Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 168
Filtrar
1.
Cell Death Discov ; 7(1): 267, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588431

RESUMO

The purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2'-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated.

2.
Aging (Albany NY) ; 13(18): 21903-21913, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551393

RESUMO

The mortality rate of young female COVID-19 patients is reported to be lower than that of young males but no significant difference in mortality was found between female and male COVID-19 patients aged over 65 years, and the underlying mechanism is unknown. We retrospectively analyzed clinical characteristics and outcomes of severely ill pre- and post-menopausal COVID-19 patients and compared with age-matched males. Of the 459 patients included, 141 aged ≤55, among whom 19 died (16 males vs. 3 females, p<0.005). While for patients >55 years (n=318), 115 died (47 females vs. 68 males, p=0.149). In patients ≤55 years old, the levels of NLR, median LDH, median c-reactive protein and procalcitonin were significantly higher while the median lymphocyte count and LCR were lower in male than in female (all p<0.0001). In patients over 55, these biochemical parameters were far away from related normal/reference values in the vast majority of these patients in both genders which were in contrast to that seen in the young group. It is concluded that the mortality of severely ill pre-menopausal but not post-menopausal COVID-19 female patients is lower than age-matched male. Our findings support the notion that estrogen plays a beneficial role in combating COVID-19.


Assuntos
COVID-19/mortalidade , Estrogênios/metabolismo , Menopausa , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , COVID-19/metabolismo , Feminino , Identidade de Gênero , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Pós-Menopausa , Pré-Menopausa , Pró-Calcitonina/sangue , Estudos Retrospectivos , SARS-CoV-2 , Fatores Sexuais
3.
Front Med (Lausanne) ; 8: 713733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490304

RESUMO

Background: SARS-CoV-2 infection was referred to sympathetic hyperactivity, which might increase the susceptibility of neuraxial anesthesia-related hypotension resulted from sympathetic inhibition. We conducted a multicenter, retrospective, propensity score matched (PSM) cohort study to determine whether COVID-19 parturients have an increased risk of hypotension after neuraxial anesthesia for cesarean delivery. Methods: Clinical data of COVID-19 parturients were collected from the electronic medical records from 1th January to 31th May, 2020 in three hospitals of Hubei Province, China. Information of Control parturients (without COVID-19) were obtained at the same institutions over a similar period in 2019. All American Society of Anaesthesiologists (ASA) Physical Status II full termed pregnant women who received cesarean delivery under neuraxial anesthesia were included. The primary objective was to obtain and compare the incidence of neuraxial anesthesia-related hypotension. Secondary objectives were the analysis of anesthetic implementation and administration, intraoperative maternal vital signs and adverse reactions, and neonatal Apgar scores at 1 and 5 min after delivery. The clinical characteristics of COVID-19 parturients were also analyzed. PSM was derived to balance the predictors for neuraxial anesthesia-related hypotension based on previous studies. Results: In present study, 101 COVID-19 parturients and 186 Control parturients were derived from 1,403 cases referenced to propensity score matching. The incidence of neuraxial anesthesia-related hypotension was 57.4% in COVID-19 parturients and 41.9% in Control parturients with an incidence risk ratio (IRR) of 1.37 (95% CI 1.08-1.74; P = 0.012; post-hoc Cramér's V = 0.15) in the PSM cohort. The incidences of nausea, vomiting, dizziness, and shaking were significantly higher in the COVID-19 group than Control group (48.5 vs. 17.2%, P < 0.001; 10.9 vs. 4.3%, P = 0.03; 18.8 vs. 3.2%, P < 0.001; 51.5 vs. 18.3%, P < 0.001; respectively). The Apgar scores at 1 min was significantly lower in newborns from COVID-19 parturients than that in Control babies (P = 0.04). Conclusions: An increased risk of neuraxial anesthesia-related hypotension in COVID-19 parturients undergoing cesarean delivery should be stressed.

