Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
J Med Virol ; 95(3): e28635, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869780

RESUMO

Hepatitis B virus (HBV) infection and type-2 diabetes mellitus (T2DM) affect millions of individuals worldwide, whereas their interplay remains largely unclear. Here, we analyzed a large cohort of 330 HBV-infected inpatients with T2DM (so-called HBV + T2DM patients) and 330 T2DM inpatients without HBV infection (T2DM patients). Poor glycemic control was defined by glycated hemoglobin (HbA1c) ≥ 7%. Among 330 HBV + T2DM patients, 252 (76%) aged ≥ 50 years, 223 (68%) were males, 205 (62%) experienced poor glycemic control. The propensity-score matching approach was applied to match patient age, gender, comorbidities, and antidiabetic treatment between T2DM + HBV and T2DM patients. Compared with T2DM patients, HBV + T2DM patients had poorer glycemic control, longer hospitalization length, and higher alanine aminotransferase (p < 0.05). HBV + T2DM patients with HBV DNA ≥ 100 IU/mL or HBsAg ≥ 0.05 IU/mL had worse HbA1c control than T2DM patients without HBV infection (p < 0.05). HBV + T2DM patients who received no anti-HBV therapy had worse HbA1c control than HBV + T2DM patients receiving anti-HBV therapy (p < 0.05). Both insulin and anti-HBV therapy were significant factors associated with glycemic control in HBV + T2DM patients. Overall, HBV + T2DM patients exhibited poorer glycemic control than T2DM patients, but their clinical outcomes were likely improved by insulin plus anti-HBV treatment. Early management of HBV infection likely contributes to better clinical outcomes in HBV-infected patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatite B , Masculino , Humanos , Feminino , Estudos Retrospectivos , Hemoglobinas Glicadas , Controle Glicêmico , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Insulina/uso terapêutico , Vírus da Hepatite B/genética
2.
J Med Virol ; 95(1): e28340, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36420584

RESUMO

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of Coronavirus Disease 2019 (COVID-19). Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a 6-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large T cell receptor/B cell receptor clones, decreased diversity, abnormal class-switch recombination, and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19+ CD138+ B cells were found in COVID-19 survivors. The proportion of CD4+ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3+ CD4- T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3+ CD4- T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Estudos Prospectivos , Linfócitos B , Anticorpos Antivirais , Sobreviventes
3.
Cell Commun Signal ; 21(1): 175, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37480108

RESUMO

BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.


Assuntos
Microglia , Hemorragia Subaracnóidea , Humanos , Fagocitose , Autofagia , Inflamação , Proteínas Quinases Associadas com Morte Celular
4.
Am J Hematol ; 98(2): 251-263, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36309982

RESUMO

1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM. +1q was identified in 53.1% of patients and verified as an independent variate for inferior overall survival (OS) (hazard ratio, 1.400; 95% confidence interval, 1.097-1.787; p = .007). Concurrence of other HRCAs (particularly t(14;16) and del(17p)) further exacerbated the outcomes of patients with +1q, suggesting prognostic heterogeneity. Thus, a risk-scoring algorithm based on four risk variates (t(14;16), hypercalcemia, ISS III, and high LDH) was developed to estimate the outcomes of patients with +1q. Of the patients, 376 evaluable patients with +1q were re-stratified into low (31.6%), intermediate (61.7%), and high risk (6.7%) groups, with significantly different progression-free survival and OS (p < .0001), in association with early relapse of the disease. The prognostic value of this model was validated in the CoMMpass cohort. While attaining undetectable MRD largely circumvented the adverse impact of +1q, it scarcely ameliorated the outcome of the patients with high risk, who likely represent a subset of patients with extremely poor survival. Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their re-stratification. The proposed simple risk-scoring model can estimate the outcomes of patients with +1q, which may help guide risk-adapted treatment for such patients.


