RESUMEN
Multinucleated microglia have been observed in contexts associated with infection, inflammation, and aging. Though commonly linked to pathological conditions, the larger cell size of multinucleated microglia might enhance their phagocytic functions, potentially aiding in the clearance of brain debris and suggesting a reassessment of their pathological significance. To assess the phagocytic capacity of multinucleated microglia and its implications for brain debris clearance, we induced their formation by inhibiting Pyk2 activity using the pharmacological inhibitor PF-431396, which triggers cytokinesis regression. Multinucleated microglia demonstrate enhanced phagocytic function, as evidenced by their increased capacity to engulf ß-amyloid (Aß) oligomers. Concurrently, the phosphorylation of Pyk2, induced by Aß peptide, was diminished upon treatment with a Pyk2 inhibitor (Pyk2-Inh, PF-431396). Furthermore, the increased expression of Lamp1, a lysosomal marker, with Pyk2-inh treatment, suggests an enhancement in proteolytic activity. In vivo, we generated an acute Alzheimer's disease (AD) model by infusing Aß into the brains of Iba-1 EGFP transgenic (Tg) mice. The administration of the Pyk2-Inh led to an increased migration of microglia toward amyloid deposits in the brains of Iba-1 EGFP Tg mice, accompanied by morphological activation, suggesting a heightened affinity for Aß. In human microglia, lipopolysaccharide (LPS)-induced inflammatory responses showed that inhibition of Pyk2 signaling significantly reduced the transcription and protein expression of pro-inflammatory markers. These results suggest that Pyk2 inhibition can modulate microglial functions, potentially reducing neuroinflammation and aiding in the clearance of neurodegenerative disease markers. This highlights Pyk2 as a promising target for therapeutic intervention in neurodegenerative diseases.
Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Modelos Animales de Enfermedad , Quinasa 2 de Adhesión Focal , Ratones Transgénicos , Microglía , Fagocitosis , Quinasa 2 de Adhesión Focal/metabolismo , Quinasa 2 de Adhesión Focal/antagonistas & inhibidores , Animales , Péptidos beta-Amiloides/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratones , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/metabolismo , Humanos , Ratones Endogámicos C57BLRESUMEN
Focus on the safety of herbal medicines has mainly been directed towards the presence of intrinsic toxicity, as found in the cases of renal and hepatic dysfunction caused by aristolochic acids. However, contamination from extrinsic hazards may impart an even greater reduction in their safety and efficacy. This study reveals that pesticides were present in the majority (88%) of a comprehensive cross-section (n = 1771) of herbal medicine samples. Alarmingly, more than half (59%) contained pesticides over the European Pharmacopoeia (EP) limit, and 43% of them contained 35 varieties of banned, extremely toxic pesticides, eight of which were detected at levels over 500 times higher than the default Maximum Residue Limit (MRL). DDTs, carbofuran, and mevinphos were confirmed as being among the most risk-inducing pesticides by three different risk assessment methods, reported to produce carcinogenic, genotoxic, reproductive, and developmental effects, in addition to carrying nephrotoxicity and hepatotoxicity. In light of these findings, and withstanding that extrinsic hazards can be controlled unlike intrinsic toxicity, the authors here strongly recommend the application of herbal medicine quality-control measures and solutions to safeguard against a neglected but certainly potentially serious health risk posed to the majority of the global population that consumes herbal medicines.
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Contaminación de Medicamentos , Medicamentos Herbarios Chinos/análisis , Plaguicidas/análisis , Carbofurano , Cromatografía de Gases , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Residuos de Plaguicidas/análisis , Medición de Riesgo , Espectrometría de Masas en Tándem/métodosRESUMEN
BACKGROUND: Hypertension is regarded as a major and independent risk factor of cardiovascular diseases, and numerous studies observed an inverse correlation between vitamin C intake and blood pressure. AIM: Our aim is to investigate the relationship between serum vitamin C and blood pressure, including the concentration differences and the correlation strength. METHOD: Two independent researchers searched and screened articles from the National Library of Medicine, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP databases, and WANFANG databases. A total of 18 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 14 English articles and 4 Chinese articles. RESULTS: In the evaluation of serum vitamin C levels, the concentration in hypertensive subjects is 15.13 µmol/L lower than the normotensive ones (mean difference = -15.13, 95% CI [-24.19, -6.06], and P = 0.001). Serum vitamin C has a significant inverse relation with both systolic blood pressure (Fisher's Z = -0.17, 95% CI [-0.20, -0.15], P < 0.00001) and diastolic blood pressure (Fisher's Z = -0.15, 95% CI [-0.20, -0.10], P < 0.00001). CONCLUSIONS: People with hypertension have a relatively low serum vitamin C, and vitamin C is inversely associated with both systolic blood pressure and diastolic blood pressure.
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Ácido Ascórbico/sangre , Presión Sanguínea , Hipertensión/fisiopatología , Deficiencia de Vitamina D/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Medición de Riesgo , Factores de Riesgo , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Vitamin D is a fat-soluble vitamin that is related to the health of the human body and is an indispensable nutrient for human beings. Some studies indicated that type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) may be associated with vitamin D deficiency, but the current understanding of this point of view remains controversial. This study aimed to evaluate the correlation between serum 25-hydroxyl vitamin D (25 [OH] D) concentration and DPN in patients with T2DM by a meta-analysis, and to provide a reference for doctors. METHODS: Relevant studies were selected from the PubMed, Cochrane Library, China National Knowledge Infrastructure, VIP databases, and Wanfang Data Knowledge Service Platform databases dating from 2000 to December 2017. A total of 75 articles related to serum 25 (OH) D and DPN were selected from 2000 to December 2017. Based on the inclusion and exclusion criteria of the literature, a quality assessment was conducted using the Newcastle-Ottawa scale, and a meta-analysis was performed by RevMan5.3 statistical software. RESULTS: Thirteen studies that involved a total of 2814 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis results, heterogeneity test showed that, Pâ<â.000 01, Iâ=â92%, calculation by random effect model revealed that, the serum concentration of 25 (OH) D in T2DM combined with DPN group was lower than that in the group without DPN (weighted mean differenceâ=â-0.74, 95% confidence interval: -1.03 to -0.46) CONCLUSIONS:: Vitamin D is associated with type 2 DPN (DPN), and vitamin D deficiency can lead to an increased risk of type 2 DPN. However, more high-quality research is needed.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Neuropatías Diabéticas/sangre , Enfermedades del Sistema Nervioso Periférico/sangre , Deficiencia de Vitamina D/etiología , Vitamina D/análogos & derivados , Adulto , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/etiología , Factores de Riesgo , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
OBJECTIVE: To comprehensively compare the effects of conventional therapy combined with intravenous vitamin C and conventional therapy on viral myocarditis in children through a meta-analysis. METHODS: Relevant articles including clinical trials of normal treatment combined with intravenous vitamin C and conventional therapy for viral myocarditis in children that were published between January 2000 and February 2018 were selected from PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and WANFANG database. The quality of the included studies was assessed using the Cochrane systematic review method (version 5.1.0); data quality was evaluated by two independent researchers. The total effective rate; LDH, CK, and CK-MB levels; and other indicators were analyzed using Rev Man 5.3 software. RESULTS: Eight studies were eligible for this meta-analysis, which included a total of 426 patients in the treatment group and 363 patients in the control group. The meta-analysis results of six studies showed that the total effective rate of intravenous vitamin C combined with conventional therapy was higher than that of conventional therapy alone [Z = 5.46, 95% confidence interval (CI): 1.21 (1.13 to 1.30), P < 0.00001]; that of five studies showed that LDH levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 3.70, 95% CI: -1.88 (-2.88 to -0.88), P = 0.0002]; that of three studies showed that CK levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 4.21, 95% CI: -0.55 (-0.81 to -0.30), P < 0.0001]; that of four studies showed that CK-MB levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 13.64, 95% CI: -1.44 (-1.65 to -1.24), P < 0.00001]; that of two studies showed that CD3 levels were higher in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 2.45, 95% CI: 0.41 (0.08-0.73), P = 0.01]; that of two studies showed no significant difference in changes in CD4 levels between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.28, 95% CI: -0.21 (-1.69 to 1.28), P = 0.78]; and that of two studies showed no significant difference in changes in CD4/CD8 between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.07, 95% CI: -0.03 (-0.73 to 0.67), P = 0.94]. CONCLUSION: The meta-analysis results showed that intravenous vitamin C combined with conventional therapy is better than the simple, conventional therapy for the treatment of viral myocarditis in children in terms of the total effective rate and LDH, CK, and CK-MB levels.
RESUMEN
A previous study on rats showed that simultaneous acupuncture stimulation at the "Bai-Hui" (GV 20) and the "Yintáng" (Ex-HN3) acupoints alleviated the state of depression to an extent similar to that achieved by pharmacotherapy. This study investigated whether the alleviation of the depressed state required simultaneous acupuncture at these two acupuncture points. For the purposes of testing the effect of acupuncture on depressive symptoms, we treated a depression model rat, where depression had been induced by using a mild water-immersion stress technique, with either acupuncture stimulation at only one acupuncture point (GV 20 or Ex-HN3) or an antidepressant, and we measured the immobile time for evaluating the state of depression. Anxiety, as a symptom commonly associated with depression, was also evaluated by measuring the number of head dips. Neither the immobile time nor the number of head dips decreased upon acupuncture stimulation. From this study, single acupuncture stimulation at either "GV 20" or "Ex-HN3" alleviated neither the state of depression nor the anxiety. The water-immersion stress used to make the depression model rats was shown not to induce anxiety; however, the stress induced by immobilizing the rats for acupuncture stimulation did lead to anxiety.
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Puntos de Acupuntura , Terapia por Acupuntura/métodos , Depresión/terapia , Animales , Conducta Animal/fisiología , Modelos Animales de Enfermedad , Masculino , Distribución Aleatoria , RatasRESUMEN
Depression is a kind of mood disorder. The incidence of depressed patients has demonstrated an upward trend in recent years. Symptoms may improve with treatments such as pharmacotherapy and cognitive-behavioral therapy, but such approaches may exert strong side effects, and therapeutic effects can be slow. We studied how acupuncture stimulation would affect depression as a method to reduce side effects. Mild depression was induced in rats by 1-week water-immersion stress. We treated these mildly depressed rats with either acupuncture stimulation at the "Bai-Hui" (GV 20) and "Yintáng" (Ex-HN3) points, or antidepressants. We then measured the immobile time and serum corticosterone level in rats. Immobile time and serum corticosterone level decreased on stimulation with acupuncture or antidepressants. These findings suggest that mild depression in rats was improved by stimulation with acupuncture The mechanisms underlying such improvement may effect HPA system activated by this stress, and inhibit the response to lead to the disorder of the hippocampal nerve cell.
Asunto(s)
Terapia por Acupuntura , Depresión/terapia , Estrés Psicológico/terapia , Animales , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/etiología , Imipramina/uso terapéutico , Inmersión , Masculino , Ratas Wistar , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológicoRESUMEN
The cortex of Eucommia ulmoides Oliver is widely used to treat kidney deficiency in traditional Chinese medicine. Its leaves have recently been reported to have anti-obesity properties in metabolic syndrome-like rat models. Due to a sharp decline in estrogen production, obesity, together with osteoporosis, are common problems in postmenopausal women. In this study, we examined the potential effect of Eucommia leaf extract (ELE) in preventing osteoporosis and obesity induced by ovariectomy (OVX). Forty-six female Wistar rats were divided into six groups: Sham-Cont, OVX-Cont, and four OVX groups administered estradiol and different concentrations of ELE 1.25%, ELE 2.5%, and ELE 5%. Treatments were administered after ovariectomy at six weeks of age and continued for 12 weeks. OVX induced a significant decrease in the bone mineral density (BMD) of the lumbar, femora, and tibiae, together with a marked increase in body mass index (BMI). The administration of 5% ELE led to a significant increase in tibial and femoral BMD, as well as significantly increased bone-strength parameters when compared with OVX-Cont rats. According to the suppressed Dpd and increased osteocalcin concentrations in ELE 5% rats, we suggest that varying proportions of bone formation and bone absorption contributed to the enhanced BMD in the femora and tibiae. In addition, significant decreases in body weight, BMI and fat tissue in 5% ELE rats were also observed. These results suggest that ELE may have curative properties for BMD and BMI in OVX rats, and could provide an alternative therapy for the prevention of both postmenopausal osteoporosis and obesity.