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Physalin A (PA) is a bioactive withanolide with multiple pharmacological properties and has been indicated to be cytotoxic to hepatocellular carcinoma (HCC) cell line HepG2. This study aims to explore the mechanisms underlying PA antitumor activity in HCC. HepG2 cells were exposed to various concentrations of PA. Cell counting kit-8 assay and flow cytometry were implemented for evaluating cell viability and apoptosis, respectively. Immunofluorescence staining was utilized for detecting autophagic protein LC3. Western blotting was employed for measuring levels of autophagy-, apoptosis- and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling-related proteins. A xenograft mouse model was established to verify the antitumor activity of PA in vivo. PA impaired HepG2 cell viability, and triggered apoptosis as well as autophagy. Inhibiting autophagy augmented PA-evoked HepG2 cell apoptosis. PA repressed PI3K/Akt signaling in HCC cells and activating PI3K/Akt reversed PA-triggered apoptosis and autophagy. PA treatment inhibited tumor growth in tumor-bearing mice. PA triggers HCC cell apoptosis and autophagy by inactivating PI3K/Akt signaling.
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BACKGROUND: Neonatal epileptic seizures cause postictal dysregulation of cerebral blood flow. Hydrogen sulfide (H2S), a mediator with vasodilator and antioxidant properties, is produced in the brain by astrocyte cystathionine ß-synthase (CBS). This study investigated whether H2S improves the cerebral vascular outcome of seizures. METHODS: Epileptic seizures were induced in newborn pigs using bicuculline. The effects of the CBS inhibitor aminooxyacetate (AOA) and the H2S donor NaHS on cerebral vascular outcome of seizures were examined in live pigs, cerebral endothelial cells, and cortical astrocytes. RESULTS: Brain H2S was elevated during seizures. AOA blocked H2S and reduced functional hyperemia in the epileptic brain. The endothelium- and astrocyte-dependent vasodilation of pial arterioles was impaired 48 h after seizures suggesting cerebral vascular dysfunction. Systemic NaHS elevated brain H2S and blocked reactive oxygen species in the epileptic brain and in primary endothelial cells and astrocytes during inflammatory and excitotoxic conditions. Postictal cerebrovascular dysfunction was exaggerated in H2S-inhibited pigs and minimized in NaHS-treated pigs. CONCLUSIONS: H2S elevation in the epileptic brain via activation of CBS contributes to functional hyperemia and exhibits cerebroprotective properties. The H2S donor NaHS enhances brain antioxidant defense and provides a therapeutic approach for preventing adverse cerebral vascular outcome of neonatal epileptic seizures. IMPACT: Epileptic seizures in neonates lead to prolonged postictal cerebral vascular dysregulation. The role of hydrogen sulfide (H2S), a mediator with vasodilator and antioxidant properties, in the epileptic brain has been explored. Astrocytes are major sites of enzymatic H2S production in the epileptic brain. Postictal cerebral vascular dysfunction is exaggerated when astrocyte H2S production is pharmacologically inhibited during seizures. Postictal cerebral vascular dysfunction is minimized when the brain H2S is elevated by systemic administration of NaHS during seizures. NaHS provides a therapeutic approach for improving cerebrovascular outcome of epileptic seizures via a mechanism that involves the antioxidant potential of H2S.
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Epilepsia , Sulfuro de Hidrógeno , Hiperemia , Animales , Porcinos , Animales Recién Nacidos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Células Endoteliales , Encéfalo , Vasodilatadores/farmacología , Convulsiones/tratamiento farmacológico , Epilepsia/tratamiento farmacológicoRESUMEN
Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.