Assuntos
Mieloma Múltiplo , Humanos , Prognóstico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estudos Retrospectivos , Aberrações Cromossômicas , Modelos de Riscos Proporcionais
5.
Immun Ageing ; 19(1): 12, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248063

RESUMO

BACKGROUND: COVID-19 patients may experience "cytokine storm" when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies. METHODS: This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization. RESULTS: At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients. CONCLUSION: Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.

6.
Bioorg Chem ; 114: 105020, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34328850

RESUMO

With the development of frame materials, metal organic frameworks (MOFs) have been successfully applied in the fields of biological small molecule analysis and fluorescent DNA detection. In this work, in view of the good adsorption characteristics of MIL-101(Cr), the highly sensitive detection of adenosine triphosphate (ATP) assisted nucleic acid exonuclease amplification by MIL-101(Cr) on the different affinity of single stranded DNA and double stranded DNA was investigated. The detection limit of ATP reaches 1.7 µM, and the platform has good applicability in biological samples. On this basis, an "AND" logic gate was successfully constructed. Superior sensitivity to ATP in the presence of exonuclease was reflected, which greatly enhanced the system's fluorescence. Importantly, the fluorescence sensing application of this nanomaterial inspired other target detection and enriched the building blocks of fluorescence sensing platform.


Assuntos
Trifosfato de Adenosina/sangue , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Trifosfato de Adenosina/química , Adsorção , Animais , Bovinos , Cromo/química , Exodesoxirribonucleases/química , Fluoresceínas/química , Fluorescência , Limite de Detecção , Lógica
7.
Molecules ; 26(4)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572409

RESUMO

Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). To celebrate the 80th birthday of Prof. Dr. Erik De Clercq on 28 March 2021, this review provides an overview of his contributions to eight approved nucleos(t)ide drugs: (i) three adenosine nucleotide analogues, namely tenofovir disoproxil fumarate (Viread®) and tenofovir alafenamide (Vemlidy®) against HIV and HBV infections and adefovir dipivoxil (Hepsera®) against HBV infections; (ii) two thymidine nucleoside analogues, namely brivudine (Zostex®) against HSV-1 and VZV infections and stavudine (Zerit®) against HIV infections; (iii) two guanosine analogues, namely valacyclovir (Valtrex®, Zelitrex®) against HSV and VZV and rabacfosadine (Tanovea®-CA1) for the treatment of lymphoma in dogs; and (iv) one cytidine nucleotide analogue, namely cidofovir (Vistide®) for the treatment of HCMV retinitis in AIDS patients. Although adefovir dipivoxil, stavudine, and cidofovir are virtually discontinued for clinical use, tenofovir disoproxil fumarate and tenofovir alafenamide remain the most important antivirals against HIV and HBV infections worldwide. Overall, the broad-spectrum antiviral potential of nucleos(t)ide analogues supports their development to treat or prevent current and emerging infectious diseases worldwide.


Assuntos
Antivirais/história , Antivirais/uso terapêutico , Descoberta de Drogas , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Aniversários e Eventos Especiais , História do Século XX , História do Século XXI , Humanos , Viroses/virologia
8.
J Org Chem ; 85(23): 15026-15037, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33175528

RESUMO

A sequential [3 + 2]/[2 + 1] annulation domino reaction of crotonate-derived sulfur ylides and Morita-Baylis-Hillman carbonates of isatins for the construction of oxospiro[bicyclo[3.1.0]hexane-6,3'-indolin] scaffolds in moderate to good yields with almost 1:1 diastereoselectivity has been developed. Mild reaction conditions and readily accessible starting materials as well as excellent functional group compatibility render this transformation a powerful tool for the synthesis of spirocyclopropyloxindoles. A gram-scale synthetic procedure was also successfully carried out and a plausible reaction mechanism could be proposed.

