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1.
Bioengineered ; 13(3): 5480-5508, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35184680

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Plantas Medicinais/química , SARS-CoV-2/efeitos dos fármacos , Antivirais/isolamento & purificação , COVID-19/patologia , COVID-19/virologia , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicina Herbária/métodos , Humanos , Medicina Tradicional Chinesa/métodos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade
2.
Microbiol Spectr ; 9(2): e0153121, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34668747

RESUMO

The microbial carbon pump (MCP) provides a mechanistic illustration of transformation of recalcitrant dissolved organic matter (DOM) in the ocean. Here, we explored and demonstrated the key roles of algae-associated microorganisms (mainly heterotrophic bacteria) in the production and transformation of carboxyl-rich alicyclic molecule (CRAM)-like DOM through a laboratory experiment involving cultures of Skeletonema dohrnii. Without the participation of the associated bacteria, CRAM-like DOM molecules were not detected via Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in algal cultures treated with antibiotics. Similarly, CRAM-like DOM were not detected in cultures of bacteria alone. Our experimental results showed that algae-associated bacteria are important in the process of converting algal-derived organic matter into CRAM-like DOM during S. dohrnii culture. Bacteroidetes (mainly Flavobacteriia) dominated the bacterial community in the stationary and degradation phases, where the predicted metabolic pathways for bacterial assemblages were mainly involved in biosynthesis, metabolism, and degradation. Facilitated by these heterotrophic bacteria, the amount and the chemodiversity of CRAM-like DOM derived from algae varied during the growth and decomposition of algal cells, and CRAM-like DOM were enriched at the later growth stage. The properties and characteristics of these CRAM-like DOM, including molecular weight, double bond equivalent, hydrogen-carbon ratio, carbon-nitrogen ratio, carbon-sulfur ratio, and modified aromaticity index increased with the growth and decay of algal cells, indicating the transformation from active to recalcitrant DOM. In contrast, the organic matter in axenic cultures of S. dohrnii mainly existed in the form of particulate organic matters (POM), and small amounts of CRAM-like DOM were detected. This study provides the first laboratory evidence to reveal and confirm the direct involvement of algae-associated microbiomes in the production and transformation of algae-derived refractory DOM, highlighting the significance of these epiphytic bacteria in marine carbon sequestration and global carbon cycling. IMPORTANCE Dissolved organic matter (DOM) serves as a major carbon and nutrient pool in oceans, and recalcitrant DOM are the primary sources for carbon sequestration in depths. Here, we demonstrate the critical roles of algae-associated microorganisms (mainly heterotrophic bacteria) in the transformation of recalcitrant dissolved organic matter through laboratory cultures of a model diatom, Skeletonema dohrnii. Our experimental results showed that in addition to affecting the growth and the physiology of S. dohrnii, algae-associated bacteria are important in processing and converting algal DOM into CRAM-like DOM. Facilitated by the associated bacteria, the amount and the chemodiversity of DOM derived from algae varied during the growth and decomposition of algal cells, and enriched recalcitrant DOM formed in the later growth stage. The properties and diversity of DOM increased with the growth and decay of algal cells, indicating the transformation from active DOM to inert organic matter. Our results confirmed that the direct involvement of algae-associated microbes in the production of CRAM-like DOM. Detailed community structure analysis of the algae-associated bacterial community and its predicted functions confirmed the involvement of certain bacterial groups (e.g., Flavobacteriia) in biosynthesis, metabolism, and degradation.


Assuntos
Bactérias/metabolismo , Carbono/metabolismo , Clorófitas/metabolismo , Fitoplâncton/microbiologia , Bactérias/química , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Biotransformação , Clorófitas/química , Clorófitas/crescimento & desenvolvimento , Clorófitas/microbiologia , Diatomáceas/química , Diatomáceas/crescimento & desenvolvimento , Diatomáceas/metabolismo , Diatomáceas/microbiologia , Lagos/química , Lagos/microbiologia , Espectrometria de Massas , Fitoplâncton/química , Fitoplâncton/crescimento & desenvolvimento , Fitoplâncton/metabolismo
3.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34446551

RESUMO

Many G protein-coupled receptors and other signaling proteins localize to the ciliary membrane for regulating diverse cellular processes. The BBSome composed of multiple Bardet-Biedl syndrome (BBS) proteins is an intraflagellar transport (IFT) cargo adaptor essential for sorting signaling proteins in and/or out of cilia via IFT. Leucine zipper transcription factor-like 1 (LZTFL1) protein mediates ciliary signaling by controlling BBSome ciliary content, reflecting how LZTFL1 mutations could cause BBS. However, the mechanistic mechanism underlying this process remains elusive thus far. Here, we show that LZTFL1 maintains BBSome ciliary dynamics by finely controlling BBSome recruitment to the basal body and its reassembly at the ciliary tip simultaneously in Chlamydomonas reinhardtii LZTFL1 directs BBSome recruitment to the basal body via promoting basal body targeting of Arf-like 6 GTPase BBS3, thus deciding the BBSome amount available for loading onto anterograde IFT trains for entering cilia. Meanwhile, LZTFL1 stabilizes the IFT25/27 component of the IFT-B1 subcomplex in the cell body so as to control its presence and amount at the basal body for entering cilia. Since IFT25/27 promotes BBSome reassembly at the ciliary tip for loading onto retrograde IFT trains, LZTFL1 thus also directs BBSome removal out of cilia. Therefore, LZTFL1 dysfunction deprives the BBSome of ciliary presence and generates Chlamydomonas cells defective in phototaxis. In summary, our data propose that LZTFL1 maintains BBSome dynamics in cilia by such a dual-mode system, providing insights into how LZTFL1 mediates ciliary signaling through maintaining BBSome ciliary dynamics and the pathogenetic mechanism of the BBS disorder as well.


Assuntos
Chlamydomonas reinhardtii/fisiologia , Cílios/fisiologia , Fototaxia , Fatores de Transcrição/fisiologia , Síndrome de Bardet-Biedl , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ligação Proteica , Transdução de Sinais
4.
Lab Invest ; 101(11): 1484-1493, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34446806

RESUMO

Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism. MIR22HG was up-regulated in the testicular tissues of mice with LOH and H2O2-treated TM3 cells (mouse Leydig cell line). Interference of MIR22HG ameliorated cell apoptosis and upregulated miR-125a-5p expression in H2O2-treated TM3 cells. Then, the interaction between MIR22HG and miR-125a-5p was confirmed with RIP and RNA pull-down assay. Further study showed that miR-125a-5p downregulated N-Myc downstream-regulated gene 2 (NDRG2) expression by targeting its 3'-UTR of mRNA. What's more, MIR22HG overexpression aggravated cell apoptosis and reduced testosterone production in TM3 cells via miR-125a-5p/NDRG2 pathway. MIR22HG knockdown elevated testosterone levels in LOH mice. In conclusion, MIR22HG up-regulated NDRG2 expression through targeting miR-125a-5p, thus promoting LC apoptosis in LOH.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Hipogonadismo/etiologia , Células Intersticiais do Testículo/fisiologia , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Animais , Apoptose , Linhagem Celular , Masculino , Camundongos , Testosterona/metabolismo
5.
Elife ; 102021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587040

RESUMO

Certain ciliary signaling proteins couple with the BBSome, a conserved complex of Bardet-Biedl syndrome (BBS) proteins, to load onto retrograde intraflagellar transport (IFT) trains for their removal out of cilia in Chlamydomonas reinhardtii. Here, we show that loss of the Arf-like 6 (ARL6) GTPase BBS3 causes the signaling protein phospholipase D (PLD) to accumulate in cilia. Upon targeting to the basal body, BBSomes enter and cycle through cilia via IFT, while BBS3 in a GTP-bound state separates from BBSomes, associates with the membrane, and translocates from the basal body to cilia by diffusion. Upon arriving at the ciliary tip, GTP-bound BBS3 binds and recruits BBSomes to the ciliary membrane for interacting with PLD, thus making the PLD-laden BBSomes available to load onto retrograde IFT trains for ciliary exit. Therefore, BBS3 promotes PLD exit from cilia via the BBSome, providing a regulatory mechanism for ciliary signaling protein removal out of cilia.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Chlamydomonas reinhardtii/metabolismo , Cílios/metabolismo , Fosfolipase D/metabolismo , Fatores de Ribosilação do ADP/genética , Chlamydomonas reinhardtii/enzimologia , Chlamydomonas reinhardtii/genética , Cílios/genética , Flagelos/enzimologia , Flagelos/genética , Flagelos/metabolismo , Fosfolipase D/genética , Transporte Proteico
6.
Huan Jing Ke Xue ; 42(1): 492-500, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372503

RESUMO

With further improvements to meet social requirements for healthy and comfortable living, the research of micro-scale thermal environments has been received increasing attention. The key to micro-scale thermal environment study is the underlying surface temperature field simulation, which requires high precision results. Taking a typical area of the Jiangning District, Nanjing City, as a study area, this study used a UAV equipped with a thermal infrared imager to obtain surface temperature data in summer and autumn because of the limitation of the traditional ground measurements. Then, the numerical simulation software of ENVI-met and PALM-4U were utilized to conduct the surface temperature filed simulation. The simulation results were further analyzed combined with measured data. The modeling results indicated that the numerical simulation has high spatial accuracy, which can be applied to the study of the urban micro-thermal environment. Furthermore, the simulation effect of the model on the artificial surface is better than that of the natural surface, and the simulation effect of the open surface is better than that of the non-open surface. The study also found that the simulation effect of ENVI-met under the influence of occlusion was better than that of PALM-4U. The vegetation occlusion PALM-4U was less effective than that of ENVI-met, although both models correctly predicted the ground temperature under the occlusion of buildings. The overall conclusion indicates that the applicability of ENVI-met is superior to that of PLAM-4U for urban micro-thermal environment simulation. The study can provide a reference for the high-resolution remote sensing research of urban micro-scale thermal environments.

7.
J Oncol ; 2021: 9365953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35251167

RESUMO

BACKGROUND: Improving the osteosarcoma (OS) patients' survival has long been a challenge, even though the disease's treatment is on the verge of progress. DNA damage response (DDR) has traditionally been associated with carcinogenesis, tumor growth, and genomic instability. No study has used DDR genes as a signature to identify the prognosis of OS. The goal of this work was to find an effective possible DDR gene biomarker for predicting OS prognosis, which may be useful in clinical diagnosis and therapy. METHODS: To assess gene methylation, univariate and multivariate cox regression analyses were performed on data from OS patients. The data were retrieved from public databases, including the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and the Gene Expression Omnibus (GEO). RESULTS: The DDR gene signature was chosen, which included seven genes (NHEJ1, RMI2, SWI5, ERCC2, CLK2, POLG, and MLH1). In the TARGET dataset, patients were categorized into two groups: high-risk and low-risk. Patients with a high-risk score revealed a shorter OS rate (hazard ratio (HR): 3.15, 95% confidence interval (CI): 1.38-4.34, P < 0.001) in comparison with the patients with a low-risk score in the TARGET as a training group. The validation of the prognostic signature accuracy was carried out in relapse and validation cohorts (TARGET, n = 75; GSE21257, n = 53). The signature was found to be an independent predictive factor for OS in multivariate cox regression analysis, and a nomogram model was developed to predict an individual's risk of OS. DDR gene signature involved in Fanconi anemia pathway, nonhomologous end-joining pathway, mismatch repair, and nucleotide excision repair pathway. CONCLUSIONS: Our study suggests that the identified novel DDR genes could be a powerful prognostic tool for prognosis evaluation and a valuable tool in predicting the risk factors in OS patients.

8.
Am J Nephrol ; 51(5): 401-410, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320986

RESUMO

BACKGROUND: Human cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that attenuates angiotensin II-induced hypertension, alleviates myocardial fibrosis, and improves heart function. However, the role of CREG in high-salt (HS) diet-induced hypertensive nephropathy is unclear. METHODS: To determine the effects and molecular mechanisms of CREG in HS diet-induced hypertensive nephropathy, we established a hypertensive nephropathy animal model in Dahl salt-sensitive (SS) rats fed a HS diet (8% NaCl, n = 20) for 8 weeks. At week 4 of HS loading, these rats were administered recombinant CREG (reCREG; 35 µg/kg·day, n = 5) and saline (n = 5) via subcutaneously implanted pumps and were also administered the vasodilator hydralazine (20 mg/kg·day, n = 5) in drinking water. We used hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemical labeling, western blotting, RT-PCR, and Tunel staining to determine the signaling pathways of CREG in HS diet-induced hypertensive nephropathy. RESULTS: After 8 weeks of HS intake, the Dahl SS rats developed renal dysfunction and severe renal fibrosis associated with reductions of 78 and 67% in CREG expression, respectively, at both mRNA and protein levels in the kidney. Administration of reCREG improved renal function and relieved renal fibrosis. Administration of CREG also inhibited monocyte infiltration and reduced apoptosis in the kidney cells. CREG overexpression upregulated forkhead box P1 expression and inhibited the transforming growth factor-ß1 signaling pathway. CONCLUSION: Our study shows that CREG protected the kidney against HS-diet-induced renal damage and provides new insights into the mechanisms underlying kidney injury.


Assuntos
Hipertensão Renal/tratamento farmacológico , Rim/patologia , Nefrite/tratamento farmacológico , Proteínas Repressoras/administração & dosagem , Cloreto de Sódio na Dieta/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Fibrose , Humanos , Hipertensão Renal/etiologia , Hipertensão Renal/patologia , Rim/efeitos dos fármacos , Masculino , Nefrite/etiologia , Nefrite/patologia , Ratos , Ratos Endogâmicos Dahl , Proteínas Recombinantes/administração & dosagem , Proteínas Repressoras/análise , Proteínas Repressoras/metabolismo
9.
Proc Natl Acad Sci U S A ; 117(5): 2496-2505, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31953262

RESUMO

Bardet-Biedl syndrome (BBS) is a ciliopathy caused by defects in the assembly or distribution of the BBSome, a conserved protein complex. The BBSome cycles via intraflagellar transport (IFT) through cilia to transport signaling proteins. How the BBSome is recruited to the basal body for binding to IFT trains for ciliary entry remains unknown. Here, we show that the Rab-like 5 GTPase IFT22 regulates basal body targeting of the BBSome in Chlamydomonas reinhardtii Our functional, biochemical and single particle in vivo imaging assays show that IFT22 is an active GTPase with low intrinsic GTPase activity. IFT22 is part of the IFT-B1 subcomplex but is not required for ciliary assembly. Independent of its association to IFT-B1, IFT22 binds and stabilizes the Arf-like 6 GTPase BBS3, a BBS protein that is not part of the BBSome. IFT22/BBS3 associates with the BBSome through an interaction between BBS3 and the BBSome. When both IFT22 and BBS3 are in their guanosine triphosphate (GTP)-bound states they recruit the BBSome to the basal body for coupling with the IFT-B1 subcomplex. The GTP-bound BBS3 likely remains to be associated with the BBSome upon ciliary entry. In contrast, IFT22 is not required for the transport of BBSomes in cilia, indicating that the BBSome is transferred from IFT22 to the IFT trains at the ciliary base. In summary, our data propose that nucleotide-dependent recruitment of the BBSome to the basal body by IFT22 regulates BBSome entry into cilia.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Corpos Basais/metabolismo , Chlamydomonas reinhardtii/metabolismo , Flagelos/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Fatores de Ribosilação do ADP/genética , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo , Chlamydomonas reinhardtii/genética , Cílios/genética , Cílios/metabolismo , Flagelos/genética , GTP Fosfo-Hidrolases/genética , Humanos , Ligação Proteica , Transporte Proteico
10.
Exp Ther Med ; 18(4): 2739-2745, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31572521

RESUMO

Interleukin (IL)-37 has an important role in autoimmune diseases by suppressing immunity and inflammation; however, the role of IL-37 in immune thrombocytopenia (ITP) has remained largely elusive. The present study aimed to investigate the expression of IL-37 and its potential role in the pathogenesis of ITP. The plasma levels and expression of IL-37 in the peripheral blood mononuclear cells of patients with active ITP, ITP patients in remission and healthy controls were measured by ELISA and reverse transcription-quantitative PCR, respectively. The levels of IL-37 in patients with ITP treated with and without glucocorticoids were also determined by ELISA. Specific anti-platelet glycoprotein (GP)IIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody-specific immobilization of platelet antigens. The mean value of plasma IL-37 in ITP patients was slightly higher than that in healthy controls, but this was not statistically significant. There was no correlation between IL-37 and anti-platelet autoantibodies, and no significant difference in the IL-37 concentration was identified between patients treated with and without glucocorticoids. In addition, the correlation between IL-37 and the platelet count was analyzed, with no statistical significance observed. It was therefore concluded that IL-37 may not have a pivotal role in the development of ITP. However, the lack of significant differences may be due to the limited number of patients in different groups. A larger number of ITP patients should be enrolled in the future work and achieve more accurate results.

11.
Mol Med Rep ; 20(1): 455-462, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180535

RESUMO

Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) were evaluated by ELISA. The expressions of IκBα and NF­κB p65 were examined by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL­6, TNF­α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF­κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS­induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Alcaloides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Licopeno/uso terapêutico , Quinolizinas/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Sinergismo Farmacológico , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
12.
Chem Biol Interact ; 306: 29-38, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954463

RESUMO

Resveratrol, found in variety of plants, is a natural stilbene structure polyphenol. It has various pharmacological effects, such as antioxidation, anti-aging, anti-inflammation, anti-cancer, antiobesity, anti-diabetes, cardioprotection, neuroprotection. Recently, anti-leukemia activities of resveratrol has been studied extensively via its effects on a variety of biological processes involving cell proliferation, apoptosis, autophagy. Current treatments of leukemia mainly rely on intensive chemotherapy or hematopoietic stem cell transplantation, however, these treatments are still with poor survival and high treatment-related mortality. Therefore, it is extremely needed to find relatively non-toxic medicines with minimal side effects but sufficient therapeutic efficacy. Resveratrol is one such potential candidate owing to its reported anti-leukemia effect. In this review, we summarized resveratrol's discovery, sources and isolation methods, administration methods, effects in different types of leukemia, pharmacokinetics and toxicities, aiming to exploit resveratrol as a potential drug candidate for anti-leukemia.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Descoberta de Drogas , Leucemia/tratamento farmacológico , Resveratrol/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Leucemia/patologia , Resveratrol/efeitos adversos , Resveratrol/química
13.
Cytokine ; 115: 8-12, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30616035

RESUMO

OBJECTIVE: To evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. METHODS: During February 2017-March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. RESULTS: 289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01-1.09], P = 0.006) and 3% (1.03 [1.00-1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8-24.2] vs. 24.0[19.9-29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05-1.13], P < 0.001) and 6% (1.06 [1.02-1.10], P < 0.01), respectively. CONCLUSIONS: High MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.


Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/patologia , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença
14.
Brain Res Bull ; 142: 176-182, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30016728

RESUMO

OBJECTIVE: To investigate the prognostic value of aspirin reaction units (ARU) in a 3-month follow-up study in a cohort of Chinese patients with first-ever ischemic stroke. METHODS: Prospective single-center survey of acute ischemic stroke patients receiving aspirin therapy. Two hundred and seventy-five Chinese patients with first-ever ischemic stroke who previously received aspirin therapy were enrolled. ARU was measured using the VerifyNow system. A cutoff of 550 ARU was used to determine the presence of aspirin resistance (AR). RESULTS: Median age at study entry was 67 years (IQR: 59-75) and 142(51.6%) were male. A total of 52 of 275 enrolled patients (18.9%) were AR. Median regression estimated a statistically significant increase in NIHSS score of 0.033 point for every 1-point increase in ARU (95% CI, 0.024 to 0.068; P < 0.001). The unfavorable outcomes distribution across the ARU quartiles ranged between 11.8% (first quartile) to 64.8% (fourth quartile). After adjusting for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the ARU, levels of ARU were associated with unfavorable outcome, and the adjusted risk of unfavorable outcome increased by 145% (OR = 2.45 [95% CI 1.46-3.87], P = 0.011) and 317% (4.17[2.76-6.15], P < 0.001), respectively. Similarly, the adjusted risk of mortality increased by 215% (OR = 3.15 [95% CI 1.98-4.73], P = 0.008) and 429% (5.29[4.02-8.17], P < 0.001), respectively. CONCLUSIONS: The results suggest that AR is a meaningful and independent marker to predict short-term functional outcome in patients with ischemic stroke.


Assuntos
Aspirina/uso terapêutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Isquemia Encefálica/epidemiologia , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia
15.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(2): 164-168, 2018 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926683

RESUMO

OBJECTIVES: To investigate the effects of Astragaloside IV (AST) on diastolic function of rat thoracic aorta rings which was injured by microvesicles derived from hypoxia/reoxygenation (H/R)-treated human umbilical vein endothelial cells (HUVECs), and the mechanism of AST. METHODS: H/R-induced endothelial microvesicles (H/R-EMVs) were generated from cultured HUVECs in vitro under the condition of hypoxia for 12 hour/Reoxygenation for 4 hour, H/R-EMVs were stored in D-Hank's solution. Male Wistar rats were underwent thoracotomy, the thoracic aorta with intact endothelium were carefully removed and cut into 3~4 mm rings. The experiment was divided into six groups. H/R-EMVs group:thoracic aortic rings of rats were incubated in culture medium and treated with H/R-EMVs in a final concentration of 10µg/ml; different doses of AST groups:thoracic aortic rings of rats were treated with 10, 20, 40, 60 mg/L AST co-incubated with 10µg/ml H/R-EMVs respectively; control group were treated with the same volume of D-Hank's solution. Duration of incubation was 4 h, each group was tested in five replicate aortic rings. Effects of AST on endothelium-dependent relaxation were detected. The production of nitric oxide (NO) and the level of endothelial NO synthase (eNOS), phosphorylated eNOS (p-eNOS, Ser-1177), serine/threonine kinase (Akt), phosphorylated Akt (p-Akt, Ser-473), extracellular regulated protein kinases (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2, Thr202/Tyr204) of rat thoracic aortic rings were detected. RESULTS: Tenµg/ml H/R-EMVs could impaire the relaxation of rat thoracic aortic rings significantly (P<0.01). Compared with H/R-EMVs group, relaxation of rat thoracic aortic rings was increased by 20, 40 and 60 mg/L AST in a concentration-dependent manner (P<0.01), the level of NO production was also enhanced (P<0.05, P<0.01). The level of t-eNOS, t-Akt and ERK1/2 was not changed, but the level of p-eNOS, p-Akt and p-ERK1/2 increased by the treatment with AST (P<0.01). CONCLUSIONS: AST could effectively ameliorate endotheliumdependent relaxation of rat thoracic aortic rings impaired by H/R-EMVs in a concentration-dependent manner, the mechanism might involve the increase in production of NO, and the protein level of p-eNOS, p-Akt and p-ERK1/2.


Assuntos
Aorta Torácica/efeitos dos fármacos , Micropartículas Derivadas de Células/patologia , Saponinas/farmacologia , Triterpenos/farmacologia , Vasodilatação , Animais , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar
16.
Oncogene ; 37(11): 1485-1502, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29321664

RESUMO

Mitochondria fission and mitophagy are fundamentally crucial to cellular physiology and play important roles in cancer progression. Developing a comprehensive understanding of the molecular mechanism underlying mitochondrial fission and mitophagy will provide novel strategies for cancer prevention and treatment. Actin has been shown to participate in mitochondrial fission and mitophagy regulation. Cofilin is best known as an actin-depolymerizing factor. However, the molecular mechanism by which cofilin regulates mitochondrial fission and mitophagy remains largely unknown. Here we report that knockdown of cofilin attenuates and overexpression of cofilin potentiates mitochondrial fission as well as PINK1/PARK2-dependent mitophagy induced by staurosporine (STS), etoposide (ETO), and carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Cofilin-mediated-PINK1 (PTEN-induced putative kinase 1) accumulation mainly depends on its regulation of mitochondrial proteases, including peptidase mitochondrial processing beta (MPPß), presenilin-associated rhomboid-like protease (PARL), and ATPase family gene 3-like 2 (AFG3L2), via mitochondrial membrane potential activity. We also found that the interaction and colocalization of G-actin/F-actin with cofilin at mitochondrial fission sites undergo constriction after CCCP treatment. Pretreatment with the actin polymerization inhibitor latrunculin B (LatB) increased and actin-depolymerization inhibitor jasplakinolide (Jas) decreased mitochondrial translocation of actin induced by STS, ETO, and CCCP. Both LatB and Jas abrogated CCCP-mediated mitochondrial fission and mitophagy. Our data suggest that G-actin is the actin form that is translocated to mitochondria, and the actin-depolymerization activity regulated by cofilin at the mitochondrial fission site is crucial for inducing mitochondrial fission and mitophagy.


Assuntos
Fatores de Despolimerização de Actina/fisiologia , Actinas/metabolismo , Dinâmica Mitocondrial/genética , Mitofagia/genética , Multimerização Proteica/genética , Fatores de Despolimerização de Actina/metabolismo , Sítios de Ligação , Células Cultivadas , Humanos , Proteínas Quinases/fisiologia , Transporte Proteico , Ubiquitina-Proteína Ligases/fisiologia
17.
J Food Sci ; 83(1): 46-52, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29194607

RESUMO

To evaluate the role of Maillard reactions in the generation of flavor compounds in Jinhua ham, the reactions of glucose and ethanal with histidine and lysine, respectively, were studied by simulating the ripening conditions of Jinhua ham. The volatile products produced were analyzed using solid phase microextraction-gas chromatography/mass spectrometry. The results showed that 8 volatile compounds were generated by the reaction of glucose and histidine and 10 volatile compounds were generated by the reaction of glucose and lysine. Reactions of ethanal with lysine and with histidine both generated 31 volatile compounds that contributed to the flavor of Jinhua ham. This indicates that histidine and lysine related to Maillard reactions possibly play important roles in the generation of the unique flavor compounds in Jinhua ham. This research demonstrates that free amino acids participate in the generation of volatile compounds from Jinhua ham via the Maillard reaction and provides a basic mechanism to explain flavor formation in Jinhua ham. PRACTICAL APPLICATION: Jinhua ham is a well-known traditional Chinese dry-cured meat product. However, the formation of the compounds comprising its special flavor is not well understood. Our results indicate that Maillard reactions occur in Jinhua ham under ripening conditions. This work illustrates the contribution of Maillard reactions to the flavor of Jinhua ham.


Assuntos
Histidina/química , Lisina/química , Reação de Maillard , Produtos da Carne/análise , Suínos , Compostos Orgânicos Voláteis/análise , Acetaldeído/química , Animais , China , Manipulação de Alimentos/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Glucose/química , Microextração em Fase Sólida/métodos , Paladar
18.
Oncotarget ; 8(33): 54572-54582, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903365

RESUMO

OBJECTIVE: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats. RESULTS: Treatment with I-MVssignificantly reduced the size of myocardial infarction, the activities of serum CK-MB and LDH, and the number of apoptotic cardiomyocytes. The activities of caspase 3, caspase 9 and caspase 12 in myocardium were also decreased significantly with I-MVs treatment. Moreover, the expression of Bax was decreased but Bcl-2 was increased. The expression of glucose regulated protein 78 (GRP78), sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phosphorylated phospholamban (p-PLB) were increased after being treated with I-MVs. CONCLUSION: I-MVs could protect hearts from I/R injury in rats through SERCA2 and p-PLB of calcium regulatory proteins to alleviate intrinsic myocardial apoptosis including mitochondrial and endoplasmic reticulum pathways.

19.
Biol Open ; 6(11): 1680-1691, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28838966

RESUMO

Intraflagellar transport (IFT) particles are composed of polyprotein complexes IFT-A and IFT-B as well as cargo adaptors such as the BBSome. Two IFT-B subunits, IFT25 and IFT27 were found to form a heterodimer, which is essential in exporting the BBSome out of the cilium but not involved in flagellar assembly and cytokinesis in vertebrates. Controversial results were, however, recorded to show that defects in IFT, flagellar assembly and even cytokinesis were caused by IFT27 knockdown in Chlamydomonas reinhardtii Using C. reinhardtii as a model organism, we report that depletion of IFT25 has no effect on flagellar assembly and does not affect the entry of the BBSome into the flagellum, but IFT25 depletion did impair BBSome movement out of the flagellum, clarifying the evolutionally conserved role of IFT25 in regulating the exit of the BBSome from the flagellum cross species. Interestingly, depletion of IFT25 causes dramatic reduction of IFT27 as expected, which does not cause defects in flagellar assembly and cytokinesis in C. reinhardtii Our data thus support that Chlamydomonas IFT27, like its vertebrate homologues, is not involved in flagellar assembly and cytokinesis.

20.
Exp Ther Med ; 13(6): 3567-3573, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28588681

RESUMO

The aim of the present study was to investigate the molecular mechanism associated with the traditional Chinese medicine formula Gui Zhu Yi Kun formula (GZYKF), in the treatment of polycystic ovary syndrome (PCOS). In this study, granulosa cells (GCs) of rats with PCOS were cultured and treated with testosterone propionate (TP) alone or with serum from rats treated with different doses of GZYKF. The effect of TP on cell growth was assayed using the MTT method. Expression levels of Beclin-1, light chain (LC)3, mechanistic target of rapamycin (mTOR), tumor suppressor p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), sestrin2 and tuberous sclerosis protein 1/2 were evaluated using quantitative polymerase chain reaction and western blotting. It was demonstrated that TP increased the expression of Beclin-1 and LC3, whereas GZYKF significantly decreased the TP-induced expression of Beclin-1 (P<0.01). Additionally, GCs treated with GZYKF exhibited significant increases in mTOR, phosphorylated mTOR and AMPKα expression levels, and significant reductions in p53 and sestrin2 expression levels were observed. In conclusion, the findings of the present study suggest that a reduction in ovarian GCs in rats with PCOS may be associated with GC autophagy. Furthermore, the effects of GZYKF in mediating the p53/AMPK pathway may inhibit GC autophagy, which suggests a possible novel mechanism underlying the treatment of PCOS with GZYKF.

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