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Tuberculosis Extrapulmonar , Tuberculosis Pleural , Tuberculosis Pulmonar , Humanos , Tuberculosis Pleural/complicaciones , Tuberculosis Pleural/epidemiología , Estudios Retrospectivos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/epidemiología , China/epidemiologíaRESUMEN
Toll-like receptor (TLR) agonists are potent immune-stimulators that hold great potential in vaccine adjuvants as well as cancer immunotherapy. However, TLR agonists in free form are prone to be eliminated quickly by the circulatory system and cause systemic inflammation side effects. It remains a challenge to achieve precise release of TLR7/8 agonist in the native form at the receptor site in the endosomal compartments while keeping stable encapsulation and inactive in nontarget environment. Here, we report a pH-/enzyme-responsive TLR7/8 agonist-conjugated nanovaccine (TNV), which responds intelligently to the acidic environment and cathepsin B in the endosome, precisely releases TLR7/8 agonist to activate its receptor signaling at the endosomal membrane, stimulates DCs maturation, and provokes specific cellular immunity. In vivo experiments demonstrate outstanding prophylactic and therapeutic efficacy of TNV in mouse melanoma and colon cancer. The endosome-targeted responsive nanoparticle strategy provides a potential delivery toolbox of adjuvants to advance the development of tumor nanovaccines.
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Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas , Endosomas , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos C57BL , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 8/agonistas , Receptores Toll-Like , VacunaciónRESUMEN
INTRODUCTION: This study was aimed to assess the prevalence of hyperuricemia and its associated risk factors among hypertensive patients in Southwest China. METHODS: From September 2013 to March 2014, a multistage, stratified sampling was conducted on 3505 hypertensive people aged 50-79 years who lived in urban communities within Chengdu and Chongqing, using a questionnaire and performing physical and biochemical measurements. RESULTS: In the study population, approximately 18.2% of all hypertensive participants had hyperuricemia (638/3505), with a prevalence rate of 21.5% in men and 16.2% in women (p < 0.05). Multivariate logistic regression analysis showed that aging, without spouse, current drinking, preferring hotpot, hypertriglyceridemia, BMI ≥ 25 kg/ m2, and central obesity were all positively correlated with hyperuricemia, whereas female gender was negatively correlated with hyperuricemia. The prevalence of hyperuricemia among hypertensive patients in urban adults aged 50-79 years in southwestern China was high, while levels of awareness were extremely low. DISCUSSION: Improved hyperuricemia health knowledge should be delivered to improve public awareness of the disease and it may need aggressive strategies aiming at the prevention and treatment of hyperuricemia. It is may necessary to encourage people to check blood uric acid levels when they first time to be diagnosed with hypertension, especially in the elderly.
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Hipertensión/complicaciones , Hiperuricemia/epidemiología , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Ácido Úrico/sangre , Anciano , China/epidemiología , Femenino , Humanos , Hipertensión/sangre , Hipertensión/epidemiología , Hiperuricemia/sangre , Hiperuricemia/etiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Factores SexualesRESUMEN
Precise monitoring of the subtle pH fluctuation during biological events remains a big challenge. Previously, we reported an ultra-pH-sensitive (UPS) nanoprobe library with a sharp pH response using co-polymerization of two tertiary amine-containing monomers with distinct pKa . Currently, we have generalized the UPS nanoparticle library with tunable pH transitions (pHt ) by copolymerization of a tertiary amine-containing monomer with a series of non-ionizable monomers. The pHt of nanoparticles is fine-tuned by the non-ionizable monomers with different hydrophobicity. Each non-ionizable monomer presents a constant contribution to pH tunability regardless of tertiary amine-containing monomers. Based on this strategy, we produced two libraries of nanoprobes with continuous pHt covering the entire physiological pH range (5.0-7.4) for fluorescent imaging of endosome maturation and cancers. This generalized strategy provides a powerful toolkit for biological studies and cancer theranostics.
