Iron regulatory protein 2 (IRP2) plays a key role in the cellular iron homeostasis and could be regulated by a variety of factors, such as oxidative stress, hypoxia and iron, etc. IRP2 depletion results in neurodegenerative movement disorder with the loss of neurons and accumulations of iron. Since oxidative stress extensively exists in several neurodegenerative diseases where iron accumulation also exists, it is important to clarify the mechanisms underlying the effects of oxidative stress on IRP2 expression and its consequence. 200 and 300 μM H2O2 could result in the reduced cell viability in SH-SY5Y cells. The intracellular levels of reactive oxygen species (ROS) were increased by 52.2 and 87.3% with 200 and 300 μM H2O2 treatments, respectively. The decreased levels of mitochondrial transmembrane potential (ΔΨm) were only observed in 300 μM H2O2-treated group. The protein levels of IRP2, but not for its mRNA levels, were observed decreased in both groups, which resulted in the lower TfR1 expression and decreased iron uptake in these cells. Pretreatment with MG132, the decreased IRP2 levels caused by H2O2 treatment could be antagonized. The protein levels of F box and leucine-rich repeat protein 5 (FBXL5), the only E3 ligase of IRP2, were observed decreased accordingly. When knockdown the intracellular FBXL5 levels by si-FBXL5, the protein levels of IRP2 were found increased with H2O2 treatment. Our results suggest that FBXL5 is involved in the degradation of IRP2 under oxidative stress in dopaminergic-like neuroblastoma cells, which implies that its role in the neuronal regulation of IRP2 in neurodegenerative diseases.
Background: Confirmed as a familial clustered case, a COVID-19 patient displaying established symptoms was simultaneously diagnosed with an HIV infection, and treated with several antiviral and compassionate drugs.Case presentation: The upper respiratory tract Nucleic Acid Testing (NAT) for the novel coronavirus continued to be positive for consecutive 49 days. During the course of treatment, it was observed that the other six cases in the family were non-HIV infected and displaying common Covid-19 symptoms, the familial cluster received parallel treatment along with the aforementioned patient, and the median time for the NAT to present as negative was 29 days. Conclusions: The results of this research indicate that the novel coronavirus attacks T lymphocyte subsets, andfurther studies with larger sample sizes are required to verify how the immune escape mechanism of the new coronavirus interacts with HIV infection.
Background SARS-CoV-2 is making deadly impact on the human lives all over the world. Therefore, we aimed to analyze the changes involved in clinical characteristics of COVID-19 patients over time. Methods We conducted a retrospective study to compare the patients whose onset of illness in January with the patients whose onset of illness in February in Wuhan, China.Results Among enrolled 896 patients, the median age was 60 years (47-69 years), 685 (76.5%) were categorized into group A (patients with illness onset in January), and 211 (23.5%) were categorized into group B (patients with illness onset in February). Compared with group B, group A had a higher rate of fever (p<0.001), the lower rate of asymptomatic (p<0.001). Group A had a higher incidence of neutrophilia (p=0.043), elevated D-miner (p<0.001), increased LDH (p=0.002), but lower incidence of normal CT scan (p=0.001). CD3 cells (p=0.015) and CD4 cells p=0.04) count significantly reduced in group A. Critical patients decreased (p=0.005) and mild patients increased (p=0.001) in group B. The fatality rate significantly decreased in group B (p=0.028).Conclusions The condition of patients with onset of illness in January were more serious than patients with onset of illness in February. It indicates that virulence showed reducing effect, but more basic research is required to support the hypothesis.
BACKGROUND Men who have sex with men (MSM) have high HIV incidence and prevalence burdens but relatively low HIV testing rates. Literature showed insufficient evidence on the efficacy of Social media (WeChat) based HIV self-testing (HIVST) kits distribution approaches among MSM and their sexual partners. OBJECTIVE This study evaluated an Social media (WeChat) based HIVST distribution intervention in increasing HIV testing uptake among MSM and their sexual partners in China. METHODS The study used a 12-month stepped-wedge randomized controlled trial design and an online survey mode. MSM who were HIV-negative or with unknown HIV status were recruited through social media marketing and outreaches by community opinion leaders between August and December 2018 in Shenyang, Beijing, Chongqing, and Shenzhen. Participants were randomly allocated to four groups, which were intervened by sequence. The intervention group received free HIVST kits on top of the control condition that participants received standard education and care. Participants were followed up from January to December 2019. Generalized linear models were used to assess HIV testing coverage and frequency difference between the intervention and the control stage. RESULTS Each group enrolled 140 eligible MSM with a total of 560 participants. Twelve participants were diagnosed with HIV infections, and 4 of them were in the follow-up period. Participants in the intervention stage were nine times likely to receive an HIV test than in the control stage (85.6% vs. 39.2%, risk ratio [RR]=9.21, 95%CI 5.92~14.33). The intervention also increased participants’ HIV testing frequency (1.48 vs. 0.59 times, risk difference [RD]=0.89, 95%CI 0.82~0.96). Moreover, the intervention increased HIV testing proportion (49.0% vs. 30.1%, RR=2.23, 95%CI 1.46~3.40) and mean HIV testing frequency (0.69 vs. 0.35 times, RD=0.26, 95%CI 0.15~0.38) among participants sexual partners who received HIVST through secondary distribution. CONCLUSIONS An Social media (WeChat) based HIVST distribution intervention effectively increased HIV testing coverage and frequency in MSM and their sexual partners. Future programs could apply this approach in HIV education and testing efforts to reduce HIV incidence. CLINICALTRIAL This study was registered at the Chinese Clinical Trials website (http://www.chictr.org.cn/index.aspx) with the registration tracking number of ChiCTR1800019453 on November 12, 2018. INTERNATIONAL REGISTERED REPORT RR2-10.2196/17788
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