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1.
Mol Psychiatry ; 27(1): 19-33, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34580416

RESUMO

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.


Assuntos
COVID-19 , Doenças Transmissíveis , Vírus da Influenza A Subtipo H1N1 , Infecção por Zika virus , Zika virus , Humanos , Prevalência
2.
Mol Psychiatry ; 27(8): 3214-3222, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35668158

RESUMO

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.


Assuntos
COVID-19 , Doenças Transmissíveis , Distúrbios do Início e da Manutenção do Sono , Gravidez , Feminino , Humanos , Idoso , COVID-19/epidemiologia , Pandemias , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Prevalência , Depressão/epidemiologia , Depressão/etiologia , SARS-CoV-2 , Ansiedade/epidemiologia , Ansiedade/etiologia , Fatores de Risco , Doenças Transmissíveis/epidemiologia
3.
Bioinformatics ; 37(21): 3715-3722, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478501

RESUMO

MOTIVATION: Precise prediction of cancer subtypes is of significant importance in cancer diagnosis and treatment. Disease etiology is complicated existing at different omics levels; hence integrative analysis provides a very effective way to improve our understanding of cancer. RESULTS: We propose a novel computational framework, named Deep Subspace Mutual Learning (DSML). DSML has the capability to simultaneously learn the subspace structures in each available omics data and in overall multi-omics data by adopting deep neural networks, which thereby facilitates the subtype's prediction via clustering on multi-level, single-level and partial-level omics data. Extensive experiments are performed in five different cancers on three levels of omics data from The Cancer Genome Atlas. The experimental analysis demonstrates that DSML delivers comparable or even better results than many state-of-the-art integrative methods. AVAILABILITY AND IMPLEMENTATION: An implementation and documentation of the DSML is publicly available at https://github.com/polytechnicXTT/Deep-Subspace-Mutual-Learning.git.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Redes Neurais de Computação , Genoma , Análise por Conglomerados , Multiômica
4.
Mol Psychiatry ; 26(9): 4982-4998, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33542468

RESUMO

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.


Assuntos
COVID-19 , Doenças Transmissíveis , Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Transtornos de Estresse Pós-Traumáticos , Infecção por Zika virus , Zika virus , Humanos , Pandemias , Prevalência , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia
5.
Br J Nutr ; 127(7): 1086-1097, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-34039459

RESUMO

Urinary Na excretion is a potential risk factor for CVD. However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterise the relative contribution of biological factors to the Na-CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour Na excretion was estimated using a single overnight urine sample. Hypertension, the metabolic syndrome and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary Na excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (sd) of the 2112 participants was 54·5 (sd 12·2) years, and they were followed up for a mean of 14·1 (sd 8·1) years. Compared with those in the lowest quartile, the highest baseline urinary Na excretion (>4·2 g/24 h) was associated with a 43 % higher CVD risk (hazard ratio, 1·43; 95 % CI 1·02, 1·99). Participants with high urinary Na excretion, hypertension or the metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35 % of the Na-CVD association), followed by systolic blood pressure (BP) (33 %), left ventricular mass (28 %) and diastolic BP (14 %). Higher urinary Na excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic BP.


Assuntos
Hipertensão , Síndrome Metabólica , Pressão Sanguínea/fisiologia , Espessura Intima-Media Carotídea , Estudos de Coortes , Humanos , Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Potássio/urina , Sódio/urina , Cloreto de Sódio na Dieta , Taiwan/epidemiologia
6.
Mycoses ; 65(9): 887-896, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35793429

RESUMO

OBJECTIVES: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM). METHODS: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China. RESULTS: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035). CONCLUSIONS: This study demonstrated that species identification helps to guide therapy and predict outcomes.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Adulto , Idoso , Criptococose/microbiologia , Cryptococcus gattii/genética , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
Mol Biol Rep ; 47(2): 1079-1087, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31792748

RESUMO

Tibetans living in the Qing-Tibet plateau show unique genetic features since they are exposed to the high altitude environment. Accordingly, it is necessary for us to analyze genetic components of the Tibetan groups. Here, genetic structure and ancestry proportions of Tibet Tibetan and Qinghai Tibetan groups are dissected by using a previously published ancestral deletion/insertion polymorphisms (DIPs) panel. Genetic distributions of the analyzed DIPs in both Tibetan groups reveal that some DIPs show relatively balanced frequency distributions with the values ranging from 0.4 to 0.6, implying that these DIPs could be used as individual identification loci for forensic applications in both groups. Besides, the cumulative power of discrimination of the panel also reflects that the panel could serve as a valuable tool for forensic individual identifications in Tibet Tibetan and Qinghai Tibetan groups. Population genetic analyses including principal component analysis, DA genetic distances, phylogenetic tree, and genetic structure reveal that two studied Tibetan groups have closer genetic affiliations with East Asian populations. Genetic differentiation analyses of two Han populations, Xinjiang Uyghur and two Tibetan groups reveal that some DIP loci might be informative for differentiating Uyghurs from the other populations.


