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1.
Fitoterapia ; : 105965, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631599

RESUMO

Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.

2.
Plants (Basel) ; 13(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38592914

RESUMO

Alfalfa (Medicago sativa L.) is an important forage crop worldwide, but molecular genetics and breeding research in this species are hindered by its self-incompatibility (SI). Although the mechanisms underlying SI have been extensively studied in other plant families, SI in legumes, including alfalfa, remains poorly understood. Here, we determined that self-pollinated pollen tubes could germinate on the stigma of alfalfa, grow through the style, and reach the ovarian cavity, but the ovules collapsed ~48 h after self-pollination. A transcriptomic analysis of dissected pistils 24 h after self-pollination identified 941 differently expressed genes (DEGs), including 784 upregulated and 157 downregulated genes. A gene ontology (GO) analysis showed that the DEGs were highly enriched in functions associated with the regulation of pollen tube growth and pollen germination. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that pentose and glucuronate interconversion, plant hormone signal transduction, the spliceosome, and ribosomes might play important roles in SI. Our co-expression analysis showed that F-box proteins, serine/threonine protein kinases, calcium-dependent protein kinases (CDPKs), bHLHs, bZIPs, and MYB-related family proteins were likely involved in the SI response. Our study provides a catalog of candidate genes for further study to understand SI in alfalfa and related legumes.

3.
Dalton Trans ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618719

RESUMO

Developing high performance noble-metal-free electrocatalysts as an alternative to Pt-based catalysts for the oxygen reduction reaction (ORR) in energy conversion devices is highly desirable. We report herein the preparation of a coordination-polymer (CP)-derived Fe/CP/C composite as an electrocatalyst for the ORR with excellent activity and stability both in solution and in Zn-air batteries. The Fe/CP/C catalyst was obtained from the pyrolysis of an iron porphyrin Fe(TPP)Cl (5,10,15,20-tetraphenyl-21H,23H-porphyrin iron(III) chloride) grafted Zn-coordination polymer with dangling functional groups 4,4'-oxybisbenzoic acid and 4,4'-bipyridine ligands. The Fe/CP/C catalyst showed much higher ORR activity with a half-wave potential (E1/2) of 0.90 V (vs. RHE) than the Fe/C catalyst (E1/2 = 0.85 V) derived from the carbon-black-supported Fe porphyrins in 0.1 M KOH solution. When Fe/CP/C was used as the cathode electrocatalyst in Zn-air batteries (ZABs), the ZABs achieved a significantly higher open circuit voltage (OCV = 1.43 V) and maximum power density (Pmax = 142.8 mW cm-2) compared with Fe/C (OCV = 1.38 V, Pmax = 104.5 mW cm-2) and commercial 20 wt% Pt/C (OCV = 1.41 V, Pmax = 117.6 mW cm-2). Using dangling functional groups in CP to increase the loading efficiency of iron porphyrins offered a facile method to prepare high-performance noble-metal-free electrocatalysts for the ORR, which may provide promising applications to energy conversion devices.

4.
Biomed Environ Sci ; 37(2): 157-169, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582978

RESUMO

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Rifampina/farmacologia , Estudos Retrospectivos , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Mutação
5.
Biodivers Data J ; 12: e115599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505126

RESUMO

Background: Chrysochroinae Laporte de Castelnau, 1835 is the very colourful subfamily of Buprestidae. There are 127 species and subspecies of the subfamily which have been recorded in China. New information: In this paper, we reported three genera, two subgenera and five species of the subfamily Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) which are all newly recorded from China. These reported taxa belong to two tribes and four genera: Chrysochroa (Chroodema) corbetti (Kerremans, 1893), Chrysochroa (Pyranthe) fulgens ephippigera White, 1843, Demochroa (Demoxantha) gratiosa indica Csiki, 1900, Xanthocatabonvouloirii (Deyrolle, 1861) (all the above four being Chrysochroini) and Cardiaspismouhotii E. Saunders, 1866 (Dicercini). The five newly-recorded species are briefly described, illustrated and supplemented with relevant biological information.

6.
Cancer Sci ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508217

RESUMO

N6-Methyladenosine (m6A) is a important process regulating gene expression post-transcriptionally. Programmed death ligand 1 (PD-L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1-associated protein (WTAP) degradation caused by ubiquitin-mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD-L1 expression in a way that was m6A-dependent. m6A "reader," Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) identified methylated PD-L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T-cell proliferation and its cancer cell-killing effects were prevented by overexpression of WTAP in vitro and in vivo. Overexpression prevented T cells from proliferating and killing CRC by maintaining the expression of PD-L1. Further evidence supporting the WTAP-PD-L1 regulatory axis was found in human CRC and organoid tissues. Tumors with high WTAP levels appeared more responsive to anti-PD1 immunotherapy, when analyzing samples from patients undergoing treatment. Overall, our findings demonstrated a novel PD-L1 regulatory mechanism by WTAP-induced mRNA epigenetic regulation and the possible application of targeting WTAP as immunotherapy for tumor hypoxia.

