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1.
Fish Shellfish Immunol ; 133: 108519, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608811

RESUMO

The terminal differentiation of B cells into plasma cells is central to the generation of protective, long-lived humoral immune responses. In mammals, interleukin-2 (IL-2) has been shown to play a role in B cell proliferation and differentiation. However, it remains unclear whether fish IL-2 is involved in B cell proliferation and differentiation. To this end, we investigated the regulatory role of IL-2 in B cell proliferation and differentiation in large yellow croaker (Larimichthys crocea). We found that L. crocea IL-2 (LcIL-2) significantly increased IgM+ B cells proliferation both in vivo and in vitro and facilitated IgM+ B cells differentiation into plasma cells. Furthermore, LcIL-2 increased the production of specific antibodies after immunization with the Vibrio alginolyticus subunit vaccine, recombinant dihydrolipoamide dehydrogenase (rDLD); simultaneous administration of LcIL-2 and rDLD prior to challenge with Vibrio parahaemolyticus or V. alginolyticus significantly increased relative percent survival. Mechanistically, LcIL-2 promoted B cell proliferation and regulated B cell differentiation by triggering the JAK-STAT5 signaling pathway. Collectively, our results demonstrated that LcIL-2 improved B cell proliferation and specific antibody production via the conserved JAK-STAT5 signaling pathway in large yellow croaker, providing valuable insights into the mechanisms underlying the IL-2-mediated regulation of the humoral immune response in fish.

2.
Front Cardiovasc Med ; 9: 973129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451919

RESUMO

Aim of the review: To assess the risk of hypovolemia for sodium-glucose cotransporter-2 (SGLT2) inhibitors treatment. Method: A systematic literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus from inception up to 4 October 2022, Data for study characteristics and outcomes of interest were extracted from each eligible study. Risk ratios (RRs) with a 95% confidence interval (CI) for hypovolemia were calculated using a random-effect model. Results: A total of 57 studies (n = 68,622) were included in our meta-analysis, with a result of 1,972 hypovolemia incidents (1,142 in the SGLT2 inhibitors group and 830 in the control group). The pooled RR was 1.12 (95% CI: 1.02-1.22). It is evident that receiving SGLT2 inhibitors increased the risk of hypovolemia. When stratified by category of SGLT2 inhibitors the result was consistent; when the subgroup was analyzed by age, the pooled RR was 1.07 (95% CI: 0.94-1.23) in patients aged ≥65 years and 1.14 (95% CI: 1.02-1.28) in those aged <65 years. When comparing the baseline estimated glomerular filtration rate (eGFR) of less than or equal to 60 mL/min/1.73 m2 with a baseline eGFR greater than 60 mL/min/1.73 m2, the pooled RR was 1.21, (95% CI: 1.00-1.46) and 1.08, (95%CI: 0.98-1.20), respectively. Conclusion: Our meta-analysis has demonstrated that SGLT2 inhibitors increased the risk of hypovolemia in patients with Type 2 Diabetes Mellitus (T2DM). It is necessary to pay attention to the risk of hypovolemia associated with SGLT2 inhibitors, especially in older individuals and those with moderate renal impairment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020156254].

3.
Artigo em Inglês | MEDLINE | ID: mdl-36564684

RESUMO

Atrazine (ATZ) is the second most commonly used herbicide worldwide, resulting in the pollution of water bodies and affecting the economic benefits of aquaculture. ATZ is known to cause liver damage in the common carp, Cyprinus carpio L., one of the most widely cultivated fish in China, but the underlying mechanisms are poorly understood. In this study, juvenile common carp Cyprinus carpio L. were exposed to three different environmental levels (0.4, 0.8, and 1.2 µg/L) of ATZ for 12 weeks and changes in the liver transcriptomes between the high-dose group and the control group were analyzed. The data showed that different levels of ATZ exposure caused hepatotoxicity in juvenile carp, shown by biochemical parameters and histopathological changes. Comparative transcriptomics showed that high-dose ATZ exposure led to alterations in the expression of various lipid metabolism-related gene changes, including genes associated with metabolic pathways, fatty acid metabolism, and fatty acid elongation. Furthermore, a connection network analysis of the top 100 differentially expressed genes (DEGs) showed a variety of associations between high-dose ATZ-induced liver damage and the principal DEGs, indicating the complexity of hepatotoxicity induced by ATZ. In conclusion, the molecular mechanisms underlying ATZ-triggered hepatotoxicity in juvenile carp are primarily related to impaired lipid metabolism.

4.
Glob Heart ; 17(1): 73, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382161

RESUMO

Background: There is no information about the clinical significance of the albumin-bilirubin (ALBI) score in patients with hypertrophic cardiomyopathy (HCM). Objective: We retrospectively performed clinical evaluations in 462 patients with HCM to estimate whether the ALBI score could be a new tool to predict mortality in HCM. Methods and Results: During a median follow-up of 4.7 years, HCM-related death occurred in 52 (11.3%) patients. Overall, there was a significant positive association between ALBI score and HCM-related death (adjusted hazard ratio [HR]: 1.79 per one standard deviation [SD] increment, 95% confidence interval [CI]: 1.36-2.35). When the score was assessed as tertiles, the adjusted HRs of HCM-related death were 1.30 (95% CI: 0.42-3.99) for the tertile 2 and 4.43 (95% CI: 1.65-11.89) for the tertile 3, compared with the tertile 1. Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Meanwhile, time-dependent ROC analysis showed ALBI score could discriminate HCM-related death at various time points (AUC ranges: 0.725-0.850). Furthermore, exploratory analysis indicated the dynamic changes of ALBI score also could predict HCM-related death. Finally, multiple linear regression analysis suggested some pathogenetic pathways associated with HCM-related adverse outcomes significantly correlated with ALBI score, and the pathways included inflammation, myocardial injury, nutritional status and some clinical characteristics, but not abnormal cardiac structure and function itself. Conclusions: Higher ALBI score is a strong independent predictor of HCM-related death in patients with HCM.


Assuntos
Bilirrubina , Cardiomiopatia Hipertrófica , Humanos , Estudos Retrospectivos , Prognóstico , Cardiomiopatia Hipertrófica/diagnóstico , Albuminas
5.
Front Psychol ; 13: 1000153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329742

RESUMO

In this study, we investigate how the influence of dual innovation affects the productivity of multinational enterprises (MNEs). Because of the rise of the knowledge-based economy, the capacity of multinational corporations (MNCs) to innovate technologically has become an increasingly important component in determining the extent to which they can compete in the global market. Models of Duality Innovation and Multinational Enterprise Performance with a Measurement of Corporate Risks from 2000 to 2015 were developed using corporate finance literature and data. The models show positive relationships between duality innovations and multinational enterprise performance. Furthermore, there has been an increasing level of corporate risks over the years when measured by both the duality innovation and multinational enterprise performance metrics. This article discusses the findings of this research project. It explains how they can help understand international enterprise performance while also explaining how to determine a potential risk profile for an individual or multiple companies. This knowledge is valuable because it helps us understand why some corporations succeed while others fail.

6.
J Phys Chem B ; 126(44): 9016-9025, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36318969

RESUMO

Ion adsorption and hydrogen bond (HB) network reconstruction in electric double layer (EDL) have a profound impact on the interface properties. The microstructure in the bulk phase of 1.00-21.30 wt.% Na2SO3 aqueous solutions are investigated by X-ray scattering, confocal Raman spectroscopy, and classical molecular dynamics. The electronic properties of SO32- adsorption and the geometric structure of the HB network in the EDL at the titanium TiO2(101) surface are studied by density functional theory (DFT) and classical molecular dynamics. The SO32- strongly weakens the fully hydrogen-bonded water (FHW) and transforms it into partial hydrogen-bonded water (PHW). The HB transformation index (HBTI = PHW/FHW) shows a linear relationship with the mass fraction of Na2SO3. The TiOb-parallel adsorption configuration of SO32- enhances the ionicity of the Ob-Ti6 bond, resulting in the formation of oxygen vacancies at the titanium passive film surface. Besides, SO32- and Na+ are enriched and thermodynamic supersaturated in the inner Helmholtz layer (IHL), and the ions are diluted in the outer Helmholtz layer (OHL). The diffusion coefficient of SO32- and water molecules in EDL decreases seriously, which is easy to causes salt scaling on the surface of titanium passive film. This work provides evidence for the destruction of titanium passive film by SO32-.

