Cyy-272, an indazole derivative, effectively mitigates obese cardiomyopathy as a JNK inhibitor.

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

Adult Kerion Celsi Caused by Trichophyton tonsurans Secondary to Black Dot Tinea Capitis.

A 34-year-old female patient presented with hair loss due to black dot tinea capitis caused by Trichophyton tonsurans for 6 months. Hair loss progressed to painful swelling for 2 months due to kerion Celsi which may be associated with treatment like topical minoxidil, antibiotic and corticosteroid previously. The patient was treated with oral Itraconazole initially without success but cured by Terbinafine eventually. It's very interesting that the patient caught kerion celsi secondary to a four-month history of hair loss due to black dot tinea capitis.

Relationship Between Myocardial Injury and Expression of PGC-1α and Its Coactivators in Chronic Keshan Disease.

OBJECTIVE: Keshan disease (KD) is a mitochondrial cardiomyopathy. The present study explored the roles of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), the key regulator of mitochondrial structure and function, and its coactivators in myocardial injury in chronic KD. Furthermore, the usefulness of these molecules in the diagnosis of chronic KD was assessed. METHODS: In the present case-control study, 43 patients with chronic KD and 30 healthy individuals living in KD endemic areas were included. The myocardial injury indicators and mRNA expression levels of PGC-1α, nuclear respiratory factor 1 (NRF1), PPARα, and estrogen-related receptor alpha (ERRα) in peripheral blood were examined. RESULTS: It was found that the levels of atrial natriuretic peptide, creatine kinase, and lactate dehydrogenase (LDH) were higher in patients with chronic KD, when compared to controls, while the level of bradykinin was lower. Furthermore, the PGC-1α, NRF1 and PPARα mRNA levels were higher in patients with KD. The area under the receiver operating characteristic curve and the optimal diagnostic threshold of LDH was 0.937 and 304.0 U/L, respectively. It is noteworthy that the area under the combined receiver operating characteristic curve was larger, when compared to that for LDH detection alone (Z=2.055, P=0.0399). The area under the curve for the "LDH+PPARα" combination was 0.984, with 96.7% sensitivity and 93.0% specificity. CONCLUSION: The combined detection of LDH and the expression of PPARα can be performed to diagnose the chronic KD.