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1.
Angew Chem Int Ed Engl ; : e202407228, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975669

RESUMO

Three functionalized thienopyrazines (TPs), TP-MN (1), TP-CA (2), and TPT-MN (3) were designed and synthesized as self-assembled monolayers (SAMs) deposited on the NiOx film for tin-perovskite solar cells (TPSCs). Thermal, optical, electrochemical, morphological, crystallinity, hole mobility, and charge recombination properties, as well as DFT-derived energy levels with electrostatic surface potential mapping of these SAMs, have been thoroughly investigated and discussed. The structure of the TP-MN (1) single crystal was successfully grown and analyzed to support the uniform SAM produced on the ITO/NiOx substrate. When we used NiOx as HTM in TPSC, the device showed poor performance. To improve the efficiency of TPSC, we utilized a combination of new organic SAMs with NiOx as HTM, the TPSC device exhibited the highest PCE of 7.7 % for TP-MN (1). Hence, the designed NiOx/TP-MN (1) acts as a new model system for the development of efficient SAM-based TPSC. To the best of our knowledge, the combination of organic SAMs with anchoring CN/CN or CN/COOH groups and NiOx as HTM for TPSC has never been reported elsewhere. The TPSC device based on the NiOx/TP-MN bilayer exhibits great enduring stability for performance, retaining ~80 % of its original value for shelf storage over 4000 h.

2.
Mol Cancer ; 21(1): 169, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999636

RESUMO

BACKGROUND: Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. RESULTS: Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10- 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). CONCLUSIONS: Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).


Assuntos
Transtornos de Deglutição , Neoplasias Nasofaríngeas , Quimiorradioterapia , Transtornos de Deglutição/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia
3.
BMC Cancer ; 22(1): 1086, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36271384

RESUMO

BACKGROUND: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. METHODS: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. RESULTS: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 µV) also had poor outcome. CONCLUSIONS: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier: NCT03243448.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Frequência Cardíaca , Resultado do Tratamento
4.
AIDS Care ; 34(8): 1041-1047, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34156890

RESUMO

Medication adherence to antiretroviral therapy (ART) among elderly people living with HIV (PLWH) is of serious concern. Our study aimed to understand the medication adherence of elderly PLWH under ART based on the health belief model (HBM). A baseline survey with a total of 529 elderly PLWH was conducted in Sichuan. Logistic and linear regression analysis, mediation analysis, and path analysis based on prior evidence were used. Only self-efficacy showed direct associations with medication adherence in the last four days (ORm = 1.37, 95%CI: 1.11, 1.70) and the last month (ORm = 1.39, 95%CI: 1.18, 1.63) in the multivariate analysis. Self-efficacy mediated the relations between perceived benefits, perceived barriers, cues to action and medication adherence. Inner relations existed within the HBM. In addition to the direct effects, perceived benefits (ß = 0.149, p = 0.031; ß = 0.093, p = 0.005), perceived barriers (ß = -0.070, p = 0.008; ß = -0.062, p = 0.012), and cues to action (ß = 0.184, p = 0.013; ß = 0.135, p = 0.014) showed indirect effects on medication adherence in the last four days and the last month, respectively. HBM may be effective in predicting medication adherence of elderly PLWH, and self-efficacy may be a crucial predictor and mediator. Efforts should be focused on how to enhance elderly PLWH's self-efficacy without neglect of other medication beliefs.


Assuntos
Infecções por HIV , Autoeficácia , Idoso , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Modelo de Crenças de Saúde , Humanos , Adesão à Medicação/psicologia , Inquéritos e Questionários
5.
Nucleic Acids Res ; 48(13): 7371-7384, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32556261

RESUMO

ZFP36L1, a CCCH-type zinc finger protein, is an RNA-binding protein that participates in controlling cellular mRNA abundance and turnover by posttranscriptional regulation. Here, we demonstrated that ZFP36L1 has an important role in host defense against influenza A virus (IAV) infection. Overexpression of ZFP36L1 reduced IAV replication via translational repression of HA, M and NS RNA segment transcripts. IAV infection upregulated cellular ZFP36L1 expression, and endogenous ZFP36L1 knockdown significantly enhanced IAV replication. ZFP36L1 directly binds to IAV NS1 mRNA in the cytoplasm and blocks the expression and function of NS1 protein. Mutation of CCCH-type zinc finger domains of ZFP36L1 lost its antiviral potential and NS1 mRNA binding. Thus, ZFP36L1 can act as a host innate defense by targeting HA, M and NS mRNA transcripts to suppress viral protein translation.


