Clinical features and risk factors in 126 patients with anti-MDA5 antibody positive dermatomyositis / 中华风湿病学杂志

Objective:To explore clinical factors of poor prognosis in patients with anti-melanoma differentiation-associated gene 5 andtibody positive dermatomyositis (MDA5-DM).Methods:One hundred and twenty-six enrolled adults with MDA5-DM were divided into the survival group and the deceased group according to the outcomes. Survival time, clinical manifestations, laboratory tests, pulmonary function tests, myositis antibodies and treatments were collected for statistical analysis. Serum concentrations of IL-15, HMGB1, and sCD163 were measured by ELISA in MDA5-DM patients and healthy controls. Mann-Whitney U nonparametric test and Student′s t-test were used to compare the continuous variables between the two groups, and χ2 or Fisher′s exact test were used for comparison of categorical variables. Cox regression analysis was used to assess the survival predictors in MDA5-DM patients. The cumulative survival rate was calculated by Kaplan-Meier curve analysis, and Log-rank tests were used to examine differences in survival curves. P<0.05 was considered statistically significant. Results:Cox multivariate regression analysis revealed that age > 57 years [ HR (95% CI)=3.05 (1.20, 7.80), P=0.020], RP-ILD [ HR (95% CI)=25.07 (5.42, 115.98), P<0.001], and levels of anti-Ro52 antibody [ HR (95% CI)=3.41 (1.36, 8.53), P=0.009] were important prognostic factors independent of multiple clinical parameters. The ELISA test results showed that the levels of serum IL-15[0.91 (0.66, 2.00)pg/ml vs. 0.51(0.39, 0.72)pg/ml, Z=-4.57, P<0.001] and HMGB1 [230.53(90.40, 394.31)ng/ml vs. 32.66 (17.82, 46.21)ng/ml, Z=-6.52, P<0.001] in MDA5-DM patients were significantly higher than those in healthy controls, but there were no significant differences in the level of serum IL-15 [1.21(0.63, 2.12)pg/ml vs. 0.91(0.68, 1.66)pg/ml, Z=-0.30, P=0.766], HMGB1[267.61(167.03, 444.23)ng/ml vs. 228.35(74.74, 344.32)ng/ml, Z=0.82, P=0.413], and sCD163 [112.70(93.45, 148.51)ng/ml vs. 132.72(96.79, 203.18)ng/ml, Z=-0.62, P=0.536] between the survival group and the deceased group. Conclusion:Older age, RP-ILD, and high levels of anti-Ro52 antibody significantly increase the risk of death in MDA5-DM patients. Intensive follow-up of patients with the above factors in the early stages may help to improve the prognosis.

Clinical characteristics of 272 cases with anti-MDA5 antibody positive dermatomyositis / 中华风湿病学杂志

Objective:To analyze the clinical features of MDA5 antibody positive dermatomyositis (MDA5-DM) and to provide evidence for early diagnosis and treatment.Methods:From March 2019 to June 2021, 272 patients with anti-MDA5-DM from the Nanjing Medical University myositis-associated interstitial lung disease cohort were enrolled, with 76 patients with anti-synthetase syndrome (ASS) as the control group. The clinical characteristics and the occurrence of interstitial lung disease were analyzed. T-test was used for normally distributed and variance-homogeneous independent samples, Mann-Whitney U test for non-normally distributed data, and chi-square test or Fisher′s exact test for dichotomous variables. Results:Among the 272 anti-MDA5-DM patients, 88.6% (241/272) developed interstitial lung disease (ILD), and 33.8% (92/272) developed rapidly progressive ILD (RP-ILD). The six-month all-cause mortality rate of anti-MDA5-DM patients was 16.9% (46/272), and it was as high as 47.8% (44/92) for those with RP-ILD. Compared with ASS patients, anti-MDA5-DM patients had a significantly higher proportion of males, arthritis, Gottron's sign, heliotrope rash, V-sign, periungual erythema, and skin ulcers ( P<0.05). The levels of ALT, AST, and ferritin were significantly increased ( P<0.05). Compared with non-RP-ILD patients, RP-ILD patients had a significantly higher proportion of males [35.9%(33/92) vs. 23.3%(42/180), χ2=4.79, P=0.029], higher levels of LDH [387 (276, 547) U/L vs. 310 (245, 400) U/L, Z=-3.67, P<0.001], ESR [45.5 (29.25, 63.25) mm/1 h vs. 31.2 (20, 51) mm/1 h, Z=-3.71, P<0.001], CRP [10.9 (4.1, 25.2) mg/L vs. 4.54 (2.58, 9.08) mg/L, Z=-4.97, P<0.001], ferritin [1 340 (650, 2 000) ng/ml vs. 556 (203, 1 186) ng/ml, Z=-4.40, P<0.001], and a higher proportion of anti-Ro52 antibody and anti-MDA5 antibody co-positivity [87.0%(80/92) vs. 52.2%(94/180), χ2=31.87, P<0.001]. Conclusion:Anti-MDA5-DM patients are prone to develop RP-ILD and have poor prognosis.

