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1.
Comput Biol Med ; 180: 109013, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39137670

RESUMEN

Antidiabetic peptides (ADPs), peptides with potential antidiabetic activity, hold significant importance in the treatment and control of diabetes. Despite their therapeutic potential, the discovery and prediction of ADPs remain challenging due to limited data, the complex nature of peptide functions, and the expensive and time-consuming nature of traditional wet lab experiments. This study aims to address these challenges by exploring methods for the discovery and prediction of ADPs using advanced deep learning techniques. Specifically, we developed two models: a single-channel CNN and a three-channel neural network (CNN + RNN + Bi-LSTM). ADPs were primarily gathered from the BioDADPep database, alongside thousands of non-ADPs sourced from anticancer, antibacterial, and antiviral peptide datasets. Subsequently, data preprocessing was performed with the evolutionary scale model (ESM-2), followed by model training and evaluation through 10-fold cross-validation. Furthermore, this work collected a series of newly published ADPs as an independent test set through literature review, and found that the CNN model achieved the highest accuracy (90.48 %) in predicting the independent test set, surpassing existing ADP prediction tools. Finally, the application of the model was considered. SeqGAN was used to generate new candidate ADPs, followed by screening with the constructed CNN model. Selected peptides were then evaluated using physicochemical property prediction and structural forecasts for pharmaceutical potential. In summary, this study not only established robust ADP prediction models but also employed these models to screen a batch of potential ADPs, addressing a critical need in the field of peptide-based antidiabetic research.

2.
ACS Appl Mater Interfaces ; 16(27): 34538-34548, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38940445

RESUMEN

Biothiol assays offer vital insights into health assessment and facilitate the early detection of potential health issues, thereby enabling timely and effective interventions. In this study, we developed ultrasmall CuMn-Histidine (His) nanozymes with multiple enzymatic activities. CuMn-His enhanced peroxidase (POD)-like activity at neutral pH was achieved through hydrogen bonding and electrostatic effects. In addition, CuMn-His possesses laccase (LAC)-like and superoxide dismutase (SOD)-like activities at neutral pH. Based on three different enzyme mimetic activities of CuMn-His at neutral pH, the colorimetric sensing array without changing the buffer solution was successfully constructed. The array was successfully used for the identification of three biothiols, glutathione (GSH), cysteine (Cys), and homocysteine (Hcy). Subsequently, excellent application results were shown in complex serum and cellular level analyses. This study provides an innovative strategy for the development of ultrasmall bimetallic nanozymes with multiple enzymatic activities and the construction of colorimetric sensing arrays.


Asunto(s)
Colorimetría , Colorimetría/métodos , Concentración de Iones de Hidrógeno , Humanos , Histidina/química , Glutatión/sangre , Glutatión/química , Glutatión/análisis , Homocisteína/sangre , Homocisteína/análisis , Compuestos de Sulfhidrilo/química , Nanoestructuras/química , Cisteína/sangre , Cisteína/análisis , Cisteína/química , Superóxido Dismutasa/química , Técnicas Biosensibles/métodos , Lacasa/química , Lacasa/metabolismo
3.
Artículo en Inglés | MEDLINE | ID: mdl-38728181

RESUMEN

BACKGROUND: Haemodynamics plays an important role in the development of vascular disease. There is currently a lack of studies evaluating the characteristics and affecting factors of the iliac vein haemodynamics in clinical practice. OBJECTIVE: The goal of this study was to use 4D flow MRI to explore the haemodynamic characteristics of iliac veins and its affecting factors in an asymptomatic population. METHODS: Thirty consecutive volunteers without venous-related symptoms or signs underwent four-dimensional postprocessing of their MRI images. Relevant parameters, the demographic data, common iliac vein-inferior vena cava angle, iliac vein area, tortuosity, iliac vein mean flow, mean velocity was computed and analysed. T tests and Spearman's tests were used for analysing. A P value of 0.05 or less was considered significant. RESULTS: Height and iliac vein area were positively correlated with flow, while degree of stenosis, and common iliac-inferior vena cava angle were negatively correlated with that. Degree of stenosis was positively correlated with velocity, but the common iliac-inferior vena cava angle and iliac vein tortuosity were negatively correlated with that. The mean flow and velocity of iliac veins in females were lower than males. The mean flow and velocity of the left iliac veins were lower than those of the right. CONCLUSION: The height, gender, tortuosity, degree of stenosis, common iliac vein-inferior vena cava angle of the iliac vein are important factors that affect flow and velocity of the iliac veins. There were differences in haemodynamic parameters of the bilateral iliac veins.

