Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
1.
World J Surg Oncol ; 21(1): 356, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37978553

RESUMO

BACKGROUND AND OBJECTIVE: It is controversial whether wrapping around the pancreaticojejunostomy (PJ) could reduce the rate of postoperative pancreatic fistula (POPF), especially in laparoscopic pancreaticoduodenectomy (LPD). This study aims to summarize our single-center initial experience in wrapping around PJ using the ligamentum teres hepatis (LTH) and demonstrate the feasibility and safety of this method. METHODS: Patients who underwent LPD applying the procedure of wrapping around the PJ were identified. The cohort was compared to the cohort with standard non-wrapping PJ. A 1:1 propensity score matching (PSM) was performed to compare the early postoperative outcomes of the two cohorts. Risk factors for POPF were determined by using univariate and multivariate logistic regression analysis. RESULTS: Overall, 143 patients were analyzed (LPD without wrapping (n = 91) and LPD with wrapping (n = 52)). After 1:1 PSM, 48 patients in each cohort were selected for further analysis. Bile leakage, DGE, intra-abdominal infection, postoperative hospital stays, harvested lymph nodes, and R0 resection were comparable between the two cohorts. However, the wrapping cohort was associated with significantly less POPF B (1 vs 18, P = 0.003), POPF C (0 vs 8, P = 0.043), and Clavien-Dindo classification level III-V (5 vs 26, P = 0.010). No patients died due to the clinically relevant POPF in the two cohorts. No patients who underwent the LTH wrapping procedure developed complications directly related to the wrapping procedure. After PSM, whether wrapping was an independent risk factor for POPF (OR = 0.202; 95%CI:0.080-0.513; P = 0.001). CONCLUSIONS: Wrapping the LTH around the PJ technique for LPD was safe, efficient, and reproducible with favorable perioperative outcomes in selected patients. However, further validations using high-quality RCTs are still required to confirm the findings of this study.


Assuntos
Laparoscopia , Ligamento Redondo do Fígado , Humanos , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Ligamento Redondo do Fígado/cirurgia , Pontuação de Propensão , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/efeitos adversos , Estudos Retrospectivos
2.
Cancer Immunol Immunother ; 70(3): 773-786, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32989553

RESUMO

The immune microenvironment plays a vital role in the progression of hepatocellular carcinoma (HCC). Thousands of immune-related genes (IRGs) have been identified, but their effects on HCC are not fully understood. In this study, we identified the differentially expressed IRGs and analyzed their functions in HCC in a systematic way. Furthermore, we constructed a diagnostic and a prognostic model using multiple statistical methods, and both models had good distinguishing performance, which we verified in several independent datasets. This diagnostic model was also adaptable to proteomic data. The combination of a prognostic risk model and classic clinical staging can effectively distinguish patients in high- and low-risk groups. Furthermore, we systematically explore the differences in the immune microenvironment between the high-risk group and the low-risk group to help clinical decision-making. In summary, we systematically analyzed immune-related genes in HCC, explored their functions, constructed a diagnostic and a prognostic model and investigated potential therapeutic schedules in high-risk patients. The model performance was verified in multiple databases. Our findings can provide directions for future research.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Imunomodulação/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Biologia Computacional , Bases de Dados Genéticas , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
3.
J Transl Med ; 13: 188, 2015 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-26071079

RESUMO

BACKGROUND: Atherosclerosis (AS) presents characteristic of a chronic inflammatory disease in which both adaptive and innate immune cells play roles. Accumulating evidence has showed the impairment of natural killer (NK) cells in atherosclerosis, however, the mechanisms of this impairment remain unclear. In this study, we investigated the expression of CD160 on NK cells and assessed its pathological roles in NK loss during atherogenesis. METHODS: CD160 expression on NK cells was measured in 49 AS patients and 41 healthy controls (HC) by flow cytometry, their inflammatory cytokine levels in sera were determined by ELSIA, and the effect of CD160 engagement on NK cells was evaluated by in vitro culture experiments. RESULTS: Compared to HC, AS patients had a significantly increased CD160 expression on peripheral NK cells and concomitantly decreased peripheral NK cell number, and increased CD160 expression was positively related to the levels of serum lipids and IFN-γ, TNF-α and IL-6 inflammation cytokines, which all are risk factors for atherogenesis, and inversely correlated with peripheral NK cell number. Furthermore, engagement of CD160 receptor on NK cells from AS patients triggers a significantly increased production of inflammation cytokines and subsequent NK cell apoptosis, and blockade of TNF-α prevented the increased apoptosis of NK cells from AS patients after CD160 engagement, indicating a critical role of TNF-α in mediating NK cell loss by CD160 engagement. RESULTS: Our results provide evidence that elevated CD160 expression on NK cells plays an important role in NK cell loss in atherosclerosis. The increased CD160 expression on NK cells might be used as an indicator for disease progression.


