYP）、丙二醛（MDA）含量及还原型谷光苷肽（GSH）、氧化型型谷光苷肽（GSSG）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性，检测尿液、血液和肾组织中的3-硫酸吲哚酚（3-IS）含量，取肾脏进行肾脏组织形态学分析，Real-time PCR检测肾组织中TNF-α、IL-1β、IL-6、TGF-β1、IL-4、IL-10、E-cadherin、Samd6、骨形成蛋白7（BMP7）、α-微管蛋白（α-tubulin）、波形蛋白（Vimentin）、纤维链接蛋白（Fibronectin）、胶原-1（Collagen-1）、α-平滑肌肌动蛋白（α-SMA）、SIRT1、SIRT3、SIRT4、紧密连接蛋白1（Claudin-1） mRNA表达，Western Blot检测肾组织中E-cadherin、Samd6、BMP7、TGF-β1、α-tubulin、Vimentin、Fibronectin、Collagen-1、α-SMA、SIRT1、SIRT3、SIRT4、Claudin-1蛋白表达。结果 与治疗前比较，七芪地黄丸及厄贝沙坦治疗1、2、3、4周空腹血糖降低，治疗2、3、4周时体重升高（P＜0.05,P＜0.01）。与模型组比较，七芪地黄丸治疗1周，七芪地黄丸及厄贝沙坦治疗2、3、4周时空腹血糖降低而体重增加，且治疗2、3、4周时与厄贝沙坦组比较，七芪地黄丸组空腹血糖降低，体重升高（P＜0.05,P＜0.01）。七芪地黄丸可显著改善肾小管上皮细胞空泡样病变以及间质纤维化和炎性浸润。与正常组比较，模型组大鼠血液中TG、TC、LDL-C、BUN、SCr、IL-1β、IL-6、TNF-α、TGF-β1以及尿液中mAlb、Cr、尿糖、SBP-1、PKM2、KIM-1、NGAL含量升高，血液、肾组织中3-IS含量明显增加，肾组织中IL-1β、IL-6、TNF-α、TGF-β1 mRNA表达明显升高，IL-4、IL-10含量和m RNA表达、血HDL-C、尿液中3-IS含量降低（P＜0.01）；肾组织中AGEs、ROS、8-OHdG、MDA含量和GSSG活性明显增加，Claudin-1 mRNA和蛋白表达升高（P＜0.01），血GSH、CAT、SOD活性、SIRT1、SIRT3、SIRT4 mRNA和蛋白表达降低（P＜0.01）；与模型组比较，七芪地黄丸及厄贝沙坦均可改善上述指标，且七芪地黄丸组改善效果优于厄贝沙坦组（P＜0.05,P＜0.01）。结论七芪地黄丸可显著降低STZ诱导的DN大鼠Glu、AGEs、炎性细胞因子、氧化应激和肾功能生物标志物，增强内源性抗氧化系统功能，改善肾组织病理学损伤，进而发挥对STZ诱导的DN保护作用。

目的 探索委陵菜酸对幽门螺杆菌(Helicobacter pylori,Hp)诱导人胃黏膜上皮细胞GES-1损伤的影响.方法 GES-1细胞与Hp共培养,给予委陵菜酸和NOD样受体家族3(NOD-like receptor family 3,NLRP3)抑制剂MCC950,考察各组细胞存活率、乳酸脱氢酶(lactate dehydrogenase,LDH)释放率、集落形成、凋亡率、线粒体膜电位和活性氧自由基(reactive oxygen species,ROS)变化;采用ELISA法检测各组细胞上清液中单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)、角质细胞趋化因子(keratinocyte chemokines,KC)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-a)、白细胞介素-1β (interleukin-1β,IL-1β)、IL-6、IL-18、IL-4和IL-10水平;采用试剂盒检测各组细胞谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)活性和丙二醛(malondialdehyde,MDA)含量;采用qRT-PCR检测各组细胞Toll样受体4(toll-like receptor 4,TLR4)、髓样分化因子88(myeloid differentiation factor 88,MyD88)、Bcl-2、Bcl-xl、Bax和Bad mRNA表达情况;采用Western blotting法检测各组细胞TLR4/NLRP3/核因子-κB (nuclear factor-κB,NF-κB)和线粒体凋亡信号通路相关蛋白表达情况.结果 委陵菜酸显著抑制Hp诱导的GES-1细胞LDH释放率(P＜0.05、0.01),促进细胞集落形成(P＜0.05、0.01),抑制细胞凋亡(P＜0.05、0.01);升高细胞线粒体膜电位(P＜0.01),降低ROS水平(P＜0.01);降低上清液中MCP-1、KC、TNF-α、IL-1β、IL-6和IL-18水平(P＜0.01),升高IL-4和IL-10水平(P＜0.01);升高细胞GSH-Px、SOD和CAT活性(P＜0.01),降低MDA含量(P＜0.01);降低细胞TLR4、MyD88、Bax、Bad mRNA表达水平(P＜0.01),升高Bcl-2、Bcl-xl mRNA表达水平和Bcl-2/Bax、Bcl-xl/Bad (P＜0.01);下调细胞TLR4、MyD88、磷酸化IκB激酶β(phosphorylated inhibitor kappa B kinase β,p-IKKβ)、p-IκBα、NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein,ASC)、半胱氨酸蛋白酶-1前体(pro-Caspase-1)、Caspase-1、硫氧还蛋白互作蛋白(thioredoxin-interacting protein,TXNIP)、pro-IL-1β、pro-IL-18、Bax、Bad、细胞色素C、凋亡酶激活因子-1(apoptotic protease activating factor-1,Apaf-1)、剪切型Caspase-9(cleaved Caspase-9)、cleaved Caspase-3和胞核p65蛋白表达水平(P＜0.01),上调Bcl-2、Bcl-xl、pro-Caspase-9、pro-Caspase-3和胞质p65蛋白表达水平(P＜0.01).结论 委陵菜酸对Hp诱导的GES-1细胞损伤具有明显保护作用,其作用机制可能与增强内源性抗氧化系统功能、抑制氧化应激、炎性反应及TLR4/NF-κB/NLRP3炎症小体信号通路激活,从而减少线粒体介导的凋亡密切相关.

This study investigated the protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori(Hp)-induced gastritis in mice and explored its possible mechanism. The chronic atrophic gastritis(CAG) model mice were randomly divided into four groups of model, total triterpenoids from C. speciosa(50 and 100 mg·kg~(-1)) and triple therapy, with C57 BL/6 J mice without Hp infection taken as the normal group. Mice in the treatment groups were given corresponding drugs once a day for 4 weeks. Then the following indexes were detected: the contents of reactive oxygen species(ROS), monocyte chemotactic protein 1(MCP-1), keratinocyte chemokines(KC), TNF-α, IL-1β, IL-6, IL-18, IL-4 and IL-10 in blood and gastric tissue, the activities and contents of LDH, MPO, SOD, GSH-Px, CAT and MDA in gastric tissue and the activities of β-glucuronidase, β-galactosidase, cathepsins B and D in blood, gastric tissue and lysosome. Besides, the mRNA expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), Bcl-2, Bcl-xl, Bax and Bad in gastric tissue were determined by quantitative real-time PCR. Western blot was employed to detect the protein expression levels of TLR4, MyD88, p-IKKβ, p-IκBα, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein(ASC), pro-caspase-1, caspase-1, thioredoxin-interacting protein(TXNIP), pro-IL-1β, pro-IL-18, Bcl-2, Bcl-xl, Bax, Bad, cytochrome C, apoptotic protease-activating factor-1(Apaf-1), pro-caspase-9, pro-caspase-3, cleaved-caspase-9, cleaved-caspase-3, poly(ADP-ribose) polymerase 1(PARP-1), cleaved-PARP-1 and cytosol and nucleus NF-κB p65 in gastric tissue. The results indicated that the total triterpenoids from C. speciosa significantly suppressed Hp proliferation, alleviated the damage to gastric mucosa and improved lymphocyte infiltration and gland atrophy. They were also effective in reducing the activities of β-glucuronidase, β-galactosidase, cathepsins B and D in blood and gastric tissue, elevating the activities of β-glucuronidase and cathepsin D in lysosomal organelles, decreasing the contents of ROS, MCP-1, KC, TNF-α, IL-1β, IL-6, IL-18 in blood, MDA content and MPO and LDH activities in gastric tissue and increasing the contents of IL-4 and IL-10 in blood and activities of SOD, CAT and GSH-Px in gastric tissue. Other phenomena were also observed after the treatment with total triterpenoids from C. speciosa, including the down-regulation of the mRNA and protein expression levels of TLR4, MyD88, Bax and Bad, the protein expression levels of p-IKKβ, p-IκBα, NLRP3, ASC, pro-caspase-1, caspase-1, TXNIP, pro-IL-1β, pro-IL-18, cytochrome C, Apaf-1, cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 and nuclear NF-κB p65, reduction of p-IKKβ/IKKβ and p-IκBα/IκBα ratios and up-regulation of the mRNA and protein expression levels of Bcl-2 and Bcl-xl, up-regulation of pro-caspase-9, pro-caspace-3, cytosol NF-κB p65 protein expression levels and Bcl-2/Bax and Bcl-xl/Bad ratios in gastric tissue. These aforementioned results suggest that the total triterpenoids from C. speciosa have significant protective effects against CAG induced by Hp, and its mechanism may be related to enhancing the function of endogenous antioxidant system, suppressing the oxidative stress and inflammatory reaction induced by Hp, correcting lysosomal dysfunction and inflammatory activation of TLR4/NF-κB/NLRP3 inflammasome signaling pathway and thus inhibiting mitochondria-mediated apoptosis.

核因子-κB(NF-κB)是一种细胞内重要的转录因子,调控包括炎症、凋亡在内多种基因的表达,在胎盘中分布广泛.本文对胎盘组织中NF-κB与先兆子痫、HELLP综合征和胎膜早破等妊娠并发症的关系研究进行综述,概括了胎盘NF-κB在这些妊娠并发症发生过程中的作用以及依赖NF-κB途径治疗相关疾病的研究进展,为胎盘相关疾病的深入研究奠定基础,为妊娠并发症疾病的诊治提供新思路.

目的:观察腐乳毛霉醇提物不同极性部位抗氧化活性及对L-O2细胞保护作用.方法:分别将腐乳毛霉醇提物萃取后的石油醚、乙酸乙酯、正丁醇及水部位进行体外抗氧化活性和对CCl4致L-O2细胞损伤的保护实验.结果:腐乳毛霉醇提物均具有较强的抗氧化、清除DPPH和ABTS自由基及FRAP能力,对CCl4引起L-O2细胞的氧化损伤具有显著的保护作用,可降低细胞内ROS及培养液中MDA含量和LDH活性,升高SOD、GSH-Px和CAT活性,从而减轻CCl4对L-O2细胞氧化损伤,其作用效果由高到低依次是乙酸乙酯、正丁醇、水和石油醚部位.结论:腐乳毛霉醇提物不同极性部位对CCl4引起L-O2细胞的氧化损伤具有显著的保护作用,其作用机制可能与抗氧化作用有关.

目的:研究木瓜总三萜对非甾体抗炎药(NSAIDs)诱导小肠损伤模型大鼠内源性超氧化物歧化酶/谷胱甘肽过氧化物酶1/过氧化氢酶(SOD/GPX1/CAT)抗氧化系统、细胞外信号调节激酶/核因子2相关因子2/血红素氧合酶-1(ERK/Nrf2/HO-1)和线粒体凋亡信号通路的影响.方法:实验大鼠随机分为正常组、模型组、木瓜总三萜(25、50和100mg/kg)组和雷贝拉唑肠溶片100mg/kg组,各组大鼠灌胃给予相应的药物,每天1次,连续1周,末次给药后禁食,次日再次给药1次;1小时后,除正常组外,其余各组灌胃给予吲哚美辛45mg/kg 1次.24小时后取血,进行血液中SOD、GSH-Px、CAT和MPO、MDA水平检测;取小肠组织进行溃疡指数和组织形态学分析;实时定量PCR检测小肠组织中SOD1、SOD2、SOD3、GPX1、CAT、Bcl-2、Bax、Caspase-3、Caspase-9基因表达;Western blot检测小肠组织中ERK1/2、p-ERK1/2、胞浆Nrf2以、胞核Nrf2、Bcl-2和Bax蛋白表达.结果:木瓜总三萜(25、50和100mg/kg)可显著降低吲哚美辛诱导小肠黏膜损伤大鼠小肠溃疡指数、病理学评分,改善小肠黏膜溃疡、黏膜及黏膜下层肿胀和炎性浸润,显著升高血液中内源性抗氧化酶活性,显著上调受损小肠组织中SOD1、SOD2、SOD3、GPX1、CAT和p-ERK1/2、胞核Nrf2、HO-1、Bcl-2表达,显著下调Bax和Caspase-3、Caspase-9表达,且随着剂量的增加,其作用效果更明显.结论:木瓜总三萜对NSAIDs诱导大鼠小肠损伤具有较好的保护作用,调节内源性SOD/GPXl/CAT抗氧化系统功能及ERK/Nrf2/HO-1和线粒体凋亡信号通路可能是其作用机制之一.

目的:制备天麻保鲜剂,考察其对天麻内生菌的抑菌作用和对鲜天麻的保鲜效果.方法:采用蒸馏法和回流提取法制备天麻保鲜剂;划线法分离纯化天麻内生菌并进行鉴定;利用天麻保鲜剂测定其对天麻内生菌的抑菌圈直径、最低抑菌浓度(MIC)、最低杀菌浓度(MBC),测定其对鲜天麻保鲜室温保存1、3、6、12月后的腐烂率、腐烂指数、总可溶性固形物含量和硬度.结果:制备的天麻保鲜剂为橙黄色透明液体,其中的丁香酚、反式茴香脑、肉桂酸、大蒜素和挥发油的含量不得少于11.9％(M/V)、4.0％(M/V)、0.10％(M/V)、0.15％ (M/V)和2.5％(V/V);从鲜天麻中分离得到细菌、霉菌和酵母菌3株内生菌,天麻保鲜剂对这3种内生菌具有较好的抑制和杀灭作用,其对鲜天麻中的细菌、霉菌和酵母菌的MIC和MBC分别为6.25、3.125、1.563 mg生药/mL和12.5、6.250、3.125 mg生药/mL,其作用效果与抑菌圈直径一致;制备的天麻保鲜剂可降低鲜天麻室温保存的腐烂率和腐烂指数,抑制鲜天麻保存过程中总可溶性固形物含量和硬度的降低(P＜0.05或P＜0.01).结论:蒸馏法和回流提取法可成功制备天麻保鲜剂;天麻保鲜剂很好地解决了新鲜天麻储存问题,在鲜天麻保鲜上具有较大的应用前景.