Assuntos
Fator 1 de Resposta a Butirato/metabolismo , Proteínas da Matriz Viral/genética , Proteínas não Estruturais Virais/genética , Células A549 , Animais , Sítios de Ligação , Fator 1 de Resposta a Butirato/química , Fator 1 de Resposta a Butirato/genética , Cães , Células HEK293 , Humanos , Vírus da Influenza A/metabolismo , Vírus da Influenza A/fisiologia , Células Madin Darby de Rim Canino , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas da Matriz Viral/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral
6.
Int J Mol Sci ; 23(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563292

RESUMO

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 µg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 µg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Células Th1 , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/farmacologia , Cricetinae , Emulsões , Humanos , Camundongos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Células Th1/imunologia
7.
Pharmacol Res ; 163: 105298, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33220422

RESUMO

Closely associated with visceral obesity, hepatic steatosis resulting from non-alcoholic fatty liver disease (NAFLD) exacerbates insulin resistance. Developing effective drugs to treat NAFLD is imperative. Here, we investigated the pharmacological mechanism of ugonin J (UJ) in controlling metabolic disorder and ameliorating NAFLD pathophysiology in diet-induced obese mice. The effects of UJ were assessed in 5-week-old C57BL/6 J mice fed a high-fat diet (HFD) for 12 weeks. UJ treatment averted HFD-induced body weight gain by reducing fat deposition in adipose tissues and reduced HFD-induced hyperlipidemia and hepatic inflammation. UJ also improved HFD-induced glucose tolerance and insulin resistance. Moreover, the mode of action of UJ was analyzed in palmitate (PA)-induced steatotic human HuS-E/2 hepatocytes and in hyperglycemia-simulating rat BRIN-BD11 pancreatic ß cells. In PA-induced steatotic human hepatocytes, UJ treatment promoted lipid clearance via pAMPK, pACC and CPT-1 upregulation and SREBP-1c downregulation. Interestingly, UJ upregulated Akt activity in hepatocytes and increased insulin secretion from ß cells in acute insulin secretion tests. Taken together, UJ improved adipocyte hypertrophy, hyperinsulinemia, hyperglycemia, hyperlipidemia and fat deposition in livers. UJ also reduced fatty acid accumulation by modulating key metabolic regulators. Our findings demonstrated the therapeutic potential of UJ for the treatment of NAFLD and diet-induced metabolic disorders.


Assuntos
Doenças Metabólicas/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Adipocinas/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Linhagem Celular , Células Cultivadas , Dieta Hiperlipídica , Ácidos Graxos/metabolismo , Glucose/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Ratos , Aumento de Peso/efeitos dos fármacos
8.
Int J Syst Evol Microbiol ; 71(11)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34731078