7.
Peptides ; 160: 170917, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36442698

RESUMO

Myocardial infarction is a predominant cause of cardiovascular diseases with high incidence and death rate worldwide. Although growing evidence has suggested that IMD has significant protective influences on the cardiovascular system, the molecular regulatory mechanism of IMD in hypoxia-induced injury caused by myocardial infarction is urgent to be elucidated. In the present study, we found hypoxia led to a noteworthy enhancement in IMD expression and IMD alleviated hypoxia-induced myocardial injury of NRCMs. Furthermore, IMD was proved to inhibit hypoxia-induced injury by regulating MALAT1. Our findings suggested MALAT1 positively regulated the mRNA and protein expression level of ULK1 and hypoxia induced autophagy of NRCMs. MALAT1 stimulated autophagy to block hypoxia-induced cell injury in NRCMs via upregulation of ULK1 expression. Autophagy suppression abolished the protective capability of IMD overexpression against hypoxia-induced myocardial injury in NRCMs. In a word, our study shed light on the central mechanism of IMD in preventing hypoxia-induced injury caused by myocardial infarction. We confirmed IMD induced autophagy and attenuated hypoxia-induced injury in cardiomyocytes via MALAT1/ULK1, which may contribute to designing effective therapeutic approaches of myocardial infarction.

8.
Poult Sci ; 102(1): 102251, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36435164

RESUMO

Aluminum (Al) is a ubiquitous environmental pollutant representing a significant global health hazard to human and animal health, including chicks. Al toxicity causes oxidative stress, leading to tissue injury, and consequently causes various diseases. NRF2 signaling is vital for protecting cells against oxidative stress. Nuclear xenobiotic receptors are activated by exogenous toxins, thereby inducing the transcription of cytochrome P450 enzyme systems (CYP450s) isoforms involved in xenobiotic metabolism and transport. However, little is known about Al-induced oxidative stress, nuclear xenobiotic receptors and fibrosis in chicks and the mechanisms involved. In this study, male chicks were treated with 0 mg/kg and 500 mg/kg Al2(SO4)3 to evaluate the mechanisms for Al-induced immunotoxicity. Histopathology revealed pathological injury, fibrin aggregation, disruption of the Nuclear Xenobiotic Receptors, and alteration of CYP450s homeostasis in Al-treated chicks due to oxidative stress. Notably, regulation of the NRF2 pathway and CYP450s and fibrosis-related genes was found to play a vital role in inhibiting immunotoxicity. This study provides new insights regarding the mechanisms of Al-induced immunotoxicity, including activation of the nuclear xenobiotic receptors, triggering oxidative stress, and altering the homeostasis of CYP450s in chicks. Further, it provides a theoretical basis for controlling Al exposure and highlights the importance of further studying its mechanisms to provide additional information for formulating preventive measures.