4.
J Wound Care ; 30(8): 594-597, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34382848

RESUMO

Given the current COVID-19 crisis, multiple clinical manifestations and related complications of COVID-19 disease, especially in lung transplant patients following post-COVID-19 pneumonia, are a major challenge. Herein, we report the therapeutic course of the first reported case of sacrococcyx pressure ulcers (PU) in a 65-year-old male COVID-19 patient who underwent lung transplantation and developed a PU following surgery. We used a combination of regulated negative pressure-assisted wound therapy system (RNPT, six treatment courses, five days per treatment course), a skin tension-relief system (an intraoperative aid in minimising wounds caused by sacrococcygeal PUs) and a gluteus maximus myocutaneous flap to repair sacrococcygeal wounds. This successfully treated case provides a reference point for the treatment of similar cases.


Assuntos
COVID-19 , Transplante de Pulmão , Lesão por Pressão , Idoso , Humanos , Masculino , SARS-CoV-2 , Retalhos Cirúrgicos
5.
Aging (Albany NY) ; 13(12): 15801-15814, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182540

RESUMO

Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide and causes high mortality of elderly patients. High-flow nasal cannula therapy (HFNC) is an oxygen delivery method for severely ill patients. We retrospectively analyzed the course of illness and outcomes in 110 elderly COVID-19 patients (≥65 years) treated with HFNC from 6 hospitals. 38 patients received HFNC (200 mmHg < PaO2/FiO2 ≤ 300 mmHg, early HFNC group), and 72 patients received HFNC (100 mmHg < PaO2/FiO2 ≤ 200 mmHg, late HFNC group). There were no significant differences of sequential organ failure assessment (SOFA) scores and APECH II scores between early and late HFNC group on admission. Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe acute respiratory distress syndrome (ARDS), longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. 24 patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2 (5.3%) in the early HFNC group. The present study suggested that the outcomes were better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC.


Assuntos
COVID-19/complicações , Cânula , Oxigenoterapia/instrumentação , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Idoso , COVID-19/mortalidade , COVID-19/terapia , China , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Análise Multivariada , Síndrome do Desconforto Respiratório/mortalidade , Estudos Retrospectivos
6.
Aging (Albany NY) ; 13(12): 16105-16123, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34118791

RESUMO

Diabetic patients are more vulnerable to cerebral ischemia-reperfusion (CIR) injury and have a worse prognosis and higher mortality after ischemic stroke than non-diabetic counterparts. Melatonin can exert neuroprotective effects against CIR injury in nondiabetic animal models. However, its effects on diabetic CIR injury and the underlying mechanisms remain unclarified. Herein, we found that melatonin administration improved neurological deficit, cerebral infarct volume, brain edema, and cell viability, reduced mitochondrial swelling, reactive oxygen species generation, and cytoplasmic cytochrome C release, and increased mitochondrial antioxidant enzymes activities, adenosine triphosphate production, and mitochondrial membrane potential in both streptozotocin-induced diabetic mice and high glucose-treated HT22 cells. Importantly, melatonin also activated protein kinase B (Akt) and sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) signaling and upregulated mitochondrial biogenesis-related transcription factors. However, these effects were largely attenuated by LY294002 (a specific Akt signaling blocker) administration. Additionally, 3-TYP (a selective SIRT3 inhibitor) and SIRT3 siRNA inhibited the above protective effects of melatonin as well as the upregulation of SIRT3 and the decrease of SOD2 acetylation but did not affect the p-Akt/Akt ratio. Overall, we demonstrate that melatonin can alleviate CIR injury in diabetic mice by activating Akt-SIRT3-SOD2 signaling and subsequently improving mitochondrial damage.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Melatonina/uso terapêutico , Mitocôndrias/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Edema Encefálico/complicações , Edema Encefálico/tratamento farmacológico , Edema Encefálico/patologia , Isquemia Encefálica/complicações , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Diabetes Mellitus Experimental/complicações , Glucose/toxicidade , Masculino , Melatonina/farmacologia , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Morfolinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos
7.
J Mol Histol ; 52(4): 705-715, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34105058

RESUMO

Lipopolysaccharide (LPS)-induced autophagy is involved in sepsis-associated myocardial injury with increased PKCß2 activation. We previously found hyperglycemia-induced PKCß2 activation impaired the expression of caveolin-3 (Cav-3), the dominant isoform to form cardiomyocytes caveolae which modulate eNOS signaling to confer cardioprotection in diabetes. However, little is known about the roles of PKCß2 in autophagy and Cav-3/eNOS signaling in cardiomyocytes during LPS exposure. We hypothesize LPS-induced PKCß2 activation promotes autophagy and impairs Cav-3/eNOS signaling in LPS-treated cardiomyocytes. H9C2 cardiomyocytes were treated with LPS (10 µg/mL) in the presence or absence of PKCß2 inhibitor CGP53353 (CGP, 1 µM) or autophagy inhibitor 3-methyladenine (3-MA, 10 µM). LPS stimulation induced cytotoxicity overtime in H9C2 cardiomyocytes, accompanied with excessive PKCß2 activation. Selective inhibition of PKCß2 with CGP significantly reduced LPS-induced cytotoxicity and autophagy (measured by LC-3II, Beclin-1, p62 and autophagic flux). In addition, CGP significantly attenuated LPS-induced oxidative injury, and improved Cav-3 expression and eNOS activation, similar effects were shown by the treatment of autophagy inhibitor 3-MA. LPS-induced myocardial injury is associated with excessive PKCß2 activation, which contributes to elevated autophagy and impaired Cav-3/eNOS signaling. Selective inhibition of PKCß2 improves Cav-3/eNOS signaling and attenuates LPS-induced injury through inhibiting autophagy in H9C2 cardiomyocytes.

8.
Front Mol Biosci ; 8: 655619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996908

RESUMO

Intestinal mucosal barrier dysfunction induced by myocardial ischemia reperfusion (IR) injury often leads to adverse cardiovascular outcomes after myocardial infarction. Early detection and prevention of remote intestinal injury following myocardial IR may help to estimate and improve prognosis after acute myocardial infarction (AMI). This study investigated the protective effect of myocardial ischemic postconditioning (IPo) on intestinal barrier injury induced by myocardial IR and the underlying cellular signaling mechanisms with a focus on the DJ-1. Adult SD rats were subjected to unilateral myocardial IR with or without ischemic postconditioning. After 30 min of ischemia and 120 min of reperfusion, heart tissue, intestine, and blood were collected for subsequent examination. The outcome measures were (i) intestinal histopathology, (ii) intestinal barrier function and inflammatory responses, (iii) apoptosis and oxidative stress, and (iv) cellular signaling changes. IPo significantly attenuated intestinal injury induced by myocardial IR. Furthermore, IPo significantly increased DJ-1, nuclear Nrf2, NQO1, and HO-1 expression in the intestine and inhibited IR-induced apoptosis and oxidative stress. The protective effect of IPo was abolished by the knockdown of DJ-1. Conversely, the overexpression of DJ-1 provided a protective effect similar to that of IPo. Our data indicate that IPo protects the intestine against myocardial IR, which is likely mediated by the upregulation of DJ-1/Nrf2 pathway.

9.
BMC Anesthesiol ; 21(1): 98, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33784983

RESUMO

BACKGROUND: Ultrasound-guided parasternal intercostal nerve block is rarely used for postoperative analgesia, and its value remains unclear. This study aimed to evaluate the effectiveness of ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in patients undergoing median sternotomy for mediastinal mass resection. METHODS: This randomized, double-blind, placebo-controlled trial performed in Renmin Hospital, Wuhan University, enrolled 41 participants aged 18-65 years. The patients scheduled for mediastinal mass resection by median sternotomy were randomly assigned were randomized into 2 groups, and preoperatively administered 2 injections of ropivacaine (PSI) and saline (control) groups, respectively, in the 3rd and 5th parasternal intercostal spaces with ultrasound-guided (USG) bilateral parasternal intercostal nerve block. Sufentanil via patient-controlled intravenous analgesia (PCIA) was administered to all participants postoperatively. Pain score, total sufentanil consumption, and postoperative adverse events were recorded within the first 24 h. RESULTS: There were 20 and 21 patients in the PSI and control group, respectively. The PSI group required 20% less PCIA-sufentanil compared with the control group (54.05 ± 11.14 µg vs. 67.67 ± 8.92 µg, P < 0.001). In addition, pain numerical rating scale (NRS) scores were significantly lower in the PSI group compared with control patients, both at rest and upon coughing within 24 postoperative hours. Postoperative adverse events were generally reduced in the PSI group compared with controls. CONCLUSIONS: USG bilateral parasternal intercostal nerve block effectively reduces postoperative pain and adjuvant analgesic requirement, with good patient satisfaction, therefore constituting a good option for mediastinal mass resection by median sternotomy.

10.
Transl Psychiatry ; 11(1): 185, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771972

RESUMO

Chronic stress is an environmental risk factor for depression and causes neuronal atrophy in the prefrontal cortex (PFC) and other brain regions. It is still unclear about the molecular mechanism underlying the behavioral alterations and neuronal atrophy induced by chronic stress. We here report that phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a mediator for chronic stress-induced depression-like behaviors and neuronal atrophy in mice. One-month chronic restraint stress (CRS) up-regulated PTEN signaling pathway in the PFC of mice as indicated by increasing levels of PTEN, p-MEK, and p-ERK but decreasing levels of p-AKT. Over-expression of Pten in the PFC led to an increase of depression-like behaviors, whereas genetic inactivation or knockdown of Pten in the PFC prevented the CRS-induced depression-like behaviors. In addition, systemic administration of PTEN inhibitor was also able to prevent these behaviors. Cellular examination showed that Pten over-expression or the CRS treatment resulted in PFC neuron atrophy, and this atrophy was blocked by genetic inactivation of Pten or systemic administration of PTEN inhibitor. Furthermore, possible causal link between Pten and glucocorticoids was examined. In chronic dexamethasone (Dex, a glucocorticoid agonist) treatment-induced depression model, increased PTEN levels were observed, and depression-like behaviors and PFC neuron atrophy were attenuated by the administration of PTEN inhibitor. Our results indicate that PTEN serves as a key mediator in chronic stress-induced neuron atrophy as well as depression-like behaviors, providing molecular evidence supporting the synaptic plasticity theory of depression.


Assuntos
Depressão , Estresse Psicológico , Animais , Glucocorticoides , Camundongos , Plasticidade Neuronal , Córtex Pré-Frontal , Estresse Psicológico/complicações
11.
Artigo em Inglês | MEDLINE | ID: mdl-33620678

RESUMO

PURPOSE: Histone deacetylase 3 (HDAC3) and silent information regulator 1 (SIRT1) are histone deacetylases that regulate important metabolic pathways and play important roles in diabetes and myocardial ischemia/reperfusion (IR) injury. In this study, we explored the protective mechanism of Bmal1-regulated autophagy mediated by the HDAC3/SIRT1 pathway in myocardial IR injury of diabetic rats. METHODS AND RESULTS: Type 1 diabetes was established by administering an intraperitoneal injection of streptozotocin. After 8 weeks, the left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min to establish a myocardial IR injury model in diabetic rats. H9c2 cardiomyocytes were exposed to high glucose concentration (30 mM) and hypoxia/reoxygenation (H/R) stimulation in vitro. The myocardial infarct size and levels of serum cTn-I, CK-MB, and LDH in diabetic rats subjected to myocardial IR injury were significantly higher. Upregulated HDAC3 and downregulated SIRT1 expression were observed in diabetic and IR hearts, along with a lower Bmal1 level. Autophagy was rapidly increased in the hearts of diabetic or non-diabetic rats in the IR group compared with the sham group, but significantly attenuated in the hearts of diabetic rats compared with the hearts of non-diabetic rats after IR insult. Consistent with decreased autophagy, we observed increased HDAC3 expression and decreased SIRT1 and Bmal1 levels in the myocardial tissue of diabetic rats after IR. Inhibition of HDAC3 by the inhibitor RGFP966 and activation of SIRT1 by the agonist SRT1720 could significantly attenuate myocardial IR injury in diabetic rats by restoring Bmal1-regulated autophagy. CONCLUSION: Based on these findings, the disordered HDAC3/SIRT1 circuit (upregulated HDAC3 and downregulated SIRT1 levels) plays an important role in aggravating myocardial IR injury in diabetic rats by downregulating Bmal1-mediated autophagy. Treatments targeting HDAC3/SIRT1 to activate the autophagy may represent a novel strategy to alleviate myocardial IR injury in diabetes.

12.
Aging (Albany NY) ; 13(4): 6182-6193, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632938

RESUMO

The incidence of chemotherapy-induced cognitive impairment (CICI) has attracted massive attention. Some studies have demonstrated the neuroprotective effects of dexmedetomidine (DEX). Here, alterations in nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy were investigated as the possible causes of DEX's neuroprotection of HT22 cells against methotrexate (MTX)-induced neurotoxicity. We used various concentrations of DEX and NCOA4-siRNA to treat MTX-induced neurotoxicity and inflammation in HT22 cells. The biomarkers of HT22 cells viability, apoptosis and inflammatory were tested. The expression of ferritinophagy markers were detected in the HT22 cells by using western blot and Immunofluorescence. We found that 10 and 50 ng/mL of DEX alleviated MTX-induced hippocampal neuronal inflammatory injuries. Meanwhile, DEX also reversed MTX-induced iron and ROS overproduction. Increasing DEX concentrations caused significant falls in the expression of ferritin heavy chain 1 (FTH1). DEX also increased vital ferritinophagy markers, NCOA4 and LC3II. NCOA4-siRNA transfection annulled the neuroprotective effects of DEX on MTX-induced inflammation in HT22 cells. Additionally, because NCOA4-siRNA disrupted ferritinophagy, DEX's inhibitory impact on MTX-induced iron and ROS overproduction in HT22 cells was also annihilated. DEX weakened MTX-provoked neurontoxicity in HT22 cells, possibly by improving NCOA4-mediated ferritinophagy. Our discoveries present further mechanisms for understanding the protective effects of DEX against MTX-induced cognitive impairment.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2 , Autofagia , Dexmedetomidina , Ferritinas/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Metotrexato , Fármacos Neuroprotetores/farmacologia , Coativadores de Receptor Nuclear , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Linhagem Celular , Disfunção Cognitiva/prevenção & controle , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Humanos , Metotrexato/administração & dosagem , Metotrexato/toxicidade
13.
Cell Death Dis ; 12(1): 43, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414413

RESUMO

The circadian clock is closely related to the development of diabetes mellitus and cardiovascular disease, and disruption of the circadian clock exacerbates myocardial ischaemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop that controls the expression pattern of the circadian nuclear receptor Rev-erbα to maintain the stability of circadian genes such as BMAL1. However, the mechanism by which the HDAC3-orchestrated Rev-erbα/BMAL1 pathway increases MI/RI in diabetes and its relationship with mitophagy have yet to be elucidated. Here, we observed that the clock genes Rev-erbα, BMAL1, and C/EBPß oscillations were altered in the hearts of rats with streptozotocin (STZ)-induced diabetes, with upregulated HDAC3 expression. Oscillations of Rev-erbα and BMAL1 were rapidly attenuated in diabetic MI/R hearts versus non-diabetic I/RI hearts, in accordance with impaired and rhythm-disordered circadian-dependent mitophagy that increased injury. Genetic knockdown of HDAC3 significantly attenuated diabetic MI/RI by mediating the Rev-erbα/BMAL1 circadian pathway to recover mitophagy. Primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA were exposed to hypoxia/reoxygenation (H/R) in vitro. The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high-glucose conditions compared with low-glucose conditions, with decreased BMAL1 expression and mitophagy levels. After H/R stimulation, high glucose aggravated H/R injury, with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 and mitophagy levels. HDAC3 and Rev-erbα siRNA can alleviate high glucose-induced and H/R-induced injury by upregulating BMAL1 to increase mitophagy. Collectively, these findings suggest that disruption of HDAC3-mediated circadian gene expression oscillations induces mitophagy dysfunction, aggravating diabetic MI/RI. Cardiac-specific HDAC3 knockdown could alleviate diabetic MI/RI by regulating the Rev-erbα/BMAL1 pathway to restore the activation of mitophagy.


