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1.
Cells ; 10(10)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34685744

RESUMO

Pulmonary epithelial cells are widely considered to be the first line of defence in the lung and are responsible for coordinating the innate immune response to injury and subsequent repair. Consequently, epithelial cells communicate with multiple cell types including immune cells and fibroblasts to promote acute inflammation and normal wound healing in response to damage. However, aberrant epithelial cell death and damage are hallmarks of pulmonary disease, with necrotic cell death and cellular senescence contributing to disease pathogenesis in numerous respiratory diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and coronavirus disease (COVID)-19. In this review, we summarise the literature that demonstrates that epithelial damage plays a pivotal role in the dysregulation of the immune response leading to tissue destruction and abnormal remodelling in several chronic diseases. Specifically, we highlight the role of epithelial-derived damage-associated molecular patterns (DAMPs) and senescence in shaping the immune response and assess their contribution to inflammatory and fibrotic signalling pathways in the lung.


Assuntos
COVID-19/imunologia , Epitélio/imunologia , Fibrose Pulmonar Idiopática/imunologia , Pulmão/imunologia , Alarminas , Animais , Senescência Celular , Técnicas de Cocultura , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibrose/metabolismo , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Imunidade , Inflamação/metabolismo , Ligantes , Necroptose , Necrose/patologia , Doença Pulmonar Obstrutiva Crônica , SARS-CoV-2 , Transdução de Sinais
2.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445145

RESUMO

The main goal of growing plants under various photoperiods is to optimize photosynthesis for using the effect of day length that often acts on plants in combination with biotic and/or abiotic stresses. In this study, Brassica juncea plants were grown under four different day-length regimes, namely., 8 h day/16 h night, 12 h day/12 h night, 16 h day/8 h night, and continuous light, and were infected with a necrotrophic fungus Alternaria brassicicola. The development of necroses on B. juncea leaves was strongly influenced by leaf position and day length. The largest necroses were formed on plants grown under a 16 h day/8 h night photoperiod at 72 h post-inoculation (hpi). The implemented day-length regimes had a great impact on leaf morphology in response to A. brassicicola infection. They also influenced the chlorophyll and carotenoid contents and photosynthesis efficiency. Both the 1st (the oldest) and 3rd infected leaves showed significantly higher minimal fluorescence (F0) compared to the control leaves. Significantly lower values of other investigated chlorophyll a fluorescence parameters, e.g., maximum quantum yield of photosystem II (Fv/Fm) and non-photochemical quenching (NPQ), were observed in both infected leaves compared to the control, especially at 72 hpi. The oldest infected leaf, of approximately 30% of the B. juncea plants, grown under long-day and continuous light conditions showed a 'green island' phenotype in the form of a green ring surrounding an area of necrosis at 48 hpi. This phenomenon was also reflected in changes in the chloroplast's ultrastructure and accelerated senescence (yellowing) in the form of expanding chlorosis. Further research should investigate the mechanism and physiological aspects of 'green islands' formation in this pathosystem.


Assuntos
Alternaria/patogenicidade , Mostardeira/microbiologia , Mostardeira/fisiologia , Necrose/microbiologia , Necrose/patologia , Fotossíntese/fisiologia , Doenças das Plantas/microbiologia , Carotenoides/metabolismo , Clorofila/metabolismo , Clorofila A/metabolismo , Fluorescência , Mostardeira/metabolismo , Necrose/metabolismo , Fotoperíodo , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia
3.
FASEB J ; 35(9): e21861, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416029

RESUMO

Duchenne muscular dystrophy (DMD) is an intractable genetic disease associated with progressive skeletal muscle weakness and degeneration. Recently, it was reported that intraperitoneal injections of ketone bodies partially ameliorated muscular dystrophy by increasing satellite cell (SC) proliferation. Here, we evaluated whether a ketogenic diet (KD) with medium-chain triglycerides (MCT-KD) could alter genetically mutated DMD in model rats. We found that the MCT-KD significantly increased muscle strength and fiber diameter in these rats. The MCT-KD significantly suppressed the key features of DMD, namely, muscle necrosis, inflammation, and subsequent fibrosis. Immunocytochemical analysis revealed that the MCT-KD promoted the proliferation of muscle SCs, suggesting enhanced muscle regeneration. The muscle strength of DMD model rats fed with MCT-KD was significantly improved even at the age of 9 months. Our findings suggested that the MCT-KD ameliorates muscular dystrophy by inhibiting myonecrosis and promoting the proliferation of muscle SCs. As far as we can ascertain, this is the first study to apply a functional diet as therapy for DMD in experimental animals. Further studies are needed to elucidate the underlying mechanisms of the MCT-KD-induced improvement of DMD.


