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AIM: The purpose of this study was to explore the effect of implementing WeChat-assisted health education for parents of infants after enterostomy. METHODS: This study retrospectively analysed the clinical data of 106 infants after enterostomy whose parents received WeChat-assisted health education in our hospital from June 2017 to June 2019. The clinical data of 92 infants after enterostomy whose parents received traditional health education in our hospital from May 2015 to May 2017 were selected as the control group. RESULTS: The care ability of the WeChat health education group was significantly better than that of the traditional health education group (P < 0.05). The care burden of the WeChat health education group was significantly lower than that of the traditional health education group (P < 0.05). The results of the WHOQOL-BREF showed that the quality of life for WeChat health education group was significantly higher than that for the traditional health education group (P < 0.05). The incidence of complications, including mucosal oedema, allergic dermatitis, faecal dermatitis and avulsion injury, in the WeChat health education group was significantly lower than that in the traditional health education group. CONCLUSION: The implementation of WeChat-assisted health education for parents of infants after enterostomy can effectively improve parents' care ability, reduce parents' care burden, improve parents' quality of life and reduce the incidence of complications in patients.
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Enterostomia , Qualidade de Vida , Educação em Saúde , Humanos , Lactente , Pais , Estudos RetrospectivosRESUMO
Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common sleep disorder characterized by repeated pharyngeal collapse with partial or complete obstruction of the upper airway. This study investigates the biomechanics of upper airway collapse of OSASH patients during natural sleep. Computerized tomography (CT) scans and data obtained from a device installed on OSASH patients, which is comprised of micro pressure sensors and temperature sensors, are used to develop a pseudo three-dimensional (3D) finite element (FE) model of the upper airway. With consideration of the gravity effect on the soft palate while patients are in a supine position, a fluid-solid coupling analysis is performed using the FE model for the two respiratory modes, eupnea and apnea. The results of this study show that the FE simulations can provide a satisfactory representation of a patient's actual respiratory physiological processes during natural sleep. The one-way valve effect of the soft palate is one of the important mechanical factors causing upper airway collapse. The monitoring data and FE simulation results obtained in this study provide a comprehensive understanding of the occurrence of OSAHS and a theoretical basis for the individualized treatment of patients. The study demonstrates that biomechanical simulation is a powerful supplementation to clinical monitoring and evaluation.
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Apneia Obstrutiva do Sono , Humanos , Palato Mole , Sono , Apneia Obstrutiva do Sono/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The simultaneous loading of multifunctional drugs has been regarded as one of the major challenges in the drug delivery system. Herein, a mesoporous silica coating was constructed on a bare metal stent surface by an evaporation-induced self-assembly method, in which both hydrophilic and hydrophobic drugs (heparin and rapamycin) were encapsulated by a one-pot method for the first time, and the release behaviors of these drugs were studied. The releasing mechanisms of these drugs were investigated in detail. Rapid release of heparin can achieve anticoagulation and endothelialization, whereas slow release of rapamycin can realize antiproliferative therapy for long term. In vitro hemocompatibility and promotion for proliferation of vein endothelial cells and the inhibition of smooth muscle cells were conducted. In vivo stent implantation results verify that the mesoporous silica coating with both heparin and rapamycin can successfully accelerate the endothelialization process and realize the antiproliferative therapy for as long as 3 months. These results indicate that this multifunctional mesoporous coating containing both hydrophilic and hydrophobic drugs might be a promising stent coating in the future.
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Portadores de Fármacos/química , Metais/química , Dióxido de Silício/química , Stents , Animais , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/toxicidade , Heparina/química , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Modelos Moleculares , Conformação Molecular , Porosidade , Coelhos , Sirolimo/químicaRESUMO
Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1+ cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development.
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Anormalidades Craniofaciais/patologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/fisiologia , Crista Neural/citologia , Receptores Imunológicos/fisiologia , Animais , Diferenciação Celular , Células Cultivadas , Embrião de Galinha , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/metabolismo , Feminino , Masculino , Camundongos , Camundongos Knockout , Crista Neural/metabolismo , Neurogênese , Proteínas RoundaboutRESUMO
SummaryFibroblast growth factor (FGF) signalling acts as one of modulators that control neural crest cell (NCC) migration, but how this is achieved is still unclear. In this study, we investigated the effects of FGF signalling on NCC migration by blocking this process. Constructs that were capable of inducing Sprouty2 (Spry2) or dominant-negative FGFR1 (Dn-FGFR1) expression were transfected into the cells making up the neural tubes. Our results revealed that blocking FGF signalling at stage HH10 (neurulation stage) could enhance NCC migration at both the cranial and trunk levels in the developing embryos. It was established that FGF-mediated NCC migration was not due to altering the expression of N-cadherin in the neural tube. Instead, we determined that cyclin D1 was overexpressed in the cranial and trunk levels when Sprouty2 was upregulated in the dorsal neural tube. These results imply that the cell cycle was a target of FGF signalling through which it regulates NCC migration at the neurulation stage.
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Embrião de Galinha/citologia , Embrião de Galinha/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Crista Neural/citologia , Animais , Caderinas/genética , Caderinas/metabolismo , Movimento Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Crista Neural/metabolismo , Tubo Neural/embriologia , Tubo Neural/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de SinaisRESUMO
Adiponectin plays a fundamental role in lipid and carbohydrate metabolism. However, its role in adipocyte differentiation remains controversial. To investigate the effect of gAd on lipid deposition in chicken adipocytes and its related signaling pathways, 200 µg/mL recombinant globular adiponectin, isoproterenol, SB253580, leucine, and rapamycin were used to treat chicken adipocytes. Results demonstrated that gAd increased the expression of endogenous adiponectin and AdipoR1 (P < 0.01); gAd inhibited triglyceride (TG) accumulation in chicken adipocyte and increased the release of free fatty acids (FFA) in medium; gAd decreased the expression of adipogenic marker genes CCAAT/enhancer binding protein alpha (C/EBPα) and fatty acid synthase (FAS), while activating the expression of lipolytic marker gene adipose triglyceride lipase (ATGL) (P < 0.01). Meanwhile, gAd activated the phosphorylation levels of p38 mitogen-activated protein kinase (p38 MAPK) and activating transcription factor 2 (ATF-2), and suppressed the phosphorylation levels of rapamycin (TOR) and p70 S6 Kinase (P < 0.01). In conclusion, the results demonstrate that gAd has an ability to inhibit lipids deposition in chicken adipocyte, which depends on the p38 MAPK/ATF-2 and TOR/p70 S6 Kinase pathways.
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Fator 2 Ativador da Transcrição/metabolismo , Adipócitos/metabolismo , Adiponectina/metabolismo , Lipídeos/biossíntese , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Fator 2 Ativador da Transcrição/antagonistas & inibidores , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adiponectina/farmacologia , Animais , Células Cultivadas , Galinhas , Fosforilação , Proteínas Recombinantes/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidores , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
OBJECTIVE: To investigate the clinical application value of Loewenstein Occupational Therapy Cognitive Assessment battery in Chinese patients with post-stroke aphasia. METHODS: Cognitive functions of 59 Chinese patients with aphasia following a stroke were assessed with the Chinese version of the second edition of LOTCA battery and their linguistic functions were tested with the Western Aphasia Battery (WAB) Scale, respectively. The Results of LOTCA were analyzed and compared across different groups, in the light of gender, age, educational background, the length of illness, and the degree of aphasia. RESULTS: Neither the score of subtests of the LOTCA nor the overall scores of LOTCA of aphasia patients with different gender and educational background differed (all P>0.05). In different age groups, apart from thinking operation (F=3.373, P=0.016), visuomotor organization (F=3.124, P=0.022), attention (F=3.729, P=0.009) and the total score (F=2.683, P=0.041), there was no difference in terms of the other subtest scores of LOTCA (all P>0.05). In the groups of different length of time with illness, apart from orientation (F=2.982, P=0.039) and attention (F=3.485, P=0.022), the score of other subtests and the total score of LOTCA were not different (all P>0.05). In the groups of different degree of aphasia, apart from attention (F=2.061, P=0.074), both the score of other subtests and the total score of LOTCA differed (all P<0.05). CONCLUSION: LOTCA might be suitable to assessing the cognitive ability of post-stroke Chinese patients with aphasia.
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Afasia , Cognição , Terapia Ocupacional , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Afasia/etiologia , Afasia/fisiopatologia , Afasia/psicologia , Afasia/terapia , Povo Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapiaRESUMO
OBJECTIVE: To determine whether kidney transplants performed during weekends have worse outcomes than those performed during weekdays. METHODS: For this systematic review, PubMed, EMBASE, and the Cochrane Library (January 2000 to January 2023) were searched. We examined the survival rates of patients and grafts for hospital inpatients admitted during weekends and those admitted during weekdays. To be included, the study had to be in English and had to provide discrete survival data around weekends versus weekdays, including patients who were admitted as inpatients over the weekend. RESULTS: Five studies (n = 163,506 patients) were examined. The hazards ratio (HR) of the survival rate of patients with weekend transplantation was 1.01 (95% confidence interval [CI], 0.96 to 1.06) when compared with patients with weekday transplantation. Patients who had renal transplant on weekends had an overall allograft survival HR of 1.01 (95% CI, 0.99 to 1.03) and death-censored allograft survival HR of 1.01 (95% CI, 0.98 to 1.04). Comparison of length of hospital stay, rejection, surgical complications, and vascular complications between renal transplants on weekends and those on weekdays showed no statistical difference. CONCLUSION: Hospital inpatients admitted for renal transplantation during weekends have a survival rate similar to that of inpatients admitted during weekdays. The weekend effect of renal transplantation was very weak; hence, transplantations done during weekends and weekdays are both appropriate.
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Transplante de Rim , Humanos , Fatores de Tempo , Hospitalização , Tempo de Internação , Transplante Homólogo , Mortalidade Hospitalar , Estudos RetrospectivosRESUMO
To achieve the optimum use and efficient thermal management of two-layer electroosmosis pumping systems in microdevices, this paper studies the transient hydrodynamical features in two-layer electroosmotic flow of power-law nanofluids in a slit microchannel and the corresponding heat transfer characteristics in the presence of viscous dissipation. The governing equations are established based on the Cauchy momentum equation, continuity equation, energy equation, and power-law nanofluid model, which are analytically solved in the limiting case of two-layer Newtonian fluid flow by means of Laplace transform and numerically solved for two-layer power-law nanofluid fluid flow. The transient mechanism of adopting conducting power-law nanofluid as a pumping force and that of pumping nonconducting power-law nanofluid are both discussed by presenting the two-layer velocity, flow rates, temperature, and Nusselt number at different power-law rheology, nanoparticle volume fraction, electrokinetic width and Brinkman number. The results demonstrate that shear thinning conducting nanofluid represents a promising tool to drive nonconducting samples, especially samples with shear thickening features. The increase in nanoparticle volume fraction promotes heat transfer performance, and the shear thickening feature of conducting nanofluid tends to suppress the effects of viscous dissipation and electrokinetic width on heat transfer.
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Inflammatory pain is the most important clinical symptom of inflammatory diseases. Despite intensive research into inflammatory pain mechanisms, the majority of analgesics available are based on mechanistic classes of compounds that have been known for many years, as a result, inflammatory pain control remains a challenge for drug design in the context of clinically unmet needs in terms of safety and efficacy. A growing literature supports that pro-inflammatory cytokine signaling plays a crucial role in the development of inflammatory pain. Modulation of the pro-inflammatory cytokine may hold the key to improved pain management. Previous studies have reported that dorsomorphin played key roles in inflammation. But the role of dorsomorphin in the formalin-induced inflammatory nociception in mice has never been reported. Here, we report a new function of dorsomorphin which can inhibit formalin-induced inflammatory nociception in mice. The antinociceptive effect of dorsomorphin mainly depended on inhibiting the p38 MAPK/c-fos signaling and regulating inflammatory mediators.
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Analgésicos , Nociceptividade , Camundongos , Animais , Medição da Dor , Analgésicos/uso terapêutico , Analgésicos/farmacologia , Dor/tratamento farmacológico , Formaldeído/farmacologia , Formaldeído/uso terapêutico , Citocinas/uso terapêuticoRESUMO
The relationship between hemiplegic shoulder pain (HSP) and subluxation is unclear. This study aimed to determine the differences of magnetic resonance imaging (MRI) findings in HSP patients with or without subluxation after stroke, and to analyze the etiology of shoulder pain. This retrospective study included 53 patients with HSP after stroke from September 2013 to February 2020. Patients underwent MRI of the shoulder because of shoulder pain. Clinical characteristics, including age, sex, stroke duration, body mass index, stroke type, visual analog scale score, Brunnstrom stage, and MRI arthrography findings of the affected shoulder, were recorded. Patients were classified into the glenohumeral subluxation (GHS) group (n = 27) or non-glenohumeral subluxation (nGHS) group (n = 26). We found that patients with HSP may be prone to bursa effusion, rotator cuff injury, ligament injury, and cartilage injury, even though there was no significant difference between the GHS and nGHS groups. MRI revealed 14 cases of long bicipital tendon-glenoid labrum injury (51.8%) in the GHS group and 6 cases (23.1%) in the nGHS group (p = 0.030). We also found 10 cases (37%) of glenoid labrum injury in the GHS group and 2 cases (7.7%) in the nGHS group (p = 0.026). Eight cases (29.6%) and 1 case (3.8%) of bone marrow edema were found in the GHS and nGHS groups, respectively (p = 0.033). Compared with painful hemiplegic shoulder patients without subluxation, patients with subluxation may be more susceptible to some injuries, such as long bicipital tendon-glenoid labrum injury, glenoid labrum injury, and bone marrow edema. During rehabilitation, physicians need to pay attention to these injuries.
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The objective of this study was to investigate whether brain volume changes occur in patients with chronic ankle instability (CAI) using voxel-based morphometry and assessing correlations with clinical tests. Structural magnetic resonance imaging data were prospectively acquired in 24 patients with CAI and 34 healthy controls. CAI symptoms and pain intensity were assessed using the Foot and Ankle Ability Measure (FAAM), Cumberland Ankle Instability Tool (CAIT), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS). The gray matter volume (GMV) of each voxel was compared between the two groups while controlling for age, sex, weight, and education level. Correlation analysis was performed to identify associations between abnormal GMV regions and the FAAM score, AOFAS score, VAS score, disease duration, and body mass index. Patients with CAI exhibited reduced GMV in the right precentral and postcentral areas, right parahippocampal area, left thalamus, left parahippocampal area, and left postcentral area compared to that of healthy controls. Furthermore, the right parahippocampal (r = 0.642, p = 0.001), left parahippocampal (r = 0.486, p = 0.016), and left postcentral areas (r = 0.521, p = 0.009) were positively correlated with disease duration. The left thalamus was positively correlated with the CAIT score and FAAM activities of daily living score (r = 0.463, p = 0.023 and r = 0.561, p = 0.004, respectively). A significant positive correlation was found between the local GMV of the right and left parahippocampal areas (r = 0.487, p = 0.016 and r = 0.763, p < 0.001, respectively) and the AOFAS score. Neural plasticity may occur in the precentral and postcentral areas, parahippocampal area, and thalamus in patients with CAI. The patterns of structural reorganization in patients with CAI may provide useful information on the neuropathological mechanisms of CAI.
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Water-soluble CdTe/ZnTe core-shell quantum dots (QDs) coated with L-cysteine were synthesized in low-temperature aqueous-phase one-pot approach. The authors measured the spectral characteristics of QDs at different pH in various buffer solutions and under different excitation laser powers. The primary results show that the absorption spectra of QDs approximately overlap and the fluorescence spectra peaks have no shift in different pH solution. The fluorescence intensity increased linearly with increasing pH. With the incubation time in borate buffer solution, the fluorescence intensity decreased a little. Under strong power laser, the QDs were photobleached rapidly. However, QDs are strongly anti-photobleaching under appropriate laser power (< 100 microW). Thus, such QDs have good biological stability and optical stability. By conjugating the QDs with transferrin protein and constructing the targeted fluorescent nanoparticles, the authors labelled the HeLa cell successfully. Photobleaching experiments in vivo show that microenvironment inside cells affect the stability and accelerate the photobleaching of QDs.
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Materiais Biocompatíveis , Pontos Quânticos , Telúrio , Compostos de Cádmio , Cisteína , Células HeLa , Humanos , Nanopartículas , Espectrometria de Fluorescência , ÁguaRESUMO
Baicalin is a flavone glycoside that possesses numerous pharmacological properties. but its protective mode of action in kidney injury induced by diabetes mellitus remains incompletely understood. Using a streptozotocin (STZ)-induced diabetic mouse model, we found that baicalin could ameliorate diabetes-induced the pathological changes of the kidney function and morphology through suppressing inflammation and oxidative stress. Furthermore, baicalin treatment could alleviate interstitial fibrosis in the diabetic kidney via inhibiting epithelial-to-mesenchymal transition (EMT), which was accompanied by a sharp upregulation of Klotho, the endogenous inhibitor of renal fibrosis. We further verified that baicalin-rescued expression of Klotho was associated with Klotho promoter hypomethylation due to aberrant methyltransferase 3a expressions. Klotho knockdown via RNA interferences largely abrogated the anti-renal fibrotic effects of Baicalin in HK2 cells. These findings suggested that baicalin could alleviate renal injury-induced by diabates through partly modulating Klotho promoter methylation, which provides new insights into the treatment of diabetic nephropathy.
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Injúria Renal Aguda/tratamento farmacológico , Metilação de DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Flavonoides/uso terapêutico , Glucuronidase/antagonistas & inibidores , Injúria Renal Aguda/metabolismo , Animais , Metilação de DNA/fisiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Flavonoides/farmacologia , Glucuronidase/biossíntese , Proteínas Klotho , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologiaRESUMO
BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.
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Adenoma/prevenção & controle , Antineoplásicos Fitogênicos/uso terapêutico , Berberina/uso terapêutico , Neoplasias Colorretais/patologia , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Berberina/administração & dosagem , Berberina/efeitos adversos , Quimioprevenção/métodos , China/epidemiologia , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Método Duplo-Cego , Humanos , Análise de Intenção de Tratamento/métodos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Plantas Medicinais/efeitos adversos , Recidiva , Segurança , Adulto JovemRESUMO
Zika virus (ZIKV) infection during gestation is deemed to be coupled to birth defects through direct impairment of the nervous system during neurogenesis. However, in this study, our data showed that ZIKV infection dramatically suppressed cranial osteogenesis, shown by Safranin O/Fast Green and alizarin red staining, in chick embryos, which provides another possibility that craniofacial bone malformation caused by ZIKV may be a major cause of ZIKV-mediated birth defects. By immunofluorescent staining and electron microcopy, we confirmed ZIKV infection in chick embryo neural tubes and sites of neural crest. Next, in vivo (chick embryos) and in vitro [primary culture of neural crest cells (NCC)] ZIKV and HNK-1 double immunofluorescent staining demonstrated that ZIKV infection inhibited the production of migratory NCC. The reduction of both AP-2α- and Pax7-positive NCC in HH10 chick embryos infected by ZIKV confirmed that abnormal development of cranial NCC also occurred in the migratory process. Whole mount in situ hybridization demonstrated that cadherin 6B expression was elevated and Slug, FoxD3, and BMP4/Msx1 expressions decreased in ZIKV-infected HH10 chick embryos, implying that epithelial-mesenchymal transition (EMT) of neural crest production was blocked by ZIKV infection. Moreover, in vivo and in vitro pHIS3 and Pax7 double immunofluorescent staining showed that NCC proliferation was repressed by ZIKV infection. C-caspase-3 and AP-2α double immunofluorescent staining in HH10 chick embryos and western blotting showed that NCC apoptosis increased following ZIKV infection. Finally, electron microscopy showed multiple autophagosomes in ZIKV-infected embryos, and western blot and LC3B immunofluorescent staining demonstrated that autophagy-related genes were activated by ZIKV infection. Taken together, our data first showed that ZIKV infection during embryogenesis could interfere with cranial neural crest development, which in turn causes aberrant cranial osteogenesis. Our results provided new insights into brain malformations induced by ZIKV infection.
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Microcefalia/diagnóstico , Microcefalia/etiologia , Crista Neural/virologia , Osteogênese , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia , Zika virus/fisiologia , Animais , Apoptose , Biomarcadores , Proliferação de Células , Embrião de Galinha , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/etiologia , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/metabolismoRESUMO
Artesunate (ART) is a semisynthetic derivative of artemisinin used in the treatment of patients with malaria, which has also been reported to have immunoregulatory, anticancer and antiinflammatory properties. The aim of the present study was to investigate the possible beneficial effects of ART on ulcerative colitis (UC) rats and to detect the possible mechanisms underlying these effects. A UC rat model was established using dextran sulfate sodium (DSS). Rats were randomly divided into the following groups: Normal control, UC model group, UC rats treated with a low, medium or high dose of ART (10, 30 and 50 mg/kg/day, respectively), and the positive control group (50 mg/kg/day 5aminosalicylic acid). The damage status of colonic mucosal epithelial tissue was investigated by hematoxylin and eosin staining, and then the weight, colon length and disease activity index (DAI) were measured. Western blotting and reverse transcriptionquantitative polymerase chain reaction analysis were used to detect the levels of cytokines associated with UC and proteins associated with Tolllike receptor 4 (TLR4)nuclear factor (NF)κB pathway. ELISA was also performed to measure the levels of inflammatory cytokines. In addition, the viability and infiltration of RAW264.7 cells were examined using Cell Counting Kit8 and Transwell assays. The results demonstrated that treatment with ART significantly alleviated the UC symptoms induced by DSS in the rat model, lowered the DAI, ameliorated pathological changes, attenuated colon shortening, inhibited the levels of proinflammatory mediators and myeloperoxidase activity, and increased hemoglobin expression. Additionally, inflammatory and apoptotic markers were found to be significantly downregulated following treatment with ART in UC rats and RAW264.7 cells. To the best of our knowledge, the present study is the first to demonstrate that ART exerts antiinflammatory effects via regulating the TLR4NFκB signaling pathway in UC.
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Artesunato/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , NF-kappa B/metabolismo , Substâncias Protetoras/uso terapêutico , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Animais , Artesunato/farmacologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colite Ulcerativa/sangue , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana , Hemoglobinas/metabolismo , Mediadores da Inflamação/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Peroxidase/metabolismo , Substâncias Protetoras/farmacologia , Células RAW 264.7 , Ratos Sprague-DawleyRESUMO
In this study, the effects of Baicalin on the hyperglycemia-induced cardiovascular malformation during embryo development were investigated. Using early chick embryos, an optimal concentration of Baicalin (6 µM) was identified which could prevent hyperglycemia-induced cardiovascular malformation of embryos. Hyperglycemia-enhanced cell apoptosis was reduced in embryos and HUVECs in the presence of Baicalin. Hyperglycemia-induced excessive ROS production was inhibited when Baicalin was administered. Analyses of SOD, GSH-Px, MQAE and GABAA suggested Baicalin plays an antioxidant role in chick embryos possibly through suppression of outwardly rectifying Cl(-) in the high-glucose microenvironment. In addition, hyperglycemia-enhanced autophagy fell in the presence of Baicalin, through affecting the ubiquitin of p62 and accelerating autophagy flux. Both Baicalin and Vitamin C could decrease apoptosis, but CQ did not, suggesting autophagy to be a protective function on the cell survival. In mice, Baicalin reduced the elevated blood glucose level caused by streptozotocin (STZ). Taken together, these data suggest that hyperglycemia-induced embryonic cardiovascular malformation can be attenuated by Baicalin administration through suppressing the excessive production of ROS and autophagy. Baicalin could be a potential candidate drug for women suffering from gestational diabetes mellitus.
Assuntos
Autofagia/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Organogênese/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Autofagia/genética , Glicemia/metabolismo , Sistema Cardiovascular/crescimento & desenvolvimento , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/patologia , Embrião de Galinha , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Embrião não Mamífero , Feminino , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/genética , Organogênese/genética , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , Estreptozocina , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoAssuntos
Antígeno B7-H1/imunologia , Proteínas de Ciclo Celular/imunologia , Proteínas Cromossômicas não Histona/imunologia , Neoplasias/imunologia , Proteínas Nucleares/imunologia , Antígeno B7-H1/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Núcleo Celular/genética , Núcleo Celular/imunologia , Proteínas Cromossômicas não Histona/genética , Instabilidade Genômica/genética , Instabilidade Genômica/imunologia , Humanos , Neoplasias/terapia , Proteínas Nucleares/genética , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , CoesinasRESUMO
AIMS: Cerebrovascular white matter lesion (WML) is a major subtype of cerebral small vessel disease. Clinical drugs are not available for WML. We investigated whether peroxisome proliferator-activated receptor-γ agonist pioglitazone, with properties of vascular protection and antiinflammation, exerts beneficial effect in hypertensive WML rats. METHODS: Stroke-prone renovascular hypertensive rats (RHRSP) were treated with pioglitazone for 12 weeks. Morris water maze experiment was conducted to assess cognition. WML was observed by Luxol fast blue staining. Smooth muscle actin-alpha, collagen I, collagen IV, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule-1 were evaluated by immunohistochemistry. Interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) in brain and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were detected. RESULTS: Pioglitazone significantly attenuated WML in corpus callosum, caudate putamen, external capsule, and internal capsule. Cognitive impairment in RHRSP was ameliorated by pioglitazone. Pioglitazone attenuated arteriolar remodeling and reduced sICAM-1 level in serum. Pioglitazone decreased the proliferation of microglia and astrocyte and lowered the expression of proinflammatory cytokines IL-1ß and TNF-α in the white matter. CONCLUSIONS: Long-term treatment of pioglitazone has beneficial effect on hypertension-induced WML and cognition decline, which may partly through its effect on attenuation of arteriolar remodeling, endothelial activation, and brain inflammation.