Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Exp Bot ; 75(1): 152-167, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37769205

RESUMO

Extensins (EXTs), a class of hydroxyproline-rich glycoprotein with multiple Ser-Pro3-5 motifs, are known to play roles in cell wall reinforcement and environmental responses. EXTs with repetitive Tyr-X-Tyr (YXY) motifs for crosslinking are referred as crosslinking EXTs. Our comprehensive study spanned 194 algal and plant species, categorizing EXTs into seven subfamilies: classical extensins (EXT I and II), arabinogalactan-protein extensins (AGP-EXTs), proline-rich extensin-like receptor kinases (PERKs), leucine-rich repeat extensins (LRX I and II), formin homology (FH) domain-containing extensins (FH-EXTs), proline-rich, arabinogalactan proteins, conserved cysteines (PAC) domain-containing extensins (PAC I and II), and eight-cysteine motif (8CM)-containing extensins (8CM-EXTs). In the examined dataset, EXTs were detected ubiquitously in plants but infrequently in algae, except for one Coccomyxa and four Chlamydomonadales species. No crosslinking EXTs were found in Poales or certain Zingiberales species. Notably, the previously uncharacterized EXT II, PAC II, and liverwort-specific 8CM-EXTs were found to be crosslinking EXTs. EXT II, featuring repetitive YY motifs instead of the conventional YXY motif, was exclusively identified in Solanaceae. Furthermore, tandem genes encoding distinctive 8CM-EXTs specifically expressed in the germinating spores of Marchantia polymorpha. This updated classification of EXT types allows us to propose a plausible evolutionary history of EXT genes during the course of plant evolution.


Assuntos
Proteínas de Plantas , Plantas , Sequência de Aminoácidos , Plantas/metabolismo , Proteínas de Plantas/metabolismo , Glicoproteínas/metabolismo , Parede Celular/metabolismo , Prolina/metabolismo
2.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3493-3504, 2024 Jul.
Artigo em Zh | MEDLINE | ID: mdl-39041121

RESUMO

Based on the processing and compatibility, this study explored the effects of components in Corni Fructus(CF) and Astragali Radix(AR) on plasma metabolomics in diabetic nephropathy rats. SD rats were randomly divided into four groups and diabetic nephropathy rat model was induced by high-fat diet combined with 30 mg·kg~(-1) streptozotocin(STZ). Histopathological observations of kidney tissue sections of rats in each group were conducted using HE, PAS, and Masson staining. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) metabolomics method was employed to investigate the effects of CF before and after wine-processing combined with AR-related components on plasma metabolites in diabetic nephropathy rats. After drug treatment, kidney tissue damage and interstitial collagen fiber deposition area in diabetic nephropathy rats were improved to varying degrees(P<0.001). The detection results of plasma metabolomics showed that 71 biomarkers related to the pathogenesis of diabetic nephropathy were identified in diseased rats, mainly involving linoleic acid metabolism, caffeine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism, retinol metabolism, and ether lipid metabolism. After drug intervention, 26 of them were significantly downregulated, with better efficacy observed in precision processed herb-pair group(P-CG_5). This study elucidated from the perspective of plasma metabolomics that P-CG_5 could improve metabolic disorders in diabetic nephropathy through pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and caffeine metabolism, providing theoretical support and experimental basis for the clinical application of CF and AR compatibility in traditional Chinese medicine.


Assuntos
Cornus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Metabolômica , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Ratos , Masculino , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Cornus/química , Astragalus propinquus/química , Vinho/análise , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo
3.
Angew Chem Int Ed Engl ; 63(8): e202318224, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38095880

RESUMO

The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 µA cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems.

