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1.
Immunity ; 49(1): 107-119.e4, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-29958798

RESUMO

Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages decreased intestinal motility and was sufficient to reverse the GI hypermotility that is associated with chemotherapy treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of prostaglandin E2 and elicited colon contraction in a paracrine manner via prostaglandin E receptor signaling in intestinal smooth muscle cells without input from the enteric nervous system. Collectively, our data identify TRPV4-expressing MMs as an essential component required for maintaining normal GI motility and provide potential drug targets for GI motility disorders.


Assuntos
Colo/fisiologia , Motilidade Gastrointestinal , Macrófagos/metabolismo , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais , Canais de Cátion TRPV/metabolismo , Animais , Receptor 1 de Quimiocina CX3C/metabolismo , Colo/fisiopatologia , Ciclo-Oxigenase 1/deficiência , Ciclo-Oxigenase 1/metabolismo , Dinoprostona/análise , Dinoprostona/metabolismo , Feminino , Mucosa Gástrica/citologia , Expressão Gênica , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Contração Muscular , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/deficiência , Canais de Cátion TRPV/genética
2.
Am J Physiol Cell Physiol ; 326(6): C1697-C1709, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38586875

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study used APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by Western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of Sirt4. Subsequently, the binding of transcription factors to Sirt4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells compared with their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.NEW & NOTEWORTHY The study reveals that in Alzheimer's disease models, SIRT4 expression increases, contributing to neuronal apoptosis and amyloid-ß deposition. Reducing SIRT4 lessens apoptosis and amyloid-ß accumulation, improving memory in mice. This process involves the mTOR pathway, regulated by STAT2 transcription factor. These findings suggest targeting the STAT2-SIRT4-mTOR axis as a potential Alzheimer's treatment strategy.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Apoptose , Modelos Animais de Doenças , Camundongos Transgênicos , Neurônios , Fator de Transcrição STAT2 , Transdução de Sinais , Sirtuínas , Serina-Treonina Quinases TOR , Animais , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Sirtuínas/metabolismo , Sirtuínas/genética , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Fator de Transcrição STAT2/metabolismo , Fator de Transcrição STAT2/genética , Peptídeos beta-Amiloides/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linhagem Celular , Proteínas Mitocondriais
3.
Cell Mol Neurobiol ; 44(1): 20, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345650

RESUMO

Alzheimer disease (AD) is an irreversible neurodegenerative disease, and astrocytes play a key role in its onset and progression. The aim of this study is to analyze the characteristics of neurotoxic astrocytes and identify novel molecular targets for slowing down the progression of AD. Single-nucleus RNA sequencing (snRNA-seq) data were analyzed from various AD cohorts comprising about 210,654 cells from 53 brain tissue. By integrating snRNA-seq data with bulk RNA-seq data, crucial astrocyte types and genes associated with the prognosis of patients with AD were identified. The expression of neurotoxic astrocyte markers was validated using 5 × FAD and wild-type (WT) mouse models, combined with experiments such as western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence. A group of neurotoxic astrocytes closely related to AD pathology was identified, which were involved in inflammatory responses and pathways related to neuron survival. Combining snRNA and bulk tissue data, ZEP36L, AEBP1, WWTR1, PHYHD1, DST and RASL12 were identified as toxic astrocyte markers closely related to disease severity, significantly elevated in brain tissues of 5 × FAD mice and primary astrocytes treated with Aß. Among them, WWTR1 was significantly increased in astrocytes of 5 × FAD mice, driving astrocyte inflammatory responses, and has been identified as an important marker of neurotoxic astrocytes. snRNA-seq analysis reveals the biological functions of neurotoxic astrocytes. Six genes related to AD pathology were identified and validated, among which WWTR1 may be a novel marker of neurotoxic astrocytes.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Doenças Neurodegenerativas/metabolismo , Análise de Sequência de RNA , RNA Nuclear Pequeno/metabolismo , Peptídeos beta-Amiloides/metabolismo , Carboxipeptidases/metabolismo , Proteínas Repressoras/metabolismo
4.
Mol Biol Rep ; 51(1): 351, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400865

RESUMO

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.


