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1.
J Org Chem ; 89(7): 5164-5169, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38536410

RESUMO

Formal total syntheses of stemonamine and cephalotaxine bearing the core cyclopenta[1,2-b]pyrrolo[1,2-a]azepine ring skeleton were achieved. The general synthetic strategy in the synthesis features the reductive oxy-Nazarov cyclization as key step, leading to the versatile construction of N-substituted spiro quaternary stereogenic centers from readily available starting materials.

2.
Medicine (Baltimore) ; 103(10): e37315, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457585

RESUMO

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036-1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55-66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Doença das Coronárias , Diabetes Mellitus , Masculino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doença das Coronárias/epidemiologia , Índices de Eritrócitos
3.
Alzheimers Res Ther ; 16(1): 15, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245771

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying molecular mechanisms were investigated. METHODS: A cellular model, N2a-APPswe, was established via lentiviral infection, and the APPswe/PSEN1dE9 transgenic mouse model was employed in the study. LC-MS/MS was applied to quantify the concentration of WT161 in the mouse brain. Western blotting, immunohistochemical staining, thioflavin-S staining and ELISA were applied to detect protein expression in cells, tissues, or serum. RNA interference was utilized to knockdown the expression of specific genes in cells. The cognitive function of mice was assessed via the nest-building test, novel object recognition test and Morris water maze test. RESULTS: Previous studies have focused mainly on the impact of HDAC inhibitors on histone deacetylase activity. Our study discovered that VPA and WT161 can downregulate the expression of multiple HDACs, such as HDAC1 and HDAC6, in both AD cell and mouse models. Moreover, they also affect the expression of APP and APP secretases (BACE1, PSEN1, ADAM10). RNA interference and subsequent vitamin C induction further confirmed that the expression of APP and APP secretases is indeed regulated by HDAC1 and HDAC6, with the JNK pathway being the intermediate link in this regulatory process. Through the above pathways, VPA and WT161 effectively reduced Aß deposition in both AD cell and mouse models and significantly improved cognitive function in AD mice. CONCLUSIONS: In general, we have discovered that the HDAC6-JNK-APP secretases cascade is an important pathway for VPA and WT161 to exert their therapeutic effects on AD. Investigations into the safety and efficacy of VPA and WT161 were also conducted, providing essential preclinical evidence for assessing these two epigenetic drugs for the treatment of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Ácidos Hidroxâmicos , Compostos de Terfenil , Camundongos , Animais , Doença de Alzheimer/genética , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Cromatografia Líquida , Ácido Aspártico Endopeptidases/metabolismo , Espectrometria de Massas em Tandem , Camundongos Transgênicos , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo
4.
Chem Asian J ; 19(1): e202300862, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37966013

RESUMO

It is essential for the widespread application of proton exchange membrane fuel cells (PEMFCs) to investigate low-cost, extremely active, and long-lasting oxygen reduction catalysts. Initial performance of PGM-free metal-nitrogen-carbon (M-N-C) catalysts for oxygen reduction reaction (ORR) has advanced significantly, particularly for Fe-N-C-based catalysts. However, the insufficient stability of M-N-C catalysts still impedes their use in practical fuel cells. In this review, we focus on the understanding of the structure-stability relationship of M-N-C ORR catalysts and summarize valuable guidance for the rational design of durable M-N-C catalysts. In the first section of this review, we discuss the inherent degrading mechanisms of M-N-C catalysts, such as carbon corrosion, demetallation, H2 O2 attack, etc. As we gain a thorough comprehension of these deterioration mechanisms, we shift our attention to the investigation of strategies that can mitigate catalyst deterioration and increase its stability. These strategies include enhancing the anti-oxidation of carbon, fortifying M-N bonds, and maximizing the effectiveness of free radical scavengers. This review offers a prospective view on the enhancement of the stability of non-noble metal catalysts.

5.
Front Endocrinol (Lausanne) ; 14: 1279450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37955008

RESUMO

Aims: We aimed to construct a prediction model of type 2 diabetes mellitus (T2DM) in a Han Chinese cohort using a genetic risk score (GRS) and a nongenetic risk score (NGRS). Methods: A total of 297 Han Chinese subjects who were free from type 2 diabetes mellitus were selected from the Tianjin Medical University Chronic Disease Cohort for a prospective cohort study. Clinical characteristics were collected at baseline and subsequently tracked for a duration of 9 years. Genome-wide association studies (GWASs) were performed for T2DM-related phenotypes. The GRS was constructed using 13 T2DM-related quantitative trait single nucleotide polymorphisms (SNPs) loci derived from GWASs, and NGRS was calculated from 4 biochemical indicators of independent risk that screened by multifactorial Cox regressions. Results: We found that HOMA-IR, uric acid, and low HDL were independent risk factors for T2DM (HR >1; P<0.05), and the NGRS model was created using these three nongenetic risk factors, with an area under the ROC curve (AUC) of 0.678; high fasting glucose (FPG >5 mmol/L) was a key risk factor for T2DM (HR = 7.174, P< 0.001), and its addition to the NGRS model caused a significant improvement in AUC (from 0.678 to 0.764). By adding 13 SNPs associated with T2DM to the GRS prediction model, the AUC increased to 0.892. The final combined prediction model was created by taking the arithmetic sum of the two models, which had an AUC of 0.908, a sensitivity of 0.845, and a specificity of 0.839. Conclusions: We constructed a comprehensive prediction model for type 2 diabetes out of a Han Chinese cohort. Along with independent risk factors, GRS is a crucial element to predicting the risk of type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Estudos Prospectivos , População do Leste Asiático , Fatores de Risco
6.
Environ Monit Assess ; 195(8): 961, 2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37454303

RESUMO

Heavy metals contaminated soils are posing severe threats to food safety worldwide. Heavy metals absorbed by plant roots from contaminated soils lead to severe plant development issues and a reduction in crop yield and growth. The global population is growing, and the demand for food is increasing. Therefore, it is critical to identify soil remediation strategies that are efficient, economical, and environment friendly. The use of biochar and slag as passivators represents a promising approach among various physicochemical and biological strategies due to their efficiency, cost-effectiveness, and low environmental impact. These passivators employ diverse mechanisms to reduce the bioavailability of metals in contaminated soils, thereby improving crop growth and productivity. Although studies have shown the effectiveness of different passivators, further research is needed globally as this field is still in its early stages. This review sheds light on the innovative utilization of biochar and slag as sustainable strategies for heavy metal remediation, emphasizing their novelty and potential for practical applications. Based on the findings, research gaps have been identified and future research directions proposed to enable the full potential of passivators to be utilized effectively and efficiently under controlled and field conditions.


Assuntos
Carvão Vegetal , Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Poluentes do Solo/isolamento & purificação , Metais Pesados/isolamento & purificação , Resíduos Industriais , Solo/química
7.
Zool Res ; 44(5): 837-847, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37501399

RESUMO

The common marmoset ( Callithrix jacchus) has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies. Epileptic marmosets have been independently reported in two Asian primate research centers. Nevertheless, the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated. Here, we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing. We identified 14 558 184 single nucleotide polymorphisms (SNPs) from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples. Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers. In addition, SNP and copy number variation (CNV) analyses suggested that the WW domain-containing oxidoreductase ( WWOX) and Tyrosine-protein phosphatase nonreceptor type 21 ( PTPN21) genes may be associated with epilepsy in marmosets. Notably, KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets. This study provides valuable population genomic resources for marmosets in two Asian primate centers. Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers, while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.


Assuntos
Callithrix , Epilepsia , Animais , Callithrix/genética , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Genética Populacional , Epilepsia/veterinária
8.
Cell Death Discov ; 9(1): 235, 2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422452

RESUMO

Despite aging is closely linked to increased aneuploidy in the oocytes, the mechanism of how aging affects aneuploidy remains largely elusive. Here, we applied single-cell parallel methylation and transcriptome sequencing (scM&T-seq) data from the aging mouse oocyte model to decode the genomic landscape of oocyte aging. We found a decline in oocyte quality in aging mice, as manifested by a significantly lower rate of first polar body exclusion (P < 0.05), and dramatically increasing aneuploidy rate (P < 0.01). Simultaneously, scM&T data suggested that a large number of differential expression genes (DEGs) and differential methylation regions (DMRs) were obtained. Next, we identified strong association of spindle assembly and mitochondrial transmembrane transport during oocyte aging. Moreover, we verified the DEGs related to spindle assembly (such as Naip1, Aspm, Racgap1, Zfp207) by real-time quantitative PCR (RT-qPCR) and checked the mitochondrial dysfunction by JC-1 staining. Pearson correlation analysis found that receptors for mitochondrial function were strongly positively correlated with abnormal spindle assembly (P < 0.05). In conclusion, these results suggested that the mitochondrial dysfunction and abnormal spindle assembly of aging oocytes ultimately may lead to increased oocyte aneuploidy.

9.
World J Gastrointest Oncol ; 15(5): 787-809, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37275445

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have attracted extensive attention as therapeutic targets in gastric cancer (GC). Circ_0003356 is known to be downregulated in GC tissues, but its cellular function and mechanisms remain undefined. AIM: To investigate the role of circ_0003356 in GC at the molecular and cellular level. METHODS: Circ_0003356, miR-668-3p, and SOCS3 expression were assessed via quantitative real time-polymerase chain reaction (qRT-PCR). Wound healing, EdU, CCK-8, flow cytometry and transwell assays were used to analyze the migration, proliferation, viability, apoptosis and invasion of GC cells. The subcellular localization of circ_0003356 was monitored using fluorescence in situ hybridization. The interaction of circ_0003356 with miR-668-3p was confirmed using RIP-qRT-PCR, RNA pull-down, and dual luciferase reporter assays. We observed protein levels of genes via western blot. We injected AGS cells into the upper back of mice and performed immunohistochemistry staining for examining E-cadherin, N-cadherin, Ki67, and SOCS3 expressions. TUNEL staining was performed for the assessment of apoptosis in mouse tumor tissues. RESULTS: Circ_0003356 and SOCS3 expression was downregulated in GC cells, whilst miR-668-3p was upregulated. Exogenous circ_0003356 expression and miR-668-3p silencing suppressed the migration, viability, proliferation, epithelial to mesenchy-mal transition (EMT) and invasion of GC cells and enhanced apoptosis. Circ_0003356 overexpression impaired tumor growth in xenograft mice. Targeting of miR-668-3p by circ_0003356 was confirmed through binding assays and SOCS3 was identified as a downstream target of miR-668-3p. The impacts of circ_0003356 on cell proliferation, apoptosis, migration, invasion and EMT were reversed by miR-668-3p up-regulation or SOCS3 down-regulation in GC cells. CONCLUSION: Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.

10.
BMC Genomics ; 24(1): 265, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37202739

RESUMO

BACKGROUND: Cattle (Bos taurus) are a major large livestock, however, compared with other species, the transcriptional specificity of bovine oocyte development has not been emphasised. RESULTS: To reveal the unique transcriptional signatures of bovine oocyte development, we used integrated multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA) to perform bioinformatic analysis of the germinal follicle (GV) and second meiosis (MII) gene expression profile from cattle, sheep, pigs and mice. We found that the expression levels of most genes were down-regulated from GV to MII in all species. Next, the multispecies comparative analysis showed more genes involved in the regulation of cAMP signalling during bovine oocyte development. Moreover, the green module identified by WGCNA was closely related to bovine oocyte development. Finally, integrated multispecies comparative analysis and WGCNA picked up 61 bovine-specific signature genes that participate in metabolic regulation and steroid hormone biosynthesis. CONCLUSION: In a short, this study provides new insights into the regulation of cattle oocyte development from a cross-species comparison.


Assuntos
Oócitos , Transcriptoma , Bovinos , Animais , Camundongos , Ovinos/genética , Suínos , Oócitos/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oogênese/genética , Perfilação da Expressão Gênica
11.
Org Lett ; 25(21): 3829-3834, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37196242

RESUMO

Magnesium(II)-catalyzed cascade reactions of N,N'-cyclic azomethine imines with indolyl-substituted isocyanides are reported herein. The method exhibited a high functional group tolerance and broad substrate scope. A series of anti-pentacyclic spiroindolines containing N,N'-fused heterocycle skeletons were obtained in up to 82% yield with 8.5:1 dr under mild reaction conditions. Intriguingly, a sequential HOAc-mediated protonation results in a diastereoenriched epimerization, which gives rise to the syn-pentacyclic spiroindolines as the sole isomers.

12.
Mol Immunol ; 154: 96-107, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36621062

RESUMO

BACKGROUND: Lactate accumulation caused by abnormal tumor metabolism can induce the formation of an inhibitory immune microenvironment through a variety of pathways, which is characterized by regulatory T cells (Treg) infiltration and effector T cells (Teff) depletion. Studies have found that the key reason why Treg cells can survive in harsh environments lies in their flexible metabolic mode, which can use lactate in tumor microenvironment (TME) as an alternative energy substance to maintain their inhibitory activity. In addition, lactate could also promote the differentiation of CD4+T cells into Treg, but the mechanism was not completely clear. The purpose of this study was to investigate the possible mechanism by which lactate is utilized by CD4+T cells to influence Th17/Treg ratio. METHODS: Basal cytokines (anti-CD3, anti-CD28, TGF-ß) and 10 mM lactate was added into Naïve CD4+T cells basal medium for 3 days. After TCR stimulation, Naïve CD4+T converted to CD4+T. Flow cytometry was used to detect the proportion of Treg cells; ELISA was used to detect the activity of LDHA, LDHB and NADH and the amount of α -Ketoglutaric Acid (α-KG) and 2-Hydroxyglutaric Acid (2HG) after lactate entered the cells; Western Blot and RT-PCR were used to detect the protein and gene expression of Foxp3, RORγt, LDHA and LDHB. In the validation experiment, lactate uptake inhibitor AZD3965, LDHA inhibitor GSK2837808A and NADH conversion inhibitor Rotenone were added respectively to observe the differentiation ratio of Treg cells and confirm the key points of metabolism; the degradation of Treg cell transcription factor Foxp3 was interfered with ubiquitination inhibitors to observe whether it co-ubiquitinated with HIF-1α; the expression and activity of LDHA, LDHB and NADH in mitochondria and cytoplasm were detected to confirm cell localization. RESULTS: When basal cytokines (anti-CD3, anti-CD28, TGF-ß) stimulated, lactate was added to the culture medium, and CD4+T cells absorbed a large amount of lactate not only through MCT1 (monocarboxylic acid transporter), but also increased the expression of lactate dehydrogenase and accelerated the intracellular metabolism of lactate. LDHB in cytoplasm mainly catalyzed the dehydrogenation of lactate to pyruvate, accompanied by the transformation reaction between NAD+ and NADH. The latter further entered the mitochondria and participates in the tricarboxylic acid cycle metabolism. In addition, lactate could significantly increase the level of LDHA in mitochondria and promote the transformation of α-KG to 2HG, accompanied by the transformation of NADH to NAD+. These metabolic changes eventually led to an increase in the intracellular 2HG/α-KG ratio. Abnormal 2HG increased the proportion of Treg by inhibiting ATP5B-mediated phosphorylation of mTOR and the synthesis of HIF-1α, causing it not be enough to ubiquitinate and degrade with Foxp3. CONCLUSIONS: Lactate plays an important role in regulating the differentiation of Treg cells, inducing the expression and function of LDHA and promoting the transformation of α-KG to 2HG may be an important mechanism.


Assuntos
Ácido Láctico , NAD , NAD/metabolismo , NAD/farmacologia , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Linfócitos T Reguladores , Diferenciação Celular , Citocinas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fatores de Transcrição Forkhead/metabolismo
13.
Biomed Environ Sci ; 36(1): 10-23, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36650678

RESUMO

Objective: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. Methods: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. Results: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. Conclusion: Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.


Assuntos
Iodo , Estado Nutricional , Humanos , Criança , Estudos Transversais , Cloreto de Sódio na Dieta/análise , China , Água
14.
Curr Pharm Biotechnol ; 24(3): 391-400, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35658884

RESUMO

The market demand for recombinant therapeutic proteins (RTPs) has promoted the development of various protein expression host and bioprocessing technologies. Since mammalian cells have the unique advantage of being able to direct the correct folding of proteins and provide post-translational processing such as complex glycosylation, the RTPs produced by them currently account for approximately 80% of the approved marketed RTPs. Among them, Chinese hamster ovary (CHO) cells are currently the preferred host cells for the production of RTPs. Production of RTPs in CHO cells involves the synthesis, processing, transport, and secretion of proteins. The secretion process of proteins is one of the key steps, which greatly limits the yield and quality of RTPs. Here, we review the recombinant protein secretion process of CHO cells and its influencing factors, and further discuss the optimization strategy for recombinant protein secretion and expression in CHO cells.


Assuntos
Cricetulus , Cricetinae , Animais , Células CHO , Proteínas Recombinantes , Glicosilação
15.
J Control Release ; 353: 738-751, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36526019

RESUMO

In the absence of adequate treatment, effective bone regeneration remains a great challenge. Exploring hydrogels with properties of excellent bioactivity, stability, non-immunogenicity, and commercialization is an important step to develop hydrogel-based bone regeneration materials. In this study, we engineered a self-assembled chelating peptide hydrogel loaded with an osteogenic metal ion cluster extracted from the processed pyritum decoction, including Fe2+, Cu2+, Zn2+, Mn2+, Mg2+, and Ca2+ ions, named processed pyritum hydrogel (PPH). We demonstrated that as a reservoir of beneficial metal ion clusters in bone regeneration, PPH has been shown to regulate a variety of genes in the process of bone regeneration. These genes are mainly involved in extracellular matrix synthesis, cell adhesion and migration, cytokine expression, antimicrobial and inflammation. Therefore, PPH accelerated the progress of various bone healing stages, and shortened the bone healing cycle by 4 weeks. Our investigation outcomes showed that the engineered metal ion cluster hydrogel is a novel, simple, and commercializable bone-regenerating hydrogel with potential clinical use.


Assuntos
Regeneração Óssea , Hidrogéis , Hidrogéis/química , Osteogênese , Peptídeos , Osso e Ossos
16.
Biol Trace Elem Res ; 201(8): 3941-3950, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36376713

RESUMO

Arsenic is an environmental contaminant, and accumulating evidence has indicated that exposure to arsenic can cause various diseases, especially cardiotoxicity. Selenium (Se) exerts a vital role in the regulation of multiple physiological activities. Recently, several studies highlighted that Se treatment can effectively antagonize the toxic effects induced by arsenic. However, the exact underlying effect and mechanism of Se on Arsenic-induced cardiotoxicity has not been explored. In the current study, the arsenic trioxide (ATO)-triggered heart damage mice model was used to explore whether Se exerts protective roles in ATO-related cardiotoxicity and its potential mechanism. Our data showed that Se treatment significantly alleviated ATO-mediated cardiotoxicity evidenced by increased weight, decreased myocardial damage markers, and improved heart functions in mice. Furthermore, we demonstrated that Se remarkably inhibited ATO-mediated oxidative stress and inflammatory responses in heart tissues. Mechanistically, we showed that Se upregulated the levels of NAD+ in cardiomyocytes of the mice challenged by ATO, and this effect involved in the activation of the NAD+ biosynthesis through the salvage pathway. Collectively, our findings demonstrated that Se protected against ATO-mediated cardiotoxicity by antioxidant and anti-inflammatory effects via increasing the NAD+ pool in mice.


Assuntos
Arsênio , Selênio , Camundongos , Animais , Trióxido de Arsênio/farmacologia , Arsênio/toxicidade , Selênio/farmacologia , NAD/farmacologia , Cardiotoxicidade , Apoptose , Estresse Oxidativo , Suplementos Nutricionais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico
17.
World J Gastrointest Oncol ; 14(12): 2393-2403, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36568948

RESUMO

BACKGROUND: Increasing evidence have shown that regional lymph node metastasis is a critical prognostic factor in gastric cancer (GC). In addition, lymph node dissection is a key factor in determining the appropriate treatment for GC. However, the association between the number of positive lymph nodes and area of lymph node metastasis in GC remains unclear. AIM: To investigate the clinical value of regional lymph node sorting after radical gastrectomy for GC. METHODS: This study included 661 patients with GC who underwent radical gastrectomy at Tianjin Medical University General Hospital between January 2012 and June 2020. The patients were divided into regional sorting and non-sorting groups. Clinicopathological data were collected and retrospectively reviewed to determine the differences in the total number of lymph nodes and number of positive lymph nodes between the groups. Independent sample t-tests were used for intergroup comparisons. Continuous variables that did not conform to a normal distribution were expressed as median (interquartile range), and the Mann-Whitney U test was used for inter-group comparisons. RESULTS: There were no significant differences between the groups in terms of the surgical method, tumor site, immersion depth, and degree of differentiation. The total number of lymph nodes was significantly higher in the regional sorting group (n = 324) than in the non-sorting group (n = 337) (32.5 vs 21.2, P < 0.001). There was no significant difference in the number of positive lymph nodes between the two groups. A total of 212 patients with GC had lymph node metastasis in the lymph node regional sorting group, including 89 (41.98%) cases in the first dissection station and 123 (58.02 %) cases in the second dissection station. Binary and multivariate logistic regression results showed that the number of positive lymph nodes (P < 0.001) was an independent risk factor for lymph node metastases at the second dissection station. CONCLUSION: Regional sorting of lymph nodes after radical gastrectomy may increase the number of detected lymph nodes, thereby improving the reliability and accuracy of lymph node staging in clinical practice.

19.
Front Bioeng Biotechnol ; 10: 1054757, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420438

RESUMO

The soil's rhizosphere is a highly active place where the exchange of substances and information occurs among plants, soils, and microorganisms. The microorganisms involved are crucial to the activities of plant growth and development, metabolism, and reproduction. Fritillaria L. medicinal plants are unique Chinese medicinal ingredients, but the continuous cropping obstacles formed in the artificial planting process is severely harmful to the growth and development of these medicinal plants. In this review, we summarized the current species and distribution of Fritillaria L. in China, and analyzed the changes in microbial diversity (mainly among bacteria and fungi) in the rhizosphere of these plants under long-term continuous cropping. The fungi showed an increasing trend in the soil rhizosphere, resulting in the transition of the soil from the high-fertility "bacterial type" to the low-fertility "fungal type" as planting years increased. Furthermore, the interaction between Fritillaria L. medicinal plants and the rhizosphere microorganisms was reviewed, and promising applications for the rhizosphere microbiome in the cultivation of Fritillaria L. medicinal plants were suggested. It is expected that this review will facilitate the in-depth understanding of rhizosphere microorganisms in the growth, accumulation of active ingredients, and disease control of Fritillaria L.

20.
J Cell Mol Med ; 26(21): 5335-5359, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36251271

RESUMO

Cardiovascular disease (CVD) is highly prevalent in an ageing society. The increased incidence and mortality rates of CVD are global issues endangering human health. There is an urgent requirement for understanding the aetiology and pathogenesis of CVD and developing possible interventions for preventing CVD in ageing hearts. It is necessary to select appropriate models and treatment methods. The D-galactose-induced cardiac ageing model possesses the advantages of low mortality, short time and low cost and has been increasingly used in the study of cardiovascular diseases in recent years. Therefore, understanding the latest progress in D-galactose-induced cardiac ageing is valuable. This review highlights the recent progress and potential therapeutic interventions used in D-galactose-induced cardiac ageing in recent years by providing a comprehensive summary of D-galactose-induced cardiac ageing in vivo and in vitro. This review may serve as reference literature for future research on age-related heart diseases.


Assuntos
Doenças Cardiovasculares , Galactose , Humanos , Estresse Oxidativo , Envelhecimento/patologia , Coração
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