Assuntos
Antígenos CD/sangue , Aterosclerose/sangue , Aterosclerose/imunologia , Movimento Celular , Células Matadoras Naturais/metabolismo , Receptores Imunológicos/sangue , Apoptose , Aterosclerose/patologia , Linfócitos T CD4-Positivos/imunologia , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/sangue
5.
Int J Mol Med ; 53(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214344

RESUMO

Osteocyte function is critical for metabolism, remodelling and regeneration of bone tissue. In the present study, the roles of regulator of G protein signalling 18 (RGS18) were assessed in the regulation of osteocyte proliferation and bone formation. Target genes and signalling pathways were screened using the Gene Expression Omnibus (GEO) database and Gene Set Enrichment Analysis (GSEA). The function of RGS18 and the associated mechanisms were analysed by Cell Counting Kit 8 assay, 5­ethynyl­2'­deoxyuridine assay, flow cytometry, reverse transcription­quantitative PCR, western blotting and immunostaining. Overlap analysis of acutely injured subjects (AIS) and healthy volunteers (HVs) from the GSE93138 and GSE93215 datasets of the GEO database identified four genes: KIAA0825, ANXA3, RGS18 and LIPN. Notably, RGS18 was more highly expressed in peripheral blood samples from AIS than in those from HVs. Furthermore, RGS18 overexpression promoted MLO­Y4 and MC3T3­E1 cell viability, proliferation and S­phase arrest, but inhibited apoptosis by suppressing caspase­3/9 cleavage. Silencing RGS18 exerted the opposite effects. GSEA of GSE93138 revealed that RGS18 has the ability to regulate MAPK signalling. Treatment with the MEK1/2 inhibitor PD98059 reversed the RGS18 overexpression­induced osteocyte proliferation, and treatment with the ERK1/2 activator 12­O­tetradecanoylphorbol­13­acetate reversed the effects of RGS18 silencing on osteocyte proliferation. In conclusion, RGS18 may contribute to osteocyte proliferation and bone fracture healing via activation of ERK signalling.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Osteócitos , Proteínas RGS , Humanos , Apoptose/genética , Proliferação de Células/genética , Proteínas de Ligação ao GTP , Transdução de Sinais , Animais , Camundongos , Células 3T3 , Proteínas RGS/genética
6.
Plasmid ; 69(3): 195-201, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22935743

RESUMO

Endothelial progenitor cells (EPCs) play a key role in restoring endothelial function and enhancing angiogenesis. Platelet-derived growth factor C (PDGF-C) is a newly discovered member of the PDGF family that binds to the PDGFR-α homodimer and the PDGFR-α/ß heterodimer. Currently, the biological effects of PDGF-C on EPCs proliferation, migration and adhesion are not well understood. In this study, the full-length coding sequence (CDS) region for the PDGF-C gene was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR). The amplified PDGF-C product was digested and inserted into the pMD 19-T simple vector and then subcloned into a pIRES2-EGFP plasmid to construct the pIRES2-EGFP-PDGF-C eukaryotic expression vector. After it was transfected to EPCs, the expression of PDGF-C protein in EPCs was verified by Western blotting analysis. Finally, we investigated the effects of PDGF-C protein overexpression on EPCs proliferation, migration and adhesion. In conclusion, we constructed a recombinant eukaryotic expression vector containing the complete CDS region of PDGF-C and expressed the full-length and functional PDGF-C protein successfully. Furthermore, PDGF-C promoted EPCs proliferation, migration and adhesion. This offers promise for the development of new therapeutic strategies for improving neovascularization and repair of blood vessel endothelium in patients with ischemic heart disease or peripheral arterial occlusive disease.