Clinical characteristics of invasive pulmonary aspergillosis in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 antibody / 中华风湿病学杂志

Objective:To investigate the clinical characteristics, risk factors, and prognosis of invasive pulmonary aspergillosis (IPA) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5-DM).Methods:A total of 55 patients with MDA5-DM were analyzed. Patients were divided into IPA (+) group (14 cases) and IPA (-) group (41 cases) based on the presence of IPA. Microbiological examination and clinical data were analyzed. Risk factor analysis was performed using Binary Logistic regression, and survival analysis was carried out using Kaplan-Meier method.Results:Aspergillus flavus (5/14, 35.7%) and Aspergillus fumigatus (4/14, 28.6%) were the most common species in MDA5-DM patients with IPA. Compared to the IPA (-) group, IPA (+) group had higher serum level of α-hydroxybutyrate dehydrogenase (246 U/L vs. 191 U/L, Z=-2.02, P=0.043) and ferritin [1 306.7(518.7, 2 977.8)ng/ml vs. 472.6(269.0, 792.1)ng/ml, Z=-2.09, P=0.036], lower CD8 + T lymphocyte counts {[111.5 (68.3, 214.0)]×10 6/L vs. [188.0(141.0, 270.0)]×10 6/L, Z=-2.18, P=0.029}, and more positive BALF GM tests [70.0%(7/10) vs. 18.9%(7/37), χ2=9.82, P=0.004]. Elevated serum ferritin was found to be an independent risk factor for IPA occurrence [adjusted OR (95% CI)=1.001 (1.000, 1.002), P=0.031)]. In addition, the 6-month cumulative survival rate was significantly lower in the IPA (+) group than in the IPA (-) group (78.6% vs. 97.6%, P=0.021). Conclusion:The mortality of MDA5-DM patients is increased after IPA infection. Elevated serum ferritin is an independent risk factor for IPA occurrence, and active prevention and treatment of IPA are expected to improve the prognosis of patients.

Clinical characteristics and prognosis of male dermatomyositis patients with positive anti-melanoma differentiation associated gene 5 antibody / 中华风湿病学杂志

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells / 中国现代医生

Objective To investigate the effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells.Methods MDA-MB-231 breast cancer cells were inoculated on the culture plate for 24h and randomly divided into 8 groups:Control group(C),ropivacaine 400μg/ml group(R),morphine 3μg/ml group(LM),morphine 30μg/ml group(MM),morphine 300μg/ml group(HM),ropivacaine 400μg/ml group+ morphine 3μg/ml group(R+LM),ropivacaine 400μg/ml+ morphine 30μg/ml group(R+MM),and ropivacaine 400μg/ml+ morphine 300μg/ml group(R+HM).After treaments of MDA-MB-231 breast cancer cells for 24h,these proliferation,migration,invasion and cell cycle were evaluated.Results When using morphine alone,the proliferation inhibitive effect was positively correlated with the concentration of morphine.The proliferation was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the proliferation was significantly inhibited(P<0.05).When using morphine combined with ropivacaine,the high concentration morphine group has a synergistic effect with ropivacaine group on proliferation inhibition(P<0.05).When using morphine alone,the migration rate decreases sequentially with the increase of morphine concentration.The migration rate was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the migration rate was inhibited(P<0.05).When using morphine combined with ropivacaine,the low and medium concentration morphine group have a synergistic effect with ropivacaine group on migration rate(P<0.05).When using morphine alone,the number of cell invasion was decreased with the concentration of morphine increasing(P<0.05).The MM and HM groups inhibited cell invasion ability.When using ropivacaine alone,the invasiveness of cells was also inhibited(P<0.05).When using morphine combined with ropivacaine,the medium and high concentration morphine groups have a synergistic effect with ropivacaine group on inhibiting cell invasion ability(P<0.05).When using morphine alone,the cell cycle progression was inhibited into G2/M Phase(P<0.05).When using ropivacaine alone,the cell cycle progression was inhibited into G2/M phase(P<0.05).The combination of low concentration morphine and ropivacaine has synergistic effect on arresting at G0/G1 and S phase(P<0.05).Conclusion Morphine combined with ropivacaine inhibits the Proliferation,migration and invasion of MDA-MB-231 breast cancer cells in a dose-dependent manner.

Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats / Atividade antiulcerogênica e antioxidante do extrato etanólico de Plantago ovata em ratos

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do ß-caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats

Abstract This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, -carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

Resumo O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do -caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Assessment of coverage and compliance of mass drug administration for lymphatic filariasis in Medak District-2021

In India Mass Drug Administration (MDA) drive is undertaken every year. In mass drug administra?on DEC and Albendazole combina?on is used. For the strategy to be effec?ve, more than 85% of those living in endemic areas must be covered by MDA. Methods: This is a cross-sec?onal study in which family clusters were selected from rural and urban areas. Informa?on about coverage, compliance with MDA and knowledge of filariasis was obtained using a ques?onnaire. Data were analysed using percentages and propor?ons. Results: In this study, about 92.51% of the study par?cipants received DEC and ABZ tablets during MDA, of which 95.14 % of par?cipants consumed the drugs. The most common cause of noncompliance was fear of side effects. Conclusion: Coverage of the popula?on with DEC and albendazole combina?on was good but compliance needs to be improved. IEC ac?vi?es should be intensified. Local leaders should be involved in the programme to increase compliance.

Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells / 中国药科大学学报

@#The aim of this study was to investigate the effect of norcantharidin (NCTD) on the proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231.Western blot was used to detect the effect of NCTD on the expression levels of apoptosis-related proteins Bax/Bcl-2, cleaved-PARP/PARP/PARP, cleved-caspase-9, cleaved-caspase-3 and MCL-1 in MDA-MB-231 cells.Also, the expression levels of autophagy-related proteins LC3-II/LC3-I, Parkin and PINK1 in MDA-MB-231 cells were measured by Western blot.Flow cytometry was used to measure the effect of NCTD on the changes of mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS).The effect of NCTD on autophagy flow in cells expressing mCherry-EGFP-LC3 was detected by a confocal microscope.Moreover, the effects of NCTD combined with chloroquine (CQ) or 3-methyladenine (3-MA) on the apoptosis of MDA-MB-231 cells were detected by flow cytometry.The results showed that NCTD significantly increased the expression levels of Bax/Bcl-2, cleaved-PARP/PARP, cleaved-caspase-9, cleasved-caspase-3 and LC3-II/LC3-I proteins, and promoted the mitochondrial translocation of Parkin, and blocked the autophagic flow in MDA-MB-231 cells. Moreover, NCTD combined with CQ accelerated apoptosis, while NCTD combined with 3-MA decreased apoptosis.These results suggest that NCTD can induce autophagy accumulation and lead to apoptosis of MDA-MB-231 cells.