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Nanopartículas , Aminas , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , PolimerizacionRESUMEN
BACKGROUND: We performed a prospective multicentre diagnostic study to evaluate the combined interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assay for detect active pulmonary tuberculosis (TB) in China. METHODS: Adult patients presenting symptoms suggestive of pulmonary TB were consecutively enrolled in three TB-specialized hospitals. Sputum specimens and blood sample and were collected from each participant at enrolment. The levels of Mycobacterium tuberculosis (MTB)-specific antigen-stimulated IFN-γ and IL-2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: Between July 2017 and December 2018, a total of 3245 patients with symptoms suggestive of pulmonary TB were included in final analysis. Of 3245 patients, 2536 were diagnosed as active TB, consisting of 1092 definite TB and 1444 clinically diagnosed TB. The overall sensitivity and specificity of IFN-γ were 83.8% and 81.5%, respectively. In addition, compared with IFN-γ, the specificity of IL-2 increased to 94.3%, while the sensitivity decreased to 72.6%. In addition, the highest sensitivity was achieved with parallel combination of IFN-γ/IL-2, with a sensitivity of 87.9%, and its overall specificity was 79.8%. The sensitivity of series combination test was 68.5%. Notably, the sensitivity of series combination test in definite TB (72.1%) was significantly higher than that in clinically diagnosed TB (65.8%). CONCLUSION: In conclusion, we develop a new immunological method that can differentiate between active TB and other pulmonary diseases. Our data demonstrates that the various IFN-γ/IL-2 combinations provides promising alternatives for diagnosing active TB cases in different settings. Additionally, the diagnostic accuracy of series combination correlates with severity of disease in our cohort.
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Mycobacterium tuberculosis , Tuberculosis Pulmonar , Adulto , Antígenos Bacterianos , China , Ensayo de Inmunoadsorción Enzimática , Humanos , Interferón gamma , Ensayos de Liberación de Interferón gamma , Interleucina-2 , Estudios Prospectivos , Tuberculosis Pulmonar/diagnósticoRESUMEN
In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.
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Comorbilidad , Pacientes Internos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Atherosclerosis is a vital cause of cardiovascular diseases. The correlation between proteinuria and atherosclerosis, however, has not been confirmed. This study aimed to assess whether there is a relationship between proteinuria and atherosclerosis. METHODS: From January 2016 to September 2020, 13,545 asymptomatic subjects from four centres in southern China underwent dipstick proteinuria testing and carotid atherosclerosis examination. Data on demography and past medical history were collected, and laboratory examinations were performed. The samples consisted of 7405 subjects (4875 males and 2530 females), excluding subjects failing to reach predefined standards and containing enough information. A multivariate logistic regression model was used to adjust the influence of traditional risk factors for atherosclerosis on the results. RESULTS: Compared with proteinuria-negative subjects, proteinuria-positive subjects had a higher prevalence rate of carotid atherosclerosis. The differences were statistically significant (22.6% vs. 26.7%, χ2 = 10.03, p = 0.002). After adjusting for common risk factors for atherosclerosis, age, sex, BMI, blood lipids, blood pressure, renal function, hypertensive disease, diabetes mellitus and hyperlipidaemia, proteinuria was an independent risk factor for atherosclerosis (OR = 1.191, 95% CI 1.015-1.398, p = 0.033). The Hosmer-Lemeshow test was used to test the risk prediction model of atherosclerosis, and the results showed that the model has high goodness of fit and strong independent variable prediction ability. CONCLUSIONS: Proteinuria is independently related to carotid atherosclerosis. With the increase in proteinuria level, the risk of carotid atherosclerotic plaque increases. For patients with positive proteinuria, further examination of atherosclerosis should not be ignored.
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Enfermedades de las Arterias Carótidas/epidemiología , Proteinuria/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Proteinuria/diagnóstico , Proteinuria/orina , Tiras Reactivas , Medición de Riesgo , Factores de Riesgo , Ultrasonografía Doppler en Color , Urinálisis/instrumentación , Adulto JovenRESUMEN
OBJECTIVE: This article analyzes factors which affect the prognosis of acute cerebral infarction (ACI) patients receiving a course of antiplatelet therapy with aspirin and (or) clopidogrel for 14 days and proposes a simple grading scale to predict the clinical effectiveness of these drugs. METHODS: We evaluated the association between ACI and risk factor (univariate analysis) on at day 14 post admission. Factors which potentially affected the 14-day prognosis of the patients were identified by logistic regression. A clinical grading scale, the DAPT score, was developed by weighing the independent predictors based on these factors. RESULTS: It is revealed that the factors which affected 14 days prognosis univariate analysis included age ≥ 50 years (P = 0.007), diabetes (P = 0.017), hypertension (P ≤ 0.001), hyperhomocysteinemia (P = 0.001), and ipsilateral carotid artery stenosis ≥ 50% (P = 0.019). Logistic regression also revealed that the factors which affected 14 days prognosis included age ≥ 50 years (P = 0.007), hypertension (P ≤ 0.001), hyperhomocysteinemia (P = 0.001), and ipsilateral carotid artery stenosis ≥ 50% (P = 0.014).The assigned values of age ≥ 50 years, Grade 1 hypertension, Grade 2 hypertension, Grade 3 hypertension, hyperhomocysteinemia, and ipsilateral carotid artery stenosis ≥ 50% were 1, 1, 2, 3, 1, and 1, respectively. We named this score (DAPT score) and it ranged between 0 and 6. Using 3 as a cutoff, the sensitivity was 90.6% and the specificity was 63.3%. CONCLUSIONS: The DAPT Score might be useful to for identifying with ACI who are suitable to receive aspirin combined with clopidogrel. Future large-scale, multi-center prospective studies are necessary.
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Infarto Cerebral , Inhibidores de Agregación Plaquetaria , Infarto Cerebral/complicaciones , Infarto Cerebral/tratamiento farmacológico , Clopidogrel/uso terapéutico , Quimioterapia Combinada , Humanos , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Noninvasive imaging strategies have been extensively investigated for in vivo mapping of sentinel lymph nodes (SLNs). However, the current imaging strategies fail to accurately assess tumor metastatic status in SLNs with high sensitivity. Here we report pH-amplified self-illuminating near-infrared nanoparticles, which integrate chemiluminescence resonance energy transfer (CRET) and signal amplification strategy, enabling accurate identification of metastatic SLNs. After draining into lymph nodes, the nanoparticles were phagocytosed and dissociated in acidic phagosomes of inflammatory macrophages to emit near-infrared luminescent light. Using these nanoparticles, we successfully differentiated tumor metastatic lymph nodes from benign ones. These nanoparticles also exhibited excellent imaging capability for early detection of metastatic SLNs in diverse animal tumor models with small tumor volume (100-200â mm3 ).
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Transferencia Resonante de Energía de Fluorescencia , Ganglios Linfáticos/patología , Linfoma/patología , Nanopartículas/química , Humanos , Concentración de Iones de HidrógenoRESUMEN
Mycobacterium abscessus is intrinsically resistant to most antimicrobial agents. The emerging infections caused by M. abscessus and the lack of effective treatment call for rapid attention. Here, we intended to construct a selectable marker-free autoluminescent M. abscessus strain (designated UAlMab) as a real-time reporter strain to facilitate the discovery of effective drugs and regimens for treating M. abscessus The UAlMab strain was constructed using the dif/Xer recombinase system. In vitro and in vivo activities of several drugs, including clofazimine and TB47, a recently reported cytochrome bc1 inhibitor, were assessed using UAlMab. Furthermore, the efficacy of multiple drug combinations, including the clofazimine and TB47 combination, were tested against 20 clinical M. abscessus isolates. The UAlMab strain enabled us to evaluate drug efficacy both in vitro and in live BALB/c mice in a real-time, noninvasive fashion. Importantly, although TB47 showed marginal activity either alone or in combination with clarithromycin, amikacin, or roxithromycin, the drug markedly potentiated the activity of clofazimine, both in vitro and in vivo This study demonstrates that the use of the UAlMab strain can significantly facilitate rapid evaluation of new drugs and regimens. The clofazimine and TB47 combination is effective against M. abscessus, and dual/triple electron transport chain (ETC) targeting can be an effective therapeutic approach for treating mycobacterial infections.