Assuntos
Inflamassomos , Doenças do Sistema Nervoso , Humanos , Inflamassomos/metabolismo , Citocinas/metabolismo , Caspase 1/metabolismo , Apoptose , Doenças do Sistema Nervoso/genética , Caspases , Peptídeos e Proteínas de Sinalização Intracelular
5.
Aging Clin Exp Res ; 36(1): 37, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345751

RESUMO

BACKGROUND: Non-invasive brain stimulation (NIBS) is a burgeoning approach with the potential to significantly enhance cognition and functional abilities in individuals who have undergone a stroke. However, the current evidence lacks robust comparisons and rankings of various NIBS methods concerning the specific stimulation sites and parameters used. To address this knowledge gap, this systematic review and meta-analysis seek to offer conclusive evidence on the efficacy and safety of NIBS in treating post-stroke cognitive impairment. METHODS: A systematic review of randomized control trials (RCT) was performed using Bayesian network meta-analysis. We searched RCT in the following databases until June 2022: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and EMBASE. We compared any active NIBS to control in terms of improving cognition function and activities of daily living (ADL) capacity following stroke. RESULTS: After reviewing 1577 retrieved citations, a total of 26 RCTs were included. High-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (mean difference 2.25 [95% credible interval 0.77, 3.66]) was identified as a recommended approach for alleviating the global severity of cognition. Dual-rTMS (27.61 [25.66, 29.57]) emerged as a favorable technique for enhancing ADL function. In terms of stimulation targets, the dorsolateral prefrontal cortex exhibited a higher ranking in relation to the global severity of cognition. CONCLUSIONS: Among various NIBS techniques, HF-rTMS stands out as the most promising intervention for enhancing cognitive function. Meanwhile, Dual-rTMS is highly recommended for improving ADL capacity.


Assuntos
Disfunção Cognitiva , Metanálise em Rede , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Atividades Cotidianas , Cognição/fisiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
6.
Geriatr Nurs ; 55: 64-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37976557

RESUMO

BACKGROUND: In this prospective study, we evaluated the usefulness of the advanced dementia prognostic tool (ADEPT) for estimating the 2-year survival of persons with advanced dementia (AD) in China. METHODS: The study predicted the 2-year mortality of 115 persons with AD using the ADEPT score. RESULTS: In total, 115 persons with AD were included in the study. Of these persons, 48 died. The mean ADEPT score was 13.0. The AUROC for the prediction of the 2-year mortality rate using the ADEPT score was 0.62. The optimal threshold of the ADEPT score was 11.2, which had an AUROC of 0.63, specificity of 41.8, and sensitivity of 83.3. CONCLUSIONS: The ADEPT score based on a threshold of 11.2 may serve as a prognostic tool to determine the 2-year survival rate of persons with AD in Chongqing, China. However, further studies are needed to explore the nature of this relationship.


Assuntos
Demência , Humanos , Estudos Prospectivos , Prognóstico , China
7.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-39289777

RESUMO

Bariatric surgery may cause intestinal microecological environment imbalance due to changes in gastrointestinal anatomy. Some patients may have complications, even regain weight. Probiotics can act on intestinal mucosa, epithelium and gut-associated lymphoid tissue to improve the intestinal microecological environment of obese patients after bariatric surgery. Probiotics can promote the production of intestinal antibacterial substances, bind specifically to receptors, decrease intestinal pH value, reduce the inflammatory factors, thus helping patients lose weight and lower blood sugar levels after bariatric surgery. Probiotics can produce lactic acid, acetic acid, lactase, etc., inhibit the growth of harmful bacteria, improve gastrointestinal symptoms of patients after bariatric surgery. Probiotics can activate the AMP-activated protein kinase signaling pathway, improve lipid metabolism, and promote the recovery of symptom indicators of nonalcoholic fatty liver disease after bariatric surgery. Probiotics can regulate the release of neurotransmitters or metabolites by the microbiota through the gut-brain axis to affect brain activity and behavior, thus helping patients improve bad mood after bariatric surgery. This article describes the intestinal microecological environment of obese patients and the change mechanism after bariatric surgery and summarizes the effects and possible mechanisms of probiotics in improving the intestinal microecological environment of obese patients after bariatric surgery, in order to provide references for promoting the clinical application of probiotics.

8.
BMC Gastroenterol ; 23(1): 312, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710166

RESUMO

BACKGROUND: Pancreatic adenocarcinoma is one of the most lethal tumors in the world with a poor prognosis. Thus, an accurate prediction model, which identify patients within high risk of pancreatic adenocarcinoma is needed to adjust the treatment and elevate the prognosis of these patients. METHODS: We obtained RNAseq data of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) from UCSC Xena database, identified immune-related lncRNAs (irlncRNAs) by correlation analysis, and identified differential expressed irlncRNAs (DEirlncRNAs) between pancreatic adenocarcinoma tissues from TCGA and normal pancreatic tissues from TCGA and Genotype-Tissue Expression (GTEx). Further univariate and lasso regression analysis were performed to construct prognostic signature model. Then, we calculated the areas under curve and identified the best cut-off value to identify high- and low-risk patients with pancreatic adenocarcinoma. The clinical characteristics, immune cell infiltration, immunosuppressive microenvironment, and chemoresistance were compared between high- and low-risk patients with pancreatic adenocarcinoma. RESULTS: We identified 20 DEirlncRNA pairs and grouped the patients by the best cut-off value. We proved that our prognostic signature model possesses a remarkable efficiency to predict prognosis of PAAD patients. The AUC for ROC curve was 0.905 for 1-year prediction, 0.942 for 2-year prediction, and 0.966 for 3-year prediction. Patients in high-risk group have poor survival rate and worse clinical characteristics. We also proved that patients in high-risk groups were in immunosuppressive status and may be resistant to immunotherapy. Anti-cancer drug evaluation was performed based on in-silico predated tool, such as paclitaxel, sorafenib, and erlotinib, may be suitable for PAAD patients in high-risk group. CONCLUSIONS: Overall, our study constructed a novel prognostic risk model based on pairing irlncRNAs, exhibited a promising prediction value in patients with pancreatic adenocarcinoma. Our prognostic risk model may help distinguish PAAD patients suitable for medical treatments.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , Adenocarcinoma/genética , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Pâncreas , Imunossupressores , Microambiente Tumoral , Neoplasias Pancreáticas
9.
J Fluoresc ; 33(3): 849-858, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36595093

RESUMO

In the study, silicon doped carbon quantum dots (Si-CQDs) was prepared by one-pot hydrothermal method with (3-aminopropyl) triethoxysilane (APTES) and o-phenylenediamine (OPD) as raw materials. Then a new ratiometric fluorescent probe (RF-probe) was successfully established for sensitively and selectively monitoring proanthocyanidins (PAs) with a linear range of 10-500 nM and limit of detection (LOD) of 5.6 nM. that is, the fluorescence (FL) intensity of Si-CQDs at 570 nm was used as the built-in reference, while dopamine (DA) reacting with 4-hexylresorcinol (4-HR) could produce a new fluorescent substance (named as azamonardine, AZMON), and its FL intensity at 480 nm was reduced because Cr(VI) could oxidize DA to generate quinone without fluorescence. In the presence of PAs, Cr(VI) was reduced to Cr(III), which caused that the amount of DA reacting with 4-HR was increased, thus the FL intensity of AZMON was recovered. Furthermore, the RF-probe was successfully used for the determination of PAs in black goji berry from two different areas and PAs capsule with satisfactory results compared to the standard HPLC method.