11.
J Environ Sci (China) ; 48: 193-199, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27745664

RESUMO

The natural gas vehicle market is rapidly developing throughout the world, and the majority of such vehicles operate on compressed natural gas (CNG). However, most studies on the emission characteristics of CNG vehicles rely on laboratory chassis dynamometer measurements, which do not accurately represent actual road driving conditions. To further investigate the emission characteristics of CNG vehicles, two CNG city buses and two CNG coaches were tested on public urban roads and highway sections. Our results show that when speeds of 0-10km/hr were increased to 10-20km/hr, the CO2, CO, nitrogen oxide (NOx), and total hydrocarbon (THC) emission factors decreased by (71.6±4.3)%, (65.6±9.5)%, (64.9±9.2)% and (67.8±0.3)%, respectively. In this study, The Beijing city buses with stricter emission standards (Euro IV) did not have lower emission factors than the Chongqing coaches with Euro II emission standards. Both the higher emission factors at 0-10km/hr speeds and the higher percentage of driving in the low-speed regime during the entire road cycle may have contributed to the higher CO2 and CO emission factors of these city buses. Additionally, compared with the emission factors produced in the urban road tests, the CO emission factors of the CNG buses in highway tests decreased the most (by 83.2%), followed by the THC emission factors, which decreased by 67.1%.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Gás Natural , Emissões de Veículos/análise , China , Cidades , Hidrocarbonetos/análise , Óxidos de Nitrogênio/análise
12.
Mar Pollut Bull ; 207: 116827, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39168088

RESUMO

Pacific oysters were sampled from 22 human-impacted sites in northeastern Japan to measure Cr, Cu, Zn, Pb, Cd, and As. The hazard quotient was slightly >1 for Cu and/or As at two sites, but <1 for all metal species and As at the other sites, indicating low human health risks. Oysters' Cu, Zn, and Pb contents were positively related to their concentrations in the sediment, while Cr and As were not. Oysters' Cu and Zn were negatively related to the inorganic nitrogen in seawater, while oysters' Pb and As showed positive relationships with the particulate organic carbon. These findings suggest that marine trophic status affects oysters' metal uptake differently among the metal species. Furthermore, oysters' Cr, Cu, Zn, and Pb contents were negatively related to their eicosapentaenoic acid content and condition index. Therefore, the nutritional conditions of oysters may influence their elimination or accumulation of these metals.


Assuntos
Bioacumulação , Monitoramento Ambiental , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Japão , Água do Mar/química , Metais Pesados/análise , Ostreidae/metabolismo , Metais/metabolismo , Sedimentos Geológicos/química
13.
Clin Med (Lond) ; 24(6): 100252, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362336

RESUMO

BACKGROUND: Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications. METHODS: We retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed. RESULTS: In a cohort of 220 patients with NDMM, attainment of MRD- offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD- duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09-0.34; P < 0.0001) or 69 % (95 % CI, 0.13-0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD- was sustained, the better the outcome was. Loss of MRD- led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0-0.24, P = 0.0008). Most patients (70 %) who lost MRD- status carried high-risk cytogenetic abnormalities (HRCAs). While MRD- was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging). CONCLUSIONS: Longitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.

14.
Toxicol Appl Pharmacol ; 272(3): 726-35, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23954767

RESUMO

Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 µM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 µM, which was much more efficient than curcumin. Both 0.5 µM C3 and 5 µM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD.


Assuntos
Acroleína/toxicidade , Curcumina/análogos & derivados , Curcumina/farmacologia , Citoproteção/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Acroleína/antagonistas & inibidores , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia
15.
Environ Sci Pollut Res Int ; 30(38): 89676-89689, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37454381

