RESUMEN
Osteoarthritis (OA) is a major cause of disability in the elderly population and represents a significant public health problem and socioeconomic burden worldwide. However, no disease-modifying therapeutics are currently available for OA due to an insufficient understanding of the pathogenesis of this disability. As a unique cell type in cartilage, chondrocytes are essential for cartilage homeostasis and play a critical role in OA pathogenesis. Mitochondria are important metabolic centers in chondrocytes and contribute to cell survival, and mitochondrial quality control (MQC) is an emerging mechanism for maintaining cell homeostasis. An increasing number of recent studies have demonstrated that dysregulation of the key processes of chondrocyte MQC, which involve mitochondrial redox, biogenesis, dynamics, and mitophagy, is associated with OA pathogenesis and can be regulated by the chondroprotective molecules 5' adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 3 (SIRT3). Moreover, AMPK and SIRT3 regulate each other, and their expression and activity are always consistent in chondrocytes, which suggests the existence of an AMPK-SIRT3 positive feedback loop (PFL). Although the precise mechanisms are not fully elucidated and need further validation, the current literature indicates that this AMPK-SIRT3 PFL regulates OA development and progression, at least partially by mediating chondrocyte MQC. Therefore, understanding the mechanisms of AMPK-SIRT3 PFL-mediated chondrocyte MQC in OA pathogenesis might yield new ideas and potential targets for subsequent research on the OA pathomechanism and therapeutics.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Condrocitos/patología , Osteoartritis/patología , Transducción de Señal , Sirtuina 3/metabolismo , Animales , Condrocitos/metabolismo , Progresión de la Enfermedad , Humanos , Mitocondrias/metabolismo , Mitocondrias/patología , Mitofagia , Osteoartritis/metabolismoRESUMEN
OBJECTIVE: Uric acid (UA) is a risk marker of CKD and SUA level in CKD 3-4 patients closely correlates with hyperuricemic nephropathy (HN) morbidity. This study was designed to evaluate the risk factors for HN in CKD 3-4 patients. METHODS: The 461 CKD 3-4 patients were recruited and all patients were divided into three groups (24 h UUA normal, underexeret, and overproduct type groups) according to the 24 h UUA level after receiving low purine food for five days. Clinical and biochemical characteristics of CKD patients were collected for the logistic regression analysis. Correlation analysis of the mRNA relative expression level of hUAT and hURAT1 with serum UA (SUA) level also was evaluated. RESULTS: There were significant increases in characteristics including average age, waist-to-height ratio (WHR), SUA levels, HN ratio, TG/HDL ratio, body mass index (BMI), blood pressure (BP), uNgal/Cr. ratio, and uKim-1/Cr. ratio in overproduct type group in comparison with the other two groups. Logistic regression analysis showed SUA, CHO, uKim-1/Cr. ratio and uNgal/Cr. ratio were independent and multiple risk factors for HN. Moreover, hUAT and hURAT1 mRNA relative expression levels were significantly correlated with SUA level in the underexeret type CKD 3-4 patients. CONCLUSIONS: These results showed SUA and other characteristics contributed to HN morbidity in CKD 3-4 patients.
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Hiperuricemia/epidemiología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Ácido Úrico/sangre , Adulto , Anciano , Presión Sanguínea , Índice de Masa Corporal , China/epidemiología , Estudios Epidemiológicos , Femenino , Humanos , Hiperuricemia/sangre , Masculino , Persona de Mediana Edad , Transportadores de Anión Orgánico/genética , Proteínas de Transporte de Catión Orgánico/genética , ARN Mensajero/análisis , Análisis de Regresión , Factores de Riesgo , Factores SexualesRESUMEN
Objective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life. Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status. Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p<0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05±12.28 vs 78.03±10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97±4.67 vs 36.2±3.36) and depression scale score (57.67±4.58 vs 38.71±3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05). Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.
RESUMEN
OBJECTIVE: To study the effect of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life in patients with sarcopenia receiving maintenance haemodialysis (MHD). METHODS: Eligible patients with sarcopenia in our hospital were randomly assigned to a control group (n = 24) and an intervention group (n = 25). The control group received conventional dialysis treatment, while the intervention group underwent mindfulness meditation combined with progressive muscle relaxation training during the interdialysis period in addition to conventional dialysis treatment. The effect of the intervention was evaluated after 12 weeks. RESULTS: There were no significant differences in the baseline values of various parameters between the two groups. Exercise capacity (sit-to-stand test,handgrip,time to 10 sit-ups) significantly improved in the intervention group after 12 weeks (32.68 ± 8.32 vs 26.50 ± 6.83; 37.42 ± 10.12 vs 28.12 ± 8.51; 19.8 ± 5.40 vs 25.29 ± 7.18) (p < 0.05). In terms of the kidney disease quality of life (KDQOLTM) score, all other dimensions except sexual function, social functioning, burden of kidney disease and work status dimensions showed significant improvement compared to the baseline (p < 0.05). In the control group, only the dialysis staff encouragement (DSE) and patient satisfaction (PS) dimensions showed slight improvements compared to the baseline (p > 0.05). When compared with the control group, the intervention group showed significant improvements in 10 dimensions of exercise capacity and KDQOLTM scores for physical function, role-physical, general health, energy, symptom/problem list, sleep, DSE, pain, cognitive function, emotional well-being and patient PS after 12 weeks (61.30 ± 5.38 vs 42.98 ± 5.73; 57.50 ± 3.55 vs 50.70 ± 3.62) (p < 0.05). Some inflammatory markers, such as the levels of interleukin-6 and high-sensitivity C-reactive protein (30.29 ± 2.96 vs 17.65 ± 3.22; 8.93 ± 0.99 vs 3.02 ± 0.34), showed a decrease during the intervention, while albumin and prealbumin levels were significantly increased compared with the baseline (30.62 ± 1.65 vs 35.60 ± 1.68; 0.32 ± 0.05 vs 0.44 ± 0.07) (p < 0.05). CONCLUSION: Combined intervention training can improve the motor ability and quality of life of patients with sarcopenia within a short period of time.
Asunto(s)
Meditación , Atención Plena , Calidad de Vida , Diálisis Renal , Sarcopenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Atención Plena/métodos , Anciano , Sarcopenia/terapia , Resultado del TratamientoRESUMEN
Monteggia fracture refers to breakage of the upper third of the ulna combined with dislocation of the radial head. It often occurs in children and adolescents and represents a combined injury. Fracture of the distal forearm is among the most common trauma suffered by children. However, distal forearm fractures have rarely been reported as having an association with Monteggia fractures. We report on a 9-year-old boy diagnosed with a type III Monteggia fracture combined with a distal forearm fracture. He underwent surgery and received rehabilitation training 1 month later. He was followed-up for 1 year. The affected limb functioned well with no sign of radial head dislocation.
RESUMEN
Trans-translation is a mechanism that fixes stalled translation course. tmRNA is the core of trans-translation and it has dual function as a tRNA and a mRNA. tmRNA recognizes the ribosome carrying truncated mRNA with specificity under the help SmpB protein. It can be directed to A site by ribosomal protein S1. At first tmRNA prolongs the genetic message on the stalled mRNA, then termination codon stops peptide synthesis to form a nascent chain with the tag sequence. Finally, tmRNA-SmpB system frees stalled ribosomes and directs degradation of the products of these frustrated protein synthesis reactions. This paper introduces the most recent studies on trans-translation.
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Escherichia coli/genética , Biosíntesis de Proteínas , Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Modelos Genéticos , ARN Mensajero/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Ribosomas/química , Ribosomas/genética , Ribosomas/metabolismoRESUMEN
In this work, we engineered the α/ß fold of mannanase Man23 based on its molecular structure analysis to obtain more stable variants. By introducing 31 single-site mutations in the α/ß fold and shuffling them, the incorporation of four mutations (K178R, K207R, N340R, and S354R) displayed a good balance between high activity and stability at higher temperature and broader pH. This quartet variant was characterized by an almost threefold increased activity and a sevenfold increased stability compared to native mannanase Man23. Our results suggest that such work is safe to increase our target protein stability with no loss of activity.