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BACKGROUND: Frailty and sarcopenia are typical geriatric conditions with a complex pathophysiology. Extracellular vesicles (EVs) are key regulators of age-related diseases, but the mechanisms underlying physical frailty, sarcopenia, and EVs are not well understood. METHODS: A systematic literature review was conducted to examine the evidence supporting an association between EVs and physical frailty and/or sarcopenia by searching the electronic databases, including the Cochrane Library, PubMed, and Embase, from January 2000 to January 2021. RESULTS: A total of 216 cross-sectional studies were retrieved, and after the removal of 43 duplicate records, the title and abstract of 167 articles were screened, identifying 6 relevant articles for full-text review. Of the studies five met the inclusion criteria, and heterogeneity among studies was high. There is controversy regarding whether frailty and/or sarcopenia are related to circulating EV levels; however, the cargo of EVs has been associated with frailty and sarcopenia in various ways, such as microRNAs, mitochondrial-derived vesicles (MDVs), and protein cargoes. CONCLUSION: Recent studies, although limited, depicted that EVs could be one of the underlying mechanisms of frailty and/or sarcopenia. There is a possibility that physical frailty and sarcopenia may have specific EV concentrations and cargo profiles; however, further research is required to fully understand the mechanisms and identify potential biomarkers and early preventative strategies for physical frailty and sarcopenia.
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Vesículas Extracelulares , Fragilidade , Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico , Sarcopenia/complicações , Fragilidade/diagnóstico , Estudos Transversais , Exame Físico , Vesículas Extracelulares/fisiologiaRESUMO
BACKGROUND: The associations of frailty with all-cause and cause-specific mortality remain unclear. Therefore, we performed this meta-analysis to fill this gap. METHODS: We searched the PubMed and Embase databases through June 2022. Prospective cohort studies or clinical trials examining frailty were evaluated, and the multiple adjusted risk estimates of all-cause and cause-specific mortality, such as death from cardiovascular disease (CVD), cancer, respiratory illness, dementia, infection, and coronavirus disease 2019 (COVID-19), were included. A random effects model was used to calculate the summary hazard ratio (HR). RESULTS: Fifty-eight studies were included for the qualitative systematic review, of which fifty-six studies were eligible for the quantitative meta-analysis, and the studies included a total of 1,852,951 individuals and more than 145,276 deaths. Compared with healthy adults, frail adults had a significantly higher risk of mortality from all causes (HR 2.40; 95% CI 2.17-2.65), CVD (HR 2.64; 95% CI 2.20-3.17), respiratory illness (HR 4.91; 95% CI 2.97-8.12), and cancer (HR 1.97; 95% CI 1.50-2.57). Similar results were found for the association between prefrail adults and mortality risk. In addition, based on the studies that have reported the HRs of the mortality risk per 0.1 and per 0.01 increase in the frailty index, we obtained consistent results. CONCLUSIONS: The present study demonstrated that frailty was not only significantly related to an increased risk of all-cause mortality but was also a strong predictor of cause-specific mortality from CVD, cancer, and respiratory illness in community-dwelling adults. More studies are warranted to clarify the relationship between frailty and cause-specific mortality from dementia, infection, and COVID-19. TRIAL REGISTRATION: PROSPERO (CRD42021276021).
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COVID-19 , Doenças Cardiovasculares , Demência , Fragilidade , Idoso , Doenças Cardiovasculares/diagnóstico , Idoso Fragilizado , Fragilidade/diagnóstico , Humanos , Vida Independente , Estudos ProspectivosRESUMO
To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.
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Sepse , Choque Séptico , Glicoproteínas , Humanos , Interleucina-10 , Norepinefrina/efeitos adversos , Pró-Calcitonina , Prognóstico , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Resultado do TratamentoRESUMO
Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family, could cause fatal diarrhea of piglets and result in numerous economic losses. Previous studies demonstrated that TGEV infection could lead to mitochondrial damage and upregulate miR-4331 level. So miR-4331 may play an important regulatory role in the control of mitochondrial function. To explore the potential role of miR-4331 in mitochondrial damage, we adopted a strategy consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in response to miR-4331 and TGEV infection. Eventually, 69 differentially expressed proteins were gained. The target of miR-4331 was identified. The effects of miR-4331 and its target RB1 on mitochondrial Ca2+ level, mitochondrial membrane potential (MMP), interleukin-1 receptor accessory protein (IL1RAP), p38 MAPK signaling pathway were investigated. The results showed that miR-4331 elevated mitochondrial Ca2+ level, reduced MMP, targets Retinoblastoma 1 (RB1), upregulated IL1RAP, and induced activation of p38 MAPK pathway during TGEV infection. RB1 was identified as the direct targets of miR-4331 and downregulated IL1RAP, suppressed the activation of p38 MPAK, and attenuated TGEV-induced mitochondrial damage. In addition, IL1RAP played a positive role in activating p38 MAPK signaling and negative role in TGEV-induced mitochondrial damage. The data indicate that miR-4331 aggravates TGEV-induced mitochondrial damage by repressing expression of RB1, promoting IL1RAP, and activating p38 MAPK pathway.
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Proteína Acessória do Receptor de Interleucina-1/metabolismo , MicroRNAs , Mitocôndrias/fisiologia , Proteína do Retinoblastoma/metabolismo , Vírus da Gastroenterite Transmissível , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Proteína Acessória do Receptor de Interleucina-1/genética , Potencial da Membrana Mitocondrial , Proteômica , Proteína do Retinoblastoma/genética , SuínosRESUMO
BACKGROUND: The association between chronic obstructive pulmonary disease (COPD), lung function and risk of type 2 diabetes mellitus (T2DM) remains controversial. We performed a meta-analysis to clarify this issue. METHODS: The PubMed and EMBASE databases were searched. Cohort studies on COPD, lung function and risk of T2DM in adults were included. A random effects model was adopted to calculate the summary risk ratio (RR) and 95% confidence interval (CI). Dose-response analysis was conducted where possible. RESULTS: A total of 13 eligible cohort studies involving 307,335 incident T2DM cases and 7,683,784 individuals were included. The risk of T2DM was significantly higher in patients with COPD than those without COPD (RR = 1.25, 95% CI 1.16-1.34). Compared to the highest category of percentage forced vital capacity (FVC%), the lowest category of FVC% was associated with a higher risk of T2DM (RR = 1.43, 95% CI 1.33-1.53). Similarly, the summary RR of T2DM for the lowest versus highest category of percentage forced expiratory volume in 1 s (FEV1%) was 1.49 (95% CI 1.39-1.60). Significant linear associations of FVC% and FEV1% with risk of T2DM were found (Pnon-linearity > 0.05); the RR of T2DM was 0.88 (95% CI 0.82-0.95) and 0.87 (95% CI 0.81-0.94) per 10% increase in FVC% and FEV1%, respectively. There was a non-significant relationship between the FEV1/FVC ratio and the risk of T2DM. CONCLUSIONS: Both COPD and impaired lung function, especially restricted ventilation dysfunction, could increase the risk of T2DM. However, these findings should be interpreted with caution due to the limited number of studies, and need to be validated by future studies.
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Diabetes Mellitus Tipo 2/epidemiologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Fatores de RiscoRESUMO
Porcine circovirus type 2 (PCV2) capsid protein (Cap) is a unique structure protein that plays pivotal roles in the process of viral replication and pathogenesis. Herein, we characterized a putative porcine Makorin RING finger protein 1 (pMKRN1) variant, an N-terminal-truncated variant of putative full-size porcine MKRN1 which has a unique expression pattern resulting from the porcine mkrn1 gene and which interacts with PCV2 Cap. A domain mapping assay showed that the C terminus of pMKRN1 and fragments (amino acids 108 to 198) of Cap are required for this interaction. PCV2 transiently upregulated pMKRN1 in PK-15 cells, but persistent viral infection downregulated pMKRN1 in major pathological tissues of PCV2-infected piglets. Overexpression of pMKRN1 significantly inhibited the generation of progeny PCV2 via ubiquitination and degradation of Cap, whereas knockout of pMKRN1 blocked Cap degradation and promoted progeny virus replication. pMKRN1 specifically targeted PCV2 Cap lysine residues 164, 179, and 191 to induce polyubiquitination and subsequent degradation. Mutation of either of the three lysine residues in the Cap protein or mutation of the histidine at residue 243 within the RING finger domain of pMKRN1 abrogated the E3 ligase activity of pMKRN1, rendering cells incapable of inducing Cap ubiquitination and degradation. Consistent with this finding, a Cap ubiquitination-deficient PCV2 strain showed enhanced virus replication and produced severe histological lesions in the lung and lymph node tissues compared with wild-type PCV2. Taken together, the results presented here suggest that PCV2 downregulates the pMKRN1 variant to avoid pMKRN1-mediated Cap ubiquitination and degradation, thus promoting viral replication and pathogenesis in its targeted tissues.IMPORTANCE Porcine circovirus type 2 is the pathogen to which pigs are the most susceptible, causing immense economic losses in the global swine industry, but whether host cells have developed some strategies to prevent viral replication is still unclear. Here, we found that porcine MKRN1 (pMKRN1) was upregulated in the early stage of PCV2 infection and mediated the polyubiquitination and degradation of Cap protein to block PCV2 replication, yet persistent PCV2 infection downregulated pMKRN1 levels to avoid degradation, promoting viral replication and pathogenesis in its targeted tissues. These data present new insight into the molecular mechanisms underlying the antiviral effects of pMKRN1 E3 ligase during PCV2 infection and also suggest potential new control measures for PCV2 outbreaks.
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Circovirus/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Ubiquitinação/genética , Replicação Viral/genética , Animais , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Infecções por Circoviridae/patologia , Infecções por Circoviridae/veterinária , Infecções por Circoviridae/virologia , Células HEK293 , Humanos , Suínos , Doenças dos Suínos/patologia , Doenças dos Suínos/virologia , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can activate NF-κB pathway in porcine intestinal epithelial cells and result in severe inflammation. Non-coding RNAs (ncRNAs) are not translated into proteins and play an important role in many biological and pathological processes such as inflammation, viral infection, and mitochondrial damage. However, whether ncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells is largely unknown. RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of mRNAs, miRNAs, and circRNAs in Mock- and TGEV-infected intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 523 mRNAs, 65 microRNAs (miRNAs), and 123 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed differentially expressed mRNAs were linked to inflammation-related pathways, including NF-κB, Toll-like receptor, NOD-like receptor, Jak-STAT, TNF, and RIG-I-like receptor pathways. The interactions among mRNA, miRNA, and circRNA were analyzed. The data showed that ssc_circ_009380 and miR-22 might have interaction relationship. Dual-luciferase reporter assay confirmed that miR-22 directly bound to ssc_circ_009380. We also observed that overexpression of miR-22 led to a reduction of p-IκB-α and accumulation of p65 in nucleus in TGEV-infected IPEC-J2 cells. In contrast, inhibition of miR-22 had the opposite effects. Moreover, silencing of ssc_circ_009380 inhibited accumulation of p65 in nucleus and phosphorylation of IκB-α. CONCLUSIONS: The data revealed that differentially expressed mRNAs and ncRNAs were primarily enriched in inflammation-related pathways and ssc_circ_009380 promoted activation of NF-κB pathway by binding miR-22 during TGEV-induced inflammation.
