Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation. In the past decade, it has been implicated in the pathogenesis of various diseases that together involve almost every organ of the body, including various cancers, neurodegenerative diseases, cardiovascular diseases, lung diseases, liver diseases, kidney diseases, endocrine metabolic diseases, iron-overload-related diseases, orthopedic diseases and autoimmune diseases. Understanding the underlying molecular mechanisms of ferroptosis and its regulatory pathways could provide additional strategies for the management of these disease conditions. Indeed, there are an expanding number of studies suggesting that ferroptosis serves as a bona-fide target for the prevention and treatment of these diseases in relevant pre-clinical models. In this review, we summarize the progress in the research into ferroptosis and its regulatory mechanisms in human disease, while providing evidence in support of ferroptosis as a target for the treatment of these diseases. We also discuss our perspectives on the future directions in the targeting of ferroptosis in human disease.
Humans ; Ferroptosis ; Autoimmune Diseases ; Cardiovascular Diseases ; Iron ; Musculoskeletal Diseases

Humans ; Locomotion ; Mesencephalon ; Midbrain Reticular Formation ; Parkinson Disease

【Objective】 To investigate the death time of patients with coronavirus disease 2019 (COVID-19). 【Methods】 The death time was calculated and analyzed using individual data and aggregated data through the daily notification of the epidemic situation and the death cases published on the website of the Heath Commission of China and provinces. 【Results】 In the 153 patients who died of COVID-19, the shortest time from onset to death was 4 days and the longest time was 50 days with the mean±standard deviation of (16.7±9.2) days. The median was 14 days and the 95% confidence interval was 4.6-42.9. The shortest time from admission to death was 1 day and the longest time was 50 days with the mean ± standard deviation of (12.1±7.8) days. The median was 11 days and the 95% confidence interval was 2-32.8. The time curve from diagnosis to death was skewed. The death time from diagnosis to death was 0 to 48 days with the mean ± standard deviation of (11.1±8.9) days. The median was 9 days, the interquartile interval was 10.5 days, and the 95% confidence interval was 0-35.4. It took 3 days from onset to admission and 1 day from admission to diagnosis. Aggregated data showed that the time from diagnosis to death of COVID-19 patients in China, China (except Hubei Province), Hubei Province and Wuhan City was 8, 9, 6 and 6 days, respectively. 【Conclusion】 The time from diagnosis to death of COVID-19 patients varied significantly, with the median time of 6-9 days in different regions.

Objective To study the underlying mechanisms through which uric acid upregulates local renin-angiotensin system in adipocytes. Methods The primary cultured rat adipocytes were administered with 0, 1, 5, 10, and 15 mg/dl uric acid for 0, 12, 24, 48, and 72 h. Some of the pre-adipocytes were infected with siRNA-TLR2 or its negative control before differentiation. Then infected mature adipocytes were treated with 10 mg/dl uric acid for 48 h. After that procedure, mRNA levels of TLR2, TNF-α, IL-6, MCP-1, AGT, ACE1, AT1R, and AT2R were detected with real-time PCR method. The protein levels of TLR2 and NF-κB were detected by Western blotting. The concentrations of angiotensinⅡ( Ang Ⅱ) in the conditioned medium or cell lysate were measured using ELISA method. Results The mRNA levels mRNA of TLR2 increased in parallel with uric acid concentration. Moreover, it also increased with the time. By contrast, TLR2 mRNA expression decreased at 72 h. Uric acid increased levels of TNF-α, IL-6, and MCP-1 in adipocytes. It was also found that uric acid upregulated RAS components, including AGT, ACE1, AT1R, AT2R, and AngⅡ. However, siRNA-TLR2 infection significantly reduced the levels of TLR2 and NF-κB. As a result, both inflammatory cytokines and RAS components were significantly decreased in adipocytes. Conclusion Uric acid up-regulates RAS expression partially via TLR2 inflammatory signaling pathway in adipocytes.

The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum. Recently, three K channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance (SK) channels, A-type K channels, and K7/KCNQ channels. In this review, we summarize the physiological and pharmacological effects of the three K channels. We also describe in detail the laboratory investigations regarding K channels as a potential therapeutic target for PD.
Animals ; Humans ; Parkinson Disease ; metabolism ; Potassium Channels ; metabolism

Objective To explore the value of the plasma miR-193a-5p level on diagnosis and monitoring the response to treatment in acute myeloid leukemia (AML). Methods Peripheral blood samples were obtained from AML patients enrolled in hematology department of the Second Hospital of Shanxi Medical University from July 2015 to December 2015, including 30 de novo AML patients, 9 patients in complete remission (CR) and 6 patients in relapse. Peripheral blood samples from 15 healthy people were randomly choosed as the health control group. Plasma miR-193a-5p expression levels were detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Results The plasma miR-193a-5p relative expression level of AML patients group [0.465 6 (0.103 1-5.000 2)] was obviously lower than that of health control group [0.766 1 (0.052 1-3.134 4)] (U= 122, P= 0.018 7). The plasma miR-193a-5p relative expression levels of de novo group and relapse AML group were significantly lower than those of CR group and health control group (P<0.05), and there was no significant difference between the CR group and health control group (U= 56, P= 0.511 9). No significant correlation was found between the plasma miR-193a-5p level and age, gender, blast percentage of the bone marrow, peripheral blood leukocyte count, platelet count, CD34+cells'percentage and so on. Conclusion The decreased plasma miR-193a-5p expression level can be served as a new and noninvasive biomarker for the evaluation of diagnosis and treatment in AML.