4.
Mol Phylogenet Evol ; 169: 107394, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35045310

RESUMO

Extremely heterogeneous topography and complex paleoclimatic history of the Qinghai-Tibet Plateau (QTP) have a key role in promoting genetic divergence among populations and lineage/species formation. Here, we sequenced one nuclear and three mitochondrial markers of 532 individuals from the entire range of the Phrynocephalus vlangalii species complex including two species, P. putjatai and P. vlangalii, endemic to the northern QTP. We integrated multilocus phylogeny, demographic analysis and geographic barrier detection to evaluate the population structure and dynamics. We found a new mitochondrial clade (PV-I) in the Gonghe County population of P. vlangalii, partial mitochondrial DNA replacement within P. vlangalii and complete mitochondrial DNA replacement between P. putjatai and P. vlangalii. Neutrality test, mismatch distribution analysis and Extended Bayesian Skyline Plot (EBSP) analysis all supported a significant expansion of the Qaidam Basin population of P. vlangalii (PV-II-2) from 0.091 to 0.026 Ma after Penultimate Glaciation. The uplift of the Arjin and Anyemanqen Mountains during the Kunhuang Movement (∼1.2 Ma) split populations of P. vlangalii in Akesai, Qaidam Basin and source of the Yellow River. The uplift of the Elashan Mountains during the second phase of the Qingzang Movement (∼2.5 Ma) contributed to the divergence of the Gonghe County population of P. vlangalii from other conspecific populations. The third phase of the Qingzang Movement (∼1.7 Ma) contributed to the divergence of the Xinghai population of P. vlangalii from P. putjatai and to the divergence of the northern populations of P. putjatai from the southern conspecific populations. Our data support the idea that the geological and climatic changes following the orogeny of the QTP may have promoted population differentiation and shaped the current population patterns of the P. vlangalii species complex in the northeastern QTP.


Assuntos
Variação Genética , Lagartos , Animais , Teorema de Bayes , China , DNA Mitocondrial/química , DNA Mitocondrial/genética , Humanos , Lagartos/genética , Filogenia , Filogeografia , Tibet
5.
Chemistry ; 28(57): e202201520, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-35848162

RESUMO

Since the water oxidation half-reaction requires the transfer of multi-electrons and the formation of O-O bond, it's crucial to investigate the catalytic behaviours of semiconductor photoanodes. In this work, a bio-inspired copper-bipyridine catalyst of Cu(dcbpy) is decorated on the nanoporous Si photoanode (black Si, b-Si). Under AM1.5G illumination, the b-Si/Cu(dcbpy) photoanode exhibits a high photocurrent density of 6.31 mA cm-2 at 1.5 VRHE at pH 11.0, which is dramatically improved from the b-Si photoanode (1.03 mA cm-2 ) and f-Si photoanode (0.0087 mA cm-2 ). Mechanism studies demonstrate that b-Si/Cu(dcbpy) has improved light-harvesting, interfacial charge-transfer, and surface area for water splitting. More interestingly, b-Si/Cu(dcbpy) exhibits a pH-dependent water oxidation behaviour with a minimum Tafel slope of 241 mV/dec and the lowest overpotential of 0.19 V at pH 11.0, which is due to the monomer/dimer equilibrium of copper catalyst. At pH ∼11, the formation of dimeric hydroxyl-complex could form O-O bond through a redox isomerization (RI) mechanism, which decreases the required potential for water oxidation. This in-depth understanding of pH-dependent water oxidation catalyst brings insights into the design of dimer water oxidation catalysts and efficient photoanodes for solar energy conversion.

6.
Proc Natl Acad Sci U S A ; 116(9): 3646-3655, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808754

RESUMO

Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous-viviparous pair of lizards (Phrynocephalus przewalskii and Phrynocephalus vlangalii) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous-viviparous pairs of lizards in different genera (Phrynocephalus, Eremias, Scincella, and Sphenomorphus) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity-viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested.


Assuntos
Evolução Molecular , Oviparidade/genética , Transcriptoma/genética , Viviparidade não Mamífera/genética , Animais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genômica , Lagartos/genética , Lagartos/crescimento & desenvolvimento , Filogenia , Placentação/genética , Gravidez , Reprodução/genética , Serpentes/genética , Serpentes/crescimento & desenvolvimento
7.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077282

RESUMO

Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3-V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production.


Assuntos
Artrite Reumatoide , Microbiota , Periodontite , Anticorpos Antiproteína Citrulinada , Autoanticorpos , Bactérias/genética , Humanos , Microbiota/genética , Periodontite/microbiologia , RNA Ribossômico 16S/genética
8.
J Formos Med Assoc ; 120(10): 1876-1883, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33341349

