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1.
J Integr Med ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34649821

RESUMO

BACKGROUND: Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs. OBJECTIVE: This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020. INCLUSION CRITERIA: Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included. DATA EXTRACTION AND ANALYSIS: Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity. RESULTS: A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = -2.14, 95% confidence interval [CI] [-2.82, -1.46], P < 0.001; heterogeneity: P < 0.001, I2 = 82%; 15 studies, n = 1063) and GAEs (WMD = -2.88, 95% CI [-5.22, -0.55], P < 0.001; heterogeneity: P < 0.001, I2 = 98%; 5 studies, n = 500) significantly improved total sleep quality, having favorable effects on subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction. Subgroup analysis showed that TCEs demonstrated superiority after 12 weeks (WMD = -2.77, 95% CI [-4.26, -1.28], P < 0.001; heterogeneity: P < 0.001, I2 = 85%; 5 studies, n = 420) and Qigong had a greater intervention effect for improving the sleep quality of older adults than Tai Chi (WMD = -3.37, 95% CI [-4.38, -2.35], P < 0.001; heterogeneity: P = 0.04, I2 = 63%; 4 studies, n = 321). Meta-regression revealed that the year of publication, sample size, mean age of participants, and percentage of females in the primary studies did not account for the overall heterogeneity. CONCLUSION: Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

2.
Cell Death Discov ; 7(1): 256, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548476

RESUMO

Alzheimer's disease (AD) is characterized by aberrant accumulation of extracellular ß-amyloid (Aß) peptides in the brain. Soluble Aß oligomers are thought to be the most neurotoxic species and are correlated with cognitive dysfunction in early AD. However, there is still no effective treatment so far. We determined that Pep63, a small peptide, had a neuroprotective effect on synaptic plasticity and memory in our previous study. Here, we developed novel and multifunctional liposomes targeting both Aß oligomers and fibrils based on a liposome delivery system. Transferrin-Pep63-liposomes (Tf-Pep63-Lip), possessing the ability for blood-brain barrier targeting, were also incorporated with phosphatidic acid (PA) and loaded with neuroprotective Pep63. We discovered that administration of Tf-Pep63-Lip could significantly reduce the Aß burden in the hippocampus, and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture Aß oligomers or fibrils and then facilitated microglial chemotaxis nearby for clearance. Simultaneously, Tf-Pep63-Lip hindered Aß1-42 aggregation and disaggregated Aß1-42 assembly due to multivalent PA-Aß. Pep63 effectively inhibited the binding between EphB2 and Aß oligomers after release from liposomes and rescued NMDA receptors trafficking, the basis of synaptic plasticity. No side effects were observed in either APP/PS1 or wild-type mice, indicating that Tf-Pep63-Lip might be safe under the dosing regimen used in our experiment. Taken together, our results suggested that Tf-Pep63-Lip may serve as a safe and efficient agent for AD combination therapy.

3.
Pharmacol Res ; 172: 105857, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34461223

RESUMO

Opioid relapse is generally caused by the recurrence of context-induced memory reinstatement of reward. However, the internal mechanisms that facilitate and modify these processes remain unknown. One of the key regions of the reward is the nucleus accumbens (NAc) which receives glutamatergic projections from the dorsal hippocampus CA1 (dCA1). It is not yet known whether the dCA1 projection to the NAc shell regulates the context-induced memory recall of morphine. Here, we used a common model of addiction-related behavior conditioned place preference paradigm, combined with immunofluorescence, chemogenetics, optogenetics, and electrophysiology techniques to characterize the projection of the dCA1 to the NAc shell, in context-induced relapse memory to morphine. We found that glutamatergic neurons of the dCA1 and gamma aminobutyric acidergic (GABA) neurons of the NAc shell are the key brain areas and neurons involved in the context-induced reinstatement of morphine memory. The dCA1-NAc shell glutamatergic input pathway and the excitatory synaptic transmission of the dCA1-NAc shell were enhanced via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) when mice were re-exposed to environmental cues previously associated with drug intake. Furthermore, chemogenetic and optogenetic inactivation of the dCA1-NAc shell pathway decreased the recurrence of long- and short-term morphine-paired context memory in mice. These results provided evidence that the dCA1-NAc shell glutamatergic projections mediated the context-induced memory recall of morphine.