4.
Life Sci ; 348: 122674, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38692507

RESUMEN

AIMS: Ubiquitin specific peptidase 5 (USP5), a member of deubiquitinating enzymes, has garnered significant attention for its crucial role in cancer progression. This study aims to explore the role of USP5 and its potential molecular mechanisms in cholangiocarcinoma (CCA). MAIN METHODS: To explore the effect of USP5 on CCA, gain-of-function and loss-of-function assays were conducted in human CCA cell lines RBE and HCCC9810. The CCK8, colony-forming assay, EDU, flow cytometry, transwell assay and xenografts were used to assess cell proliferation, migration and tumorigenesis. Western blot and immunohistochemistry were performed to measure the expression of related proteins. Immunoprecipitation and immunofluorescence were applied to identify the interaction between USP5 and Y box-binding protein 1 (YBX1). Ubiquitination assays and cycloheximide chase assays were carried out to confirm the effect of USP5 on YBX1. KEY FINDINGS: We found USP5 is highly expressed in CCA tissues, and upregulated USP5 is required for the cancer progression. Knockdown of USP5 inhibited cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro, along with suppressed xenograft tumor growth and metastasis in vivo. Mechanistically, USP5 could interact with YBX1 and stabilize YBX1 by deubiquitination in CCA cells. Additionally, silencing of USP5 hindered the phosphorylation of YBX1 at serine 102 and its subsequent translocation to the nucleus. Notably, the effect induced by USP5 overexpression in CCA cells was reversed by YBX1 silencing. SIGNIFICANCE: Our findings reveal that USP5 is required for cell proliferation, migration and EMT in CCA by stabilizing YBX1, suggesting USP5-YBX1 axis as a promising therapeutic target for CCA.


Asunto(s)
Neoplasias de los Conductos Biliares , Movimiento Celular , Proliferación Celular , Colangiocarcinoma , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Ratones Desnudos , Proteína 1 de Unión a la Caja Y , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/genética , Animales , Ratones , Línea Celular Tumoral , Proteína 1 de Unión a la Caja Y/metabolismo , Proteína 1 de Unión a la Caja Y/genética , Ubiquitinación , Ratones Endogámicos BALB C , Masculino , Endopeptidasas/metabolismo , Endopeptidasas/genética , Regulación Neoplásica de la Expresión Génica , Femenino
5.
Food Microbiol ; 120: 104449, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38431336

RESUMEN

This research investigated the presence of Burkholderia gladioli pathovar cocovenenans (BGC) in wet rice and starch products, Tremella, and Auricularia auricula in Guangzhou, China. It examined BGC growth and bongkrekic acid (BA) production in wet rice noodles and vermicelli with varying rice flour, edible starch ratios, and oil concentrations. A qualitative analysis of 482 samples revealed a detection rate of 0.62%, with three positive for BGC. Rice flour-based wet rice noodles had BA concentrations of 13.67 ± 0.64 mg/kg, 2.92 times higher than 100% corn starch samples (4.68 ± 0.54 mg/kg). Wet rice noodles with 4% soybean oil had a BA concentration of 31.72 ± 9.41 mg/kg, 5.74 times higher than those without soybean oil (5.53 ± 1.23 mg/kg). The BA concentration correlated positively (r = 0.707, P < 0.05) with BGC contamination levels. Low temperatures (4 °C and -18 °C) inhibited BGC growth and BA production, while higher storage temperatures (26 °C and 32 °C) promoted BGC proliferation and increased BA production. Reducing edible oil use and increasing edible starch can mitigate the risk of BGC-related food poisoning in wet rice noodles and vermicelli production. Further research is needed to find alternative oils that do not enhance BA production. Strengthening prevention and control measures is crucial across the entire production chain to address BGC contamination and BA production.


