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1.
Adv Ther ; 38(2): 1227-1244, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33367985

RESUMO

INTRODUCTION: Biliary tract cancer (BTC) comprises infrequently occurring neoplasms with poor prognoses. Red blood cell-related parameters are commonly reported prognostic factors. We aimed to compare and evaluate the clinical value of red blood cell-related parameters and develop a prognostic nomogram. METHODS: The analysis involved 418 patients with BTC who underwent surgery from December 2003 to April 2017. Patients were divided into training and validation cohorts. Red blood cell-related parameters were compared using Kaplan-Meier analysis, the area under receiver-operating characteristic curve (AUC), and C-index. Predictive abilities were evaluated using Cox regression. We developed a nomogram incorporating superior parameters verified using calibration curves, internal validation, and subgroup analysis. The nomogram was compared with the tumour-node-metastasis staging system through ROC, C-index, and Kaplan-Meier analysis. RESULTS: A combined parameter comprising haemoglobin, albumin, lymphocytes, and platelets (HALP), which was superior to other red blood cell-related parameters, indicated a high risk of worse overall survival when low. Univariate analysis revealed that HALP together with other clinical characteristics was associated with overall survival. Multivariate analysis revealed that HALP, tumour-node-metastasis staging, and operative outcome were independent predictors of poor overall survival. Internal validation proved the predictive value of the nomogram. Additional statistical analyses established the advantages of the nomogram vs. tumour-node-metastasis staging. CONCLUSION: HALP was a superior red blood cell-related parameter and an independent predictor of prognosis. Our nomogram based on HALP, tumour-node-metastasis staging, and operative outcome is a promising model for predicting overall survival.

3.
Acta Neurol Belg ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33156945

RESUMO

Gliosarcoma (GSM) is a rare central nervous system tumor. Clinical management of it is similar to glioblastoma (GBM). However, due to a few comparative studies exist, uncertainty and disagreements remain in the literatures. To assess the available evidence on the value of different treatments and to carry out an up-to-date evaluation to summarize the evidence for the optimal treatment in GSM patients. Free words were used to search for the relevant studies without language limitations in electronic databases including PubMed, Ovid EMBASE, Cochrane Central Register of Controlled Trials from inception to September 15, 2019. Pooled hazard ratio (HR) with 95% confidence interval (CI) were calculated using a random-effects model. The main endpoint was all-cause mortality. Overall, 10 studies published between 2008 and 2018 including 803 patients were selected for the meta-analysis. Temozolomide (TMZ)-dominated chemotherapy was associated with a reduced risk of overall survival (OS), with HR 0.49 (95% CI 0.37-0.66). The pooled HR of OS was 0.40 (95% CI 0.29-0.56) between radiotherapy and without radiotherapy. The pooled HR (0.52, 95% CI 0.32-0.85) indicated gross total resection (GTR) had a positive impact on OS in GSM. In patients with GSM, survival benefits as currently performed are associated with TMZ-dominated chemotherapy and high-dose radiotherapy. Our systematic review and meta-analysis also demonstrate GTR is associated with a reduction in all-cause mortality in patients with primary GSM.

4.
Hepatology ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33169424

RESUMO

We have read with great interest the article published in Hepatology by Jeffrey S. Morris et al(1). The authors carried out a retrospective study including 767 patients with hepatocellular carcinoma (HCC) and 200 healthy individuals as a control group to comprehensively construct a risk score from circulating biomarkers, and predict survival in HCC patients.

5.
Stem Cells Dev ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176606

RESUMO

Appropriate orthopedic force led to bone remodeling of mandibular condyle, while overloaded orthopedic force (OOF) induced condylar bone absorption. Bone absorption is ascribed to the imbalanced activities between osteoclasts and osteoblasts, mechanism of which remains unclear. This study aimed to observe the condylar changes induced by overloaded orthopedic force by mandible advancement appliance and to further investigate the role of mTOR and RANKL/OPG in osteoclastic differentiation of stem cells in vivo and in vitro. In vivo, the results of micro-CT analysis indicated that condylar bone resorption was induced by OOF through mandibular advancement appliance since 2 weeks and worsened time-dependently. Morphologically, cartilage thickness was reduced, subchondral cortical bone line appeared uncontinuous, subchondral bone exhibited irregular-shaped and owned uneven surface. The bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) decreased accomplished with the increased Trabecular separation (Tb.Sp) determined by micro-CT. Additionally, based on immunofluorescent labeling, OOF activated both osteoclasts and osteoblasts, but osteoclastogenesis prevailed over osteogenesis. The mTOR activation and ratio of RANKL/OPG in osteoblasts (OBs) were elevated by OOF. In vitro, the results of Western blot and PCR consistently suggested that the mTOR and RANKL/OPG ratio were upregulated by overloaded mechanical stretch. Pretreatment with mTOR inhibitor, rapamycin, could attenuate the activation of mTOR and the secretion of RANKL in OBs. Interestingly, based on the Trap staining, the supernatant of OBs exposed to OOF could promote osteoclastic differentiation of mesenchymal stem cells (MSCs), while its role was weakened by inhibition of mTOR in OBs. Collectively, OOF induced condylar bone absorption, in the process, osteoclastogenesis was prominent than osteogenesis. The activation of mTOR and secretion of RANKL/OPG was enhanced by OOF and involved in promoting MSCs differentiating into osteoclasts.