Assuntos
Relógios Circadianos/genética , Diabetes Mellitus Experimental/genética , Histona Desacetilases/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Elementos Reguladores de Transcrição/genética , Animais , Modelos Animais de Doenças , Humanos , Masculino , Ratos
15.
Front Med (Lausanne) ; 7: 608259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262996

RESUMO

Background and Aim: The global pandemic of COVID-19 has posed an enormous threat to the economy and people's lives across various countries. Patients with COVID-19 most commonly present with respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. We aimed to study the relationship between GI symptoms and disease prognosis in patients with COVID-19. Methods: In a single-center and retrospective cohort study, the outcomes in COVID-19 patients with or without GI symptoms were compared. The propensity score is a conditional probability of having a particular exposure (COVID-19 patients with GI symptoms vs. without GI symptoms) given a set of baseline measured covariates. Survival was estimated using the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank-test. To explore the GI symptoms associated with ARDS, non-invasive ventilator treatment, tracheal intubation, tracheotomy, and CRRT, univariable and multivariable COX regression models were used. Results: Among 1,113 eligible patients, 359 patients with GI symptoms and 718 without GI symptoms had similar propensity scores and were included in the analyses. Patients with GI symptoms, as compared with those without GI symptoms, were associated with a similar risk of death, but with higher risks of ARDS, non-invasive mechanical ventilation in COVID-19 patients, respectively. Conclusions: The presence of GI symptoms was associated with a high risk of ARDS, non-invasive mechanical ventilation and tracheal intubation in patients with COVID-19 but not mortality.

16.
Mediators Inflamm ; 2020: 6369898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122968

RESUMO

[This corrects the article DOI: 10.1155/2020/2094948.].

17.
Int Immunopharmacol ; 89(Pt A): 107070, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33039965

RESUMO

OBJECTIVES: To describe the humoral immune feature of patients with coronavirus disease 2019 (COVID-19). METHODS: The levels of total immunoglobulins (IgG, IgM, IgA, and IgE), complement (C3, C4) results were retrospectively analyzed in COVID-19 patients. Univariable and multivariable logistic regression were performed to explore the risk factors associated with the in-hospital death. RESULT: A total of 236 patients were enrolled in this study, of which 169 were transferred to another institution or discharged (survival group) and 67 died in hospital (non-survival group). Compared with survivors, the levels of IgA and IgE in non-survivors increased significantly, and level of complement C3 decreased. Non-survivors also showed higher incidence of chest tightness, breath shortness and dyspnoea; higher levels of inflammatory indicators, leukocytes and neutrophils; and low levels of lymphocyte subsets. Multivariable regression showed increasing odds of in-hospital death associated with older age (HR: 1.099; 95%CI: 1.057-1.143; p < 0.0001), d-dimer greater (HR: 1.294; 95%CI: 1.138-1.473; p < 0.0001) and decreased complement C3 level (HR: 0.073; 95%CI: 0.007-0.722; p = 0.025) on admission. Finally, in survival COVID-19 patients whose humoral immunity was re-examined, C3 levels tended to increase, while in non-survivors it decreased. CONCLUSION: Low level of complement C3 may be an alert to the admitted COVID-19 patients with additional management. Inhibition of the complement pathway might be an effective therapeutic to COVID-19 patients.


Assuntos
COVID-19/imunologia , Complemento C3/análise , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Humanos , Imunoglobulina A/análise , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
18.
Aging (Albany NY) ; 12(19): 18833-18843, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051404

RESUMO

The coronavirus disease 2019 (COVID-19) became a global pandemic. Males, compared to females, seem to be more susceptible to COVID-19, but related evidence is scarce, especially in severe patients. We explored sex differences in clinical characteristics and potential risk factors for mortality in severe COVID-19 patients. In this retrospective cohort study, we included all severe COVID-19 patients admitted to Eastern Renmin Hospital of Wuhan University, Wuhan, China, with a definitive clinical outcome as of Apr 10, 2020. Of the included 651 patients, 332 were male, and 319 were female. Males and females did not differ in age and underlying comorbidities. Males were more likely than females to report fever and develop serious complications, including acute respiratory distress syndrome, secondary infection, acute cardiac injury, coagulopathy, acute kidney injury and arrhythmia. Further, males had much higher mortality relative to females. Multivariable regression showed neutrophilia (odds ratio 6.845, 95% CI 1.227-38.192, p=0.028), thrombocytopenia (19.488, 3.030-25.335, p=0.002), hypersensitive troponin I greater than 0.04 pg/mL (6.058, 1.545-23.755, p=0.010), and procalcitonin greater than 0.1 ng/mL (6.350, 1.396-28.882, p=0.017) on admission were associated with in-hospital death. With either of these risk factors, the cumulative survival rate was relatively lower in males than in females. In conclusion, males are more likely than females to develop serious complications and progress to death. The potential risk factors of neutrophilia, thrombocytopenia, hypersensitive troponin I greater than 0.04 pg/mL and procalcitonin more than 0.1 ng/mL may help clinicians to identify patients with poor outcomes at an early stage, especially in males.