RESUMO

BACKGROUND/PURPOSE: Concurrent sexually transmitted infections (STIs) are not uncommon in at-risk populations, for which control requires integrated testing, treatment and prevention. METHODS: From May, 2019 to February, 2020, multiplex real-time PCR assays were prospectively performed to detect Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) in the urine and rectal/vaginal swab specimens collected from HIV-positive patients with a history of STIs or symptoms suggestive of STIs. Patients confirmed to have acquired STIs were treated according to treatment guidelines. RESULTS: During the study period, 430 participants (99.1% men who have sex with men and median age 37 years) were included. The overall prevalence of CT, NG, and/or TV infection was 30.0%, including 24.7%, 12.1%, and 0.2% for CT, NG, and TV infection, respectively. The factors associated with CT, NG, and/or TV infection were hepatitis B surface antigen (HBsAg) seropositivity (AOR, 2.76; 95% CI, 1.22-6.26), recently acquired hepatitis C virus (HCV) infection (AOR, 5.62; 95% CI, 1.99-15.88), using mobile dating application (AOR, 2.08; 95% CI, 1.13-3.83), and oral sex (AOR, 2.12; 95% CI, 1.04-4.32). The rates of CT, NG, and/or TV infection were 50.0% in participants with recent HCV infection, 44.2% in those with HBsAg positivity, and 35.9% in those with incident syphilis. Among participants completing test-of-cure visits, the microbiological cure rate was 91.7% and 90.0% for chlamydia and gonorrhea, respectively. CONCLUSION: HIV-positive participants had a high prevalence of CT and/or NG, especially those coinfected with viral hepatitis and syphilis. Our results strongly support integrated STI services in the population.


Assuntos
Infecções por Chlamydia , Coinfecção , Gonorreia , Infecções por HIV , Minorias Sexuais e de Gênero , Adulto , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Coinfecção/epidemiologia , Feminino , Gonorreia/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Neisseria gonorrhoeae , Prevalência , Comportamento Sexual
9.
BMC Evol Biol ; 19(1): 114, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170905

RESUMO

BACKGROUND: The Qinghai-Tibetan Plateau (QTP) is the world's highest and largest plateau, but the role of its uplift in the evolution of species or biotas still remains poorly known. Toad-headed lizards of the reproductively bimodal genus Phrynocephalus are a clade of agamids, with all viviparous species restricted to the QTP and adjacent regions. The eastern part of the range of the viviparous taxa is occupied by three closely related but taxonomically controversial species, P. guinanensis, P. putjatia and P. vlangalii. Here, we combined genetic (mitochondrial ND4 gene and nine microsatellite loci), morphological (11 mensural and 11 meristic variables), and ecological (nine climatic variables) data to explore possible scenarios that may explain the discordance between genetic and morphological patterns, and to test whether morphological divergence is associated with local adaptation. RESULTS: We found weak genetic differentiation but pronounced morphological divergence, especially between P. guinanensis and P. vlangalii. Genetically, the species boundary was not so clear between any species pair. Morphologically, the species boundary was clear between P. guinanensis and P. vlangalii but not between other two species pairs. Body size and scale characters accounted best for morphological divergence between species. Morphological divergence was related to habitat types that differ climatically. CONCLUSIONS: Our study provides evidence for genetic and morphological divergence among the three closely related viviparous species of Phrynocephalus lizards, and supports the idea that natural selection in spatially heterogeneous environments can lead to population divergence even in the presence of gene flow. Our study supports the hypothesis that the evolutionary divergence between viviparous Phrynocephalus species was a consequence of environmental change after the uplift of the QTP.


Assuntos
Variação Genética , Lagartos/anatomia & histologia , Lagartos/genética , Animais , Teorema de Bayes , China , Clima , DNA Mitocondrial/genética , Feminino , Genética Populacional , Geografia , Haplótipos/genética , Masculino , Polimorfismo Genético , Análise de Componente Principal , Especificidade da Espécie
10.
Fish Shellfish Immunol ; 63: 297-303, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28232280

RESUMO

Ferritin plays important roles in iron storage, detoxification, and immune response. Here, a ferritin gene (PcFer) was identified in Procambarus clarkii, an economically important freshwater crayfish. Full-length PcFer cDNA was 1022-bp, including a 135-bp 5'-untranslated region (UTR) with a typical iron responsive element, a 374-bp 3'-UTR, and a 513-bp open reading frame encoding a polypeptide of 170 amino acids which contained the Ferritin domain. PcFer has ion binding sites, a ferrihydrite nucleation center, and an iron ion channel. PcFer is phylogenetically closely-related to Pacifastacus leniusculus and Eriocheir sinensis ferritins. Real-time quantitative reverse-transcription PCR analysis showed that PcFer was expressed in all tested P. clarkii tissues, and expressed most in hepatopancreas. After challenge with various heavy metals and lipopolysaccharide, respectively, the hepatopancreatic expression levels of PcFer were markedly upregulated. These results suggest that expression of PcFer might be involved in immune defense and protection of P. clarkii against heavy metal stress.