RESUMO

Nanoscale zero-valent iron (nZVI) has a high removal affinity toward arsenic (As). However, the agglomeration of nZVI reduces the removal efficiency of As and, thus, limit its application. In this study, we report an environmentally friendly novel composite of Chlorella vulgaris-supported nanoscale zero-valent iron (abbreviated as CV-nZVI) that exhibits a fast and efficient removal of As(III) from As-contaminated water. Scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS), X-ray diffractometry (XRD), attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS) were used to characterize and analyze the CV-nZVI. These results indicated that the stabilization effect of C. vulgaris reduced the nZVI agglomeration and enhanced the reactivity of nZVI. The experiments showed a removal efficiency of 99.11% for As(III) at an optimum pH of 7.0. The adsorption kinetics and isotherms followed the pseudo-second-order kinetic model and Langmuir adsorption isotherm with the superior maximum adsorption capacities of 34.11 mg/g for As(III). The FTIR showed that the As(III) was adsorbed on the CV-nZVI surface by complexation reaction, and XPS indicated that oxidation reaction was also involved. After five reuse cycles, the removal efficiency of As(III) by CV-nZVI was 32.93%, suggesting that the CV-nZVI had some reusability and regeneration. Overall, this work provides a practical and highly efficient approach for As remediation in As-contaminated water, and simultaneously resolves the agglomeration problems of nZVI nanoparticles.


Assuntos
Arsênio , Chlorella vulgaris , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Ferro/química , Adsorção , Água
16.
Oxid Med Cell Longev ; 2023: 4383332, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36703912

RESUMO

Accumulating evidence has demonstrated that neural stem cells (NSCs) have regenerative capacity after brain injuries, such as in aneurysmal subarachnoid hemorrhage (SAH). The reactive oxygen species (ROS)-induced NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome triggers inflammatory responses and pyroptosis of cells; however, whether ROS-induced neuroinflammation modulates the fate of endogenous NSCs after SAH remains largely unknown. In this study, the level of IL-1ß was increased in the cerebrospinal fluid (CSF) of patients with SAH. In an endovascular perforation model of SAH in mice, the secretion of IL-1ß increased to a peak at 24 h following SAH, and the expression of Caspase1 and NLRP3 was elevated in the hippocampus. Primary cultured NSCs were incubated with hemoglobin (Hb) to mimic SAH in vitro. The cell viability, LDH release, intracellular ROS levels, scanning electron microscopy (SEM), and the expression of NLRP3 and pyroptosis indicators (GSDMD, ASC, and Caspase-1) in NSCs after SAH were examined to investigate the process of pyroptosis. We found that pyroptotic death featuring cellular swelling, cell membrane pore formation and elevated IL-1ß was increased in cultured primary NSCs after Hb treatment, as was the expression of NLRP3, ASC, Caspase-1, and GSDMD. In addition, we found that ROS-induced pyroptosis of NSCs by activating the NLRP3/GSDMD pathway. These findings suggest that pyroptosis of NSCs induced by Hb can impede neural regeneration after SAH.


Assuntos
Células-Tronco Neurais , Hemorragia Subaracnóidea , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Inflamassomos/metabolismo , Caspase 1/metabolismo , Células-Tronco Neurais/metabolismo , Hemoglobinas
17.
Int Immunopharmacol ; 121: 110397, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37302369

RESUMO

Dry eye disease (DED) is a multifactorial disease, and oxidative stress plays a crucial role in its pathogenesis. Recently, multiple studies have shown that upregulation of autophagy can protect the cornea from oxidative stress damage. The present study investigated the therapeutic effects of salidroside, the main component of Rhodiola crenulata, in both in vivo and in vitro dry eye models. The results showed that topical eye drop treatment with salidroside restored corneal epithelium damage, increased tear secretion, and reduced cornea inflammation in the DED mice. Salidroside activated autophagy through AMP-activated protein kinase (AMPK)-sirtuin-1 (Sirt1) signaling pathway, which promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This process restored antioxidant enzyme activity, reduced reactive oxygen species (ROS) accumulation, and alleviated oxidative stress. The application of autophagy inhibitor chloroquine and AMPK inhibitor Compound C reversed the therapeutic efficacy of salidroside, validating the above findings. In conclusion, our data suggest that salidroside is a promising candidate for DED treatment.


Assuntos
Proteínas Quinases Ativadas por AMP , Antioxidantes , Animais , Camundongos , Antioxidantes/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 1/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Autofagia , Fator 2 Relacionado a NF-E2/metabolismo
18.
Heliyon ; 9(12): e22873, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125480

RESUMO

Objectives: The spread of SARS-Cov-2 remains a global concern along with the emergence of variants. This study aims to characterize the epidemiological and clinical features of hospitalized patients who were dragonized with five different variants of SARS-CoV-2 during the past 3 years. Methods: This retrospective study recruited 432 COVID-19 patients who were hospitalized in the First Hospital of Changsha from January 2020 to August 2022. Clinical records on clinical symptoms, laboratory profiles, and chest CT images was collected. The epidemiological and clinical features were compared between COVID-19 patients infected with either the wild-type, Omicron variant or pre- Omicron variants (e.g., Alpha, Beta, Delta). Results: A total of 432 laboratory-confirmed COVID-19 inpatients were dialogized during three waves, including 247 cases during the wild-type transmission period, 65 cases during the transmission period of pre-Omicron variants, and 119 cases during the transmission period of Omicron variants. The proportion of moderately or severely ill inpatients showed a gradual decline from the wild-type transmission period to the Omicron transmission period. The common symptoms of inpatients infected with SARS-CoV-2 wildtype strains included fever (67.61 %), cough (57.89 %), fatigue (33.60 %), and shortness of breath (12.15 %). In contrast, patients infected with other variants mostly showed upper respiratory symptoms. Based on chest CT images, a lower degree of acute pulmonary infection was observed among inpatients infected with the Omicron variants than those infected with the wild-type strain (31.09 % vs 93.12 %, p-value<0.01). Conclusions: Compared with the wild-type strain, SARS-CoV-2 variants of concern, especially the Omicron variant, mostly caused a lower degree of acute pulmonary infection, indicating the reduced disease severity and mortality among hospitalized COVID-19 patients.

19.
Int J Infect Dis ; 128: 157-165, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36608788

RESUMO

OBJECTIVES: The effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV). METHODS: We analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated. RESULTS: Children who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV. CONCLUSION: Oseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children.


Assuntos
Coinfecção , Vírus da Influenza A , Influenza Humana , Criança , Humanos , Pré-Escolar , Oseltamivir/uso terapêutico , Antivirais/uso terapêutico , Criança Hospitalizada , Coinfecção/tratamento farmacológico , Vírus da Influenza B , Resultado do Tratamento
20.
Nutrients ; 14(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35807863

RESUMO

Under-five years of age is a critical period for children's growth and development. Nutritional deficiency during this period is associated with wasting, underweight and stunting. We aimed to conduct an epidemiological study using data derived from the GBD2019 to found the global distribution and changing trends of nutritional deficiencies among children under 5 years old, as well as the correlation between social development status and nutritional deficiencies. Nutritional deficiencies in children under 5 years has been substantially improved in the past decade; however, the progress has been unevenly distributed globally. The incidence and DALY rate decreased with the increase of socio-demographic index. In 2019, the incidence (51,872.0 per 100,000) was highest in Central Sub-Saharan Africa and the DALY rate (5597.1 per 100,000) was the highest in Western Sub-Saharan Africa. Among five subcategories of nutritional deficiencies in children under 5 years, vitamin A deficiency accounted for the largest proportion of incident cases (100,511,850, 62.1% in 2019), while the proportion of DALYs caused by protein-energy malnutrition was the highest (9,925,276, 62.0%). Nutritional deficiency in some countries remains worrisome, for whom policies guarantees and sustained efforts to control nutritional deficiencies are urgently needed.


Assuntos
Saúde Global , Desnutrição , África Subsaariana/epidemiologia , Criança , Pré-Escolar , Humanos , Desnutrição/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Magreza/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA