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1.
Cardiology ; 149(3): 286-296, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38228115

RESUMO

INTRODUCTION: This study aimed to explore the function of miR-135a in the progress of atrial fibrosis and the mechanism of miR-135a/SIRT1 (sirtuin 1) in human cardiac fibroblasts and mouse cardiac fibroblasts (MCFs) mediating the regulation of atrial fibrosis by mitochondrial oxidative respiration function. METHODS: Using Ang II (angiotensin II) to induce fibrosis in HCFs (human corneal fibroblasts) and MCF (Michigan Cancer Foundation, MCF) cells in vitro, the miRNA-seq results of previous studies were validated. Proliferative and invasive ability of HCFs and MCFs was detected by Cell Counting Kit-8 assay (CCK-8) and scratch experiment after overexpressing miR-135a in HCFs and MCF cells. Protein and mRNA expression was tested using Western blot and qPCR. The target of miR-135a was verified as SIRT1 by a luciferase reporter assay and the activities of the mitochondrial respiratory enzyme complexes I, II, III, and IV were determined colorimetrically. The activities of malondialdehyde, reactive oxygen species, and superoxide dismutase in cells were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: miR-135a expression was elevated in HCFs and MCFs cells in the Ang II group than control group. Overexpression of miR-135a could promote the proliferation, migration, oxidative stress, as well as fibrosis of cardiac fibroblasts and suppresses mitochondrial activity. In addition, we found SIRT1 was a target gene of miR-135a. What is more, the findings showed miR-135a promoted fibrosis in HCFs and MCFs cells acting through regulation of SIRT1. CONCLUSIONS: miR-135a mediates mitochondrial oxidative respiratory function through SIRT1 to regulate atrial fibrosis.


Assuntos
Fibroblastos , Fibrose , Átrios do Coração , MicroRNAs , Sirtuína 1 , MicroRNAs/metabolismo , MicroRNAs/genética , Sirtuína 1/metabolismo , Sirtuína 1/genética , Humanos , Camundongos , Animais , Fibroblastos/metabolismo , Átrios do Coração/patologia , Átrios do Coração/metabolismo , Proliferação de Células/genética , Angiotensina II , Estresse Oxidativo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas
2.
Proteomics ; 23(2): e2200362, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36254857

RESUMO

Enterovirus A71 (EV71) infection can cause hand, foot, and mouth disease (HFMD) and severe neurological complications in children. However, the biological processes regulated by EV71 remain poorly understood. Herein, proteomics and metabonomics studies were conducted to uncover the mechanism of EV71 infection in rhabdomyosarcoma (RD) cells and identify potential drug targets. Differential expressed proteins from enriched membrane were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics technology. Twenty-six differential proteins with 1.5-fold (p < 0.05) change were detected, including 14 upregulated proteins and 12 downregulated proteins. The upregulated proteins are mainly involved in metabolic process, especially in the glycolysis pathway. Alpha-enolase (ENO1) protein was found to increase with temporal dependence following EV71 infection. The targeted metabolomics analysis revealed that glucose absorption and glycolysis metabolites were increased after EV71 infection. The glycolysis pathway was inhibited by knocking down ENO1 or the use of a glycolysis inhibitor (dichloroacetic acid [DCA]); and we found that EV71 infection was inhibited by depleting ENO1 or using DCA. Our study indicates that EV71 may reprogram glucose metabolism by activating glycolysis, and EV71 infection can be inhibited by interrupting the glycolysis pathway. ENO1 may be a potential target against EV71, and DCA could act as an inhibitor of EV71.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Enterovirus/metabolismo , Enterovirus Humano A/metabolismo , Proteômica , Infecções por Enterovirus/metabolismo , Proteínas/metabolismo , Metabolômica , Redes e Vias Metabólicas
3.
Org Biomol Chem ; 20(26): 5230-5233, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35621003

RESUMO

The clinically used DNA-alkylating drug streptozotocin (STZ) was investigated using a simple work-up as an O-methylating agent to transform various carboxylic acids, sulfonic acids and phosphorous acids into corresponding methyl esters, and did so with yields of up to 97% in 4 h at room temperature. Good substrate tolerance was observed, and benefited from the mild conditions and compatibility of the reaction with water.