Assuntos
Movimento Celular , Proliferação de Células , Células Endoteliais/metabolismo , Linfocinas/metabolismo , Plasmídeos/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/citologia , Animais , Adesão Celular , Forma Celular , Células Cultivadas , Clonagem Molecular , Células Endoteliais/citologia , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Linfocinas/genética , Masculino , Plasmídeos/genética , Fator de Crescimento Derivado de Plaquetas/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Células-Tronco/metabolismo , Transfecção
7.
Front Surg ; 10: 1153531, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37266002

RESUMO

Objective: This study aims to summarize our single-center initial experience in laparoscopic pancreatic operation (LPO) combined with hepatic arterial resection and reconstruction, as well as to demonstrate the feasibility, safety, and key surgical procedure for LPO. Methods: We retrospectively analyzed 7 patients who had undergone LPO combined with hepatic arterial resection and reconstruction in our center from January 2021 to December 2022. The clinical data of these 7 patients were collected and analyzed. Results: In our case series, two patients underwent passive arterial resection and reconstruction due to iatrogenic arterial injury, and five patients underwent forward arterial resection and reconstruction due to arterial invasion. The arterial anastomosis was successful in 5 cases, including 2 cases of end-to-end in situ and 3 cases of arterial transposition, and the vascular reconstruction time was 38.28 ± 15.32 min. There were two conversions to laparotomy. The postoperative recovery of all patients was uneventful, with one liver abscess (Segment 4) and no Clavien III-IV complications. We also share valuable technical feedback and experience gained from the initial practice. Conclusions: Based on the surgeon's proficiency in open arterial resection and reconstruction and laparoscopic technique. This study demonstrated the feasibility of total laparoscopic hepatic arterial resection and reconstruction in properly selected cases of arterial involvement or iatrogenic arterial injury. Our initial experience provides valuable information for laparoscopic pancreas surgery with arterial resection and reconstruction.

8.
J Clin Med ; 12(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36675418

RESUMO

BACKGROUND: The relationship between the prognostic nutritional index (PNI) and the prognosis of malignancy has been increasingly mentioned in recent research. This study aimed to construct nomograms based on the PNI to predict tumor progression and survival in patients with unresectable hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: The development set included 785 patients who underwent their first TACE between 2012 and 2016, and the validation set included 336 patients who underwent their first TACE between 2017 and 2018. The clinical outcomes included the time to progression (TTP) and overall survival (OS). Cox regression was applied to screen for independent risk factors of TTP and OS in the development set, and PNI-based nomograms were constructed for TTP and OS. The predictive performance of nomograms was conducted through the C-index, calibration curves, and decision analysis curves in the development set and validation set. RESULTS: After multivariate analysis, the prognostic predictors of both TTP and OS included portal vessel invasion, extrahepatic metastasis, tumor number, alpha-fetoprotein (AFP) level, longest tumor diameter, and PNI. Furthermore, the Child-Pugh classification and platelets (PLTs) were independent risk factors for OS only. Nomograms for predicting TTP and OS were constructed using TTP and OS prognostic factors. In the development set and the validation set, the C-index of the TTP nomograms was 0.699 (95% confidence interval (CI): 0.680-0.718) and 0.670 (95%CI: 0.638-0.702), and the C-index of the OS nomograms was 0.730 (95%CI: 0.712-0.748) and 0.700 (95%CI: 0.665-0.723), respectively. CONCLUSION: Nomograms based on the PNI can effectively predict tumor progression and survival in patients with unresectable HCC undergoing TACE.

