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2.
Cell Prolif ; 56(11): e13493, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37128180

RESUMO

Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+ ) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p-PI3K, AKT1, p-AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.


Assuntos
Cicatriz Hipertrófica , Humanos , Ratos , Animais , Cicatriz Hipertrófica/metabolismo , Hiperplasia/metabolismo , Cálcio/metabolismo , Cicatrização , Movimento Celular , Fibroblastos/metabolismo , Proliferação de Células , Fosfatidilinositol 3-Quinases/metabolismo
3.
Immunology ; 167(2): 233-246, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35753028

RESUMO

Intestinal intraepithelial lymphocytes (IELs) play a crucial role in host defence against pathogens in the intestinal mucosa. The development of intestinal IELs is distinct from peripheral T lymphocytes and remains elusive. Fas-associated protein with death domain (FADD) is important for T cell development in the thymus. Here we describe a novel function of FADD in the IEL development. FADD (S191A), a mouse FADD mutant at Ser191 to Ala mimicking constitutively unphosphorylated FADD, promoted a rapid expansion of TCRαß+ IELs, not TCRγδ+ IELs. Mechanism investigation indicated that the dephosphorylation of FADD was required for cell activation mainly in TCRαß+ CD8+ T cells. Consistently, FADD (S191A) as dephosphorylated FADD led to a high NF-κB activation in the TCR-dependent cell expansion. In addition, The FADD (S191A)-induced abnormal IEL populations resulted in the increased incidence and severity of colitis in mice. In summary, FADD signalling is involved in the intestinal IEL development and might be a regulator for intestinal mucosal homeostasis.


Assuntos
Linfócitos Intraepiteliais , Receptores de Antígenos de Linfócitos T alfa-beta , Animais , Linfócitos T CD8-Positivos/metabolismo , Proteína de Domínio de Morte Associada a Fas/genética , Proteína de Domínio de Morte Associada a Fas/metabolismo , Mucosa Intestinal/metabolismo , Linfócitos Intraepiteliais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo
4.
Burns ; 48(4): 872-879, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34456097

RESUMO

BACKGROUND: Although treatment of burn patients has significantly improved in recent decades, major burns remain fatal. Therefore, the evaluation of the death risk of the patients with extensive burns is very important. The ratio between the serum levels of aspartate transaminase and alanine transaminase (De Ritis ratio) was an independent predictor of poor outcomes in patients with acute ischemic stroke, cardiac surgery, non-metastatic renal cell carcinoma, and upper urinary tract urothelial carcinoma. Our aim was to determine whether the ratio between the serum levels of AST and ALT (De Ritis ratio) was useful to assess prognosis in extensively burned patients. METHODS: We conducted a single-center cohort study at the Burns Department of Changhai Hospital. This retrospective observational analysis was performed based on the clinical data of major burn patients admitted between May 1, 2005 and April 30, 2018. Univariate and multivariate logistic regression analyses were performed on variables such as age, sex, total body surface area (TBSA), De Ritis ratio, and serum albumin level, which may affect mortality in major burn patients. We assessed their diagnostic value and found the cut-off value by receiver operative characteristic (ROC) curve analysis. We used the Kaplan-Meier curve to display the impact of the De Ritis ratio and serum albumin level on survival in burn patients. RESULTS: A total of 351 patients with extensive burns were included in the study. The cohort predominantly consisted of males (74.64%), and most of the patients (78.35%) had been burned by a flame. Age, TBSA, inhalation, and the De Ritis ratio were found to be independent risk factors for the 30-days mortality of major burn patients, while age, TBSA, inhalation, and the De Ritis ratio were independent risk factors for 90-day mortality. Further, the De Ritis ratio was a better mortality predictor than serum albumin in severely burned patients, whose area under ROC for 30-day and 90-day mortality was 0.771 (95% confidence intervals [CI], 0.708-0.835) and 0.750 (95% CI, 0.683, 0.818). CONCLUSIONS: The De Ritis ratio was useful as a prognostic indicator for major burn patients, which can be conveniently obtained through blood examination. Regardless of whether the prediction was for 30-day or 90-day mortality, the accuracy remained high. Moreover, compared to serum albumin level, the De Ritis ratio was superior in assessing the prognosis of extensively burned patients.


Assuntos
Queimaduras , Carcinoma de Células de Transição , AVC Isquêmico , Neoplasias da Bexiga Urinária , Alanina Transaminase , Aspartato Aminotransferases , Queimaduras/complicações , Estudos de Coortes , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Albumina Sérica , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
5.
Front Med (Lausanne) ; 8: 709642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869410

RESUMO

Objective: We conducted a systematic review and meta-analysis to comprehensively estimate the incidence and mortality of acute respiratory distress syndrome (ARDS) in overall and subgroups of patients with burns. Data sources: Pubmed, Embase, the Cochrane Library, CINAHL databases, and China National Knowledge Infrastructure database were searched until September 1, 2021. Study selection: Articles that report study data on incidence or mortality of ARDS in patients with burns were selected. Data extraction: Two researchers independently screened the literature, extracted data, and assessed the quality. We performed a meta-analysis of the incidence and mortality of ARDS in patients with burns using a random effects model, which made subgroup analysis according to the study type, inclusion (mechanical ventilation, minimal burn surface), definitions of ARDS, geographic location, mean age, burn severity, and inhalation injury. Primary outcomes were the incidence and mortality of burns patients with ARDS, and secondary outcomes were incidence for different subgroups. Data synthesis: Pooled weighted estimate of the incidence and mortality of ARDS in patients with burns was 0.24 [95% confidence interval (CI)0.2-0.28] and 0.31 [95% CI 0.18-0.44]. Incidences of ARDS were obviously higher in patients on mechanical ventilation (incidence = 0.37), diagnosed by Berlin definition (incidence = 0.35), and with over 50% inhalation injury proportion (incidence = 0.41) than in overall patients with burns. Patients with burns who came from western countries and with inhalation injury have a significantly higher incidence of ARDS compared with those who came from Asian/African countries (0.28 vs. 0.25) and without inhalation injury (0.41 vs. 0.24). Conclusion: This systematic review and meta-analysis revealed that the incidence of ARDS in patients with burns is 24% and that mortality is as high as 31%. The incidence rates are related to mechanical ventilation, location, and inhalation injury. The patients with burns from western countries and with inhalation injury have a significantly higher incidence than patients from Asian/African countries and without inhalation injury. Systematic Review Registration: identifier: CRD42021144888.

6.
Cancer Lett ; 519: 237-249, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34324862

RESUMO

Melanoma is a highly metastatic cancer that requires effective and targeted curative therapy. Annexin A10 (ANXA10), a member of the annexin family, is a calcium- and phospholipid-binding protein. Considerable evidence indicates that ANXA10 is involved in tumour progression, but little is known about its role in melanoma development. In this study, we find that ANXA10 expression is significantly upregulated, and correlates with melanoma progression. ANXA10 knockout profoundly reduces cell migration and the metastatic activity of melanoma. In addition, ANXA10 knockout induces the N- to E-cadherin switch by upregulating SMAD6, an inhibitory SMAD in the TGF-ß/SMAD pathway. The negative regulation of SMAD6 by ANXA10 is dependent on PKD1. ANXA10 interacts with PKD1 and inhibits E3 ligase TRIM41-targeted PKD1 degradation. In B16F10 melanoma cells, protein levels of ANXA10 and PKD1 are inversely correlated with SMAD6 level, but correlated with cell migration. Interestingly, ANXA10 and SMAD6 levels are inversely correlated in clinical samples of melanoma progression. Our findings suggest that the ANXA10-PKD1-SMAD6 axis is a new target for therapeutic strategies against melanoma metastasis.