Assuntos
Dieta Cetogênica , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Distrofia Muscular de Duchenne/dietoterapia , Distrofia Muscular de Duchenne/fisiopatologia , Triglicerídeos/química , Triglicerídeos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Feminino , Fibrose/dietoterapia , Fibrose/patologia , Inflamação/dietoterapia , Inflamação/patologia , Cetonas/sangue , Cetose , Masculino , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/patologia , Necrose/dietoterapia , Necrose/patologia , Ratos , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Triglicerídeos/uso terapêutico
4.
Nat Commun ; 12(1): 4402, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285231

RESUMO

Acute kidney injury (AKI) is morphologically characterized by a synchronized plasma membrane rupture of cells in a specific section of a nephron, referred to as acute tubular necrosis (ATN). Whereas the involvement of necroptosis is well characterized, genetic evidence supporting the contribution of ferroptosis is lacking. Here, we demonstrate that the loss of ferroptosis suppressor protein 1 (Fsp1) or the targeted manipulation of the active center of the selenoprotein glutathione peroxidase 4 (Gpx4cys/-) sensitize kidneys to tubular ferroptosis, resulting in a unique morphological pattern of tubular necrosis. Given the unmet medical need to clinically inhibit AKI, we generated a combined small molecule inhibitor (Nec-1f) that simultaneously targets receptor interacting protein kinase 1 (RIPK1) and ferroptosis in cell lines, in freshly isolated primary kidney tubules and in mouse models of cardiac transplantation and of AKI and improved survival in models of ischemia-reperfusion injury. Based on genetic and pharmacological evidence, we conclude that GPX4 dysfunction hypersensitizes mice to ATN during AKI. Additionally, we introduce Nec-1f, a solid inhibitor of RIPK1 and weak inhibitor of ferroptosis.


Assuntos
Injúria Renal Aguda/patologia , Ferroptose/fisiologia , Túbulos Renais/patologia , Traumatismo por Reperfusão/patologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Cisplatino/administração & dosagem , Cisplatino/toxicidade , Modelos Animais de Doenças , Células Epiteliais , Feminino , Ferroptose/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Células HT29 , Transplante de Coração/efeitos adversos , Humanos , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Masculino , Camundongos , Camundongos Transgênicos , Microssomos Hepáticos , Proteínas Mitocondriais/metabolismo , Células NIH 3T3 , Necrose/tratamento farmacológico , Necrose/etiologia , Necrose/patologia , Oxirredutases/genética , Oxirredutases/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Cultura Primária de Células , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia
5.
Sultan Qaboos Univ Med J ; 21(2): e297-e301, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34221479

RESUMO

Objectives: Bone failure due to avascular necrosis (AVN) is a complex pathological phenomenon. Analysis of molecular changes in the bone matrix may help to shed light on the disease process and guide management. This study aimed to explore changes in bone quality and structural damage caused by sickle cell disease (SCD)-induced AVN using Raman spectroscopy. Methods: A total of 10 necrotic femoral heads were obtained from seven SCD patients who underwent total hip replacements. The femoral heads were cut in half and scanned using Raman spectroscopy in correlation with preoperative magnetic resonance imaging to identify necrotic and healthy control areas. Subsequently, samples were examined to determine changes in bone mineralisation, crystallinity, carbonate content, collagen cross-linking and mineral and collagen fibril orientation. Results: Significant changes were observed in bone mineral content, mineral-to-organic content and collagen fibril orientation in necrotic compared to control areas (P ≤0.050). Conclusion: The necrotic samples displayed severe structural damage and loss of mineral and organic contents. Similar Raman signals have been reported in other metabolic bone diseases such as osteoporosis, thereby potentially supporting the use of medical treatment in AVN to promote bone quality.


Assuntos
Anemia Falciforme/complicações , Necrose da Cabeça do Fêmur/patologia , Análise Espectral Raman/métodos , Anemia Falciforme/terapia , Densidade Óssea , Remodelação Óssea , Calcificação Fisiológica , Matriz Extracelular , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/cirurgia , Humanos , Necrose/induzido quimicamente , Necrose/patologia , Necrose/cirurgia
7.
Front Immunol ; 12: 676828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290701

RESUMO

In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.


Assuntos
COVID-19/complicações , Hipofaringe/patologia , SARS-CoV-2/isolamento & purificação , Úlcera/patologia , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Autopsia , Plaquetas/metabolismo , Plaquetas/patologia , COVID-19/mortalidade , COVID-19/patologia , COVID-19/fisiopatologia , Trato Gastrointestinal/patologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Humanos , Hipofaringe/virologia , Imuno-Histoquímica , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/virologia , Linfócitos/metabolismo , Monócitos/metabolismo , Membrana Mucosa/patologia , Músculo Esquelético/patologia , Necrose/patologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Trombose/patologia , Úlcera/virologia
8.
Sci Rep ; 11(1): 15073, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34302001

RESUMO

The estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.


Assuntos
Colite/genética , Metabolismo Energético/genética , Doenças Inflamatórias Intestinais/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Receptores de Estrogênio/genética , Animais , Apoptose/genética , Proliferação de Células/genética , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Homeostase/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Microbiota/genética , Necrose/genética , Necrose/metabolismo , Necrose/patologia
9.
J Zoo Wildl Med ; 52(2): 853-857, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130436

RESUMO

Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.


Assuntos
Doenças dos Símios Antropoides/patologia , Eosinofilia/veterinária , Miocardite/veterinária , Miocárdio/patologia , Pan troglodytes , Animais , Eosinofilia/patologia , Evolução Fatal , Masculino , Miocardite/patologia , Necrose/patologia , Necrose/veterinária
10.
Ecotoxicol Environ Saf ; 221: 112423, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34146985

RESUMO

Tetrabromodiphenyl ether (BDE-47) is widely used as commercial flame retardants that can be released into the environment and finally enter human body through the food chain. It has been identified to generate neurotoxicity, but little is known about auditory damage and the underlying mechanism following BDE-47 exposure. This study aimed to assess the cell viability with BDE-47 concentration ranging from 0 to 150 µM in mouse organ of Corti-derived cell lines (HEI-OC1). Aryl hydrocarbon receptor (AhR) as an environmental sensor, reactive oxygen species (ROS), NLRP3 inflammasome and p38 MAPK pathways were detected. Results: (1) BDE-47 inhibited the viability in a time- and dose-dependent way in HEI-OC1 cells. Cell cycle was arrested in G1 phase by BDE-47; (2) Elevated intracellular ROS, LDH levels and necrosis were found, which was alleviated by pretreatment with ROS scavenger N-acetylcysteine (NAC); (3) AhR plays an essential role in ligand-regulated transcription factor activation by exogenous environmental compounds. We found increased expression of AhR and decreased downstream targets of CYP 1A1 and CYP 1B1 in BDE-47-treated HEI-OC1 cells, which was reversed by the AhR antagonist CH-223191 for 2 h before BDE-47 exposure. No significant change was detected in CYP 2B; (4) Enhanced expressions of NLRP3 and caspase-1 were induced by BDE-47, with up-regulations of both pro-inflammatory factors for IL-1ß, IL-6 and TNF-α, and anti-inflammatory factors for IL-4, IL-10 and IL-13, but down-regulation for IL-1α; (5) Additionally, the p38 MAPK signaling pathway was activated with increased phosphorylation levels of MKK/3/6, p38 MAPK and NF-kB. Overall, our findings illustrate a role of AhR in ROS-induced necrosis of cochlear hair cells by BDE-47 exposure, in which NLRP3 inflammasome and p38 MAPK signaling pathways are activated. The current study first elucidates the sense of hearing damage induced by BDE-47, and cell-specific or mixture exposures in vivo or human studies are needed to confirm this association.


Assuntos
Retardadores de Chama/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Éteres Difenil Halogenados/toxicidade , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Inflamassomos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Necrose/induzido quimicamente , Necrose/metabolismo , Necrose/patologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Life Sci Alliance ; 4(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34130995

RESUMO

The early-stage pathologies of frontotemporal lobal degeneration (FTLD) remain largely unknown. In VCPT262A-KI mice carrying VCP gene mutation linked to FTLD, insufficient DNA damage repair in neural stem/progenitor cells (NSCs) activated DNA-PK and CDK1 that disabled MCM3 essential for the G1/S cell cycle transition. Abnormal neural exit produced neurons carrying over unrepaired DNA damage and induced early-stage transcriptional repression-induced atypical cell death (TRIAD) necrosis accompanied by the specific markers pSer46-MARCKS and YAP. In utero gene therapy expressing normal VCP or non-phosphorylated mutant MCM3 rescued DNA damage, neuronal necrosis, cognitive function, and TDP43 aggregation in adult neurons of VCPT262A-KI mice, whereas similar therapy in adulthood was less effective. The similar early-stage neuronal necrosis was detected in PGRNR504X-KI, CHMP2BQ165X-KI, and TDPN267S-KI mice, and blocked by embryonic treatment with AAV-non-phospho-MCM3. Moreover, YAP-dependent necrosis occurred in neurons of human FTLD patients, and consistently pSer46-MARCKS was increased in cerebrospinal fluid (CSF) and serum of these patients. Collectively, developmental stress followed by early-stage neuronal necrosis is a potential target for therapeutics and one of the earliest general biomarkers for FTLD.


Assuntos
Degeneração Lobar Frontotemporal/patologia , Células-Tronco Neurais/metabolismo , Proteína com Valosina/metabolismo , Animais , Ciclo Celular , Linhagem da Célula/genética , Células Cultivadas , Dano ao DNA/genética , Dano ao DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Degeneração Lobar Frontotemporal/líquido cefalorraquidiano , Degeneração Lobar Frontotemporal/genética , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Necrose/metabolismo , Necrose/patologia , Células-Tronco Neurais/patologia , Neurônios/metabolismo , Proteína com Valosina/genética
12.
Pan Afr Med J ; 38: 236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046141

RESUMO

Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus (TEN-like ACLE) is a rare manifestation of systemic lupus erythematosus (SLE). Because of its rarity, little is known about this entity. In this report, we describe a case of two women previously diagnosed with SLE that presented TEN-like skin lesions. The common elements in both patients were the initial disposition of the lesions on the photoexposed areas, the positivity of Nikolsky´s sign, the discrete mucosal attrition compared to that observed during TEN, and the simultaneous appearance of dermatological lesions with an extra-cutaneous flare of lupus disease. The skin biopsy in both cases showed epidermal necrosis with an identification of lupus band on direct immunofluorescence. Systemic corticosteroids were used with a good evolution after 2 weeks. Skin damage is an indicator of disease activity, and careful search for extracutaneous involvement is obligatory to prevent further complications.


Assuntos
Corticosteroides/administração & dosagem , Lúpus Eritematoso Cutâneo/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Doença Aguda , Adulto , Biópsia , Feminino , Humanos , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/patologia , Necrose/patologia , Pele/patologia , Síndrome de Stevens-Johnson/patologia
13.
Med Sci Monit ; 27: e929884, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33967266