4.
BMJ Open ; 11(8): e046798, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400450

RESUMO

OBJECTIVE: To systematically assess the efficacy and safety of dexmedetomidine as an anaesthesia adjuvant for cleft lip and palate (CLP) repair in children. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang (up to October 2020). Studies in languages other than English and Chinese were excluded. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) evaluating the impact of dexmedetomidine on emergence agitation (EA), the need for postoperative rescue analgesics, postoperative nausea and vomiting (PONV), and other adverse events in paediatric patients during CLP repair. DATA EXTRACTION AND SYNTHESIS: The quality of evidence was assessed by using the Cochrane Review Methods and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were screened, extracted and assessed by two independent authors. Outcomes were reported as a risk ratio (RR) with a 95% CI. A random-effect model was used when heterogeneity was detected. RESULTS: Thirteen studies including 1040 children met the inclusion criteria. The incidence of EA was significantly decreased in the dexmedetomidine group (RR, 0.19; 95% CI 0.10 to 0.36; p<0.00001; I2=56%) as compared with the control group. Paediatric patients receiving dexmedetomidine had lower postoperative analgesic requirements (RR, 0.27; 95% CI 0.10 to 0.73; p=0.01; I2=84%) and a lower incidence of respiratory adverse events (RR, 0.49; 95% CI 0.31 to 0.78; p=0.003; I2=0%). There were no significant differences in the risk of PONV and cardiovascular adverse events. CONCLUSIONS: There was a lack of high-quality studies in this field. Perioperative administration of dexmedetomidine reduced the need for postoperative rescue analgesics and the incidence of EA in children without side effects undergoing CLP repair. However, further verification with larger samples and higher-quality RCTs is needed.


Assuntos
Anestesia , Fenda Labial , Dexmedetomidina , Criança , Fenda Labial/cirurgia , Dexmedetomidina/uso terapêutico , Humanos , Palato , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle
5.
J Cell Physiol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34270095

RESUMO

Beta 1,4-galactosyltransferase (B4GALT)-family glycosyltransferases are involved in multiple biological processes promoting cancer progression, regulating the dynamic network of cancer cell proliferation and apoptosis, and are associated with metastasis. However, their roles in the dysregulation of expressions and functions in hepatocellular carcinoma (HCC) remain unclear. Herein, bioinformatic approaches have been applied to investigate their expression profiles, and to obtain correlations between gene expressions and clinicopathological parameters as well as downstream target genes in HCC. Multiple databases were used to screen the expressions of B4GALT family members in tumor tissues, and to evaluate their prognostic value among HCC patients in different aspects. Results indicated an overall upregulation of B4GALTs' transcription levels in tumor tissues and a strong correlation with poor prognosis. Through Gene Ontology analysis, gene set enrichment analysis, and verification of single-cell RNA sequencing data, we established a connection between the B4GALT family and microtubule spindle assembly, which particularly highlighted the role of B4GALT4 in this phenomenon. B4GALT4 knockdown downregulated the production of lumican, and repressed the expressions of polo-like kinase 1 and RHAMM by regulating the transforming growth factor-beta pathway, thus suggesting that B4GALT4 is a critical promotor for HCC. We believe that these studies will provide valuable insight into the role of B4GALT family members in HCC and lead to the development of new strategies to improve the outcomes for patients with HCC.

6.
Ann Transl Med ; 9(12): 962, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277762

RESUMO

Background: Pulsatile gonadotropin-releasing hormone (GnRH) therapy may restore function of the hypothalamus-pituitary-gonad axis and induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism (CHH). The study sought to test the reliability of a newly developed Innopump® hormone pump, and to confirm the efficacy and safety of pulsatile GnRH therapy (by Innopump® hormone pump) in CHH patients. Methods: From November 2017 to November 2018, 28 male patients with CHH were treated with pulsatile GnRH at Peking Union Medical College Hospital, Beijing Chaoyang Hospital, and Shandong Provincial Hospital. A prospective, self-controlled, 7-day clinical trial was conducted. The primary outcome measures were the efficacy and safety of pulsatile GnRH therapy (which was administered via the Innopump® hormone pump). The secondary outcome measures included total serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels. Results: All of the patients participated the clinical study. For 7 days, a dosage prescribed by doctors was accurately administered by the Innopump® hormone pump, and recorded by the pump. During the treatment, LH and FSH levels gradually increased to 2.66±1.74 and 5.05±3.03 IU/L, respectively. Upper respiratory tract infection in 1 patient and slight nausea in another patient were reported, which were confirmed to be unrelated to the pulsatile GnRH therapy. Conclusions: The Innopump® hormone pump was found to be reliable in drug administration, and to have an accurate alarming system. It effectively and safely treated patients with CHH. Pulsatile GnRH therapy may produce a physiological pattern of GnRH secretion, and re-establish pituitary-gonad axis function by increasing gonadotropin levels.