RESUMO

A growing interest in fungi that occur within symptom-less plants and lichens (endophytes) has uncovered previously uncharacterized species in diverse biomes worldwide. In many temperate and boreal forests, endophytic Coniochaeta (Sacc.) Cooke (Coniochaetaceae, Coniochaetales, Sordariomycetes, Ascomycota) are commonly isolated on standard media, but rarely are characterized. We examined 26 isolates of Coniochaeta housed at the Gilbertson Mycological Herbarium. The isolates were collected from healthy photosynthetic tissues of conifers, angiosperms, mosses and lichens in Canada, Sweden and the United States. Their barcode sequences (nuclear ribosomal internal transcribed spacer and 5.8S; ITS rDNA) were ≤97% similar to any documented species available through GenBank. Phylogenetic analyses based on two loci (ITS rDNA and translation elongation factor 1-alpha) indicated that two isolates represented Coniochaeta cymbiformispora, broadening the ecological niche and geographic range of a species known previously from burned soil in Japan. The remaining 24 endophytes represented three previously undescribed species that we characterize here: Coniochaeta elegans sp. nov., Coniochaeta montana sp. nov. and Coniochaeta nivea sp. nov. Each has a wide host range, including lichens, bryophytes and vascular plants. C. elegans sp. nov. and C. nivea sp. nov. have wide geographic ranges. C. montana sp. nov. occurs in the Madrean biome of Arizona (USA), where it is sympatric with the other species described here. All three species display protease, chitinase and cellulase activity in vitro. Overall, this study provides insight into the ecological and evolutionary diversity of Coniochaeta and suggests that these strains may be amenable for studies of traits relevant to a horizontally transmitted, symbiotic lifestyle.


Assuntos
Ascomicetos , Filogenia , Animais , Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Canadá , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Endófitos/classificação , Endófitos/isolamento & purificação , Técnicas de Tipagem Micológica , Análise de Sequência de DNA , Suécia , Estados Unidos
9.
Org Biomol Chem ; 18(28): 5354-5358, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32643742

RESUMO

With an iron catalyst playing dual roles as a radical initiator and terminator, we report a selective remote C-H functionalization to access δ-azido sulfonamides through a radical relay process. The reaction of N-fluorosulfonamide furnishes the corresponding products in excellent yields with high regioselective control. The key to success is the highly efficient iron-mediated redox azido transfer to the in situ generated carbon radical. The products provide incentives for drug discovery and ligand designs.

10.
Mediators Inflamm ; 2020: 1702935, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343229

RESUMO

Helminthostachys zeylanica is a traditional folk herb used to improve inflammation and fever in Taiwan. Previous studies showed that H. zeylanica extract could ameliorate lipopolysaccharide-induced acute lung injury in mice. The aim of this study was to investigate whether H. zeylanica water (HZW) and ethyl acetate (HZE) extracts suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in asthmatic mice, and decreased the inflammatory response and oxidative stress in tracheal epithelial cells. Human tracheal epithelial cells (BEAS-2B cells) were pretreated with various doses of HZW or HZE (1 µg/ml-10 µg/ml), and cell inflammatory responses were induced with IL-4/TNF-α. In addition, female BALB/c mice sensitized with ovalbumin (OVA), to induce asthma, were orally administered with HZW or HZE. The result demonstrated that HZW significantly inhibited the levels of proinflammatory cytokines, chemokines, and reactive oxygen species in activated BEAS-2B cells. HZW also decreased ICAM-1 expression and blocked monocytic cells from adhering to inflammatory BEAS-2B cells in vitro. Surprisingly, HZW was more effective than HZE in suppressing the inflammatory response in BEAS-2B cells. Our results demonstrated that HZW significantly decreased AHR and eosinophil infiltration, and reduced goblet cell hyperplasia in the lungs of asthmatic mice. HZW also inhibited oxidative stress and reduced the levels of Th2 cytokines in bronchoalveolar lavage fluid. Our findings suggest that HZW attenuated the pathological changes and inflammatory response of asthma by suppressing Th2 cytokine production in OVA-sensitized asthmatic mice.


Assuntos
Asma/tratamento farmacológico , Citocinas/biossíntese , Eosinófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Hipersensibilidade Respiratória/tratamento farmacológico , Células Th2/imunologia , Traqueófitas , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Eosinófilos/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
11.
Biochem Biophys Res Commun ; 518(4): 732-738, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31472967

RESUMO

Zika virus (ZIKV) is an emerging vector-borne virus that is associated with severe congenital cerebral anomalies in fetuses and paralytic Guillain-Barré syndrome in adults. In the current global health crisis, there are no vaccines or therapeutics available for the treatment of ZIKV infection. In the present study, we evaluated the efficacy of the protoberberine alkaloid, palmatine, in inhibiting ZIKV and Japanese encephalitis virus (JEV). Palmatine was shown to bind to restricted viruses, inhibit ZIKV infection, and resist ZIKV-induced cytopathic effects. Palmatine was also shown to inhibit JEV infection in multiple cell lines. Overall, the effects of palmatine in disrupting ZIKV binding, entry, and stability indicate that this small molecule would be a good starting point for the development of treatments aimed at inhibiting ZIKV infection.


