RESUMEN
Bladder cancer is a highly prevalent malignancy. Asiaticoside (AC), a triterpenoid derivative, exhibits antitumor effect on different tumors. This study aimed to explore the role and mechanism of AC on bladder cancer. J82 and T24 cells were treated with AC and/or propofol, and nude mice were subcutaneously administrated with T24 cells. The effect and mechanism of AC and/or propofol were explored by cell counting kit-8, transwell, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry and western blot assays both in vitro and in vivo. Cell viability of J82 and T24 cells was inhibited by AC with a IC50 value of 2.43 µM and 2.16 µM, and by propofol with a IC50 value of 42.51 µM and 48.37 µM, respectively. AC or propofol alone decreased cell proliferation, invasion, and immune escape with the increased ferroptosis, as well as downregulating the level of the PI3K/AKT pathway in both animal and cell experiments. The effect of propofol on the above-mentioned indicators was further enhanced with the co-treatment of AC in vitro and in vivo. Taken together, AC promoted the ameliorative effect of propofol on bladder cancer involved in PI3K/AKT pathway.
Asunto(s)
Ferroptosis , Ratones Desnudos , Propofol , Triterpenos , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Animales , Triterpenos/farmacología , Humanos , Propofol/farmacología , Ferroptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Invasividad Neoplásica , Escape del Tumor/efectos de los fármacos , Sinergismo Farmacológico , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Arthritis is relatively common among middle-aged and older people and is a significant public health problem. However, research on the relationship between arthritis and mental health in older populations is currently limited. METHODS: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey. The 10-item Center for Epidemiologic Studies Depression Scale and 7-item Generalized Anxiety Disorder Scale were used to evaluate depressive and anxiety symptoms. Arthritis status was self-reported. Linear and logistic regression analyses were conducted to assess the impact of arthritis on depression, anxiety, and comorbid depression/anxiety symptoms. RESULTS: A total of 11,104 participants aged ≥65 years (mean age, 83.1 ± 11.1 years) were included in the analysis. We detected positive associations of arthritis with depression symptoms (adjusted odds ratio [OR]: 1.57, 95 % confidence interval [CI] 1.33 to 1.86), anxiety symptoms (adjusted OR: 1.48, 95 % CI: 1.15 to 1.90), and comorbid depression/anxiety symptoms (adjusted OR: 1.88, 95 % CI: 1.41 to 2.5) in the older adult population. Participants with arthritis had higher anxiety (adjusted linear regression coefficient: 0.43, 95 % CI: 0.24 to 0.63) and depression (adjusted linear regression coefficient: 0.87, 95 % CI: 0.57 to 1.14) scores compared with those without arthritis. In addition, there were no significant interaction effects between arthritis and participant characteristics on depression symptoms, anxiety symptoms, or comorbid depression/anxiety symptoms. CONCLUSIONS: Arthritis was positively associated with depression symptoms, anxiety symptoms, and comorbid depression/anxiety symptoms among older adults. Further cohort studies are needed to validate these associations.
Asunto(s)
Artritis , Depresión , Persona de Mediana Edad , Humanos , Anciano , Anciano de 80 o más Años , Depresión/epidemiología , Depresión/complicaciones , Estudios Transversales , Autoinforme , Ansiedad/epidemiología , Ansiedad/complicaciones , Artritis/epidemiología , China/epidemiologíaRESUMEN
Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.
Asunto(s)
Pulmón , Macrófagos Alveolares , Mitocondrias , Fosforilación Oxidativa , Animales , Macrófagos Alveolares/metabolismo , Mitocondrias/metabolismo , Ratones , Pulmón/metabolismo , Adaptación Fisiológica , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Estrés del Retículo Endoplásmico , Ratones Noqueados , Apoptosis , Ratones Endogámicos C57BL , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Femenino , Glucólisis , Adenosina Trifosfato/metabolismo , Proteínas del Grupo de Alta MovilidadRESUMEN
OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease, of which the pathogens is remains obscure. Viral infection, particularly Epstein Barr viru (EBV) infection, has been considered a common pathogenic factor. This study suggests that c-Maf may be an important target in T cell differentiation during SLE progression, providing a potentially new perspective on the role of viral infection in the pathogenesis of autoimmune diseases. METHODS: Cytokines of EBV-infected SLE patients were measured by ELISA and assessed in conjunction with their clinical data. IFN-α, c-Maf, and the differentiation of Th17/Treg cells in SLE patients and MRL/LPR mice were analyzed using FCM, WB, RT-PCR, etc. Following the infection of cells and mice with EBV or viral mimic poly (dA:dT), the changes of the aforementioned indicators were investigated. The relationship among IFN-α, STAT3, c-Maf and Th17 cells was determined by si-RNA technique. RESULTS: Many SLE patients are found to be complicated by viral infections; Further, studies have demonstrated that viral infection, especially EBV, is involved in SLE development. This study showed that viral infections might promote IFN-α secretion, inhibit c-Maf expression by activating STAT3, increase Th17 cell differentiation, and lead to the immune imbalance of Th17/Treg cells, thus playing a role in the onset and progression of SLE. CONCLUSION: This study demonstrates that EBV infections may contribute to SLE development by activating STAT3 through IFN-α, inhibiting c-Maf, and causing Th17/Treg immune imbalance. Our work provided a new insight into the pathogenesis and treatment of SLE.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Interferón-alfa , Lupus Eritematoso Sistémico , Ratones Endogámicos MRL lpr , Proteínas Proto-Oncogénicas c-maf , Linfocitos T Reguladores , Células Th17 , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/virología , Células Th17/inmunología , Humanos , Animales , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Linfocitos T Reguladores/inmunología , Ratones , Interferón-alfa/inmunología , Interferón-alfa/metabolismo , Femenino , Adulto , Herpesvirus Humano 4/inmunología , Proteínas Proto-Oncogénicas c-maf/inmunología , Proteínas Proto-Oncogénicas c-maf/genética , Masculino , Diferenciación Celular/inmunología , Progresión de la Enfermedad , Persona de Mediana Edad , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/inmunología , Adulto JovenRESUMEN
Chitinase plays a positive role in the pathogenicity of Bacillus thuringiensis to insect pests. We used touchdown PCR to clone the chitinase (Schi) gene from Bacillus thuringiensis serovar sotto (Bt sotto) chromosomal DNA. Our DNA sequencing analysis revealed that the Bt sotto Schi gene consists of an open reading frame (ORF) of 2067 nucleotides with codes for the chitinase precursor. We also found that the putative promoter consensus sequences (the -35 and -10 regions) of the Bt soto Schi gene are identical to those of the chiA71 gene from Bt Pakistani, the chiA74 gene from Bt kenyae and the ichi gene from Bt israelensis. The Schi chitinase precursor is 688 amino acids long with an estimated molecular mass of 75.75 kDa and a theoretical isoelectric point of 5.74, and contains four domains, which are, in sequence, a signal peptide, an N-terminal catalytic domain, a fibronectin type III like domain and a C-terminal chitin-binding domain. Sequence comparison and the evolutionary relationship of the Bt sotto Schi chitinase to other chitinase and chitinase-like proteins are also discussed