Objective To investigate the effect of over-expression of human ribonuclease inhibitor suppresses invasion and migration of transplanted bladder cancer .Methods The T24 cells were stably transfected with pIRES2-EGFP-RI and pIRES2-EG-FP plasmid respectively .Using the cell transfected with pIRES2-EGFP and untransfected cell as controls .and the positive clones were screened by G418 ,respectively ;Tumor cells of the three groups at 2 × 106 were respectively injected into the back of BALB/C nude mice to establish the xenograft models .Change of micro-blood vessels in tumor tissue and expression of CD31 were detected by Immunohisto-chemical and HE staining .Immunohisto-chemical assay was used to detect the expression of RI ,MMP-2 ,MMP-9 ,E-cadherin ,N-cadherin ,Vimentin ,Snail ,Slug ,Twist in the tumors .Results Animal experiment showed that the T24-RI cells group significantly inhibited the growth of bladder cancer compared with the other two control groups .Compared with the T24 and T24 vector cells groups ,the microvessel density in tumor tissue of T24-RI group was notably reduced and the expressions of MMP-2 , MMP-9 ,N-cadherin ,Vimentin ,Snail ,Slug ,Twist significantly were decreased simultaneously ,while the expressions of RI and E-cadherin were increased .Conclusion up-regulation RI can inhibit the growth of transplanted bladder cancer in nude mice by decrea-sing the expression of invasion protein and EM T protein .

Objective To compare the efficacy of conventional radiotherapy and Tomo radiotherapy com -bined with zoledronic acid in spinal metastase .Methods Seventy -nine patients with spinal metastases in our department of Air Force General Hospital were recruited from January 2011 to December 2012 .All patients were divided into two groups:group A:39 cases were treated with conventional radiotherapy combined with zoledronic ( PTV:30~40 Gy/10~20 f);40 patients with target in target Tomo radiotherapy combined with zoledronic acid were separated into group B(PTV/GTV/40~50 Gy/50~60 Gy/15~20 f).Results The overall following -up rate was 96.2%.The total response rate was 88.61%,the analgesic effect of radiotherapy in group A and group B were 84.62%、92.5%,respectively.The average pain scores were decreased by 2.55 and 3.54 in two gourps u-sing a numerical rating scale;the average pain relieve time were 7.25d and 8.32d,respectively;the median last-ing time of pain relieves were 6.68 and 8.41months;and the pain recurrence rate were 25.81% and 5.41% in corresponding group A and group B .The main acute side effects were hematologic toxicity , in which occurring rates were 12.82%and 12.5%in RTOG gradeⅠ,23.08% and 20%in RTOG grade Ⅱ,2.56% and 2.5% in RTOG gradeⅢ,2.46%and 0%in RTOG grade Ⅳin group A and group B,respectively.There were no signifi-cant differences in pain relief rate ,start-effect time,lasting time and acute side effects between the two different radiotherapy methods .However ,the decreased degree of pain relief and recurrence rate were obviously decreased in group B when compared with group A ,and the differences were statistically significance (P<0.05).Conclu-sion Target in target Tomo radiotherapy combined with zoledronic acid in the treatment of spinal metastasies is safe and effective,mild toxicity,and the degree of pain relief was significantly improved .Moreover,pain recurrence rate is lower than conventional radiotherapy .Hence ,it is worth of recommendation in clinical practice .

Objective To analyze the setup errors of bone metastases patients by tomotherapy with megavoltage CT (MVCT) and calculate the CTV-PTV margins.Methods 30 patients with bone metastases were enrolled.All patients received tomotherapy,fixed with body net and received MVCT scanning before radiation.The MVCT images were registered with the kilovoltage CT (kVCT) images,the setup errors of X (lateral),Y (vertical),Z (longitudina) and Roll (transverse profile rotation) were obtained according to the formula M =2.5Σ+0.7σ calculated CTV-PTV margin.Results 30 patients were received 494 MVCT images.The errors of systemic±random were (2.85±0.77) mm,(3.11±0.95) mm,(2.21±0.55) mm,and (0,55±0.24)° on X,Y,Z and Roll directions,respectively.The CTV-PTV margins were 3.64 mm,4.17 mm,and 2.86 mm on X,Y,Z directions,respectively.Conclusion The application of image-guided technology for bone metastases can correct positioning in time,which greatly reduces setup errors of the fractionated treatment,further improves the treat accuracy and has a positive value in guiding clinical radiotherapy.