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Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β 3-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.
RESUMO
Objective To evaluate the value and security of the use of medical thoracoscopy in the diagnosis of elderly patients with un‐known pleural effusion and to analyze the finally pathological results .Methods STORZ medical thoracoscopy was used to retrospectively study the 68 patients with unknown pleural effusion .Multiple punch biopsy was taken in the questionable diseased regions under direct vi‐sion .The changes of patients′condition in intraoperative and postoperative ,and the causes of pleural effusion were observed .Results Sixty‐three cases were confirmed in 68 cases of patients with unexplained pleural effusion ,the diagnostic rate was 92 .6% .In all cases ,26 cases (38 .2% ) were tuberculosis ,31 cases (45 .6% ) were malignant tumor ,3 cases (4 .4% ) were chronic pus chest and Aspergillus infection in 1 case(1 .5% ) ,a large number of aspergillus hyphae were found in biopsy tissue .Non‐specific inflammatory changed in 7 cases (10 .3% ) ,in which 2 patients were eventually diagnosed with pleural effusion caused by pulmonary schistosomiasis ,and the rest cases were still un‐known .All cases had no serious complications .Conclusion Medical thoracoscopy have a good effect in diagnosing elderly patients with un‐explained pleural effusion ,which could be easily and safely performed .The primary cause of unexplained pleural effusion in elder patients may be malignant tumor ,followed by tuberculosis .