Assuntos
Anexinas/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Canais de Cátion TRPP/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Caderinas/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Células HEK293 , Células HaCaT , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologia
7.
Signal Transduct Target Ther ; 6(1): 235, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34131110

RESUMO

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder for many people associated with poor health. Although there are some clinical drugs for IBD treatment, the development of effective therapeutics on IBD patients has always been necessary. Here, we show that externalized phosphatidylserine (PS) is observed on the surface of colonic capillaries. Annexin A5 (ANXA5) with high affinity for PS has a good targeting to the colon and effectively alleviates experimental colitis. In contrast, ANXA5 mutant (A5m) lacking the PS-binding ability, has no accumulation in the colon and no therapeutic effects on colitis. Mechanistic investigations indicate that ANXA5 reduces the inflammatory cell infiltration by inhibiting endothelial cell activation dependent on PS-binding ability. With the increasing of PS exposure on activated HUVECs (human umbilical vein endothelial cells), ANXA5 binding induces the internalization of TLR4 via PS-dependent endocytosis. We provide new insights on the molecular mechanism of ANXA5 for its anti-inflammatory effect. Our data suggest that PS-externalization is a potential target of ANXA5 aiming at targeted drug delivery (TDD) for IBD treatment.


Assuntos
Capilares/metabolismo , Colo/irrigação sanguínea , Colo/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Fosfatidilserinas/metabolismo , Animais , Anexina A5/metabolismo , Capilares/patologia , Colo/patologia , Feminino , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/terapia , Camundongos , Camundongos Endogâmicos BALB C
8.
Zhonghua Shao Shang Za Zhi ; 37: 1-10, 2021 Mar 24.
Artigo em Chinês | MEDLINE | ID: mdl-33874705

RESUMO

Objective: To explore the epidemiological characteristics and treatment outcomes of inhalation injury patients combined with burn area less than 30% total body surface area (TBSA) admitted to the First Affiliated Hospital of Naval Medical University. Methods: Retrospective observational study with performed on medical records of 266 inhalation injury patients combined with burn area less than 30% TBSA who were admitted to the First Affiliated Hospital of Naval Medical University from January 2008 to September 2016 and met the inclusion criteria. The gender, age, injured site, injurious factors of inhalation injury, degree of inhalation injury, combined total burn area, way of tracheotomy, time of tracheotomy, whether conducted mechanical ventilation or not, whether in intensive care unit (ICU) or not, microbial culture results of bronchoalveolar lavage, total hospitalization days, ICU days, mechanical ventilation days, and whether respiratory infections occurred or not. Single factor and multivariate linear regression analysis was used to screen out the risk factors impacting the total hospitalization days, ICU days, and mechanical ventilation days of patients. Single factor and multivariate logistic regression analysis was used to screen out the risk factors impacting respiratory infections of patients. Results: The 266 patients included 190 males and 76 females, with the majority age of above and equal to 21 and below 65 years (217 patients). Confined space was the major injured site. Hot air was the major factor of inhalation injury. Mild and moderate inhalation injuries were commonly seen in patients. The combined total burn area was 9.00 (3.25, 18.00) %TBSA. In 111 patients who were conducted with tracheotomy, the most were conducted before admitted to the First Affiliated Hospital of Naval Medical University. The total hospitalization days of patients were 27 (10, 55) days. The ICU days of 160 patients were 15.5 (6.0, 40.0) days. The mechanical ventilation days of 109 patients were 6.0 (1.3, 11.5) days. A total of 119 patients were diagnosed with respiratory infections, with 548 strains including 35 types of pathogens were isolated, mainly of Gram-negative bacteria. Single factor linear regression analysis showed age, injurious factors of inhalation injury, combined total burn area, degree of inhalation injury, way of tracheotomy, whether conducted mechanical ventilation or not, and whether respiratory infections occurred or not were the risk factors impacting the total hospitalization days of patients (95% confidence interval (CI)=-0.397-0.001, -0.395--0.053, 0.015-0.028, 0.009-0.263, 0.008-0.319, -0.419--0.176, 0.242-0.471, 0.340-0.555, P<0.1). Multivariate linear regression analysis showed smoke inhalation, mechanical ventilation, and respiratory infections were the independent risk factors impacting the total hospitalization days of patients (95% CI=-0.384-0.082, 0.022-0.271, 0.261-0.506, P<0.05 or P<0.01). Single factor linear regression analysis showed injurious factors of inhalation injury, combined total burn area, degree of inhalation injury, way of tracheotomy, whether conducted mechanical ventilation or not, and whether respiratory infections occurred or not were the risk factors impacting the ICU days of patients (95% CI=0.053-0.502, 0.006-0.010, -0.018-0.457, -0.022-0.428, -0.575--0.241, -0.687--0.018, 0.132-0.486, 0.369-0.678, P<0.1). Multivariate linear regression analysis showed that no tracheotomy and respiratory infections were the independent risk factors impacting the ICU days of patients (95% CI=-0.414--0.084, 0.278-0.601, P<0.01). Single factor linear regression analysis showed injured site, injurious factors of inhalation injury, combined total burn area, degree of inhalation injury, way of tracheotomy, and whether respiratory infections occurred or not were the risk factors impacting mechanical ventilation days of patients (95% CI=-0.565--0.034, 0.145-0.946, 0.051-1.188, 0.001-0.009, 0.127-0.847, 0.436-1.162, -1.243--0.229, 0.005-0.605, P<0.1). Multivariate linear regression analysis showed open space inhalation, smoke inhalation, severe inhalation injury, no tracheotomy, prophylactic tracheotomy, and respiratory infections were the independent risk factors impacting mechanical ventilation days of patients (95% CI=-0.588--0.127, 0.138-0.560, 0.143-0.848, -0.909--0.330, -1.008--0.015, 0.007-0.519, P<0.05 or P<0.01). Single factor logistic regression analysis showed age, injured site, degree of inhalation injury, combined total burn area, way of tracheotomy, and whether conducted mechanical ventilation or not were the risk factors impacting respiratory infections of patients (95% CI=0.840-1.362, 0.641-1.044, 1.122-1.526, 1.028-1.661, 1.344-2.405, 1.460-2.612, 0.744-1.320, 0.241-0.424, 2.331-4.090, P<0.1). Multivariate logistic regression analysis showed prophylactic tracheotomy, no tracheotomy, and mechanical ventilation were the independent risk factors impacting respiratory infections of patient (95% CI=0.430-0.641, 0.290-0.511, 2.152-8.624, P<0.05 or P<0.01). Conclusions: The inhalation injury patients combined with burn area less than 30% TBSA are mainly young and middle-aged males. Confined space, smoke inhalation, mechanical ventilation, respiratory infection, and way of tracheotomy are influencing factors of the outcomes in hospital of inhalation injury patients combined with burn area less than 30% TBSA. Additionally, prophylactic tracheotomy shows its potential role in avoiding respiratory infection for patients with moderate or severe degree of inhalation injury.

9.
Respir Care ; 66(6): 1029-1038, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33774597

RESUMO

BACKGROUND: Until now, transfusion-related acute lung injury (TRALI) has been considered the leading cause of blood transfusion-related diseases and death. In addition, there is no clinically effective treatment plan for TRALI. The aim of this study was to systematically summarize the literature on risk factors for TRALI in critical patients. METHODS: Electronic searches (up to March 2020) were performed in the Cochrane Library, Web of Knowledge, Embase, and PubMed databases. We included studies reporting on the risk factors of TRALI for critical patients and extracted risk factors. A total of 13 studies met the inclusion criteria. RESULTS: We summarized and analyzed the potential risk factors of TRALI for critical patients in 13 existing studies. Host-related factors were age (odds ratio [OR] 1.16 [95% CI 1.08-1.24]), female sex (OR 1.26 [95% CI 1.16-1.38]), tobacco use status (OR 3.82 [95% CI 1.91-7.65]), chronic alcohol abuse (OR 3.82 [95% CI 2.97-26.83]), positive fluid balance (OR 1.24 [95% CI 1.08-1.42]), shock before transfusion (OR 4.41 [95% CI 2.38-8.20]), and American Society of Anesthesiologists (ASA) score of the recipients (OR 2.72 [95% CI 1.43-5.16]). The transfusion-related factors were the number of transfusions (OR 1.40 [95% CI 1.14-1.72]) and units of fresh frozen plasma (OR 1.21 [95% CI 1.01-1.46]). The device-related factor was mechanical ventilation (OR 4.13 [95% CI 2.20-7.76]). CONCLUSIONS: The risk factors that were positively correlated with TRALI in this study included number of transfusions and units of fresh frozen plasma. Age, female sex, tobacco use, chronic alcohol abuse, positive fluid balance, shock before transfusion, ASA score, and mechanical ventilation may be potential risk factors for TRALI. Our results suggest that host-related risk factors may play a more important role in the occurrence and development of TRALI than risk factors related to blood transfusions.


Assuntos
Lesão Pulmonar Aguda , Lesão Pulmonar Aguda Relacionada à Transfusão , Lesão Pulmonar Aguda/epidemiologia , Lesão Pulmonar Aguda/etiologia , Feminino , Humanos , Respiração Artificial/efeitos adversos , Fatores de Risco
10.
Burns ; 47(3): 594-600, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32893051

RESUMO

BACKGROUND: Extensive burns is one of the most common severe injuries, with a high annual death rate. Previous studies showed that the neutrophil to lymphocyte ratio (NLR) is a prognostic factor for some inflammatory diseases. However, until now, no study has evaluated the clinical prognostic value of NLR in extensively burned patients. The aim of this study was to investigate the prognostic value of NLR in this medical condition to provide clinical guidance. METHODS: 271 patients diagnosed with extensive burns were analysed retrospectively between 2005 and 2018 in the Department of Burn Surgery of Changhai Hospital. NLR cut-off values at the first 3 days of hospitalization were calculated by the ROC analysis. RESULTS: Of the 271 patients in this study, the majority (82.3%) were injured by flame. The median total body surface area (TBSA) was 55% (IQR, 40% to 85%) and the median full thickness burn (FTB) was 20% (IQR, 3%-44%). The patients' NLR declined within the first 3 days after admission, and we found that NLR was negatively correlated with the ventilator-free days at day 28 (r = -0.127, P = 0.048). In a multivariate logistic regression analysis, higher admission NLR was independently predictive of higher mortality. According to the ROC curve, the best cut-off values for day 1 (or admission day), day 2 and day 3 NLR were 14, 13 and 7.5, respectively. We then performed a survival analysis, finding that those NLR above the cut-off point had decreased overall survival compared to those with NLR below the cut-off point (p = 0.023, 0.045 and 0.019 for day 1, 2, and 3, respectively). CONCLUSIONS: NLR continuously decreased in the first 3 days of hospitalization. Admission NLR above 14 is associated with a decreased survival in patients with extensive burns. These findings demonstrate that NLR has prognostic value in these patients.


Assuntos
Queimaduras/mortalidade , Linfócitos/classificação , Neutrófilos/classificação , Análise de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Queimaduras/complicações , Queimaduras/cirurgia , China , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estatísticas não Paramétricas
11.
Immunobiology ; 225(5): 152007, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32962825

RESUMO

The soluble form of the migration inhibitory factor receptor cluster of differentiation 74 (sCD74) has previously been shown to be elevated during the development of acute lung injury (ALI) in mice. However, the biological role of increased sCD74 in ALI remans poorly understood. Synthesized recombinant sCD74 protein was administered to mice intratracheally. Pro-inflammatory genes in lung tissue and the inflammatory factors in bronchoalveolar lavage fluid (BALF) were analyzed using RT-PCR and ELISA, respectively. Additionally, RAW264.7, A549, and human umbilical vein endothelial cells (HUVEC) were treated with sCD74, and the resulting pro-inflammatory factor protein and gene expression levels were analyzed in the supernatants and cell lysates. Meanwhile, the level of nuclear factor (NF)-κB components in cell lysates after stimulating macrophages with sCD74 was also assessed. After administration of 0.5 mg/kg body weight sCD74 to mice, the expression of Tnfa, Mip2, and Il6 increased in lung tissues after 2 h by 2.1-, 3.4-, and 2.8-fold, respectively. Moreover, the BALF concentrations of TNF-α and MIP-2 reached maximal levels of 560 and 107 pg/mL at 8 h compared to those in the saline group, respectively. Similarly, TNFA, MIP2, and IL6 expression increased by 4.0-, 11.8-, and 2.6-fold, respectively, 2 h after stimulating macrophages with 1000 ng/mL sCD74. The levels of phospho-IκB and phospho-p65 were also significantly increased in the cytoplasm and nucleus of macrophages following sCD74 stimulation. Taken together, these results suggest that sCD74 is a critical cellular factor involved in the lung acute inflammatory response through nuclear factor-κB signaling.


Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Pulmão/imunologia , NF-kappa B/imunologia , Células A549 , Animais , Antígenos de Diferenciação de Linfócitos B/genética , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Transdução de Sinais
12.
J Biol Chem ; 295(41): 14214-14221, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32796034

RESUMO

T-cell activation is a critical part of the adaptive immune system, enabling responses to foreign cells and external stimulus. In this process, T-cell antigen receptor (TCR) activation stimulates translocation of the downstream kinase PKCθ to the membrane, leading to NF-κB activation and thus transcription of relevant genes. However, the details of how PKCθ is recruited to the membrane remain enigmatic. It is known that annexin A5 (ANXA5), a calcium-dependent membrane-binding protein, has been reported to mediate PKCδ activation by interaction with PKCδ, a homologue of PKCθ, which implicates a potential role of ANXA5 involved in PKCθ signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKCθ to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKCθ upon TCR engagement and blocked the recruitment of CARMA1-BCL10-MALT1 signalosome, which provides a platform for the catalytic activation of IKKs and subsequent activation of canonical NF-κB signaling in activated T cells. As a result, NF-κB activation was impaired in ANXA5-KO T cells. T-cell activation was also suppressed by ANAX5 knockdown in primary T cells. These results demonstrated a novel role of ANXA5 in PKC translocation and PKC signaling during T-cell activation.


Assuntos
Anexina A5/imunologia , Ativação Linfocitária , Proteína Quinase C-theta/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Animais , Anexina A5/genética , Humanos , Células Jurkat , Camundongos , Proteína Quinase C-theta/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia
13.
Exp Ther Med ; 20(1): 227-234, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32509009

RESUMO

Acute lung injury (ALI) and respiratory distress syndrome are common, potentially lethal injuries that predominantly occur following chest trauma. Circular RNAs (circRNAs) are stable conserved non-coding RNAs that are widely expressed in different organs. To the best of our knowledge, no previous studies have shown whether circRNAs are involved in traumatic lung injury (TLI). The aim of the present study was to identify highly expressed circRNAs in plasma samples from patients with TLI and explore their potential functions in the pathogenesis of TLI. A high-throughput circRNA microarray was used to investigate the expression profile of circRNAs in plasma samples from five patients with TLI and paired control samples. Subsequently, a total of five abnormally expressed circRNAs were investigated using reverse transcription-quantitative PCR (RT-qPCR). A bioinformatics analysis was performed to predict a competitive endogenous RNA (ceRNA) network. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the main biological processes and pathways. Finally, additional samples were tested to identify the expression profiles of the selected circRNAs. Among the 310 circRNAs that were highly expressed in the microarray analysis, 60 were upregulated and 250 were downregulated in patients with TLI. RT-qPCR results indicated that two downregulated circRNAs (circ_102927 and circ_100562) and one upregulated circRNA (circ_101523) matched the microarray results. The bioinformatics analysis constructed a targeting network based on the three validated circRNAs. GO and KEGG analyses identified the top ten enriched annotations. The expression of homo sapiens circular RNA 102927 (hsa_circRNA_102927) in the plasma of patients with TLI was 0.34-fold compared with the control group in expanded size validation. The results of the present study identified the differentially expressed circRNAs in the plasma of patients with TLI and provided evidence that highly expressed circRNAs involved in the ceRNA network may serve a role in the pathophysiology of TLI.

14.
Wound Repair Regen ; 26(2): 172-181, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29719102

RESUMO

Hypertrophic scar pain, pruritus, and paresthesia symptoms are major and particular concerns for burn patients. However, because no effective and satisfactory methods exist for their alleviation, the clinical treatment for these symptoms is generally considered unsatisfactory. Therefore, their risk factors should be identified and prevented during management. We reviewed the medical records of 129 postburn hypertrophy scar patients and divided them into two groups for each of three different symptoms based on the University of North Carolina "4P" Scar Scale: patients with scar pain requiring occasional or continuous pharmacological intervention (HSc pain, n = 75) vs. patients without such scar pain (No HSc pain, n = 54); patients with scar pruritus requiring occasional or continuous pharmacological intervention (HSc pruritus, n = 63) vs. patients without such scar pruritus (No HSc pruritus, n = 66); patients with scar paresthesia that influenced the patients' daily activities (HSc paresthesia, n = 31) vs. patients without such scar paresthesia (No HSc paresthesia, n = 98). Three multivariable logistic regression models were built, respectively, to identify the risk factors for hypertrophic burn scar pain, pruritus, and paresthesia development. Multivariable analysis showed that hypertrophic burn scar pain development requiring pharmacological intervention was associated with old age (odds ratio [OR] = 1.046; 95% confidence interval [CI], 1.011-1.082, p = 0.009), high body mass index (OR = 1.242; 95%CI, 1.068-1.445, p = 0.005), 2-5-mm-thick postburn hypertrophic scars (OR = 3.997; 95%CI, 1.523-10.487, p = 0.005), and 6-12-month postburn hypertrophic scars (OR = 4.686; 95%CI, 1.318-16.653, p = 0.017). Hypertrophic burn scar pruritus development requiring pharmacological intervention was associated with smoking (OR = 3.239; 95%CI, 1.380-7.603; p = 0.007), having undergone surgical operation (OR = 2.236; 95%CI, 1.001-4.998; p = 0.049), and firm scars (OR = 3.317; 95%CI, 1.237-8.894; p = 0.017). Finally, hypertrophic burn scar paresthesia development which affected the patients' daily activities was associated with age (OR = 1.038; 95%CI, 1.002-1.075; p = 0.040), fire burns (OR = 0.041; 95%CI, 0.005-0.366; p = 0.004, other burns vs. flame burns), and banding and contracture scars (OR = 4.705; 95%CI, 1.281-17.288, p = 0.020).


Assuntos
Queimaduras/patologia , Cicatriz Hipertrófica/patologia , Dor/fisiopatologia , Parestesia/fisiopatologia , Prurido/fisiopatologia , Cicatrização/fisiologia , Adulto , Índice de Massa Corporal , Queimaduras/complicações , Queimaduras/fisiopatologia , Cicatriz Hipertrófica/complicações , Cicatriz Hipertrófica/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Parestesia/etiologia , Prurido/etiologia , Fluxo Sanguíneo Regional/fisiologia , Fatores de Risco
15.
Histol Histopathol ; 32(8): 761-766, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28078661

RESUMO

Wound infection caused by Staphylococcus aureus (S. aureus) is a critical clinical problem due to long hospitalization times, significant morbidity and mortality, as well as considerable medical resource consumption. With the emergence of methicillin-resistant S. aureus (MRSA) strains, current antibiotic treatments are becoming ineffective in combatting S. aureus infection. Thus, a novel therapeutic strategy is required. Recent studies discovered that several cytokines in the infected wound area play protective roles against S. aureus infection. This review summarizes recent discoveries regarding the role of cytokines-mediated responses in host defense against S. aureus skin infection, and discusses their implications for future immunotherapy and vaccine development.


Assuntos
Citocinas/imunologia , Dermatopatias/imunologia , Dermatopatias/microbiologia , Infecções Estafilocócicas/imunologia , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/imunologia , Quimiotaxia , Humanos , Imunoterapia , Interferon gama/imunologia , Interleucina-1/imunologia , Interleucina-17/imunologia , Interleucina-33/imunologia , Interleucinas/imunologia , Staphylococcus aureus Resistente à Meticilina , Neutrófilos/imunologia , Pele/microbiologia , Dermatopatias/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Cicatrização , Interleucina 22
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