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1.
Neural Regen Res ; 18(1): 183-188, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799540

RESUMO

Icariin, a major prenylated flavonoid found in Epimedium spp., is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer's disease. In this study, we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer's disease. We performed behavioral tests, pathological examination, and western blot assay, and found that memory deficits of the model mice were obviously improved, neuronal and synaptic damage in the cerebral cortex was substantially mitigated, and amyloid-ß accumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day. Furthermore, deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed, including the insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3-kinase, protein kinase B, and glycogen synthase kinase 3ß, and the levels of glucose transporter 1 and 3 were markedly increased. These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer's disease by regulating brain insulin signaling and glucose transporters, which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer's disease.

2.
Neural Regen Res ; 18(1): 189-193, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35799541

RESUMO

Lamotrigine (LTG) is a widely used drug for the treatment of epilepsy. Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer's disease. However, the underlying molecular mechanisms remain unclear. In this study, amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice were used as a model of Alzheimer's disease. Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months. The cognitive functions of animals were assessed using Morris water maze. Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay. The cell damage in the brain was investigated using hematoxylin and eosin staining. The levels of amyloid-ß and the concentrations of interleukin-1ß, interleukin-6 and tumor necrosis factor-α in the brain were measured using enzyme-linked immunosorbent assay. Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction. We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice; alleviated damage to synapses and nerve cells in the brain; and reduced amyloid-ß levels, tau protein hyperphosphorylation, and inflammatory responses. High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer's disease-related neuropathologies may have been mediated by the regulation of Ptgds, Cd74, Map3k1, Fosb, and Spp1 expression in the brain. These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer's disease. Furthermore, these data indicate that LTG may be a promising therapeutic drug for Alzheimer's disease.

3.
Neural Regen Res ; 18(2): 434-438, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900442

RESUMO

Triggering receptor expressed on myeloid cells-like 2 (TREML2) is a newly identified susceptibility gene for Alzheimer's disease (AD). It encodes a microglial inflammation-associated receptor. To date, the potential role of microglial TREML2 in neuroinflammation in the context of AD remains unclear. In this study, APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression. In addition, lipopolysaccharide (LPS) stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD. Our results show that TREML2 levels gradually increased in the brains of APP/PS1 mice during disease progression. LPS stimulation of primary microglia led to the release of inflammatory cytokines including interleukin-1ß, interleukin-6, and tumor necrosis factor-α in the culture medium. The LPS-induced microglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knockdown. LPS increased the levels of microglial M1-type polarization marker inducible nitric oxide synthase. This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown. Furthermore, the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown. LPS stimulation increased the levels of NLRP3 in primary microglia. The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown. In summary, this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation. These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

4.
Clin. transl. oncol. (Print) ; 24(10): 1998–2009, octubre 2022. graf
Artigo em Inglês | IBECS | ID: ibc-207955

RESUMO

The Wnt/β-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). A number of studies have focused on the aberrant hypermethylation of the DKK family proteins and its role in regulating the activation of specific signaling pathways. However, the exact way by which DKK regulates the signaling pathway caused by Core protein of HCV has not been reported. In the present study, we evaluated the expression level of DKK and its aberrant promoter methylation to investigate the involvement of epigenetic regulation in hepatoma cell lines. The transcription and protein expression of DKK1 was significantly increased, whereas the transcription and protein expression levels of DKK2, DKK3, and DKK4 were significantly decreased following overexpression of Core protein. Pyrosequencing indicated that hypermethylation of DKK3 was increased. This was associated with increased expression of Dnmt1. The investigation of the molecular mechanism indicated that HCV Core protein interacted with Dnmt1, which combined with the promoter of DKK3, leading to methylation of DKK3. Functional studies indicated that Core protein promoted the growth, migration and invasion of cancer cells. However, upregulation of the expression of DKK3 and/or the knockdown of the expression of Dnmt1 inhibited the growth, migration and invasion of cancer cells. Taken together, the data indicated that epigenetic silencing of DKK3 caused by Dnmt1 activated the Wnt/β-catenin pathway in HCV Core-mediated HCC. Therefore, DKK3 may be a potential diagnostic and therapeutic target for HCC. (AU)


Assuntos
Humanos , Proteínas Adaptadoras de Transdução de Sinal , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Peptídeos e Proteínas de Sinalização Intercelular , Via de Sinalização Wnt , beta Catenina , Hepatite C , Neoplasias Hepáticas
5.
J Environ Public Health ; 2022: 1244660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36089973

RESUMO

The distribution of human resources has a direct impact on the HR utilization rate in businesses, which in turn has an impact on the profitability and labor productivity of those businesses. As a result, this article develops an enterprise HR optimal allocation model based on PSO. The concepts of HR and HR allocation are introduced, and a programme for implementing optimal HR allocation in businesses is provided from the perspectives of scale prediction, structure analysis, and implementation. An HR configuration optimization model is established, providing a specific method of quantitative management for HR configuration optimization, at the same time starting from operability, based on the methods of system analysis and quantitative evaluation, and an improved PSO is created to address this issue. Results from numerical simulations demonstrate this algorithm's effectiveness. According to the experimental findings, the improved PSO has a quick convergence rate and a roughly 5% lower average error rate than the conventional algorithm. Moreover, this algorithm's accuracy is roughly 94%. This method offers some targeted tactics for optimizing HR configuration.


Assuntos
Algoritmos , Big Data , Humanos , Recursos Humanos
6.
Front Oncol ; 12: 898141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091164

RESUMO

Background: Integration of 4D-CT ventilation function images into esophageal cancer radiation treatment planning aimed to assess dosimetric differences between different functional lung (FL) protection strategies and radiotherapy techniques. Methods: A total of 15 patients with esophageal cancer who had 4D-CT scans were included. Lung ventilation function images based on Jacobian values were obtained by deformation image registration and ventilation imaging algorithm. Several different plans were designed for each patient: clinical treatment planning (non-sparing planning), the same beam distribution to FL-sparing planning, three fixed-beams FL-sparing intensity-modulated radiation therapy (IMRT) planning (5F-IMRT, 7F-IMRT, 9F-IMRT), and two FL-sparing volumetric modulated arc therapy (VMAT) planning [1F-VMAT (1-Arc), 2F-VMAT (2-Arc)]. The dosimetric parameters of the planning target volume (PTV) and organs at risk (OARs) were compared and focused on dosimetric differences in FL. Results: The FL-sparing planning compared with the non-sparing planning significantly decreased the FL-Dmean, V5-30 and Lungs-Dmean, V10-30 (Vx: volume of receiving ≥X Gy), although it slightly compromised PTV conformability and increased Heart-V40 (P< 0.05). The 5F-IMRT had the lowest PTV-conformability index (CI) but had a lower Lungs and Heart irradiation dose compared with those of the 7F-IMRT and 9F-IMRT (P< 0.05). The 2F-VMAT had higher PTV-homogeneity index (HI) and reduced irradiation dose to FL, Lungs, and Heart compared to those of the 1F-VMAT planning (P< 0.05). The 2F-VMAT had higher PTV conformability and homogeneity and decreased FL-Dmean, V5-20 and Lungs-Dmean, V5-10 but correspondingly increased spinal cord-Dmean compared with those of the 5F-IMRT planning (P< 0.05). Conclusion: In this study, 4D-CT ventilation function image-based FL-sparing planning for esophageal cancer can effectively reduce the dose of the FL. The 2F-VMAT planning is better than the 5F-IMRT planning in reducing the dose of FL.

