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1.
J Cell Sci ; 135(6)2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35142363

RESUMO

TDP-43 (also known as TARDBP) is a nuclear splicing factor functioning in pre-mRNA processing. Its C-terminal 35-kDa fragment (TDP-35) forms inclusions or aggregates in cytoplasm, and sequesters full-length TDP-43 into the inclusions through binding with RNA. We extended the research to investigate whether TDP-35 inclusions sequester other RNA-binding proteins (RBPs) and how RNA-binding specificity has a role in this sequestration process. We have characterized T-cell restricted intracellular antigen-1 (TIA1) and other RBPs that can be sequestered into the TDP-35 inclusions through specific RNA binding, and found that this sequestration leads to the dysfunction of TIA1 in maturation of target pre-mRNA. Moreover, we directly visualized the dynamic sequestration of TDP-43 by the cytoplasmic TDP-35 inclusions by live-cell imaging. Our results demonstrate that TDP-35 sequesters some specific RBPs and this sequestration is assisted by binding with RNA in a sequence-specific manner. This study provides further evidence in supporting the hijacking hypothesis for RNA-assisted sequestration and will be beneficial to further understanding of the TDP-43 proteinopathies.


Assuntos
Esclerose Lateral Amiotrófica , Proteinopatias TDP-43 , Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Corpos de Inclusão/metabolismo , RNA/genética , RNA/metabolismo , Precursores de RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteinopatias TDP-43/metabolismo
2.
Postgrad Med J ; 99(1173): 708-714, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37117041

RESUMO

PURPOSE: The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. METHODS: In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. RESULTS: After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to <7.55 mg/dL for men, 5.63 mg/dL to <6.42 mg/dL for women) as reference, the highest quintiles of SUA were associated with an elevated risk of all cause (HR: 1.34, 95% CI 1.00 to 1.80) in the crude model, but the association was not significant after adjusting for multiple comparisons. The association between low SUA and mortality and the dose-response analysis on the non-linearity of SUA-mortality relationship were not statistically significant. CONCLUSIONS: Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.


Assuntos
Doenças Cardiovasculares , Hipertensão , Masculino , Humanos , Feminino , Estudos de Coortes , Ácido Úrico , Estudos Prospectivos , Fatores de Risco , Hipertensão/epidemiologia , China/epidemiologia
3.
Acta Biochim Biophys Sin (Shanghai) ; 55(5): 736-748, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37171184

RESUMO

Nine polyglutamine (polyQ) proteins have already been identified that are considered to be associated with the pathologies of neurodegenerative disorders called polyQ diseases, but whether these polyQ proteins mutually interact and synergize in proteinopathies remains to be elucidated. In this study, 4 polyQ-containing proteins, androgen receptor (AR), ataxin-7 (Atx7), huntingtin (Htt) and ataxin-3 (Atx3), are used as model molecules to investigate their heterologous coaggregation and consequent impact on cellular proteostasis. Our data indicate that the N-terminal fragment of polyQ-expanded (PQE) Atx7 or Htt can coaggregate with and sequester AR and Atx3 into insoluble aggregates or inclusions through their respective polyQ tracts. In vitro coprecipitation and NMR titration experiments suggest that this specific coaggregation depends on polyQ lengths and is probably mediated by polyQ-tract interactions. Luciferase reporter assay shows that these coaggregation and sequestration effects can deplete the cellular availability of AR and consequently impair its transactivation function. This study provides valid evidence supporting the viewpoint that coaggregation of polyQ proteins is mediated by polyQ-tract interactions and benefits our understanding of the molecular mechanism underlying the accumulation of different polyQ proteins in inclusions and their copathological causes of polyQ diseases.