7.
Cells ; 10(5)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069424

RESUMO

Cells undergo proliferation and apoptosis, migration and differentiation via a number of cell surface receptors, most of which are heavily glycosylated. This review discusses receptor glycosylation and the known roles of glycans on the functions of receptors expressed in diverse cell types. We included growth factor receptors that have an intracellular tyrosine kinase domain, growth factor receptors that have a serine/threonine kinase domain, and cell-death-inducing receptors. N- and O-glycans have a wide range of functions including roles in receptor conformation, ligand binding, oligomerization, and activation of signaling cascades. A better understanding of these functions will enable control of cell survival and cell death in diseases such as cancer and in immune responses.

8.
Biomed Res Int ; 2021: 6635452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954188

RESUMO

Objective: The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. Methods: Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1ß were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. Results: LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1ß levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. Conclusion: LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.


Assuntos
Apoptose , Inflamação/patologia , Intestinos/patologia , Intestinos/fisiopatologia , Receptor Gatilho 1 Expresso em Células Mieloides/antagonistas & inibidores , Doença Aguda , Animais , Inflamação/complicações , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Lipopolissacarídeos , Masculino , NF-kappa B/metabolismo , Permeabilidade , Ratos Sprague-Dawley , Transdução de Sinais , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo
9.
Zhen Ci Yan Jiu ; 46(2): 164-7, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788439

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on postoperative sore throat (POST) and postoperative nausea and vomiting (PONV) after endotracheal intubation and general anesthesia. METHODS: According to the random number table, 60 patients of gastrointestinal surgery under general anesthesia with tracheal intubation were randomly divided into EA group (30 cases) and control group (30 cases). Patients in the EA group were given acupuncture at Shaoshang (LU11) 30 minutes before general anesthesia, and EA at Chize (LU5) and Hegu (LI4) continued until the operation was completed. The incidence and severity of POST and visual analogue scale (VAS) score at 12, 24, and 48 h after surgery, and the incidence and severity of PONV at 12, 24 h after surgery were analyzed, respectively. RESULTS: The incidence and severity of POST and PONV, and VAS score in the EA group were significantly lower than those in the control group 12 h and 24 h after surgery (P<0.05). Both groups had significant reductions in VAS score at 24 h and 48 h after surgery compared with that at 12 h (P<0.05). CONCLUSION: EA can significantly improve the prognosis of patients on sore throat and reduce the incidence of PONV.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Eletroacupuntura , Faringite , Humanos , Náusea , Faringite/etiologia , Faringite/terapia , Vômito
10.
Asian J Androl ; 23(1): 69-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32985417

RESUMO

46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.

11.
Ann Palliat Med ; 10(2): 1727-1738, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33302634

RESUMO

BACKGROUND: Chronic myelogenous leukemia (CML) is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells. CML is a relatively rare disease, mainly affecting elderly patients, but the prevalence of CML is expected to increase dramatically. The tyrosine kinase inhibitors (TKIs) have changed the CML patients' treatment patterns and improved its treatment effect, but drug resistance still remains a significant problem to be solved. Therefore, the identification of biomarkers of CML resistance involved therein is essential for treatment and prognosis prediction. METHODS: Bioinformatics was used to analyze and construct a lncRNA-miRNA-mRNA network of CML resistance to dasatinib and predict key lncRNAs. RESULTS: By screening differentially expressed genes in CML resistant to dasatinib and comprehensively analyzing their functions and signal pathways, the core genes in these differential genes were found, and by predictive analysis of the upstream targets of these core genes. Finally, a network diagram containing lncRNA, miRNA, and mRNA was constructed. CONCLUSIONS: MALAT1 as a lncRNA may be a tumor suppressor in patients with CML. According to our data, MALAT1 may have potential role as a molecular biomarker for the occurrence and development of CML resistance to dasatinib.


Assuntos
Dasatinibe , Resistencia a Medicamentos Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , RNA Longo não Codificante , Idoso , Dasatinibe/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
12.
Zhen Ci Yan Jiu ; 45(11): 888-94, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269832

RESUMO

OBJECTIVE: To explore the protective effect of electroacupuncture (EA) on hepatic ischemia-reperfusion injury (HIRI) and the expression of high mobility group protein 1 (HMGB1) in liver tissues in rats. METHODS: A total of 40 male SD rats were randomly divided into 4 groups, namely sham control, HIRI model, "Ganshu"(BL18) -"Yanglingquan"(GB34) and non-acupoint group, with 10 rats in each group. The HIRI model was induced by blocking the arteries, veins and bile ducts supplying the middle and left lobes of the liver for 1 h, and reperfusion for 4 h to induce an area of about 70% HIRI. EA was applied to bila-teral BL18 and GB34, or non-acupoints about 6-8 mm to the bilateral BL18 for 30 min before modeling. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were measured by using an automatic biochemical analyzer. Serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and HMGB1 levels were assayed by ELISA. Hematoxylin - eosin (H.E.) staining was used to observe histopathological changes of the liver tissue by using tissue injury scaling (0-3 scores). The expression of HMGB1 protein in liver tissues was detected by immunohistochemical staining, Western blot and PCR, separately. RESULTS: Following modeling and compared with the sham group, the levels of serum ALT, AST, TNF-α, IL-6, and HMGB1 contents, the number of HMGB1 immunoreaction (IR)-positive cells, and HMGB1 protein and mRNA were significantly increased (P<0.01). After the treatment, the contents of serum ALT, AST, TNF-α, IL-6, and HMGB1, liver HMGB1 IR-positive cells, protein and mRNA were considerably down-regulated in the BL18-GB34 group (P<0.05), rather than in the non-acupoint group (P>0.05) in contrast to the model group. H.E. stain showed a higher liver injury score in the model group than in the sham group (P<0.01), and a lower liver injury score in the BL18-GB34 group (not the non-acupoint group) relevant to the model group (P<0.05). CONCLUSION: EA of BL18 and GB34 points has a protective effect on ischemic liver injury in rats with HIRI, which may be associated with its functions in inhibiting the migration and release of HMGB1 from the nucleus to the cytoplasm and in down-regulating the expression of inflammatory factors.


Assuntos
Eletroacupuntura , Proteína HMGB1 , Traumatismo por Reperfusão , Animais , Proteína HMGB1/genética , Fígado , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/terapia
13.
Zhongguo Zhen Jiu ; 40(10): 1108-12, 2020 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-33068355

RESUMO

OBJECTIVE: To observe the effect of acupuncture technique of Tiaoxin Tongdu on learning-memory ability and expressions of hippocampal vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) in rats with vascular dementia (VD), and to explore the mechanism of acupuncture technique of Tiaoxin Tongdu for VD. METHODS: A total of 24 male SD rats were randomly divided into a sham operation group, a model group, a medication group and an acupuncture group after Morris water maze test, 6 rats in each group. VD model was established by permanent ligation of bilateral common carotid arteries in the model group, the medication group and the acupuncture group. Treatment was given on the next day after successful modeling. The rats in the acupuncture group were treated with acupuncture at "Baihui" (GV 20), "Shenting" (GV 24), "Shuigou" (GV 26), "Dazhui" (GV 14), "Fengfu" (GV 16), "Mingmen" (GV 4), "Neiguan" (PC 6), "Daling" (PC 7) and "Laogong" (PC 8) for 30 min; the rats in the medication group were treated with nimodipine solution (0.0625 g/kg) by gavage, once a day, for 2 weeks. Morris water maze test was used to detect the behavior of rats before modeling, 2 weeks after modeling and after intervention; after intervention, the expressions of VEGF and Ang-1 protein in hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the average escape latency of rats in the model group was prolonged (P<0.01), and the times of crossing the original platform were reduced (P<0.01). Compared with the model group, the average escape latency of rats in the medication group and acupuncture group was significantly shortened (P<0.01), and the times of crossing the original platform were increased (P<0.01, P<0.05). Compared with the sham operation group, the expressions of VEGF and Ang-1 protein in hippocampus in the model group were increased (P<0.05, P<0.01). Compared with the model group, the expressions of VEGF and Ang-1 protein in the hippocampus in the medication group and acupuncture group were significantly increased (P<0.01, P<0.05). CONCLUSION: The acupuncture technique of Tiaoxin Tongdu can significantly improve the learning and memory ability of VD rats, and its mechanism may be related to up-regulating the expressions of VEGF and Ang-1 protein in hippocampus and inducing angiogenesis.


Assuntos
Terapia por Acupuntura , Demência Vascular/terapia , Aprendizagem , Memória , Ribonuclease Pancreático/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Hipocampo/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
14.
Glycoconj J ; 37(4): 423-433, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32583304

RESUMO

Aberrant glycosylation is a featured characteristic of cancer and plays a role in cancer pathology; thus an understanding of the compositions and functions of glycans is critical for discovering diagnostic biomarkers and therapeutic targets for cancer. In this study, we used MALDI-TOF-MS analysis to determine the O-glycan profiles of prostate cancer cells metastasized to bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP) in comparison to immortalized RWPE-1 cells derived from normal prostatic tissue. Prostate cancer (CaP) cells exhibited an elevation of simple/short O-glycans, with a reduction of complex O-glycans, increased O-glycan sialylation and decreased fucosylation. Core 1 sialylation was increased dramatically in all CaP cells, and especially in PC-3 cells. The expression of Neu5Acα2-3Galß1-3GalNAc- (sialyl-3T antigen) which is the product of α2,3-sialyltransferase-I (ST3Gal-I) was substantially increased. We therefore focused on exploring the possible function of ST3Gal-I in PC-3 cells. ST3Gal-I silencing studies showed that ST3Gal-I was associated with PC-3 cell proliferation, migration and apoptosis. Further in vivo studies demonstrated that down regulation of ST3Gal-I reduced the tumor size in xenograft mouse model, indicating that sialyl-3T can serve as a biomarker for metastatic prostate cancer prognosis, and that ST3Gal-I could be a target for therapeutic intervention in cancer treatment.


Assuntos
Antígenos Virais de Tumores/metabolismo , Neoplasias da Próstata/metabolismo , Sialiltransferases/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Glicosilação , Humanos , Masculino , Camundongos Endogâmicos BALB C , Células PC-3 , Polissacarídeos/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Sialiltransferases/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
World J Pediatr ; 16(5): 471-479, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32048234

RESUMO

BACKGROUND: A large number of studies pointed that being delivered by cesarean section (CS) would affect the health outcomes of offspring, however, whether CS would affect the risk of childhood leukemia remained uncertain. This study conducted a meta-analysis to quantitatively evaluate whether being delivered by CS would influence the onset of childhood leukemia. METHODS: PubMed, Embase and Web of Science databases were searched from 3rd June, 1950 to 13th October, 2019 to identify the literature, which examined the relationship between CS and childhood leukemia. This study used Newcastle-Ottawa Scale to assess the quality of literature. Subgroup analyses were conducted on region, mode of delivery, design of the study and number of confounders adjusted. Egger's test and Begg's test were performed to evaluate possible publication bias. RESULTS: The pooled odds ratio (OR) estimates illustrated that children delivered by CS had a higher risk of developing leukemia [OR 1.10, 95% confidence interval (CI) 1.04-1.17, P = 0.002] and lymphoblastic leukemia (OR 1.12, 95% CI 1.03-1.23, P = 0.009), while a significant association for myeloid leukemia was not observed (OR 1.05, 95% CI 0.92-1.20, P = 0.451). Results of subgroup analyses indicated that elective CS would increase the risk of childhood lymphoblastic leukemia (OR 1.16, 95% CI 1.06-1.27, P = 0.002). However, a statistical relationship between emergency CS and lymphoblastic leukemia was not observed (OR 1.07, 95% CI 0.93-1.23, P = 0.364). CONCLUSIONS: CS would increase the risk of childhood lymphoblastic leukemia. It is worth noting that subgroup analyses shows that elective CS rather than emergency CS increases the risk of lymphoblastic leukemia in offspring.

16.
Asian J Androl ; 22(4): 390-395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31464203

RESUMO

Partial congenital hypogonadotropic hypogonadism (PCHH) is caused by an insufficiency in, but not a complete lack of, gonadotropin secretion. This leads to reduced testosterone production, mild testicular enlargement, and partial pubertal development. No studies have shown the productivity of spermatogenesis in patients with PCHH. We compared the outcomes of gonadotropin-induced spermatogenesis between patients with PCHH and those with complete congenital hypogonadotropic hypogonadism (CCHH). This retrospective study included 587 patients with CHH who were treated in Peking Union Medical College Hospital (Beijing, China) from January 2008 to September 2016. A total of 465 cases were excluded from data analysis for testosterone or gonadotropin-releasing hormone treatment, cryptorchidism, poor compliance, or incomplete medical data. We defined male patients with PCHH as those with a testicular volume of ≥4 ml and patients with a testicular volume of <4 ml as CCHH. A total of 122 compliant, noncryptorchid patients with PCHH or CCHH received combined human chorionic gonadotropin and human menopausal gonadotropin and were monitored for 24 months. Testicular size, serum luteinizing hormone levels, follicle-stimulating hormone levels, serum total testosterone levels, and sperm count were recorded at each visit. After gonadotropin therapy, patients with PCHH had a higher spermatogenesis rate (92.3%) than did patients with CCHH (74.7%). During 24-month combined gonadotropin treatment, the PCHH group took significantly less time to begin producing sperm compared with the CCHH group (median time: 11.7 vs 17.8 months, P < 0.05). In conclusion, after combined gonadotropin treatment, patients with PCHH have a higher spermatogenesis success rate and sperm concentrations and require shorter treatment periods for sperm production.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Hipogonadismo/tratamento farmacológico , Síndrome de Kallmann/tratamento farmacológico , Menotropinas/uso terapêutico , Contagem de Espermatozoides , Testículo/patologia , Adolescente , Quimioterapia Combinada , Hormônio Foliculoestimulante/sangue , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipogonadismo/congênito , Hipogonadismo/genética , Hipogonadismo/patologia , Síndrome de Kallmann/genética , Síndrome de Kallmann/patologia , Estimativa de Kaplan-Meier , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Índice de Gravidade de Doença , Espermatogênese , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Mol Immunol ; 117: 20-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31731055

RESUMO

BACKGROUND: LncRNA NEAT1 was associated with the tumorigenesis of multiple myeloma (MM). However, the mechanisms of M2 macrophage polarization involved with NEAT1 in MM are still unknown. METHODS: Bone marrow samples, multiple myeloma cells RPMI 8226 and monocyte cell line THP-1 were used in this study. The expression of NEAT1 and miR-214 was modified by transfection with the shNEAT1 or miR-214 inhibitor. The expression of NEAT1, miR-214 and B7-H3 in MM patient tissues and cells was analyzed by RT-qPCR. ELISA assay was used to determine the release of B7-H3 in the supernatant of cell culture. The patient survival curve was analyzed using Kaplan-Meier method. The macrophage polarization markers were examined by RT-qPCR and western blotting. The interaction between NEAT1, miR-214 and B7-H3 was analyzed by Dual-Luciferase reporter and RIP assays. AG490 was used to block the JAK2/STAT3 signaling. Co-culture of THP-1 and RPMI 8226 cells was used for macrophage polarization. RESULTS: NEAT1 and B7-H3 were up-regulated, but miR-214 was obviously down-regulated in MM patients. B7-H3, NEAT1 and miR-214 were associated with overall survival time of MM patients. NEAT1 silencing induced miR-214 and inhibited the expression and release of B7-H3 and then suppressed M2 macrophage polarization via inhibiting the JAK2/STAT3 signaling. NEAT1 directly targeted miR-214, and miR-214 directly bound to B7-H3. MiR-214 inhibitor reversed the down-regulation and release of B7-H3 and M2 macrophage polarization caused by shNEAT1. The specific JAK2/STAT3 signaling inhibitor AG490 abrogated M2 macrophage polarization. CONCLUSION: NEAT1 promoted M2 macrophage polarization by sponging miR-214 and then regulating B7-H3, thus accelerating MM progression via the JAK2/STAT3 signaling pathway. Our study revealed novel mechanisms of M2 macrophage polarization and provided new potential clinical therapeutic targets for MM.


Assuntos
Antígenos B7/imunologia , Macrófagos/imunologia , MicroRNAs/imunologia , Mieloma Múltiplo/imunologia , RNA Longo não Codificante/imunologia , Antígenos B7/metabolismo , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Ativação de Macrófagos , Macrófagos/metabolismo , MicroRNAs/metabolismo , Mieloma Múltiplo/metabolismo , RNA Longo não Codificante/metabolismo
18.
Sci Rep ; 9(1): 18248, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796756

RESUMO

Vascular dementia (VaD) is a complex disorder caused by reduced blood flow in the brain. However, there is no effective pharmacological treatment option available until now. Here, we reported that low-dose levamlodipine besylate could reverse the cognitive impairment in VaD mice model of right unilateral common carotid arteries occlusion (rUCCAO). Oral administration of levamlodipine besylate (0.1 mg/kg) could reduce the latency to find the hidden platform in the MWM test as compared to the vehicle group. Furthermore, vehicle-treated mice revealed reduced phospho-CaMKII (Thr286) levels in the hippocampus, which can be partially restored by levamlodipine besylate (0.1 mg/kg and 0.5 mg/kg) treatment. No significant outcome on microglia and astrocytes were observed following levamlodipine besylate treatment. This data reveal novel findings of the therapeutic potential of low-dose levamlodipine besylate that could considerably enhance the cognitive function in VaD mice.


Assuntos
Anlodipino/administração & dosagem , Demência Vascular/tratamento farmacológico , Niacina/análogos & derivados , Nootrópicos/administração & dosagem , Anlodipino/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Microglia/efeitos dos fármacos , Niacina/administração & dosagem , Niacina/uso terapêutico , Nootrópicos/farmacologia
19.
Pharm Biol ; 57(1): 717-728, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622116

RESUMO

Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion. Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia. Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 µg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n = 10/group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6-8 in the model. Results: In the gouty arthritis rat model, BHA at a higher dosage (50 µg) demonstrated a strong anti-inflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1ß, IL-8, IFN-γ, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 µg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%. Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Gotosa/tratamento farmacológico , Ácido Hialurônico/farmacologia , Hiperuricemia/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Artrite Gotosa/patologia , Butiratos/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Hiperuricemia/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Ácido Úrico/sangue
20.
Theranostics ; 9(19): 5672-5680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534510

RESUMO

Autophagy is a dynamic and complicated catabolic process. Imaging autophagic flux can clearly advance knowledge of its pathophysiology significance. While the most common way autophagy is imaged relies on fluorescent protein-based probes, this method requires substantial genetic manipulation that severely restricts the application. Small fluorescent probes capable of tracking autophagic flux with good spatiotemporal resolution are highly demanable. Methods: In this study, we developed a small-molecule fluorogenic probe (AFG-1) that facilitates real-time imaging of autophagic flux in both intact cells and live mice. AFG-1 is inspired by the cascading nitrosative and acidic microenvironments evolving during autophagy. It operates over two sequential steps. In the first step, AFG-1 responds to the up-regulated peroxynitrite at the initiation of autophagy by its diphenylamino group being oxidatively dearylated to yield a daughter probe. In the second step, the daughter probe responds to the acidic autolysosomes at the late stage of autophagy by being protonated. Results: This pathway-dependent mechanism has been confirmed first by sequentially sensing ONOO- and acid in aqueous solution, and then by imaging autophagic flux in live cells. Furthermore, AFG-1 has been successfully applied to visualize autophagic flux in real-time in live mice following brain ischemic injury, justifying its robustness. Conclusion: Due to the specificity, easy operation, and the dynamic information yielded, AFG-1 should serve as a potential tool to explore the roles of autophagy under various pathological settings.


Assuntos
Autofagia/efeitos dos fármacos , Corantes Fluorescentes/metabolismo , Animais , Linhagem Celular , Microambiente Celular , Endotélio/metabolismo , Endotélio/patologia , Corantes Fluorescentes/química , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Estresse Nitrosativo , Ácido Peroxinitroso/metabolismo
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