Assuntos
Proteínas de Artrópodes/genética , Astacoidea/genética , Ferritinas/genética , Lipopolissacarídeos/farmacologia , Metais Pesados/toxicidade , Poluentes Químicos da Água/toxicidade , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Astacoidea/imunologia , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Ferritinas/química , Ferritinas/metabolismo , Imunidade Inata , Filogenia , Reação em Cadeia da Polimerase/veterinária , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Distribuição Tecidual
11.
Int J Cancer ; 136(4): 936-44, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24975040

RESUMO

The role of cetuximab in treatment-related hematologic toxicity is not clear. We performed a meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of ≥grade 3 hematologic toxicity events (HTEs) associated with cetuximab. PubMed, EMBASE, and Web of Knowledge databases as well as abstracts presented at American Society of Clinical Oncology conferences and ClinicalTrials.gov were searched to identify relevant studies. Eligible studies included RCTs in which cetuximab in combination with chemotherapy or chemoradiotherapy was compared with chemotherapy or chemoradiotherapy alone. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. A total of 11,234 patients with a variety of advanced solid tumors from 18 RCTs were included in the meta-analysis. Compared with chemotherapy alone, the addition of cetuximab was associated with increased risks of ≥grade 3 leucopenia/neutropenia and anemia events in colorectal cancer, with RRs of 1.16 (95% CI 1.05-1.27, p=0.002; incidence, 21.0 vs. 18.0%) and 2.67 (95% CI 1.53-4.65, p=0.01; incidence, 4.0 vs. 2.0%), respectively. Cetuximab was also associated with an increased risk of leucopenia/neutropenia in nonsmall cell lung cancer (NSCLC) (RR: 1.15; 95% CI 1.08-1.22, p<0.01). Additionally, K-ras wild type in the case of colorectal cancer patients was more vulnerable to ≥grade 3 leucopenia or neutropenia events in cetuximab group (RR: 1.31; 95% CI 1.11-1.54, p=0.001). With present evidence, cetuximab in conjunction with chemotherapy or chemoradiotherapy, compared with chemotherapy or chemoradiotherapy alone, was associated with increased slight risk of ≥grade 3 HTEs, especially in colorectal cancer and NSCLC.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Cetuximab , Humanos , Mutação , Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Proteínas ras/genética
12.
Mol Carcinog ; 54(12): 1613-25, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25358452

RESUMO

Triple-negative breast cancer (TNBC) is difficult to treat because there is no targeted therapy available. Clinical studies have demonstrated that S-phase kinase-associated protein 2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) are highly expressed in TNBC. Therefore, therapeutic strategies designed to downregulate LRP6 or Skp2 may play an important clinical role in the treatment of TNBC. However, the regulatory effects of many drugs on Skp2 and LRP6 expression are currently unknown. In the present study, combined treatment with chrysin and 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (5GG) synergistically induced apoptosis and cell cycle arrest and inhibited cell proliferation and colony formation in AU565 and MDA-MB-231 human breast cancer cells. Furthermore, the combination of chrysin and 5GG suppressed tumor growth in nude mice with xenografted MDA-MB-231 cells by downregulating the phospho-LRP6 (pLRP6) and Skp2 proteins. Overall, our findings suggested that the combination of chrysin and 5GG has a potential therapeutic value in treating breast cancer, particularly for TNBC associated with Skp2/LRP6 overexpression, and hence warrants further investigation.


Assuntos
Flavonoides/farmacologia , Taninos Hidrolisáveis/farmacologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Proteínas Quinases Associadas a Fase S/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Xenoenxertos/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus
13.
Biomarkers ; 19(1): 56-62, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24308720

RESUMO

BACKGROUND: The UGT1A1*28 polymorphism is known as a biomarker of irinotecan-induced neutropenia in Caucasians. However, in Asians, the UGT1A1*28 mutation is much less frequent. METHODS: A meta-analysis was performed to assess the association of the UGT1A1*6 and UGT1A1*28 with neutropenia in Asians. RESULTS: In a combination test of the two variations, patients with severe neutropenia displayed a 155% higher mutational load than those that were not neutropenic (ORG = 2.55; 95% CI: 1.82-3.58). CONCLUSIONS: In Asians, a combination test of UGT1A1*6 and UGT1A1*28 might be a potential biomarker of irinotecan-induced neutropenia, an observation that will need additional trials for confirmation.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/análogos & derivados , Glucuronosiltransferase/genética , Neutropenia/genética , Povo Asiático , Camptotecina/efeitos adversos , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Irinotecano , Neutropenia/induzido quimicamente , Polimorfismo Genético , Risco
14.
Int J Antimicrob Agents ; 63(1): 107028, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37931850