Assuntos
Doenças Neurodegenerativas , Proteostase , Humanos , Peptídeos/química , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Ataxina-3/genética , Ataxina-3/metabolismo
4.
Chem Biodivers ; 20(8): e202300841, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37462846

RESUMO

Three undescribed glycoside constituents, macrophyllosides E-G and a pair of iridoid glycosides genticrasides A/B, together with eleven known glycoside compounds were isolated from the roots of Gentiana crassicaulis Duthie ex Burk. Their structures were identified by means of spectra analysis and data comparison with previous literatures. Interestingly, the glucose moieties in macrophylloside E and F possess free anomeric hydroxy groups. Genticrasides A/B, identified as a pair of iridoid originated lactones, have not been reported from Gentianaceae family up to now. The anti-inflammatory effects of selected compounds were also evaluated through the nitric oxide (NO) production inhibition in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells. In which, macrophyllosides G and D showed NO inhibitory activities with rates of 76.14±4.02 % and 52.44±8.29 % at 100 µg/mL.


Assuntos
Gentiana , Gentiana/química , Raízes de Plantas/química , Glicosídeos Iridoides/farmacologia , Iridoides/análise , Macrófagos , Óxido Nítrico
5.
Zhonghua Nan Ke Xue ; 29(2): 131-137, 2023 Feb.
Artigo em Zh | MEDLINE | ID: mdl-37847084

RESUMO

OBJECTIVE: To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11-1 o'clock position on urinary continence and erectile function in BPH patients. METHODS: We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% ï¼»24/36ï¼½ vs 43.25% ï¼»20/48ï¼½, P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% ï¼»12/36ï¼½ vs 56.25% ï¼»28/48ï¼½, P = 0.018) and 12 months (25% ï¼»9/36ï¼½ vs 47.92% ï¼»23/48ï¼½, P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). CONCLUSION: Modified PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.


Assuntos
Disfunção Erétil , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Disfunção Erétil/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Mucosa , Resultado do Tratamento
6.
Eur Arch Psychiatry Clin Neurosci ; 272(5): 859-871, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35079855

RESUMO

Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Recompensa , Esquizofrenia/diagnóstico por imagem
7.
J Perianesth Nurs ; 37(4): 501-508, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35256251

RESUMO

PURPOSE: The aim of this meta-analysis was to assess the effectiveness of leg compression versus control in preventing spinal anesthesia induced hypotension during cesarean delivery. DESIGN: A meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Embase, Web of Science and CENTRAL were searched for RCTs that compared leg compression with control for prevention of hypotension in patients undergoing elective cesarean delivery under spinal anesthesia. The primary outcome was the incidence of hypotension. Subgroup analysis was performed according to leg compression methods. Secondary outcomes included nausea and vomiting, the number of vasopressor requirement, and the rates of neonatal Apgar scores ≤7 and umbilical cord blood pH ≤ 7.2. FINDINGS: Twelve studies involving 787 patients were included in this meta-analysis. There was a significant reduction of the incidence of hypotension with leg compression versus control (RR 0.45, 95% CI 0.32 to 0.62, I2 = 81%). Subgroup analysis suggested that leg wrapping may be more effective in preventing hypotension compared with elastic stockings and sequential compression mechanical devices. Leg compression also reduced maternal nausea and vasopressors requirement, but did not impact on neonatal outcomes. CONCLUSIONS: Leg compression, especially leg wrapping, decreases the incidence and severity of hypotension after spinal anesthesia in caesarean delivery. As a simple, non-pharmacologic and cost-effective intervention, leg wrapping can be used for prevention of spinal anesthesia induced hypotension in caesarean delivery, either alone or in combination with vasopressors.


Assuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão Controlada , Hipotensão , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Cesárea/efeitos adversos , Cesárea/métodos , Feminino , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Hipotensão/prevenção & controle , Hipotensão Controlada/efeitos adversos , Recém-Nascido , Perna (Membro) , Náusea/complicações , Náusea/tratamento farmacológico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasoconstritores
8.
Biochem J ; 477(21): 4295-4312, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33094816

RESUMO

Ubiquitin-specific protease 19 (USP19) is a member of the deubiquitinating (DUB) enzymes that catalyze removing the ubiquitin signals from target proteins. Our previous research has demonstrated that USP19 up-regulates the protein level and aggregation of polyQ-expanded huntingtin through the involvement of heat shock protein 90 (HSP90). Here, we present solution structures of the CS1, CS2 and UbL domains of USP19 and structural insights into their domain interactions. We found that the tandem CS domains fold back to interact with the C-terminal USP domain (USPD) intra-molecularly that leads to inhibition of the catalytic core of USP19, especially CS1 interacts with the embedded UbL domain and CS2 does with the CH2 catalytic core. Moreover, CS2 specifically interacts with the NBD domain of HSP90, which can activate the DUB enzyme. A mechanism of auto-inhibition of USP19 and activation by HSP90 is proposed, on which USP19 modulates the protein level of polyQ-expanded huntingtin in cells. This study provides structural and mechanistic insights into the modulation of protein level and aggregation by USP19 with the assistance of HSP90.


Assuntos
Endopeptidases/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Enzimas Desubiquitinantes/metabolismo , Humanos , Proteína Huntingtina/metabolismo , Peptídeos/metabolismo , Ubiquitina/metabolismo , Ubiquitinação
9.
Acta Pharmacol Sin ; 39(8): 1294-1304, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29323338

RESUMO

Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells. Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and upregulated anti-inflammatory cytokines (IL-10 and TGF-ß1) in LPS-treated RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear translocation of NF-κB by preventing the degradation of IκB-α. UTI pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK was found to function upstream of the IκB-α/NF-κB signaling pathway. Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via promotion of p62-associated Keap1 degradation. However, JNK was not involved in mediating the anti-oxidative stress effects of UTI. In summary, this study shows that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting the JNK/NF-κB and PI3K/Akt/Nrf2 pathways.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Glicoproteínas/farmacologia , Inflamação/tratamento farmacológico , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Serina Proteinase/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Citocinas/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Fator de Transcrição RelA/metabolismo
10.
Cell Biochem Biophys ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954352

RESUMO

Hepatocellular carcinoma (HCC), a widely prevalent malignancy strongly linked to inflammation, remains a significant public health concern. Triggering receptor expressed on myeloid cells 1 (TREM1), a modulator of inflammatory responses identified in recent years, has emerged as a crucial facilitator in cancer progression. Despite its significance, the precise regulatory mechanism of TREM1 in HCC metastasis remains unanswered. In the present investigation, we observed aberrant upregulation of TREM1 in HCC tissues, which was significantly linked to poorer overall survival. Inhibition of TREM1 expression resulted in a significant reduction in HCC Huh-7 and MHCC-97H cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) process. Furthermore, inhibiting TREM1 decreased protein expressions of toll-like receptor 2/4 (TLR2/4) and major myeloid differentiation response gene 88 (MyD88), leading to the inactivation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in HCC cells. Notably, these effects were reversed by treatment with TLR2-specific agonist (CU-T12-9), indicating a potential crosstalk between TREM1 and TLR2/4. Mechanistic studies revealed a direct interaction between TREM1 and both TLR2 and TLR4. In vivo studies demonstrated that inhibition of TREM1 suppressed the growth of HCC cells in the orthotopic implant model and its metastatic potential in the experimental lung metastasis model. Overall, our findings underscore the role of TREM1 inhibition in regulating EMT and metastasis of HCC cells by inactivating the TLR/PI3K/AKT signaling pathway, thereby providing deeper mechanistic insights into how TREM1 regulates metastasis during HCC progression.

