RESUMEN
OBJECTIVE: We conducted this study to determine the impact of serum glycosaminoglycan hyaluronan (HA) on the prognosis of coronavirus disease 2019 (COVID-19). METHODS: A total of 497 hospitalized patients with COVID-19 were included. Patients were divided into two subgroups based on the severity of infection: mild (n=344) and severe (n=153). The levels of HA, lymphocyte count, C-reactive protein (CRP), ferritin, interleukin 6 (IL-6), and D-dimer were measured and the correlation of these parameters with the prognosis of COVID-19 was assessed. RESULTS: The mean HA level of the severe group was significantly higher than that of the mild group (204.4 ng/mL versus 850.6 ng/mL, P<0.01). In receiver operating characteristic curve analysis, an HA level ≥607.8 ng/mL predicted severe COVID-19 with a sensitivity of 62.3% and specificity of 88.6%. Multivariate regression analysis demonstrated that serum HA level was a significant predictor of disease severity (odds ratio=60.56, P<0.01). CONCLUSION: Our findings show that higher serum HA concentrations are associated with severe COVID-19 disease. Early analysis of HA level in patients with COVID-19 might effectively predict disease severity.
Asunto(s)
COVID-19 , Ácido Hialurónico , Índice de Severidad de la Enfermedad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , COVID-19/sangre , COVID-19/diagnóstico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Ácido Hialurónico/sangre , Interleucina-6/sangre , Recuento de Linfocitos , Pronóstico , Estudios Retrospectivos , Curva ROCRESUMEN
The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.
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Antígeno B7-H1 , Quinasa 5 Dependiente de la Ciclina , Inmunoterapia , Fotoquimioterapia , Fotoquimioterapia/métodos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Inmunoterapia/métodos , Animales , Quinasa 5 Dependiente de la Ciclina/metabolismo , Quinasa 5 Dependiente de la Ciclina/antagonistas & inhibidores , Humanos , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Ratones , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , ClorofilidasRESUMEN
The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs. To amplify the immunotherapeutic effect, a chimeric peptide-based and optical controlled CECR2 competitor (designated as N-PB) is constructed to enhance the nuclear targeted delivery of Bro and initiate an immunogenic cell death (ICD). In vivo results indicate a favorable breast cancer targeting ability and primary tumor suppression effect of N-PB under optical irradiation. Importantly, N-PB downregulates CSF-1 by competitive inhibition of CECR2 and NF-κB(RelA) interactions, thus inhibiting immunosuppressive M2-like TAMs while improving the antitumorigenic M1-like phenotype. Ultimately, the systemic anti-tumor immunity is activated to suppress the metastatic breast cancer in an optical controlled manner. This study provides a promising therapeutic target and reliable strategy for metastatic breast cancer treatment by interrupting immunosuppressive crosstalk between tumor cells and macrophages.
Asunto(s)
Neoplasias de la Mama , Regulación hacia Abajo , Inmunoterapia , Factor Estimulante de Colonias de Macrófagos , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Animales , Humanos , Inmunoterapia/métodos , Regulación hacia Abajo/efectos de los fármacos , Factor Estimulante de Colonias de Macrófagos/metabolismo , Línea Celular Tumoral , Ratones , Ratones Endogámicos BALB C , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos , Núcleo Celular/metabolismo , Factor de Transcripción ReIA/metabolismo , Metástasis de la NeoplasiaRESUMEN
In order to understand the pollution status of metals in the riparian soils along the Wujiang River, 26 sampling sites in the mainstream and tributary streams were selected for investigation. The geo-accumulation index (Igeo), Nemerow integrated pollution index, and potential ecological risk index were applied to evaluate the contamination status and ecological risks of metals. Results revealed that the average concentrations of As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn were 12.20, 0.51, 84.01, 57.42, 922.57, 38.37, 38.06, and 127.82 mg/kg, respectively. The metal contamination degree and ecological risks in the upper reaches were significantly higher than those in the middle and lower reaches of the Wujiang River. Cd was the dominant contamination metal. Significant non-carcinogenic and carcinogenic risks of metals were found in children based on the hazard index and carcinogenic risk. As was the main non-carcinogenic and carcinogenic pollutant metal in both adults and children. According to principal component analysis, hierarchical clustering analysis, and absolute principal component scores-multiple linear regression, anthropogenic sources (mining and agricultural activities) contributed most to Zn, Pb, Cr, Cd, Cu, and Ni, with contribution rates of 89.14, 82.32, 74.46, 72.12, 68.52, and 61.02%, respectively. Natural sources contributed most to Mn, with a contribution rate of 83.07%. Unidentified sources contributed most to As, with a contribution rate of 47.27%.
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Cadmio , Suelo , Adulto , Niño , Humanos , Plomo , Ríos , China , Medición de RiesgoRESUMEN
Sarcopenia is a process in which skeletal muscle mass and strength are gradually declining, resulting a main health challenge for the old adults. Mitochondria can maintain the integrity of structure and function of skeletal muscle by improving biosynthesis, antioxidant defense, fusion/fission dynamics and mitophagy. Mitochondrial dysfunction is a important factor leading to the complex etiology of sarcopenia. Exercise can regulate mitochondrial quality control pathways by activating mitochondrial biogenesis and mitophagy to maintain optimal mitochondrial function, thereby delaying and preventing the onset and progression of sarcopenia.
RESUMEN
Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.
Asunto(s)
Humanos , Envejecimiento/genética , Terapia por Ejercicio , MicroARNs/genética , Músculo Esquelético , Sarcopenia/terapiaRESUMEN
Sarcopenia is an aging-related disease with a significant reduction in mass and strength of skeletal muscle due to the imbalance between protein synthesis and degradation. Autophagy acts as a conserved mechanism regulating the balance of protein metabolism in body and can be regulated by multiple signaling pathways such as AMP-activated protein kinase (AMPK), insulin like growth factor (IGF)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) and phosphatidylinositol 3 kinase (PI3K)/Akt/mTOR induced by exercise. Exercise-activated autophagy regulates skeletal muscle remodeling and homeostasis under different physiological and pathological conditions, which is the key to skeletal muscle health maintenance. This article reviewed the regulator roles and potential molecular mechanisms of varying exercise-induced autophagy in the prevention, treatment and rehabilitation of sarcopenia.