Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases.

Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood. Melatonin, which has a wide range of physiological effects, is an endocrine hormone mainly secreted by the pineal gland. Its biological effects include its antioxidant, antiaging, analgesic, and hypnotic effects and its ability to stabilize the circadian rhythm. In recent years, research on cartilage homeostasis and melatonin has been increasing, and melatonin has gradually been used in the treatment of cartilage-related diseases. Therefore, this article will briefly review the role of melatonin in cartilage homeostasis, including its anti-inflammatory effects and effects in protecting cartilage from damage by other factors and promoting chondrocyte growth and the expression of cartilage-related genes. Based on the above, the current status and future developmental direction of melatonin in the treatment of cartilage-related diseases are also discussed, demonstrating the broad prospects of melatonin in maintaining cartilage homeostasis and treating cartilage injury-related diseases.

Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions.

Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.

Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.

Significance of SHP-1 and SHP-2 expression in human papillomavirus infected Condyloma acuminatum and cervical cancer.

Human papillomaviruses (HPVs) are a group of DNA viruses that infect the skin and mucous membranes. Type HPV6/11 is closely related to Condyloma acuminatum, while HPV16/18 is the principal cause of cervical cancer. In this study, we examined the expression of protein tyrosine phosphatases SHP-1 and SHP-2 in Condyloma acuminatum, cervical cancer and the relationship between SHP-1/SHP2 expression and HPV infection. Forty Condyloma acuminatum cases, 20 cervical cancer cases and 20 normal human foreskins were examined for HPV infection by in situ hybridization and the expression of SHP-1 and SHP-2 were examined by immunohistochemistry. Results demonstrated that positive expression rates of HPV6/11, HPV16/18, and HPV31/33 were 98%, 10%, and 7.5% in Condyloma acuminatum, 10%, 85%, and 25% in cervical cancer. Only one normal foreskin demonstrated positive staining for HPV16/18. Positive expression rates of SHP-1 and SHP-2 were 80% and 85% in Condyloma acuminatum, 85% and 90% in cervical cancer. The SHP-1 and SHP-2 expressions were mainly distributed in the prickle layer of Condyloma acuminatum and were diffusely distributed in cervical cancer cells. Only 35% and 30% of foreskins demonstrated weak staining in the basal layer cells. There were statistically significant correlations among the infection of HPV and the expression of SHP-1 and SHP-2 in both Condyloma acuminatum and cervical cancer (P < 0.05). SHP-1 expression has a positive correlation with SHP-2 expression. Our results demonstrate putative roles of SHP-1 and SHP-2 in the progression of both Condyloma acuminatum and cervical cancer after HPV infection.