Assuntos
Povo Asiático/genética , Etnicidade/genética , Loci Gênicos , Genética Populacional , Mutação INDEL , Polimorfismo Genético , Alelos , China , Frequência do Gene , Geografia , Humanos , Desequilíbrio de Ligação , Tibet
8.
Acta Pharmacol Sin ; 41(12): 1576-1586, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33037404

RESUMO

Type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) regulates the intracellular Ca2+ release from endoplasmic reticulum in human embryonic stem cells (hESCs), cardiovascular progenitor cells (CVPCs), and mammalian cardiomyocytes. However, the role of IP3R2 in human cardiac development is unknown and its function in mammalian cardiomyocytes is controversial. hESC-derived cardiomyocytes have unique merits in disease modeling, cell therapy, and drug screening. Therefore, understanding the role of IP3R2 in the generation and function of human cardiomyocytes would be valuable for the application of hESC-derived cardiomyocytes. In the current study, we investigated the role of IP3R2 in the differentiation of hESCs to cardiomyocytes and in the hESC-derived cardiomyocytes. By using IP3R2 knockout (IP3R2KO) hESCs, we showed that IP3R2KO did not affect the self-renewal of hESCs as well as the differentiation ability of hESCs into CVPCs and cardiomyocytes. Furthermore, we demonstrated the ventricular-like myocyte characteristics of hESC-derived cardiomyocytes. Under the α1-adrenergic stimulation by phenylephrine (10 µmol/L), the amplitude and maximum rate of depolarization of action potential (AP) were slightly affected in the IP3R2KO hESC-derived cardiomyocytes at differentiation day 90, whereas the other parameters of APs and the Ca2+ transients did not show significant changes compared with these in the wide-type ones. These results demonstrate that IP3R2 has minimal contribution to the differentiation and function of human cardiomyocytes derived from hESCs, thus provide the new knowledge to the function of IP3R2 in the generation of human cardiac lineage cells and in the early cardiomyocytes.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias Humanas/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Miócitos Cardíacos/metabolismo , Regulação para Baixo , Humanos , Receptores Adrenérgicos alfa 1/metabolismo
9.
Am J Physiol Cell Physiol ; 317(6): C1183-C1193, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532716

RESUMO

Dual-specificity phosphatase 1 (DUSP1) is differentially expressed in cumulus cells of different physiological states, but its specific function and mechanism of action remain unclear. In this study, we explored the effects of DUSP1 expression inhibition on cell cycle progression, proliferation, apoptosis, and lactate and cholesterol levels in cumulus cells and examined reactive oxygen species levels, mitochondrial function, autophagy, and the expression of key cytokine genes. The results showed that inhibition of DUSP1 in cumulus cells caused abnormal cell cycle progression, increased cell proliferation, decreased apoptosis rates, increased cholesterol synthesis and lactic acid content, and increased cell expansion. The main reason for these effects was that inhibition of DUSP1 reduced ROS accumulation, increased glutathione level and mitochondrial membrane potential, and reduced autophagy levels in cells. These results indicate that DUSP1 limits the biological function of bovine cumulus cells under normal physiological conditions and will greatly contribute to further explorations of the physiological functions of cumulus cells and the interactions of the cumulus-oocyte complex.


Assuntos
Apoptose/genética , Ciclo Celular/genética , Células do Cúmulo/metabolismo , Fosfatase 1 de Especificidade Dupla/genética , Mitocôndrias/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Autofagia/genética , Bovinos , Proliferação de Células/genética , Colesterol/metabolismo , Células do Cúmulo/citologia , Fosfatase 1 de Especificidade Dupla/antagonistas & inibidores , Fosfatase 1 de Especificidade Dupla/metabolismo , Feminino , Regulação da Expressão Gênica , Glutationa/metabolismo , Ácido Láctico/metabolismo , Potencial da Membrana Mitocondrial/genética , Estresse Oxidativo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
10.
Cell Physiol Biochem ; 46(1): 107-117, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29587274

RESUMO

BACKGROUND/AIMS: Alzheimer disease (AD) is a common neurodegenerative disease that is characterized by the deposition of beta-amyloid peptide and formation of intracellular neurofibrillary tangles. Due to the failure of various clinical trials of novel drugs for AD, effective drugs for AD treatment are urgently required. METHODS: In this study, we used the classic APP/PS1 mouse model to explore the neuroprotective effects of a new compound, bajijiasu, and the mechanisms involved. Behavioral tests and western blotting were performed to assess the beneficial effects of bajijiasu in APP/PS1 mice. RESULTS: Morris water maze and Y-maze test results showed that oral administration of bajijiasu (35 mg/kg/day and 70 mg/kg/day) improved learning and memory abilities in APP/PS1 mice. Bajijiasu reduced ROS and MDA levels in both the hippocampus and cortex. Moreover, western blotting results showed that bajijiasu protected neurons from apoptosis, elevated the expression levels of neurotrophic factors, and alleviated endoplasmic reticulum stress in both the hippocampus and cortex. CONCLUSION: These results indicate that the mechanisms underlying the effects of bajijiasu on AD might be related to beta-amyloid-downstream pathologies, particularly endoplasmic reticulum stress.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Dissacarídeos/uso terapêutico , Estresse do Retículo Endoplasmático , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Animais , Caspase 3/metabolismo , Córtex Cerebelar/efeitos dos fármacos , Córtex Cerebelar/metabolismo , Dissacarídeos/química , Dissacarídeos/farmacologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Presenilina-1/genética , Presenilina-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
Acta Pharmacol Sin ; 38(12): 1663-1672, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28713161

RESUMO

Emerging evidence suggests that Ca2+ signals are important for the self-renewal and differentiation of human embryonic stem cells (hESCs). However, little is known about the physiological and pharmacological properties of the Ca2+-handling machinery in hESCs. In this study we used RT-PCR and Western blotting to analyze the expression profiles of genes encoding Ca2+-handling proteins; we also used confocal Ca2+ imaging and pharmacological approaches to determine the contribution of the Ca2+-handling machinery to the regulation of Ca2+ signaling in hESCs. We revealed that hESCs expressed pluripotent markers and various Ca2+-handling-related genes. ATP-induced Ca2+ transients in almost all hESCs were inhibited by the inositol-1,4,5-triphosphate receptor (IP3R) blocker 2-APB or xestospongin C. In addition, Ca2+ transients were induced by a ryanodine receptor (RyR) activator, caffeine, in 10%-15% of hESCs and were blocked by ryanodine, whereas caffeine and ATP did not have additive effects. Moreover, store-operated Ca2+ entry (SOCE) but not voltage-operated Ca2+ channel-mediated Ca2+ entry was observed. Inhibition of sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) by thapsigargin induced a significant increase in the cytosolic free Ca2+ concentration ([Ca2+]i). For the Ca2+ extrusion pathway, inhibition of plasma membrane Ca2+ pumps (PMCAs) by carboxyeosin induced a slow increase in [Ca2+]i, whereas the Na+/Ca2+ exchanger (NCX) inhibitor KBR7943 induced a rapid increase in [Ca2+]i. Taken together, increased [Ca2+]i is mainly mediated by Ca2+ release from intracellular stores via IP3Rs. In addition, RyRs function in a portion of hESCs, thus indicating heterogeneity of the Ca2+-signaling machinery in hESCs; maintenance of low [Ca2+]i is mediated by uptake of cytosolic Ca2+ into the ER via SERCA and extrusion of Ca2+ out of cells via NCX and PMCA in hESCs.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Trifosfato de Adenosina/farmacologia , Compostos de Boro/farmacologia , Cálcio/análise , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Humanos , Compostos Macrocíclicos/farmacologia , Oxazóis/farmacologia , Tioureia/análogos & derivados , Tioureia/farmacologia
13.
Plant Physiol Biochem ; 207: 108393, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38290344

RESUMO

Dimethylarsenate [DMAs(V)] can be produced by some soil microorganisms through methylation of inorganic arsenic (As), especially in anoxic paddy soils. DMAs(V) is more phytotoxic than inorganic As and can cause the physiological disorder straighthead disease in rice. Rice cultivars vary widely in the resistance to DMAs(V), but the mechanism remains elusive. Here, we investigated the differences in DMAs(V) uptake, translocation, and reduction to dimethylarsenite [DMAs(III)], as well as the effects on the metabolome, between two rice cultivars Mars and Zhe733. We found that Mars was 11-times more resistant to DMAs(V) than Zhe733. Mars accumulated more DMAs(V) in the roots, whereas Zhe733 translocated more DMAs(V) to the shoots and reduced more DMAs(V) to DMAs(III). DMAs(III) was more toxic than DMAs(V). Using heterologous expression and in vitro enzyme assays, we showed that the glutathione-S-transferases OsGSTU17 and OsGSTU50 were able to reduce DMAs(V) to DMAs(III). The expression levels of OsGSTU17 and OsGSTU50 were higher in the shoot of Zhe733 compared to Mars. Metabolomic analysis in rice shoots showed that glutathione (GSH) metabolism was perturbed by DMAs(V) toxicity in Zhe733. Application of exogenous GSH significantly alleviated the toxicity of DMAs(V) in Zhe733. Taken together, the results suggest that Mars is more resistant to DMAs(V) than Zhe733 because of a lower root-to-shoot translocation and a smaller capacity to reduce DMAs(V) to DMAs(III).


Assuntos
Arsênio , Arsenicais , Oryza , Poluentes do Solo , Ácido Cacodílico/metabolismo , Oryza/metabolismo , Arsenicais/metabolismo , Metilação , Glutationa/metabolismo , Solo , Arsênio/toxicidade , Arsênio/metabolismo
14.
Exp Gerontol ; 194: 112514, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971132

RESUMO

Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). The transcriptional coactivator PPARγ coactivator 1 (PGC-1a) has been identified as a key regulator of mitochondrial biogenesis and function. However, the precise structure/function relationship between PGC-1a and mitochondrial quality control remains incompletely understood. In this study, we investigated the impact of PGC-1a on AD pathology and its underlying mechanisms with a specific focus on mitochondrial axonal transport. Additionally, we generated two PGC-1α mutants by substituting leucine residues at positions 148 and 149 within the LKKLL motif or at positions 209 and 210 within the LLKYL motif with alanine. Subsequently, we examined the effects of these mutants on mutAPP-induced abnormalities in anterograde and retrograde axonal transport, disrupted mitochondrial distribution, and impaired mitophagy. Mutagenesis studies revealed that the LLKYL motif at amino acid position 209-210 within PGC-1α plays an essential role in its interaction with estrogen-related receptors (ERRα), which is necessary for restoring normal mitochondrial anterograde axonal transport, maintaining proper mitochondrial distribution, and ultimately preventing neuronal apoptosis. Furthermore, it was found that the Leu-rich motif at amino acids 209-210 within PGC-1α is crucial for rescuing mutAPP-induced impairment in mitophagy and loss of membrane potential by restoring normal mitochondrial retrograde axonal transport. Conversely, mutation of residues 148 and 149 in the LKKLL motif does not compromise the effectiveness of PGC-1α. These findings provide valuable insights into the molecular determinants governing specificity of action for PGC-1α involved in regulating mutAPP-induced deficits in mitochondrial axonal trafficking. Moreover, they suggest a potential therapeutic target for addressing Alzheimer's disease.

15.
Int J Biol Macromol ; 256(Pt 2): 128451, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029910

RESUMO

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses.


Assuntos
Transdução de Sinais , Peixe-Zebra , Animais , Ubiquitinação , Imunidade Inata , Antivirais
16.
Sci Rep ; 14(1): 9669, 2024 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-38671072

RESUMO

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p < 0.001). In patients with major thoracic injury, older age and higher injury survival scale account for higher mortality rate. Effective surgical stabilization of rib fractures shortened the ICU stay and helped achieve better performance in EIT. Thoracoscope-assisted rib fixation is suggested in severe trauma cases.


Assuntos
Impedância Elétrica , Fraturas das Costelas , Traumatismos Torácicos , Humanos , Fraturas das Costelas/cirurgia , Fraturas das Costelas/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Traumatismos Torácicos/cirurgia , Traumatismos Torácicos/diagnóstico por imagem , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Cirurgia Torácica Vídeoassistida/métodos , Escala de Gravidade do Ferimento , Tomografia/métodos
17.
World J Clin Cases ; 11(15): 3658-3663, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37383900

RESUMO

BACKGROUND: Pulmonary sequestrations often lead to serious complications such as infections, tuberculosis, fatal hemoptysis, cardiovascular problems, and even malignant degeneration, but it is rarely documented with medium and large vessel vasculitis, which is likely to result in acute aortic syndromes. CASE SUMMARY: A 44-year-old man with a history of acute Stanford type A aortic dissection status post-reconstructive surgery five years ago. The contrast-enhanced computed tomography of the chest at that time had also revealed an intralobar pulmonary sequestration in the left lower lung region, and the angiography also presented perivascular changes with mild mural thickening and wall enhancement, which indicated mild vasculitis. The intralobar pulmonary sequestration in the left lower lung region was long-term unprocessed, which was probably associated with his intermittent chest tightness since no specific medical findings were detected but only positive sputum culture with mycobacterium avium-intracellular complex and Aspergillus. We performed uniportal video-assisted thoracoscopic surgery with wedge resection of the left lower lung. Hypervascularity over the parietal pleura, engorgement of the bronchus due to a moderate amount of mucus, and firm adhesion of the lesion to the thoracic aorta were histopathologically noticed. CONCLUSION: We hypothesized that a long-term pulmonary sequestration-related bacterial or fungal infection can result in focal infectious aortitis gradually, which may threateningly aggravate the formation of aortic dissection.

18.
RSC Adv ; 13(14): 9347-9352, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36959885

RESUMO

In the synthesis of dimethyl carbonate (DMC) by transesterification, CH3ONa has been commonly applied as a homogeneous catalyst due to its high catalytic activity, but its stability is unsatisfactory. Here, by studying the influence of ionic liquid base strength on transesterification, we prepared an organic base catalyst, potassium imidazole (KIm), with high catalytic activity and stability, which solved the problem of catalyst deactivation in transesterification. The results showed that when KIm was used in the synthesis of DMC from propylene carbonate (PC) and methanol (MeOH), the chemical equilibrium could be reached within 3 minutes and the yield of DMC reached 73.03%, indicating that KIm performed better in transesterification than the majority of previously reported catalysts. In addition, the activity of the catalyst had hardly decreased after ten cycles of reaction, which can well meet the requirements of industrial production.

19.
J Nutr Sci ; 12: e16, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843973

RESUMO

The present study aimed to investigate the relationship between dietary patterns and the risk of type 2 diabetes mellitus (T2DM) among Taiwanese individuals. Data were collected using a nationwide cohort study (2001-15) from the Triple-High Database. Dietary intake was assessed using the twenty-group food frequency questionnaire and used to calculate alternate Mediterranean diet (aMED) and Dietary Approaches to Stop Hypertension (DASH) scores. Principal component analysis (PCA) and partial least-squares (PLS) regression were used to derive dietary patterns, with incident T2DM as the outcome. Multivariable-adjusted hazard ratios and 95 % confidence intervals were calculated using time-dependent Cox proportional hazards (Cox PH) regression analysis, and subgroup analyses were performed. A total of 4705 participants were enrolled in the study, and 995 had newly developed T2DM during the median 5⋅28-year follow-up period (30⋅7 per 1000 person-years). Six dietary patterns were extracted (PCA: Western, prudent, dairy and plant-based; PLS: health-conscious, fish-vegetable and fruit-seafood). The highest aMED score quartile had a 25 % (hazard ratio 0⋅75; 95 % CI 0⋅61, 0⋅92; P = 0⋅039) lower risk of T2DM than the lowest quartile. This association remained significant after adjustment (adjusted hazard ratio 0⋅74; 95 % CI 0⋅60, 0⋅91; P = 0⋅010), and no effect modifier was found for aMED. The DASH scores, PCA and PLS dietary patterns were not significant after adjustment. In conclusion, high adherence to a MED-type dietary pattern by Taiwanese foods was associated with a lower risk of T2DM in the Taiwanese population, regardless of unhealthy lifestyle habits.


Assuntos
Diabetes Mellitus Tipo 2 , Dieta Mediterrânea , Animais , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco , Taiwan/epidemiologia
20.
Int J Rheum Dis ; 26(7): 1358-1362, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36793153

RESUMO

Pyomyositis is an uncommon clinical scenario; it is usually associated with predisposing factors, including poorly controlled diabetes mellitus, trauma history, and immunocompromise. We discuss the case of an elderly woman with a 20-year history of diabetes mellitus and remissive breast cancer after modified radical mastectomy and subsequent chemotherapy 28 years previously. The patient presented with severe shoulder pain and gradual swelling. After examination, pyomyositis was diagnosed and debridement surgery was performed. Culture of the wound samples showed the growth of Streptococcus agalactiae. During hospitalization, primary biliary cholangitis (PBC) was diagnosed incidentally, accompanied by poor glycemic control. After treatment with antibiotics for pyomyositis and ursodeoxycholic acid for PBC, the infection resolved in 8 weeks, and her glycemic control was improved after PBC treatment. It is possible that the long-term untreated PBC worsened insulin resistance and aggravated diabetes mellitus in this patient. To the best of our knowledge, this is the first reported case of pyomyositis caused by an unusual pathogen, S. agalactiae, in a patient with newly diagnosed PBC.


Assuntos
Neoplasias da Mama , Cirrose Hepática Biliar , Piomiosite , Humanos , Feminino , Idoso , Piomiosite/diagnóstico , Piomiosite/tratamento farmacológico , Streptococcus agalactiae , Neoplasias da Mama/complicações , Mastectomia/efeitos adversos
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