7.
Front Psychol ; 13: 935875, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092060

RESUMO

The California Verbal Learning Test-Second Edition (CVLT-II), is a commonly used tool to assess episodic memory. This study analyzed learning and memory characteristics in a cognitively healthy Chinese population, as well as the effects of age, sex and education on CVLT-II factors. In total, 246 healthy people aged 20-80 years and 29 persons with multiple sclerosis (MS) were included in this study and completed the CVLT-II. Factors including total learning, learning strategy, serial position effects, short-delay free and cued recall, long-delay free and cued recall, repetitions and intrusions during recall, hits and false positives of recognition, and total recognition discriminability were calculated. The effects of age, sex and education on these factors were analyzed using ANCOVA or independent two-sample t-tests and further confirmed by multiple regression analysis. The regression-based normative data were then computed by the equivalent scores method. Moreover, differences in learning and memory were compared between persons with MS and age-, sex- and education-matched healthy individuals. Most CVLT-II factors significantly differed between different age and education groups; in particular, better performance in total learning, recall, semantic clustering and recognition was observed in the younger and more educated groups than in the older and less educated groups. Male participants showed higher recency effect scores, more repetitions and fewer hits than female participants. Compared with healthy individuals, persons with MS showed extensive impairments in memory processes, such as learning, recall, learning strategy and recognition (p < 0.05). These findings indicated that verbal learning and memory were highly dependent on age and educational level but not strongly affected by sex. The CVLT-II effectively assesses episodic memory impairment in the Chinese-speaking population.

8.
Front Cell Dev Biol ; 10: 962990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092716

RESUMO

As aging becomes a global burden, the incidence of hip fracture (HF), which is the most common fracture in the elderly population and can be fatal, is rapidly increasing, and its extremely high fatality rate places significant medical and financial burdens on patients. Fractures trigger a complex set of immune responses, and recent studies have shown that with aging, the immune system shows decreased activity or malfunctions in a process known as immune senescence, leading to disease and death. These phenomena are the reasons why elderly individuals typically exhibit chronically low levels of inflammation and increased rates of infection and chronic disease. Macrophages, which are key players in the inflammatory response, are critical in initiating the inflammatory response, clearing pathogens, controlling the innate and adaptive immune responses and repairing damaged tissues. Tissue-resident macrophages (TRMs) are widely present in tissues and perform immune sentinel and homeostatic functions. TRMs are combinations of macrophages with different functions and phenotypes that can be directly influenced by neighboring cells and the microenvironment. They form a critical component of the first line of defense in all tissues of the body. Immune system disorders caused by aging could affect the biology of macrophages and thus the cascaded immune response after fracture in various ways. In this review, we outline recent studies and discuss the potential link between monocytes and macrophages and their potential roles in HF in elderly individuals.

9.
Gynecol Endocrinol ; : 1-5, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097348

RESUMO

OBJECTIVE: The aim of this retrospective analysis was to explore whether an elevated ALT level before pregnancy is associated with a reduction in live birth rate after IVF-FET. DESIGN: Retrospective observational study. SETTING: Shiyan People's Hospital, China between January 2019 and December 2019. PATIENTS: Women aged ≤ 40 years. INTERVENTION(S): Freeze-thawed embryo transfer (FET). MAIN OUTCOME MEASURE(S): The live birth rate, which was defined as the delivery of a live baby after 24 weeks of gestation. RESULTS: The analysis included 365 FET cycles. There was a significant difference between groups in the live birth rate (p < .05), which was highest for the low ALT tertile and lowest for the high ALT tertile. Multiple regression analysis with adjustment for multiple potential confounders revealed that the odds of live birth were decreased for each one standard deviation increase in ALT (OR = 0.56, 95%CI = 0.42-0.75, p < .0001) and lower for the high ALT tertile than for the low ALT tertile (OR = 0.38, 95%CI = 0.19-0.75, p = .0055). Smooth curve fitting showed an inverse relationship between ALT and live birth rate. CONCLUSION: Our findings indicate that relatively small elevations in baseline serum ALT level can have a clinically relevant impact on the success of FET.

10.
Biomol Ther (Seoul) ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097885

RESUMO

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

11.
Clin Neurophysiol ; 143: 48-55, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36108521

RESUMO

OBJECTIVE: To investigate the overall incidence and associated factors of epileptiform discharges in children during sevoflurane anesthesia. METHODS: Our group systematically searched the PubMed, Cochrane library (Central) and EMBASE for the relevant trials from their inception until September 2020. The primary endpoint was the incidence of epileptiform discharges during sevoflurane induction. The secondary endpoints were the incidence of different types of epileptiform discharges, factors associated with these epileptiform events, and other adverse events such as seizure-like movements. RESULTS: After screening of 713 records, eleven studies involving 448 participants were included into the final analysis. Meta-analysis indicated that the overall incidence of Epileptiform EEG discharges was 38.1% (95%confidence interval [CI], 19.1%-59.2%) during sevoflurane anesthesia in children. Subgroup analysis showed that the incidence of these EEG patters was lower when participants were inducted by using the low initial concentration of sevoflurane, compared with the high initial concentration sevoflurane (1.7%, 95%CI, 0.0% to 8.4% versus 47.7%, 95%CI, 25.5% to 70.3%, P < 0.05). The longer exposure (>3 min) of high concentration sevoflurane during induction showed higher rate of epileptiform discharges than a shorter exposure (≤3 min) (48.4%, 95%CI, 20.1% to 77.3% versus 5.7%, 95%CI, 0.00% to 23.5%; P < 0.05). No significant difference for the incidence of epileptiform discharges was observed in subgroup analysis of addition of nitrous oxide (69.2%, 95%CI, 34.0% to 95.7% versus 41.3%, 95%CI, 15.6% to 69.7%, Pï¹¥0.05) and type of EEG monitoring (26.9%, 95%CI, 3.8% to 60.7% versus 53.1%, 95%CI, 25.4% to 79.8%, Pï¹¥0.05). CONCLUSIONS: The incidence of epileptiform EEG events in children during sevoflurane anesthesia varied from 19.1%-59.2%. The low initial concentration technique and shorter exposure time of high concentration sevoflurane may be associated with a decreased incidence of these epileptiform discharges in EEG. SIGNIFICANCE: Epileptiform EEG discharges during sevoflurane anesthesia in children should arouse clinicians' attention. The use of low initial concentration technique and shorter exposure time of high concentration sevoflurane may be associated with a lower occurrence of these paradoxical events.

12.
Scanning ; 2022: 8716823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111266

RESUMO

Objective: To investigate the meniscus characteristics of knee osteoarthritis and its guiding significance for minimally invasive surgery. Methods: A total of 100 patients with knee meniscus sports injuries who were treated in our hospital from January 2019 to January 2022 were selected as the research subjects and were grouped according to the interval between injury and surgery, with an interval of 2 months: the early group (53 cases) within 2 months and the delayed group (47 cases) with an interval of more than 2 months. The distribution of intraoperative complications in the two groups was observed and recorded, and the changes in pain degree, joint range of motion, knee joint function, and quality of life scores before and after operation were compared between the two groups. Results: The postoperative VAS score, range of motion, Lysholm score, IKDC knee subjective function score, and quality of life score were significantly improved in both groups (P < 0.05). The incidence of intra-articular cartilage injury in the delayed group was significantly higher than that in the early group (P < 0.05). The patellofemoral cartilage injury was the main part of intra-articular cartilage injury in the two groups, and the incidence of patellofemoral cartilage injury in the delayed group was significantly higher than that in the early group (P < 0.05). The cartilage damage was mainly cartilage damage, and the grades I-II and III-IV cartilage damages were significantly increased in the extension group. Conclusion: Meniscal injury in knee osteoarthritis has certain microscopic characteristics. In this paper, the microscopic classification of meniscus injury in knee osteoarthritis is helpful to guide microscopic surgery and improve the minimally invasive knee osteoarthritis effect of surgical treatment.


Assuntos
Traumatismos em Atletas , Traumatismos do Joelho , Menisco , Osteoartrite do Joelho , Traumatismos em Atletas/complicações , Humanos , Traumatismos do Joelho/complicações , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Menisco/diagnóstico por imagem , Menisco/cirurgia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Qualidade de Vida
13.
Adv Mater ; : e2206528, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36120846

RESUMO

Crystal phase engineering is an important strategy for designing noble-metal-based catalysts with optimized activity and stability. From the thermodynamic point of view, it remains a great challenge to synthesize unconventional phases of noble metals. Here, a new class of Pd-based nanostructure with unconventional rhombohedral Pd20 Sb7 phase has been successfully synthesized. Benefiting from the high proportion of the unique exposed Pd20 Sb7 (003) surface, Pd20 Sb7 rhombohedra display much enhanced ethanol oxidation reaction (EOR) and oxygen reduction reaction (ORR) performance compared with commercial Pd/C. Moreover, Pd20 Sb7 rhombohedra are also demonstrated as effective air cathode in non-aqueous Li-air battery with an overpotential of only 0.24 V. Density functional theory calculations reveal that the unique exposed facets of Pd20 Sb7 rhombohedra can not only reduce the excessive adsorption of CH3 CO* to CH3 COOH on Pd for promoting EOR process, but also weaken the CO binding and CO poisoning. This work provides a new class of unconventional intermetallic nanomaterials with enhanced electrocatalytic activity. This article is protected by copyright. All rights reserved.

14.
Toxicol Ind Health ; : 7482337221127148, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36120900

RESUMO

C/EBP-homologous protein (CHOP) and histone H3 lysine 4 (H3K4) methylation have been verified to be correlated with apoptosis, whereas their biological function in arsenic-induced hepatocyte apoptosis through the mitochondrial pathway is still unclear. This study aimed to explore the specific regulatory mechanism of CHOP and H3K4me1/2 in arsenic-induced mitochondrial apoptosis in hepatocytes. Apoptosis and proliferation results showed arsenic promoted apoptosis and inhibited cell growth in BRL-3A cells. Meanwhile, arsenic treatment significantly upregulated the 78-kDa glucose-regulated protein (GRP78), CHOP, su(var)-3-9,enhancer-of-zeste,trithorax (SET) domain containing 7/9 (SET7/9), H3K4me1/2, BIM and BAX expression, while markedly downregulated lysine-specific histone demethylase 1 (LSD1) and BCL2 expression. After down-regulating CHOP, LSD1, and (su(var)-3-9,enhancer-of-zeste,trithorax) domain-containing protein 7/9 (SET7/9) in BRL-3A cells by siRNA, silencing CHOP and SET7/9 notably attenuated the pro-apoptotic and anti-proliferative effects of arsenic treatment on BRL-3A cells, which was reversed after inhibiting LSD1. In addition, our results suggested that knockdown of CHOP altered the expression of mitochondrial-associated proteins BCL2 and BIM, whereas knockdown of LSD1 and SET7/8 regulated the level of H3K4me1/2 modification and BAX protein. Coupled with chromatin immunoprecipitation results, we found that the level of CHOP in the promoter regions of BCL2 and BIM was significantly increased in BRL-3A cells exposed to 30 µmol/L NaAsO2 for 24 h, whereas the levels of H3K4me1/2 in the promoter regions of BAX were unchanged. Collectively, these data indicated that arsenic triggered the mitochondrial pathway to induce hepatocyte apoptosis by up-regulating the levels of CHOP and H3K4me1/2.

15.
Int J Mol Med ; 50(5)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36129150

RESUMO

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 3B on p. 1092, the western blots shown for 'Bax' in the MCF-7 group and 'Cleaved Caspase-8' in the MDA-MB-231 group were strikingly similar, such that these may have been the identical data re-used in the same figure. The authors have subsequently re­examined their data, and realize that the Cleaved Caspase-8 blots were incorrectly used in Fig. 3B during the process of assembling this figure (i.e., the western blots were duplicated, and these were correctly shown as the data for Bax in the MCF-7 group). Furthermore, the authors have realized that the western blots selected for the Cleaved Caspase-3 experiment in the western blots shown in Fig. 5D on p. 1093 were not as clear as they could have been, and also requested that the data here be changed for those from one of the repeated experiments. Consequently, the revised versions of Figs. 3 and 5, containing the correct data for the Cleaved Caspase-8 blots in the MDA-MB-231 group in Fig. 3B and the replacement Cleaved Caspase-3 blots in Fig. 5C, are shown on the next page. These errors did not affect the major conclusions reported in the paper. All the authors agree to the publication of this corrigendum, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. The authors regret the error that went unnoticed during the compilation of the figures in question, and apologize to the readership for any confusion that this may have caused. [International Journal of Molecular Medicine 40: 1089-1095, 2017; DOI: 10.3892/ijmm.2017.3081].

16.
Neurosurgery ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129281

RESUMO

BACKGROUND: In-stent stenosis (ISS) is a delayed complication that can occur after pipeline embolization device use when treating intracranial aneurysms (IAs). OBJECTIVE: To assess the incidence, predictors, and outcomes of ISS. METHODS: This was a retrospective, multicenter, observational study. All patient data were collected from a PLUS registry study. We collected data from patients with IA who completed digital subtraction angiography at follow-up and divided patients into "non-ISS," "mild ISS," or "severe ISS" groups. Multivariate logistic regression analysis was conducted to determine predictors of ISS. RESULTS: A total of 1171 consecutive patients with 1322 IAs participated in this study. Angiographic follow-up was available for 662 patients with 728 IAs, and the mean follow-up time was 9 months. ISS was detected in 73 cases (10.03%), including 61 mild ISS cases and 12 severe ISS cases. Univariate and multivariable analysis demonstrated that current smoking history (mild ISS: OR 2.15, 95% CI 1.122-4.118, P = .021; severe ISS: OR 5.858, 95% CI 1.186-28.93, P = .030) and cerebral atherosclerosis (mild ISS: OR 5.694, 95% CI 3.193-10.15, P = .001; severe ISS: OR 6.103, 95% CI 1.384-26.91, P = .017) were independent predictors of ISS. Compared with the other groups, the severe ISS group had higher rate of ischemic stroke (33.3%). CONCLUSION: ISS occurs in approximately 10.03% of cases at a mean follow-up of 9 months. Statistically, current smoking history and cerebral atherosclerosis are the main predictors of ISS. Severe ISS may be associated with higher risk of neurological ischemic events in patients with IA after pipeline embolization device implantation.

17.
Br J Ophthalmol ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126102

RESUMO

BACKGROUND/AIMS: Congenital cataract is the leading cause of visual disability and blindness in childhood. ßB1-crystallin (CRYBB1) comprises about 1/10th of crystallin structural proteins, forming heteromers to maintain lens transparency. We previously reported a CRYBB1 mutation (c.347T>C, p.L116P) affecting 16 patients in a congenital nuclear cataract family. In this study, we investigate the underlying pathogenic mechanism of ßB1-L116P. METHODS: Protein isolation, size-exclusion chromatography, spectroscopy, Uncle stability screens and molecular dynamics simulations were used to assess ßA3- and ßB1-crystallin thermal stability, structural properties and heteromer formation. RESULTS: Cells that overexpressed ßB1-L116P tended to form aggregates and precipitations under heat-shock stress. Thermal denaturation and time-dependent turbidity experiments showed that thermal stability was significantly impaired. Moreover, protein instability appeared to increase with elevated concentrations detected by the Uncle system. Additionally, ßA3 had a relative protective effect on ßB1-L116P after heteromers were formed, although ßA3 was relatively unstable and was usually protected by basic ß-crystallins. Molecular dynamic simulations revealed that L116P mutation altered the hydrophobic residues at the surface around the mutant site, providing solvents more access to the internal and hydrophobic parts of the protein. CONCLUSIONS: Decreased ßB1-crystallin thermal stability in the presence of the cataract-related L116P mutation contributes significantly to congenital cataract formation. Moreover, its formation of heteromers with ßA3 protects against the low thermal stability of ßB1-L116P.

18.
Methods ; 207: 29-37, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36087888

RESUMO

DNA-binding proteins actively participate in life activities such as DNA replication, recombination, gene expression and regulation and play a prominent role in these processes. As DNA-binding proteins continue to be discovered and increase, it is imperative to design an efficient and accurate identification tool. Considering the time-consuming and expensive traditional experimental technology and the insufficient number of samples in the biological computing method based on structural information, we proposed a machine learning algorithm based on sequence information to identify DNA binding proteins, named multi-view Least Squares Support Vector Machine via Hilbert-Schmidt Independence Criterion (multi-view LSSVM via HSIC). This method took 6 feature sets as multi-view input and trains a single view through the LSSVM algorithm. Then, we integrated HSIC into LSSVM as a regular term to reduce the dependence between views and explored the complementary information of multiple views. Subsequently, we trained and coordinated the submodels and finally combined the submodels in the form of weights to obtain the final prediction model. On training set PDB1075, the prediction results of our model were better than those of most existing methods. Independent tests are conducted on the datasets PDB186 and PDB2272. The accuracy of the prediction results was 85.5% and 79.36%, respectively. This result exceeded the current state-of-the-art methods, which showed that the multi-view LSSVM via HSIC can be used as an efficient predictor.

19.
BMC Womens Health ; 22(1): 377, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114524

RESUMO

BACKGROUND: Considering the unique biological behavior of cervical adenocarcinoma (AC) compared to squamous cell carcinoma, we now lack a distinct method to assess prognosis for AC patients, especially for intermediate-risk patients. Thus, we sought to establish a Silva-based model to predict recurrence specific for the intermediate-risk AC patients and guide adjuvant therapy. METHODS: 345 AC patients were classified according to Silva pattern, their clinicopathological data and survival outcomes were assessed. Among them, 254 patients with only intermediate-risk factors were identified. The significant cutoff values of four factors (tumor size, lymphovascular space invasion (LVSI), depth of stromal invasion (DSI) and Silva pattern) were determined by univariate and multivariate Cox analyses. Subsequently, a series of four-, three- and two-factor Silva-based models were developed via various combinations of the above factors. RESULTS: (1) We confirmed the prognostic value of Silva pattern using a cohort of 345 AC patients. (2) We established Silva-based models with potential recurrence prediction value in 254 intermediate-risk AC patients, including 12 four-factor models, 30 three-factor models and 16 two-factor models. (3) Notably, the four-factor model, which includes any three of four intermediate-risk factors (Silva C, ≥ 3 cm, DSI > 2/3, and > mild LVSI), exhibited the best recurrence prediction performance and surpassed the Sedlis criteria. CONCLUSIONS: Our study established a Silva-based four-factor model specific for intermediate-risk AC patients, which has superior recurrence prediction performance than Sedlis criteria and may better guide postoperative adjuvant therapy.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
20.
Front Cell Infect Microbiol ; 12: 942334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061859

RESUMO

Herpes simplex virus type 2 (HSV-2) is a common human pathogen that establishes lifelong latency in neurons of the nervous system. The number of severe central nervous system infections caused by the virus has increased recently. However, the pathogenesis of HSV-2 infection in the nervous system is not fully understood. Here, we demonstrated global proteomic changes in the brain tissue in BALB/c mice vaginally infected with HSV-2. Data are available via ProteomeXchange with identifier PXD034186. A total of 249 differentially expressed proteins were identified in infected brain tissue. The GO and KEGG enrichment analysis of these proteins indicated that they were mainly involved in the regulation of synapse formation and synaptic excitability. In addition, genes affecting autophagy, the development of other neurodegenerative diseases, and signaling pathways relevant to other neurologic diseases were identified. Additional experiments, comparing the brain tissue of asymptomatic and symptomatic mice showed a differential expression of proteins involved in synapse formation and synaptic transmission. Others were involved in autophagy, addiction, and signaling pathways of other neurologic diseases. These results suggest that changes in synaptic structure and function, as well as autophagy, may be related to the development of neurologic abnormalities that follow HSV-2 infection. We also identified a protein GluN2A encoded by Grin2a was continuously expressed at high levels after infection. We propose that GluN2A may be a key molecule in the pathogenesis of HSV-2-induced neurologic diseases.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Animais , Encéfalo/patologia , Feminino , Herpes Simples/metabolismo , Herpesvirus Humano 2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteoma/metabolismo , Proteômica
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