7.
World J Gastrointest Oncol ; 12(9): 1014-1030, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33005295

RESUMO

BACKGROUND: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

8.
Shanghai Kou Qiang Yi Xue ; 29(3): 231-236, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33043337

RESUMO

PURPOSE: The aim of this study was to investigate the molecular mechanism of autophagy and apoptosis induced by cyclic mechanical stretch and the potential role of autophagy in stretch-induced apoptosis of myoblasts. METHODS: Loading model of L6 myoblasts was established in vitro. The cells were then subjected to cyclic mechanical stretch involving 3 s of 15% stretch alternating with 3 s of relaxation. The cells were collected after mechanical stretch for 6 h, 12 h and 24 h, respectively. Control cells were cultured on the same plates without mechanical strain. Apoptosis of myoblasts was assessed by Hoechst 33258 staining and Annexin V binding and propidium iodide staining. Autophagy was determined by MDC staining and transmission electron microscopy(TEM). The level of proteins associated with apoptosis and autophagy was detected by Western blot. The data were analyzed with SPSS 17.0 software package. RESULTS: The results of Hoechst 33258 staining and Annexin V binding and propidium iodide staining indicated that mechanical stretch notably induced apoptosis of myoblasts. Caspase inhibitor z-VAD-fmk effectively abrogated apoptosis of myoblasts, indicating mechanical stretch induced caspase-dependent apoptosis. In addition, the results of TEM, MDC staining and Western blot proved that mechanical stretch elicited autophagy of myoblasts. Inhibition of autophagy using 3-MA enhanced caspase-dependent apoptosis induced by mechanical stretch. CONCLUSIONS: Cyclic mechanical stretch induced apoptosis and autophagy of myoblasts time-dependently. Protective autophagy, acting as the compensatory mechanism, inhibited caspase-dependent apoptosis induced by mechanical stretch.


Assuntos
Autofagia , Apoptose , Linhagem Celular , Mioblastos
9.
Artigo em Inglês | MEDLINE | ID: mdl-32876735

RESUMO

Neoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry. Our analysis reveals that patients carried with TP53 neoantigen have a longer overall survival than others (p = 0.0371) and they showed higher Immune score (p = 0.0441), higher cytotoxic lymphocytes infiltration (p = 0.0428), and higher CYT score (p = 0.0388). In contrast, the prognosis is not associated with TMB and neoantigen load. Our study draws a preliminary conclusion that it is not TMB or neoantigen load but the TP53 specific neoantigen is related to overall survival of HCC patients. We suggest that the TP53 neoantigen may affect prognosis by regulating anti-tumor immunity and that the TP53 neoantigen may be harnessed as potential targets for immunotherapies of HCC.

10.
Cancer Res Treat ; 52(4): 1199-1210, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32718144

RESUMO

PURPOSE: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI's optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram's clinical utility. RESULTS: One hundred twenty-four patients were included. The SIRI's optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). CONCLUSION: The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

11.
Infect Genet Evol ; 85: 104419, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32540428

RESUMO

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. Considering that new drug development is a time-consuming process, drug repositioning may facilitate rapid drug discovery dealing with sudden infectious diseases. Here, we compared the differences between the virtual structural proteins of SARS-CoV-2 and SARS-CoV, and selected a pocket mainly localizing in the fusion cores of S2 domain for drug screening. A virtual drug design algorithm screened the Food and Drug Administration-approved drug library of 1234 compounds, and 13 top scored compounds were obtained through manual screening. Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex. Hence, it is worth further exploring eltrombopag as a potential drug for the treatment of SARS-CoV-2 infection.

12.
Mol Med Rep ; 22(1): 317-327, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377749

RESUMO

Facial jaw muscle is involved in the occurrence, development, treatment and maintenance of maxillofacial deformities. The structure and function of this tissue can be altered by changes in external stimuli, and orthodontists can regulate its reconstruction using orthopedic forces. The PI3K/Akt signaling pathway is most well­known for its biological functions in cell proliferation, survival and apoptosis. In the present study, the effects of the PI3K/Akt signaling pathway in cyclic stretch­induced myoblast apoptosis were investigated. For this purpose, L6 rat myoblasts were cultured under mechanical stimulation and treated with the PI3K kinase inhibitor, LY294002, to elucidate the role of the PI3K/Akt signaling pathway. Cells were stained with Hoechst 33258 to visualize morphological changes and apoptosis of myoblasts, and western blotting was performed to detect expression of Akt, phosphorylated (p)­Akt (Ser473), glycogen synthase kinase 3ß (GSK­3ß) and p­GSK­3ß (Ser9). After addition of PI3K inhibitor, the expression of total Akt and GSK­3ß did not significantly differ among groups; however, the levels of p­Akt and p­GSK­3ß were lower in inhibitor­treated groups than in those treated with loading stress alone. In addition, the rate of apoptosis in myoblasts subjected to cyclic stretch increased in a time­dependent manner, peaking at 24 h. Collectively, it was also demonstrated that the PI3K/Akt/GSK­3ß pathway plays an important role in stretch­induced myoblast apoptosis.

13.
Endocrine ; 69(2): 294-302, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32399892

RESUMO

PURPOSE: Indicators to assess early liver damage and disease progression in nonalcoholic fatty liver disease (NAFLD) remain unsatisfactory. Albumin binding function has been reported to be an early indicator of liver damage in hepatitis and liver cirrhosis. However, its role in NAFLD patients is unknown. METHODS: An age/sex-matched, case-control study was performed. Albumin-binding capacity (ABiC) and albumin metal ion binding ability, assessed by ischemia modified albumin (IMA), were measured. Correlation analysis was performed to assess the association of albumin binding function with liver function enzymes and noninvasive liver fibrosis markers. RESULTS: A total of 80 NAFLD patients and 41 healthy controls were included. Albumin binding function was significantly lower in NAFLD (ABiC: 196.00%, p < 0.001; IMA transformed (IMAT): 0.461, p < 0.001; and IMAT/albumin: 0.947 × 10-2, p < 0.001) than controls (ABiC: 211.00%; IMAT: 0.575; and IMAT/albumin: 1.206 × 10-2). Albumin binding function was also found to be significantly different among healthy participants and different severity groups of NAFLD (p < 0.001). Besides, albumin binding function showed positive correlation with BMI (ABiC: r = -0.247, p = 0.011; IMAT: r = -0.243, p = 0.013; IMAT/albumin: r = -0.254, p = 0.009) and FIB-4 index (ABiC: r = 0.230, p = 0.029). The ROC curve suggested that albumin binding function combined with BMI and triglyceride may predict the presence of NAFLD (area under ROC (AUROC) = 0.935, p < 0.001). CONCLUSION: Our findings suggest albumin binding function is a novel biomarker for early liver damage and disease progression in NAFLD.

14.
Arch Virol ; 165(1): 97-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734749

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has spread globally and emerged as an urgent public health threat. Bacteriophages are considered an effective weapon against multidrug-resistant pathogens. In this study, we report a novel lytic phage, kpssk3, which is able to lyse CRKP and degrade exopolysaccharide (EPS). The morphological characteristics of kpssk3 observed by transmission electron microscopy, including a polyhedral head and a short tail, indicate that it belongs to the family Podoviridae. A one-step growth curve revealed that kpssk3 has a latent period of 10 min and a burst size of 200 plaque-forming units (pfu) per cell. kpssk3 was able to lyse 25 out of 27 (92.59%) clinically isolated CRKP strains, and it also exhibited high stability to changes in temperature and pH. kpssk3 has a linear dsDNA genome of 40,539 bp with 52.80% G+C content and 42 putative open reading frames (ORFs). No antibiotic resistance genes, virulence factors, or integrases were identified in the genome. Based on bioinformatic analysis, the tail fiber protein of phage kpssk3 was speculated to possess depolymerase activity towards EPS. By comparative genomics and phylogenetic analysis, it was determined that kpssk3 is a new T7-like virus and belongs to the subfamily Autographivirinae. The characterization and genomic analysis of kpssk3 will promote our understanding of phage biology and diversity and provide a potential strategy for controlling CRKP infection.


Assuntos
Farmacorresistência Bacteriana , Klebsiella pneumoniae/virologia , Podoviridae/classificação , Sequenciamento Completo do Genoma/métodos , Composição de Bases , Carbapenêmicos , Genoma Viral , Concentração de Íons de Hidrogênio , Lisogenia , Microscopia Eletrônica de Transmissão , Filogenia , Podoviridae/genética , Podoviridae/fisiologia , Termodinâmica , Proteínas da Cauda Viral/genética
15.
Ann Transl Med ; 7(20): 578, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807559

RESUMO

Magnesium is a vital cation that takes part in many cellular processes. Magnesium balance can be disturbed in multiple conditions, and differences in magnesium concentration can be responsible for numerous physiological and pathological processes. Magnesium deficiency is commonly associated with liver diseases, and may result from low nutrient uptake, greater urinary secretion, low serum albumin concentration, or hormone inactivation. In turn, low magnesium content in serum and liver tissue can lead to the progression of these diseases, due to a disruption in mitochondrial function, defective protein kinase C (PKC) translocation, inflammatory responses, oxidative stress, or metabolic disorders. Furthermore, magnesium supplementation can improve liver function in certain liver diseases. This paper comprehensively reviews the changes in magnesium concentrations associated with liver cirrhosis, alcoholic liver disease (ALD), liver cancer, and viral hepatitis, and explains how such changes may in turn impact these disease processes.

16.
BMC Neurol ; 19(1): 266, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684908

RESUMO

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.


Assuntos
Doenças do Sistema Nervoso Central , Inflamação , Linfoma de Células T Periférico , Adulto , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Esteroides/uso terapêutico
17.
Ann Med ; 51(7-8): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714153

RESUMO

Albumin is the most abundant plasma protein and albumin infusion is commonly used. Conventionally, the biologic and therapeutic effects of albumin have been thought to be due to its oncotic properties. However, albumin has a variety of biologic functions, including molecular transport, anti-oxidation, anti-inflammation, endothelial stabilisation, anti-thrombotic effects, and the adjustment of capillary permeability. Despite this, the functions of albumin have not been thoroughly investigated. Recent studies have shown non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, and liver failure to be associated with impairments in albumin function, which are associated with impairments in liver function and disease prognosis. Post-translational modifications of albumin cause structural modifications that affect protein function. Recently, the concentration of albumin associated with normal function, the 'efficient albumin concentration', has been attracting more interest. In addition, although many biologic markers, including albumin concentration, are widely used for the assessment of early liver dysfunction in patients with liver diseases, the predictive values are unsatisfactory. However, clinical evidence has suggested that albumin function may represent a novel biomarker of early impairment in liver function. In this review, we summarise the factors affecting albumin function and discuss the clinical significance of impairments in albumin function in various liver diseases.Key messagesThe importance of albumin depends not only on its concentration, but also on its various physiological functions.Impaired albumin function has been reported in a variety of liver diseases, and is associated with disease severity and prognosis, thereby proposing the concept of 'effective albumin concentration'.Albumin dysfunction occurs earlier than other conventional indicators, and albumin dysfunction may be a new biomarker of early impairment in liver function.Many exogenous and endogenous factors lead to post-translational modifications of albumin, which alters the three-dimensional structure of albumin, resulting in a decrease in its biological activity.


Assuntos
Hepatopatias/sangue , Albumina Sérica Humana/fisiologia , Humanos , Testes de Função Hepática
18.
Shanghai Kou Qiang Yi Xue ; 28(3): 259-263, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489412

RESUMO

PURPOSE: This study was aimed to figure out the way that cyclic-stretch influenced the apoptosis of myoblasts and evaluate the importance of PERK and its possible mechanism involved. METHODS: L6 rat myoblasts were cultured in vitro and mechanical stimulation model was constructed successfully. The myoblasts were imposed tension for 0, 2, 6, 12 and 24 hours respectively by multi-channel cell stress loading system. The force value was 15% cell deformation and the frequency was 10 cycles/min. Each cycle was consisted of stretch for 3 seconds and relaxation for 3 seconds, and the group without tension was used as the control group. The apoptotic myoblasts were dyed by DAPI and observed through fluorescence microscopy to detect the apoptosis rate; the mRNA levels of PERK and CHOP in different groups were detected by real-time PCR and protein levels of PERK and p-PERK in different groups were detected by Western blot. PERK inhibitor was used to clear the role of PERK in apoptosis induced by cyclic-stretch and clarify the relationship between the endoplasmic reticulum stress and apoptosis induced by cyclic-stretch. SPSS 17.0 software package was used to analyze the data statistically. RESULTS: DAPI nuclear stain showed that cyclical tensile stress can induce apoptosis in vitro cultured myoblast. Apoptosis rate showed a trend of rising gradually over time, peaked at 24 h. After dealt with the inhibitor of PERK, the apoptosis rate of the 24 h group under the cyclic stretch showed no difference compared with the control. The results of real- time PCR showed that the mRNA of CHOP was increased with the extension loading time, while the mRNA of PERK showed no difference compared with the control. Western blot results showed that the protein level of p-PERK was increased with the extension of loading time, while the expression of PERK showed no difference compared with the control group. When PERK inhibitor added, the mRNA level of CHOP along with the protein expression level of p-PERK showed no significant difference compared to the control. CONCLUSIONS: PERK signaling pathway is involved in the apoptosis of myoblasts induced by cyclic stretch, and the possible mechanism may be closely related to the phosphorylation of PERK.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Mioblastos , eIF-2 Quinase , Animais , Estresse do Retículo Endoplasmático/fisiologia , Ratos , Transdução de Sinais , eIF-2 Quinase/metabolismo
19.
J Clin Neurosci ; 66: 156-164, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31088767

RESUMO

BACKGROUND: We studied patients with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with or without lymphoma and measured risk factors suggestive of an underlying lymphoma and follow-up outcomes. METHODS: CLIPPERS patients associated with or without lymphoma were included into this study. Clinical presentations were documented, risk factors suggestive of an underlying lymphoma were tested, and prognostic differences in terms of death were compared. RESULTS: Ten patients had a diagnosis of CLIPPERS associated with lymphoma, with 6 B-cell non-Hodgkin lymphoma, 2 T-cell non-Hodgkin lymphoma and 2 Hodgkin lymphoma. Using multivariate logistic analysis, the following 3 independent risk factors were found to be related to a final diagnosis of lymphoma: hyperreflexia (HR 16.56; 95% CI 1.03-265.29; p = 0.032), elevated protein in CSF (HR 11.59; 95% CI 1.24-108.39; p = 0.047), and recurrences between 2 months and 1 year after treatment (HR 29.27; 95% CI 2.09-409.58; p = 0.012). The model calibration was satisfactory (p = 0.392 with the Hosmer-Lemeshow test), and the discrimination power was good (area under the receiver operating characteristic curve 0.921; p < 0.001, 95% CI 0.826-1.000). Patients with CLIPPERS associated with lymphoma had higher mortality rate and lymphoma was a significant predictor of total mortality (HR 0.040; 95% CI 0.006-0.262; p = 0.001). CONCLUSIONS: Hyperreflexia, elevated protein in CSF and recurrences between 2 months and 1 year after treatment are risk factors suggesting an underlying lymphoma. Relapses during high-dose steroids maintenance therapy can be indicative of lymphoma, too. Patients having CLIPPERS associated with lymphoma have a worse prognosis than those without lymphoma.


Assuntos
Encefalopatias/diagnóstico , Linfoma/diagnóstico , Ponte/patologia , Adulto , Encefalopatias/tratamento farmacológico , Encefalopatias/etiologia , Feminino , Humanos , Inflamação , Linfoma/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ponte/diagnóstico por imagem , Esteroides/uso terapêutico
20.
Medicine (Baltimore) ; 98(4): e14201, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30681592

RESUMO

RATIONALE: Concomitant cryoglobulinemic vasculitis and cold agglutinin disease (CAD) is an extremely uncommon clinical scenario. The role of bortezomib in the treatment of cryoglobulinemic vasculitis needs further investigation. PATIENT CONCERNS: A 72-year-old Chinese woman presented with a 25-year history of cyanosis of the extremities after cold exposure, which worsened and was accompanied with purpuric skin lesions and proteinuria in recent years. Laboratory data demonstrated hemolysis. Cold agglutinin and cryoglobulin tests were positive. There was no evidence for malignancies after blood, image, and pathologic tests. DIAGNOSES: Concomitant cryoglobulinemic vasculitis and CAD. INTERVENTIONS: The patient was treated with bortezomib-based regimen, including bortezomib, cyclophosphamide, and dexamethasone. OUTCOMES: The patient responded well to the treatment. Both symptoms and laboratory tests significantly improved. The patient's condition was in a state of sustained remission in the 6-month follow-up. LESSONS: This rare case promotes further understanding of these 2 diseases and suggests that bortezomib is a promising treatment in type I cryoglobulinemic vasculitis.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Bortezomib/uso terapêutico , Crioglobulinemia/tratamento farmacológico , Vasculite/tratamento farmacológico , Idoso , Anemia Hemolítica Autoimune/complicações , Crioglobulinemia/complicações , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Resultado do Tratamento , Vasculite/complicações
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