Asunto(s)
Burkholderia gladioli , Oryza , Ácido Bongcréquico/análisis , Aceite de Soja/análisis , Almidón , Contaminación de Alimentos/análisis , Harina/análisis
6.
Membranes (Basel) ; 14(3)2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38535278

RESUMEN

The hydrogen flux inhibition of Pd-Ru membranes under exposure to 1-10% NH3 at 673-773 K was investigated. The Pd-Ru membranes were characterized by XRD, SEM, XPS, and hydrogen permeation tests. The results show that when exposed to 1-10% NH3 at 723 K for 6 h, the hydrogen flux of Pd-Ru membranes sharply decreases by 15-33%, and the decline in hydrogen flux becomes more significant with increasing temperatures. After the removal of 1-10% NH3, 100% recovery of hydrogen flux is observed. XPS results show that nitrogenous species appear on the membrane surface after NH3 exposure, and the hydrogen flux inhibition may be related to the competitive adsorption of nitrogenous species. By comparing the hydrogen flux of Pd-Ru membranes exposed to 10% NH3 with 10% N2, it is indicated that the rapid decrease in hydrogen flux is due to the concentration polarization and competitive adsorption of nitrogenous species. The competitive adsorption effect is attenuated, while the concentration polarization effect becomes more pronounced with increasing temperature.

7.
Mar Environ Res ; 196: 106419, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38408405

RESUMEN

Previous studies have reported the correlations between bacterial communities and coral bleaching, but the knowledge of fungal roles in coral bleaching is still limited. In this study, the taxonomic and functional diversities of fungi in unbleached, partly bleached and bleached stony coral Acropora intermedia were investigated through the ITS-rRNA gene next-generation sequencing. An unexpected diversity of successfully classified fungi (a total of 167 fungal genera) was revealed in this study, and the partly bleached coral samples gained the highest fungal diversity, followed by bleached and unbleached coral samples. Among these fungi, 122 genera (nearly 73.2%) were rarely found in corals in previous studies, such as Calostoma and Morchella, which gave us a more comprehensive understanding of coral-associated fungi. Positively correlated fungal genera (Calostoma, Corticium, Derxomyces, Fusicolla, Penicillium and Vishniacozyma) and negative correlated fungal genera (Blastobotrys, Exophiala and Dacryopinax) with the coral bleaching were both detected. It was found that a series of fungal genera, dominant by Apiotrichum, a source of opportunistic infections, was significantly enriched; while another fungal group majoring in Fusicolla, a probiotic fungus, was distinctly depressed in the bleached coral. It was also noteworthy that the abundance of pathogenic fungi, including Fusarium, Didymella and Trichosporon showed a rising trend; while the saprotrophic fungi, including Tricladium, Botryotrichum and Scleropezicula demostrated a declining trend as the bleaching deteriorating. The rising of pathogenic fungi and the declining of saprotrophic fungi revealed the basic rules of fungal community transitions in the coral bleaching, but the mechanism of coral-associated fungal interactions still lacks further investigation. Overall, this is an investigation focused on the differences of fungal communities at taxonomic and functional levels in stony coral A. intermedia under different bleaching statuses, which provides a better comprehension of the correlations between fungal communities and the coral bleaching.


Asunto(s)
Antozoos , Micobioma , Poríferos , Animales , Bacterias , Arrecifes de Coral
8.
Artículo en Inglés | MEDLINE | ID: mdl-38294750

RESUMEN

Objective: The objective of this study was to investigate the clinical phenotype and genetic etiology of Glanzmann's thrombasthenia in a consanguineous pedigree. Methods: Clinical data and ancillary test results were collected from pedigrees with Glanzmann's thrombasthenia. High-throughput sequencing was used to detect variants in the proband. Candidate variants were verified by Sanger sequencing. Results: Two patients in the pedigree were homozygous for the c.2248C>T (p. Arg750Ter) variant of the ITGB3 gene. The parents and maternal grandmother, who didn't have any recurrent haemorrhage, were found to carry a heterozygous c.2248C>T variant of the ITGB3 gene, which was absent in the aunt and paternal grandmother. Conclusion: The homozygous variant c.2248C>T (p. Arg750Ter) in the ITGB3 gene underlies the disease in this pedigree. This diagnosis will facilitate genetic counselling in this pedigree for better patient management and life guidance.