9.
Heliyon ; 9(8): e18494, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37529335

RESUMO

Background: This retrospective study analyzed the prognostic value of preoperative prealbumin (PAB) levels in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolisation (TACE). Methods: Four hundred and two patients diagnosed with unresectable HCC were included in this retrospective study. All patients underwent their first TACE procedure. Based on PAB levels before the first TACE, 402 patients were classified as having low PAB levels and high PAB levels. Potential confounding factors between the two groups were eliminated using. Propensity Score Matching (PSM) analysis. The time to progression (TTP) and overall survival (OS) of the two groups were compared using Kaplan-Meier curves before and after PSM. Risk factors for poor prognosis were determined using univariate and multivariate Cox proportional hazards models. Results: Before PSM, the high PAB level group had a significantly longer median TTP and OS than the low PAB level group (all P values < 0.0001). After PSM, the high PAB level group still had a significantly longer median TTP and OS than the low PAB level group (all P values < 0.05). After PSM, low PAB level was found to be an independent predictor of shorter OS (HR = 0.656; 95% CI:0.448-0.961; P = 0.03). The subgroup analysis before PSM showed that low PAB levels increased the risk of poor prognosis in most subgroups. Conclusions: Low preoperative PAB levels are associated with poor prognosis in patients with unresectable HCC after TACE.

10.
J Gene Med ; 14(9-10): 570-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22941868

RESUMO

BACKGROUND: To explore the anti-tumor effect of high-intensity focused ultrasound (HIFU) combined with herpes simplex virus thymidine kinase (HSV-TK) gene-loaded ultrasound-targeted microbubbles on VX2 rabbit liver tumors. METHODS: Seventy-five New Zealand white rabbits were randomly divided into five groups after the models of VX2 rabbit liver tumors were established: (a) HIFU group; (b) HIFU and HSV-TK group (HIFU + HSV-TK); (c) HIFU, HSV-TK and ultrasound group (HIFU + HSV-TK + US); (d) HIFU, HSV-TK gene-loaded microbubbles and ultrasound group (HIFU + HSV-TK-MBs + US); and (e) HSV-TK gene-loaded microbubbles and ultrasound group (HSV-TK-MBs + US). After 2 weeks of VX2 liver tumor implantation, rabbits in groups (a), (b), (c) and (d) received HIFU to establish rabbit models of residual tumor by ablating 80% of the tumor volume. After HIFU ablation, rabbits in different groups received MBs wrapped around HSV-TK or HSV-TK solution via marginal ear veins and/or local ultrasonic irradiation to the tumor. Six rabbits in each group were sacrificed 48 h after the corresponding treatment, and tumors were extracted for in vitro experiments. Thymidine kinase mRNA was detected by the real-time polymerase chain reaction. The green fluorescent protein expression in liver tumor was detected by western blotting and immunohistochemistry. Tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. The growth curves of VX2 liver tumors and survival curves of rabbits were compared. RESULTS: Forty-eight hours after treatment, TK mRNA and protein were the highest in the HIFU + HSV-TK + US + MBs group and the HSV-TK + US + MBs group (p < 0.05). At 48 h after treatment, the apoptotic index of tumor cells in HIFU + HSV-TK-MBs + US group was the highest (p < 0.05). Compared to other groups, HIFU combined with MBs wrapped HSV-TK suicide gene significantly inhibited tumor growth in vivo (p < 0.05) and prolonged the survival time of animals (p < 0.05). CONCLUSIONS: HIFU combined with HSV-TK gene-loaded ultrasound-targeted MBs significantly inhibited the growth of VX2 rabbit liver tumors in vivo and prolonged the survival time of the animals, providing a novel gene delivery method and a novel strategy for liver tumor treatment.


Assuntos
Terapia Genética/métodos , Neoplasias Hepáticas Experimentais/terapia , Microbolhas/uso terapêutico , Simplexvirus/genética , Timidina Quinase/genética , Ultrassom Focalizado Transretal de Alta Intensidade/métodos , Animais , Apoptose/genética , Expressão Gênica , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/patologia , Coelhos , Timidina Quinase/metabolismo , Resultado do Tratamento
11.
J Surg Res ; 176(2): 666-71, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22381173

RESUMO

BACKGROUND: NBD (NEMO binding domain) peptides could selectively inhibit the inflammation induced NF-κB activity, while sparing the protective functions of basal NF-κB activity. The aim of this study was to determine whether NBD peptides inhibited the transcriptional activity of nuclear factor-κB (NF-κB) during liver transplant ischemia-reperfusion injury (IRI), without affecting its basal function. MATERIALS AND METHODS: Sprague Dawley (SD) rats were performed orthotropic liver transplantation according to the Kamada technique. Donors were given NBD peptides (8 mg/kg, intraperitoneal) 2 h before surgery (n = 24) and the controls were treated with the same volume of physiologic saline (n = 24). An additional 16 animals in normal condition (did not undergo any surgery) were also divided into two groups and given the same treatment as above to assess the effect of NBD peptides on basal function. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF-α), IKK (IκB kinase) complex phosphorylation, IκBα degradation, NF-κB transcriptional activity, apoptosis, and performed a morphologic study of liver tissues at 3, 6, and 24 h after portal vein reperfusion and in normal condition (n = 8). RESULTS: Pretreatment with NBD peptides significantly improved liver function, attenuating liver parenchymal cell damage, apoptosis by down-regulating TNF-α level, inhibiting IKK complex phosphorylation, IκBα degradation, and NF-κB transcriptional activity, but had no effect in normal condition. CONCLUSION: NBD peptides attenuated hepatic IRI by preventing NF-κB activation, without affecting basal NF-κB activity.


Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Fígado , Peptídeos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Quinase I-kappa B/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , NF-kappa B/metabolismo , Peptídeos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas de Ligação a RNA , Ratos , Ratos Sprague-Dawley , Ativação Transcricional/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
12.
J Surg Res ; 174(2): 359-68, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21392795

RESUMO

BACKGROUND: Suppression of histone deacetylase 11 (HDAC11) can promote IL-10 expression in mouse macrophages RAW264.7 and induce immune tolerance. This study is to further investigate the role of HDAC11 in tolerance induction via Kupffer cells (KCs) following orthotopic liver transplantation (OLT) in rats. MATERIALS AND METHODS: KCs isolated from BALB/c mice were divided into pHDAC11, adHDAC11, and pCV group (treated with HADC11-shRNA, adenovirus encoding HDAC11, and control vector, respectively). IL-10 expression was determined after lipopolysaccharide treatment. The expression of MHC-II and co-stimulatory molecules on KCs surface was evaluated by flow cytometry. T cell proliferation was measured by [(3)H]-thymidine incorporation after culturing with aforementioned three groups, treated KCs, respectively. OLT was performed in rats after Ad-HDAC11 and pHDAC11 treatment. Blood samples were collected for biochemical studies, and postoperative survival was examined. RESULTS: IL-10 expression was inhibited and promoted by Ad-HDAC11 and HDAC11-shRNA in KCs, respectively. MHC-II and co-stimulatory molecules on KCs surface as well as T cell proliferation were significantly inhibited and induced in pHDAC11 and Ad-HDAC11 compared with pCV, respectively. Serum IL-2, TNF-α, and IFN-γ levels were significantly lower in pHDAC11 and higher in Ad-HDAC11 compared with pCV, respectively, while IL-4 and IL-10 were the reverse. Postoperative survival, liver function, and histology were different among the three groups. CONCLUSIONS: Suppression of HDAC11 can promote IL-10 expression in KCs and induce tolerance following OLT in rats. Consequently, HDAC11 may be a key component of this immune regulation system and a promising target for development of novel drugs of gene therapy for inducing tolerance in clinical liver transplantation.


Assuntos
Histona Desacetilases/metabolismo , Interleucina-10/metabolismo , Células de Kupffer/fisiologia , Transplante de Fígado/imunologia , Tolerância ao Transplante , Animais , Apresentação de Antígeno , Proliferação de Células , Citocinas/sangue , Fígado/patologia , Testes de Função Hepática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Linfócitos T/fisiologia , Transplante Homólogo
13.
Biochem Pharmacol ; 202: 115137, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35700758

RESUMO

ß2-microglobulin (B2M) has been established to impair cognitive function. However, no treatment is currently available for B2M-induced cognitive dysfunction. Itaconate is a tricarboxylic acid (TCA) cycle intermediate that exerts neuroprotective effects in several neurological diseases. The amino-ß-carboxymuconate-semialdehyde-decarboxylase (ACMSD)/picolinic acid (PIC) pathway is a crucial neuroprotective branch in the kynurenine pathway (KP). The present study sought to investigate whether Itaconate attenuates B2M-induced cognitive impairment and examine the mediatory role of the hippocampal ACMSD/PIC pathway. We demonstrated that 4-Octyl Itaconate (OI, an itaconate derivative) significantly alleviated B2M-induced cognitive dysfunction and hippocampal neurogenesis impairment. OI treatment also increased the expression of ACMSD, elevated the concentration of PIC, and decreased the level of 3-HAA in the hippocampus of B2M-exposed rats. Furthermore, inhibition of ACMSD by TES-991 significantly abolished the protections of Itaconate against B2M-induced cognitive impairment and neurogenesis deficits. Exogenous PIC supplementation in hippocampus also improved cognitive performance and hippocampal neurogenesis in B2M-exposed rats. These findings demonstrated that Itaconate alleviates B2M-induced cognitive impairment by upregulation of the hippocampal ACMSD/PIC pathway. This is the first study to document Itaconate as a promising therapeutic agent to ameliorate cognitive impairment. Moreover, the mechanistic insights into the ACMSD/PIC pathway improve our understanding of it as a potential therapeutic target for neurological diseases beyond B2M-associated neurocognitive disorders.


Assuntos
Carboxiliases , Disfunção Cognitiva , Aminoácidos , Animais , Carboxiliases/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Hipocampo/metabolismo , Ácidos Picolínicos , Ratos , Succinatos
14.
Food Res Int ; 161: 111491, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192866

RESUMO

Ethylene plays a crucial role in regulating fruit ripening, quality, and defense response. However, the mechanism(s) responsible for wound-induced ethylene regulation of fruit physiology at a network level is unclear. We used mass spectrometry (MS) to identify differences in the physiological response between fresh-cut fruits of wild-type (WT) tomato and an ethylene receptor mutant (SlETR-3) (also referred to as Nr) during storage. We found that Nr mutants exhibited better appearance and quality, as well as higher ethylene levels during the first 3 d of storage at 4 °C. Thirty-seven (0 h), eighty-two (12 h) and twelve (24 h) differentially abundant proteins were identified between the fresh-cut slices of the two genotypes during storage at the designated timepoints. In particular, antioxidant enzymes, such as ascorbate peroxidase, glutathione S-transferase, and peroxiredoxin were highly expressed in WT fruit, which was associated with higher H2O2 production, and high levels of transcription of cell-wall degrading enzymes. Leucine aminopeptidase, a marker enzyme for response to wounding exhibited higher levels in the Nr mutant, which is consistent with its higher production of ethylene. Collectively, our results provide a deeper insight into the ethylene-induced physiological regulatory network that is activated in fresh-cut tomatoes.


Assuntos
Solanum lycopersicum , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Etilenos/farmacologia , Glutationa Transferase/metabolismo , Peróxido de Hidrogênio/metabolismo , Leucil Aminopeptidase/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Peroxirredoxinas/metabolismo , Proteômica
15.
Artigo em Inglês | MEDLINE | ID: mdl-35010339

RESUMO

(1) Background: In the context of a children friendly city, accessibility and safety are the basic needs of children's pedestrian school travel. This study proposes a comprehensive evaluation method of pedestrian accessibility and safety for children's school travel. (2) Methods: Firstly, the school travel network was constructed by simulating the path of children walking to school. Secondly, from the meso and micro dimensions, the impact factors of pedestrian accessibility and safety were combed out, and an evaluation index system was constructed. Finally, pedestrian accessibility and safety were evaluated based on the Space Syntax analysis and ArcGIS spatial analysis, and the results were superimposed and spatially differentiated. The new evaluation method was tested in the Jintang Road area in Hedong District, Tianjin, China. (3) Results: The pedestrian accessibility and safety of children's school travel road in the study area needed to be improved. It was found that the main impact factors were the effective walking width, the spatial connectivity, the visual integration, the obstruction of pedestrian safety, the completeness of crossing facilities and the influence of traffic flow and put forward optimization strategies. After optimized simulation verification, the overall improvement was achieved. (4) Conclusion: The evaluation method is helpful to calculate the pedestrian accessibility and safety of children's school travel, and help decision makers determine the design and management strategies of child-friendly streets.


Assuntos
Acidentes de Trânsito , Pedestres , Acidentes de Trânsito/prevenção & controle , Humanos , Segurança , Instituições Acadêmicas , Caminhada
16.
Artigo em Inglês | MEDLINE | ID: mdl-34639591

RESUMO

(1) Background: school travel is an important part of a child's daily activities. A comfortable walking environment can encourage children to walk to school. The existing methods of evaluating walking environments are not specific to children's walks to school. (2) Methods: this study proposes a method of evaluating walking comfort in children traveling to school at street scale. Related indexes were selected that reflect children's school travel behavior and their needs in street environments based on walking environment audit tools. Factor analysis was then used to calculate the relative weight of each index. (3) Results: the new evaluation method was tested in the neighborhoods around the First Central Primary School in Hedong District, Tianjin, China. The walking comfort for children's school travel was evaluated in eight indexes: effective street width; street flatness; street cleanliness; interface diversity; buffer; shade coverage; green looking ratio; and sound decibels. Different classes and types of streets were found to have various vulnerabilities. (4) Conclusions: this evaluation method can accurately locate the weak spots in streets to improve the local policymakers' perception of street environments, which can greatly facilitate the implementation of precise measures to promote children walking to school.


Assuntos
Instituições Acadêmicas , Caminhada , Criança , China , Humanos , Características de Residência , Viagem
17.
Magn Reson Med ; 63(5): 1193-200, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20432290

RESUMO

The purpose of this study is (1) to determine the correlation between T(1rho) and T(2) and degenerative grade in intervertebral discs using in vivo 3.0-T MRI, and (2) to determine the association between T(1rho) and T(2) and clinical findings as quantified by the SF-36 Questionnaire and Oswestry Disability Index. Sixteen subjects participated in this study, and each completed SF-36 and Oswestry Disability Index questionnaires. MRI T(1rho) and T(2) mapping was performed to determine T(1rho) (77 discs) and T(2) (44 discs) in the nucleus of the intervertebral disc, and T(2)-weighted images were acquired for Pfirrmann grading of disc degeneration. Pfirrmann grade was correlated with both T(1rho) (r = -0.84; P < 0.01) and T(2) (r = -0.61; P < 0.01). Mixed-effects models demonstrate that only T(1rho) was associated with clinical questionnaires (R(2) (SF-36) = 0.55, R(2) (O.D.I.) = 0.56; P < 0.05). Although the averaged values of T(1rho) and T(2) were significantly correlated, they presented differences in spatial distribution and dynamic range, thus suggesting different sensitivities to tissue composition. This study suggests that T(1rho) may be sensitive to early degenerative changes (corroborating previous studies) and clinical symptoms in intervertebral disc degeneration.


Assuntos
Deslocamento do Disco Intervertebral/diagnóstico , Disco Intervertebral/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Hepatobiliary Pancreat Dis Int ; 9(6): 579-83, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21134825

RESUMO

BACKGROUND: Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive human tumors. At present, surgical resection is the only potentially curative treatment. Early neck division is inadequate when invasion of the superior mesenteric artery (SMA) is suspected or in cases of replaced or accessory right hepatic artery. Malignant periampullary tumors often invade retroperitoneal peripancreatic tissues and a positive resection margin is associated with a poor long-term survival. DATA SOURCES: English-language medical databases, PubMed, ELSEVIER and SPRINGERLINK, were searched for articles on "posterior approach pancreaticoduodenectomy", "superior mesenteric artery first approach", "retroperitoneal tissue", "hanging maneuver", and related topics. RESULTS: The modification allowed the surgeon to early identify the nonresectability of a replaced right hepatic artery if present, enabling complete dissection of the right side of the SMA and portal vein as well as complete excision of the retroportal pancreatic lamina. CONCLUSION: Pancreaticoduodenectomy with early retropancreatic dissection is a useful and safe technical variant, which is indicated for the improvement of the safety and curative effect of the procedure.


Assuntos
Adenocarcinoma/cirurgia , Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adenocarcinoma/mortalidade , Dissecação/métodos , Dissecação/mortalidade , Humanos , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/mortalidade , Procedimentos Cirúrgicos Vasculares/métodos , Procedimentos Cirúrgicos Vasculares/mortalidade
19.
Zhonghua Gan Zang Bing Za Zhi ; 18(1): 32-6, 2010 Jan.
Artigo em Zh | MEDLINE | ID: mdl-20128966

RESUMO

OBJECTIVE: To explore the effects of HBsAg pulsed dendritic vaccination on anti-HBs production in immunosuppressed rats after liver transplantation (LT). METHODS: Brown-Norway liver allografts were transplanted into Lewis recipients. The transplanted Lewis rats were injected with EK506 (2 mg/kg) and randomly divided into two groups: rats in HBsAg-DCs group (n = 15) were intraperitoneally injected with HBsAg pulsed DCs at 14 d and 28 d after LT, and rats in the HBsAg group (n = 15) were injected with HBsAg (200 mul) once a week for 12 weeks. Rats without any immunosuppressive treatment after LT served as controls (n = 5). IL-2 and IFN-gamma mRNA expression in spleen were analyzed by RT-PCR, serum IL-2, IFN-gamma and anti-HBs were detected by ELISA. RESULTS: High dose of FK506 resulted in the immunosuppressed in LT rats, as evident by low production of IL-2 and IFN-gamma, and without liver rejection compared to rats in the control group. HBsAg-DCs induced high titer of anti-HBs antibody, however, titer of anti-HBs were seldom detectable in the HBsAg group at 1, 2 and 3 mouth after vaccination. CONCLUSION: The capacity of HBsAg-DCs to induce anti-HBs in immunosuppressed rats suggested that DC vaccine may prevent HBV recurrence in liver transplanted patients.


Assuntos
Células Dendríticas/imunologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B , Hepatite B/prevenção & controle , Terapia de Imunossupressão , Adjuvantes Imunológicos/farmacologia , Animais , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/sangue , Imunossupressores/administração & dosagem , Transplante de Fígado/imunologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Prevenção Secundária , Baço/imunologia , Baço/metabolismo
20.
Zhonghua Gan Zang Bing Za Zhi ; 18(4): 276-9, 2010 Apr.
Artigo em Zh | MEDLINE | ID: mdl-20460047

RESUMO

OBJECTIVE: To observe the effect of ultrasound microbubble carrying herpes simplex virus thymidine kinase hepatocellular carcinoma in mice. METHODS: Kunming mice were inoculated subcutaneously with H22 tumor cells. 40 male mice bearing subcutaneous hepatoma were randomized into 4 groups: PBS (group A), HSV1-TK (group B), HSV1-TK (group C), and microbubble carrying HSV1-TK (group D) were injected into the tail vein every 3 days. Mice in group C and D were exposed to ultrasound. The expression of TK protein was detected by western blot. Ganciclovir (GCV) was intraperitoneally injected at a dose of 100 mg x kg (-1) x d(-1) in group B, group C and group D. The tumor size was measured every 2 days. RESULTS: TK gene could be injected precisely into hepatocellular carcinoma with ultrasound monitor, and the expression of TK protein was found in all 4 groups. Expression in group D was higher than others (P < 0.05). The rate of tumor growth inhibition were 0 in group A, 3.90%+/-1.80% in group B, 22.70%+/-2.86% in group C, 41.25%+/-3.20% in group D (group B vs group C, P < 0.05; group D vs group C, P < 0.05; group D vs group B, P < 0.05). CONCLUSION: Ultrasound microbubble not only improve target gene therapy, but also enhance transfection efficiency.


Assuntos
Carcinoma Hepatocelular/terapia , Terapia Genética , Neoplasias Hepáticas/terapia , Timidina Quinase/genética , Animais , Linhagem Celular Tumoral , Genes Transgênicos Suicidas , Masculino , Camundongos , Camundongos Endogâmicos , Microbolhas , Simplexvirus/genética , Simplexvirus/metabolismo , Resultado do Tratamento , Ultrassom
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA