RESUMO
Objective: To compare the positioning effect of three-dimensional reconstruction technology and Hook-wire puncture operation on small pulmonary nodules during video-assisted thoracoscopic surgery (VATS), and evaluate its effectiveness, efficiency, and safety. Methods: The subjects of this study were 50 patients with small pulmonary nodules admitted to the Department of Cardiothoracic Surgery of Heilongjiang Provincial Hospital from January 2020 to December 2022, and all underwent thoracoscopic surgical resection. All study subjects met the inclusion criteria, grouping according to the intraoperative positioning method, the control group (n = 25) used Hook-wire puncture positioning, and the observation group (n = 25) used three-dimensional reconstruction technology. The positioning effect, pain level, and postoperative complications were compared between the two groups. Results: The incidence rate of complications after puncture was 16.00% in the control group and 4.00% in the observation group, the complication rate in the observation group was significantly lower; the positioning success rate of the observation group was 96.00%, which was higher than that of the control group (92.00%). The operation time (32.25±6.08) min was lower than (38.50±7.12) min in the control group. The two groups had no statistical significance in the wedge resection success rate, VAS score, and complication rate (P > .05). Conclusion: Three-dimensional reconstruction technology mainly makes preliminary judgments on the location, shape, size, and relationship between nodules and surrounding tissues based on preoperative CT scan images. It can select suitable scanning locations, map puncture paths, and anchor them in and around small lung nodules. The operation is simple, and the positioning success rate is high. The existence of three-dimensional reconstruction technology to position the guide wire can quickly shorten the time to detect lesions, shorten the time of VATS, reduce the occurrence of pulmonary infection in patients, and improve the prognosis.
RESUMO
Objective: To investigate the effectiveness of strengthen psychological intervention in 85 clients who had pneumonia caused by a novel coronavirus. Methods: As the study's subjects, 162 new coronavirus pneumonia clients admitted to our hospital between January 2020 and September 2020 had their clinical records retrospectively examined. According to different nursing methods, 162 patients with new coronavirus pneumonia were separated into a control team (n=77) and an experimental team (n=85). The test group received the intense psychological intervention, whereas the controlling team only received standard nursing care. The two groups' treatment compliance and nursing satisfaction were observed, the self-rating symptom scale (SCL-90) scores and coping style (MCMQ) grades of the two teams prior to and after the interference was contrasted, and the nursing quality of the two teams was contrasted. Results: In terms of compliance, the overall treatment compliance rate of patients in the experimental group increased significantly. In terms of the psychological state of the experimental group, significant improvements were observed in all psychological dimensions of the patients in the experimental group, including a reduction in negative emotions and an increase in nursing satisfaction. In terms of self-coping, patients in the experimental group showed significant improvement in various dimensions. And the quality of nursing care in the experimental group has been significantly improved. Conclusion: This study highlights the importance of intensive psychological intervention in the overall care of COVID-19 patients and its role in improving patient treatment compliance, negative emotions, self-coping styles and patient health.
RESUMO
OBJECTIVE: To investigate the effectiveness of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on improvement of clinical symptoms in patients with spinocerebellar ataxia type 3 (SCA3). METHODS: Sixteen SCA3 participants diagnosed by genetic testing were enrolled in this sham-controlled and double-blind trial. They received either a 2-week 10-Hz rTMS intervention or sham stimulation targeting the vermis and cerebellum. The Scale for Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale were completed at baseline and poststimulation. RESULTS: Compared with baseline, the HF-rTMS group demonstrated a significant improvement in the total Scale for Assessment and Rating of Ataxia ( P < 0.0001) and the International Cooperative Ataxia Rating Scale scores ( P = 0.002). After 2-week treatment, the real group exhibited decreasing pattern in 3 subgroups, especially for limb kinetic function ( P < 0.0001). CONCLUSIONS: Short-term HF-rTMS treatment is a potentially promising and feasible tool for rehabilitation in patients with SCA3. Studies with long-term follow-up need to be carried out in the future and further need to assess gait, limb kinetic function, speech and oculomotor disorders.
Assuntos
Eletroconvulsoterapia , Doença de Machado-Joseph , Humanos , Estimulação Magnética Transcraniana , Doença de Machado-Joseph/terapia , Ataxia/terapia , Cerebelo , Método Duplo-Cego , Resultado do TratamentoRESUMO
As part of their treatment, lung cancer patients frequently endure thoracic oncological surgery, with preoperative chemotherapeutic interventions being the common approach. However, the potential impact of these chemotherapeutic regimens on cutaneous wound healing outcomes following surgery remains the topic of considerable clinical interest. This meta-analysis sought to evaluate comprehensively the effect of preoperative chemotherapeutic regimens on cutaneous wound healing in lung cancer patients following thoracic oncological surgery. Extensive literature searches were conducted using the leading databases PubMed, Embase, Cochrane Library and Scopus. Eight studies out of 1342 identified satisfied the inclusion criteria. Consideration was given to both randomized controlled trials (RCTs) and observational studies. Data pertaining to study characteristics, patient demographics, chemotherapeutic regimens and wound healing outcomes were extracted with great attention to detail. The examination of these varied studies provided insights into the fluctuations in rates of recovery following treatment, incidences of wound infections and frequencies of surgical complications. The research studies provided odds ratios for recovery that varied significantly in magnitude from 0.95 to 0.38, with regard to the probability of wound infection. Furthermore, a range of odds ratios for complications were disclosed, with certain odds ratios displaying narrow confidence intervals. The complexity of the effect of preoperative chemotherapy on wound closure subsequent to thoracic oncologic surgery is highlighted by our findings. The results underscore the need for individualized treatment strategies for lung cancer patients undergoing surgical procedures that strike a balance between patient safety and optimal clinical outcomes.
Assuntos
Neoplasias Pulmonares , Cicatrização , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Cuidados Pré-Operatórios/métodos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Due to the global increase in thoracic interventions, there is greater emphasis on refining post-operative care. The purpose of this study was to validate the visual analogue scale (VAS) as the valid method for measuring post-operative pain in thoracic surgery patients. From January 2020 to June 2022, this cross-sectional study investigated 240 adult patients who underwent elective thoracic surgeries in Thoracic Surgery Department of Heilongjiang Provincial Hospital. The participants were instructed to rate their discomfort using VAS at predetermined intervals after surgery. The following demographic and clinical information was recorded: age, gender, type of thoracic surgery, and history of chronic pain. Results showed a progressive decline in post-operative VAS scores over 72 h: 8.2 immediately after surgery, 6.0 at 24 h, 5.4 at 48 h, and 3.6 by 72 h. There were notable correlations between VAS scores and chronic pain history, with moderately positive correlation of 0.40 being observed. Mean scores for males and females were 3.8 and 3.9, respectively. The analysis by age revealed comparable mean scores for age categories below and above 40. With the exception of thoracic wall resection, which resulted in an average VAS score of 4.1 ± 1.0 (p < 0.05), the type of surgery had the minimal effect on variability of pain scores. The VAS is a reliable method for evaluating post-thoracic surgery discomfort. Given the substantial impact of pain history on VAS scores, there is an urgent need for personalized pain management strategies to improve post-operative care.
RESUMO
OBJECTIVE: To study the safety of alginate based gastric mucosal protective adhesive and its feasibility as a submucosal injection. METHODS: The feasibility of using alginate-based gastric mucosal protective gel as submucosal injection was evaluated by in vitro gastric mucosal uplift test in pigs and in vivo gastric mucosal uplift test in rats. The safety of alginate based gastric mucosa protective adhesive was evaluated by cytotoxicity test, acute toxicity test and oral mucosa stimulation test according to GB/T 16886 series standard of biological evaluation of medical devices. RESULTS: After injection of different concentrations of alginate base mucosal protective adhesive solution, the uplift height was significantly higher than that of normal saline (P<0.05). Gastric mucosal protection glue has no cytotoxic oral mucosal irritation or acute toxicity. CONCLUSIONS: Gastric mucosa protector is a promising new medical device product with feasibility and good biocompatibility as submucosal uplift injection agent.
Assuntos
Adesivos , Alginatos , Animais , Estudos de Viabilidade , Mucosa Gástrica , Injeções , Ratos , SuínosRESUMO
Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between ß-amyloid (Aß) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aß and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aß. It was found that lycopene attenuated Aß-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aß-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aß-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aß-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aß-induced neurotoxicity.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Carotenoides/farmacologia , Córtex Cerebral/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/fisiologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Relação Dose-Resposta a Droga , Licopeno , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismoRESUMO
Ionizing radiation (IR) is one of the key contributors that cause male infertility by disturbing spermatogenesis. Lycopene, a carotenoid with strong antioxidant properties, was shown to protect against oxidative damage induced by IR in several experimental models. The present study was designed to explore the possible protective effects of lycopene against IR-induced testicular damage in C57BL/6 mice. Mice were administered lycopene (20 mg/kg) by oral gavage for seven consecutive days prior to a single dose of whole-body X-ray irradiation (4 Gy, 1 Gy/min). We observed that lycopene remarkably augmented sperm motility and reduced sperm abnormalities in mice following IR exposure. Histopathological analyses also revealed that lycopene ameliorated the structural damage of seminiferous tubules and enhanced the regeneration of seminiferous epithelium following IR stress. Moreover, lycopene attenuated IR-induced oxidative stress, as evidenced by a decreasing lipid peroxidation level and an increase in the antioxidant enzyme superoxide dismutase activity. In addition, lycopene reduced the γH2AX expression and the number of TUNEL-positive cells in the germinal epithelium, as well as restoring the imbalance of Bax/Bcl-2 expression induced by IR exposure. Furthermore, lycopene prevented mitochondrial membrane potential depolarization and ATP reduction and preserved the activities of mitochondrial complexes I-IV in the testes of mice after exposure to IR. Lycopene also improved mitochondrial biogenesis in testes of mice exposed to IR, presenting as restored expressions of PGC-1α, Nrf1, and Tfam. Taken together, our results suggest that lycopene alleviates IR-induced testicular damage, and the underlying mechanism involves at least in part the inhibition of the mitochondrial apoptotic pathway and the maintenance of mitochondrial respiration and biogenesis. The beneficial effect of lycopene highlights the therapeutic potential of this plant-derived antioxidant against impaired spermatogenesis and male infertility induced by IR.
RESUMO
The effects of neurotoxicant cadmium (Cd) exposure on brain development have not been well elucidated. To investigate this, we have herein subjected pregnant mice to low-dose Cd throughout gestation. Using single-cell RNA sequencing (scRNA-seq), we explored the cellular responses in the embryonic brain to Cd exposure, and identified 18 distinct cell subpopulations that exhibited varied responses to Cd. Typically, Cd exposure impeded the development and maturation of cells in the brain, especially progenitor cells such as neural progenitor cells (NPCs) and oligodendrocyte progenitor cells (OPCs). It also caused significant cell subpopulation shifts in almost all the types of cells in the brain. Additionally, Cd exposure reduced the dendritic sophistication of cortical neurons in the offspring. Importantly, these changes led to aberrant Ca2+ activity in the cortex and neural behavior changes in mature offspring. These data contribute to our understanding of the effects and mechanisms of Cd exposure on brain development and highlight the importance of controlling environmental neurotoxicant exposure at the population level.
Assuntos
Encéfalo , Cádmio , Análise de Célula Única , Transcriptoma , Animais , Camundongos , Cádmio/toxicidade , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Masculino , Neurônios/metabolismo , Neurônios/efeitos dos fármacosRESUMO
Electrochemical Immunosensing (EI) combines electrochemical analysis and immunology principles and is characterized by its simplicity, rapid detection, high sensitivity, and specificity. EI has become an important approach in various fields, such as clinical diagnosis, disease prevention and treatment, environmental monitoring, and food safety. However, EI multi-component detection still faces two major bottlenecks: first, the lack of cost-effective and portable detection platforms; second, the difficulty in eliminating batch differences and accurately decoupling signals from multiple analytes. With the gradual maturation of biochip technology, high-throughput analysis and portable detection utilizing the advantages of miniaturized chips, high sensitivity, and low cost have become possible. Meanwhile, Artificial Intelligence (AI) enables accurate decoupling of signals and enhances the sensitivity and specificity of multi-component detection. We believe that by evaluating and analyzing the characteristics, benefits, and linkages of EI, biochip, and AI technologies, we may considerably accelerate the development of EI multi-component detection. Therefore, we propose three specific prospects: first, AI can enhance and optimize the performance of the EI biochips, addressing the issue of multi-component detection for portable platforms. Second, the AI-enhanced EI biochips can be widely applied in home care, medical healthcare, and other areas. Third, the cross-fusion and innovation of EI, biochip, and AI technologies will effectively solve key bottlenecks in biochip detection, promoting interdisciplinary development. However, challenges may arise from AI algorithms that are difficult to explain and limited data access. Nevertheless, we believe that with technological advances and further research, there will be more methods and technologies to overcome these challenges.
RESUMO
Objective: The effectiveness of tissue engineering materials combining porcine small intestine submucosa (SIS) and umbilical cord mesenchymal stem cells (UC-MSCs) on uterine injury in female rat after full-thickness uterine resection was evaluated as a basis for clinical treatment of postoperative uterine injury. Methods: After complex culture with SIS and UC-MSCs, cell adhesion, growth, and proliferation were assessed. Before the implantation, a surgical procedure of bilateral full-thickness uterine resection (0.5-2.0 cm long and 0.3 cm wide) was performed to obtain the rat uterine injury model, while the sham-operated rats were used as controls. Hematoxylin-eosin (H&E) staining results and fertility of female rats in each group were assessed to determine the critical resection length of the full-thickness uterine resection. Then SIS or UC-MSCs-SIS were implanted into the female rats from the uterine injury group, followed by assessments of H&E staining, the expression of ki67, α-SMA, and leukemia inhibitory factor (LIF), and fertility to determine the effectiveness of SIS and UC-MSCs-SIS on uterine injury in female rat. Results: At 24, 48, and 72 h, the cells grew progressively on the SIS material. In the 1.5 cm and 2.0 cm groups, the pregnancy rate, proportion of the uterus supporting live embryo growth, number of live embryos, and proportion of live embryos were all significantly less than those in the 0.5 cm and sham-operated groups. In the 2.0 cm group, there was little tissue regeneration at the center of the injury and not conducive to subsequent assessment. The UC-MSCs-SIS and SIS groups were better on morphological development, cell proliferation, LIF expression, and fertility than the control group. Conclusions: UC-MSCs show good adhesion, growth, and proliferation on the SIS scaffold material. The optimal resection length in full-thickness uterine resection on female rat is 1.5 cm. UC-MSCs-SIS is the effective treatment for repairing a injury after the full-thickness resection of the uterus in this research. Impact Statement The acquired severe uterus injury is a serious condition, which prone to uterine adhesions. Postoperative endometrial repairment and prevention of intrauterine adhesion recurrence are two major clinical challenges. Fortunately, the development of tissue engineering technology makes repairing a uterine injury possible. There are two main contributions from this study. First, due to ethical requirements, it is difficult to assess the repairing effect on uterus by invasive experiments in a clinical practice. Therefore, we constructed a full-thickness uterine injury rat model, which allows us to assess the repairing effect of treatments after severe uterine injuries in vivo. Second, it explored the effect of using a combination of and umbilical cord mesenchymal stem cells and small intestine submucosa materials on improving uterine repairments, providing a potential possibility for a future clinical practice.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Feminino , Gravidez , Ratos , Endométrio/metabolismo , Suínos , Cordão Umbilical , Útero/lesões , Útero/metabolismoRESUMO
The basilar artery has the most perioperative complications in stenting compared to the other intracranial arteries. We aim to study whether the procedural safety in stenting for basilar stenosis has improved. This study was a single-arm, non-randomized trial that included historically controlled patients for comparison. Between January 2012 and March 2019, 147 consecutive patients with symptomatic basilar stenoses receiving elective stenting treatment were included in current basilar artery stenting (BAS) group. The prospectively collected and registered 120 patients by the same interventional team from September 2001 to November 2011 were set as historical BAS group for control. A total of 267 individuals were included in this study, with a mean age of 59.5â ±â 8.1 years. The proportion of patients with lesion length >15 mm was 26.5% (39/147) in the current BAS group versus 4.2% (5/120) in the historical BAS group. We found significant differences between these 2 groups in Mori A (17.7% vs 42.5%) and Mori C patients (42.9% vs 13.3%). The proportion of patients receiving preoperative high-resolution magnetic resonance (HRMRI) evaluation was 83.0% (122/147) in the current BAS group versus 20.8% (25/120) in the historical group (Pâ <â .05). Balloon-expendable stent (BES) (nâ =â 1), Wingspan (nâ =â 34), and Enterprise (nâ =â 112) stents were placed in the current BAS group. In contrast, only balloon-expendable stent (BES) (nâ =â 48) and Wingspan (nâ =â 72) were deployed in the historical BAS group. The incidence of the safety endpoint (SE) was 4.1% (involving 6 patients) in the current BAS group versus 11.7% (involving 14 patients) in the historical BAS group (Pâ <â .05). In multivariate analysis, no risk factor was associated with the occurrence of the safety endpoint (SE). When BAS cases operated by the surgical team accumulated to 120 to 150, the incidence of complications decreased significantly. This is the largest sample size study to discuss the safety of BAS. The significantly decreased incidence of complications indicates that the improving technical measures and the accumulation of operation experience are necessary.