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Antibacterianos/farmacología , Clofazimina/farmacología , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mycobacterium abscessus/efectos de los fármacos , Amicacina/farmacología , Animales , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Claritromicina/farmacología , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Sinergismo Farmacológico , Transporte de Electrón/efectos de los fármacos , Complejo III de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/metabolismo , Femenino , Ingeniería Genética/métodos , Luminiscencia , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/enzimología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/patología , Mycobacterium abscessus/genética , Mycobacterium abscessus/metabolismo , Imagen Óptica/métodos , Recombinasas/genética , Recombinasas/metabolismo , Roxitromicina/farmacologíaRESUMEN
Activation of the NLRP3 inflammasome plays an important role in high glucose- induced endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). Dulaglutide, a newly developed glucagon-like peptide-1 receptor (GLP-1R) agonist, has been approved for the management of T2DM. In the current study, we aimed to investigate whether dulaglutide possesses a protective effect against high glucose- induced activation of the NLRP3 inflammasome. Our results indicate that dulaglutide treatment prevented high glucose- induced generation of reactive oxygen species (ROS) and protein carbonyl, as well as the expression of NADPH oxidase 4 (NOX-4) in human umbilical vein endothelial cells (HUVECs). Dulaglutide treatment could inhibit high glucose- induced release of lactate dehydrogenase (LDH) and the expression of TXNIP. Dulaglutide suppressed high glucose- induced activation of NLRP3 inflammasome by reducing the expression of NLRP3, ASC, and cleaved caspase 1 (P10). Notably, dulaglutide treatment suppressed high glucose- induced maturation of IL-1ß and IL-18. Mechanistically, our findings indicate that SIRT1 was involved in this process by showing that knockdown of SIRT1 by transfection with SIRT1 siRNA abolished the inhibitory effects of dulaglutide on IL-1ß and IL-18 secretion via suppression of NLRP3, ASC, and p10. These data suggest that dulaglutide might serve as a potential drug for the treatment of cardiovascular complications in T2DM patients.
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Células Endoteliales/efectos de los fármacos , Péptidos Similares al Glucagón/análogos & derivados , Glucosa/farmacología , Fragmentos Fc de Inmunoglobulinas/farmacología , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteínas Recombinantes de Fusión/farmacología , Proteínas Adaptadoras de Señalización CARD/metabolismo , Proteínas Portadoras/metabolismo , Caspasa 1/metabolismo , Péptidos Similares al Glucagón/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamasomas/metabolismo , L-Lactato Deshidrogenasa/metabolismo , NADPH Oxidasa 4/metabolismo , Carbonilación Proteica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismoRESUMEN
Epilepsy is a common manifestation of glioma patients and negatively impacts on quality of life and neurocognitive function. The risk of preoperative seizures in patients with glioma is currently under discussion. We aimed to evaluate the relationship between tumor locations in the cerebrum and preoperative seizures in patients with glioma. PubMed, EMBASE, Web of Science, China Biology Medicine, and the Cochrane Library were systematically searched from inception to July 15, 2017, for original studies including reports of preoperative seizures in patients with gliomas in different brain regions. The pooled odds ratio (OR) and 95% confidence interval (CI) of the meta-analysis for preoperative seizure risk stratified by cerebrum regions were calculated. The quality of evidence was assessed per outcome, using the approach of the Grades of Recommendation, Assessment, Development and Evaluation. Overall, 4323 participants in 16 population-based studies were included in this meta-analysis. The meta-analysis indicated that gliomas in the frontal lobe (OR = 1.51, 95% CI = 1.09-2.09, P = 0.013) were associated with a higher risk for preoperative seizure compared to occipital lobe involved (OR = 0.53, 95% CI = 0.32-0.88, P = 0.014). Regarding the other three lobe involved gliomas, no difference was found between the incidence of preoperative seizures and tumor location. Current limited data suggest that frontal gliomas were associated with a higher risk of preoperative seizures, while gliomas in the occipital lobe were associated with a lower seizure risk. Further RCT studies recruiting larger sample sizes are required to validate these results and guide clinical practice.
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Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/patología , Glioma/complicaciones , Glioma/patología , Convulsiones/etiología , Neoplasias Encefálicas/epidemiología , Glioma/epidemiología , Humanos , Incidencia , Periodo Preoperatorio , Convulsiones/epidemiologíaRESUMEN
Neonatal asphyxia leads to cerebrovascular disease and neurological complications via a mechanism that may involve oxidative stress. Carbon monoxide (CO) is an antioxidant messenger produced via a heme oxygenase (HO)-catalyzed reaction. Cortical astrocytes are the major cells in the brain that express constitutive HO-2 isoform. We tested the hypothesis that CO, produced by astrocytes, has cerebroprotective properties during neonatal asphyxia. We developed a survival model of prolonged asphyxia in newborn pigs that combines insults of severe hypoxia, hypercapnia, and acidosis while avoiding extreme hypotension and cerebral blood flow reduction. During the 60-min asphyxia, CO production by brain and astrocytes was continuously elevated. Excessive formation of reactive oxygen species during asphyxia/reventilation was potentiated by the HO inhibitor tin protoporphyrin, suggesting that endogenous CO has antioxidant effects. Cerebral vascular outcomes tested 24 and 48 h after asphyxia demonstrated the sustained impairment of cerebral vascular responses to astrocyte- and endothelium-specific vasodilators. Postasphyxia cerebral vascular dysfunction was aggravated in newborn pigs pretreated with tin protoporphyrin to inhibit brain HO/CO. The CO donor CO-releasing molecule-A1 (CORM-A1) reduced brain oxidative stress during asphyxia/reventilation and prevented postasphyxia cerebrovascular dysfunction. The antioxidant and antiapoptotic effects of HO/CO and CORM-A1 were confirmed in primary cultures of astrocytes from the neonatal pig brain exposed to glutamate excitotoxicity. Overall, prolonged neonatal asphyxia leads to neurovascular injury via an oxidative stress-mediated mechanism that is counteracted by an astrocyte-based constitutive antioxidant HO/CO system. We propose that gaseous CO or CO donors can be used as novel approaches for prevention of neonatal brain injury caused by prolonged asphyxia. NEW & NOTEWORTHY Asphyxia in newborn infants may lead to lifelong neurological disabilities. Using the model of prolonged asphyxia in newborn piglets, we propose novel antioxidant therapy based on systemic administration of low doses of a carbon monoxide donor that prevent loss of cerebral blood flow regulation and may improve the neurological outcome of asphyxia.
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Arteriolas/efectos de los fármacos , Asfixia Neonatal/tratamiento farmacológico , Astrocitos/efectos de los fármacos , Boranos/farmacología , Dióxido de Carbono/metabolismo , Carbonatos/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Trastornos Cerebrovasculares/prevención & control , Fármacos Neuroprotectores/farmacología , Piamadre/irrigación sanguínea , Animales , Animales Recién Nacidos , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Arteriolas/metabolismo , Arteriolas/fisiopatología , Asfixia Neonatal/complicaciones , Asfixia Neonatal/metabolismo , Asfixia Neonatal/fisiopatología , Astrocitos/metabolismo , Astrocitos/patología , Velocidad del Flujo Sanguíneo , Células Cultivadas , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/metabolismo , Trastornos Cerebrovasculares/fisiopatología , Modelos Animales de Enfermedad , Femenino , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo-Oxigenasa 1/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Sus scrofa , Factores de Tiempo , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Pulmonary nontuberculous mycobacteria (NTM) disease is of increasing public health concern in China. Information is limited regarding risk factors associated with this disease in China. The objective of this study was to describe the epidemiology of pulmonary disease due to NTM in Southern China. METHODS: We retrospectively reviewed the medical records of pulmonary NTM patients registered in the Guangzhou Chest Hospital with positive mycobacterial cultures during 2013-2016. We described sex, age, residence, treatment history, laboratory examination results and comorbidities of pulmonary NTM patients. RESULTS: Among the 607 NTM cases, the most prevalent species were Mycobacterium avium complex (44.5%), Mycobacterium abscessus complex (40.5%), Mycobacterium kansasii (10.0%) and Mycobacterium fortuitum (2.8%). The male:female ratio was significantly lower among patients infected with rapidly growing mycobacteria (RGM) than among those with slowly growing mycobacteria (SGM). The risk of developing SGM disease significantly increased with advancing age. In addition, pulmonary RGM diseases were more common in migrant population than resident population. Notably, patients with pulmonary RGM diseases were significantly more likely to have bronchiectasis underlying noted than those with SGM diseases. No significant difference was observed in in vitro drug susceptibility among NTM species. CONCLUSION: Our data illustrate that the M. avium complex is the most predominant causative agent of pulmonary NTM disease in Southern China. Female, migrant population, the presence of bronchiectasis are independent risk factors for pulmonary diseases due to RGM. In addition, the prevalence of SGM increases significantly with advancing age.
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Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Adolescente , Adulto , Distribución por Edad , Antibióticos Antituberculosos/uso terapéutico , China/epidemiología , Comorbilidad , Femenino , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Micobacterias no Tuberculosas , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Adulto JovenRESUMEN
Our aim is to investigate the prevalence and risk factors associated with hypertension among the Chinese Qiang population. From September 2012 to March 2013, a cross-sectional study was conducted in urban and rural communities of the Qiang population using multistage cluster sampling. A total of 2676 people aged above 20 years were enrolled in the analysis. Standardized mercury sphygmomanometer was used to measure the blood pressure twice after a 10-minute seated rest, and the average blood pressure was obtained. The hypertension prevalence among the population aged above 20 years was 13.9%, and age-standardized prevalence was 12.3%. Male and female prevalence of hypertension, as well as the prevalence in urban and rural areas, all increased with age. There were no significant differences between males and females and between urban and rural residents. Among hypertensive patients, 44.2% were aware of their hypertension, 38.0% were undergoing antihypertensive treatment, but only 10.5% achieved blood pressure control. Multivariate logistic regression analysis showed that the risk factors of hypertension included age, low income, overweight and obesity, family history of hypertension. The prevalence of hypertension in Chinese Qiang adults is significantly lower than the national level. Awareness, treatment, and control rates of hypertension were low in the Qiang population. Thus, hypertension-related health knowledge should be more aggressively delivered to improve public awareness and the capacity of community health services should be strengthened.
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Pueblo Asiatico/estadística & datos numéricos , Presión Sanguínea , Conocimientos, Actitudes y Práctica en Salud , Hipertensión/etnología , Adulto , Factores de Edad , Anciano , Antihipertensivos/uso terapéutico , China/epidemiología , Estudios Transversales , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Renta , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug into pyrazinoic acid (POA) by Mycobacterium tuberculosis has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report how a new PZA resistance determinant, the Asp67Asn substitution in Rv2783, confers M. tuberculosis resistance to PZA. Expression of the mutant allele but not the wild-type allele in M. tuberculosis recapitulates the PZA resistance observed in clinical isolates. In addition to catalyzing the metabolism of RNA and single-stranded DNA, Rv2783 also metabolized ppGpp, an important signal transducer involved in the stringent response in bacteria. All catalytic activities of the wild-type Rv2783 but not the mutant were significantly inhibited by POA. These results, which indicate that Rv2783 is a target of PZA, provide new insight into the molecular mechanism of the sterilizing activity of this drug and a basis for improving the molecular diagnosis of PZA resistance and developing evolved PZA derivatives to enhance its antituberculosis activity.