Endothelin-1 impairs skeletal muscle myogenesis and development via ETB receptors and p38 MAPK signaling pathway.

Myopenia is a condition marked by progressive decline of muscle mass and strength and is associated with aging or obesity. It poses the risk of falling, with potential bone fractures, thereby also increasing the burden on family and society. Skeletal muscle wasting is characterized by a reduced number of myoblasts, impaired muscle regeneration and increased muscle atrophy markers (Atrogin-1, MuRF-1). Endothelin-1 (ET-1) is a potent vasoconstrictor peptide. Increased circulating levels of ET-1 is noted with aging and is associated with muscular fibrosis and decline of strength. However, the regulatory mechanism controlling its effect on myogenesis and atrophy remains unknown. In the present study, the effects of ET-1 on myoblast proliferation, differentiation and development were investigated in C2C12 cells and in ET-1-infused mice. The results show that ET-1, acting via ETB receptors, reduced insulin-stimulated cell proliferation, and also reduced MyoD, MyoG and MyHC expression in the differentiation processes of C2C12 myoblasts. ET-1 inhibited myoblast differentiation through ETB receptors and the p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Additionally, ET-1 decreased MyHC expression in differentiated myotubes. Inhibition of proteasome activity by MG132 ameliorated the ET-1-stimulated protein degradation in differentiated C2C12 myotubes. Furthermore, chronic ET-1 infusion caused skeletal muscle atrophy and impaired exercise performance in mice. In conclusion, ET-1 inhibits insulin-induced cell proliferation, impairs myogenesis and induces muscle atrophy via ETB receptors and the p38 MAPK-dependent pathway.

[The Health-Seeking Experience of Patients With Sjögren's Syndrome].

BACKGROUND: The multiple symptoms of Sjögren's syndrome lead patients affected by this disease to seek medical advice from different medical disciplines and specialists. Diagnoses are often made many years after initial onset, resulting in mental and physical exhaustion and misunderstandings. PURPOSE: This study was designed to explore the health-seeking experiences of patients with Sjögren's syndrome. METHODS: Qualitative research methods and purposive sampling were used. Fourteen patients with Sjögren's syndrome were interviewed by the first author, and the collected data were analyzed using content analysis. RESULTS: Four themes were revealed from the data, including: (1) distressing symptoms; (2) difficulty in diagnosis; (3) concerns about drug side effects; and (4) facing the disease. The participants initially sought medical attention when they began experiencing early onset symptoms that caused discomfort or annoyance. Their doctors' failure to provide proper diagnoses during the long health-seeking process caused a great deal of suffering to the participants. Although related medications should be taken for life, the participants reported taking lower-than-prescribed dosages out of fear of side-effects. The participants explored their process of coping with the disease, which began with denial and ended with acceptance. By learning from their health-seeking process, participants realized that they needed to take proper care of themselves, adapt to life with their disease, and control related symptoms. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: To facilitate the early diagnosis of Sjögren's syndrome, healthcare professionals should improve their awareness of this condition and refer patients with related symptoms to rheumatologists and immunologists. Effective early diagnosis and treatment can help these patients reduce the time and effort involved in unproductive doctor's visits, allowing them to better continue as productive members of society and to maintain a good quality of life.

Ziwuliuzhu Acupuncture Modulates Clock mRNA, Bmal1 mRNA and Melatonin in Insomnia Rats.

Background: In clinics, Ziwuliuzhu acupuncture is widely considered an effective method of treating insomnia; however, there is currently limited information available regarding its possible mechanisms. Although the method of Ziwuliuzhu acupuncture possesses a unique rhythmic pattern. Objectives: In this study, we have creatively combined the traditional Chinese medicine of Ziwuliuzhu with a modern biological rhythm to investigate the internal mechanism of insomnia. Methods: Pathological tissue from the hypothalamus was analyzed using hematoxylin-eosin staining. The level of TNF (tumor necrosis factor)-α in the SCN (suprachiasmatic nucleus) area of the hypothalamus was detected in situ using the TUNEL fluorescence staining assay. The concentration of hypothalamic melatonin was detected using the enzyme-linked immunosorbent assay (ELISA). The mRNA expression of Clock and Bmal1 was measured using RT-qPCR. Results: In the Ziwuliuzhu acupuncture groups, the structural damage in the hypothalamic neurons was alleviated compared to the model group and the expression of inflammatory factors was reduced. The mRNA expression levels of Clock and Bmal1 were significantly increased (p < 0.05). The concentration of melatonin was significantly increased (p < 0.001). Although there were no significant differences between the treatment groups (diazepam group, Nazi group, Najia group, and routine group) (p > 0.05). Conclusion: Ziwuliuzhu acupuncture alleviated neuronal damage and modulated the inflammatory reaction in the hypothalamus of rats with insomnia. Moreover, Ziwuliuzhu acupuncture increased the expression levels of Clock and Bmal1 mRNA, and MT content. This study has potentially highlighted one of the mechanisms through which Ziwuliuzhu acupuncture can be used to treat insomnia.

An investigation of total bacterial communities, culturable antibiotic-resistant bacterial communities and integrons in the river water environments of Taipei city.

The intensive use of antibiotics may accelerate the development of antibiotic-resistant bacteria (ARB). The global geographical distribution of environmental ARB has been indicated by many studies. However, the ARB in the water environments of Taiwan has not been extensively investigated. The objective of this study was to investigate the communities of ARB in Huanghsi Stream, which presents a natural acidic (pH 4) water environment. Waishuanghsi Stream provides a neutral (pH 7) water environment and was thus also monitored to allow comparison. The plate counts of culturable bacteria in eight antibiotics indicate that the numbers of culturable carbenicillin- and vancomycin-resistant bacteria in both Huanghsi and Waishuanghsi Streams are greater than the numbers of culturable bacteria resistant to the other antibiotics tested. Using a 16S rDNA sequencing approach, both the antibiotic-resistant bacterial communities (culture-based) and the total bacterial communities (metagenome-based) in Waishuanghsi Stream exhibit a higher diversity than those in Huanghsi Stream were observed. Of the three classes of integron, only class I integrons were identified in Waishuanghsi Stream. Our results suggest that an acidic (pH 4) water environment may not only affect the community composition of antibiotic-resistant bacteria but also the horizontal gene transfer mediated by integrons.

Asystole in ultrabrief pulse electroconvulsive therapy.

OBJECTIVES: Ultrabrief (UB) pulse electroconvulsive therapy (ECT) has been gaining popularity in recent years because of its improved cognitive adverse effect profile compared with treatments triggered by brief pulses. When delivered at maximal charge, UB pulses are administered for 8 seconds. Because electrical stimulation triggers a parasympathetic surge and transient asystole, we checked whether UB pulses delivered for 8 seconds were associated with prolonged cardiac pause compared with maximal charge delivered for 4 seconds with brief pulses. METHODS: This is a retrospective study of cardiac pause length of all patients undergoing ECT treatment at The Johns Hopkins Hospital during 1 year. RESULTS: Electrocardiac pause length for patients undergoing ECT with right unilateral placement at maximal charge was not affected by pulse width. However, we did find cardiac pause length to be sensitive to 2- versus 4-second duration stimuli using brief pulses (P < 0.0001). CONCLUSIONS: Notwithstanding the clear limitations of small sample size and retrospective design, we found that right unilateral ECT was not affected by pulse width when maximal charge was delivered.