Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Effect of temperature on the risk of varicella in Lu'an City / 预防医学

Objective@#To examine the effect of temperature on the risk of varicella in Lu'an City, Anhui Province, so as to provide insights into varicella prevention and control. @*Methods@#Data on incidence of varicella in Lu'an City from 2010 to 2021 were collected from Chinese Disease Prevention and Control System, and meteorological data in Lu'an City were also collected from National Meteorological Science Data Center and China National Urban Air Quality Real-Time Publishing Platform during the same period. The effect of temperature on the risk of varicella was examined using a distributed lag non-linear model (DLNM) and subgroup analyses for gender and age were conducted. The effects of extremely low and high temperatures on the cumulative risk of varicella and trends in the cumulative risk of varicella over time were analyzed using a time-varying DLNM. @*Results@# Totally 25 318 varicella cases were reported in Lu'an City from 2010 to 2021, including 15 013 men (59.30%) and 10 305 women (40.70%). The median number of varicella cases was 4 (interquartile range, 6) cases, and the daily median air temperature was 17.50 (interquartile range, 15.80) ℃, with the lowest temperature recorded as -5.80 ℃ and the highest temperatures as 34.90 ℃. The results from the DLNM showed that the extremely low temperatures reduced the risk of varicella (RR=0.522, 95%CI: 0.375-0.728) in relative to median temperature, while extremely high temperature increased the risk of varicella (RR=1.604, 95%CI: 1.112-2.316). Subgroup analysis revealed the effect curve for men was similar to total populations (extremely low temperature: RR=0.497, 95%CI: 0.331-0.746; extremely high temperature: RR=1.978, 95%CI: 1.260-3.106), and the effect of temperature on varicella risk was mainly concentrated among children at ages of 6 to 12 years (extremely low temperature: RR=0.426, 95%CI: 0.247-0.736; extremely high temperature: RR=2.431, 95%CI: 1.378-4.288). The results from the time-varying DLNM revealed that the cumulative risk of varicella due to both extremely low and high temperatures appeared a tendency towards a rise over years (P<0.05). @*Conclusions@#Low temperature may reduce the risk of varicella, while high temperature increases the risk of varicella in Lu'an City, which is more remarkable among men and children at ages of 6 to 12 years. The cumulative risk of varicella at both extremely low and high temperatures shows a tendency towards a rise over years.

Evaluation of cardiac safety of hydroxyrutaecarpine, hERG channel inhibitor / 药学学报

Drug-induced long QT syndrome (LQTS) has become an important clinical research topic, and the occurrence of acquired long QT syndrome (acLQTS) is mainly caused by drug inhibition of the human ether-α-go-go related gene (hERG) channel. The hERG gene encodes the α subunit of the fast-activating delayed rectifying potassium ion channel (Ikr), which plays an important role in the process of action potential phase 3 repolarization and is also the target of most antiarrhythmic drugs. The purpose of this study was to investigate the effect of hydroxyrutaecarpine (HRU) on the hERG channel and to evaluate its cardiotoxicity. The whole cell patch clamp technique was used to detect the effects of HRU on the current and kinetics of the hERG channel, and to confirm the binding site on the hERG channel. PCR was used to determine the effect of HRU on hERG mRNA expression. Western blotting was used to detect the effects of HRU on the expression of hERG protein and transcription factor Sp1. Immunofluorescence was used to confirm the effects of HRU on localization and expression of hERG protein and transcription factor Sp1. Studies have shown that transient HRU can inhibit hERG current and shorten the inactivation time constant. Its binding sites to the hERG channel are F656 and Y652. After incubation for 24 h, HRU can reduce the expression of hERG protein, inhibit the hERG current, reduce the level of hERG mRNA, and reduce the expression of transcription factor Sp1 in the nucleus and hERG protein in the cytoplasm. Immunofluorescence experiments also showed the same results suggesting that the inhibition of Sp1 expression by HRU is the cause of the decreased expression of hERG mRNA. In conclusion, the acute inhibition of HRU accelerates the channel inactivation process and reduces the inactivation time constant by binding to the F656 and Y652 sites in the hERG channel, thus reducing the hERG current. In addition, HRU also inhibits the expression of hERG protein, mainly by inhibiting the expression of transcription factor Sp1, the transcription function of hERG channel protein is down-regulated, so that the hERG protein is reduced.

Layer-specific strain assessment on left ventricular function before and after PCI in patients with ST segment elevation myocardial infarction / 中华心血管病杂志

Objective: To evaluate the changes of left ventricular function in patients with ST segment elevation myocardial infarction (STEMI) before PCI and within 24 hours after PCI by layer-specific strain, and to explore the value of this new assessment method for quantitative monitoring on the myocardial function in STEMI patients. Methods: A total of 40 patients with acute anterior wall myocardial infarction, who underwent PCI in Affiliated Hospital of Jiangsu University during July 2017 to July 2018, were included in this prospective cohort study. According to the symptom to balloon time (STB), the patients were divided into STB ≤6 hours group (26 cases) and STB 6-12 hours group (14 cases). Echocardiography was performed before, immediately, 3 hours and 24 hours after PCI. Echocardiographic indexes including endocardial myocardial longitudinal strain (LS-endo), 18-segment full-thickness myocardial longitudinal strain (LS) of left ventricle and left ventricular global longitudinal strain (GLS) were measured. The mean LS-endo and LS values of myocardial segments in infarcted area (IALS-endo, IALS) and the mean LS-endo and LS values of myocardial segments in non-infarcted area (NIALS-endo, NIALS) were calculated. Results: There were 34 males and 6 females in this cohort and age was (62±10) years. In STB≤6 hours group, the IALS-endo value ((13.7±4.9)% vs. (10.0±2.7)%, P<0.05) and NIALS-endo value ((17.0±2.9)% vs. (14.6±2.9)%, P<0.05) were significantly higher at 24 hours after PCI than those before PCI. In the group of STB 6-12 hours, IALS-endo decreased immediately after PCI ((6.7±3.3)% vs. (11.9±6.5)%, P<0.05), and there was a rising trend at 3 hours after PCI (P>0.05). At 24 hours after PCI, the index was higher than that immediately after PCI ((13.6±8.4)% vs. (6.7±3.3)%, P<0.05). The NIALS-endo value was significantly higher at 24 hours after PCI than that before PCI ((17.1±2.1)% vs. (14.5±3.2)%, P<0.05). In the STB 6-12 hours group, the decrease rate of IALS-endo immediately after PCI was higher than that in the STB ≤6 hours group (93% (13/14) vs. 35% (9/26), P<0.001). In STB ≤6 hours group, the NIALS value at 24 hours after PCI was higher than that before PCI (P<0.05), and there was no significant difference in IALS, NIALS and GLS at other time points (P>0.05). Conclusions: Layered LS is superior to full-thickness LS and GLS in evaluating left ventricular function in STEMI patients. LS measured by echocardiography can continuously and quantitatively evaluate the changes of left ventricular myocardial function in STEMI patients before and after PCI.

Meta-analysis of androgen deprivation therapy for prostate cancer related with diabetes / 药物评价研究

Objective To examine whether androgen deprivation therapy (ADT) is associated with increased risk of diabetes in men with prostate cancer (Pca).Methods The study data were systematically searched from Medline,Embase,and Cochrane Library Central Register.Studies comparing ADT vs control aimed at treating Pca,reporting diabetes as outcome were included.Results Eight studies met inclusion criteria with a total of 65 695 ADT users and 91 893 non-ADT users investigating the relationship between ADT and diabetes.The incidence of diabetes was 39％ higher in ADT groups,and significant association was observed in overall analysis [RR =1.39,95％CI(1.27-1.53),P ＜ 0.01].In subgroup-analyses stratified by ADT types,diabetes was found to be significantly associated with gonadotropin-releasing hormone (GnRH) alone [RR =1.45,95％CI(1.36-1.54),P ＜ 0.01),GnRH plus oral anti-androgen (AA) [RR =1.40,95％CI(1.01-1.93),P ＜ 0.01] and Orchiectomy [RR =1.34,95％CI(1.20-1.50),P ＜ 0.01],but not with AA alone [RR =1.33,95％CI(0.75-2.36),P =0.33].Conclusions ADT,especially GnRH alone,GnRH plus AA and orchiectomy can increase the incidence of diabetes in patients with Pca.

Induction cell damage and change of nuclear factor-kappa B expression by bromoxynil in SH-SY5Y cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the cytotoxicity of bromoxynil on SH-SY5Y cells and its effect on the expression of nuclear factor-kappa B (NF-κB) and I kappa B alpha (IκBα) in SH-SY5Y cells.</p><p><b>METHODS</b>SH-SY5Y cells were exposed to bromoxynil (10, 50, or 100 µmol/L) for 24 and 48 h, and other SH-SY5Y cells, which were used as a control, were exposed only to dimethyl sulfoxide. After 24 and 48 h of exposure, the morphological changes of these cells were observed under an inverted microscope, and the cytotoxicity of bromoxynil was measured by MTT assay. The cellular proliferation was examined by cell counting after 12, 24, 48, 72, and 96 h of exposure. After 24 h of exposure, the expression of NF-κB was evaluated by Western blot and immunocytochemistry, and the expression of IκBα was evaluated by Western blot.</p><p><b>RESULTS</b>The cellular proliferation inhibition rates (CPIRs) of 50 and 100 µmol/L groups were significantly higher than that of the control group after 24 and 48 h of exposure (P < 0.05); the CPIR was significantly higher after 48 h than after 24 h in the two groups (P < 0.05). The growth curve revealed that these groups began to show differences in cell count at the 24th of exposure and that the differences were even more marked as the exposure went on (F = 17.15, P < 0.05). The control group had a significantly increased cell count at the 48th, 72nd, and 96th h of exposure (P < 0.05); the 10 and 50 µmol/L groups had a significantly increased cell count at the 72nd and 96th h of exposure (P < 0.05); the 100 µmol/L group showed no significant change in cell count during 96h of exposure. The 50 and 100 µmol/L groups hada significantly longer cell doubling time than the control group (P < 0.05). The immunocytochemistry showed that as the dose of bromoxynil increased, the brownish yellow particles in the cytoplasm and nuclei became darker, the expression of NF-κB was upregulated, and the nuclear translocation of NF-κB was increased. The Western blot showed that the 100 µmol/L group had significantly higher expression of NF-κB in the nuclei than the control group (P < 0.05) and that the 50 and 100 µmol/L groups had significantly lower expression of IκBα in total proteins than the control group (P < 0.05).</p><p><b>CONCLUSION</b>Bromoxynil can inhibit the proliferation of SH-SY5Y cells under this experimental condition, which may be related to activation of NF-κB.</p>

Study on mechanism of trimethyltin chloride-induced apoptosis in PC12 cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of trimethyltin chloride (TMT) on proliferation, apoptosis, oxidative damage, and NF-κB expression in PC12 cells in vitro.</p><p><b>METHODS</b>PC12 cells were treated with 0, 0.3125, 0.6250, 1.2500, 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 24 and 48 h, and MTT assay was used to evaluate cell viability. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 12 and 24 h, and flow cytometry was used to measure the apoptotic rates of cells. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 6 h, and the reactive oxygen species (ROS) and glutathione (GSH) levels were measured. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 12 h, and Western blot was used to measure NF-κB levels.</p><p><b>RESULTS</b>Compared with solvent controls, the PC12 cells treated with 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 24 h showed significantly decreased cell viability (P < 0.05); the PC12 cells treated with 1.2500, 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 48 h showed significantly decreased cell viability (P < 0.05). The PC12 cells treated with 1.2500, 2.5000, 5.0000, and 10.0000 µmol/L TMT for 12 h had apoptotic rates of 15.30% ± 0.75%, 18.90% ± 0.61%, 22.00% ± 0.60%, and 36.50% ± 0.66%, respectively, and the PC12 cells treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 24 h had apoptotic rates of 28.6% ± 0.40%, 43.54% ± 2.00%, 65.73% ± 0.71%, and 74.67% ± 0.40%, respectively, all significantly higher than those of the control group (12 h: 12.80% ± 1.00%, 24h: 16.83% ± 0.25%) (P < 0.05). The ROS fluorescence intensities of the PC12 cells treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT were 1.42, 1.71, 1.78, and 1.89 times that of the control group (P < 0.05); the PC12 cells treated with 2.50, 5.00, and 10.00 µmol/L TMT had GSH levels of 0.17 ± 0.0, 0.20 ± 0.04, and 0.07 ± 0.03 µmol/µg protein, significantly lower than that of the control group (0.30 ± 0.01 µmol/L protein) (P < 0.05). The PC12 cells treated with 2.50, 5.00, and 10.00 µmol/L TMT had significantly higher expression of NF-κB p65 than the control group (P < 0.05).</p><p><b>CONCLUSION</b>Under our laboratory conditions, TMT can significantly inhibit proliferation and induce apoptosis in PC12 cells, which may be related to oxidative stress and NF-κB signaling pathway activation.</p>