9.
ACS Appl Mater Interfaces ; 16(3): 3116-3125, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38224533

RESUMEN

High concentrations of reactive oxygen and nitrogen species (RONS) are key characteristics of inflammatory sites. Scavenging RONS at the site of inflammation is an effective therapeutic strategy. This study introduces ultrasmall Cu2O@His nanoparticles with RONS-scavenging ability for the treatment of inflammatory bowel disease (IBD) in mice. The strong coordination between the nitrogen atom in histidine (His) and copper enhances the dispersion and stability of Cu2O@His. Due to their small size and large surface area, Cu2O@His exhibits outstanding RONS-clearing ability. Importantly, Cu2O@His can target mitochondrial sites and repair damaged mitochondria. With excellent dispersion and scavenging RONS ability, Cu2O@His demonstrates good efficacy in treating mouse IBD. This work provides a new paradigm for developing nanozymes with an ultrasmall size and multiple scavenging RONS abilities.


Asunto(s)
Cobre , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Histidina , Antiinflamatorios , Especies Reactivas de Oxígeno , Especies de Nitrógeno Reactivo , Nitrógeno
10.
Animals (Basel) ; 14(2)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38254417

RESUMEN

In order to explore the main regulatory genes and related pathways of growth traits, transcriptome sequencing was first performed on the brain, liver, and muscle tissues of 3-month-old M. armatus with different growth rates. By comparative transcriptome analysis of fast-growing and slow-growing groups of M. armatus, a total of 2887 DEGs were screened, of which 59 up-regulated genes and 105 down-regulated genes were detected in the brain, 146 up-regulated genes and 202 down-regulated genes were detected in the liver, and 529 up-regulated genes and 1846 down-regulated genes were detected in muscle, including insulin-like growth factor binding protein 1a (IGFBP1A), insulin-like growth factor binding protein 1b (IGFBP1B), myosin, light chain 1 (MYL1), and myoglobin (MB). Through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we identified a total of 288 significantly enriched GO entries and 68 significantly enriched KEGG pathways related to growth, such as skeletal muscle tissue development, insulin-like growth factor binding, and the mitotic cell cycle. These key genes and signaling pathways may play a key role in regulating the growth of M. armatus. Digging into the regulatory mechanisms of these key genes will provide a theoretical basis for further exploration of the molecular mechanisms related to the growth and development of M. armatus, and help to breed new varieties of M. armatus with rapid growth.

11.
Chemosphere ; 350: 140963, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38114022

RESUMEN

Previous studies have revealed links between metal(loid)s and health problems; however, the link between metal(loid)s and obesity remains controversial. We evaluated the cross-sectional association between metal(loid) exposure in whole blood and obesity among the general population. Vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), thallium (T1), and lead (Pb) were measured in 3029 subjects in Guangdong Province (China) using ICP-MS. The prevalence of overweight and obesity (OWO) and abdominal obesity (AOB) was calculated according to body mass index (BMI) and waist circumference (WC), respectively. Multivariate analysis showed that elevated blood Cu, Cd, and Pb levels were inversely associated with the risk of OWO, and these associations were confirmed by a linear dose-response relationship. Elevated blood Co concentration was associated with a decreased risk of AOB. A quantile g-computation approach showed a significantly negative mixture-effect of 13 metal(loid)s on OWO (OR: 0.96; 95% CI: 0.92, 0.99). Two metals-Ni and Mo-were inversely associated with the risk of OWO but positively associated with AOB. We cross-grouped the two obesity measurement types and found that the extremes of metal content were present in people with AOB only. In conclusion, blood Cu, Mo, Ni, Cd, and Pb were inversely associated with the risk of OWO. The presence of blood Co may be protective, while Ni and Mo exposure might increase the risk of AOB. The association between metal(loid) exposure and obesity warrants further investigation in longitudinal cohort studies.