Assuntos
Alcaloides de Berberina/farmacologia , Efeito Citopatogênico Viral/efeitos dos fármacos , Ligação Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Células A549 , Animais , Linhagem Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Humanos , RNA Viral/genética , RNA Viral/metabolismo , Células Vero , Replicação Viral/genética , Zika virus/genética , Zika virus/fisiologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
12.
Cytokine ; 113: 380-392, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30389230

RESUMO

INTRODUCTION: Resveratrol has been reported to alleviate inflammatory responses and oxidative stress in mesangial cells and in several types of renal injury in animal models. Previously, the active resveratrol derivatives from the roots of Vitis thunbergii Sieb. & Zucc. (Vitaceae) were shown to have significant anti-platelet and anti-oxidative activities. However, the anti-inflammatory mechanisms of these resveratrol derivatives in rat mesangial cells (RMCs) have not been clarified fully. METHODS: The protective mechanisms of resveratrol derivatives involved in tumor necrosis factor-α (TNF-α)-induced inflammatory responses were assessed by Western blot analysis, real-time PCR, and RT-PCR. The involvement of various signaling molecules in these responses was investigated using selective pharmacological inhibitors. RESULTS: Nontoxic concentrations of the resveratrol derivatives significantly attenuated cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) expression in RMCs challenged by TNF-α. These resveratrol derivatives inhibited TNF-α-activated ERK1/2 and JNK1/2 without affecting p38 phosphorylation. Next, we demonstrated that TNF-α induced NF-κB activation, translocation, and promoter activity, which was inhibited by pretreatment with resveratrol derivatives in RMCs. CONCLUSION: The protective mechanisms of resveratrol derivatives against TNF-α-stimulated inflammatory responses via cPLA2/COX-2/PGE2 inhibition was caused by the attenuation of the JNK1/2, ERK1/2, and NF-κB signaling pathways in RMCs.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células Mesangiais/metabolismo , Resveratrol/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Fosfolipases A2 do Grupo IV/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Células Mesangiais/patologia , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Arch Insect Biochem Physiol ; 102(1): e21592, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276235

RESUMO

Ferritin, which is ubiquitous among all living organisms, plays a crucial role in maintaining iron homeostasis, immune response, and detoxification. In the present research, we identified an iron-binding protein, ferritin heavy chain subunit, from Papilio xuthus and named PxFerHCH. The complete complementary DNA of PxFerHCH was 1,252 bp encoding a sequence of 211 amino acids, which includes an iron-responsive element. Phylogenetic analysis showed that PxFerHCH is clustered with Manduca sexta and Galleria mellonella ferritin heavy chain subunits. Expression levels of PxFerHCH in various tissues were analyzed by reverse transcription quantitative polymerase chain reaction, and the results exhibited that PxFerHCH was expressed in all tissues with the highest expression in the fat body. The relative expression level of PxFerHCH in response to bacterial (Escherichia coli and Staphylococcus aureus) challenges sharply increased by about 12 hr postinfection (hpi) and then decreased at 24 hpi. In addition, the iron-binding capacity and antioxidation activity of recombinant PxFerHCH protein were also investigated. These results reveal that PxFerHCH might play an important role in defense against bacterial infection.


Assuntos
Apoferritinas/metabolismo , Borboletas/metabolismo , Ferro/metabolismo , Sequência de Aminoácidos , Animais , Apoferritinas/genética , Apoferritinas/isolamento & purificação , Sequência de Bases , Borboletas/genética , Borboletas/imunologia , Escherichia coli , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Staphylococcus aureus
14.
BMC Complement Altern Med ; 19(1): 368, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836013

RESUMO

BACKGROUND: Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling. METHODS: Helminthostachys zeylanica (HZ) is used widely as a common herbal medicine to relieve fever symptoms and inflammatory diseases in Asia. In the present study, we evaluated whether HZ has therapeutic effects on obesity, NAFLD and insulin resistance. The protective effects of HZ extract were examined using free fatty acid-induced steatosis in human HuS-E/2 cells and a high-fat diet-induced NAFLD in mice. RESULTS: The major components of the HZ extract are ugonins J and K, confirmed by HPLC. Incubation of human hepatocytes, HuS-E/2 cells, with palmitate markedly increased lipid accumulation and treatment with the HZ extract significantly decreased lipid deposition and facilitated AMPK and ACC activation. After 12 weeks of a high-fat diet with HZ extract treatment, the HFD mice were protected from hyperlipidemia and hyperglycemia. HZ extract prevented body weight gain, adipose tissue expansion and adipocyte hypertrophy in the HFD mice. In addition, fat accumulation was reduced in mice livers. Moreover, the insulin sensitivity-associated index, which evaluates insulin function, was also significantly restored. CONCLUSIONS: These results suggest that HZ has a promising pharmacological effect on high-fat diet-induced obesity, hepatic steatosis and insulin resistance, which may have the potential for clinical application.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Traqueófitas , Adipócitos/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química
15.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370145

RESUMO

Chitin synthase is a critical enzyme that catalyzes N-acetylglucosamine to form chitin, which plays an important role in the growth and development of insects. In this study, we identified a chitin synthase gene (CHS) with a complete open reading frame (ORF) of 3180 bp from the genome database of Diaphorina citri, encoding a protein of 1059 amino acid residues with the appropriate signature motifs (EDR and QRRRW). Reverse transcription-quantitative PCR (RT-qPCR) analysis suggested that D. citri CHS (DcCHS) was expressed throughout all developmental stages and all tissues. DcCHS had the highest expression level in the integument and fifth-instar nymph stage. Furthermore, the effects of diflubenzuron (DFB) on D. citri mortality and DcCHS expression level were investigated using fifth-instar nymph through leaf dip bioassay, and the results revealed that the nymph exposed to DFB had the highest mortality compared with control group (Triton-100). Silencing of DcCHS by RNA interference resulted in malformed phenotypes and increased mortality with decreased molting rate. In addition, transmission electron microscopy (TEM) and fluorescence in situ hybridization (FISH) also revealed corresponding ultrastructural defects. Our results suggest that DcCHS might play an important role in the development of D. citri and can be used as a potential target for psyllid control.


Assuntos
Quitina Sintase/genética , Genoma de Inseto , Hemípteros/genética , Proteínas de Insetos/genética , Ninfa/genética , Interferência de RNA , Sequência de Aminoácidos , Animais , Quitina Sintase/antagonistas & inibidores , Quitina Sintase/metabolismo , Citrus/parasitologia , Diflubenzuron/farmacologia , Frutas/parasitologia , Regulação da Expressão Gênica no Desenvolvimento , Hemípteros/efeitos dos fármacos , Hemípteros/enzimologia , Hemípteros/crescimento & desenvolvimento , Controle de Insetos , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Muda/efeitos dos fármacos , Muda/genética , Ninfa/efeitos dos fármacos , Ninfa/crescimento & desenvolvimento , Ninfa/metabolismo , Fases de Leitura Aberta , Filogenia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
16.
Int J Mol Sci ; 21(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861829

RESUMO

Chitin deacetylase (CDA) is a chitin degradation enzyme that strictly catalyzes the deacetylation of chitin to form chitosan, which plays an important role in regulating growth and development, as well as the immune response. In this study, a chitin deacetylase 3 gene (CDA3) was identified with a complete open reading frame (ORF) of 1362 bp from the genome database of Diaphorina citri, encoding a protein of 453 amino acids. Spatiotemporal expression analysis suggested that D. citri CDA3 (DcCDA3) had the highest expression level in the integument and third-instar nymph stage. Furthermore, DcCDA3 expression level can be induced by 20-hydroxyecdysone (20E). Injection of Escherichia coli and Staphylococcus aureus induced the upregulation of DcCDA3 in the midgut, while DcCDA3 was downregulated in the fat body. After silencing DcCDA3 by RNA interference, there was no influence on the D. citri phenotype. In addition, bactericidal tests showed that recombinant DcCDA3 inhibited gram-positive bacteria, including S. aureus and Bacillus subtilis (B. subtilis). In conclusion, our results suggest that DcCDA3 might play an important role in the immune response of D. citri.