11.
Huan Jing Ke Xue ; 44(4): 2093-2102, 2023 Apr 08.
Artigo em Zh | MEDLINE | ID: mdl-37040959

RESUMO

To reveal the characteristics and key impact factors of phytoplankton communities in different types of lakes, sampling surveys for phytoplankton and water quality parameters were conducted at 174 sampling sites in a total of 24 lakes covering urban, countryside, and ecological conservation areas of Wuhan in spring, summer, autumn, and winter 2018. The results showed that a total of 365 species of phytoplankton from nine phyla and 159 genera were identified in the three types of lakes. The main species were green algae, cyanobacteria, and diatoms, accounting for 55.34%, 15.89%, and 15.07% of the total number of species, respectively. The phytoplankton cell density varied from 3.60×106-421.99×106 cell·L-1, chlorophyll-a content varied from 15.60-240.50 µg·L-1, biomass varied from 27.71-379.79 mg·L-1, and the Shannon-Wiener diversity index varied from 0.29-2.86. In the three lake types, cell density, Chla, and biomass were lower in EL and UL, whereas the opposite was true for the Shannon-Wiener diversity index. NMDS and ANOSIM analysis showed differences in phytoplankton community structure (Stress=0.13, R=0.048, P=0.2298). In addition, the phytoplankton community structure of the three lake types had significant seasonal characteristics, with chlorophyll-a content and biomass being significantly higher in summer than in winter (P<0.05). Spearman correlation analysis showed that phytoplankton biomass decreased with increasing N:P in UL and CL, whereas the opposite was true for EL. Redundancy analysis (RDA) showed that WT, pH, NO3-, EC, and N:P were the key factors that significantly affected the variability in phytoplankton community structure in the three types of lakes in Wuhan (P<0.05).


Assuntos
Cianobactérias , Diatomáceas , Fitoplâncton , Lagos/análise , Clorofila/análise , Clorofila A
12.
J Chin Med Assoc ; 85(11): 1093-1097, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35797551

RESUMO

BACKGROUND: Infrared ear thermometry is widely used in clinical practice due to its noninvasive, convenient, and quick sampling. However, its accuracy and feasibility in anesthetized patients have not yet been established. METHODS: We conducted this cross-sectional study to evaluate the agreement between infrared ear temperature and nasopharyngeal temperature in general anesthetized patients and its performance in intraoperative hypothermia, defined as nasopharyngeal temperature <36°C. Adult female patients who underwent gynecological surgery under general anesthesia were enrolled in this study. Infrared ear temperature by Braun ThermoScan PRO 4000 (Braun GmbH, Kronberg, Germany) and nasopharyngeal temperature were measured simultaneously before, during, and after surgery. The agreement between the two temperatures was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The diagnostic performance of the infrared ear thermometer for hypothermia was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Fifty-six patients with 168 pairs of simultaneous infrared ear and nasopharyngeal temperatures were included in this analysis. The mean infrared ear temperature was consistently higher than the nasopharyngeal temperature throughout surgery, but the differences were small (0.22, 0.13, and 0.06°C before, during, and after surgery, respectively). The ICC between the two temperatures before, during, and after surgery was 0.70, 0.75, and 0.80, respectively, and 93.5% of the differences fell within the 95% limits of agreement of ±0.5°C. An infrared ear thermometer had high diagnostic accuracy for hypothermia, with an area under the ROC curve of 0.95 (95% confidence interval [CI], 0.92-0.98). The cutoff of infrared ear temperature for hypothermia was 36.2°C with a sensitivity of 0.89 (95% CI, 0.71-0.98) and a specificity of 0.87 (95% CI, 0.81-0.92). CONCLUSION: The infrared ear temperature is in good agreement with the nasopharyngeal temperature in general anesthetized patients without hyperthermia and has high performance for detecting hypothermia. An infrared ear thermometer can be a diagnostic tool for intraoperative hypothermia.


Assuntos
Hipotermia , Adulto , Humanos , Feminino , Hipotermia/diagnóstico , Temperatura , Estudos Transversais , Temperatura Corporal , Termômetros
13.
Asian J Psychiatr ; 78: 103306, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36308992

RESUMO

Impairments of translating emotional salience into effortful behavior are core features of anhedonia in cohorts with major depressive disorder. Glutamate metabolism is considered to be involved in this process, but the empirical study is relatively few. Therefore, the present study aimed to examine the correlations between glutamate level in pregenual anterior cingulate, anhedonia, and emotion-behavior decoupling in patients with major depressive disorder. Fifteen individuals diagnosed with major depressive disorder and ten healthy individuals were recruited. All participants were asked to complete self-report instruments for anhedonia and the computerized anticipatory and consummatory pleasure task, and the in vivo glutamate levels were measured by proton magnetic resonance spectroscopy. Thus, a potential lower glutamate levels in pregenual anterior cingulate in individuals with major depressive disorder were founded to be positively correlated with the ability of pleasure experiencing. The mechanism of glutamate in pregenual anterior cingulate in anhedonia in patients with major depressive disorder may be reflected in the early pleasurable experience stage, rather than in the transformation of emotional experience to motivation or reward-seeking behavior, which may be different from that in schizophrenia.