circNEIL3 regulates the proliferation, migration and invasion of breast cancer MDA-MB-231 cells through targeting miR-4784 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：研究环状RNA nei样DNA糖化酶3（circNEIL3）和微小RNA（miR）-4784对乳腺癌细胞MDA-MB-231的增殖、迁移和侵袭的影响。方法：收集2018年1月至2019年12月在济南市中西医结合医院经组织病理诊断为乳腺癌并行手术切除的45例乳腺癌患者的癌组织和配对癌旁组织，qPCR法检测乳腺癌组织、癌旁组织中circNEIL3和miR-4784的相对水平。将circNEIL3的小干扰RNA（si-circNEIL3）、miR-4784模拟物、si-circNEIL3+miR-4784抑制物分别转染MDA-MB-231细胞，采用CCK-8法、平板克隆实验、划痕愈合实验、Transwell实验检测circNEIL3和miR-4784表达对细胞活力、克隆形成、迁移和侵袭的影响。双荧光素酶报告基因实验、RNA免疫沉淀（RIP）和RNA pull-down实验检测circNEIL3和miR-4784之间相互作用。结果：乳腺癌组织中circNEIL3呈高表达（P<0.05），miR-4784呈低表达（P<0.05）。干扰circNEIL3显著降低MDA-MB-231细胞活力、克隆形成数、划痕愈合率以及侵袭数（均P<0.05）。过表达miR-4784显著降低MDA-MB-231细胞活力、克隆形成数、划痕愈合率以及侵袭数（均P<0.05）。双荧光素酶报告基因实验、RIP和RNA pull-down实验均证实circNEIL3与miR-4784可直接结合，干扰circNEIL3能明显上调miR-4784表达（P<0.05），过表达circNEIL3能明显下调miR-4784表达（P<0.05）。抑制miR-4784表达部分逆转干扰circNEIL3对MDA-MB-231细胞活力、克隆形成、迁移和侵袭的抑制作用（P<0.05）。结论：干扰circNEIL3通过靶向上调miR-4784表达抑制MDA-MB-231细胞的增殖、迁移和侵袭。

Effect of Pravastatin on Levels of Malondealdehyde (MDA) And Endothelin-1 (ET-1) Preeclampsia Model Rats

@#Introduction: Pravastatin is known to have a number of pleiotropic effects including reducing endothelial dysfunction, anti-inflammatory, antioxidants, conangiogenic, and antitrombotic. Pravastatin through the pleitropic effect is expected to be one of the alternative therapies to prevent preeclampsia. The limited strategy for prevention and treatment of preeclampsia is due to the unknown etiology and pathogenesis. These two markers are thought to contribute to the occurrence of preeclampsia although they cause it in two different pathways. MDA is a marker of oxidative stress as an end product of lipid peroxidation. ET-1 is a vasoconstrictor that plays a role in the pathogenesis of preeclampsia through increasing anti-angiogenic properties. Aim: to determine the effect of pravastatin on serum levels of MDA and ET-1 in preeclampsia rat models. Methods: This study consisted of 5 groups; negative control/ K(-) consisted of normal pregnant rats, positive control/ K(+) consisted of rat model of preeclampsia (rat model of preeclampsia induced by administration of L-NAME at a dose of 125 mg/kg BW/day since gestational age 13-19 days), treatment groups 1, 2, and 3 (rat model of preeclampsia given pravastatin with 3 different doses; 2 mg/day (P1), 4 mg/day (P2) and 8 mg/day(P3)) at 13-19 days of gestation. The rat model of preeclampsia was determined based on blood pressure > 140/90 with urine protein > +1. After termination, blood was drawn to measure serum MDA and ET-1 levels. Results: Serum levels of MDA and ET-1 were decreased in groups P2 and P3 compared to groups K(+). Statistically, there was a significant difference in the mean levels of MDA (p=0.001) and ET-1 (p=0.000) between each group. Conclusion: Pravastatin can prevent preeclampsia by decreasing MDA and ET-1.

Possible mechanism of 191 measles attenuated live vaccine strains inhibiting the proliferation of triple negative breast cancer MDA-MB-231 cells based on proteomics technology / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：基于蛋白质组学技术探讨麻疹减毒活疫苗191株（MV-Hu191）在体内外对三阴性乳腺癌MDA-MB-231、4T1细胞的影响及其作用机制。方法：采用CCK-8法检测MV-Hu191对MDA-MB-231和4T1细胞增殖的影响；液相色谱-质谱联用技术分析MV-Hu191处理对MDA-MB-231细胞中蛋白质谱的影响，多重数据库筛选蛋白质谱中的典型差异蛋白质并进行GO、KEGG、亚细胞定位与功能注释。瘤内注射1×106 TCID50 MV-Hu191干预4T1细胞移植瘤模型小鼠，流式细胞术检测小鼠脾组织中T细胞亚群，ELISA法检测小鼠血清TNF-α和IL-6含量。结果：体外实验结果表明，MV-Hu191具有抑制MDA-MB-231和4T1细胞增殖的作用，差异均具有统计学意义（P<0.01）。蛋白质组学分析结果显示，MV-Hu191作用MDA-MB-231细胞后明显上调蛋白质有38个、下调有12个；差异表达的蛋白质主要参与细胞黏附、信号受体激活、细胞代谢、应激反应等生物学过程，22个差异蛋白质亚细胞定位位于细胞外，KEGG功能分类显示与免疫调节功能相关的差异蛋白质最多且均为上调蛋白，包括C4A、C8B、SERPINF2、A2M、SERPINC1、CTSB、SERPING1、C5；PPI预测发现免疫相关差异蛋白与CD4、CD8、TNF-α及IL-6相互关联。体内实验结果显示，MV-Hu191干预组小鼠脾组织中CD4+ T细胞数量略高于对照组，但差异无统计学意义（P>0.05），CD4+/CD8+ T细胞比值明显高于对照组（P<0.05），血清TNF-α和IL-6含量显著上升（均P<0.01）。结论：MV-Hu191显著抑制MDA-MB-231、4T1细胞增殖及拮抗4T1细胞荷瘤小鼠成瘤性，其机制可能是MV-Hu191通过激活免疫效应分子实现抗肿瘤作用。

The inhibitory effect of Licochalcone B on the triple negative breast cancer cell MDA-MB-231 and its mechanism / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨甘草查尔酮B（LCB）对三阴性乳腺癌（TNBC）MDA-MB-231细胞的抑制作用及其机制。方法: 常规培养MDA-MB-231细胞，用不同浓度LCB处理后，采用CCK-8法、免疫荧光法、FCM和WB法分别检测MDA-MB-231细胞的增殖活力、细胞核内DNA双链断裂标志物γ-H2AX的表达，以及细胞周期和周期调控、丝裂原活化蛋白激酶（MAPK）、内质网应激信号途径相关蛋白的表达水平。结果: LCB能显著抑制乳腺癌MDA-MB-231细胞的增殖活力（P<0.05），使γ-H2AX阳性细胞数和蛋白表达水平均显著升高（均P<0.05）、G2/M和S期的细胞数量均明显增加（均P<0.05）、MAPK家族主要成员细胞外调节激酶1/2（ERK1/2）和p38MAPK蛋白的磷酸化水平均显著上调（均P<0.05），还使内质网应激途径相关蛋白Bip、ATF4和CHOP的表达均显著上调（均P<0.05）。结论: LCB能够显著抑制MDA-MB-231细胞的增殖活力、诱导DNA损伤和细胞周期阻滞于G2/M和S期，LCB对MDA-MB-231细胞的抑制作用可能与其激活MAPK和内质网应激信号通路相关。

In vivo antioxidant activity of rabbiteye blueberry (Vaccinium ashei cv. 'Brightwell') anthocyanin extracts / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Blueberries are rich in phenolic compounds including anthocyanins which are closely related to biological health functions. The purpose of this study was to investigate the antioxidant activity of blueberry anthocyanins extracted from 'Brightwell' rabbiteye blueberries in mice. After one week of adaptation, C57BL/6J healthy male mice were divided into different groups that were administered with 100, 400, or 800 mg/kg blueberry anthocyanin extract (BAE), and sacrificed at different time points (0.1, 0.5, 1, 2, 4, 8, or 12 h). The plasma, eyeball, intestine, liver, and adipose tissues were collected to compare their antioxidant activity, including total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and glutathione-peroxidase (GSH-PX/GPX) content, and the oxidative stress marker malondialdehyde (MDA) level. The results showed that blueberry anthocyanins had positive concentration-dependent antioxidant activity in vivo. The greater the concentration of BAE, the higher the T-AOC value, but the lower the MDA level. The enzyme activity of SOD, the content of GSH-PX, and messenger RNA (mRNA) levels of Cu,Zn-SOD, Mn-SOD, and GPX all confirmed that BAE played an antioxidant role after digestion in mice by improving their antioxidant defense. The in vivo antioxidant activity of BAE indicated that blueberry anthocyanins could be developed into functional foods or nutraceuticals with the aim of preventing or treating oxidative stress-related diseases.

Morphine counteracts the effects of paclitaxel in triple-negative breast cancer cells

Background & objectives: Several studies have provided evidence that opioids may play a role in cancer recurrence and metastasis. Multiple research data indicate that morphine can act as a proliferative or suppressive agent on tumour cells depending on the applied concentration. Therefore, this study was aimed to investigate whether the presence of clinically relevant concentrations of morphine has any effect on the efficacy of paclitaxel, a widely used chemotherapeutic drug, on the viability and apoptosis of human triple-negative breast cancer cell line. Methods: MDA.MB.231 cells were treated with paclitaxel in the presence or absence of morphine and examined for cell proliferation by the MTT assay. In addition, the effect of morphine on paclitaxel- induced apoptosis was investigated by flow cytometric assay and by the ratio of Bax/Bcl-2 mRNA expression levels with quantitative real-time (qRT)-PCR. Results: Morphine significantly increased the proliferation of breast cancer cells at low concentrations (0.1-2.5 ?M) but higher concentrations showed cytotoxic effect. Pre-treatment with 0.1 or 1 ?M of morphine decreased the paclitaxel-induced cytotoxicity, the proportion of apoptotic cell, and the ratio of Bax/Bcl-2 mRNA expressions. Interpretation & conclusions: Our data suggest that morphine promotes breast cancer cell viability at clinically relevant plasma concentrations and reduces the apoptotic effect of paclitaxel. This interaction may be very important in clinical settings; however, more studies are needed to explore the plausible mechanisms of interaction and to correlate such findings through in vivo animal studies as well as clinically.

Clinical analysis of elderly patients with anti-MDA5 antibody-positive dermatomyositis / 中华老年医学杂志

Objective:To retrospectively analyze the clinical characteristics of elderly patients with anti-MDA5 antibody-positive dermatomyositis.Methods:Data of 62 patients with anti-MDA5 antibody-positive dermatomyositis admitted to Second Xiangya Hospital from May 2016 to December 2019 were collected and patients were divided into an elderly group(≥60 years old, 17 cases)and a non-elderly group(<60 years old, 45 cases). The clinical manifestations, laboratory test resuls, treatment and prognosis of the patients in both groups were statistically analyzed.Results:A total of 62 patients with anti-MDA5 antibody-positive dermatomyositis were included in this study, including 17 elderly patients(27.4%)with an average age of(65.5±5.3)years and 45 non-elderly patients(72.6%)with an average age of(46.5±8.4)years.Compared with non-elderly patients, older patients had a shorter disease duration[(1.6±1.0)months vs.(3.7±3.3)months, t=3.883, P<0.001], a higher proportion of patients with exertional dyspnea(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024)and with combined positive anti-Ro-52 antibodies(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024), and a higher mortality rate[(12/17 or 70.6%) vs.(8/45 or 17.8%, χ2=15.748, P<0.001)]. In contrast, fewer elderly patients than non-elderly patients had the Heliotrope's sign(9/17 or 41.2% vs.38/45 or 57.8%), χ2=5.07, P=0.024). Conclusions:Elderly patients with anti-MDA5 antibody-positive dermatomyositis have a unique clinical phenotype with an acute onset, atypical rashes, severe pulmonary lesions, making treatment difficult, and have a poor prognosis.

Effects of tanshinone B regulating LRP6/Wntl/p-catenin pathway on cognitive function of mice with vascular dementia / 中国药理学通报

Aim To explore the protective mechanism of tanshinone B on cognitive dysfunction in mice with vascular dementia.Methods C57BL/6 male mice were divided into control group, vascular dementia model group(VD group), tanshinone B group(TSB 2,4,8 mg·kg-1), donepezil hydrochloride group(1 mg·kg-1), according to the random number table method.The VD model was constructed by the coarctation of bilateral common carotid arteries in mice.Ten days after the successful modeling, the low, medium, and high-dose tanshinone B groups were intraperitoneally injected with tanshinone B, the positive control medicine group was intraperitoneally injected with donepezil hydrochloride, once a day, and the mice in control group and VD group were injected intraperitoneally with the same amount of normal saline for 20 d.Morris water maze test was used to detect the learning and memory ability of mice in each group; the cortex and hippocampus of each group were separated, and MDA, SOD and GSH-Px were determined by spectrophotometry; the pathological changes in the hippocampus of each group were observed by HE staining.The expression of p-LRP6, LRP6, Wnt1 and β-catenin protein in the hippocampus of each group of mice were detected by Western blot.Results Compared with control group, the ability of memory was reduced, the content MDA increased(P<0.01), SOD and GSH-Px activities decreased(P<0.01), and significant pathological damage in hippocampus, the expression of p-LRP6, Wnt1, and β-catenin protein was significantly reduced in VD group(P<0.01).Compared with VD group, the learning and memory abilities of the mice were improved, the content of MDA decreased(P<0.01), the activities of SOD and GSH-Px increased(P<0.01), and the pathological damage in hippocampus was significantly improved.The expression of Wnt1 and β-catenin protein increased significantly in TSB treatment group(P<0.01).Conclusions TSB can improve the cognitive dysfunction of VD mice, and its mechanism may be related to the activation of the LRP6/Wnt1/β-catenin pathway in hippocampus.

The Potentiality of Citral in Targeting Breast Cancer Multicellular Tumour Spheroids (MTS)

@#Introduction: As the high incidence of breast cancer has a profound impact on a global scale, there is a critical need to improve the clinical outcome of the patients, including efforts to utilize bioactive natural products as treatment or preventive measures. Citral, the essential oil of lemongrass has been reported to possess cytotoxicity in breast cancer cell line . The aim of present study was to determine the capability of citral in targeting aldehyde dehydrogenase-positive (ALDH+) cells in breast cancer cells. Methods: Both MCF-7 and MDA-MB-231 cells were cultured in serum-free media to generate multicellular tumour spheroids for the evaluation of citral as an antiproliferative agent. The cells were treated with identified IC50 (50±4.30 µM and 56±3.17 µM of citral, respectively) to investigate the cytotoxicity of citral. Staining using Propidium Iodide (PI) and Hoechst 33342 was carried out to determine cell proliferation and viability. Finally, ALDH+ cells were quantified via ALDEFLUOR assay. Analysis of differences was carried out by analysis of variance (ANOVA) and independent t-test with p<0.05 considered statistically significant. Results: The size of spheroids in both cancer cell lines were reduced after treatment with the citral. PI and Hoechst 33342 staining also revealed that citral gave rise to a mixture of cells that are normal and undergoing apoptosis and necrosis. ALDEFLUOR assay analysis revealed citral significantly (p <0.05 ) inhibited the population of ALDH+ cells in MCF7 cells. Conclusion: It was demonstrated that citral reduced the ALDH+ cell population in MCF7 breast cancer spheroids by inhibiting the ALDH activity.

Piperine suppresses growth and migration of human breast cancer cells through attenuation of Rac1 expression

@# Objective: To investigate the effect of piperine on human breast cancer cells. Methods: The effect of piperine on proliferation and migration of human breast cancer cells, MCF-7 and MDA-MB-231, was investigated using colony formation assays, wound healing assays, Matrigel migration assays, flow cytometry, RT-qPCR, and Western blotting assays. Results: Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation. Cell reduction at the G 0 / G 1 phase and cell arrest at the G 2 /M phase were observed in breast cancer cells. However, the significant effect was only demonstrated in MDA-MB-231 cells. Moreover, cancer cell migration was suppressed by piperine at low concentration. RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression. Conclusions: Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.