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1.
Pain Manag Nurs ; 25(1): 34-45, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37268491

RESUMO

OBJECTIVES: To assess the effectiveness of cold therapy for pain and anxiety associated with chest tube removal. DESIGN: A Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Articles were searched from Cochrane Library, PubMed, Embase, CINAHL, ProQuest, Airiti Library, China National Knowledge Infrastructure, and the National Digital Library of Theses and Dissertations in Taiwan. REVIEW/ANALYSIS METHODS: Eight electronic databases were searched from inception to August 20, 2022. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of the included studies. Using a random-effects model, we calculated Hedges' g and its associated confidence interval to evaluate the effects of cold therapy. Cochrane's Q test and an I2 test were used to detect heterogeneity, and moderator and meta-regression analyses were conducted to explore possible sources of heterogeneity. Publication bias was assessed using a funnel plot, Egger's test, and trim-and-fill analysis. RESULTS: We examined 24 trials involving 1,821 patients. Cold therapy significantly reduced pain during and after chest tube removal as well as anxiety after chest tube removal (Hedges' g: -1.28, -1.27, and -1.80, respectively). Additionally, the effect size of cold therapy for reducing anxiety after chest tube removal was significantly and positively associated with that of cold therapy for reducing pain after chest tube removal. CONCLUSIONS: Cold therapy can reduce pain and anxiety associated with chest tube removal.


Assuntos
Tubos Torácicos , Dor , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ansiedade/terapia , Crioterapia
2.
J Transl Med ; 21(1): 519, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37533007

RESUMO

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Coração
3.
Int J Mol Sci ; 24(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37108148

RESUMO

Depression is a mental illness that has a serious negative impact on physical and mental health. The pathophysiology of depression is still unknown, and therapeutic medications have drawbacks, such as poor effectiveness, strong dependence, adverse drug withdrawal symptoms, and harmful side effects. Therefore, the primary purpose of contemporary research is to understand the exact pathophysiology of depression. The connection between astrocytes, neurons, and their interactions with depression has recently become the focus of great research interest. This review summarizes the pathological changes of neurons and astrocytes, and their interactions in depression, including the alterations of mid-spiny neurons and pyramidal neurons, the alterations of astrocyte-related biomarkers, and the alterations of gliotransmitters between astrocytes and neurons. In addition to providing the subjects of this research and suggestions for the pathogenesis and treatment techniques of depression, the intention of this article is to more clearly identify links between neuronal-astrocyte signaling processes and depressive symptoms.


Assuntos
Astrócitos , Depressão , Humanos , Transdução de Sinais , Neurônios , Neuritos
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(11): 1189-1194, 2022 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-36398542

RESUMO

OBJECTIVES: To investigate the level of 25 hydroxyvitamin D [25(OH)D] in late preterm infants and the effect of vitamin D3 supplementation on the neurobehavioral development of infants and young children. METHODS: In this prospective study, 161 late preterm infants who were admitted from June 2017 to June 2020 were enrolled. According to the level of 25(OH)D in umbilical cord blood, they were divided into three groups: sufficiency group (n=52), insufficiency group (n=53), and deficiency group (n=56). Each group was further divided into subgroup A (vitamin D3 800 IU/d) and subgroup B (individualized vitamin D3 supplementation) using a random number table. The levels of 25(OH)D were measured at 3 months after birth and at the corrected ages of 10 months and 18 months. The neurobehavioral development levels were determined by the Gesell Developmental Scale at the corrected ages of 10 months and 18 months. RESULTS: Within 24 hours and 3 months after birth, the insufficiency group and the deficiency group had a significantly lower level of 25(OH)D than the sufficiency group (P<0.05), and the insufficiency group had a significantly higher level of 25(OH)D than the deficiency group (P<0.05). In the deficiency group, subgroup B had a significantly higher level of 25(OH)D than subgroup A (P<0.05) at 3 months after birth. At the corrected ages of 10 months and 18 months, the insufficiency and deficiency groups had significantly lower scores of five functional areas of the Gesell Development Scale than the sufficiency group (P<0.05). Compared with the insufficiency group, the deficiency group had a significantly lower score of language at the corrected age of 10 months and a significantly lower score of gross motor at the corrected age of 18 months (P<0.05). Compared with subgroup A of the deficiency group, subgroup B had a significantly higher score of adaptive ability at the corrected age of 10 months and significantly higher scores of adaptive ability and response ability at the corrected age of 18 months (P<0.05). CONCLUSIONS: There is a significant difference in the level of 25(OH)D in umbilical cord blood in late preterm infants. Individualized vitamin D supplementation appears to be more effective for the treatment of vitamin D deficiency. Vitamin D level at birth and in early infancy has certain influence on neurobehavioral development.


Assuntos
Colecalciferol , Sangue Fetal , Lactente , Criança , Recém-Nascido , Humanos , Pré-Escolar , Colecalciferol/farmacologia , Estudos Prospectivos , Recém-Nascido Prematuro , Suplementos Nutricionais , Vitamina D
5.
Exp Cell Res ; 396(1): 112244, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860814

RESUMO

PD1/PDL1 pathway plays a critical role in cancer immune responses. The immune checkpoint inhibitors of PD1/PDL1 have been well explored and developed for immunotherapies of solid tumors. Recently, various monoclonal antibodies targeting the PD1/PDL1 pathway have emerged and achieved remarkable success in clinical trials. However, challenges with these monoclonal antibodies have appeared during cancer therapies, including predictors of response, patient selection, and innate resistance. Thus, a competitive antagonist of native PD1/PDL1, with smaller size and lower side-effect, is required for future cancer therapies. In this study, we utilized a protein evolution system of phage-assisted continuous evolution (PACE) to evolve PD1 continuously. Our results indicated that the newly evolved PD1 bound to PDL1 with higher affinity. The interactome analysis further suggested that these evolved PD1s exhibited higher specificity with PDL1. Therefore, these evolved PD1s may be applied as a new tool for tumor immunotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Evolução Molecular Direcionada/métodos , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/química , Antígeno B7-H1/genética , Sítios de Ligação , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica/efeitos dos fármacos , Genes Reporter , Células HEK293 , Humanos , Luciferases/genética , Luciferases/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida/métodos , Mutagênicos/farmacologia , Biblioteca de Peptídeos , Plasmídeos/química , Plasmídeos/metabolismo , Receptor de Morte Celular Programada 1/química , Receptor de Morte Celular Programada 1/genética , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
6.
J Nurs Scholarsh ; 53(2): 154-160, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33395500

RESUMO

PURPOSE: To examine the effects of health coaching on self-management and quality of life (QOL) in patients with chronic kidney disease (CKD) and to evaluate whether self-efficacy and patient activation mediate the effect of health coaching on self-management and QOL. DESIGN AND METHODS: A single-center, parallel-group, randomized controlled trial. A total of 108 patients with stages 1 to 3a CKD participated in the study. Participants were randomly assigned to a health-coaching intervention group or a usual care control group. Participants' QOL (World Health Organization Quality of Life Scale), self-management (CKD Self-Management instrument), patient activation (Patient Activation Measure), and self-efficacy (CKD Self-Efficacy instrument) were measured at baseline, immediately after, and 6 weeks after the intervention. FINDINGS: Health coaching improved QOL, self-management, patient activation, and self-efficacy at postintervention and at 12 weeks' follow-up. Health coaching had a significant indirect effect on QOL through improvements in patient activation. Health coaching exerted a significant indirect effect on self-management through improvements in self-efficacy and patient activation. CONCLUSIONS: The findings demonstrated that health coaching can effectively improve QOL and self-management. A health-coaching intervention can raise self-efficacy and activation levels through which self-management and QOL further improve. CLINICAL RELEVANCE: Health-coaching strategies can be used to assist patients with early-stage CKD in reaching their health goals and becoming activated in self-management of their diseases.


Assuntos
Tutoria , Participação do Paciente/estatística & dados numéricos , Relações Profissional-Paciente , Qualidade de Vida , Insuficiência Renal Crônica/terapia , Autoeficácia , Autogestão/psicologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Cardiovasc Nurs ; 36(5): 446-453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33273251

RESUMO

BACKGROUND: The Hypertension Self-care Profile Behavior (HTN-SCPB) scale is a self-report instrument with which a patient's self-care behavior can be assessed. However, its psychometric properties for adult patients with hypertension in Vietnam require clarification. OBJECTIVE: The aim of this study was to translate the HTN-SCPB scale into Vietnamese and to assess its psychometric properties. METHODS: The study included 220 adult patients with hypertension. To evaluate test-retest reliability, 133 participants were tested twice with a 3-week interval between tests. For construct validity, exploratory factor analysis was used to assess factor structure, and confirmatory factor analysis was used to evaluate the structural model fit of the scale. RESULTS: Reliability was confirmed by internal consistency (Cronbach α = 0.79) and test-retest reliability (intraclass correlation coefficient, 0.88). The Kaiser-Meyer-Olkin value was 0.75, and Bartlett's test of sphericity was significant (P < .001) and adequate for exploratory factor analysis. A 5-factor structure was obtained, and the factors were named as follows: "advanced self-management skills," "adverse health behaviors," "medication adherence," "diet-related knowledge regarding hypertension," and "information skills." Confirmatory factor analysis revealed that the model fit indices were acceptable (root-mean-square error of approximation, 0.07) or slightly less than the good fit values (comparative fit index, 0.85; incremental fit index, 0.85; goodness-of-fit index, 0.88; adjusted goodness-of-fit index, 0.84; and Tucker-Lewis index, 0.82). CONCLUSIONS: The Vietnamese HTN-SCPB scale had satisfactory validity and reliability for assessing self-care behaviors in patients with hypertension in Vietnam.


Assuntos
Hipertensão , Autocuidado , Adulto , Povo Asiático , Análise Fatorial , Humanos , Hipertensão/diagnóstico , Hipertensão/terapia , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
8.
Int J Nurs Pract ; 27(2): e12920, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33590947

RESUMO

AIM: To assess the effects of self-management interventions on systolic blood pressure, diastolic blood pressure, self-efficacy, medication adherence and body mass index in older adults with hypertension. BACKGROUND: Effective treatment of hypertension may require the practice of self-management behaviours. However, evidence on effects of self-management interventions on blood pressure, self-efficacy, medication adherence and body mass index in older adults with hypertension is lacking. DESIGN: A systematic review and meta-analysis. DATA SOURCES: CINAHL, Cochrane Library, Embase, Ovid-Medline, PubMed, Scopus, Web of Science and other sources were searched to October 2020. REVIEW METHODS: Data were analysed using Comprehensive Meta-Analysis 2.0 and quality assessment was done using ROB 2.0. The pooled effect sizes were reported as Hedges' g values with corresponding 95% confidence intervals using a random-effects model. RESULTS: Twelve randomized controlled trials met our inclusion criteria. The results revealed that self-management interventions significantly decreased blood pressure and increased self-efficacy and medication adherence in older adult patients with hypertension, with no significant effect on body mass index. CONCLUSIONS: Self-management interventions have considerable beneficial effects in older adults with hypertension. Health care providers should implement self-management interventions to strengthen the patient's role in managing their health.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Adesão à Medicação , Autoeficácia , Autogestão/métodos , Idoso , Humanos , Hipertensão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Nutr Neurosci ; 23(2): 101-109, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29804517

RESUMO

Objective: The alternate healthy eating index has been associated with depression. However, results reported in the literature are inconsistent. The present meta-analysis determined the association between the AHEI or AHEI-2010 and depression in adults without chronic disease.Methods: Nine electronic databases and the reference lists of identified studies were systematically searched for studies published up to December 2016. Articles examining the association between depression and the AHEI or AHEI-2010 in adults were included.Results: We identified eight observational studies with 10 effect sizes involving a total of 38,360 participants. When both the AHEI and AHEI-2010 were considered, the dietary index score was associated with a significant reduction in depression risk (odds ratio OR=0.70, 95% confidence interval CI=0.57-0.87). However, the subgroup analysis indicated that the AHEI-2010 (OR=0.69, 95% CI=0.56-0.89), but not the AHEI (OR=0.60, 95% CI=0.30-1.17), was significantly associated with reduced odds of depression. The heterogeneity among the included studies was significantly high (Q=48.9, P<0.01, I2=81.60%).Discussion: Our findings suggest that the AHEI-2010 is associated with a reduction in depression risk. However, well-designed randomized controlled trials must be conducted to confirm the causal relationship between the AHEI-2010 and depression.


Assuntos
Depressão/epidemiologia , Dieta Saudável , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Risco
10.
J Sep Sci ; 43(7): 1382-1392, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31981302

RESUMO

The present study aimed to develop a strategy involving quantitative analysis of multicomponents by single marker in combination with high-performance liquid chromatography fingerprint qualitative analysis for performing the quality control of Aurantii Fructus. The content of 12 components (eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, meranzin, poncirin, naringenin, nobiletin, tangeretin, and auraptene) in samples was determined using reliable relative correction factors that were obtained using naringin as an internal reference standard. The new method demonstrated good applicability, and no significant differences were observed between the external standard method and the new method as determined by calculating standard method difference. Qualitative evaluation of samples was conducted using similarity analysis, hierarchical cluster analysis, and quality fluctuation analysis. Chromatographic fingerprint data were divided into three groups by similarity and hierarchical cluster analyses, and seven components may have a more significant impact on the quality of Aurantii Fructus in quality fluctuation analysis. Overall, the study suggests that the qualitative and quantitative analyses of multicomponents using quantitative analysis of multicomponents by single marker combined with chromatographic fingerprinting can be considered good quality criteria for performing quality control and providing technical support for the further pharmacological and pharmaceutical research of Aurantii Fructus.


Assuntos
Citrus/química , Frutas/química , Cromatografia Líquida de Alta Pressão , Cumarínicos/análise , Dissacarídeos/análise , Flavanonas/análise , Flavonas/análise , Flavonoides/análise , Hesperidina/análogos & derivados , Hesperidina/análise
11.
Acta Pharmacol Sin ; 40(4): 425-440, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30382185

RESUMO

Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. The 2VO rats were orally administered CZ-7 (10, 20, 40 mg/kg) from day 27 to day 53 post-surgery. Morris water maze tests conducted at day 48-51 revealed that CZ-7 administration significantly reduced the escape latency in 2VO rats. After the rats were sacrificed on day 53, morphological studies using Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that administration of CZ-7 markedly attenuated the pathological changes in CA1-CA3 area of the hippocampus, including neuronal cell loss, nuclear shrinkage, and dark staining of neurons, and significantly decreased the chronic cerebral hypoperfusion-induced cell loss. Klüver-Barrera staining study revealed that CZ-7 administration significantly improved the white matter lesions. 8-OHdG and reactive oxygen species (ROS) immunofluorescent analyses showed that CZ-7 administration significantly decreased oxidative stress in CA1-CA3 area of the hippocampus. Finally, we found that the CZ-7-improved oxidative stress might be mediated via the Nrf2 pathway, evidenced by the double immunofluorescent staining of Nrf2 and the elevation of expression levels of oxidative stress proteins HO-1 and NQO1. In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses.


Assuntos
Antioxidantes/metabolismo , Artéria Carótida Primitiva/efeitos dos fármacos , Demência Vascular/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Demência Vascular/metabolismo , Demência Vascular/patologia , Masculino , Estrutura Molecular , Ratos , Ratos Wistar
12.
J Clin Nurs ; 23(1-2): 82-90, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23311545

RESUMO

AIMS AND OBJECTIVES: The specific aims of this study were as follows: (1) to describe psychosocial adjustment in adults with end-stage renal disease who underwent maintenance peritoneal dialysis; (2) to explore the influence of demographics, clinical variables, symptom distress and social support on psychosocial adjustment and (3) to determine predictive factors of psychosocial adjustment. BACKGROUND: Proper psychosocial adjustment is important for patients with end-stage renal disease to cope with multiple stressors of their disease and to balance their lives within the restrictions imposed by peritoneal dialysis treatment. Knowledge on psychosocial adjustment in patients receiving long-term peritoneal dialysis has been limited. DESIGN: The study was based on a predictive correlational design. METHOD: One hundred peritoneal dialysis patients were recruited from outpatient peritoneal dialysis clinics of a general hospital in Taipei, Taiwan. Data were collected with the study questionnaires, including the Physical Symptom Distress Scale, the Social Support Scale and the Psychosocial Adjustment to Illness Scale - self-report. RESULTS: The mean score on the Psychosocial Adjustment to Illness Scale was 359.7 (SD = 40.0), indicating that these participants were moderately struggling in adjusting to their illness. Symptom distress, family social support and financial status explained 38.3% of the variance in psychosocial adjustment (F3,96 = 21..5, p < 0.001). CONCLUSIONS: The level of psychosocial adjustment in peritoneal dialysis patients is suboptimal. Overall, the patients with high physical symptom distress, weak family social support and poor financial status reported deficient psychosocial adjustment to their illness. IMPLICATIONS FOR PRACTICE: The findings of this study are relevant to the understanding of preconditions that enable peritoneal dialysis patients to successfully adjust to the disease and its diverse consequences. Patients with insufficient income, higher symptom distress and less family social support have a greater risk of psychosocial maladjustment. Medical professionals may use these variables to identify higher risk groups for early intensive intervention.


Assuntos
Adaptação Fisiológica , Diálise Peritoneal/psicologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Affect Disord ; 348: 107-115, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101523

RESUMO

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test. Changes in astrocyte GJs function and morphology were observed by dye transfer and transmission electron microscopy, respectively. Expression and phosphorylation of connexin 43 (Cx43) were analyzed by Western blot. Also, considering the close relationship between depression and neuroinflammation, we determined the inflammatory response in serum with ELISA kits and analyzed the expression of inflammation-related proteins with Western blot. RESULTS: Hig ameliorated CUS-induced depression-like behavior in rats. Hig administration improved gap junctional dysfunction in astrocytes, reduced gap junctional gaps and elevated the expression of Cx43 and decreased the phosphorylation of Cx43. Meanwhile, Hig administration was also able to attenuate the inflammatory response that occurs after CUS in rats. LIMITATIONS: For the role of Cx43 in depression, we did not validate it more deeply in animal models with knockout Cx43. In addition, GJs dysfunction might be associated with the inflammatory response seen in depression, but this needs to be further investigated. CONCLUSIONS: Hig ameliorates depression and exerts its antidepressant effect possibly by improving the dysfunctional GJs between astrocytes and the inflammatory response.


Assuntos
Alcaloides , Astrócitos , Conexina 43 , Tetra-Hidroisoquinolinas , Humanos , Ratos , Animais , Conexina 43/metabolismo , Conexina 43/farmacologia , Doenças Neuroinflamatórias , Junções Comunicantes/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo
14.
Phytomedicine ; 123: 155238, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128394

RESUMO

BACKGROUND: Ischemic stroke, a severe and life-threatening neurodegenerative condition, currently relies on thrombolytic therapy with limited therapeutic window and potential risks of hemorrhagic transformation. Thus, there is a crucial need to explore novel therapeutic agents for ischemic stroke. Ginsenoside Rg1 (Rg1), a potential neuroprotective agent, exhibits anti-ischemic effects attributed to its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Nevertheless, the precise underlying mechanism of action remains to be fully elucidated. PURPOSE: This study aimed to explore whether Rg1 exerts anti-ischemic stroke effects by inhibiting pyroptotic neuronal cell death through modulation of the chemokine like factor 1 (CKLF1)/ C-C chemokine receptor type 5 (CCR5) axis. METHODS: In this study, the MCAO model was used as an ischemic stroke model, and experimental tests were performed after 6 hours of ischemia. The anti-ischemic effect of Rg1 was examined by TTC staining, nissl-staining and neurobehavioral tests. In the in vitro experiments, PC12 cells were subjected to stimulation with CKLF1's mimetic peptide C27 to assess the potential of CKLF1 to induce focal neuronal cell death. Additionally, the impact of CKLF1 mimetic peptide C27, antagonistic peptide C19, and CCR5 inhibitor MVC on PC12 cells subjected to oxygen-glucose deprivation (OGD) and subsequently treated with Rg1 was investigated. In vivo, Rg1 treatment was examined by quantitative real-time PCR (qPCR), ELISA, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and co-immunoprecipitate (Co-IP) assays to perspective whether Rg1 treatment reduces CKLF1/CCR5 axis-induced pyroptotic neuronal cell death. In addition, to further explore the biological significance of CKLF1 in ischemic stroke, CKLF1-/- rats were used as the observation subjects in this study. RESULTS: The in vitro results suggested that CKLF1 was able to induce neuronal cells to undergo pyroptosis. In vivo pharmacodynamic results showed that Rg1 treatment was able to significantly improve symptoms in ischemic stroke rats. In addition, Rg1 treatment was able to inhibit the interaction between CKLF1 and CCR5 after ischemic stroke and inhibited CKLF1/CCR5 axis-induced pyroptosis. The results of related experiments in CKLF1-/- rats showed that Rg1 lost its therapeutic effect after CKLF1 knockdown. CONCLUSION: Our findings indicate that the activation of the NLRP3 inflammasome is initiated by the CKLF1/CCR5 axis, facilitated through the activation of the NF-κB pathway, ultimately resulting in the pyroptosis of neuronal cells. Conversely, Rg1 demonstrates the capability to mitigate neuronal cell damage following CKLF1-induced effects by suppressing the expression of CKLF1. Thus, CKLF1 represents a crucial target for Rg1 in the context of cerebral ischemia treatment, and it also holds promise as a potential target for drug screening in the management of ischemic stroke.


Assuntos
Isquemia Encefálica , Ginsenosídeos , AVC Isquêmico , Traumatismo por Reperfusão , Humanos , Ratos , Animais , AVC Isquêmico/tratamento farmacológico , Piroptose , Receptores de Quimiocinas/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Receptores CCR5/uso terapêutico
15.
Ageing Res Rev ; 96: 102286, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38561044

RESUMO

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.


Assuntos
Doenças Neuroinflamatórias , Receptores CCR5 , Humanos , Receptores CCR5/metabolismo , Transdução de Sinais
16.
ScientificWorldJournal ; 2013: 124973, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23589703

RESUMO

This cross-sectional research study explored differences in health-promoting behavior and resilience among three groups of chronic kidney disease patients (high-risk, early chronic kidney disease; early CKD and pre-end stage renal disease; pre-ESRD) treated at the Nephrology outpatient clinic in northern Taiwan. A total of 150 CKD outpatients were interviewed using structured questionnaires including a CKD Health to Promote Lifestyle Scale, and resilience scale. We found that the pre-ESRD group had lower resilience than either high-risk or early CKD groups. Factors affecting pre-ESRD resilience were gender, occupational status, diabetes and health-promoting behaviors. Factors affecting resilience of the high-risk group included level of education and health-promoting behaviors while factors affecting resilience in the early CKD group involved whether they are employed and health promoting behaviors. A significant positive correlation was found between health promoting behavior and resilience in all study subjects. Multiple regression analysis found that factors which could effectively predict resilience in patients at high-risk for CKD were gender, whether the patient had a job, nutrition, self-actualization, and stress level, accounting for 69.7% of the variance. Therefore, nursing education should focus on health promotion advocacy throughout the life of not only patients but also their families.


Assuntos
Comportamentos Relacionados com a Saúde , Promoção da Saúde/estatística & dados numéricos , Qualidade de Vida/psicologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/psicologia , Resiliência Psicológica , Comportamento de Redução do Risco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Taiwan/epidemiologia
17.
Asian Biomed (Res Rev News) ; 17(4): 163-172, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37860679

RESUMO

Background: American ginseng has an obvious anti-fatigue effect, but the effective material basis is still unclear. The spectrum-effect relationship is a scientific method that studies the correlations between chemical spectra and pharmacological effect. Objective: To reveal the real bioactive compounds in American ginseng saponin (AGS) based on a study of the underlying correlations between these compounds' occurrence in rat serum after their intake of AGS and the anti-fatigue effect of AGS. Methods: We utilized ultra-performance liquid chromatography (UPLC) with quadrupole and time-of-flight mass spectrometry (Q-TOF-MS) to analyze the extract of AGS and its constituents in serum after oral administration in rats. The anti-fatigue effect of AGS in rats was measured using the time weight-bearing swimming technique, the content of blood urea nitrogen, hepatic glycogen, and blood lactic acid. The relationship between the peak area values in fingerprints from rat serum and pharmacodynamic parameters of AGS was established using correlation analysis with partial least square regression (PLSR) method and gray correlation method. Results: We detected and identified 22 compounds from extract, and 8 prototype components from serum. Through PLSR and gray correlation method, it was found that the ginsenosides Re, Rb1, and Rb2 were significantly positively related to the pharmacodynamic data. Conclusions: Based on the spectrum-effect relationship, PLSR and gray correlation method can be used to screen for the anti-fatigue components available in AGS. Such an approach is of practical significance as it provides an effective means for exploring the material basis for the efficacy of American ginseng, particularly as an anti-fatigue agent.

18.
Biomed Pharmacother ; 167: 115545, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37734259

RESUMO

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

19.
J Adv Res ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37926143

RESUMO

BACKGROUND: Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. AIM OF REVIEW: In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH.

20.
Eur J Med Chem ; 261: 115787, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37690263

RESUMO

Since tyrosine kinase inhibitor (TKI) could reverse ABCG2-mediated drug-resistance, novel chlorin e6-based conjugates of Dasatinib and Imatinib as photosensitizer (PS) were designed and synthesized. The results demonstrated that conjugate 10b showed strongest phototoxicity against HepG2 and B16-F10 cells, which was more phototoxic than chlorin e6 and Talaporfin. It could reduce efflux of intracellular PS by inhibiting ABCG2 in HepG2 cells, and localize in mitochondria, lysosomes, golgi and ER, resulting in higher cell apoptosis rate and ROS production than Talaporfin. Moreover, it could induce cell autophagy and block cell cycle in S phase, and significantly inhibit tumor growth and prolong survival time on BALB/c nude mice bearing HepG2 xenograft tumor to a greater extent than chlorin e6. Consequently, compound 10b could be applied as a promising candidate PS due to its good water-solubility and stability, low drug-resistance, high quantum yield of 1O2 and excellent antitumor efficacy in vitro and in vivo.


Assuntos
Fotoquimioterapia , Porfirinas , Animais , Camundongos , Humanos , Fármacos Fotossensibilizantes , Camundongos Nus , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Porfirinas/farmacologia
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