19.
Int J Surg ; 82: 172-178, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32891829

RESUMO

BACKGROUND: This study aimed to describe the epidemiologic and clinical characteristics of coronavirus disease 2019 (COVID-19) in surgical patients and medical staff. METHODS: A single-center case series of 1586 consecutive surgical patients was selected at our hospital from January 13 to March 12, 2020. The epidemiological and clinical characteristics of COVID-19 were analyzed and followed up to May 20, 2020. The transmission of COVID-19 between the surgical patients and medical staff was also recorded. RESULTS: Seventeen (1.07%) surgical patients were diagnosed with COVID-19, with a high incidence in the thoracic department (9.37%), and the median age was 58 years (IQR, 53-73). The median time from hospital admission to COVID-19 diagnosis was 9.0 days (7.0-12.0) and was 6.0 days (4.0-7.0) from the day of surgery to COVID-19 diagnosis. Eleven (64.70%) patients suffered from pulmonary infection before surgery. When COVID-19 was diagnosed, common symptoms were fever (82.35%) and cough (94.12%), and most (82.35%) neutrophil/lymphocyte ratios were high (>3.5). Chest computed tomography (CT) (82.35%) showed bilateral dense shadows. Surgical patients with COVID-19 stayed in the hospital for approximately 35.0 days (25.5-43.0), with a mortality rate of 11.76%. Sixteen medical staff were infected with COVID-19 in the early stage. CONCLUSIONS: In this series of 1586 surgical patients, the COVID-19 infection rate was 1.07%, with an especially high incidence among patients with thoracic diseases. Middle-aged and elderly patients with preoperative pulmonary infection were more susceptible to COVID-19 infection after surgery. Medical staff were infected with COVID-19 and should take protective measures to protect themselves.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa do Paciente para o Profissional , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adulto , Idoso , COVID-19 , Infecções por Coronavirus/diagnóstico , Feminino , Febre , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Estudos Retrospectivos , SARS-CoV-2 , Avaliação de Sintomas , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
Int J Infect Dis ; 100: 441-448, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947052

RESUMO

BACKGROUND: To determine whether abnormal coagulation parameters are associated with disease severity and poor prognosis in patients with 2019 Corona Virus Disease (COVID-19). METHODS: A systematic literature search was conducted using the databases PubMed, Embase, and Web of sciences until April 25, 2020. We included a total of 15 studies with 2277 patients. Platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), and fibrinogen (FIB) were collected and analyzed. The statistical results were expressed as the effect measured by mean difference (MD) with the related 95% confidence interval (CI). RESULTS: The PLT level of severe cases was lower than that of mild cases, while the levels of PT, D-D, and FIB were higher than those of mild cases (P < 0.05). The level of APTT had no statistical difference between two groups (P > 0.05). PT of ICU patients was significantly longer (P < 0.05) than that of non-ICU patients. In non-survivors, PT and D-D were higher, yet PLT was lower than that of survivors (P < 0.05). There was no significant difference in APTT between survivors and non-survivors (P > 0.05). The funnel plot and Egger's regression test demonstrated that there was no publication bias. CONCLUSIONS: Our data support the notion that coagulopathy could be considered as a risk factor for disease severity and mortality of COVID-19, which may help clinicians to identify the incidence of poor outcomes in COVID-19 patients.


Assuntos
Betacoronavirus , Coagulação Sanguínea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , COVID-19 , Infecções por Coronavirus/mortalidade , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/mortalidade , Prognóstico , Tempo de Protrombina , SARS-CoV-2 , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...