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Perfilação da Expressão Gênica , Mucosa Intestinal/citologia , NF-kappa B/metabolismo , RNA não Traduzido/genética , Vírus da Gastroenterite Transmissível/fisiologia , Animais , Sequência de Bases , Linhagem Celular , Redes Reguladoras de Genes , Inflamação/genética , Inflamação/virologia , RNA Mensageiro/genética , Análise de Sequência de RNA , SuínosRESUMO
In this letter, aggregation from two-photon absorption (2PA) molecules in living cells were firstly observed and the related aggregation induced emission (AIE) properties were investigated as a cell tracer for L ((Z)-3-(4-(Bis(4-ethoxyphenyl) amino)phenyl)-2-(4-amino-phenyl)- acrylonitrile cyano-substituted ) based on triphenylamine with D-π-A model. L was further used as a two-photon absorption (2PA, λex = 900, λem = 550 nm δ = 156 GM) live-cell marker for real-time, long-term cell growth and proliferation monitoring, with rapidly adhering whole intracellular membrane-rich system. Remarkably, different from existing organic AIE chromophores and other commercially available probes, L exhibited intense intracellular-AIE property with stable nuclear envelope (NE) staining under two-photon excited microscopy (TPEM) through detailed in cellulo studies.
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Corantes Fluorescentes/química , Membrana Nuclear/química , Fótons , Proliferação de Células , Células Hep G2 , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Fatores de Tempo , Células Tumorais CultivadasRESUMO
BACKGROUND AND AIMS: Abnormal microRNA (miRNA) expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD). Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. METHODS: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls) were also collected for further validation by quantitative real-time PCR ( qRT-PCR ). RESULTS: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC ≥ 1.3 or ≤ 0.77 and p<0.05). In addition, the transcription of 1271 mRNAs was up-regulated, while the expression of 777 mRNAs transcripts was down-regulated (FC ≥ 2.0 or ≤ 0.5 and p<0.05). Furthermore, integrated analysis of differentially expressed miRNA and their target mRNAs demonstrated that 2 miRNA (miR-22 and miR-183) were increased while their potential target mRNAs were decreased. 3 miRNA (miR-101, miR-197 and miR-660) were decreased while their potential target mRNAs were increased. The above findings from microarray screening were confirmed by qRT-PCR in more samples. The results were consistent with those observed in the microarray assays. CONCLUSION: Our study highlights the possibility that miRNA-target gene network may be involved in the pathogenesis of GD and could provide new insights into understanding the pathophysiological mechanisms of GD.
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Doença de Graves/patologia , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Redes Reguladoras de Genes , Doença de Graves/genética , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Glândula Tireoide/metabolismo , Regulação para Cima , Adulto JovemRESUMO
To determine the potential role of interleukin-21 (IL-21) / IL-21 receptor (IL-21R) in the pathogenesis of autoimmune thyroid disease (AITD) mainly known as Graves' disease (GD) and Hashimoto's thyroiditis (HT). IL-21 and IL-21R of peripheral blood samples and/or thyroid tissues from AITD patients and healthy controls were analyzed by ELISA, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry and immunohistochemistry. In vitro, the mRNA and protein of inflammatory cytokines of cultured peripheral blood mononuclear cells (PBMCs) upon recombinant human IL-21 (rhIL-21) stimulation were detected. There was an increased serum concentration of IL-21 in untreated GD and HT patients, and IL-21(+)CD3(+)CD8(-)T cells were significantly increased in PBMCs of HT patients compared with healthy volunteers. The IL-21 mRNA expression in PBMCs increased dramatically in GD and HT patients, and marked augmentations of IL-21 and IL-21R mRNA in thyroid tissues of HT patients were observed. Immunohistochemical staining confirmed the expression of IL-21R protein in HT thyroid cells and lymphocytes. In vitro, PBMCs from GD cultured with rhIL-21 induced increased IL-17A but decreased IL-4 production, while from HT stimulated by rhIL-21 induced augmented production of IFN-γ. In conclusion, the expression of IL-21 and IL-21R were up-regulated in AITD and may be involved in the pathogenesis of the disease through augmenting aberrant immune cascade.
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Doença de Graves/imunologia , Doença de Hashimoto/imunologia , Interleucinas/metabolismo , Receptores de Interleucina-21/metabolismo , Adulto , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Interferon gama , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Interleucinas/genética , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-21/genética , Proteínas Recombinantes/administração & dosagem , Glândula Tireoide/imunologia , Glândula Tireoide/ultraestruturaRESUMO
Objective: Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization. Methods: This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes. Results: The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities (P < .001), lower surgical rates (P = .002), and delayed surgical times (P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications. Conclusions: Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research.