7.
Zootaxa ; 5410(3): 301-316, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480240

RESUMO

In this paper, two new species of Buprestis subgenus Akiyamaia Kurosawa, 1988 are described: B. (A.) gengmini Qi & Song, new species from Yunnan Province, China and B. (A.) wenii Qi & Song, new species from Yen Bai Province, Vietnam. The descriptions and illustrations of two new species are provided, and the diagnostic characters are provided to distinguish the two new species from other related species. A key is given for identification of all Akiyamaia species.The holotype of B. (A.) costipennis (Fairmaire, 1891) and pictures of living individuals are illustrated for the first time.


Assuntos
Besouros , Animais , Distribuição Animal , China
8.
Sci Adv ; 10(10): eadm7565, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38446887

RESUMO

Given the important advantages of the mid-infrared optical range (2.5 to 25 µm) for biomedical sensing, optical communications, and molecular spectroscopy, extending quantum information technology to this region is highly attractive. However, the development of mid-infrared quantum information technology is still in its infancy. Here, we report on the generation of a time-energy entangled photon pair in the mid-infrared wavelength band. By using frequency upconversion detection technology, we observe the two-photon Hong-Ou-Mandel interference and demonstrate the time-energy entanglement between twin photons at 3082 nm via the Franson-type interferometer, verifying the indistinguishability and nonlocality of the photons. This work is very promising for future applications of optical quantum technology in the mid-infrared band, which will bring more opportunities in the fields of quantum communication, precision sensing, and imaging.

9.
Int J Med Sci ; 21(4): 690-702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464829

RESUMO

Hyperoside is a natural flavonol glycoside widely found in plants and has been reported to have a variety of pharmacological effects, including anticancer abilities. In this study, we demonstrated for the first time that hyperoside inhibited the proliferation of bladder cancer cells in vitro and in vivo. Moreover, hyperoside could not only induce cell cycle arrest, but also induce apoptosis of a few bladder cancer cells. Quantitative proteomics, bioinformatics analysis and Western blotting confirmed that hyperoside induced the overexpression of EGFR, Ras and Fas proteins, which affects a variety of synergistic and antagonistic downstream signaling pathways, including MAPKs and Akt, ultimately contributing to its anticancer effects in bladder cancer cells. This study reveals that hyperoside could be a promising therapeutic strategy for the prevention of bladder cancer.


Assuntos
Quercetina/análogos & derivados , Transdução de Sinais , Neoplasias da Bexiga Urinária , Humanos , Pontos de Checagem do Ciclo Celular , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Apoptose , Carcinogênese/genética , Receptores ErbB/genética , Proliferação de Células , Linhagem Celular Tumoral
10.
Front Vet Sci ; 11: 1301852, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322168

RESUMO

Objective: The objective of this study was to investigate the impact of dietary deficiency and supplementation of calcium, zinc, copper, cobalt, manganese or selenium on minerals content in the longissimus dorsi (LD), biceps femoris (BF) and triceps brachii (TB) of grazing Mongolian sheep. Methods: We randomly divided 98 sheep into 7 treatment groups and fed them specific diets for 60 days: a total mineral nutrition diet (LCG), a calcium deficiency diet (LCa), a zinc deficiency diet (LZn), a copper deficiency diet (LCu), a cobalt deficiency diet (LCo), a manganese deficiency diet (LMn) and a selenium deficiency diet (LSe). Then 7 sheep from each group were slaughtered and samples of LD, BF and TB were collected for mineral content analysis. The remaining sheep in each group were subsequently fed specific diets for an additional 41 days: a total mineral nutrition diet (SCG), a calcium supplementation diet (SCa), a zinc supplementation diet (SZn), a copper supplementation diet (SCu), a cobalt supplementation diet (SCo), a manganese supplementation diet (SMn) and a selenium supplementation diet (SSe). Afterward, all sheep were slaughtered, and muscle samples were collected and analyzed. Results: Significant findings emerged that LCa decreased sulfur (S) content in BF and increased Ca content in LD and BF, while SCa increased S and Ca content in BF and TB, respectively (P < 0.05). LZn decreased Zn, S, and potassium (K) content in LD and BF, while SZn increased Zn and S content in LD and BF, respectively (P < 0.05). LCu decreased Cu and iron (Fe) content in LD and TB, while SCu increased Fe content in TB (P < 0.05). LCo decreased phosphorus, S, K, Ca, Mn, Fe, Cu, and Zn content in LD (P < 0.05). LMn decreased Mn content and increased K content in TB, while SMn decreased K content in BF and TB (P < 0.05). LSe and SSe decreased and increased Se content in LD, BF, and TB, respectively (P < 0.05). Conclusion: Dietary mineral levels have varying effects on lamb meat minerals content. It is important to ensure an adequate intake of minerals in the diet to enhance the mineral nutrition of lamb meat.

11.
J Colloid Interface Sci ; 661: 588-597, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38308897

RESUMO

Interactions between nanoparticles and the mucus layer are crucial to understand the behaviours in biological environments and design drug delivery systems. In this study, we developed a kinetic deposition model for the dynamic mucin-nanoparticle interactions using quartz crystal microbalance with dissipation (QCM-D). We investigated the effects of the physiochemical properties of several nanoparticles (including size, charge, and shape) and the physiological conditions on the mucin-nanoparticle interaction. Interestingly, layered double hydroxide (LDH) nanoparticles showed stronger interactions with the mucus layer compared to other types of nanoparticles due to their unique plate-like morphology. In specific for sheet-like LDH nanoparticles, our model found that their equilibrium adsorption capacity (Qe) followed the Langmuir adsorption isotherm, and the adsorption rate (k1) increased proportionally with the nanoparticle concentration. In addition, the particle size and thickness affected Qe and the surface coverage. Furthermore, bovine serum albumin (BSA) coating dramatically increased k1 of LDH nanoparticles. We proposed a novel mechanism to elucidate mucin-nanoparticle interactions, shedding light on the synergistic roles of drag force (Fd), repulsive force (Fr), and adsorptive force (Fa). These findings offer valuable insights into the complex mucin-nanoparticle interactions and provide guidance for the design of drug delivery systems.


Assuntos
Mucinas , Nanopartículas , Adsorção , Tamanho da Partícula , Técnicas de Microbalança de Cristal de Quartzo , Propriedades de Superfície , Soroalbumina Bovina/química
12.
Chemosphere ; 352: 141508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38387658

RESUMO

Recycled PET (rPET) is gaining popularity for use in the production of new food contact materials (FCMs) under the context of circular economy. However, the limited information on contaminants in rPET from China and concerns about their potential risk are major obstacles to their use in FCM in China. Fifty-five non-volatile compounds were tentatively identified in 126 batches of hot-washed rPET flakes aimed for food packaging applications in China. Although the 55 substances are not necessarily migratable and may not end up in the contacting media, their presence indicates a need for proper management and control across the value chain. For this reason, the 55 substances prioritized on the basis of level of concerns and in-silico genotoxicity profiler. Among them, dimethoxyethyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate were classified as level V substances, and Michler's ketone and 4-nitrophenol were both categorized as level V substances and had the genotoxic structure alert, while 2,4,5-trimethylaniline was specified with genotoxic structure alert. The above substances have high priority and may pose a potential risk to human health, therefore special attention should be paid to their migration from rPET. Aside from providing valuable information on non-volatile contaminants present in hot-washed rPET flakes coming from China, this article proposed a prioritization workflow that can be of great help to identify priority substances deserving special attention across the value chain.


Assuntos
Dibutilftalato , Contaminação de Alimentos , Humanos , China , Dibutilftalato/análise , Contaminação de Alimentos/análise , Reciclagem
13.
J Hazard Mater ; 467: 133663, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38325095

RESUMO

Incorporating spent coffee grounds into single-use drinking straws for enhanced biodegradability also raises safety concerns due to increased chemical complexity. Here, volatile organic compounds (VOCs) present in coffee ground straws (CGS), polylactic acid straws (PLAS), and polypropylene straws (PPS) were characterized using headspace - solid-phase microextraction and migration assays, by which 430 and 153 VOCs of 10 chemical categories were identified by gas chromatography - mass spectrometry, respectively. Further, the VOCs were assessed for potential genetic toxicity by quantitative structure-activity relationship profiling and estimated daily intake (EDI) calculation, revealing that the VOCs identified in the CGS generally triggered the most structural alerts of genetic toxicity, and the EDIs of 37.9% of which exceeded the threshold of 0.15 µg person-1 d-1, also outnumbering that of the PLAS and PPS. Finally, 14 VOCs were prioritized due to their definite hazards, and generally higher EDIs or detection frequencies in the CGS. Meanwhile, the probability of producing safer CGS was also illustrated. Moreover, it was uncovered by chemical space that the VOCs with higher risk potentials tended to gather in the region defined by the molecular descriptor related to electronegativity or octanol/water partition coefficient. Our results provided valuable references to improve the chemical safety of the CGS, to promote consumer health, and to advance the sustainable development of food contact materials.