Assuntos
Angioplastia com Balão , Stents , Humanos , Pessoa de Meia-Idade , Idoso , Constrição Patológica , Resultado do Tratamento , Estudo Historicamente Controlado , Stents/efeitos adversosRESUMO
BACKGROUND: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer's disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. OBJECTIVE: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. METHODS: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger's test. RESULTS: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMDâ=â-0.86, 95% CI: -1.67 to -0.05, pâ=â0.04) and zeaxanthin (SMDâ=â-0.59; 95% CI: -1.12 to -0.06, pâ=â0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMDâ=â0.21, 95% CI: -0.68 to 0.26, pâ=â0.39), ß-carotene (SMDâ=â0.04, 95% CI: -0.57 to 0.65, pâ=â0.9), lycopene (SMDâ=â-0.12, 95% CI: -0.96 to 0.72, pâ=â0.78), and ß-cryptoxanthin (SMDâ=â-0.09, 95% CI: -0.83 to 0.65, pâ=â0.81) did not achieve significant differences. CONCLUSION: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Carotenoides/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Licopeno/sangue , Zeaxantinas/sangue , beta Caroteno/sangueRESUMO
OBJECTIVE: To investigate the effects of microwave irradiation on the expression and regulation of heat shock proteins (HSPs) in primary cultured rat hippocampal neurons. METHODS: Neurons were exposed to 90 mW/cm(2) microwave irradiation for 10 minutes. Western blot was used to determine the expression of HSP27, HSP70, HSP90 and heat shock factor 1 (HSF1) at 0, 3, 6, 12 and 24 hour respectively. Real-time RT-PCR was used to determine the mRNA expression of HSF1. DNA-binding activity of HSF1 was measured by electrophoretic mobility shift assay (EMSA). RESULTS: The protein expression of HSP27 was significantly increased by 22%, 36%, 18% at 3, 6, 12 h, respectively (P < 0.05). The protein expression of HSP70 was significantly increased by 23%, 32%, 26% at 3, 6, 12 h, respectively (P < 0.05, P < 0.01). The protein expression of HSP90 was significantly increased by 27%, 33% at 6, 12 h, respectively (P < 0.05, P < 0.01). The DNA-binding activity of HSF1 was stimulated, however, no significant change of the expression of HSF1 was observed on both the mRNA and protein levels. CONCLUSION: The transcriptional activity of HSF1 is activated by microwave irradiation, which promotes the expression of HSPs. Heat shock response which contributes to establish a cytoprotective state is induced by microwave irradiation in primary cultured rat hippocampal neurons.
Assuntos
Proteínas de Choque Térmico/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Micro-Ondas/efeitos adversos , Animais , Células Cultivadas , Neurônios/metabolismo , RatosRESUMO
Lead (Pb) exhibits serious adverse effects on the central nervous system, and the major pathogenic mechanism of Pb toxicity is oxidative stress. As one of the carotenoid family members with potent antioxidant properties, lycopene has shown its protections by inhibiting oxidative stress damage in numerous models of neurotoxicity. The current study was designed to explore the possible protective property in primary cultured rat hippocampal neurons challenged with Pb. We observed that 5 µM lycopene pretreatment for 4 h efficiently ameliorated Pb-caused damage in cell viability, accumulation of reactive oxygen species (ROS), and apoptosis in a dose-dependent manner. Moreover, lycopene (5 µM) attenuated the 50 µM Pb-induced mitochondrial ROS production, improved the activities of mitochondrial respiratory chain enzymes and ATP production, and ameliorated the 50 µM Pb-induced depolarization of mitochondrial membrane potential as well as opening of mitochondrial permeability transition pores. In addition, 5 µM lycopene restored the imbalance of Bax/Bcl-2, inhibited translocation of cytochrome c, and reduced caspase-3 activation. Taken together, these findings indicate that lycopene antagonizes against Pb-induced neurotoxicity and the underlying mechanism probably involves reduction of mitochondrial oxidative damage and mitochondria-mediated apoptosis.
RESUMO
Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. Oxidative stress and mitochondrial dysfunction are widely accepted as central pathogenic mechanisms of MeHg-mediated neurotoxicity. Lycopene, a carotenoid compound, is a potent antioxidant with demonstrated neuroprotective properties in several experimental models of oxidative damage. The present study was designed to investigate whether lycopene could provide protective effects against MeHg-induced neurotoxicity in cultured rat cerebellar granule neurons (CGNs). The cultured CGNs were pretreated with different dose of lycopene for 2h, followed by the challenge with 500nM MeHg for 12h. It was found that MeHg exposure caused the loss of cell viability and the LDH release. Furthermore, we demonstrated that MeHg exposure significantly elevated intracellular reactive oxygen species generation and mitochondria-derived superoxide production, caused disruption of mitochondrial membrane potential and opening of mPTP, inhibited mitochondrial complex enzyme activities (complex III and complex IV), reduced ATP generation and decreased mtDNA copy numbers and mtDNA transcript levels. However, each of these oxidative damages was efficiently attenuated by lycopene pretreatment. Collectively, these results suggest that lycopene affords protection against MeHg-induced neurotoxicity in CGNs, and these beneficial effects of lycopene may be attributable to its roles in preventing mitochondrial dysfunction.
Assuntos
Carotenoides/farmacologia , Cerebelo/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Fármacos Neuroprotetores/farmacologia , Animais , Sobrevivência Celular , Células Cultivadas , Cerebelo/metabolismo , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/metabolismo , Licopeno , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
Association studies of presenilin-2 (PSEN2) polymorphisms and sporadic Alzheimer's disease (AD) have yielded inconsistent results, possibly because single studies often lack sufficient statistical power. In this study, we performed a meta-analysis to evaluate the association of the two most extensively studied PSEN2 polymorphisms, rs8383 and 5'indel, with the risk of sporadic AD. We systematically reviewed relevant studies retrieved by Medline, Pubmed, Embase, AlzGene, and CNKI. Data were analyzed using the Stata (v11.0) software package. The fixed effects model or random-effects model were applied depending on between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's funnel plots. Overall, the meta-analysis included 6 case-control studies for each polymorphism with 2186 confirmed AD cases and 2507 healthy controls in total. Analysis suggested a significant association between SNP rs8383 polymorphism and AD risk with no evidence of between-study heterogeneity or publication bias. In contrast, we found no evidence for an association between the 5'indel polymorphism and AD risk. Further stratified analyses by apolipoprotein ε4 status or ethnicity also failed to reveal a statistically significant association between the 5'indel polymorphism of PSEN2 and AD risk. Our analysis supports the hypothesis that the PSEN2 rs8383 polymorphism is associated with an enlarged risk of sporadic AD. However, larger scale association studies are necessary to further validate the association of PSEN2 polymorphisms with sporadic AD risk and to define potential gene-gene interactions.
Assuntos
Doença de Alzheimer/genética , Polimorfismo de Nucleotídeo Único , Presenilina-2/genética , Predisposição Genética para Doença , Humanos , Mutação INDELRESUMO
A deficiency of maternal thyroid hormones (THs) during pregnancy may have severe impacts on fetal brain development. However, the cellular targets of THs and their underlying mechanisms are still unclear. In this study, we found that maternal hypothyroidism during pregnancy in mice inhibited neurogenesis in the embryonic telencephalon and caused learning and memory impairment in the offspring. To explore the underlying mechanisms, we treated cultured mouse embryonic neural stem cells (eNSCs) with a physiological level of 3, 5, 3'-triiodo-L-thyronine (T3). We found that T3 promoted the neuronal differentiation of eNSCs, while inhibiting astrocytic differentiation. In addition, the proliferation and maintenance of eNSCs were inhibited by T3. Furthermore, the TH receptor alpha 1 (TRα1) was detected in the eNSCs both in vivo and in vitro. Silencing TRα1 protein expression with specific siRNA eliminated the effects of T3 on eNSCs. We also found that T3 decreased STAT3 phosphorylation and STAT3-DNA binding activity through TRα1. The over expression of STAT3 attenuated the promotive effects of T3 on neuronal differentiation of eNSCs. Taken together, these results suggest that T3 promotes the neuronal differentiation of eNSCs by inhibiting STAT3 signaling activity through TRα1 and contributes to early neurogenesis in the embryonic telencephalon. Our studies reveal the physiological effects of TH in regulating eNSCs differentiation and suggest that eNSCs are one of the major cellular targets in the central nervous system by which TH influences early brain development. These findings also provide new insights into the mechanisms of neurological deficits caused by TH deficiency during embryogenesis.
Assuntos
Células-Tronco Neurais/efeitos dos fármacos , Neurogênese , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Receptores alfa dos Hormônios Tireóideos/metabolismo , Tri-Iodotironina/farmacologia , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/efeitos dos fármacos , Feminino , Hipotireoidismo/induzido quimicamente , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco Neurais/citologia , Fosforilação , Gravidez , Propiltiouracila/administração & dosagem , Propiltiouracila/efeitos adversos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Telencéfalo/citologia , Telencéfalo/embriologia , Telencéfalo/metabolismo , Receptores alfa dos Hormônios Tireóideos/genética , Tri-Iodotironina/metabolismoRESUMO
Mortalin (mtHsp70) is a mitochondrial heat shock protein critical for maintaining the functional integrity of mitochondrial proteins. Our previous study demonstrated that mortalin overexpression protected against Aß-induced neurotoxicity through a mitochondria-dependent mechanism, but the molecular details remained unclear. Recent biochemical studies implicate opening of the mitochondrial permeability transition pore (mPTP) in Aß-mediated mitochondrial dysfunction. The present study investigated the effect of mortalin overexpression on Aß-induced mPTP activation and ensuing neuronal apoptosis. Mortalin overexpression inhibited mPTP activation and protected SH-SY5Y neurons against Aß-induced apoptosis. Compared to controls, neurons overexpressing mortalin also demonstrated superior intracellular free calcium regulation, lower mitochondrial reactive oxygen species generation, and decreased Bax/Bcl-2 ratios in response to Aß treatment. Mortalin overexpression suppressed activation of the mitochondrial apoptotic cascade as demonstrated by inhibition of cytochrome c release and caspase-3 activation. Our results indicate that the cytoprotective efficacy of mortalin under Aß-induced stress is mediated, at least in part, by inhibition of mPTP opening. Demonstration of the neuroprotective action of mortalin provides additional insights into the pathogenic mechanisms of Aß toxicity and defines possible molecular targets for therapeutic intervention.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Apoptose/fisiologia , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Citocromos c/metabolismo , Proteínas de Choque Térmico HSP70/genética , Humanos , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Amyloid-beta peptide (Aß) is shown to be toxic to the mitochondria and implicates this organelle in the pathogenesis of Alzheimer's disease. Previous studies suggest that targeting mitochondria for protection may be a useful strategy to reduce Aß-induced neurotoxicity. Mortalin is the mitochondrial located member of the heat shock protein 70 family, which serves as a major mitochondrial molecular chaperone and plays a key role in mitochondrial import of proteins. Several studies have demonstrated the protective potential of Hsp75 overexpression against apoptosis induced by various forms of stresses. To investigate whether mortalin overexpression could provide protective effects on Aß toxicity, SH-SY5Y cells were used to transfect human mortalin gene and then treated with Aß(1-42) for 24h. It is found that overexpression of mortalin efficiently attenuated Aß(1-42)-induced cell viability damage and apoptosis. Additionally, inhibition of mortalin expression by mortalin-specific siRNA oligonucleotides sensitized SH-SY5Y cells to Aß(1-42)-induced neurotoxicity. Furthermore, mortalin overexpression significantly inhibited the Aß(1-42)-induced depolarization of mitochondrial membrane potential, reversed the Aß(1-42)-induced reduction in cytochrome c oxidase activity and ATP generation, and suppressed the Aß(1-42)-induced reactive oxygen species accumulation and lipid peroxidation. Together, our results suggest that mortalin can afford protection against Aß(1-42)-induced neurotoxicity in SH-SY5Y cells. These beneficial effects of mortalin overexpression may be attributable to its roles in maintaining mitochondrial function and reducing oxidative stress.