Assuntos
Proantocianidinas , Pontos Quânticos , Corantes Fluorescentes , Silício , Carbono , Oxirredução , Dopamina
10.
Surg Endosc ; 37(6): 4421-4430, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36781469

RESUMO

BACKGROUND AND AIMS: Chromoendoscopy with Lugol's staining is used to screen for early esophageal squamous cell carcinoma (ESCC). Its efficacy is greatly limited by unstandardized defoaming preparation. This study aimed to confirm whether pre-procedure oral administration of pronase could improve the diagnostic performance of Lugol chromoendoscopy in high-risk patients being screened for early ESCC. METHODS: A total of 955 patients at-risk were prospectively recruited for screening for ESCC. Patients were randomly assigned (1:1) to groups with or without (control group) pronase administration. Endoscopic diagnosis of early ESCC was based on the presence of pink-color sign in Lugol's unstained area, and a biopsy was routinely conducted if the Lugol's unstained lesion was larger than 0.5 cm. The early cancer detection rate was used as the primary endpoint. RESULTS: Pre-procedure oral administration of pronase improved mucosal visibility during Lugol chromoendoscopy (P = 0.008). There were no differences in the number of Lugol's unstained lesions between the 2 groups (23.27% [111/477] vs. 25.11% [120/478], P = 0.508). Meaningfully, the detection rate of ESCC (confirmed by histopathology) was significantly higher in the pronase group than in the control group (27.03% [30/111] vs. 17.50% [21/120], P = 0.041), as well as the detection rate of lesions with pink-color sign during chromoendoscopy (35.14% [39/111] vs. 13.33% [16/120], P < 0.001). The diagnostic performance of Lugol chromoendoscopy had improved with the use of pronase (area under the curve = 0.85 vs. 0.69, P = 0.019), accompanied by an increased sensitivity (86.67% vs. 47.62%, P = 0.004). There was no difference in the adverse events between the 2 groups (P = 0.793). CONCLUSIONS: Pre-procedure oral administration of pronase significantly increased the detection rate of early ESCC and optimized the diagnostic performance of Lugol chromoendoscopy, which should be recommended during routine endoscopic screening for early ESCC in high-risk patients. TRIAL REGISTRATION: Pronase improves efficacy of Lugol chromoendoscopy screening on esophageal cancerous lesions (NCT02030769).


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Pronase , Esofagoscopia/métodos , Estudos Prospectivos , Corantes
11.
Health Commun ; 38(14): 3346-3356, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36419354

RESUMO

Recently, the World Health Organization noted the increasing signs of pandemic fatigue around the world and repeatedly warned the public to continue to stay cautious. The current study explores whether social media use plays a role in the formation and development of pandemic fatigue. Drawing on a survey of 849 social media users in China, the findings indicated that different social media behaviors play different roles in affecting pandemic fatigue. Specifically, social interaction use is negatively associated with pandemic fatigue, mediated by more social support and reduced hopelessness. Active content use contributes to pandemic fatigue development, an association explained by information overload and desensitization. Notably, passive content use is found to trigger reactance but is negatively associated with pandemic fatigue, which is fully mediated by reduced information overload. This study seeks to understand how pandemic fatigue is associated with social media use and to explicate the underlying mechanism. The implications of the findings and directions for future research are discussed.


Assuntos
Pandemias , Mídias Sociais , Humanos , Afeto , China/epidemiologia , Fadiga
12.
Drug Chem Toxicol ; 46(6): 1100-1107, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36220803

RESUMO

Inhalation of high concentrations of phosgene often causes pulmonary edema, which obstructs the airway and causes tissue hypoxia. There is currently no specific antidote. This study was performed to investigate the effect behind pentoxifylline (PTX) treatment for phosgene-induced lung injury in rat models. Rats were exposed to phosgene. The protein levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and occludin proteins in lung tissue were determined. The effect of both prophylactic and therapeutic administration of PTX (50 mg/kg and 100 mg/kg) was evaluated. The lung permeability index and HIF-1α protein level increased, the arterial blood oxygenation index (PaO2/FIO2 ratio) and occludin protein level decreased significantly 6 h after phosgene exposure (P < 0.05). PTX exerted protective effects by HIF-1α-VEGF-occludin signaling pathway to some extent. Moreover, prophylactic, but not therapeutic administration of PTX (100 mg/kg), exhibited a significant protective effect. Pretreatment with PTX protected against phosgene-induced lung injury, possibly by inhibiting differential expression of HIF-1α, VEGF, and occludin.


Assuntos
Pneumopatias , Lesão Pulmonar , Pentoxifilina , Fosgênio , Ratos , Animais , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/prevenção & controle , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Fosgênio/toxicidade , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ocludina/genética , Fatores de Crescimento do Endotélio Vascular , Hipóxia/induzido quimicamente , Hipóxia/tratamento farmacológico
13.
J Pak Med Assoc ; 73(4): 901-904, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37052011

RESUMO

Pancreatic cancer is a highly malignant digestive tract tumour with a poor prognosis. We herein report the case of a 58-year-old female who presented, in June 2019, because of upper abdominal discomfort after eating. Initially, the patient was diagnosed with chronic non-atrophic gastritis with erosion and multiple gastric polyps by gastroscopic examination. Subsequently, CT and MRI examinations revealed that dilatation of the pancreatic duct and low-density nodular shadows enhanced in the neck and body of the pancreas. Endoscopic ultrasonography identified the echo foci in the same position. Additionally, a high-level of CA19-9 in the patient's serum was noted, which was a tumour marker of pancreatic cancer. Finally, the patient was diagnosed with poorly differentiated pancreatic cancer with squamous carcinoma and plasmacytoid microcystic adenoma. In conclusion, imaging examination has exhibited a vital functional role in the diagnosis of many cancers, which help gain valuable treatment time and prolong the life of patients.


Assuntos
Neoplasias Císticas, Mucinosas e Serosas , Neoplasias Pancreáticas , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Pâncreas , Neoplasias Pancreáticas
14.
Immunology ; 166(2): 169-184, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35263451

RESUMO

T cell inhibitory receptors can regulate the proliferation or function of T cells by binding to their ligands and present a unique opportunity to manage destructive immune responses during porcine islet xenotransplantation. We applied ex vivo porcine islet xenotransplantation and in vitro mixed lymphocyte-islet reaction models to assess immune checkpoint receptor expression profiles in recipient T cells, investigated whether CTLA4 or VISTA immunoglobulin (Ig) combination therapy alone could suppress porcine islet xenograft rejection and further analyzed its potential immune tolerance mechanism. Recipient T cells expressed moderate to high levels of CTLA4, PD-1, TIGIT and VISTA, and the frequency of CTLA4+ CD4+ , TIGIT+ CD4+ , VISTA+ CD4+ and VISTA+ CD8+ T cells was positively correlated with porcine islet xenograft survival time in xenotransplant recipients. Combined treatment with CTLA4Ig and VISTAIg selectively inhibited recipient CD4+ T cell hyper-responsiveness and proinflammatory cytokine production and significantly delayed xenograft rejection. SOCS1 deficiency in CD4+ T cells stimulated by xenogeneic islets facilitated hyper-responsiveness and abolished the suppressive effect of combination therapy on recipient T cell-mediated porcine islet damage in vivo and in vitro. Further mechanistic studies revealed that combined treatment significantly induced SOCS1 expression and inhibited the Jak-STAT signalling pathway in wild-type recipient CD4+ T cells stimulated by xenogeneic islets, whereas SOCS1 deficiency resulted in Jak-STAT signalling pathway activation in recipient CD4+ T cells. We demonstrated a major role for CTLA4 and VISTA as key targets in CD4+ T cell hyper-responsiveness and porcine islet xenograft rejection. The selective inhibition of CD4+ T cell immunity by CTLA4Ig/VISTAIg is based on SOCS1-dependent signalling.


Assuntos
Transplante das Ilhotas Pancreáticas , Animais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Antígeno CTLA-4 , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Tolerância Imunológica , Transplante das Ilhotas Pancreáticas/métodos , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/genética , Suínos , Transplante Heterólogo/métodos
15.
J Neuroinflammation ; 19(1): 121, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35624482

RESUMO

BACKGROUND: The complex pathophysiology of epilepsy hampers the development of effective treatments. Although more than ten kinds of anti-seizures drugs (ASDs) have good effects on seizure control worldwide, about 30% of patients still display pharmacoresistance against ASDs. Neuroinflammation seems to play a crucial role in disease progression. G protein-coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis. However, the role of GPR120 in epilepsy remains unclear. In this study, we aimed to explore the mechanism of GPR120 in epilepsy. METHODS: Male adult C57BL/6 mice were intracranially injected with kainic acid (KA) to establish epilepsy model, and the adeno associated virus (AAV) was administered intracranially at 3 weeks before KA injection. VX765 was administered by intragastric administration at 30 min before KA induced and an equal dose administrated twice a day (10 a.m. and 4 p.m.) lasting 7 days until the mice were killed. Western blot analysis, immunofluorescence staining, video monitoring of seizure, LFP recording, Nissl staining were performed. RESULTS: GPR120 was increased in both the hippocampus and cortex in the KA-induced model with temporal lobe epilepsy (TLE), and both were most highly expressed at 7 days after KA injection. Overexpression of GPR120 significantly alleviated epileptic activity, reduced neuronal death after status epilepticus (SE), downregulated the expression of IL-1ß, IL-6, IL-18, and pyrin domain-containing protein 3 (NLRP3) inflammasome, whereas knockdown GPR120 showed the opposite effect. The effects of GPR120 knockdown were reversed by VX765 inhibition cysteinyl aspartate specific proteinase-1 (Caspase-1). CONCLUSION: GPR120 modulates epileptic seizure activity and affects neuronal survival in KA-induced mouse model of temporal lobe epilepsy. Furthermore, GPR120 regulated neuroinflammation in epileptic animals through NLRP3/Caspase-1/IL-1ß signaling pathway.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Estado Epiléptico , Animais , Caspases , Epilepsia/induzido quimicamente , Epilepsia do Lobo Temporal/induzido quimicamente , Humanos , Inflamassomos , Ácido Caínico/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Receptores Acoplados a Proteínas G/genética , Estado Epiléptico/induzido quimicamente
16.
J Transl Med ; 20(1): 250, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659682

RESUMO

Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients' survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies.


Assuntos
Neoplasias Gástricas , Microambiente Tumoral , Hemoglobinas Glicadas/metabolismo , Humanos , Estresse Oxidativo/genética , Prognóstico , Neoplasias Gástricas/patologia , Microambiente Tumoral/genética
17.
J Med Virol ; 94(6): 2684-2693, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34905230

RESUMO

Currently, the studies focused on the immune response to hepatitis B vaccination in Chinese human immunodeficiency virus (HIV)-positive patients are limited. In this study, the participants with an initial hepatitis B surface antibody (HBsAb) titer <10 mIU/ml were assigned to Cohort 1 to receive a standard dose of recombinant hepatitis B vaccine, and participants with an initial HBsAb titer between 10 and 100 mIU/ml were assigned to Cohort 2 to receive a single reinforced recombinant vaccine. In Cohort 1, the immune and high response rates in HIV-positive patients were 93.4%/81.4%, 87.4%/51.5%, and 83.2%/40.7% at 1-3 months, 1 year, and 2 years postvaccination. Multivariate analysis showed that only age and HIV RNA status at baseline were independent factors related to sustained immune response at 2 years postvaccination. In Cohort 2, the high immune response rates in HIV-positive patients were 78.8%, 60.6%, and 51.5% at 1-3 months, 1 year, and 2 years postvaccination. The immune or high response rates did not differ between HIV-positive patients and healthy controls at 1-3 months postvaccination in these two cohorts; however, HBsAb titers were significantly lower in HIV-positive patients. This study summarized the 2-year data of immune response to hepatitis B vaccination and analyzed the factors related to sustained immune response at 2 years postvaccination in Chinese HIV-positive patients.


Assuntos
Soropositividade para HIV , Hepatite B , HIV , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B , Humanos , Imunidade , Estudos Retrospectivos , Vacinação
18.
J Obstet Gynaecol Res ; 48(7): 1938-1944, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35508300

RESUMO

OBJECTIVE: To intervene the insomnia symptoms of perimenopausal women by auricular point seed burying combined with fire dragon pot moxibustion, in order to improve the quality of sleep and life of the participants. METHODS: Seventy female participants with perimenopausal insomnia who were treated with Chinese medicine techniques from January 2020 to October 2020 were randomly divided into a control group and an observation group, with 35 participants in each group. Participants in the control group were treated with the traditional Chinese medicine nursing intervention of burying seeds at auricular points. And participants in the observation group were additionally treated with fire dragon pot moxibustion. After 10 weeks of intervention, the Pittsburgh Sleepiness Index (PSQI), self-assessment scores of anxiety (SAS) and depression (SDS), and treatment efficacy of the two groups were compared, respectively. RESULTS: Before the intervention, there was no statistically significant difference in general information, sleep index scores, SAS, SDS scores between the two groups (p > 0.05). After the intervention, the SAS, SDS, and PSQI scores were significantly lower than the control group. Compared with the control group, the time to fall asleep was shorter and the duration of total sleep was longer in the observation group (p < 0.05). The treatment efficacy was better in the observation group (p < 0.05). CONCLUSION: Auricular point seed burying combined with fire dragon pot moxibustion therapy can be more effect than auricular point seed burying alone in treating perimenopausal women with insomnia.


Assuntos
Moxibustão , Distúrbios do Início e da Manutenção do Sono , Pontos de Acupuntura , Feminino , Humanos , Perimenopausa , Sementes , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
19.
Sensors (Basel) ; 22(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36080881

RESUMO

Non-contact vital sign detection technology has brought a more comfortable experience to the detection process of human respiratory and heartbeat signals. Ensemble empirical mode decomposition (EEMD) is a noise-assisted adaptive data analysis method which can be used to decompose the echo data of frequency modulated continuous wave (FMCW) radar and extract the heartbeat and respiratory signals. The key of EEMD is to add Gaussian white noise into the signal to overcome the mode aliasing problem caused by original empirical mode decomposition (EMD). Based on the characteristics of clutter and noise distribution in public places, this paper proposed a static clutter filtering method for eliminating ambient clutter and an improved EEMD method based on stable alpha noise distribution. The symmetrical alpha stable distribution is used to replace Gaussian distribution, and the improved EEMD is used for the separation of respiratory and heartbeat signals. The experimental results show that the static clutter filtering technology can effectively filter the surrounding static clutter and highlight the periodic moving targets. Within the detection range of 0.5 m~2.5 m, the improved EEMD method can better distinguish the heartbeat, respiration, and their harmonics, and accurately estimate the heart rate.


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Humanos , Radar , Razão Sinal-Ruído , Sinais Vitais
20.
Sensors (Basel) ; 22(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36081156

RESUMO

This paper presents a novel substrateless packaging solution for the D-band active e mixer MMIC module, using a waveguide line with a glide-symmetric periodic electromagnetic bandgap (EBG) hole configuration. The proposed packaging concept has the benefit of being able to control signal propagation behavior by using a cost-effective EBG hole configuration for millimeter-wave- and terahertz (THz)-frequency-band applications. Moreover, the mixer MMIC is connected to the proposed hollow rectangular waveguide line via a novel wire-bond wideband transition without using any intermediate substrate. A simple periodical nail structure is utilized to suppress the unwanted modes in the transition. Additionally, the presented solution does not impose any limitations on the chip's dimensions or shape. The packaged mixer module shows a return loss lower than 10 dB for LO (70-85 GHz) and RF (150-170 GHz) ports, achieving a better performance than that of traditional waveguide transitions. The module could be used as a transmitter or receiver, and the conversion loss shows good agreement in multiple samples. The proposed packaging solution has the advantages of satisfactory frequency performance, broadband adaptability, low production costs, and excellent repeatability for millimeter-wave- and THz-band systems, which would facilitate the commercialization of millimeter-wave and THz products.

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