Asunto(s)
Arsénico , Metales Pesados , Humanos , Estudios Transversales , Cadmio/análisis , Sobrepeso/epidemiología , Obesidad Abdominal/epidemiología , Plomo/análisis , Estudios Longitudinales , Arsénico/análisis , Níquel/análisis , Molibdeno/análisis , Cobalto/análisis , China/epidemiología , Metales Pesados/análisis , Monitoreo del Ambiente
12.
Toxins (Basel) ; 15(11)2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37999509

RESUMEN

Aflatoxins are liver carcinogens and are common contaminants in unpackaged peanut (UPP) oil. However, the health risks associated with consuming aflatoxins in UPP oil remain unclear. In this study, aflatoxin contamination in 143 UPP oil samples from Guangdong Province were assessed via liquid chromatography-tandem mass spectrometry (LC-MS). We also recruited 168 human subjects, who consumed this oil, to measure their liver functions and lipid metabolism status. Aflatoxin B1 (AFB1) was detected in 79.72% of the UPP oil samples, with levels ranging from 0.02 to 174.13 µg/kg. The average daily human intake of AFB1 from UPP oil was 3.14 ng/kg·bw/day; therefore, the incidence of liver cancer, caused by intake of 1 ng/kg·bw/day AFB1, was estimated to be 5.32 cases out of every 100,000 persons per year. Meanwhile, Hepatitis B virus (HBV) infection and AFB1 exposure exerted a synergistic effect to cause liver dysfunction. In addition, the triglycerides (TG) abnormal rate was statistically significant when using AFB1 to estimate daily intake (EDI) quartile spacing grouping (p = 0.011). In conclusion, high aflatoxin exposure may exacerbate the harmful effects of HBV infection on liver function. Contamination of UPP oil with aflatoxins in Guangdong urgently requires more attention, and public health management of the consumer population is urgently required.


Asunto(s)
Aflatoxinas , Humanos , Aflatoxinas/toxicidad , Aflatoxinas/análisis , Aceite de Cacahuete/análisis , Contaminación de Alimentos/análisis , Aflatoxina B1/toxicidad , Aflatoxina B1/análisis , China/epidemiología
13.
Anal Chim Acta ; 1278: 341744, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37709473

RESUMEN

Liver function tests play a vital role in accurately diagnosing liver diseases, monitoring treatment outcomes, and assessing liver damage severity. Here, we introduce a novel approach to develop a smartphone-assisted portable colorimetric sensor for rapid detection of three liver function biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). This sensor is based on the inherent enzyme-like activities of hollow MnO2 (H-MnO2). The H-MnO2 is synthesized via a self-template sacrifice and in situ oxidation strategy, utilizing a manganese-based Prussian blue analogue (Mn-PBA) as a sacrificial template. The resulting H-MnO2 exhibits a polycrystalline structure with a large specific surface area. By encapsulating the H-MnO2 in sodium alginate, we construct a portable sensing platform facilitating specific and rapid colorimetric detection of the three liver function biomarkers with the assistance of a smartphone. The developed sensor demonstrates outstanding sensitivity and stability, achieving detection limits of 4.9 U L-1, 3.6 U L-1, and 0.99 U L-1 for AST, ALT, and ALP, respectively. Importantly, this work introduces an innovative in situ oxidation method for fabricating hollow nanozymes, offering a cost-effective and convenient assay for liver function biomarkers detection.


Asunto(s)
Colorimetría , Compuestos de Manganeso , Óxidos , Teléfono Inteligente , Fosfatasa Alcalina , Biomarcadores , Colorantes , Hígado
14.
Nat Commun ; 14(1): 4211, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452049

RESUMEN

Aqueous zinc batteries are ideal candidates for grid-scale energy storage because of their safety and low-cost aspects. However, the production of large-format aqueous Zn batteries is hindered by electrolyte consumption, hydrogen gas evolution and accumulation, and Zn dendrites growth. To circumvent these issues, here we propose an "open" pouch cell design for large-format production of aqueous Zn batteries, which can release hydrogen gas and allow the refilling of the electrolyte components consumed during cell cycling. The cell uses a gel electrolyte containing crosslinked kappa (k)-carrageenan and chitosan. It bonds water molecules and hinders their side reaction with Zn, preventing electrolyte leakage and fast evaporation. As a proof-of-concept, we report the assembly and testing of a Zn | |ZnxV2O5·nH2O multi-layer "open" pouch cell using the carrageenan/chitosan gel electrolyte, which delivers an initial discharge capacity of 0.9 Ah and 84% capacity retention after 200 cycles at 200 mA g‒1, 370 kPa and 25 °C.


Asunto(s)
Quitosano , Zinc , Carragenina , Metales , Electrólitos , Hidrógeno , Agua
15.
Food Res Int ; 171: 113084, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37330837

RESUMEN

Facing the increasing occurrence of "big six" Escherichia coli outbreaks linked to fresh produce, chlorine-based sanitisers are widely used for fresh produce decontamination in recent years. However, latest finding that chlorine may induce E. coli cells into a viable not nonculturable (VBNC) state is bringing a new challenge to the fresh produce industry. VBNC cells are undetectable by the plate count test, and yet they retain pathogenicity and are more antibiotic-resistant than culturable cells. As a result, their eradication is critical to ensure the safety of fresh produce. Understanding VBNC cells at the metabolic level may provide a breakthrough for their eradication. Therefore, this study was carried out to collect the VBNC pathogenic E. coli (O26:H11, O121:H19, and O157:H7) cells from chlorine-treated pea sprouts and characterise them using NMR-based metabolomics. From the globally increased metabolite contents detected in the VBNC E. coli cells as compared to the culturable cells, mechanisms underlying E. coli's VBNC induction were elucidated. These include rendering the energy generation scheme to become more compatible with the lowered energy needs, disaggregating protein aggregates to release amino acids for osmoprotection and later resuscitation, as well as increasing cAMP content to downregulate RpoS. These identified metabolic characteristics can inspire future development of targeted measures for VBNC E. coli cell inhibition. Our methods can also be applied to other pathogens to help lower the risk of overall foodborne diseases.


Asunto(s)
Cloro , Escherichia coli O157 , Cloro/farmacología , Virulencia , Metaboloma
16.
Front Pharmacol ; 14: 1187818, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37256223

RESUMEN

Background and aims: Renal damage in severe coronavirus disease 2019 (COVID-19) is highly associated with mortality. Finding relevant therapeutic candidates that can alleviate it is crucial. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have been shown to be harmless to COVID-19 patients, but it remains elusive whether ACEIs/ARBs have protective benefits to them. We wished to determine if ACEIs/ARBs had a protective effect on the renal damage associated with COVID-19, and to investigate the mechanism. Methods: We used the envelope (E) protein of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) to induce COVID-19-like multiple organ damage and observed renal fibrosis. We induced the epithelial-mesenchymal transformation of HK-2 cells with E protein, and found that olmesartan could alleviate it significantly. The protective effects of olmesartan on E protein-induced renal fibrosis were evaluated by renal-function assessment, pathologic alterations, inflammation, and the TGF-ß1/Smad2/3 signaling pathway. The distribution of high-mobility group box (HMGB)1 was examined after stimulation with E protein and olmesartan administration. Results: E protein stimulated HMGB1 release, which triggered the immune response and promoted activation of TGF-ß1/Smad2/3 signaling: both could lead to renal fibrosis. Olmesartan regulated the distribution of HMGB1 under E protein stimulation. Olmesartan inhibited the release of HMGB1, and reduced the inflammatory response and activation of TGF-ß1/Smad2/3 signaling. Olmesartan increased the cytoplasmic level of HMGB1 to promote the autophagic degradation of TGF-ß1, thereby alleviating fibrosis further. Conclusion: Olmesartan alleviates E protein-induced renal fibrosis by regulating the release of HMGB1 and its mediated autophagic degradation of TGF-ß1.

