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1.
Genomics ; 116(2): 110808, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364976

RESUMO

Immunotherapy is currently approved for CRC whose tumors have high MSI-H. To find additional biomarkers for immunotherapy in CRC, targeted sequencing was performed on tumor tissues from a discovery cohort of 161 CRC patients. Validation cohorts from the cBioPortal were also used for survival and tumor cell infiltration analyses. The FAT1-mutated CRC group often co-occurred with MSI events and displayed a higher tumor mutational burden compared to the FAT1 wild-type CRC. Overall survival was higher in patients with FAT1 mutations than in patients with wild type FAT1. The altered PI3K-AKT pathway and immune pathways were enriched in the FAT1-mutated CRC. A higher infiltration rate of immune cells including CD4+ T cells, CD8+ T cells, macrophages M1 and regulatory T cells were also observed in the colorectal tumors with FAT1 mutation compared to tumors with wild type FAT1. The results showed that CRC patients with FAT1 mutations exhibited an immunotherapy-favorable profile.


Assuntos
Neoplasias Colorretais , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/genética , Mutação , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Imunidade , Prognóstico , Caderinas/genética
2.
Ann Surg ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38088199

RESUMO

OBJECTIVE: To examine the outcomes of intestinal autotransplantation (IATx) in patients with locally advanced or recurrent colon cancer (LACC or LRCC) invading the superior mesenteric artery (SMA). BACKGROUND: SMA Involvement in LACC or LRCC is deemed unresectable and is associated with a poor prognosis. Combined extended resections of multiple organs together with SMA, followed by IATx may offer favorable clinical outcomes. However, data on its safety and efficacy are scarce. DESIGN: This retrospective cohort study included patients undergoing IATx between May 2018 and December 2022 in intestinal transplant programs at two university-affiliated hospitals in China. Patients with LACC or LRCC concomitantly with SMA contact of more than 180° were included. Patients with a locoregional peritoneal, pelvic, or distal metastasis were excluded. RESULTS: Ten patients underwent either IATx combined with pancreaticoduodenectomy (n=8) or IATx alone (n=2). Eight patients (80%) were male, and the median age was 55 years (range, 32 - 71 y). The Kaplan-Meier estimates for recurrence-free survival and overall survival at 3 years after IATx were 68% and 80%, respectively. No perioperative deaths occurred. All ten patients experienced postoperative complications including Clavien-Dindo grade I (n=1), grade II (n=4), grade IIIa (n=1), grade IIIb (n=3) and grade IVa (n=1), which comprised acute venous thromboses, upper gastrointestinal hemorrhage, anastomotic leak, gastropareses and significant pleural effusions. With an average follow-up of 23.9 months, eight patients (80%) were currently alive without evidence of disease. CONCLUSION: Extended resection for LACC or LRCC invading SMA can be performed safely and is associated with prolonged survival.

3.
Ultrason Sonochem ; 100: 106636, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37837708

RESUMO

Ultrasound combined with low temperature treatment is a new food processing technology. In this study, low temperature, three ultrasound power levels, and their combinations were adopted in the must before fermentation to study their effects on Merlot red wine. The results showed that ultrasound combined with low temperature pretreatment increased the total and monomer contents of anthocyanins and phenols, affected the color of the wine, and significantly increased its antioxidant capacity. In particular, 240 W of ultrasound combined with low temperature pretreatment reduced the bad odors (caprylic acid, benzaldehyde, and 1-ethanol content) and improved the flower and fruit aroma (1-octanol and phenethyl acetate), as well as the aftertaste, thus improving the quality of the wine. Ultrasound combined with low temperature pretreatment positively affected the quality of Merlot red wine.


Assuntos
Vitis , Vinho , Fenóis/análise , Antocianinas/análise , Vinho/análise , Temperatura , Antioxidantes/análise , Fermentação , Frutas/química
4.
Fish Shellfish Immunol ; 140: 108967, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37488041

RESUMO

The tryptophan-kynurenine (TRP-KYN) pathway is involved in several biological functions, including immunosuppression, inflammatory response, and tumor suppression. Six TRP-KYN pathway-related genes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 2 (IDO2), aminoadipate aminotransferase (AADAT), glutamate oxaloacetate transaminase 2 (GOT2), kynurenine monooxygenase (KMO), and kynureninase (KYNU) have been identified and cloned from the jawless vertebrate lamprey (Lampetra japonica) to gain insights into their evolution and characterization. Expression distribution showed that the key gene Lj-TDO was highly expressed in the oral gland. Real-time quantitative PCR showed that TRP-KYN pathway-related genes were significantly overexpressed after multi-stimulation. RNA interference showed that Lj-IDO2 knockdown regulated the expression of inflammatory factors. In conclusion, our study successfully clarified the ancestral features and functions of the TRP-KYN pathway, while providing valuable insights into the involvement of this pathway in the immune responses of a jawless vertebrate.