Assuntos
Café , Compostos Orgânicos Voláteis , Humanos , Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Octanóis , Polipropilenos
14.
Mol Nutr Food Res ; 68(4): e2200771, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356045

RESUMO

SCOPE: Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia-induced early DR as well as the underlying mechanisms. METHODS AND RESULTS: Wild-type (WT) and nuclear factor erythroid 2-related factor 2 (Nrf2)-knockout C57BL/6 mice of type 1 diabetes and high glucose (HG)-induced RF/6A cells are used as in vivo and in vitro models, respectively. This study finds that SYR protects the retinal structure and function in diabetic mice and reduces the permeability and apoptosis of HG-treated RF/6A cells. Meanwhile, SYR distinctly mitigates inflammation and oxidative stress in vivo and vitro. The retinal microvascular damages are suppressed by SYR via downregulating hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. Whereas, SYR-provided protective effects are diminished in Nrf2-knockout mice, indicating that SYR improves DR progression by activating Nrf2. Similarly, SYR cannot exert protective effects against HG-induced oxidative stress and endothelial injury in small interfering RNA (siRNA)-Nrf2-transfected RF/6A cells. CONCLUSION: In summary, SYR suppresses oxidative stress via activating Nrf2 antioxidant pathway, which ameliorates retinal microvascular damage by downregulating HIF-1α/VEGF, thereby alleviating early DR progression.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Furanos , Lignanas , Camundongos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Camundongos Endogâmicos C57BL , Inflamação , Estresse Oxidativo
15.
BMC Genomics ; 25(1): 220, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413895

RESUMO

BACKGROUND: The appropriate mineral nutrients are essential for sheep growth and reproduction. However, traditional grazing sheep often experience mineral nutrient deficiencies, especially copper (Cu), due to inadequate mineral nutrients from natural pastures. RESULTS: The results indicated that dietary Cu deficiency and supplementation significantly reduced and elevated liver concentration of Cu, respectively (p < 0.05). FOXO3, PLIN1, ACTN2, and GHRHR were identified as critical genes using the weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR), and receiver operating characteristic curve (ROC) validation as potential biomarkers for evaluating Cu status in grazing sheep. Combining these critical genes with gene functional enrichment analysis, it was observed that dietary Cu deficiency may impair liver regeneration and compromise ribosomal function. Conversely, dietary Cu supplementation may enhance ribosomal function, promote lipid accumulation, and stimulate growth and metabolism in grazing sheep. Metabolomics analysis indicated that dietary Cu deficiency significantly decreased the abundance of metabolites such as cholic acid (p < 0.05). On the other hand, dietary Cu supplementation significantly increased the abundance of metabolites such as palmitic acid (p < 0.05). Integrative analysis of the transcriptome and metabolome revealed that dietary Cu deficiency may reduce liver lipid metabolism while Cu supplementation may elevate it in grazing sheep. CONCLUSIONS: The Cu content in diets may have an impact on hepatic lipid metabolism in grazing sheep. These findings provide new insights into the consequences of dietary Cu deficiency and supplementation on sheep liver and can provide valuable guidance for herders to rationalize the use of mineral supplements.


Assuntos
Cobre , Fígado , Ovinos , Animais , Cobre/farmacologia , Fígado/metabolismo , Suplementos Nutricionais , Minerais/metabolismo , Perfilação da Expressão Gênica , Expressão Gênica
16.
Clin Lab ; 70(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38213211

RESUMO

BACKGROUND: A fetus with increased copy number of chromosome 20 was identified by NIPT. Here we utilize several genetic tests and analyses to illuminate the etiology of such aneuploidy. METHODS: Amniotic fluid cells were extracted from pregnant woman and sent for karyotype and chromosomal microarray analysis (CMA). Trio pedigree analysis was conducted with Chromosome Analysis Suite and uniparental disomy (UPD)-tool software. RESULTS: CMA identified consistent results, which were 2 regions of homozygosity: arr[GRCh37]20p12.2q11.1 (11265096_26266313)hmz and arr[GRCh37]20q11.21q13.2(29510306_54430467)hmz. The trio pedigree analysis discovered that the fetal chromosome 20 was the entire maternal UPD mosaic with isodisomy and heterodisomy. CONCLUSIONS: When a large segment of chromosome is homozygous, appropriate genetic tests are required to find the potential mechanisms for UPD formation.


Assuntos
Cromossomos Humanos Par 20 , Dissomia Uniparental , Gravidez , Feminino , Humanos , Dissomia Uniparental/genética , Cromossomos Humanos Par 20/genética , Diagnóstico Pré-Natal/métodos , Cariotipagem , Feto
17.
BMC Genomics ; 25(1): 113, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273232

RESUMO

The corpora allata-corpora cardiaca (CA-CC) is an endocrine gland complex that regulates mosquito development and reproduction through the synthesis of juvenile hormone (JH). Epoxidase (Epox) is a key enzyme in the production of JH. We recently utilized CRISPR/Cas9 to establish an epoxidase-deficient (epox-/-) Aedes aegypti line. The CA from epox-/- mutants do not synthesize epoxidated JH III but methyl farneosate (MF), a weak agonist of the JH receptor, and therefore have reduced JH signalling. Illumina sequencing was used to examine the differences in gene expression between the CA-CC from wild type (WT) and epox-/- adult female mosquitoes. From 18,034 identified genes, 317 were significantly differentially expressed. These genes are involved in many biological processes, including the regulation of cell proliferation and apoptosis, energy metabolism, and nutritional uptake. In addition, the same CA-CC samples were also used to examine the microRNA (miRNA) profiles of epox-/- and WT mosquitoes. A total of 197 miRNAs were detected, 24 of which were differentially regulated in epox-/- mutants. miRNA binding sites for these particular miRNAs were identified using an in silico approach; they target a total of 101 differentially expressed genes. Our results suggest that a lack of epoxidase, besides affecting JH synthesis, results in the diminishing of JH signalling that have significant effects on Ae. aegypti CA-CC transcriptome profiles, as well as its miRNA repertoire.


Assuntos
Aedes , MicroRNAs , Animais , Feminino , Hormônios Juvenis/metabolismo , Aedes/genética , Aedes/metabolismo , Corpora Allata/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Expressão Gênica
18.
Cardiovasc Diabetol ; 23(1): 19, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195474

RESUMO

AIMS: Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, the underlying mechanism remains unclear. The role of vascular endothelial growth factor-B (VEGF-B) in DCM is little known. In present study, we aimed to investigate whether Mel alleviated DCM via regulation of VEGF-B and explored its underlying mechanisms. METHODS AND RESULTS: We found that Mel significantly alleviated cardiac dysfunction and improved autophagy of cardiomyocytes in type 1 diabetes mellitus (T1DM) induced cardiomyopathy mice. VEGF-B was highly expressed in DCM mice in comparison with normal mice, and its expression was markedly reduced after Mel treatment. Mel treatment diminished the interaction of VEGF-B and Glucose-regulated protein 78 (GRP78) and reduced the interaction of GRP78 and protein kinase RNA -like ER kinase (PERK). Furthermore, Mel increased phosphorylation of PERK and eIF2α, then up-regulated the expression of ATF4. VEGF-B-/- mice imitated the effect of Mel on wild type diabetic mice. Interestingly, injection with Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration of GSK2656157 (GSK), an inhibitor of phosphorylated PERK abolished the protective effect of Mel on DCM. Furthermore, rapamycin, an autophagy agonist displayed similar effect with Mel treatment; while 3-Methyladenine (3-MA), an autophagy inhibitor neutralized the effect of Mel on high glucose-treated neonatal rat ventricular myocytes. CONCLUSIONS: These results demonstrated that Mel attenuated DCM via increasing autophagy of cardiomyocytes, and this cardio-protective effect of Mel was dependent on VEGF-B/GRP78/PERK signaling pathway.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Melatonina , Humanos , Camundongos , Ratos , Animais , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Miócitos Cardíacos , Fator B de Crescimento do Endotélio Vascular , Melatonina/farmacologia , Chaperona BiP do Retículo Endoplasmático , Diabetes Mellitus Experimental/tratamento farmacológico , Transdução de Sinais , Autofagia , Glucose
19.
Chin J Integr Med ; 30(1): 34-41, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37076638

RESUMO

OBJECTIVE: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway. METHODS: Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC50) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. RESULTS: Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05). CONCLUSION: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Caspase 3/metabolismo , Proteína X Associada a bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Chaperona BiP do Retículo Endoplasmático , Células HeLa , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Estresse do Retículo Endoplasmático , Linhagem Celular Tumoral
20.
Gastrointest Endosc ; 99(3): 387-397.e6, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37858760

RESUMO

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Colorretais/patologia , Estudos Prospectivos , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento
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