RESUMO

Voriconazole-associated hepatotoxicity is a common condition that generally manifests as elevated liver enzymes and can lead to drug discontinuation. Careful monitoring of voriconazole-associated hepatotoxicity is needed but there are no specific plasma biomarkers for this condition. Metabolomics has emerged as a promising technique for investigating biomarkers associated with drug-induced toxicity. The aim of this study was to use targeted metabolomics to evaluate seven endogenous metabolites as potential biomarkers of voriconazole-associated hepatotoxicity. Patients undergoing therapeutic drug monitoring of voriconazole were classified into a hepatotoxicity group (18 patients) or a control group (153 patients). Plasma samples were analysed using ultra-high-performance liquid chromatography coupled to mass spectrometry. Metabolite concentrations in the two groups were compared. Areas under the receiver operating characteristic (AUROC) curves generated from logistic regressions were used to correlate the concentrations of these seven metabolites with voriconazole trough concentrations and conventional liver biochemistry tests. Glycocholate and α-ketoglutarate levels were significantly higher in the hepatotoxicity group compared with the control group (false discovery rate-corrected P < 0.001 and P = 0.024, respectively). The metabolites glycocholate (AUROC = 0.795) and α-ketoglutarate (AUROC = 0.696) outperformed voriconazole trough concentrations (AUROC = 0.555) and approached the performance of alkaline phosphatase (AUROC = 0.876) and total bilirubin (AUROC = 0.815). A panel of glycocholate combined with voriconazole trough concentrations (AUROC = 0.827) substantially improved the performance of voriconazole trough concentrations alone in predicting hepatotoxicity. In conclusion, the panel integrating glycocholate with voriconazole trough concentrations has great potential for identifying voriconazole-associated hepatotoxicity.


Assuntos
Antifúngicos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Voriconazol/efeitos adversos , Antifúngicos/uso terapêutico , Ácidos Cetoglutáricos , Monitoramento de Medicamentos/métodos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Biomarcadores , Ácido Glicocólico
15.
Adv Ther ; 41(7): 2966-2977, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38743241

RESUMO

INTRODUCTION: A target trough concentration (Cmin) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. METHODS: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. RESULTS: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018). CONCLUSIONS: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.


Assuntos
Antibacterianos , Monitoramento de Medicamentos , Neutropenia Febril , Neoplasias Hematológicas , Teicoplanina , Humanos , Teicoplanina/administração & dosagem , Teicoplanina/uso terapêutico , Teicoplanina/farmacocinética , Masculino , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Monitoramento de Medicamentos/métodos , Estudos Prospectivos , Idoso , Adulto , Neutropenia Febril/tratamento farmacológico , Relação Dose-Resposta a Droga , Resultado do Tratamento , Adulto Jovem
16.
Nat Commun ; 15(1): 5882, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003268

RESUMO

Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s-1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching -14.11 mA cm-2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.

17.
Front Plant Sci ; 14: 1279540, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034583

RESUMO

The 70-kDa heat shock proteins (Hsp70s) are chaperone proteins involved in protein folding processes. Truncated Hsp70 (Hsp70T) refers to the variant lacking a conserved C-terminal motif, which is crucial for co-chaperone interactions or protein retention. Despite their significance, the characteristics of Hsp70Ts in plants remain largely unexplored. In this study, we performed a comprehensive genome-wide analysis of 192 sequenced plant and green algae genomes to investigate the distribution and features of Hsp70Ts. Our findings unveil the widespread occurrence of Hsp70Ts across all four Hsp70 forms, including cytosolic, endoplasmic reticulum, mitochondrial, and chloroplast Hsp70s, with cytosolic Hsp70T being the most prevalent and abundant subtype. Cytosolic Hsp70T is characterized by two distinct lineages, referred to as T1 and T2. Among the investigated plant and green algae species, T1 genes were identified in approximately 60% of cases, showcasing a variable gene count ranging from one to several dozens. In contrast, T2 genes were prevalent across the majority of plant genomes, usually occurring in fewer than five gene copies per species. Sequence analysis highlights that the putative T1 proteins exhibit higher similarity to full-length cytosolic Hsp70s in comparison to T2 proteins. Intriguingly, the T2 lineage demonstrates a higher level of conservation within their protein sequences, whereas the T1 lineage presents a diverse range in the C-terminal and SBDα region, leading to categorization into four distinct subtypes. Furthermore, we have observed that T1-rich species characterized by the possession of 15 or more T1 genes exhibit an expansion of T1 genes into tandem gene clusters. The T1 gene clusters identified within the Laurales order display synteny with clusters found in a species of the Chloranthales order and another species within basal angiosperms, suggesting a conserved evolutionary relationship of T1 gene clusters among these plants. Additionally, T2 genes demonstrate distinct expression patterns in seeds and under heat stress, implying their potential roles in seed development and stress response.

18.
Diagnostics (Basel) ; 13(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36673016

RESUMO

Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.

19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(12): 1607-10, 2012 Dec.
Artigo em Zh | MEDLINE | ID: mdl-23469596

RESUMO

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) combined general anesthesia on myocardial injury of high blood sugar patients with coronary heart disease (CHD) in the perioperative phase. METHODS: Recruited were 40 senile patients with glycosylated hemoglobin (HbA1c) more than 6.5%. They were more than 60 years old. They received post-traumatic fracture reduction surgery of four limbs. They were randomly assigned to two groups, Group N (treated by general intravenous anesthesia) and Group D (treated by EA combined with general intravenous anesthesia), 20 in each group. All patients were maintained anesthesia by propofol, fentanyl, and vecuronium. Prior to the induction of anesthesia, patients in Group D received induction of EA at Neiguan (PC6) and Baihui (DU20) for 20 min, which lasted to the end of the surgery. At before intubation (T0), immediately after intubation (T1), 5 min (T2), immediately after extubation (T3), 5 min (T4), 60 min (T5), 180 min (T6), the fast blood glucose (FBG), plasma vasoactive substance TXB2 and 6-K-prostacycline (6-K-PGF1alpha) were detected in the two groups. The glucose coefficient of variation (GluCV) and the ratio of TXB2/6-K-PGF1alpha were calculated. The changes of ST-segment elevation (mV, sampling 1 min after each time point, and the mean calculated) was recorded. RESULTS: There was no statistical difference in all the tested values between the two groups at T0 (P>0.05). The FBG, ST elevation, and the ratio of TXB2/6-K-PGF1alpha were significantly higher at each time point than at T0 in Group N (P<0.05), while there was no statistical difference in Group D (P>0.05). The ratio of TXB2/6-K-PGF1alpha and ST elevation were significantly higher in Group N than in Group D (P<0.01). The TXB2 and 6-K-PGF1alpha were significantly higher at each time point than at T0 in the two groups (P<0.05). The increment of TXB2 was obviously lower in Group D than in Group N (P<0.05), but the increment of 6-K-PGF1alpha was obviously higher in Group D than in Group N (P<0.05). CONCLUSION: EA could reduce the perioperative stress response to the injury of coronary vascular endothelial cells, and improve myocardial ischemia and CHD patients' prognosis by regulating the central nervous system, the cardiovascular active substances, and anti-oxygen free radicals.


Assuntos
Analgesia por Acupuntura , Doença das Coronárias/metabolismo , Doença das Coronárias/cirurgia , Eletroacupuntura , Idoso , Anestesia Geral , Glicemia/análise , Epoprostenol/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica , Miocárdio/metabolismo , Tromboxano A2/metabolismo
20.
Front Psychol ; 13: 830842, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310288

RESUMO

This research adopted the unified theory of acceptance and use of technology (UTAUT) to emphasize the use of the PX Pay mobile payment app for PX Mart, the most popular supermarket in Taiwan, and examine the degree of involvement as a moderator. The influence of factors related to PX Mart's target customer groups on their shopping intentions and usage behaviors were discussed, with subsequent benefits and optimization directions. This study indicated the following results. First, performance expectations, ease-of-use expectations, and social impact enhance consumers' behavioral intention and behavioral intention significantly influence usage behavior. Second, gender has no significant moderating effect on the proposed model. Third, age has a moderating effect from performance expectations and ease-of-use expectations, social influence on behavioral intention. Fourth, use is more significantly affected by perceived stakeholders for customers over age 50 than for those age 30-39. Fifth, the degree of involvement significantly affects the relationship between behavioral intention and usage behavior in terms of social influence and facilitating conditions effects. Finally, we provided academic and practical implications and make contributions to both the online payment industry and academia.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA