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1.
Acta Parasitol ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33813654

RESUMO

PURPOSE: Prevention of ocular surface (OS) Demodex infestation plays an important role in OS hygiene and variety of factors may be associated with it, in which diabetes mellitus (DM) or dry eye disease (DED) has caught the attention of most scholars. However, there has been no research on whether there was a potential interaction between DM and DED in the process of OS Demodex infestation. This cross-sectional study was implemented in Zhujiang Hospital of Southern Medical University. METHODS: Ophthalmologic interviews, questionnaires, and examinations were conducted. Factors including general information, DM status, dry eye condition, etc. were collected to study the correlation of DM and DED on OS Demodex infestation. RESULTS: After statistical analysis, we found that both DM (P < 0.001) and DED (P = 0.013 < 0.05) are closely associated with OS Demodex infestation. Compared with DED, DM has higher priority association with OS Demodex infestation, and patients with both diseases have a significant higher risk of OS Demodex infestation (R = 0.197, P < 0.001). Meanwhile, age (R = 0.299, P < 0.001) and hypertension (P < 0.05) were also correlated with OS Demodex infestation. CONCLUSION: This study provides a new evidence-based basis for clinical prevention and management of OS Demodex infestation.

2.
Brain Res Bull ; 171: 162-171, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33811955

RESUMO

Orofacial ectopic pain can often arise following nerve injury. However, the exact mechanism responsible for orofacial ectopic pain induced by trigeminal nerve injury remains unknown. The α2δ-1 and glutamate N-methyl-d-aspartic acid receptor (NMDAR) interactions have been demonstrated to participate in neuropathic pain regulation in the spinal cord. In this study, a rat model of inferior alveolar nerve transection (IANX) was used to investigate the role of α2δ-1-NMDAR1 interaction in the trigeminal ganglion (TG) in regard to the regulation of orofacial ectopic pain. Western blot (WB) analysis indicated that α2δ-1 and NMDAR1 in the TG were substantially higher in IANX rats than they were in sham/naive rats. Additionally, immunofluorescence (IF) results revealed that α2δ-1 and NMDAR1 were co-expressed and distributed within neurons and activated satellite glial cells in the TG. Co-immunoprecipitation (Co-IP) results indicated that α2δ-1-NMDAR1 complex levels in the TG were higher in IANX rats than they were in sham rats. Furthermore, the results of behavioral tests demonstrated that intra-TG injection of gabapentin (α2δ-1 inhibitory ligand) or memantine hydrochloride (NMDAR antagonist) reversed the decrease in mechanical head-withdrawal threshold (HWT) in IANX rats. Moreover, inhibition of α2δ-1 by intra-TG administration of gabapentin suppressed the upregulation of the NMDAR1 protein, and the inhibition of NMDAR by intra-TG administration of memantine hydrochloride inhibited the increased expression of α2δ-1 protein induced by IANX. In conclusion, the physical and functional interaction between α2δ-1 and NMDAR1 is critical for the development of orofacial ectopic pain, indicating that α2δ-1, NMDAR1, and the α2δ-1-NMDAR1 complex may represent potential targets for the treatment of orofacial ectopic pain.

3.
Proc Biol Sci ; 288(1948): 20210073, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33823666

RESUMO

Both anthropogenic impacts and historical climate change could contribute to population decline and species extinction, but their relative importance is still unclear. Emerging approaches based on genomic, climatic and anthropogenic data provide a promising analytical framework to address this question. This study applied such an integrative approach to examine potential drivers for the endangerment of the green peafowl (Pavo muticus). Several demographic reconstructions based on population genomes congruently retrieved a drastic population declination since the mid-Holocene. Furthermore, a comparison between historical and modern genomes suggested genetic diversity decrease during the last 50 years. However, climate-based ecological niche models predicted stationary general range during these periods and imply the little impact of climate change. Further analyses suggested that human disturbance intensities were negatively correlated with the green peafowl's effective population sizes and significantly associated with its survival status (extirpation or persistence). Archaeological and historical records corroborate the critical role of humans, leaving the footprint of low genomic diversity and high inbreeding in the survival populations. This study sheds light on the potential deep-time effects of human disturbance on species endangerment and offers a multi-evidential approach in examining underlying forces for population declines.