Assuntos
Ácidos Carboxílicos , Ésteres , DNA/metabolismo , Metilação , Estreptozocina
4.
Chemistry ; 26(35): 7747-7766, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32086844

RESUMO

Sodium-ion batteries (SIBs) have attracted much attention due to their abundance, easy accessibility, and low cost. All of these advantages make them potential candidates for large-scale energy storage. The P2-type layered transition-metal oxides (Nax TMO2 ; TM=Mn, Co, Ni, Ti, Fe, V, Cr, and a mixture of multiple elements) exhibit good Na+ ion conductivity and structural stability, which make them an excellent choice for the cathode materials of SIBs. Herein, the structural evolution, anionic redox reaction, some challenges, and recent progress of Nax TMO2 cathodes for SIBs are reviewed and summarized. Moreover, a detailed understanding of the relationship of chemical components, structures, phase compositions, and electrochemical performance is presented. This Review aims to provide a reference for the development of P2-type layered transition-metal oxide cathode materials for SIBs.

5.
J Hepatol ; 69(1): 51-59, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29524531

RESUMO

BACKGROUND & AIMS: Acetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Herein, we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP. METHODS: Male Balb/C mice were treated with or without antibiotics and a single dose of orally administered APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period). RESULTS: In agreement with previous findings, hepatic injury was markedly enhanced at ZT12 compared with ZT0. Interestingly, upon antibiotic treatment, ZT12 displayed a protective effect against APAP hepatotoxicity similar to ZT0. Moreover, mice that received the cecal content from ZT12 showed more severe liver damage than mice that received the cecal content from ZT0. 16S sequencing data revealed significant differences in the cecal content between ZT0 and ZT12 in the compositional level. Furthermore, metabolomic analysis showed that the gut microbial metabolites were also different between ZT0 and ZT12. Specifically, the level of 1-phenyl-1,2-propanedione (PPD) was significantly higher at ZT12 than ZT0. Treatment with PPD alone did not cause obvious liver damage. However, PPD synergistically enhanced APAP-induced hepatic injury in vivo and in vitro. Finally, we found Saccharomyces cerevisiae, which could reduce intestinal PPD levels, was able to markedly alleviate APAP-induced liver damage at ZT12. CONCLUSIONS: The gut microbial metabolite PPD was responsible, at least in part, for the diurnal variation of hepatotoxicity induced by APAP by decreasing glutathione levels. LAY SUMMARY: Acetaminophen (APAP) induced acute liver failure because of over dose is a leading public health problem. APAP-induced liver injury exhibits diurnal variation, specifically APAP causes more severe liver damage when taken at night compared with in the morning. Herein, we showed that gut microbial metabolite, 1-phenyl-1,2-propanedione is involved in the rhythmic hepatotoxicity induced by APAP, by depleting hepatic glutathione (an important antioxidant) levels. Our data suggest gut microbiota may be a potential target for reducing APAP-induced acute liver injury.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/microbiologia , Ritmo Circadiano/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Analgésicos não Narcóticos/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C
6.
Clin Lab ; 64(3): 311-319, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29739115

RESUMO

BACKGROUND: ATP-binding cassette sub-family G member 2 (ABCG2), an ABC transport protein involved in the efflux of anticancer compounds, has been reported to have altered expression levels in several cancers including breast, colon, and gastric cancer, etc. However, its expression change (up- or down-regulated in cancer) is still contradictory. METHODS: We performed immunohistochemistry to examine ABCG2 expression in the microarray with 90 pairs of colon cancer and their adjacent normal tissues. To find the expression of ABCG2 in lymphatic node metastasis (N1) and N0, we performed immunofluorescence, analyzed by Confocal technology. RESULTS: Compared to adjacent normal tissues, the percentage and density of positive cells expressing ABCG2 in colon cancer were significantly increased. In addition, ABCG2 expression in plasma membrane was related to lymph node metastasis in colon cancer, which was further verified to be downregulated by 2.7-fold in N1 to N0 through immunofluorescent analysis. CONCLUSIONS: ABCG2 expression in colon cancer was up-regulated, and its expression was decreased in the plasma membrane of colon cancer with lymphatic node metastasis (N metastasis).


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Biomarcadores Tumorais/biossíntese , Membrana Celular/metabolismo , Neoplasias do Colo/metabolismo , Proteínas de Neoplasias/biossíntese , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Serial de Tecidos , Adulto Jovem
7.
Molecules ; 23(9)2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30213061

RESUMO

A versatile and practical "on-water" protocol was newly developed to synthesize quinazolinones using o-bromobenzonitrile as a novel starting material. Studies have found that air as well as water plays an important role in synthesis of quinazolinones. Further investigation indicated that dihydroquinazolinones can be prepared with this protocol under the protection of N2. The protocol can be extended to other substrates and various quinazolinones and dihydroquinazolinones were obtained. o-Bromobenzamide, o-aminobenzonitrile, and o-aminobenzamide were also evaluated as starting materials, and the results further proved the versatility of this protocol, especially towards dihydroquinazolinones.


Assuntos
Benzamidas/química , Quinazolinonas/síntese química , Água/química , Estrutura Molecular , Nitrilas/química , Quinazolinonas/química
8.
Int J Mol Sci ; 16(6): 13339-55, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-26110380

RESUMO

Thlaspi arvense is a well-known annual farmland weed with worldwide distribution, which can be found from sea level to above 4000 m high on the Qinghai-Tibetan Plateau (QTP). In this paper, a phylogeographic history of T. arvense including 19 populations from China was inferred by using three chloroplast (cp) DNA segments (trnL-trnF, rpl32-trnL and rps16) and one nuclear (n) DNA segment (Fe-regulated transporter-like protein, ZIP). A total of 11 chloroplast haplotypes and six nuclear alleles were identified, and haplotypes unique to the QTP were recognized (C4, C5, C7 and N4). On the basis of molecular dating, haplotypes C4, C5 and C7 have separated from others around 1.58 Ma for cpDNA, which corresponds to the QTP uplift. In addition, this article suggests that the T. arvense populations in China are a mixture of diverged subpopulations as inferred by hT/vT test (hT ≤ vT, cpDNA) and positive Tajima's D values (1.87, 0.05 < p < 0.10 for cpDNA and 3.37, p < 0.01 for nDNA). Multimodality mismatch distribution curves and a relatively large shared area of suitable environmental conditions between the Last Glacial Maximum (LGM) as well as the present time recognized by MaxEnt software reject the sudden expansion population model.


Assuntos
Núcleo Celular/genética , DNA de Cloroplastos/genética , DNA de Plantas/genética , Ecossistema , Modelos Biológicos , Thlaspi/classificação , Thlaspi/genética , China , Evolução Molecular , Variação Genética/genética , Filogenia , Filogeografia , Análise de Sequência de DNA
9.
J Cancer ; 15(12): 3724-3737, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911385

RESUMO

Background: Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is crucial for treatment and drug development. Methods: In this study, we established a C57B/6N mouse model of colon carcinogenesis using azoxymethane-dextran sodium sulfate (AOM-DSS) treatment for 14 weeks to identify proteins associated with colon cancer. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted on the cell membrane components enriched in the colonic mucosa. Additionally, tumor tissues and adjacent normal colon tissues were collected from patients with colon cancer for comparative protein and metabolite analyses. Results: In total, 74 differentially expressed proteins were identified in the tumor tissue samples from AOM/DSS-treated mice compared to both the adjacent tissue samples from AOM/DSS-treated mice and tissue samples from saline-treated control mice. Bioinformatics analysis revealed eight downregulated proteins enriched in the branched-chain amino acids pathway (valine, leucine, and isoleucine degradation). Moreover, these proteins are already known to be associated with the survival rate of patients with cancer. Targeted metabolomics showed increased levels of valine, leucine, and isoleucine in tumor tissues compared to those in adjacent normal tissues in patients with colon cancer. Furthermore, a real-time PCR experiment demonstrated that Aldehyde dehydrogenase, mitochondrial (short protein name ALDH2, gene name Aldh2) and Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (short protein name HCDH, gene name Hadh) (two genes) in the pathway of branched-chain amino acids) were downregulated in patients with colon cancer (colon tumor tissues vs. their adjacent colon tissues). ALDH2 expression was further validated by western blotting in AOM/DSS-treated mouse model and in clinical samples. Conclusion: This study highlighted the inactivation of the branched-chain amino acid degradation pathway in colon cancer and identified ALDH2 and HCDH as potential biomarkers for diagnosing colon cancer and developing new therapeutic strategies.

10.
Fundam Clin Pharmacol ; 38(4): 767-779, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38342488

RESUMO

BACKGROUND: The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of nirmatrelvir (NMV) are unknown in Chinese patients with COVID-19. OBJECTIVES: To understand the PK, as well as PK-PD characteristics of NMV for optimizing the dose in Chinese patients with COVID-19. METHODS: We enrolled 141 participants who received NMV 300 mg/ritonavir (RTV) 100 mg b.i.d. for 5 days. The NMV concentrations were analyzed using 251 blood samples. PK/PD of NMV was investigated in these COVID-19 patients using a nonlinear mixed-effects model. RESULTS: The patients had a mean age of 82 years (range, 34-97). The absorption rate constant and apparent clearance of NMV in this Chinese cohort were 0.253 h-1 and 6.83 L/h, respectively, similar to Caucasian patients. No covariates affected NMV clearance. Predicted peak (Cmax) and trough concentration (Cmin) under 300 mg NMV/100 mg RTV b.i.d. were 4004 and 1498 ng/mL, respectively. Although higher AUC and Cmin were weakly associated with a slight increase in the number of cycle threshold (CT) of viral genes, no significant correlation was found, indicating a weak relationship between drug exposure and efficacy (CT). CONCLUSIONS: In all, our findings suggest no ethnic PK differences, a weak and clinically insignificant relationship between drug exposure and efficacy, suitable dosage for Chinese patients (including the elderly) based on PK parameters, and the need for further studies to determine optimal regimens for high-risk patients due to inter-individual variability.


Assuntos
Tratamento Farmacológico da COVID-19 , Ritonavir , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Idoso de 80 Anos ou mais , Ritonavir/farmacocinética , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/farmacologia , Adulto , Antivirais/farmacocinética , Antivirais/farmacologia , Antivirais/administração & dosagem , Povo Asiático , SARS-CoV-2 , China , COVID-19 , População do Leste Asiático
11.
Heliyon ; 10(11): e31878, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882332

RESUMO

The molecular pathology of lung injury in patients with Corona Virus Disease 2019 (COVID-19) remain unclear. In this study, we performed a proteomic study of lung tissues from seven patients with COVID-19, and eight without. Lung parenchymal tissues with COVID-19 were obtained from autopsy samples, while control samples were obtained from paracancerous tissues. Proteins were extracted using phenol extraction. A tandem mass tag-based quantitative proteomic approach combined with bioinformatic analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. A total of 6,602, and 6,549 proteins were identified in replicates 1 and 2, respectively. Of these, 307, and 278, respectively, were identified as differentially expressed proteins (DEPs). In total, 216 DEPs were identified in this study. These proteins were enriched in 189 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The downregulated proteins are mainly involved in focal adhesion (n = 5), and the PI3K-Akt signaling pathway (n = 4). The upregulated proteins were related to neutrophil extracellular trap (NET) formation (n = 16), and the phagosome pathway (n = 11). The upregulated proteins in these two pathways interact with one another. Further immunohistochemistry verified NET enrichment in the tissues with COVID-19 compared to the controls. Our results systematically outlined the proteomic profiles of the lung's response to SARS-CoV-2 infection and indicated that NET formation was hyper-activated. These results will hopefully provide new evidence for understanding the mechanism behind fatal COVID-19.

12.
Int J Antimicrob Agents ; 64(2): 107215, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38795930

RESUMO

OBJECTIVE: To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. METHODS: Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. RESULTS: Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. CONCLUSIONS: The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

13.
Food Chem ; 453: 139612, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38772306

RESUMO

Fusarium oxysporum and Botrytis cinerea are the main pathogens that cause fruit decay and reduce the postharvest shelf life of cherry tomatoes. Boosting the potency of natural products requires implementing structural modification to combat postharvest pathogens. Herein, we developed a novel Vanillin-Deep Eutectic Agent (V-DEA) from natural compounds and evaluated its effectiveness against tomato fruit rot pathogens. The results demonstrated that V-DEA suppressed mycelium growth and spore germination of F. oxysporum and B. cinerea by enhancing cell membrane permeability, increasing lipid peroxidation, and inhibiting enzyme activities. Importantly, using 8-mM V-DEA successfully prevented postharvest decay in cherry tomatoes, while 4-mM significantly extended their shelf life by reducing weight loss and shriveling, and enhancing key fruit qualities such as total soluble solids, ascorbic acid, tartaric acid, and lycopene. In conclusion, V-DEA exhibits dual properties as a potent pathogen inhibitor and antioxidant activity, thus prolonging the shelf life of cherry tomatoes.


Assuntos
Benzaldeídos , Botrytis , Conservação de Alimentos , Frutas , Fusarium , Doenças das Plantas , Solanum lycopersicum , Solanum lycopersicum/microbiologia , Solanum lycopersicum/química , Solanum lycopersicum/crescimento & desenvolvimento , Benzaldeídos/farmacologia , Benzaldeídos/química , Botrytis/crescimento & desenvolvimento , Botrytis/efeitos dos fármacos , Conservação de Alimentos/métodos , Frutas/química , Frutas/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Fusarium/metabolismo , Armazenamento de Alimentos
14.
Cell Host Microbe ; 32(1): 48-62.e9, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38056458

RESUMO

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF.


Assuntos
Acetaminofen , Falência Hepática Aguda , Humanos , Camundongos , Animais , Acetaminofen/efeitos adversos , Acetaminofen/metabolismo , Magnésio/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/farmacologia , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo
15.
Foods ; 12(3)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36765957

RESUMO

This study proposed to investigate the generation mechanism of raisins-derived volatile compounds during unsaturated fatty acids oxidation (UFAO) using a mixture of fatty acids (FAs) and four individual FA at different time intervals (0, 4, 8, 12, 16, and 20 days; 60 °C). During the sun-drying of 'Thompson Seedless' grapes (Vitis vinifera L.), a total of 39 UFAO-derived volatiles were characterized by the GC-MS. Firstly a pH value of 4.2 was optimized to proceed with a raisin drying-like UFAO model reaction. Afterward, GC-MS quantification revealed 45 UFAO-derived volatiles, and the maximum numbers of compounds were identified in the interaction of all FAs (39) following linoleic acid (29), erucic acid (27), oleic acid (25), and linolenic acid (27). Pentanoic acid, (E,E)-2,4-octadienal, and n-decanoic acid were only quantified in all FAs, linoleic acid, and erucic acid, respectively. This study showed that all FAs reactions were found to be responsible for the generation of a greater number of UFAO-derived volatiles with higher concentrations.

16.
Antioxidants (Basel) ; 12(3)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36978866

RESUMO

Litchi's post-harvest pericarp browning is one of the main constraints that drastically affect its visual attributes and market potential. Therefore, the vanillin-taurine Schiff base (VTSB) compound prepared from natural compounds of vanillin and taurine exhibited higher DPPH-radical-scavenging invitro antioxidant activity than vanillin. VTSB first-time report to mitigate the postharvest browning of litchi fruit. In this study, litchi fruits were dipped in 0.3 mM (based on pre-experiment) VTSB solution and stored at 25 ± 1 °C for six days to examine their effects on browning and postharvest quality. Fruit treated with VTSB had lower levels of browning degree (BD), browning index (BI), weight loss, soluble quinone (SQ), relative electrolyte leakage (REL), and malondialdehyde (MDA) than control fruit. Additionally, total anthocyanins and phenolic concentrations, Total soluble solids (TSS), and 2,2-diphenyl-1-picrylhydrazyl-free radical scavenging activity (DPPH-RSA) were preserved higher in VTSB-treated litchi fruit. The levels of Ascorbate peroxidase (APX), Superoxide dismutase (SOD), and Catalase (CAT) were higher in treated fruit, whereas polyphenol oxidase (PPO) and Peroxidase (POD) were decreased during the postharvest period. This study suggested that VTSB would be very useful for different post-harvest problems in the fruit and vegetable industry.

17.
J Glob Antimicrob Resist ; 32: 98-103, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36708768

RESUMO

OBJECTIVES: To assess the virological outcomes, prevalence of HIV drug resistance mutation (DRM), and correlates in Butuo County. METHODS: We conducted a cross-sectional study. Virological failure (VF) was defined as HIV-1 RNA ≥1000 copies/mL and on antiretroviral therapy (ART) for ≥6 months. Genotypic drug resistance was performed among VF cases. Correlates of DRM were identified using multivariate logistic regression. RESULTS: The overall virological suppression rate was 85.3%; DRM was detected in 42.6% (517/1215) VF cases and 6.2% of the sample patients. A total of 90.9% of patients were infected with HIV-1 CRF07_BC subtype. The prevalence of DRM to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) were 46.0% and 96.9%, respectively. The most prevalent mutation for NRTI was M184V (84.5%). Lamivudine (3TC), emtricitabine (FTC), and abacavir (ABC) had the highest resistance rates. For NNRTI, K103N (60.7%), nevirapine (NVP), and efavirenz (EFV) had the highest resistance rates and cross resistance to rilpivirine (RPV), doravirine (DOR), and etravirine (ETR). Ritonavir boosted lopinavir (LPV/r) resistance rate was extremely low. The occurrence of DRM was associated with age at ART ≤18 years, baseline CD4 count ≤200 cells/mL, NVP-based regimen, and ART duration >3 years. CONCLUSION: A relatively high proportion of VF and broad DRM for NRTI and NNRTI were observed, causing high-level resistance to first-line NRTI, NNRTI, and next generation NNRTI. Our findings necessitate the implementation of scaling up virological monitoring, adherence support, and timely switching to an LPV/r-containing regimen when patients with VF to reduce the occurrence of DRM.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Nevirapina/uso terapêutico , Lamivudina , Emtricitabina , Lopinavir/uso terapêutico , Mutação
18.
Am J Bot ; 99(8): e326-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22837414

RESUMO

PREMISE OF THE STUDY: Microsatellite markers were developed in Saussurea gnaphalodes to investigate its genetic variation and population structure. METHODS AND RESULTS: Using the combined biotin capture method, 46 microsatellite primer sets were isolated and characterized across 48 S. gnaphalodes individuals from three Tibetan populations. Seventeen of these markers showed polymorphism, and the number of alleles ranged from two to 17. The observed and expected heterozygosities per population ranged from 0 to 0.938 and from 0 to 0.905, respectively. CONCLUSIONS: These markers provide a useful tool to investigate the genetic diversity and population structure of S. gnaphalodes, and to facilitate further studies on conservation and utilization.


Assuntos
Primers do DNA/genética , Repetições de Microssatélites/genética , Polimorfismo Genético , Saussurea/genética , Alelos , Sequência de Bases , DNA de Plantas/genética , Loci Gênicos , Marcadores Genéticos , Variação Genética , Genética Populacional , Heterozigoto , Dados de Sequência Molecular , Folhas de Planta/classificação , Folhas de Planta/genética , Saussurea/classificação , Análise de Sequência de DNA , Especificidade da Espécie
19.
J Appl Toxicol ; 32(10): 796-803, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21725986

RESUMO

Carbon tetrachloride (CCl4) is a well-established model for screening hepato-protective drugs. The aim of the present study was to evaluate the potential protective effects of a novel soluble ß-glucan salecan on acute liver injury induced by CCl4 in mice and to further explore the underlying mechanisms. Mice were given salecan (40 mg kg⁻¹) or phosphate-buffered saline for 3 days prior to treatment with a single intraperitoneal dose of CCl4 (1 ml kg⁻¹ body weight). Animals were sacrificed at 0, 12, 24, 48, 72 and 96 h post-injection of CCl4. Serum liver enzyme levels, histology, lipid peroxidation, glutathione (GSH) content, expression of antioxidant enzymes and hepatocyte proliferation were subsequently evaluated. The serum levels of hepatic enzyme markers were markedly reduced in the salecan pretreatment group compared with the control group. Histopathological examination of the livers revealed that hepatocellular degeneration and necrosis were significantly attenuated at an early stage during CCl4 intoxication and liver recovery was markedly accelerated at a later stage in salecan pre-administered mice. Furthermore, salecan administration remarkably alleviated lipid peroxidation and restored GSH depletion. Meanwhile, the expression of antioxidant genes was significantly elevated in the salecan-treated group. Interestingly, the administration of salecan remarkably enhanced hepatocyte proliferation in the recovery phase after CCl4 injection. Taken together, these results demonstrated that salecan exhibits a protective action on acute hepatic injury induced by CCl4 through attenuating oxidative stress and accelerating hepatocyte regeneration.


Assuntos
Intoxicação por Tetracloreto de Carbono/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Polissacarídeos Bacterianos/uso terapêutico , Substâncias Protetoras/uso terapêutico , beta-Glucanas/uso terapêutico , Agrobacterium/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Fígado/fisiologia , Regeneração Hepática/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Solubilidade , beta-Glucanas/química , beta-Glucanas/isolamento & purificação , beta-Glucanas/metabolismo
20.
Clin Drug Investig ; 42(11): 1009-1016, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36239914

RESUMO

BACKGROUND AND OBJECTIVES: Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects. METHODS: This is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study. RESULTS: Sixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration-time curve from time zero to the last measurable concentration and area under the plasma concentration-time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported. CONCLUSIONS: Food slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04057729.


Assuntos
Interações Alimento-Droga , Humanos , Masculino , Estudos Cross-Over , Voluntários Saudáveis , Área Sob a Curva , Administração Oral , Disponibilidade Biológica , China
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