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The effects of high doses of folic acid (FA) during pregnancy on anxiety- and depression-like behaviors in adolescent offspring mice were determined and the potential underlying mechanisms were elucidated. Pregnant C57BL/6 mice were randomly assigned to Control (2 mg/kg in feed), high FA (20 mg/kg in feed), and ultrahigh FA (40 mg/kg in feed) groups. The physiological development of the offspring, their preweaning neurobehavioral milestones, and adolescent behaviors indicative of anxiety and depression were assessed. High doses of FA during pregnancy delayed key developmental milestones such as pinna detachment, fur appearance, and incisor eruption. Furthermore, it triggered anxiety-like behavior in the passive avoidance test and led to depression-like behavior, as reflected by reduced movement distance in the center zone and decreased shuttling frequency in the light-dark box test and open field test. Additionally, brain tissues of the offspring exhibited increased expression of the microglia marker ionized calcium-binding adaptor molecule 1 and the Nod-like receptor protein 3 inflammasome. These findings suggest that high doses of FA during pregnancy may impair physiological development and increase the susceptibility of the offspring to anxiety- and depression-like behaviors, potentially mediated through the induction of low-grade inflammation in the brain.
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BACKGROUND: Despite extensive research on muscle loss in people living with HIV (PLWH), the prevalence and contributing factors specifically among middle-aged men remain unclear. This study aimed to determine the prevalence of low muscle mass within this demographic and to identify associated factors. METHODS: A total of 378 men living with HIV were enrolled in the study. They were classified into low muscle mass group if they displayed a skeletal muscle index (SMI) <7.00 kg/m2 or fell within the lowest quintile of SMI based on the criteria established by the Asian Working Group for Sarcopenia 2019. RESULTS: Out of the 378 men living with HIV enrolled, 351 had normal muscle mass, while 27 (7.1%) had low muscle mass. Antiretroviral drugs Zidovudine (AZT) (OR = 0.246, P = 0.022) and higher serum albumin levels (OR = 0.899, P = 0.026) were found to be protective factors against low muscle mass according to quintile grouping. Strong positive associations between SMI and body mass index (BMI), nutritional risk index (NRI), oedema index and fat-free mass index (FFMI) (R > 0.5, P < 0.001) were observed. In addition, both BMI (sensitivity = 0.741, specificity = 0.906) and NRI (sensitivity = 0.963, specificity = 0.601) had high sensitivity and specificity in diagnosing low muscle mass, with critical values of 19.85 and 114.177 for BMI and NRI, respectively. The oedema index was the most effective measure of body composition in detecting abnormal fluid retention with high sensitivity (92.6%) and moderate specificity (71.8%) in identifying individuals with low muscle mass. Notably, PLWH with low muscle mass participants had a significantly higher prevalence (92.6%) of a high oedema index compared with those with normal muscle mass (28.2%). This observation indicates that individuals with HIV who experience reduced muscle mass is commonly accompanied with abnormal fluid retention within the body. CONCLUSIONS: Antiretroviral medication types, specifically Zidovudine, BMI and NRI can be independent risk factors for low muscle mass in men with HIV. These factors, along with BMI, could be used conveniently to predict low muscle mass. Furthermore, the association between the oedema index and muscle mass suggests that observing signs of oedema may indicate a risk of low muscle mass in PLWH.
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Infecções por HIV , Músculo Esquelético , Humanos , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Músculo Esquelético/patologia , Pessoa de Meia-Idade , Índice de Massa Corporal , Adulto , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Composição Corporal , Fatores de RiscoRESUMO
OBJECTIVE: To investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH). METHODS: This research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels. RESULTS: The result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P < 0.001) or protease inhibitors/integrase strand transfer inhibitors (PI/INSTI) (OR = 5.167, P < 0.001) were significantly linked to hypertriglyceridemia. Cross-sectional and longitudinal analyses from 2021 to 2023 emphasized that changes in BMI interact with antiretroviral treatment regimens to affect TG levels in PLWH (Pinteraction < 0.05). Especially in the AZT-based drug regimen, the correlation between BMI and TG is more prominent. CONCLUSION: The interaction between ART regimens and BMI influences TG levels in PLWH, indicating that weight management is crucial for reducing the risk of hypertriglyceridemia in this population.
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Índice de Massa Corporal , Infecções por HIV , Triglicerídeos , Zidovudina , Humanos , Masculino , Triglicerídeos/sangue , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/sangue , Estudos Longitudinais , Adulto , Pessoa de Meia-Idade , Zidovudina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Relação Cintura-Quadril , Hipertrigliceridemia/sangue , Terapia Antirretroviral de Alta AtividadeRESUMO
The aim of the present study was to investigate the role of endoplasmic reticulum (ER) stress in bisphenol A (BPA) - induced hepatic lipid accumulation as well as the protective effects of Sulforaphane (SFN) in this process. Human hepatocyte cell line (LO2) and C57/BL6J mice were used to examine BPA-triggered hepatic lipid accumulation and the underlying mechanism. Hepatic lipid accumulation, triglycerides (TGs) levels, the expression levels of lipogenesis-related genes and proteins in the ER stress pathway were measured. It was revealed that BPA treatment increased the number of lipid droplets, the levels of TG and mRNAs expression of lipogenesis-related genes, and activated the ER stress pathway. These changes were inhibited by an ER stress inhibitor 4-phenylbutyric acid. SFN treatment abrogated BPA-altered hepatic lipid metabolism and ameliorated BPA-induced ER stress-related markers. Together, these findings suggested that BPA activated ER stress to promote hepatic lipid accumulation, and that SFN reversed those BPA effects by alleviating ER stress.
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Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Fígado/metabolismo , Metabolismo dos Lipídeos , Estresse do Retículo Endoplasmático , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lipídeos/farmacologiaRESUMO
Correction for 'The synergic effect between Mo species and acid sites in Mo/HMCM-22 catalysts for methane aromatization' by Ding Ma et al., Phys. Chem. Chem. Phys., 2005, 7, 3102-3109, https://doi.org/10.1039/B502794B.
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Many studies have shown that there were similarity between tumorigenesis and gametogenesis. Our previous work found that cancer-testis (CT) genes could serve as a novel source of candidate of cancer. Here, by analysing The Cancer Genome Atlas (TCGA) database, we characterized a CT gene, SPANXC, which is expressed only in testis. The SPANXC was reactivated in lung adenocarcinoma (LUAD) tissues. And the expression of SPANXC was associated with prognosis of LUAD. We also found that the activation of SPANXC was due to the promoter hypomethylation of SPANXC. Moreover, SPANXC could modulate cell metastasis both in vitro and in vivo. Mechanistically, we found that SPANXC could bind to ROCK1, a metastasis-related gene, and thus SPANXC may regulate cell metastasis partly through interaction with ROCK1 in LUAD. Together, our results demonstrated that the CT expression pattern of SPANXC served as a crucial role in metastasis of LUAD. And these data further corroborated the resemblance between processes of germ cell development and tumorigenesis, including migration and invasion.
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Adenocarcinoma de Pulmão/secundário , Biomarcadores Tumorais/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Prognóstico , Regiões Promotoras Genéticas , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Associadas a rhoRESUMO
Cancer-testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis-specific expressed protein-coding genes and 863 testis-specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein-coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10-13 ) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = -0.28, P = 1.20 × 10-3 ). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down-regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up-regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease-free interval and progression-free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT.
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Biomarcadores Tumorais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/mortalidade , Testículo/metabolismo , Testículo/patologia , TranscriptomaRESUMO
Our previous work demonstrated cancer-testis (CT) genes as a new source of candidate driver of cancer. Recently, mounting evidence indicates that long noncoding RNAs (lncRNAs) with CT expression pattern could play a pivotal role in cancer biology. Here, we characterized a conserved CT long noncoding RNA (CT-lncRNA), PCAT6, which is expressed exclusively in the testis and is reactivated in liver hepatocellular carcinoma (LIHC) tissues due to the highly frequent amplification. The expression in LIHC was correlated with clinical prognosis in TCGA data. Knockdown of PCAT6 could inhibit cell proliferation and migration in hepatocellular carcinoma (LIHC) cells. Gene set enrichment analysis (GSEA) based on coexpression network revealed that PCAT6 was involved in similar cilium-related pathways in the testis and LIHC tissues. However, PCAT6 was mainly positively correlated with gametogenesis-related pathways in the testis but was coexpressed with mitotic cell cycle genes in LIHC. Together, our data demonstrated that CT-lncRNA PCAT6 represents the similarity and difference between tumorigenesis and gametogenesis. The CT expression pattern and important role in LIHC oncogenesis make PCAT6 an ideal target for LIHC diagnosis and therapy.
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Amplificação de Genes/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Análise de Sobrevida , TransfecçãoRESUMO
The acid properties of Mo/HMCM-22 catalyst, which is the precursor form of the working catalyst for methane aromatization reaction, and the synergic effect between Mo species and acid sites were studied and characterized by various characterization techniques. It is concluded that Brønsted and Lewis acidities of HMCM-22 are modified due to the introduction of molybdenum. We suggest a monomer of Mo species is formed by the exchange of Mo species with the Brønsted acid sites. On the other hand, coordinate unsaturated sites (CUS) are suggested to be responsible for the formation of newly detected Lewis acid sites. Computer modelling is established and coupling with experimental results, it is then speculated that the effective activation of methane is properly accomplished on Mo species accommodated in the 12 MR supercages of MCM-22 zeolite whereas the Brønsted acid sites in the same channel system play a key role for the formation of benzene. A much more pronounced volcano-typed reactivity curve of the Mo/HMCM-22 catalysts, as compared with that of the Mo/HZSM-5, with respect to Mo loading is found and this can be well understood due to the unique channel structure of MCM-22 zeolite and synergic effect between Mo species and acid sites.
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Ácidos/química , Hidrocarbonetos Aromáticos/química , Metano/química , Modelos Químicos , Modelos Moleculares , Molibdênio/química , Zeolitas/química , Sítios de Ligação , Catálise , Simulação por Computador , Hidrocarbonetos Aromáticos/análise , Espectrometria de Massas , Molibdênio/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Zeolitas/análiseRESUMO
Guest(metal)-zeolite interactions in a two component heterogeneous catalyst have been investigated by high-field and high-speed (27)Al MAS NMR, and two-dimensional (27)Al MQ MAS NMR experiments as well as ab initio DFT methods. It was established that strong interactions between guest and zeolite occur in a metal/zeolite system, with the metal anchored to the tetrahedral aluminum framework site through two oxygen bridges. It disturbs the tetrahedral environment of associated aluminum framework, changing AlO(4) geometry from near T(d) to C(2v); this enables us to resolve this species from the undisturbed aluminum framework species in high-field (27)Al MAS NMR and two-dimesional (27)Al MQ MAS NMR experiments.