4.
Curr Oncol ; 28(2): 1354-1365, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805318

RESUMO

OBJECTIVE: For patients with esophageal squamous cell carcinoma, preoperative chemoradiotherapy followed by planned esophagectomy is used as a curative treatment modality. However, the impact of radiotherapy dose remains undefined. METHOD: A total of 141 patients with stage III esophageal squamous cell carcinoma (ESCC; as defined by the 7th American Joint Committee on Cancer), receiving preoperative chemoradiotherapy followed by esophagectomy between 2000 and 2015 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were retrospectively reviewed. The radiotherapy dose of preoperative chemoradiotherapy (36 Gy before 2009 and 50-50.4 Gy after 2009) and other clinicopathological parameters were collected and correlated with the response to chemoradiotherapy and treatment outcome. RESULT: Of these 141 patients, the radiotherapy dose was 36 Gy in 59 (42%) patients and 50 Gy in 82 (58%) patients. A complete pathological response was noted in 12 (20%) of 59 patients receiving 36 Gy radiotherapy, and 37 (45%) of 82 patients receiving 50 Gy radiotherapy (p = 0.002). The three-year overall survival and disease-free survival rates were 31% and 25% in patients receiving 36 Gy radiotherapy, and 54% and 46% in patients receiving 50-50.4 Gy radiotherapy, respectively (p = 0.023 for overall survival; p = 0.047 for disease-free survival). Multivariate analysis showed that a higher radiotherapy dose was associated with increased pathological complete response (p = 0.003, hazard ratio: 3.215), better overall survival (p = 0.024, hazard ratio: 1.585), and superior disease-free survival (p = 0.049, hazard ratio: 1.493). However, higher radiotherapy doses revealed more surgical complications, including acute respiratory distress syndrome (p = 0.048) and anastomosis leaks (p = 0.004). CONCLUSION: For patients with locally advanced ESCC, preoperative chemoradiotherapy with higher radiotherapy doses led to increased pathologic complete response rates and improved survival.

5.
Langmuir ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849275

RESUMO

The oxygen vacancy caused by ultrathin structures would be introduced into the semiconductor photocatalyst to boost its photocatalytic activity. Herein, ultrathin Bi2O3-Bi2WO6 nanosheet composites have been successfully synthesized via a facile hydrothermal method. Compared to pure Bi2WO6 nanosheets, the Bi2O3-Bi2WO6 nanosheet composites possess abundant oxygen vacancies, which was confirmed by the positron annihilation spectra. The ultrathin Bi2O3-Bi2WO6 nanosheet composites exhibited remarkable photocatalytic degradation performance for oxytetracycline compared with that of pure Bi2WO6 nanosheets. The excellent photocatalytic activities of Bi2O3-Bi2WO6 composites could be attributed to the heterojunction structure and the oxygen vacancies caused by ultrathin structures.

6.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802643

RESUMO

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.


Assuntos
Quimiocina CCL20/metabolismo , Docetaxel/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Docetaxel/farmacologia , Humanos , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Colloid Interface Sci ; 596: 225-232, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33848742

RESUMO

Glycoproteins play crucial roles in many biological events such as protein folding, information transmission, nerve conduction, and molecular recognition. Some glycoproteins serve as disease biomarkers in clinical settings. However, selective detection of glycoprotein often faces great challenges, owing to its low abundance in complex biological samples. In this case, develop a highly sensitive and selective approach for glycoprotein detection is urgently needed. Molecularly imprinted polymers (MIPs) have proved to be an ideal absorbent material in detection and separation science. Herein, a novel biomass activated carbon-derived imprinted polymer (BAC@PEI/PBA/MIPs) was fabricated for selective recognition of glycoprotein. The as-prepared BAC@PEI/PBA/MIPs was synthesized using waste tea derived carbon as matrix, albumin chicken egg (OVA) as template, and dopamine as functional monomer. Branched polyethyleneimine (PEI) was covalently bonded on the BAC surface to increase the number of boronic acid moieties. Benefiting from the self-polymerization of dopamine and multi-boronic acid sites, a great number of recognition sites were presented under mild conditions. The static adsorption experiment showed that the BAC@PEI/PBA/MIPs exhibited a high binding capacity of 196.2 mg/g, rapid adsorption dynamics of 40 min, excellent selectivity and satisfactory reusability for OVA. Furthermore, the practicability of BAC@PEI/PBA/MIPs was verified by isolation of OVA from egg white. The good binding performance and facile preparation process make BAC@PEI/PBA/MIPs attractive for glycoprotein recognition, indicating its potential applications in biomedical research and clinical diagnostics.

8.
Pain Physician ; 24(2): E203-E210, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33740357

RESUMO

BACKGROUND: Percutaneous full-endoscopic surgery was recently developed for the treatment of cervical foraminal stenosis and posterolateral disc herniation. However, there are no studies involving endoscopic surgery to treat cervical spondylotic myelopathy (CSM). OBJECTIVES: To observe the safety, feasibility, and efficacy of posterolateral full-endoscopic ventral decompression (PLEVD) via computed tomography (CT)-guided surgery in patients with single-level CSM. STUDY DESIGN: A prospective cohort study. SETTING: The First Affiliated Hospital of Gannan Medical College. METHODS: From May 2018 to August 2019, 21 patients with single-level CSM underwent CT-guided PLEVD. The posterolateral angle was measured during surgery. The neurologic condition was evaluated via the Japanese Orthopaedic Association (JOA) score and recovery rate, and a Visual Analog Scale (VAS) was used to measure pain relief. The maximum spinal canal diameter (MSCD) was measured on pre- and postoperative CT images. RESULTS: The mean length of follow-up was 11.3 ± 5.3 months. The average posterolateral angle was 36.0° ± 5.6°. The mean VAS score of limbs significantly decreased after surgery. The mean JOA score improved during the follow-up period. Nineteen of the 21 patients achieved good or excellent outcomes, and 2 patients had fair outcomes according to the JOA score 6 months after surgery. The average MSCD was enlarged from 0.55 ± 0.15 cm preoperatively to 1.02 ± 0.18 cm postoperatively. LIMITATIONS: This study was nonrandomized and provides only preliminary clinical results for single-level CSM. CONCLUSION: Under appropriate indications, PLEVD under CT guidance is an available and safe technique for treating single-level CSM.

9.
J Alzheimers Dis ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33749643

RESUMO

BACKGROUND: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. OBJECTIVE: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. METHODS: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged >  60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-ß peptide (Aß) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. RESULTS: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (-6.51, -10.57 to -2.45) compared to placebo. DHA lower the Aß40 levels (-40.57, -79.79 to -1.35) compared to placebo (p <  0.05), and folic acid + DHA reduced the Aß42 (-95.59, -150.76 to -40.43) and Aß40 levels (-45.75, -84.67 to -6.84) more than DHA (p <  0.05). CONCLUSION: Folic acid and DHA improve cognitive function and reduce blood Aß production in MCI patients. Combination therapy may be more beneficial in reducing blood Aß-related biomarkers.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33719403

RESUMO

The rational design of advanced electrocatalysts and energy-saving electrolysis strategies is highly desirable for achieving high-efficiency electrochemical H2 generation yet challenging. In this work, we report highly branched Pd hydride nanodendrites (PdH-NDs) formed by a very facial solvothermal method and a succedent chemical H intercalation method in N,N-dimethylformamide. The electrocatalytic performance of PdH-NDs is experimentally and theoretically correlated with the morphology and composition, which has demonstrated substantially enhanced electrochemical activity and stability for formate oxidation reaction and hydrogen evolution reaction in alkaline electrolyte compared with Pd nanodendrites. Density functional theory calculations suggest a downshift of the Pd d-band center of PdH-NDs due to the dominant Pd-H ligand effects that weaken the binding energies of the intermediate catalytic species and toxic carbon monoxide. The asymmetric formate electrolyzer based on bifunctional PdH-ND electrocatalysts is first constructed, which only requires a low voltage of 0.54 V at 10 mA cm-2 for continuous H2 generation. This study reveals significant insights about the morphology/composition-performance relationship for palladium hydrides with bifunctional electroactivity.

12.
Medicine (Baltimore) ; 100(11): e24949, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725966

RESUMO

ABSTRACT: Currently, no effective prognostic model of clear cell renal cell carcinoma (ccRCC) based on immune cell infiltration has been developed. Recent studies have identified 6 immune groups (IS) in 33 solid tumors. We aimed to characterize the expression pattern of IS in ccRCC and evaluate the potential in predicting patient prognosis. The clinical information, immune subgroup, somatic mutation, copy number variation, and methylation score of patients with TCGA ccRCC cohort were downloaded from UCSC Xena for further analysis. The most dominant IS in ccRCC was the inflammatory subgroup (immune C3) (86.5%), regardless of different pathological stages, pathological grades, and genders. In the C3 subgroup, stage IV (69.1%) and grade 4 (69.9%) were the least presented. Survival analysis showed that the IS could effectively predict the overall survival (OS) (P < .0001) and disease-specific survival (DSS) (P < .0001) of ccRCC alone, of which group C3 (OS, HR = 2.3, P < .001; DSS, HR = 2.84, P < .001) exhibited the best prognosis. Among the most frequently mutated ccRCC genes, only VHL and PBRM1 were found to be common in the C3 group. The homologous recombination deficiency score was also lower. High heterogeneity was observed in immune cells and immunoregulatory genes of IS. Notably, CD4+ memory resting T cells were highly infiltrating, regulatory T cells (Treg) showed low infiltration, and most immunoregulatory genes (such as CX3CL1, IFNA2, TLR4, SELP, HMGB1, and TNFRSF14) were highly expressed in the C3 subgroup than in other subgroups. Enrichment analysis showed that adipogenesis, apical junction, hypoxia, IL2 STAT5 signaling, TGF-beta signaling, and UV response DN were activated, whereas E2F targets, G2M checkpoint, and MYC targets V2 were downregulated in the C3 group. Immune classification can more accurately classify ccRCC patients and predict OS and DSS. Thus, IS-based classification may be a valuable tool that enables individualized treatment of patients with ccRCC.


Assuntos
Carcinoma de Células Renais/classificação , Imunofenotipagem/métodos , Neoplasias Renais/classificação , Subpopulações de Linfócitos/imunologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Quimiocina CX3CL1 , Variações do Número de Cópias de DNA/imunologia , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica/imunologia , Proteína HMGB1 , Humanos , Interferon-alfa , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Metilação , Mutação/imunologia , Gradação de Tumores , Estadiamento de Neoplasias , Selectina-P , Valor Preditivo dos Testes , Prognóstico , Membro 14 de Receptores do Fator de Necrose Tumoral , Transdução de Sinais/imunologia , Análise de Sobrevida , Receptor 4 Toll-Like , Fatores de Transcrição , Proteína Supressora de Tumor Von Hippel-Lindau
13.
Chin J Nat Med ; 19(2): 120-133, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33641783

RESUMO

Pulmonary arterial hypertension (PAH) is a devastating pulmonary circulation disease lacking high-efficiency therapeutics. The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata, a well-known traditional chinese medicine with cardiopulmonary protection capacity, on PAH by exploiting functional lipidomics. The rat model with PAH was successfully established for first, following Rhodiola crenulata water extract (RCE) treatment, then analysis of chemical constituents of RCE was performed, additional morphologic, hemodynamic, echocardiographic measurements were examined, further targeted lipidomics assay was performed to identify differential lipidomes, at last accordingly mechanism assay was done by combining qRT-PCR, Western blot and ELISA. Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls, mostly assigned to acylcarnitines, phosphatidylcholines, sphingomyelin associated with the PAH development. Excitingly, RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH. Furthermore, RCE was observed to reduce autophagy, confirmed by significantly inhibited PPARγ, LC3B, ATG7 and upregulated p62, and inactivated LKB1-AMPK signal pathway. Notably, we accurately identified the constituents in RCE, and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy. Altogether, RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH. This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.

14.
Elife ; 102021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33787493

RESUMO

The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The synaptic transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of synaptic transmission remains poorly understood. Here we show that in Caenorhabditis elegans, the male environment increases the hermaphrodite cholinergic transmission at the neuromuscular junction (NMJ), which alters hermaphrodites' locomotion velocity and mating efficiency. We identify that the male-specific pheromones mediate this synaptic transmission modulation effect in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to the male pheromones specifically increases the accumulation of presynaptic CaV2 calcium channels and clustering of postsynaptic acetylcholine receptors at cholinergic synapses of NMJ, which potentiates cholinergic synaptic transmission. Thus, our study demonstrates a circuit mechanism for synaptic modulation and behavioral flexibility by sexual dimorphic pheromones.

15.
Sci Total Environ ; 773: 145583, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582359

RESUMO

Graphitic carbon nitride (g-C3N4) has emerged as a most promising photocatalyst, non-toxicity and low density, but it is plagued by low activity due to the small specific surface area and poor quantum efficiency. Morphological engineering and coupling with other materials to form hybrids have proven to be effective strategies for enabling high photocatalytic performances. Here, neodymium oxide (Nd2O3) coupled tubular g-C3N4 composites had been facilely synthesized by a solvent evaporation and high-temperature calcination method to realize efficient photocatalytic activity of hydrogen production and NO removal. A series of characterizations, such as XRD, ESR, in-situ DRIFTS, etc., were used to analyze the physical and chemical properties of the bifunctional photocatalyst, which demonstrated that the composite material had more active sites and a faster electron transfer rate. The optimal sample (1 wt% Nd2O3/CN-T) had a H2 generation rate of 4355.34 µmol·g-1·h-1, which was 9.46 times than that of original g-C3N4 obtained through heating melamine (CN-M). In addition, the NO removal rate was also 32.32% higher than that of original CN-M. On the basis of the above photocatalytic experimental results and characterizations, a possible mechanism or pathway was proposed and illustrated. This work could provide a feasible strategy to fabricate tubular g-C3N4-based composites with rare earth metal oxides (dual-factor regulation) to simultaneously enhance photocatalytic hydrogen production and NO removal efficiently (double application).

16.
Int J Mol Med ; 47(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33576441

RESUMO

Coronavirus disease 2019 (COVID­19) is an acute infectious pneumonia caused by a novel type of coronavirus infection. There are currently no clinically available specific drugs for the treatment of this virus. The process of host invasion is the key to viral infection, and it is a mechanism that needs to be considered when exploring antiviral drugs. At present, studies have confirmed that angiotensin­converting enzyme II (ACE2) is the main functional receptor through which severe acute respiratory syndrome coronavirus (SARS­CoV­2) invades host cells. Therefore, a number of studies have focused on this field. However, as ACE2 may play a dual role in mediating susceptibility and immunity to SARS­CoV­2 infection, the role of ACE2 in viral infection is controversial. Beginning with the physiological function of ACE2, the present review article summarizes the influence of the ACE2 content on the susceptibility to the virus and acute lung injury. Drug mechanisms were taken as the starting point, combined with the results of clinical trials, specifically elaborating upon and analyzing the efficacy of several ACE2­centered therapeutic drugs and their potential effects. In addition, the current status of ACE2 as a targeted therapy for COVID­19 is discussed in order to provide new insight into the clinical prevention and treatment of COVID­19.


Assuntos
/fisiologia , Antivirais/farmacologia , /terapia , Interações Hospedeiro-Patógeno/fisiologia , /antagonistas & inibidores , /virologia , Doenças Cardiovasculares/etiologia , Cloroquina/análogos & derivados , Cloroquina/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Indóis/farmacologia , Terapia de Alvo Molecular , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 239-242, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554827

RESUMO

OBJECTIVE: To establish quantitative surface plasmon resonance (SPR) assay for antibodies against human platelet antigen-1a (HPA-1a). METHODS: Recombinant protein was fixed on the chip surface by amino coupling method. SPR assay was used to detect the standard antibodies against HPA-1a at different conceatration. The optimal experimental parameters were determined, and standard curves were constructed with linear regression. Moreover, the sensitivity, specificity, accuracy and precision of the assay were evaluated. RESULTS: The quantitative SPR assay for HPA-1a antibodies was established. The determination ranges were 0-20 IU, with accuracy (recovery rate) was 97.75%-103.08%. The intra-assay precision [coefficients of variation (CV)] was 3.53%-4.29%, and the inter-assay precision (CV) was 2.08%-4.40%. For specificity test, several kinds of monoclonal and human antibodies against platelet membrane protein were tested and no positive result was observed. CONCLUSION: The established quantitative SPR assay for HPA-1a antibodies shows good sensitivity, specificity, accuracy and precision, and this rapid and simple method provides a new reference method for scientific research and clinical antibody detection.


Assuntos
Antígenos de Plaquetas Humanas , Plaquetas , Humanos , Isoanticorpos , Ressonância de Plasmônio de Superfície
18.
Environ Toxicol ; 36(6): 1070-1079, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33522089

RESUMO

Glaucoma is the main reason for irreversible blindness, and pathological increased intraocular pressure is the leading risk factor for glaucoma. It is reported that trabecular meshwork cell injury is closely associated with the elevated intraocular pressure. The current study aimed to investigate the role of small nucleolar RNA host gene 3 (SNHG3) in human trabecular meshwork (HTM) cells under oxidative stress. A series of experiments including real-time quantitative polymerase chain reaction, subcellular fractionation assay, western blot analysis, cell counting kit-8 assay, RNA pull down, flow cytometry analysis, and RNA immunoprecipitation assay were used to explore the biological function and regulatory mechanism of SNHG3 in HTM cells under oxidative stress. First, we observed that H2 O2 induced SNHG3 upregulation in HTM cells. Then, we found that SNHG3 silencing alleviated H2 O2 -induced oxidative damage in HTM cells. Moreover, snail family transcriptional repressor 2 (SNAI2) knockdown alleviated the oxidative damage induced by H2 O2 in HTM cells. Mechanistically, SNHG3 bound with ELAV like RNA binding protein 2 (ELAVL2) to stabilize SNAI2. Finally, SNAI2 overexpression counteracted the effect of SNHG3 silencing on H2 O2 -treated HTM cells. In conclusion, our results demonstrated that SNHG3 cooperated with ELAVL2 to modulate cell apoptosis and extracellular matrix accumulation by stabilizing SNAI2 in HTM cells under oxidative stress.


Assuntos
Estresse Oxidativo , Malha Trabecular , Apoptose , Células Cultivadas , Matriz Extracelular/metabolismo , Humanos , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Regulação para Cima
19.
Org Lett ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528266

RESUMO

A new, efficient approach toward the preparation of 2-aryl-2,3-dihydrobenzofuran scaffolds through the Cu/SPDO-catalyzed [3 + 2] cycloaddition between quinone ester and styrene derivatives has been developed. The procedure features excellent enantioselectivities (up to 99% ee), high yields (up to 96%), and broad substrate tolerance. Additionally, asymmetric synthesis of natural corsifurans A and B from commercially available starting materials has also been achieved in two or three steps using this reaction as a key transformation.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33418958

RESUMO

BACKGROUND: To assess the presence of adverse pathological features at the time of salvage total laryngectomy (TL) associated with oncologic outcome. METHODS: Ninety patients with persistent/locally recurrent disease and who subsequently underwent salvage TL after definitive treatment by radiation alone (RTO) or concurrent chemo-radiation (CCRT) from 2009 to 2018 were retrospectively enrolled. Kaplan-Meier methods were used to estimate overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: Lymphovascular invasion (LVI), perineural invasion, positive margin, and stage IV disease were associated with worse survival in the univariate analysis. In the multivariate analysis, the presence of LVI and positive margin were both independent negative predictors in OS (LVI: adjusted hazard ratio (aHR) = 2.537, 95% CI: 1.163-5.532, p = 0.019; positive margin: aHR = 5.68, 95% CI: 1.996-16.166, p = 0.001), DSS (LVI: aHR = 2.975, 95% CI: 1.228-7.206, p = 0.016); positive margin: aHR = 11.338, 95% CI: 2.438-52.733, p = 0.002), and DFS (LVI: aHR 2.705, 95% CI: 1.257-5.821, p = 0.011; positive margin (aHR = 6.632, 95% CI: 2.047-21.487, p = 0.002). CONCLUSIONS: The presence of LVI and positive margin were both associated with poor OS, DSS, and DFS among patients who underwent salvage TL after failure of RTO/CCRT. The role of adjuvant therapy for high-risk patients after salvage TL to improve the chance of survival requires more investigation in the future.


Assuntos
Quimiorradioterapia , Laringectomia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos
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