Assuntos
Amidoidrolases/imunologia , Hemípteros/imunologia , Proteínas de Insetos/imunologia , Amidoidrolases/química , Amidoidrolases/genética , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/imunologia , Hemípteros/química , Hemípteros/genética , Imunidade , Proteínas de Insetos/química , Proteínas de Insetos/genética , Transcriptoma
17.
J Plant Res ; 131(3): 411-428, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29569170

RESUMO

We present a comparative study of the floral structure and development of Nartheciaceae, a small dioscorealean family consisting of five genera (Aletris, Lophiola, Metanarthecium, Narthecium, and Nietneria). A noticeable diversity existed in nine floral characters. Analyses of their respective character states in the light of a phylogenetic context revealed that the flowers of Nartheciaceae, whose plesiomorphies occur in Aletris and Metanarthecium, have evolved toward in all or part of Lophiola, Narthecium, and Nietneria: (1) loss of a perianth tube; (2) stamen insertion at the perianth base; (3) congenital carpel fusion; (4) loss of the septal nectaries; (5) unilocular style; (6) unfused lateral carpellary margins in the style; (7) flower with the median outer tepal on the abaxial side; (8) flower with moniliform hairs; and (9) flower with weak monosymmetry. We further found that, as the flowers developed, the ovary shifted its position from inferior to superior. As a whole, their structure changes suggest that the Nartheciaceae flowers have evolved in close association with pollination and seed dispersal. By considering inferior ovaries and the presence of septal nectaries as plesiomorphies of Nartheciaceae, we discussed evolution of the ovary position and septal nectaries in all the monocots.


Assuntos
Flores/crescimento & desenvolvimento , Magnoliopsida/crescimento & desenvolvimento , Evolução Biológica , Flores/anatomia & histologia , Flores/genética , Magnoliopsida/anatomia & histologia , Magnoliopsida/genética , Néctar de Plantas , Polinização , Dispersão de Sementes
20.
J Nat Prod ; 80(2): 246-253, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28169537

RESUMO

Chemical investigation of the rhizomes of Helminthostachys zeylanica led to the isolation of eight new flavonoids including six cyclized geranylflavonoids, ugonins V-X (1-3), (10R,11S)-ugonin N (4), (10R,11S)-ugonin S (5), and ugonin Y (6), as well as two quercetin glucosides, quercetin-4'-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (7) and quercetin-3-O-ß-d-glucopyranosyl-4'-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (8). The structures of these compounds were established by spectroscopic analyses and acid hydrolysis of the sugar moiety. Among the isolated compounds, 1, 2, 5, 6, ugonins J-S (9-13), ugonstilbene A (14), and ugonin L (23) were evaluated for their anti-inflammatory activity on lipopolysaccharide-induced nitric oxide (NO) production in microglial cells. Except for 1, 5, and 13, all other compounds inhibited NO production with IC50 values of 6.2-10.1 µM and were more potent than the positive control, pyrrolidine dithiocarbamate. Compounds 1, 2, 5, 6, and 10-13 were tested for antiosteoporotic activities, and ugonin K (10) exhibited the highest inhibitory activity against RANKL-induced osteoclast differentiation in RAW264.7 cells with an IC50 value of 1.8 ± 0.2 µM.


Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Gleiquênias/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Magnoliopsida/química , Osteoporose/tratamento farmacológico , Rizoma/química , Animais , Anti-Inflamatórios não Esteroides/química , Flavonoides/química , Glucosídeos/análise , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Quercetina/farmacologia , Células RAW 264.7/efeitos dos fármacos , Taiwan
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