9.
Front Endocrinol (Lausanne) ; 13: 960835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237185

RESUMO

Objective: To investigate the effects and mechanism of hyperinsulinemia on the metabolic switch to ß-hydroxybutyrate (BHB) absorption and utilization under a starvation or hypoxic environment in proximal tubular epithelial cells. Methods: A high-fat diet-induced hyperinsulinemia model in ZDF rats was used to test the expression of key enzymes/proteins of ketone body metabolism in the kidney. Notably, 12-week-old renal tubule SMCT1 specific knockout mice (SMCT1 flox/floxCre+) and control mice (SMCT1 flox/floxCre-) were used to confirm the roles of SMCT1 in kidney protection under starvation. The changes of key enzymes/proteins of energy metabolism, mitochondrial function, and albumin endocytosis in HK2 cells under low glucose/hypoxic environments with or without 50 ng/mL insulin were studied. Silent information regulation 2 homolog 3 (SIRT3) was overexpressed to evaluate the effect of hyperinsulinemia on the metabolic switch to BHB absorption and utilization through the SIRT3/SMCT1 pathway in HK2 cells. Results: In ZDF rats, the expression of HMGCS2 increased, the SMCT1 expression decreased, while SCOT remained unchanged. In renal tubule SMCT1 gene-specific knockout mice, starvation for 48 h induced an increase in the levels of urine retinol-binding protein, N-acetyl-ß-glucosaminidase, and transferrin, which reflected tubular damages. In HK2 cells under an environment of starvation and hypoxia, the levels of key enzymes related to fatty acid oxidation and ketone body metabolism were increased, whereas glucose glycolysis did not change. The addition of 2 mmol/l BHB improved ATP production, mitochondrial biosynthesis, and endocytic albumin function, while cell apoptosis was reduced in HK2 cells. The addition of 50 ng/ml insulin resulted in the decreased expression of SMCT1 along with an impaired mitochondrial function, decreased ATP production, and increased apoptosis. The overexpression of SIRT3 or SMCT1 reversed these alterations induced by a high level of insulin both in low-glucose and hypoxic environments. Conclusions: The increased absorption and utilization of BHB is part of the metabolic flexibility of renal tubular epithelial cells under starvation and hypoxic environments, which exhibits a protective effect on renal tubular epithelial cells by improving the mitochondrial function and cell survival. Moreover, hyperinsulinemia inhibits the absorption of BHB through the inhibition of the SIRT3/SMCT1 pathway.


Assuntos
Hiperinsulinismo , Sirtuína 3 , Inanição , Ácido 3-Hidroxibutírico , Trifosfato de Adenosina , Albuminas/metabolismo , Animais , Células Epiteliais/metabolismo , Glucose/metabolismo , Hexosaminidases/metabolismo , Insulina/metabolismo , Corpos Cetônicos , Camundongos , Camundongos Knockout , Ratos , Proteínas de Ligação ao Retinol , Sirtuína 3/metabolismo , Transferrinas
10.
Nat Commun ; 13(1): 6421, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307431

RESUMO

Many plants associate with arbuscular mycorrhizal fungi for nutrient acquisition, while legumes also associate with nitrogen-fixing rhizobial bacteria. Both associations rely on symbiosis signaling and here we show that cereals can perceive lipochitooligosaccharides (LCOs) for activation of symbiosis signaling, surprisingly including Nod factors produced by nitrogen-fixing bacteria. However, legumes show stringent perception of specifically decorated LCOs, that is absent in cereals. LCO perception in plants is activated by nutrient starvation, through transcriptional regulation of Nodulation Signaling Pathway (NSP)1 and NSP2. These transcription factors induce expression of an LCO receptor and act through the control of strigolactone biosynthesis and the karrikin-like receptor DWARF14-LIKE. We conclude that LCO production and perception is coordinately regulated by nutrient starvation to promote engagement with mycorrhizal fungi. Our work has implications for the use of both mycorrhizal and rhizobial associations for sustainable productivity in cereals.


Assuntos
Medicago truncatula , Micorrizas , Rhizobium , Medicago truncatula/microbiologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Micorrizas/fisiologia , Simbiose , Rhizobium/metabolismo , Nutrientes
11.
Biochem Pharmacol ; 205: 115294, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36241099

RESUMO

Combination therapy can enhance therapeutic effect by activation of multiple downstream pathways. The present study was aimed to investigate a novel strategy to successfully inhibit the EGFR pathway in EGFR wild and mutated types lung cancer by combination method. Topotecan (TPT) and crizotinib (CRI) were used to evaluate the effect on EGFR-wild, primary and secondary mutant non-small cell lung cancer (NSCLC) cell lines (H1299, HCC827 and H1975 cells). The combination group significantly inhibited the lung cancer growth with combination index (CI) < 1, and they synergistically induced the cell apoptosis by disrupting the balance of Bax and Bcl-xL, loss of mitochondrial membrane potential (MMP), and accumulation of reactive oxygen species (ROS). In addition, EGFR downstream signaling pathways including AKT, ERK, JNK, and p38 MAPK were regulated when treated with the combination regimen. Meanwhile, a nano-liposomes co-loaded CRI and TPT was prepared and exhibited strong cytotoxicity to the lung cancer cells especially H1299 and H1975 cells. The animal study confirmed the synergy between TPT and CRI from the results that they remarkable repressed the tumor growth with the inhibition rate of 81.32 %. The nano-liposomes of TPT and CRI achieved an optimal curative effect (71.52 % of inhibition rate) at 2 mg/kg. Moreover, the synergistic mechanism of the combination was consistent with the in vitro cell experiment by regulating EGFR signaling pathways. Collectively, we proposed a preclinical rationale and potential formulation for the use of a combination therapy consisting of the topoisomerase inhibitor TPT and the ALK-TKI CRI for treatment of lung cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Neoplasias Pulmonares/metabolismo , Crizotinibe/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Espécies Reativas de Oxigênio , Receptores ErbB/metabolismo , Inibidores da Topoisomerase/uso terapêutico , Quinazolinas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína X Associada a bcl-2 , Topotecan/farmacologia , Topotecan/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral , Proteínas Quinases p38 Ativadas por Mitógeno , Resistencia a Medicamentos Antineoplásicos
12.
RSC Adv ; 12(37): 24252-24259, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36128528

RESUMO

We design and synthesize a novel 1,8-naphthalimide-based fluorescent probe MNP that features the dual capabilities of tracking lysosomes in living HeLa cells and sensitively detecting Fe3+ ions in aqueous solution. The MNP is obtained by modifying the morpholine group with a lysosomal targeting function and the piperazine group with an Fe3+ ion recognition function on the 1,8-naphthalimide matrix. In the presence of Fe3+ ions, the MNP acts as a recognition ligand to coordinate with the central Fe3+ ion, and the protonated [MNPH]+ is eventually generated, in which significant fluorescence enhancements are observed due to the intramolecular photo-induced electron transfer (PET) process being blocked. The limit of detection of Fe3+ ions is as low as 65.2 nM. A cell imaging experiment shows that the MNP has low cytotoxicity and excellent lysosomal targeting ability. Therefore, the MNP offers a promising tool for lysosomal tracking and relevant life process research.

13.
Cancer Manag Res ; 14: 2313-2321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958950

RESUMO

Objective: To investigate the significance of fibrinogen (Fib) in combination with the neutrophil to lymphocyte ratio (NLR) in predicting the prognosis of patients with gastric cancer. Methods: The preoperative peripheral blood-related indicators of 281 gastric cancer patients were reviewed retrospectively, and the differences in relationship indicators between the survival and death groups were compared and analyzed. The COX regression analysis and Kaplan-Meier Curve (K-M) were used to assess the prognostic significance of Fib combined with NLR in patients with gastric cancer. Results: ① The difference between the survival and death groups of patients with gastric cancer was statistically significant in the high and low Fib and NLR levels (X 2=6.868 and 17.051, respectively, all P <0.01).② The correlation between Fib and NLR was remarkable (r=0.266, P=0.000).③ The F-NLR classifications showed statistically significant difference between the survival and death groups for gastric cancer patients (X 2=20.200, P=0.000).④ Except for Fib and the middle/low classification of F-NLR, which was P<0.05, and the rest were all P<0.01. There was a substantial statistical difference between F-NLR classifications, Fib and NLR.⑤ F-NLR was found to be a predictive factor of death in patients with gastric cancer in COX regression analysis (P=0.000).⑥Patients with F-NLR scores of "0", "1" and "2" had 5-year survival rates of 92.6%, 64.0% and 47.2%, respectively, and 3-year survival rates of 92.6%, 74.3% and 51.9%, respectively (all P=0.000). Conclusion: The combination of Fib and NLR (F-NLR) improves the accuracy of prognosis in patients with gastric cancer.

14.
Insects ; 13(8)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36005357

RESUMO

Manipulator modificaputis Vrsanský and Bechly, 2015 (Manipulatoridae, Corydioidea) is a purported predatory cockroach from Cretaceous Myanmar amber, based on a single male. It is distinctive by the nimble head, elongate pronotum and legs, and particularly by the extraordinarily long maxillary palpi. In the present study, we redescribe Manipulator modificaputis based on six new fossils including males and females, and comment on the original description. The closely related Manipulatoides obscura gen. & sp. nov. is proposed on the basis of five fossils, including males and females. It differs from Manipulator in weaker spination of the legs, including the type-C forefemoral spination instead of the type-A of Manipulator. Some undetermined adults and nymphs are also described. We discuss the ethology of Manipulatoridae and speculate that they might feed on flowers. They are unlikely to be specialized predators since they lack necessary weaponry for capturing prey; in contrast, their unique morphotype appears to be suitable for efficient foraging and locomotion amid flowering twigs. The possibility of being kleptoparasites of the spider-web is also discussed. In addition, regenerated four-segmented tarsi are found from the new species.

15.
Cell Rep ; 40(7): 111215, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35977519

RESUMO

Interferons (IFNs) are essential in antiviral defense, antitumor effects, and immunoregulatory activities. Although methionine oxidation is associated with various physiological and pathophysiological processes in plants, animals, and humans, its role in immunity remains unclear. We find that the redox cycling of signal transducer and activator of transcription 2 (STAT2) is an intrinsic cellular biological process, and that impairment of the redox status contributes to STAT2 methionine oxidation, inhibiting its activation. IFN protects STAT2 from methionine oxidation through the recruitment of methionine sulfoxide reductase MSRB2, whose enzymatic activity is enhanced by N-acetyltransferase 9 (NAT9), a chaperone of STAT2 defined in this study, upon IFN treatment. Consequently, loss of Nat9 renders mice more susceptible to viral infection. Our study highlights the key function of methionine oxidation in immunity, which provides evidence for the decline of immune function by aging and may provide insights into the clinical applications of IFN in immune-related diseases.


Assuntos
Imunidade Inata , Fator de Transcrição STAT2/metabolismo , Transdução de Sinais , Animais , Homeostase , Humanos , Metionina , Camundongos , Oxirredução , Fator de Transcrição STAT1/metabolismo
16.
J Nutr Biochem ; 109: 109121, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35940511

RESUMO

Fasting/feeding cycles regulate clock-lipid-bile acid (BA) metabolic homeostasis, and gut microbiota also participates in connecting circadian rhythms with BA metabolism. To investigate the cyclical nature of microbial-metabolism-host interactions, sixty male C57BL/6 mice were randomized into three feeding regimens with a chow diet: 24 h ad libitum (AC), 12 h nighttime feeding (NC) or 12 h daytime feeding (DC). Five weeks later, the mice were sacrificed at six-hour intervals over 24 hours. Daytime feeding abolished hepatic rhythmic expressions of Per1, Cry1/2 and Rev-erbα or changed the acrophase of Clock, Bmal1 and Per2, also the rhythmic expression of genes Hsl, Fas, Acc, Srebp-1c in lipid homeostasis and Cyp7a1, Cyp7b1, Cyp8b1, Lrh-1 and Shp in bile acid metabolism compared with their ad libitum and dark-fed companions. Furthermore, daytime feeding upregulated the levels of fecal primary BA, secondary BA and unconjugated BA at ZT0 and decreased their levels at ZT12. Meanwhile, daytime feeding altered the diversity of gut microbiota and microbiota compositions, with obviously higher abundance of Firmicutes and F/B ratio, and significantly lower abundance of Verrucomicrobia, as well as altered fluctuations of Akkermansia, Lactobacillus and Parabacteroides. In conclusion, shifting food intake to the rest phase caused a desynchronization in the liver between circadian rhythm and metabolism, as well as abnormal circadian variations in fecal BA profiles and gut microbiota.


Assuntos
Ácidos e Sais Biliares , Microbioma Gastrointestinal , Fatores de Transcrição ARNTL/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Ritmo Circadiano/genética , Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Esteroide 12-alfa-Hidroxilase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
17.
BMC Cardiovasc Disord ; 22(1): 357, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931987

RESUMO

BACKGROUND: There is limited evidence regarding the relationship between lipid parameters and vascular mechanical characteristics in the normotensive population without diabetes mellitus. The aim of this study was to identify an association between lipid parameters and changes in vascular mechanical characteristics between men and women, and in women before and after menopause. METHODS: Six hundred-seventy patients who underwent vascular functional testing and who fulfilled the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants were from the Qinghai-Tibet Plateau (Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China; mean altitude: 3860 m). Trained clinical physicians assessed brachial-ankle pulse wave velocity (Ba-PWV) and augmentation index adjusted to a 75-beats-per-minute heart rate (AIx@75). To investigate the relationship between lipid parameters and vascular mechanical characteristics in different sexes and menstrual stages, partial correlation analysis and multiple linear regression were used. RESULTS: The 670 participants comprised 445 women (103 post-menopausal). Mean Ba-PWV and AIx@75 were 1315.56 ± 243.41 cm/s and 25.07% ± 15.84%, respectively. Men had greater Ba-PWV values compared with women (1341.61 ± 244.28 vs 1302.39 ± 242.17 cm/s, respectively; P < 0.05), while AIx@75 values were higher in women compared with men (27.83% ± 15.85% vs 19.64% ± 14.40%, respectively; p < 0.001). In the partial correlation analysis adjusted for age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (HDL-C) were associated with Ba-PWV in both men and women (p < 0.05); however, the magnitude was larger in men. Statistical significance was not seen for AIx@75 among both men and women. Multiple linear regression analysis revealed that TC (ß = 0.165, p = 0.024) and non-HDL-C (ß = 0.151, p = 0.042) remained independent predictors of change in Ba-PWV in men after adjusting for age, mean arterial pressure, waist circumference, hemoglobin, platelet count, fasting blood glucose, estimated glomerular filtration rate, and uric acid. After adjusting for traditional cardiovascular risk factors, pre-menopausal women had a similar association to that of men between LDL-C (ß = 0.126, p = 0.030), non-HDL-C (ß = 0.144, p = 0.013), TC/HDL-C (ß = 0.162, p = 0.005), LDL-C/HDL-C (ß = 0.142, p = 0.013) and Ba-PWV; however, post-menopausal women had no association between the lipid parameters and vascular function. CONCLUSIONS: Overall, TC and non-HDL-C were independent associated factors for vascular compliance alterations evaluated through Ba-PWV in normotensive men. In pre-menopausal women, LDL-C, non-HDL-C, TC/HDL-C and LDL-C/HDL-C were independent associated factors for vascular compliance alterations. After controlling for traditional risk factors, lipid profiles were not associated with these metrics for AIx@75, which can measure the amplification of reflex flow, because of the high number of confounding factors that do not genuinely reflect changes in vascular characteristics. Lipid factors did not appear to be linked to vascular function in post-menopausal women.


Assuntos
Diabetes Mellitus , Rigidez Vascular , Índice Tornozelo-Braço , Colesterol , HDL-Colesterol , LDL-Colesterol , Estudos Transversais , Feminino , Humanos , Lipoproteínas , Masculino , Análise de Onda de Pulso , Fatores de Risco , Tibet , Rigidez Vascular/fisiologia
18.
FEBS J ; 289(23): 7545-7560, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35792704

RESUMO

Lipid-laden macrophages are considered as the main source of foam cells in atherosclerosis; however, the mechanism for macrophage foam cell formation remains unknown. Here, we explore the mechanism behind foam cell formation to potentially identify a novel treatment for atherosclerosis. Our data demonstrated that leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) increased in the atherosclerotic plaques of LDLR-/- mice fed with a Western diet. LRPPRC was also upregulated in mice peritoneal macrophages and RAW 264.7 cells treated with oxidative low density lipoprotein, whereas knockdown of LRPPRC by transfecting with small interfering (Si)-LRPPRC in RAW 264.7 cells decreased foam cell formation. Furthermore, Si-LRPPRC promoted autophagy and increased the expression of cholesterol efflux protein ATP-binding cassette transporter A1 in RAW 264.7 cells. Moreover, intervention with MHY1485 in RAW 264.7 cells revealed that autophagy was inhibited by LRPPRC via the Akt-mechanistic target of rapamycin pathway. Taken together, we confirm for the first time that LRPPRC is increased within the atherosclerotic plaques of mice and enhances the process of foam cell formation. The knockdown of LRPPRC inhibited foam cell formation by activating macrophage autophagy. Our findings indicate that the regulation of macrophage LRPPRC expression may be a novel strategy for ameliorating atherosclerosis.

19.
J Clin Hypertens (Greenwich) ; 24(8): 1035-1043, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35791888

RESUMO

White-coat hypertension (WCH) is associated with increased cardiovascular risks. To investigate the relationship between WCH and left ventricular hypertrophy (LVH), the authors recruited 706 participants who underwent anthropometric measurements, blood laboratory analysis, 24h ambulatory blood pressure monitoring (ABPM), and echocardiography. The authors defined WCH as elevated office BP but normal ABPM over 24h, daytime, and nighttime periods. The authors compared the proportion of LVH between the true normotension (NT) and the WCH population, and further assessed the associations between BP indexes and LVH in the two groups, respectively. The proportion of LVH was significantly higher in the WCH group than in NT participants (19.70% vs. 13.12%, P = .036). In the NT group, 24h SBP, 24h PP, daytime SBP, daytime PP and SD of nighttime SBP were associated with LVH after adjustment for demographic and blood biochemical data (all P < .05). In the WCH population, LVH was associated with 24h SBP, nighttime SBP, nighttime MAP, and office SBP after adjustment (all P < .05). However, on forward logistic regression analysis with all the BP indexes listed above, only 24h SBP (OR = 1.057, 1.017-1.098, P < .001) in the NT group, and nighttime MAP (OR = 1.114, 1.005-1.235, P < .05) and office SBP (OR = 1.067, 1.019-1.117, P < .001) in the WCH group were still significantly associated with LVH. Our study suggests that the proportion of LVH is higher in WCH patients than in the NT population. Furthermore, elevated nighttime MAP and office SBP may play critical roles in the development of LVH in the WCH population.


Assuntos
Hipertensão , Hipertensão do Jaleco Branco , Pressão Arterial , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertensão do Jaleco Branco/complicações , Hipertensão do Jaleco Branco/diagnóstico , Hipertensão do Jaleco Branco/epidemiologia
20.
Chem Biol Interact ; 363: 110009, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35697133

RESUMO

Fumonisins (FBs) are widespread Fusarium toxins commonly found in corn. This study aimed to establish the mechanism of oxidative stress via the Nrf2 signaling pathway associated with FB1-induced toxicity in mice testis. Male mice were fed with 5 mg/kg FB1 diet for 21 or 42 days, the expression of inflammatory related genes, apoptosis related genes and Nrf2 pathway genes were detected by RT-qPCR, Western blot and immunohistochemical. Furthermore, Sertoli cell was treatment with FB1. Cell viability was measured by CCK8 assay, ROS level and apoptosis related genes were detected by immunofluorescence staining. The results showed that FB1 had toxic effects on testis, which could increase the ROS level of Sertoli cells, affect the Keap1-Nrf2 pathway related factors, destroy the oxidative balance of testis, lead to the occurrence of inflammation and the initiation of apoptosis, and finally destroy the testicular tissue structure and affect the formation of sperm.


Assuntos
Fumonisinas , Animais , Apoptose , Fumonisinas/toxicidade , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sementes/metabolismo , Transdução de Sinais , Espermatozoides/metabolismo , Testículo/metabolismo
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