17.
Chem Biodivers ; 20(4): e202300267, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36971209

RESUMEN

In the present study, a new polyoxygenated cembranoid named sarcomililatol H (1) as well as six known terpenes 2-7 with different skeletons were isolated from South China Sea soft coral Sarcophyton mililatensis. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the structure of the new compound 1 was established. This new cembranoid was characterized by the presence of the rarely encountered tetrahydropyran ring with the ether linkage across C-2 and C-12. By applying the time-dependent density functional theory electronic circular dichroism (TDDFT ECD) approach, the absolute configuration of sarcomililatol H (1) was determined. All of the isolates were subjected to the anti-inflammatory and anti-tumor bioassays. However, none of them was active in these evaluations. Additionally, the preliminary virtual screening of inhibitory against SARS-CoV-2 by molecular docking showed that diterpene 1 could be regarded as a SARS-CoV-2 main protease (Mpro ) inhibitor (binding energy: -7.63 kcal/mol). The discovery of these terpenes has expanded the chemical diversity and complexity of terpenes from the species S. mililatensis.


Asunto(s)
Antozoos , COVID-19 , Diterpenos , Animales , Terpenos/química , Antozoos/química , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Diterpenos/química , Estructura Molecular
18.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36768306

RESUMEN

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A-F (1-6) and four known analogs (7-10). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga Kα radiation (λ = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)-α inhibitory activity (IC50 = 9.5 µmol/L), similar to the positive control dexamethasone (IC50 = 8.7 µmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC50 > 50 µmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.


Asunto(s)
Antozoos , Diterpenos , Animales , Estructura Molecular , Antozoos/química , Simulación del Acoplamiento Molecular , Resonancia Magnética Nuclear Biomolecular , Diterpenos/farmacología , Diterpenos/química
19.
Biomed Pharmacother ; 159: 114242, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36652729

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, which has seriously affected human health worldwide. The discovery of therapeutic agents is extremely urgent, and the viral structural proteins are particularly important as potential drug targets. SARS-CoV-2 envelope (E) protein is one of the main structural proteins of the virus, which is involved in multiple processes of the virus life cycle and is directly related to pathogenesis process. In this review, we present the amino acid sequence of the E protein and compare it with other two human coronaviruses. We then explored the role of E protein in the viral life cycle and discussed the pathogenic mechanisms that E protein may be involved in. Next, we summarize the potential drugs against E protein discovered in the current studies. Finally, we described the possible effects of E protein mutation on virus and host. This established a knowledge system of E protein to date, aiming to provide theoretical insights for mitigating the current COVID-19 pandemic and potential future coronavirus outbreaks.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Mutación , Secuencia de Aminoácidos
20.
J Fungi (Basel) ; 9(1)2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36675922

RESUMEN

As one core of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), Guangdong is facing some serious coastal environmental problems. Fungi are more vulnerable to changes in coastal environments than bacteria and archaea. This study investigated the fungal diversity and composition by high-throughput sequencing and detected basic parameters of seven environmental factors (temperature, dissolved oxygen, pH, salinity, total organic carbon, total nitrogen, and total phosphorus) at 11 sites. A total of 2056 fungal operational taxonomic units (OTUs) belonging to 147 genera in 6 phyla were recovered; Archaeorhizomyces (17.5%) and Aspergillus (14.19%) were the most dominant genera. Interestingly, a total of 14 genera represented the first reports of coastal fungi in this study. Furthermore, there were nine genera of fungi that were significantly correlated with environmental factors. FUNGuild analysis indicated that saprotrophs and pathogens were the two trophic types with the highest proportions. Saprotrophs were significantly correlated with total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP), while pathogens were significantly correlated with pH. This study provides new scientific data for the study of the diversity and composition of fungal communities in coastal ecosystems.

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