Assuntos
Anedonia , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Ácido Glutâmico/metabolismo , Emoções
14.
Sci Rep ; 11(1): 7815, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837238

RESUMO

Polyglutamine (polyQ) expansion of proteins can trigger protein misfolding and amyloid-like aggregation, which thus lead to severe cytotoxicities and even the respective neurodegenerative diseases. However, why polyQ aggregation is toxic to cells is not fully elucidated. Here, we took the fragments of polyQ-expanded (PQE) ataxin-7 (Atx7) and huntingtin (Htt) as models to investigate the effect of polyQ aggregates on the cellular proteostasis of endogenous ataxin-3 (Atx3), a protein that frequently appears in diverse inclusion bodies. We found that PQE Atx7 and Htt impair the cellular proteostasis of Atx3 by reducing its soluble as well as total Atx3 level but enhancing formation of the aggregates. Expression of these polyQ proteins promotes proteasomal degradation of endogenous Atx3 and accumulation of its aggregated form. Then we verified that the co-chaperone HSJ1 is an essential factor that orchestrates the balance of cellular proteostasis of Atx3; and further discovered that the polyQ proteins can sequester HSJ1 into aggregates or inclusions in a UIM domain-dependent manner. Thereby, the impairment of Atx3 proteostasis may be attributed to the sequestration and functional loss of cellular HSJ1. This study deciphers a potential mechanism underlying how PQE protein triggers proteinopathies, and also provides additional evidence in supporting the hijacking hypothesis that sequestration of cellular interacting partners by protein aggregates leads to cytotoxicity or neurodegeneration.


Assuntos
Ataxina-3/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Chaperonas Moleculares/metabolismo , Doenças Neurodegenerativas/metabolismo , Peptídeos/metabolismo , Agregados Proteicos/genética , Agregação Patológica de Proteínas/metabolismo , Proteostase/genética , Proteínas Repressoras/metabolismo , Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Ataxina-3/química , Ataxina-3/genética , Células HEK293 , Humanos , Proteína Huntingtina/metabolismo , Corpos de Inclusão/metabolismo , Espaço Intracelular/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Agregação Patológica de Proteínas/genética , Domínios Proteicos/genética , Proteólise , Proteínas Repressoras/química , Proteínas Repressoras/genética , Transdução de Sinais/genética , Solubilidade , Transfecção
15.
Front Neurosci ; 15: 742973, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759792

RESUMO

Purpose: Tension-type headache (TTH), the most prevalent primary headache disorder, imposes an enormous burden on the people of the world. The quest to ease suffering from this neurological disorder has sustained research interest. The present study aimed at evaluating the amplitude of low-frequency oscillations (LFOs) of the brain in multiple frequency bands in patients with TTH. Methods: To address this question, 63 participants were enrolled in the study, including 32 TTH patients and 31 healthy controls (HCs). For all the participants, amplitude of low-frequency fluctuation (ALFF) was measured in six frequency bands (conventional frequency bands, 0.01-0.08 Hz; slow-2, 0.198-0.25 Hz; slow-3, 0.073-0.198 Hz; slow-4, 0.027-0.073 Hz; slow-5, 0.01-0.027 Hz; and slow-6, 0-0.01 Hz), and the differences between TTH patients and HCs were examined. To explore the relationship between the altered ALFF brain regions in the six frequency bands and the Visual Analog Scale (VAS) score in the TTH patients, Pearson's correlation analysis was performed. Results: In all the six frequency bands, a decreased ALFF value was detected, and regions showing reduced ALFF values were mostly located in the middle frontal gyrus and superior gyrus. A frequency-dependent alternating characterization of intrinsic brain activity was found in the left caudate nucleus in the slow-2 band of 0.198-0.25 Hz and in the right inferior frontal orbital gyrus in the slow-5 band of 0.01-0.027 Hz. For the correlation results, both the left anterior cingulate and paracingulate gyri and right superior parietal gyrus showed a positive correlation with the VAS score in the slow-4 frequency band of 0.027-0.073 Hz. Conclusion: The ALFF alterations in the brain regions of TTH patients are involved in pain processing. The altered LFOs in the multiple regions may help promote the understanding of the pathophysiology of TTH. These observations could also allow the future treatment of TTH to be more directional and targeted and could promote the development of TTH treatment.

16.
Transl Pediatr ; 10(10): 2409-2417, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765464

RESUMO

BACKGROUND: The present study aimed to investigate the P-wave changes in intracavitary electrocardiography (IC-ECG) during catheterization with a peripherally inserted central catheter (PICC) in order to provide guidance for the accurate localization of the tip of the PICC. METHODS: A total of 106 newborns who needed a PICC were randomly divided into two groups-a study group and a control group-using a random number table, with 53 cases in each group. In the study group, the ECG monitor was connected after the successful puncture and insertion of the PICC into the right sternoclavicular joint, and the position of the catheter tip was determined according to the P-wave changes on the IC-ECG. Localization X-rays were taken at the same time. In the control group, after the successful routine puncture and insertion of the PICC into the location to a predetermined length, localization X-rays were taken. The accuracy, procedure duration, and cost of the two localization methods were evaluated. RESULTS: The accuracy of the localization in the study group was 92.5%, but the difference was not significant when compared with the control group (P>0.05). The duration of the procedure in the study group was 5.12±1.57 minutes, and the cost was 7.12±0.56 yuan, both of which were significantly different when compared with the control group (P<0.05). CONCLUSIONS: P-wave changes during IC-ECG have high accuracy in determining the location of the tip of the PICC. It is also a simple method and has certain clinical application value. TRIAL REGISTRATION: Chinese Clinical Trial Registry (number: ChiCTR2100047660).

17.
Infect Dis Poverty ; 9(1): 141, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046120

RESUMO

In the past five months, success in control the national epidemic of coronavirus disease 2019 (COVID-19) has been witnessed in China. The implementation of public health measures accounts for the success which include different interventions in the early or later stages of the outbreak. It is clear that although not all measures were universally effective worldwide, their achievements have been significant. More solidarity is needed to deal with this global pandemic with more learning and understanding. Understanding which of the public health interventions implemented in China were effective may provide ideas for international epidemic control.


Assuntos
Infecções por Coronavirus/prevenção & controle , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Saúde Pública/métodos , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Diagnóstico Precoce , Humanos , Controle de Infecções/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Saúde Pública/normas , SARS-CoV-2
18.
Zhonghua Yan Ke Za Zhi ; 45(6): 550-5, 2009 Jun.
Artigo em Zh | MEDLINE | ID: mdl-19957680

RESUMO

OBJECTIVE: To evaluate the combined effect of topical rapamycin (RAPA) eye drop in nanometer vector and poly (lactic acid) (PLA) wafers of cyclosporine A (CsA) in the prevention of acute allograft rejection after rabbit corneal transplantation. Methods It was an experimental study. RAPA was incorporated into the nanometer particles and CsA was incorporated into PLA wafers. A was syngeneic control whose both donor and recipient are New Zealand rabbit. Gray donor corneas were implanted into the 102 recipients of New Zealand albino rabbits with corneal neovascularization who were randomly divided into B, C, D, E, F, G 6 groups to receive the different types of therapy: B was no therapy control; C was eye drop of nanometer vector but no RAPA twice a day, 28 days; D was PLA wafers in the anterior chamber of rabbit eyes but no drugs; E was 0.5% RAPA eye drop of nanometer vector twice a day, 28 days; F was PLA wafers of CsA in the anterior chamber of rabbit eyes; G was PLA wafers of CsA in the anterior chamber of rabbit eyes and 0.5% RAPA eye drop of nanometer vector eye drop twice a day for 28 days together. Postoperative evaluation included slit-lamp biomicroscopy, histopathology and immunohistology, Cytokines related with neovascularization and immunosuppression in the corneal tissue by RT-PCR. The graft survival was assessed by One-Way ANOVA and q test. RESULTS: Corneal allograft survival time: A (100.00 +/- 0.00), B (8.44 +/- 1.24), C (8.89 +/- 2.57), D (8.56 +/- 2.30), E (43.11 +/- 5.58), F (43.67 +/- 9.54), G (72.00 +/- 15.34) d. Group G led to a statistically significant prolongation of transplant survival and was superior than group E and F which was a statistical prolongation compared with group B, C and D (qGE = 11.42, qGF = 11.24, qEB = 13.64, qEC = 13.38, qED = 13.46, qFB = 13.82, qFC = 13.56, qFD = 13.64; P < 0.01). Immunohistopathologically, the grafts were subjected to an immune response contained a dense infiltrate of neutrophils, CD4+ and CD8+ T lymphocytes in the group B, C and D. This cellular infiltrate was a significant reduction in group E,F,G. RT-PCR showed that the gene expression of IL-2 was inhibited earlier (3 days) in group F, G and VEGF gene expression being suppressed later (14 days) in group E, G. CONCLUSIONS: Combined therapy with topical application of RAPA eye drop of nanometer vector and CsA PLA wafers can significantly prolong the survival of allograft at high-risk. Moreover, topical combined treatment of them is more effective, lower dosage, less side-effects and cheaper than the treatment with topical individual immunosuppressive drug.


Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Animais , Transplante de Córnea , Sistemas de Liberação de Medicamentos , Ácido Láctico/uso terapêutico , Nanopartículas/uso terapêutico , Poliésteres , Polímeros/uso terapêutico , Coelhos
19.
Zhonghua Nan Ke Xue ; 9(1): 45-7, 2003 Feb.
Artigo em Zh | MEDLINE | ID: mdl-12680332

RESUMO

OBJECTIVES: To investigate the difference of BPH incidence in two groups. METHODS: 309 cadres and 314 farmers over 60 years old in district of Wannan have been investigated. The investigation included prostate volume (V), IPSS, L, Qmax, residual urine (R) and dietary constituents. RESULTS: The intake of animal protein in cadres is more than that in farmers (u = 24.10, P < 0.01), and the incidence rate of BPH is significantly higher (91.1% vs 11.8%, chi 2 = 24.64, P < 0.001). Logistic regression shows that the intake of animal protein has a parallel relationship with BPH. CONCLUSIONS: In the district of Wannan, the incidence of BPH in cadres is significantly higher than that of farmers, and it may be correlated with the amount of animal protein intake.


Assuntos
Dieta , Hiperplasia Prostática/epidemiologia , Idoso , China/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , População Rural , População Urbana
20.
Huan Jing Ke Xue ; 35(1): 292-8, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24720218

RESUMO

To evaluate the enantioselective toxicity of chiral pesticide coexisting with heavy metal, the enantioselective toxicity of Rac-, S-metolachlor alone and coexisting with Zn2+ on Scenedesmus obliquus was studied by using standard toxic testing method. The results showed that the trend of the enantioselective toxicity of Rac- and S-metolachlor coexisting with Zn2+ was similar to that of Rac- and S-metolachlor alone. The growth inhibition rate of Scenedesmus obliquus was decreased by the coexistence of Zn2+ with high concentrations of metolachlor. The inhibition rates with 0.30 mg x L(-1) Rac- and S-metolachlor alone at 24 h were 49.61% and 59.73%, and in the coexistence of Zn2+ the values were 38.41% and 42.52%, respectively. The enantioselective toxicity of Rac- and S-metolachlor was expanded and the toxicity of S-metolachlor increased greater than that of Rac-metolachlor. The coexistence of Zn2+ showed partial increase in toxicity of metolachlor in low concentrations, while there was antagonistic effect in high content of metolachlor. The trend of Chlorophyll content of Scenedesmus obliquus at 96 h was in accordance with the growth inhibition.


Assuntos
Acetamidas/toxicidade , Herbicidas/toxicidade , Scenedesmus/efeitos dos fármacos , Zinco/química , Clorofila/análise , Poluentes Químicos da Água/toxicidade
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