Assuntos
Cinurenina , Triptofano , Animais , Triptofano/metabolismo , Cinurenina/análise , Cinurenina/metabolismo , Lampreias/genética , Lampreias/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Imunidade Inata/genética
5.
Clin Transplant ; 37(3): e14865, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36416299

RESUMO

INTRODUCTION: Sensitization to human leukocyte antigen (HLA) creates an immunological barrier to intestinal transplantation (ITx). Current desensitization therapies are limited and ineffective in the most highly sensitized patients. A co-transplanted whole liver transplant can protect a kidney, heart, or intestinal allograft from antibody-mediated injury. Whether an auxiliary partial liver allograft provides effective protection for highly sensitized intestinal transplant recipients is unknown. METHODS: Two patients with strong HLA donor-specific antibody at high titer against their deceased donors underwent combined auxiliary partial liver and ITx across a positive cross-match. The left lateral lobes from the combined-graft recipients and the right liver lobes from the deceased donors were transplanted as a domino procedure to other four patients. RESULTS: Two combined-graft recipients have had an uneventful postoperative course without major complications at a 12- and 24-month follow-up, respectively. Intestinal graft function has been excellent with no evidence of humoral or cellular rejection. While a positive cross-match turned negative, titers of donor-specific HLA antibodies gradually declined over time after transplant. The left liver lobes procured from the combined-graft recipients were successfully transplanted into two pediatric patients (age 1.9, 2.4 years) and the right lobes from two deceased donors were successfully transplanted into two adult patients. All transplant procedures went well, without post-operative complications related to the splitting technique. CONCLUSION: Our results indicate that an auxiliary liver transplant can effectively protect a co-transplanted intestinal allograft against rejection and suggest that this combined procedure may serve as a useful therapeutic adjunct for a highly sensitized intestinal transplant candidate.


Assuntos
Transplante de Rim , Adulto , Humanos , Criança , Transplante de Rim/métodos , Rim , Anticorpos , Fígado , Transplante Homólogo
6.
Front Microbiol ; 14: 1241309, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249454

RESUMO

The epidemic of alcohol abuse affects millions of people worldwide. Relevant evidence supports the notion that the gut microbiota (GM) plays a crucial role in central nervous system (CNS) function, and its composition undergoes changes following alcohol consumption. Therefore, the purpose of this study was to investigate the effect of reconstructing the gut microbiota by fecal microbiota transplantation (FMT) on alcohol dependence. Here, we established an alcohol dependence model with C57BL/6J mice and proved that FMT treatment improved anxiety-like behavior and alcohol-seeking behavior in alcohol-dependent mice. Additionally, we found that the expression of the intestinal intercellular tight junction structure proteins ZO-1 and occludin was significantly increased after FMT. FMT repaired intestinal permeability in alcohol-dependent mice and decreased the levels of lipopolysaccharide (LPS) and proinflammatory factors. Moreover, the serotonin (5-hydroxytryptamine, 5-HT) content was significantly increased in alcohol-dependent mouse intestinal and brain tissues after receiving the fecal microbiome from healthy mice. 16S rRNA sequencing demonstrated that FMT markedly reshaped the composition of the gut microbiota and elicited changes in the intestinal barrier and 5-HT levels. Collectively, our results revealed that FMT has a palliative effect on alcohol dependence and explored the underlying mechanisms, which provides new strategies for the treatment of alcohol dependence.

7.
Am J Transplant ; 22(12): 3053-3060, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36066568

RESUMO

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8 months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.


Assuntos
Transplante de Rim , Doadores Vivos , Humanos , Colesterol , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/etiologia , Transplantados
8.
J Nutr Biochem ; 110: 109146, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36049672

RESUMO

Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Obesos , Jejum , Memória de Curto Prazo , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Obesidade/metabolismo , Lipídeos , Metabolismo dos Lipídeos
9.
Front Hum Neurosci ; 16: 960350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034119

RESUMO

Objective: Despite its prevalence, insomnia disorder (ID) remains poorly understood. In this study, we used machine learning to analyze the functional connectivity (FC) disturbances underlying ID, and identify potential predictors of treatment response through recurrent transcranial magnetic stimulation (rTMS) and pharmacotherapy. Materials and methods: 51 adult patients with chronic insomnia and 42 healthy age and education matched controls underwent baseline anatomical T1 magnetic resonance imaging (MRI), resting-stage functional MRI (rsfMRI), and diffusion weighted imaging (DWI). Imaging was repeated for 24 ID patients following four weeks of treatment with pharmacotherapy, with or without rTMS. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into ID and control groups based on their FC, and derive network and parcel-based FC features contributing to each model. The number of FC anomalies within each network was also compared between responders and non-responders using median absolute deviation at baseline and follow-up. Results: Subjects were classified into ID and control with an area under the receiver operating characteristic curve (AUC-ROC) of 0.828. Baseline FC anomaly counts were higher in responders than non-responders. Response as measured by the Insomnia Severity Index (ISI) was associated with a decrease in anomaly counts across all networks, while all networks showed an increase in anomaly counts when response was measured using the Pittsburgh Sleep Quality Index. Overall, responders also showed greater change in all networks, with the Default Mode Network demonstrating the greatest change. Conclusion: Machine learning analysis into the functional connectome in ID may provide useful insight into diagnostic and therapeutic targets.

10.
Comput Intell Neurosci ; 2022: 4988636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990151

RESUMO

The rapid development of power semiconductor devices is helping to realize a low-carbon society and provide a better life for everyone. Power semiconductors not only are used in many large-scale industrial control fields such as power transmission and control in power grids, rail transit traction systems, and defense weapons and equipment, but also play a vital role in daily equipment such as home appliances, medical electronics, and electronic communications; all devices such as power steering in cars, battery chargers, cell phones, and microwave ovens utilize power electronics. This research mainly focuses on the high-voltage LDMOS device model and its implementation. Based on the in-depth study of the structure and physical mechanism of high-voltage LDMOS devices, with the help of BSIM4 core model, which is now very mature and widely used in industry, the drift region of high-voltage LDMOS is mainly modeled, and the drift region of LDMOS is modeled as a variable resistance controlled by voltage. Finally, Verilog-A language and neural network method are used to establish a compact model of LDMOS. The improved model is applied to LDMOS and can better fit the output characteristics with self-heating effect.


Assuntos
Eletrônica , Semicondutores , Eletrodos , Desenho de Equipamento , Redes Neurais de Computação
11.
Brain Res Bull ; 188: 1-10, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35850188

RESUMO

The anterior nucleus of the paraventricular thalamus (aPVT) integrates various synaptic inputs and conveys information to the downstream brain regions for arousal and pain regulation. Recent studies have indicated that the PVT plays a crucial role in the regulation of chronic pain, but the plasticity mechanism of neuronal excitability and synaptic inputs for aPVT neurons in neuropathic pain remains unclear. Here, we report that spinal nerve ligation (SNL) significantly increased the neuronal excitability and reset the excitatory/inhibitory (E/I) synaptic inputs ratio of aPVT neurons in mice. SNL significantly increased the membrane input resistance, firing frequency, and the half-width of action potential. Additionally, SNL enlarged the area of afterdepolarization and prolonged the rebound low-threshold spike following a hyperpolarized current injection. Further results indicate that an inwardly rectifying current density was decreased in SNL animals. SNL also decreased the amplitude, but not the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), nor the amplitude or frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) of aPVT neurons. Moreover, SNL disrupted the E/I synaptic ratio, caused a decrease in weighted tau and half-width of averaged sIPSCs, but did not change these physiological properties of averaged sEPSCs. Finally, pharmacological activation of the GABAA receptor at aPVT could effective relieve SNL-induced mechanical allodynia in mice. These results reveal the plasticity of intrinsic neuronal excitability and E/I synaptic balance in the aPVT neurons after nerve injury and it may play an important role in the development of pain sensitization.


Assuntos
Neuralgia , Nervos Espinhais , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Camundongos , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Tálamo
12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(4): 405-409, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35426277

RESUMO

Objective: To investigate the application and effectiveness of metatarsal mortise and tenon shortening osteotomy in the treatment of macrodactyly in children. Methods: The clinical data of 17 children with macrodactyly (18 feet and 27 toes) admitted between January 2018 and January 2020 were retrospectively analyzed. There were 12 males (12 feet and 18 toes) and 5 females (6 feet and 9 toes); the age ranged from 1 to 13 years, with a median age of 5 years. All children were treated with metatarsal mortise and tenon shortening osteotomy. Ten cases of single-segment metatarsals were shortened, 7 cases of 2-segment metatarsals, and 1 case of 3-segment metatarsals; involved 1 foot of single toe, 9 feet of 2 toes, 3 feet of 3 toes, 3 feet of 4 toes, and 2 feet of 5 toes. Five cases had lameness, and 1 case had limited walking with the big toes of both feet, and there was no obvious pain in all children. X-ray films showed that the involved phalanges were thickened and increased in 18 feet, and the deformity of the distal segment was heavier than that of the proximal segment in 13 feet, and the two were similar in 5 feet. The length of metatarsal shortening was 0.7-2.5 cm, with an average of 1.2 cm. The clinical healing of shortened metatarsal fractures in children was observed after operation, and the occurrence of related complications was recorded. Results: All 17 children were followed up 6-22 months, with an average of 14 months. All incisions healed by first intention. The osteotomy ends of 27 toes were clinically healed after operation, and the healing time was 4-8 weeks. No nonunion, fracture displacement, malunion, epiphyseal plate premature closure, and needle tract infection occurred. Conclusion: Metatarsal mortise and tenon shortening osteotomy is a good osteotomy method. It can improve the stability of the osteotomy end and increase the contact surface of the osteotomy end, which is conducive to the healing of the osteotomy end and is suitable for the treatment of macrodactyly.


Assuntos
Fraturas Ósseas , Hallux Valgus , Ossos do Metatarso , Adolescente , Criança , Pré-Escolar , Feminino , Dedos/anormalidades , Hallux Valgus/cirurgia , Humanos , Lactente , Deformidades Congênitas dos Membros , Masculino , Ossos do Metatarso/cirurgia , Metatarso , Osteotomia/métodos , Estudos Retrospectivos , Resultado do Tratamento
13.
Pharmgenomics Pers Med ; 15: 55-64, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35125881

RESUMO

OBJECTIVE: This study aimed to explore the pathogenic genes and mutation sites of macrodactyly. METHODS: Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the whole-exome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes. RESULTS: In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p.E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p.G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway. CONCLUSION: Mutation of the PIK3CA gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites.

14.
Molecules ; 27(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35209020

RESUMO

Puerarin (PUR) and gastrodin (GAS) are often used in combined way for treating diseases caused by microcirculation disorders. The current study aimed to investigate the absorption and transportation mechanism of PUR and GAS and their interaction via Caco-2 monolayer cell model. In this work, the concentration in Caco-2 cell of PUR and GAS was determined by HPLC method. The bidirectional transport of PUR and GAS and the inhibition of drug efflux including verapamil and cyclosporine on the transport of these two components were studied. The mutual influence between PUR and GAS, especially the effect of the latter on the former of the bidirectional transport were also investigated. The transport of 50 µg·mL-1 PUR in Caco-2 cells has no obvious directionality. While the transport of 100 and 200 µg·mL-1 PUR presents a strong directionality, and this directionality can be inhibited by verapamil and cyclosporine. When PUR and GAS were used in combination, GAS could increase the absorption of PUR while PUR had no obvious influence on GAS. Therefore, the compatibility of PUR and GAS is reasonable, and GAS can promote the transmembrane transport of PUR, the effect of which is similar to that of verapamil.


Assuntos
Álcoois Benzílicos/metabolismo , Glucosídeos/metabolismo , Absorção Intestinal , Isoflavonas/metabolismo , Álcoois Benzílicos/química , Álcoois Benzílicos/farmacocinética , Transporte Biológico , Células CACO-2 , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Glucosídeos/química , Glucosídeos/farmacocinética , Humanos , Isoflavonas/química , Isoflavonas/farmacocinética , Cinética , Estrutura Molecular , Permeabilidade , Reprodutibilidade dos Testes
16.
ACS Omega ; 6(43): 29126-29136, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34746601

RESUMO

The electric field method proved in the lab and oil fields is an effective and fast way to significantly improve oil recovery, which can be applied to greatly realize the urgent-need requirements for energy, especially in tight sandstones. Generally, the changed molecular groups treated with an electric field modulate the wettability of reservoirs, affecting the final oil recovery. Herein, the investigation of the impact of the electric field on the molecular groups of reservoirs is imperative and meaningful. In this paper, tight sandstones were placed into a particular instrument and subjected to various strengths of the electric field. Nine treated powders and one untreated powder of tight sandstones were processed by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) experiments. FTIR results show that the electric field decreases aromatic groups, C-O groups, COOH groups, and aliphatic groups, whereas it increases C=C groups, C=O groups, and OH groups. Interestingly, the changes in C-O groups, C=O groups, COOH groups, and OH groups are all the competitive results of production and consumption during the treatment process. With regard to C-O groups and COOH groups, the consumption has an advantage over the production on the content of functional groups, and the situations for C==O groups and OH groups exhibit a contrary trend. The fitted result of XPS proves the fact that the electric field improves C=O groups, OH groups, and COOR groups, whereas it reduces C-O groups, supporting that the molecular groups can be mutually transformed during the electric field treatment. The obtained knowledge is beneficial to the study of electric field-related technologies on the molecular groups of reservoirs.

17.
Transl Neurosci ; 12(1): 335-345, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34594577

RESUMO

Alzheimer's disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.

18.
Biochem Biophys Res Commun ; 580: 20-27, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34607259

RESUMO

Melatonin has been well documented for its neuroprotective role through inhibiting oxidative stress against traumatic brain injury (TBI). However, the specific role of melatonin and the exact effects on cell responses (neurons, astrocytes, and microglia) in different brain regions are unclear. Here, we subjected mice to closed head injury, to establish a repeated mild TBI model and detect neuronal activity and glial responses in cognition-related brain regions after melatonin administration. Melatonin only showed cognitive enhancement if administered during early pathological stages, but not in late (chronic) stages. Additionally, we observed a significant increase in neuronal activity and inhibition of astrocyte reactivation in medial prefrontal cortex and hippocampus, but not in other cognitive deficit related brain regions. Furthermore, by activating astrocytes in these brain regions, we found neuronal activity upregulation and cognitive improvement following melatonin treatment. Therefore, we concluded that melatonin administration during the early stages of TBI is necessary to inhibit astrocyte reactivation and to promote cognitive function. Our results provide evidence for use of melatonin for cognitive improvement after TBIs.


Assuntos
Astrócitos/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Melatonina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Astrócitos/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Masculino , Camundongos
19.
Gastroenterol Rep (Oxf) ; 9(4): 350-356, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34567567

RESUMO

BACKGROUND: The aim of this study was to assess whether the autologous internal iliac artery and vein could be used as an interpositional graft for vascular reconstruction in segmental intestinal allografts and autografts. METHODS: Thirty-four intestinal transplants (19 living-related allografts and 15 autografts) were conducted in our programs between January 2011 and January 2019. Patient characteristics, type of vascular reconstruction, and post-operative complications were reviewed. RESULTS: There were 20 males and 14 females with a median age of 35 years. Of 34 grafts, 22 (64.7%) (11 allografts and 11 autografts) were revascularized using the autologous internal iliac artery and vein for reconstruction. Vascular reconstruction on the back table took 21 ± 6 min to complete. Both total operative time and cold ischemia time tended to be longer in the vascular-reconstruction group than in the direct-anastomosis group (530 ± 226 vs 440 ± 116 and 159 ± 49 vs 125 ± 66 min, respectively), but these differences were not significant. The incidence of vascular thrombosis tended to be higher in the direct-anastomosis group than in the vascular-reconstruction group (16.7% vs 0%, P = 0.118). At a median follow-up of 36.9 months, no stenosis or pseudoaneurysms developed. In 19 allografts, acute rejection occurred in 4 (21.1%) and chronic rejection occurred in 1 (5.2%). CONCLUSIONS: Our results indicate that the use of an autologous internal iliac interposition graft greatly facilitates intestinal graft implantation and minimizes the risk of vascular complications.

20.
J Bone Oncol ; 30: 100385, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34401227

RESUMO

BACKGROUND: Ewing sarcoma (ES) of bone is accounting for the second most common type of primary bone cancer in children and adolescents. However, the patterns of distant metastasis (DM) and the effect of the sites of DM on survival outcomes were not investigated. AIMS: This study aimed to investigate the patterns of DM and the prognostic factors related to outcomes in primary metastatic ES of the bone. METHODS: Patients who were diagnosed with primary metastatic ES between 2010 and 2018 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis, log-rank tests, and Cox proportional-hazards regression models were used for statistical analyses. RESULTS: We identified 277 patients in this study and 95.3% of them (n = 264) receiving chemotherapy. A total of 371 sites of DM were observed. Lung was the most common distant metastatic site (n = 182, 49.1%), followed by bone (n = 139, 37.5%), distant lymph node (n = 26, 7.0%), liver (n = 14, 3.8%), and brain (n = 10, 2.7%). Three-year cause-specific survival (CSS) was 56.1% in the entire cohort. Older age (hazard ratio [HR] 2.210, P < 0.001) and bone metastasis (HR 1.903, P = 0.002) were the independent prognostic factors associated with inferior CSS. Similar results were found in those with bone-only metastasis (n = 80) or lung-only metastasis (n = 117), which showed that patients with bone-only metastasis had an inferior CSS compared to those with metastases only to the lung (HR 1.926, P = 0.005). CONCLUSIONS: Lung and bone are the most frequently distant metastatic sites in patients with primary metastatic ES of bone. Bone metastasis is an independent risk factor for inferior survival.

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