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Osteosarcopenia is defined as the concurrent occurrence of osteopenia/osteoporosis and sarcopenia. The aim of the current study was to perform a systematic review with meta-analysis to determine the global prevalence, risk factors and clinical outcomes of osteosarcopenia. This review was registered in PROSPERO (CRD42022351229). PubMed, Cochrane, Medline and Embase were searched from inception to February 2023 to retrieve eligible observational population-based studies. Pooled osteosarcopenia prevalence was calculated with 95% confidence interval (CI), and subgroup analyses were performed. The risk factor of osteosarcopenia and its association with clinical outcomes were expressed as odds ratio (OR) and hazard ratio (HR), respectively. Heterogeneity was estimated using the I2 test. Study quality was assessed using validated instruments matched to study designs. The search identified 55 158 studies, and 66 studies (64 404 participants, mean age from 46.6 to 93 years) were analysed in the final analysis, including 48 cross-sectional studies, 17 cohort studies and 1 case-control study. Overall, the pooled prevalence of osteosarcopenia was 18.5% (95% CI: 16.7-20.3, I2 = 98.7%), including 15.3% (95% CI: 13.2-17.4, I2 = 97.6%) in men and 19.4% (95% CI: 16.9-21.9, I2 = 98.5%) in women. The prevalence of osteosarcopenia diagnosed using sarcopenia plus osteopenia/osteoporosis was 20.7% (95% CI: 17.1-24.4, I2 = 98.55%), and the prevalence of using sarcopenia plus osteoporosis was 16.1% (95% CI: 13.3-18.9, I2 = 98.0%). The global osteosarcopenia prevalence varied in different regions with 22.9% in Oceania, 21.6% in Asia, 20.8% in South America, 15.7% in North America and 10.9% in Europe. A statistically significant difference was found in the subgroups of the study population between the hospital (24.7%) and community (12.9%) (P = 0.001). Frailty (OR = 4.72, 95% CI: 2.71-8.23, I2 = 61.1%), malnutrition (OR = 2.35, 95% CI: 1.62-3.40, I2 = 50.0%), female sex (OR = 5.07, 95% CI: 2.96-8.69, I2 = 73.0%) and higher age (OR = 1.10, 95% CI: 1.06-1.15, I2 ==86.0%) were significantly associated with a higher risk for osteosarcopenia. Meta-analysis of cohort studies showed that osteosarcopenia significantly increased the risk of fall (HR = 1.54, 95% CI: 1.20-1.97; I2 = 1.0%, three studies), fracture (HR = 2.13, 95% CI: 1.61-2.81; I2 = 67.8%, seven studies) and mortality (HR = 1.75, 95% CI: 1.34-2.28; I2 = 0.0%, five studies). Despite the heterogeneity arising from varied definitions and criteria, our findings highlight a significant global prevalence of osteosarcopenia and its negative impact on clinical health. Standardizing diagnostic criteria for osteosarcopenia would be advantageous in the future, and early detection and management should be emphasized in this patient population.
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Fraturas Ósseas , Osteoporose , Sarcopenia , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sarcopenia/diagnóstico , Estudos Transversais , Estudos de Casos e Controles , Osteoporose/epidemiologia , Osteoporose/diagnósticoRESUMO
Autoimmune thyroid disease (AITD) is a multifactorial disease with a genetic susceptibility and environmental factors. The thyroid stimulating hormone receptor gene (TSHR) which is expressed on the surface of the thyroid epithelial cell is thought to be the main auto-antigen and a significant candidate for genetic susceptibility to AITD. This case-control study aimed at evaluating the association between single nucleotide polymorphisms (SNP) of TSHR and AITD in a Chinese Han population. We recruited 404 patients with Graves' disease (GD), 230 patients with Hashimoto's thyroiditis (HT) and 242 healthy controls. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform was used to detect five SNPs (rs179247, rs12101255, rs2268475, rs1990595, and rs3783938) in TSHR gene. The frequencies of allele T and TT genotype of rs12101255 in GD patients were significantly increased compared with those of the controls (P=0.004/0.015, OR=1.408/1.446). The allele A frequency of rs3783938 was greater in HT patients than in the controls (P=0.025, OR=1.427). The AT haplotype (rs179247-rs12101255) was associated with an increased risk of GD (P=0.010, OR=1.368). The allele A of rs179247 was associated with ophthalmopathy in GD patients. These data suggest that the polymorphisms of rs12101255 and rs3783938 are associated with GD and HT, respectively.
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Doença de Graves/genética , Doença de Hashimoto/genética , Receptores da Tireotropina/genética , Adulto , Povo Asiático/genética , Feminino , Genótipo , Haplótipos , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: Inflammation is one of the pathogenesis of frailty, Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are newly proposed inflammatory indicators. This study aimed to explore the relationship between NLR, PLR and frailty in elderly inpatient with comorbidity. METHODS: Inpatient elderly with comorbidity in our geriatric department from January 2015 to December 2018 were selected, and three groups, which included frailty, pre-frailty and robust, were divided by 5-item FRAIL scale. General data of the patients were collected, and comprehensive geriatric assessment was performed. NLR and PLR were calculated by neutrophil, lymphocyte and platelet in blood. SPSS24.0 software was used for analysis. RESULTS: CONCLUSION: Although results from the present study revealed associations between frailty and neutrophil and NLR in elderly inpatient with comorbidity, the potential role of these inflammation indicators on frailty needs further prospective investigation and researches involving larger population to improve its reliability.
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Fragilidade , Neutrófilos , Humanos , Idoso , Contagem de Plaquetas , Pacientes Internados , Reprodutibilidade dos Testes , Linfócitos , Plaquetas , Inflamação , Comorbidade , Contagem de Linfócitos , Estudos RetrospectivosRESUMO
BACKGROUND: Depression in the elderly is a serious and often underdiagnosed psychiatric disorder that has been linked to adverse outcomes in the hospital setting. This study aims to evaluate the prevalence of depressive symptoms and associated factors among elderly hospital inpatients. METHODS: The cross-sectional study included 411 consecutively hospitalized patients aged 60 years and older. Participants were evaluated within 48 hours of admission using an interviewer-administered questionnaire including the Geriatric Depression Scale and comprehensive geriatric assessment to provide basic demographic and clinical information. RESULTS: Most of the participants were male (64.5%), with a mean (SD) age of 75.9 (8.1) years between 60 and 97 years. The prevalence of depressive symptoms was 32.8%. Univariate analysis showed significant associations between depressive symptoms and older age, female gender, lower body mass index, number of chronic diseases, impaired family function, impaired cognition, malnutrition, increased frailty, and decreased ability to perform activities of daily living. After logistic regression, variables that remained significantly associated with depression were cognitive decline (odds ratio =1.97, 95% CI: 1.09-3.55), poor family function (odds ratio =2.01, 95% CI: 1.10-3.66), and frailty (odds ratio =5.07, 95% CI: 1.95-13.20). Depressive symptoms were independently associated with prolonged hospital length. CONCLUSION: Depressive symptoms were prevalent among hospitalized elderly and independently associated with cognitive decline, poor family function, and frailty. Therefore, it is essential to screen for depression and perform a comprehensive geriatric assessment in these patients to identify and manage depressive symptoms.
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Disfunção Cognitiva/psicologia , Depressão/epidemiologia , Relações Familiares/psicologia , Fragilidade/psicologia , Pacientes Internados/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Doença Crônica , Estudos Transversais , Depressão/diagnóstico , Transtorno Depressivo/epidemiologia , Feminino , Avaliação Geriátrica , Humanos , Pacientes Internados/psicologia , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Centros de Atenção TerciáriaRESUMO
Ki-67 is a nuclear protein that has been used in cancer diagnostic because of its specific cell-cycle dependent expression profile. After quantifying and characterising the expression level of Ki-67, as a function of the cell cycle, we found out that the two main splice variants of the protein (i.e. α and ß) are differently regulated in non-cancerous and cancerous cells both at mRNA and protein level. We were able to correlate the presence of the α variant of the protein with the progression through the interphase of cell cycle. We also observed that the different expression profiles correspond to different degradation pathways for non-cancerous and cancerous cells. Furthermore, Ki-67 is continuously regulated and degraded via proteasome system in both cell types, suggesting an active control of the protein. However we also observed a putative extranuclear elimination pathway of Ki-67 where it is transported to the Golgi apparatus. Our evidence in the different expression of the splice variants may represent a milestone for the development of new targets for cancer diagnostic and prognostic. Additionally, the unexpected extranuclear elimination of Ki-67 strongly suggests that this protein must be looked at also outside of the "nuclear box", as thought to date.
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Processamento Alternativo , Antígeno Ki-67/genética , Neoplasias/genética , Ciclo Celular , Núcleo Celular/metabolismo , Células Cultivadas , Complexo de Golgi/metabolismo , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Antígeno Ki-67/metabolismo , Neoplasias/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transporte ProteicoRESUMO
We present a two-photon (2P, 800 nm) PDT cyclometalated Iridium(iii) complex (Ir-Es) that targets the intracellular nucleus. The complex is capable of migrating sequentially from the nucleus to mitochondria and inducing dual-damage under light exposure. This study suggests that with minor modification of the terminal moieties of complexes, their final intracellular destinations and PDT efficiency can be significantly impacted.
Assuntos
Antineoplásicos/farmacologia , Núcleo Celular/metabolismo , Complexos de Coordenação/farmacologia , Irídio/química , Fotoquimioterapia , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , DNA/genética , Dano ao DNA/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Irídio/efeitos da radiação , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Raios UltravioletaRESUMO
OBJECTIVES: To explore the proteomic changes in thyroid tissue from GD patients and find new biomarkers for the prevention, diagnosis as well as the treatment of GD. DESIGN AND METHODS: Group1 included five thyroid specimens of GD cases and 5 normal thyroid tissue samples which were removed surgically and collected. The proteins were extracted from these thyroid tissues and then the differentially expressed protein spots were identified by MALDI-TOF-MS. The interested proteins were further validated in more specimens (group2: 11 pathological thyroid specimens and 7 normal thyroid tissue samples). RESULTS: A total of 34 differentially expressed proteins were observed, and the majority of these proteins were involved in endoplasmic reticulum stress (ER-stress), oxidative stress, energy metabolism, cytoskeleton and movement. The overexpression of calreticulin(CALR) and heat shock 70kDa protein 5(HSPA5) was further validated. CONCLUSION: Alltogether, abundant new candidate molecules, especially proteins related to ER-stress, were found to be involved in the pathogenesis of GD.
Assuntos
Calreticulina/metabolismo , Doença de Graves/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteômica , Glândula Tireoide/metabolismo , Adulto , Chaperona BiP do Retículo Endoplasmático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Glândula Tireoide/patologia , Adulto JovemRESUMO
As a semi-autonomous organelle, the eukaryotic mitochondrion possesses an individual DNA and protein synthesizing system. Therefore, the mitochondrial DNA-targeting probes are powerful tools to understand the functions in physiological processes. Herein, we report a novel Ru(ii) complex (HLRu) based on a phenanthroline derivative to target mitochondrial DNA. The nonlinear optical property study revealed a reverse nonlinear optical refraction character from self-focusing to self-defocusing response before and after complexation with Ru(ii). Furthermore, the two-photon absorption and high biocompatibility of complex HLRu highlight its potential applications in biological processes. It was found that complex HLRu specifically binds to mitochondrial DNA in living cells and enables imaging of tissues with minimal auto-fluorescence. As a result, this complex HLRu probe offers a promising platform to directly monitor mitochondrial DNA in living cells.