RESUMO

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common tumors. Transarterial chemoembolization (TACE) is the first choice of treatment for intermediate HCC and an important treatment option for advanced HCC. This retrospective study compared the prognosis between patients showing coagulative necrosis and patients showing liquefactive necrosis after the first TACE procedure. MATERIAL AND METHODS We divided 171 patients with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC into 2 groups; a coagulative necrosis group (79 patients) and a liquefactive necrosis group (92 patients). The coagulative and liquefactive necroses were identified by computed tomography after the first TACE procedure. Kaplan-Meier analysis was used to identify the differences in the overall survival (OS) and progression-free survival (PFS) between the 2 groups, and the associated risk factors and safety of TACE were analyzed. RESULTS The median OS durations were 23.27±1.40 months and 8.83±2.15 months (P=0.004) and the median PFS durations were 9.33±0.96 months and 3.70±0.44 months (P=0.002) in the coagulative necrosis and liquefactive necrosis groups, respectively. Intrahepatic in situ progression, new intrahepatic metastasis, and extrahepatic progression occurred significantly earlier in the liquefactive necrosis group (P<0.05). Univariate analysis and multivariate analyses showed liquefactive necrosis was the main risk factor for OS. There was no significant difference in the hepatic function impairment or post-embolism syndrome after TACE. CONCLUSIONS After the first TACE procedure, the patients with liquefactive necrosis experienced recurrence and metastasis earlier and had a worse prognosis. Therefore, these patients should be considered for earlier administration of targeted therapies or immunotherapies after TACE.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Necrose/patologia , Necrose/terapia , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
16.
Biosci Trends ; 15(2): 107-117, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33952802

RESUMO

Differentiating treatment necrosis from tumor recurrence poses a diagnostic conundrum for many clinicians in neuro-oncology. To investigate the potential role of circulating tumor cells (CTCs) detection in differentiating tumor recurrence and treatment necrosis in brain gliomas, we retrospectively analyzed the data of 22 consecutive patients with tumor totally removed and new enhancing mass lesion(s) showed on MRI after initial radiotherapy. The 22 patients were finally classified into tumor recurrence group (n = 10) and treatment necrosis group (n = 12), according to evidence from the clinical course (n = 11) and histological confirmation (n = 11). All 22 patients received CTCs detection, and DSC-MRP and 11C-MET-PET were performed on 20 patients (90.9%) and 17patients (77.3%) respectively. The data of the diagnosis efficacy to differentiate the two lesions by CTC detection, MPR and PET were analyzed by ROC analysis. The mean CTCs counts were significantly higher in the tumor recurrence group (6.10 ± 3.28) compared to the treatment necrosis group (1.08 ± 2.54, p < 0.001). The ROC curve showed that an optimized cell count threshold of 2 had 100% sensitivity and 91.2% specificity with AUC = 0.933 to declare tumor recurrence. The diagnostic efficacy of CTC detection was superior to rCBV of DSC-MRP and rSUVmax in MET-PET. Furthermore, we observed that CTCs detection could have a potential role in predicting tumor recurrence in one patient. Our research results preliminarily showed the potential value of CTC detection in differentiating treatment necrosis from tumor recurrence in brain gliomas, and is worthy of further confirmation with large samples involved.


Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Recidiva Local de Neoplasia/diagnóstico , Células Neoplásicas Circulantes/patologia , Lesões por Radiação/diagnóstico , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Encéfalo/cirurgia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Diagnóstico Diferencial , Feminino , Glioma/sangue , Glioma/diagnóstico , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose/sangue , Necrose/diagnóstico , Necrose/patologia , Recidiva Local de Neoplasia/sangue , Tomografia por Emissão de Pósitrons , Curva ROC , Lesões por Radiação/sangue , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Estudos Retrospectivos , Temozolomida/uso terapêutico
17.
Sci Rep ; 11(1): 9828, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972618

RESUMO

The Southwestern Atlantic rocky reef ecosystems are undergoing significant changes due to sun-corals (Tubastraea tagusensis and T. coccinea) invasion. At Búzios Island, on the northern coast of São Paulo State, where the abundance of T. tagusensis is particularly high, some colonies are displaying tissue necrosis, a phenomenon never reported for this invasive nor any other azooxanthellate coral species. Using next-generation sequencing, we sought to understand the relationship between T. tagusensis tissue necrosis and its microbiota. Thus, through amplicon sequencing, we studied both healthy and diseased coral colonies. Results indicate a wide variety of bacteria associated with healthy colonies and an even higher diversity associated with those corals presenting tissue necrosis, which displayed nearly 25% more microorganisms. Also, as the microbial community associated with the seven healthy colonies did not alter composition significantly, it was possible to verify the microbial succession during different stages of tissue necrosis (i.e., initial, intermediate, and advanced). Comparing the microbiome from healthy corals to those in early tissue necrosis suggests 21 potential pathogens, which might act as the promoters of such disease.


Assuntos
Antozoários/microbiologia , Espécies Introduzidas , Microbiota , Animais , Oceano Atlântico , Brasil , Sequenciamento de Nucleotídeos em Larga Escala , Necrose/microbiologia , Necrose/patologia , Necrose/veterinária
18.
Sci Rep ; 11(1): 9512, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947887

RESUMO

The role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.


Assuntos
Proteína HMGB1/sangue , Necroptose/fisiologia , Necrose/sangue , Necrose/patologia , Sepse/sangue , Sepse/patologia , Idoso , Apoptose/fisiologia , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/mortalidade , Prognóstico , Estudos Prospectivos , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Sepse/mortalidade , Choque Séptico/sangue , Choque Séptico/mortalidade , Choque Séptico/patologia
19.
J Med Case Rep ; 15(1): 178, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33865452

RESUMO

BACKGROUND: Sarcoidosis is pathologically characterized by the formation of non-necrotizing epithelioid cell granulomas. However, pathological findings of patients with sarcoidosis have rarely revealed necrosis. We report here on a patient with sarcoidosis which needed to be distinguished from infectious disease because of marked necrosis in the lymph nodes. CASE PRESENTATION: A 46-year-old Japanese woman was referred to our hospital due to a dry cough and appetite loss. A chest X-ray and computed tomography revealed markedly enlarged mediastinal and hilar lymph nodes and hepatosplenomegaly. Surgical biopsy of these lymph nodes was performed in order to make a diagnosis. Pathological findings revealed epithelioid cell granuloma with marked necrosis that suggested infectious etiology such as mycobacterial and fungal infections. In addition to the pathological findings, immunoglobulin A (IgA) antibody for Mycobacterium avium complex (MAC), enlargement of lymph nodes and hepatosplenomegaly indicated disseminated MAC, while sarcoidosis was considered as another important differential diagnosis according to elevated angiotensin-converting enzyme, soluble interleukin-2 receptor and uveitis. While waiting for the results of the cultures of acid-fast bacilli, the symptoms of cough and consumption had worsened, and initiation of therapy was required before the confirmed diagnosis. The therapy for MAC was initiated because it was feared that immunosuppressive therapy containing corticosteroid for sarcoidosis could worsen the patient's condition if MAC infection was the main etiology. However, the treatment for MAC was not effective, and it was clarified that no acid-fast bacilli were cultured in the liquid culture medium, so the diagnosis was corrected to sarcoidosis after reconsideration of clinical and pathological findings. Prednisolone (30 mg/day) was administered orally, and the patient's symptoms and radiological findings improved. CONCLUSION: Sarcoidosis must be considered even if pathological findings reveal marked necrosis, because rare cases of sarcoidosis exhibit extensive necrosis in lymph nodes. It is extremely important to carefully examine the clinical and pathological findings through discussion with the examining pathologist to reach the correct diagnosis.


Assuntos
Granuloma/patologia , Linfonodos/patologia , Linfadenopatia/diagnóstico por imagem , Necrose/patologia , Sarcoidose/patologia , Biópsia , Feminino , Granuloma/diagnóstico por imagem , Hepatomegalia/diagnóstico por imagem , Humanos , Japão , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Esplenomegalia/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
Molecules ; 26(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925707

RESUMO

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely fragile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage generates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular microscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations particularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.


Assuntos
Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Moduladores de Tubulina/uso terapêutico , Tubulina (Proteína)/genética , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Necrose/tratamento farmacológico , Necrose/genética , Necrose/patologia , Neoplasias/genética , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Ligação Proteica , Tubulina (Proteína)/efeitos dos fármacos , Moduladores de Tubulina/química
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