Comparative efficacy analysis of laparoscopic-assisted transanal total mesorectal excision vs laparoscopic transanal mesorectal excision for low-lying rectal cancer

BACKGROUND With the continuous development of laparoscopic techniques in recent years,laparoscopic total mesorectal excision(LapTME)and laparoscopic-assisted transanal total mesorectal excision(TaTME)have gradually become important surgical techniques for treating low-lying rectal cancer(LRC).However,there is still controversy over the efficacy and safety of these two surgical modalities in LRC treatment.AIM To compare the efficacy of LapTME vs TaTME in patients with LRC.METHODS Ninety-four patients with LRC who visited and were treated at the Affiliated Hengyang Hospital of Hunan Normal University&Hengyang Central Hospital between December 2022 and March 2024 were selected and divided into the LapTME(n=44)and TaTME(n=50)groups.Clinical operation indexes,postoperative recovery indicators,and postoperative complications were recorded.The anal resting pressure(ARP),anal maximum systolic pressure(MSP),and maximum tolerated volume(MTV)of the anal canal were also measured.The intestinal function of patients was evaluated by the Memorial Sloan Kettering Cancer Center(MSKCC)bowel function questionnaire.Serum norepinephrine(NE),adrenaline(AD),and cortisol(Cor)levels were measured.The Quality of Life Questionnaire Core 30(QLQC30)was used for quality of life assessment.RESULTS Compared with the LapTME group,the surgery time in the TaTME group was longer;intraoperative blood loss was low;time of anal exhaust,first postoperative ambulation,intestinal recovery,and hospital stay were shorter;and the distal incisal margin and specimen lengths were longer.The TaTME group also showed higher ARP,MSP,and MTV values and higher MSKCC and QLQ-C30 scores than the LapTME group 3 months postoperatively.Cor,AD,and NE levels were lower in the TaTME group than those in the LapTME group during recovery.CONCLUSION We demonstrated that TaTME better improved anal function,reduced postoperative stress,and accelerated postoperative recovery and,hence,was safer for patients with LRC.

香青兰总黄酮调控TMAO介导的JAK/STAT轴抗大鼠动脉粥样硬化及RAW264.7细胞炎症的研究

目的探讨香青兰总黄酮(total flavonoids of Dracocephalum Moldavica L.,TFDM)抗大鼠动脉粥样硬化(atherosclerosis,AS)及三甲胺氮氧化物(trimethylamine N-oxide,TMAO)加剧的小鼠巨噬细胞RAW264.7炎症的保护作用及其可能的作用机制。方法采用高脂饲料喂养联合腹腔注射维生素D3的方法建立SD大鼠AS模型,分为对照组、模型组、辛伐他汀组(15 mg·kg^(-1))、TFDM组(60、30、15 mg·kg^(-1)),建模同时进行给药处理,持续8周。生化检测方法检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平。HE染色检测主动脉组织病理变化,ELISA试剂盒检测血清中TMAO、IL-1β、IL-6及肝脏组织中TNF-α的表达,Western blot法检测主动脉中JAK、STAT、TNF-α蛋白的表达。此外,体外培养RAW264.7巨噬细胞,采用LPS+TMAO建立巨噬细胞炎症模型,TFDM(100、50、25 mg·L^(-1))进行干预。CCK-8测定细胞活力及增殖,RT-qPCR法检测细胞中TNF-α、IL-6、JAK、STAT mRNA的表达。结果TFDM可明显下调大鼠血清TC、TG、LDL-C水平及血清TMAO、IL-1β、IL-6和肝脏TNF-α的水平,减少主动脉的斑块沉积,下调主动脉中TNF-α、JAK、STAT的蛋白表达。此外,TFDM干预可明显下调TNF-α、IL-6、JAK、STAT mRNA的表达及JAK、STAT蛋白的表达。结论TFDM可降低血清中TMAO的含量,从而抑制JAK/STAT炎症信号通路,减缓炎症的发生,发挥抗AS作用。

Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation

OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.

Fang-Xia-Dihuang decoction inhibits breast cancer progression induced by psychological stress via down-regulation of PI3K/AKT and JAK2/STAT3 pathways:An in vivo and a network pharmacology assessment

Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.

Effects of acupuncture combined with drug anesthesia on stress reaction and cognitive function in senior patients with total hip arthroplasty

Objective: To investigate the effects of acupuncture combined with anesthesia on stress and cognitive function in senior patients with total hip arthroplasty. Methods: A total of 89 patients who underwent total hip replacement between January 2016 and May 2018 were collected. According to whether acupuncture anesthesia was applied during total hip replacement, the patients were divided into acupuncture combined anesthesia group and drug anesthesia group. Fasting venous blood (3mL) was collected before the operation without electrical stimulation and after the operation. Cortisol (Cor) and β-endorphin (β-EP) were detected by radioimmunoassay, and neuron-specific enolase (NSE) was detected by electrochemical luminescence immunoassay. The levels of s-100β protein (s-100β), c-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were determined by ELISA. Flow cytometry was used to determine the ratio of T cell subsets (CD3+) and natural killer cells (NK cells) in the blood. Results: The levels of Cor, β-EP, NSE, S-100β, CRP, TNF-α and the ratio of NK cell, CD3+ between the two groups have no significant differences before operation (P>0.05). Serum levels of Cor, β-EP, NSE, S-100β, CRP and TNF-α in patients in the acupuncture combined with drug anesthesia group and the single drug anesthesia group were significantly higher than those before surgery (P<0.05). In addition, serum levels of Cor, β-EP, NSE, S-100β, CRP, TNF-α in the acupuncture combined with anesthesia group were significantly lower than those in the drug group alone (P<0.05). There was no significant difference in NK cell and CD3+ ratio between postoperative and preoperative in the acupuncture combined with drug anesthesia group (P>0.05). The ratio of NK cells and CD3+ in the pure drug anesthesia group was significantly lower than that before surgery (P<0.05). Conclusion: Acupuncture combined with drug anesthesia can effectively reduce the inflammatory stress response of patients undergoing total hip arthroplasty, relieve the immune suppression caused by surgery and anesthesia, reduce the damage to the nervous system, and have a good influence in the cognitive function of the senior patients.

Study and analysis of oxidative stress and cell apoptosis in retinal tissue of diabetic model rats after total flavonoids of onion treatment

Objective:To study the effect of total flavonoids of onion treatment on oxidative stress and cell apoptosis in the retinal tissue of diabetic model rats.Methods:Male SD rats were selected as experimental animals and randomly divided into control group, diabetes group, low-dosage total flavonoids group (total flavonoids L group) and high-dose total flavonoids (total flavonoids H group), intraperitoneal injection of streptozotocin was adopted to make diabetes model, and the total flavonoids L group and H group received lavage of 100 mg/kg and 200 mg/kg total flavonoids of onion for intervention. After 8 weeks of intervention, retinal tissue was collected and the degree of oxidative stress and cell apoptosis were determined.Results:P2X7, ROS, -OH, O2-, H2O2, FADD, p-JNK, caspase-8 and caspase-3 levels in retinal tissue of diabetes group were significantly higher than those of control group while Mn-SOD, CAT, GSH, AsA, NGF, BDNF and CNTF levels were significantly lower than those of control group;P2X7, ROS, -OH, O2-, H2O2, FADD, p-JNK, caspase-8 and caspase-3 levels in retinal tissue of total flavonoids L group and total flavonoids H group were significantly lower than those of diabetes group while Mn-SOD, CAT, GSH, AsA, NGF, BDNF and CNTF levels were significantly higher than those of diabetes group;P2X7, ROS, -OH, O2-, H2O2, FADD, p-JNK, caspase-8 and caspase-3 levels in retinal tissue of total flavonoids H group were significantly lower than those of total flavonoids L group while Mn-SOD, CAT, GSH, AsA, NGF, BDNF and CNTF levels were significantly higher than those of total flavonoids L group.Conclusion:Total flavonoids of onion have inhibiting effect on the oxidative stress and cell apoptosis in retinal tissue of diabetic model rats.

Effect of epidural anesthesia combined with total intravenous anesthesia on stress response and coagulation function in and after laparoscopic surgery

Objective:To study the effect of epidural anesthesia combined with total intravenous anesthesia on stress response and coagulation function in and after laparoscopic surgery. Methods: A total of 219 cases of patients who underwent laparoscopic cholecystectomy in our hospital between August 2014 and February 2017 were collected and divided into control group (n=125) who accepted total intravenous anesthesia alone and observation group (n=94) who accepted epidural anesthesia combined with total intravenous anesthesia after the anesthesia scheme was reviewed. Perioperative stress response and coagulation function were compared between two groups of patients.Results: Before operation, differences in the serum stress index contents and peripheral blood coagulation index levels were not statistically significant between two groups of patients. In operation and 2 h after operation, serum stress indexes Cor, Ang-Ⅰ, Ang-Ⅱ and NE contents of observation group were significantly lower than those of control group;peripheral blood coagulation indexes PT, TT and APTT levels were significantly higher than those of control group while TXA2, TXB2 and FBG levels were significantly lower than those of control group.Conclusions: Epidural anesthesia combined with total intravenous anesthesia can effectively alleviate the systemic stress response and reduce the hypercoagulable state in and early after laparoscopic surgery.

Inflammatory response, stress response and urodynamic changes after total pelvic floor reconstruction in patients with pelvic organ prolapse

Objective: To investigate the changes of inflammatory response, stress response and urodynamic changes after total pelvic floor reconstruction in patients with pelvic organ prolapse. Methods: According to random data table method, 80 cases of pelvic organ prolapse were randomly divided into the control group (n=40) and observation group (n=40), patients in the control group were given conventional vaginal hysterectomy plus vaginal wall repair sugery and the observation group received total pelvic floor reconstruction. The levels of the serum inflammatory factor,oxidative stress before and after surgery, and postoperative urodynamic changes were compared. Results: The levels of serum hs-CRP, IL-1β,TNF-α, NE, E and Ins in the two groups before treatment were not statistically significant. Compared with the group before treatment, the levels of hs-CRP, IL-1β, TNF-α, NE, E were significantly increased in both groups after treatment, and the observation group levels were significantly lower than those in the control group after treatment;in terms of urodynamics, the postoperative maximal bladder volume and Qmax were significantly higher in the observation group than in the control group, the postoperative levels of PdetQMax, PdetMax and PVR in the observation group were significantly lower than those in the control group. Conclusion: Compared with vaginal hysterectomy plus vaginal wall repair sugery, total pelvic floor reconstruction can light the patient's inflammation, stress response and improve the patient's urinary function, and the overall effect is better which has important clinical value.

Static and Thermal Analysis of Aluminium (413,390,384 and 332) Piston Using Finite Element Method

The main objective of this research was to examine the suitability of aluminium alloy to design a piston of an internal combustion engine for improvement in weight and cost reduction. The piston was modelled using Autodesk Inventor 2017 software. The modelled piston was then imported into Ansys for further analysis. Static structural and thermal analysis were carried out on the pistons of the four different materials namely: Al 413 alloy, Al 384 alloy, Al 390 alloy and Al332 alloy to determine the total deformation, equivalent Von Mises stress, maximum shear stress, and the safety factor. The results of the study revealed that, aluminium 332 alloy piston deformed less compared to the deformations of aluminium 390 alloy piston, aluminium 384 alloy piston and aluminium 413 alloy piston. The induced Von Mises stresses in the pistons of the four different materials were found to be far lower than the yield strengths of all the materials. Hence, all the selected materials including the implementing material have equal properties to withstand the maximum gas load. All the selected materials were observed to have high thermal conductivity enough to be able to withstand the operating temperature in the engine cylinders.

JAK-STAT信号传导通路与痛性糖尿病周围神经病变关系的研究进展

痛性糖尿病周围神经病变(PDPN)作为糖尿病并发症之一,是以疼痛为主要表现的一类神经病变,属于神经病理性疼痛的一种。JAK-STAT(The Janus kinase/signal transducer and activator of tran-scriptions)信号通路是一种由多种细胞因子介导的信号传导通路,与PDPN的病理机制密切相关。JAK-STAT信号通路通过与Nrf2通路相互作用介入到抗氧化应激过程,进而发挥神经细胞保护作用。JAK-STAT信号通路可以作为治疗痛性糖尿病周围神经病变一个潜在的治疗靶点。

地菍总黄酮对高脂饮食联合链脲佐菌素诱导糖尿病肾病小鼠脂质过氧化的影响

[目的]探讨地菍总黄酮(total Flavonoids from Melastoma dodecandrum Lour.,TFMD)对糖尿病肾病(DN)小鼠脂质过氧化的作用,对TFMD在肾脏功能保护及抗脂质过氧化方面的药用价值进行探索,为瑶药地菍的临床应用研究提供试验依据。[方法]将90只SPF级雄性C57BL/6J小鼠随机分成2组:空白组(n=10)及造模组(n=80)。空白组小鼠给予普通饲料,造模组小鼠给予高脂饲料,连续饲养6周后,各组小鼠禁食不禁水12 h后,造模组小鼠腹腔注射链脲佐菌素(STZ)0.05 g/kg,空白组小鼠注射等剂量柠檬酸钠缓冲液,连续注射5 d后,分别在末次注射72 h及1周后测量各组小鼠空腹血糖(FBG)。将连续2次FBG≥16.7 mmol/L的小鼠随机分为5组:DN模型组(高脂饲料)、二甲双胍组(高脂饲料+0.5 g/kg二甲双胍)及TFMD高(高脂饲料+1.2 g/kg TFMD)、中(高脂饲料+0.8 g/kg TFMD)、低(高脂饲料+0.6 g/kg TFMD)剂量组,每组10只,连续给药10周。给药过程中观察小鼠一般生理状况,每周检测FBG。给药10周后,使用代谢笼收集各组小鼠24 h尿液,剪尾采血检测各组小鼠FBG,计算各组小鼠肾脏指数;同时检测各组小鼠尿液中尿蛋白(UP)和尿微量白蛋白(MAU)、血清尿素氮(BUN)和血清肌酐(SCr)水平及肾脏组织中谷胱甘肽(GSH)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平。Western blotting检测各组小鼠肾脏组织Nephrin、podocin、PTGS2、ACSL4蛋白的表达量;制作各组小鼠肾脏组织HE及PAS染色切片并观察病理改变。[结果]与空白组相比,DN模型组小鼠体重、GSH和SOD水平均极显著降低(P<0.01),FBG、肾脏指数、MAU、UP、SCr、BUN及MDA水平均极显著升高(P<0.01),肾脏组织Nephrin、podocin蛋白表达量均极显著降低(P<0.01),PTGS2、ACSL4蛋白表达量显著升高(P<0.05),肾脏组织光镜下可见严重损伤,表明DN模型构建成功。与DN模型组相比,TFMD能改善DN小鼠的消瘦状况,极显著或显著降低小鼠肾脏指数及FBG(P<0.01;P<0.05),极显著降低小鼠体内UP、MAU、SCr、BUN水平(P<0.01),显著提高小鼠肾脏组织Nephrin、podocin水平(P<0.05),TFMD组小鼠肾脏组织损伤得到不同程度恢复。与DN模型组相比,TFMD显著或极显著提高小鼠肾脏组织GSH和SOD活性(P<0.05;P<0.01),极显著或显著降低MDA水平(P<0.01;P<0.05),显著或极显著下调肾脏组织中脂质过氧化相关蛋白PTGS2、ACSL4的表达(P<0.05;P<0.01),提升机体抗氧化能力及减缓机体脂质过氧化及其产物堆积。[结论]TFMD可明显延缓高脂饮食联合STZ诱导小鼠DN的发生发展进程,其机制与调控脂质过氧化及氧化应激、调控PTGS2/ACSL4信号通路相关。

人参总皂苷对K562细胞STAT5表达的影响

目的探讨人参总皂苷(TSPG)对人红白血病细胞株(K562细胞)信号转导与转录因子5(STAT5)表达的影响。方法紫外-可见分光光度法测定血红蛋白含量及Wright′s染色法检测TSPG诱导K562细胞向红系细胞分化的变化;免疫细胞化学观察TSPG作用前后K562细胞STAT5表达的变化;以ELISA和Western blotting法检测TSPG处理前后K562细胞的细胞质和细胞核中STAT5含量的变化。结果TSPG(200mg/L)诱导K562细胞6h、12h、24h后,随着TSPG作用K562细胞时间的延长,细胞中血红蛋白的含量逐渐增加;而加入AG490(40μmol/L)部分抑制了K562细胞中血红蛋白含量的增加。免疫细胞化学染色可见对照组K562细胞的细胞质和细胞核着色浅淡;经TSPG 200mg/L作用12h后,K562细胞的细胞质和细胞核着色明显加深,表达增强,与对照组相比差异有统计学意义(P<0.05);TSPG(200mg/L)诱导K562细胞6h、12h、24h后,随着TSPG作用K562细胞时间的延长,细胞质和细胞核中STAT5的表达逐渐增强。结论TSPG能增强K562细胞STAT5的表达,这可能是TSPG诱导K562细胞向红系细胞分化的作用机制之一。

JAK-STAT通路介导gx-50针对神经元的抗氧化保护作用的研究

gx-50已被证明在阿尔茨海默症中具有神经保护作用,然而其抗氧化机制在很大程度上仍然是未知的。为探究gx-50对在阿尔茨海默症中处于氧化应激状态的神经元细胞起到的保护作用,本文通过测定细胞内活性氧(ROS)水平、细胞内总超氧化物歧化酶(SOD)活性和细胞分泌物丙二醛(MDA)含量检测gx-50在细胞水平的抗氧化能力。并检测了gx-50在细胞和组织水平对于JAK-STAT信号通路和caspase-3蛋白表达水平的影响。结果表明,gx-50可以使暴露于β淀粉样蛋白(Aβ)的PC12细胞分泌的ROS和MDA水平降低,并保护胞内总SOD酶活性;gx-50可以在细胞和组织水平活化JAK-STAT信号通路,可以降低PC12细胞内caspase-3蛋白活性亚基的相对表达水平;而JAK2的特异性抑制剂,AG490,逆转了gx-50的以上抗氧化保护作用。这表明gx-50可以通过活化JAK-STAT通路,一定程度上减弱神经元所受到的氧化损伤,对神经元起到保护作用,因此在阿尔茨海默症预防治疗方面具有一定的应用前景。

卷柏总黄酮通过调节Nrf2/HO-1信号通路减轻机械通气相关性肺损伤的机制

目的探讨卷柏总黄酮(TFST)调控Nrf2/HO-1信号通路对机械通气相关性肺损伤(VALI)的影响。方法选取健康SPF级雄性SD大鼠40只,采用随机数字表法分为4组,每组10只。对照组仅对大鼠插管不进行机械通气;模型组采用潮气量30 mL/kg,通气频率60次/min,吸氧浓度FiO 221%,吸呼比1∶2,通气时间4 h制备大鼠VALI模型;TFST组于造模前2周开始每天1次卷柏总黄酮混悬液800 mg/kg灌胃给药;ML385组,卷柏总黄酮预保护2周并在机械通气前1 h,将ML385(Nrf2抑制剂)30 mg/kg注射于大鼠腹腔。结束后处死大鼠并收集大鼠支气管肺泡灌洗液(BALF)使用ELISA法测定其中IL-6及TNF-α浓度;且收集大鼠肺组织进行HE染色观察其病理学变化后作肺损伤评分,比较各组大鼠肺组织湿重干重比(W/D),检测肺组织中丙二醛(MDA)水平,WST-8法测定肺组织超氧化物歧化酶(SOD)水平,采用Western blot法检测肺组织Nrf2及HO-1蛋白的水平。结果与对照组比较,模型组的肺组织W/D值及MDA含量,肺损伤评分及BALF中IL-6、TNF-α升高,肺组织中SOD含量,Nrf2、HO-1蛋白水平降低(均P<0.05)。与模型组比较,TFST组的肺组织W/D值及MDA含量降低,肺损伤减轻及BALF中IL-6、TNF-α降低,SOD含量,Nrf2、HO-1蛋白水平增加(P<0.05);ML385组则较TFST组大鼠肺损伤加重,肺组织W/D值及MDA含量,BALF中IL-6、TNF-α升高,SOD含量,Nrf2、HO-1蛋白水平降低(P<0.05)。结论卷柏总黄酮可通过调节Nrf2/HO-1通路激活抗氧化途径改善大鼠机械通气相关肺损伤。

Rac1突变重组体的构建及对JAK/STAT信号通路的影响

通过构建Rac1突变体,研究Rac1激活对肾小球系膜细胞(MES)JAK2/STAT3信号通路的影响.以Rac1目的基因为模板,在引物中设计突变,扩增突变体Rac1(G12V)的目的基因,与PiggyBac(PB-FLAG)载体质粒连接,构建突变重组体PB-Rac1(G12V),并运用脂质体核酸试剂转染系膜细胞.比较正常组、Rac1(G12V)突变组中系膜细胞的ROS含量及NADPH氧化酶活性;Elisa法检测细胞因子TGF-β表达水平;Western blot法检测系膜细胞中JAK2/STAT3信号及FN蛋白的表达.结果表明,成功构建了Rac1(G12V)持续磷酸化突变体并在MES细胞中表达,与正常组相比,Rac1(G12V)激活突变MES细胞NADPH氧化酶的活性和ROS含量明显增加;JAK2/STAT3信号通路激活,TGF-β和FN表达明显增加.Rac1能激活系膜细胞氧化应激和JAK2/STAT3信号通路,并促进TGF-β及FN的表达.

L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.

Insulin resistance in H pylori infection and its association with oxidative stress

AIM: To determine the insulin resistance (IR) and oxidative status in H pylori infection and to find out if there is any relationship between these parameters and insulin resistance. METHODS: Fifty-five H pylori positive and 48 H pylori negative patients were enrolled. The homeostasis model assessment (HOMA) was used to assess insulin resistance. Serum total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined in all subjects. RESULTS: The total antioxidant capacity was significantly lower in H pylori positive group than in H pylori negative group (1.36 ± 0.33 and 1.70 ± 0.50, respectively; P < 0.001), while the total oxidant status and oxidative stress index were significantly higher in H pylori positive group than in H pylori negative group (6.79 ± 3.40 and 5.08 ± 0.95, and 5.42 ± 3.40 and 3.10 ± 0.92, respectively; P < 0.001). Insulin resistance was significantly higher in H pylori positive group than in H pylori negative group (6.92 ± 3.86 and 3.61 ± 1.67, res- pectively; P < 0.001). Insulin resistance was found to be significantly correlated with total antioxidant capacity (r = -0.251, P < 0.05), total oxidant status (r = 0.365, P < 0.05), and oxidative stress index (r = 0.267, P < 0.05). CONCLUSION: Insulin resistance seems to be associated with increased oxidative stress in H pylori infection. Further studies are needed to clarify the mechanisms underlying this association and elucidate the effectof adding antioxidant vitamins to H pylori eradication therapy on insulin resistance during H pylori infection.

Effects of total glucosides of peony on immunological hepatic fibrosis in rats

AIM: To study the effects of total glucosides of peony (TGP) on immunological hepatic fibrosis induced by human albumin in rats.METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into: Normal group, model group, TGP (60 and 120 mg/kg) treatment groups and colchicines (0.1 mg/kg) treatment group. On the day before the rats were killed, those in TGP or colchicine groups received TGP or colchicine as above from the first day of tail vein injection of human albumin. The rats in normal and model groups were only administered with the same volume of vehicle. At the end of the 16th wk, rats in each group were killed. Blood and tissue specimens were taken. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), content of malondialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were measured by biochemical methods. Serum procollagen type Ⅲ (PC Ⅲ) and laminin (LN) were determined by radioimmunoassay. Liver collagen level was determined by measuring hydroxyproline content in fresh liver samples. Hepatic tissue sections were stained with hematoxylin-eosin and examined under a light microscope.RESULTS: Histological results showed that TGP improved the human albumin-induced alterations in the liver structure, alleviated lobular necrosis and significantly lowered collagen content. The antifibrotic effect of TGP was also confirmed by decreased serum content of LN and PCⅢ in TGP-treated group. Moreover, the treatment with TGP effectively reduced the hydroxyproline contentin liver homogenates. However, the level of ALT and AST increased in fibrotic rat but had no significance compared with normal control, whereas the ratio of A/G decreased without significance. TGP had no effect on level of ALT, AST and the ratio of A/G. Furthermore, TGP treatment significantly blocked the increase in MDA and NO, associated with a partial elevation in liver total antioxidant capacity including SOD and GSH-px.CONCLUSION: TGP has beneficial effects on hepaticfibrosis in rats by inhibition of collagen synthesis and decreasing oxidative stress.

Investigation of the short-term stress distribution in stopes and drifts backfilled with cemented paste backfill

Cemented paste backfill(CPB) is largely used in underground mines worldwide.A key issue associated with application of CPB is to estimate the stresses in backfilled stopes and on barricades.Recent numerical and experimental results show that arching effect is absent shortly after the placement of CPB in stopes.However,stress decreases in barricade drift with increasing distance between the measurement points and drawpoint have also been observed,demonstrating arching effect shortly after the pouring of CPB.To explain these paradoxes,CPB is considered as Bingham fluid having a yield shear stress.Three dimensional analytical solutions are proposed to evaluate the short-term total stresses in backfilled stopes and on barricades,accounting for the CPB's yield shear stress-induced arching effect.Stress diminution due to such arching effect in the backfilled stopes and on barricades is indeed obtained.But the reduction becomes insignificant using typical yield shear stress and stope geometry.More analyses indicate that the typical yield shear stress values do not fully correspond to field conditions where the yield shear stress would increase exponentially due to apparent consolidation(loss of water by drainage,a phenomenon similar to the desiccation of overly saturated fine-grained materials).

Action of trichostatin A on Alzheimer’s disease-like pathological changes in SH-SY5Y neuroblastoma cells

The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the nuclear factor erythroid 2-related factor 2(Nrf2) and Kelch-like epichlorohydrin-related protein-1(Keap1) signaling pathway, amyloid β-peptide 25–35(Aβ25–35) was used to induce Alzheimer’s disease-like pathological changes in SH-SY5 Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5 Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5 Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5 Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5 Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage.