Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
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.

2.
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.

3.
Arch Virol ; 2019 Nov 16.
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.

4.
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.

5.
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
6.
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
7.
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
9.
Front Immunol ; 9: 240, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29483920

RESUMO

Dendritic epidermal T cells (DETCs) and dermal Vγ4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between Vγ4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that Vγ4 T cell-derived IL-17A inhibited IGF-1 production by DETCs to delay skin wound healing. Epidermal IL-1ß and IL-23 were required for Vγ4 T cells to suppress IGF-1 production by DETCs after skin injury. Moreover, we clarified that IL-1ß rather than IL-23 played a more important role in inhibiting IGF-1 production by DETCs in an NF-κB-dependent manner. Together, these findings suggested a mechanistic link between Vγ4 T cell-derived IL-17A, epidermal IL-1ß/IL-23, DETC-derived IGF-1, and wound-healing responses in the skin.


Assuntos
Interleucina-17/imunologia , Células de Langerhans/imunologia , Pele/lesões , Linfócitos T/imunologia , Cicatrização/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/imunologia , Humanos , Fator de Crescimento Insulin-Like I/imunologia , Fator de Crescimento Insulin-Like I/metabolismo , Interferon gama/genética , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Queratinócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Cultura Primária de Células , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Pele/citologia , Pele/imunologia , Linfócitos T/metabolismo
10.
J Tissue Eng Regen Med ; 12(2): e905-e917, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28097806

RESUMO

A porous structure is critically important for wound dressing or tissue engineering scaffolds. However, the influence of the pore sizes on cell proliferation, tissue regeneration and the underlying mechanism remains unclear. In this study, silicone rubber membranes with different pore sizes were prepared using certain constituents of liquid silicone rubber precursor/liquid paraffin/hexane based on our previous studies. It was found that pore size had a significant impact on cell proliferation and wound healing. The CCK8 analysis revealed that the membrane with a certain pore size (110.47 µm, middle pore membrane, MPM) was suitable for cell proliferation compared with the membranes with other pore sizes (218.03 µm, large pore membrane, LPM; 5.27 µm, small pore membrane, SPM; non-porous membrane, NPM). Further studies demonstrated that the MPM promoted cell proliferation via activating the Wnt/ß-catenin signalling pathway. More importantly, wound healing experiments showed that 7 days post-wounding, the rate of wound healing was 89.25% with the MPM, which was significantly higher than with LPM, SPM or NPM. The in vivo data indicated that wound healing was accelerated by treatment with a silicone rubber membrane with a pore size of 110.47 µm. Our results strongly suggest that different pore structures might affect cell proliferation and wound healing and that a silicone rubber membrane with a specific pore size could potentially be used as a promising wound dressing. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Membranas Artificiais , Regeneração/efeitos dos fármacos , Elastômeros de Silicone/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Camundongos Endogâmicos BALB C , Porosidade , Antígeno Nuclear de Célula em Proliferação/metabolismo , Reepitelização/efeitos dos fármacos , Reepitelização/genética , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética , beta Catenina/metabolismo
11.
Front Immunol ; 8: 1557, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225596

RESUMO

Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL-15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and IGF-1 were positively correlated in wounded epidermis. Together, our data indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic wound repair, suggesting IL-15 as a potential therapeutic agent for managing diabetic wound healing.

12.
J Invest Dermatol ; 137(12): 2513-2522, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28733202

RESUMO

Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1ß and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αß T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A.


Assuntos
Rejeição de Enxerto/imunologia , Interleucina-17/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Transplante de Pele , Animais , Quimiocina CCL20/metabolismo , Quimiocinas/metabolismo , Feminino , Interleucina-23/metabolismo , Ligantes , Linfonodos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores CCR6/metabolismo , Pele/imunologia , Pele/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
13.
Cell Physiol Biochem ; 42(5): 1755-1768, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28746918

RESUMO

Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism. METHODS: C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis. RESULTS: This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. CONCLUSION: This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-15/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Epidérmicas , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/patologia , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/genética , Interleucina-15/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Cicatrização/efeitos dos fármacos
14.
Sci Rep ; 7(1): 6028, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28729536

RESUMO

Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis. Moreover, IGF-1 drives keratinocytes to produce IL-15. The activation of IL-15 is dependent on mTOR, and conversely, mTOR regulates IGF-1 production in DETC, in a classic feedback regulatory loop. Our data suggest that in the setting of diabetes, reduced IGF-1, impaired mTOR pathway activation and reduced IL-15 in the epidermis function coordinately to promote altered DETC homeostasis and delayed skin wound closure.


Assuntos
Células Epidérmicas/metabolismo , Homeostase , Interleucina-15/biossíntese , Subpopulações de Linfócitos T/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Biomarcadores , Diabetes Mellitus Experimental , Células Epidérmicas/imunologia , Imunofenotipagem , Fator de Crescimento Insulin-Like I/metabolismo , Queratinócitos/metabolismo , Camundongos , Modelos Biológicos , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Cicatrização
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA