METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis.

Doxorubicin (DOX) has toxic effects on the heart, causing cardiomyopathy and heart injury, but the underlying mechanisms of these effects require further investigation. This study investigated the role of DOX in promoting ferroptosis to induce myocardial injury. AC16 cardiomyocyte and neonatal rat ventricle cardiomyocytes were used as an in vitro model to study the molecules involved in myocardial injury using gene silencing, ectopic expression, and RNA immunoprecipitation. Messenger RNA and protein level analyses showed that DOX treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. Furthermore, a lack of miR-7-5p expression led to increased levels of transferrin receptor, promoting the uptake of iron and production of lipid reactive oxygen species and demonstrating that DOX-induced ferroptosis occurs in AC16 cells. Additionally, we found that miR-7-5p targets METTL14 in AC16 cells. Meanwhile, the role of METTL14/KCNQ1OT1/miR-7-5p axis in regulating ferroptosis in neonatal rat ventricle cardiomyocytes was also confirmed. Our results indicate that selectively inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury.

Video-assisted selective lateral neck dissection for papillary thyroid carcinoma.

BACKGROUND: The minimally invasive video-assisted thyroidectomy (MIVAT) for thyroid benign nodules and central neck dissection (CND) for papillary thyroid microcarcinoma (PTMC) have been applied, presently, we attempted to perform video-assisted selective lateral neck dissection (VASLND) for papillary thyroid carcinoma (PTC). METHODS: Twenty-six consecutive PTC patients with unilateral tumor (size <4.0 cm) and suspected lymph node metastasis at level III, IV, or IIa were included from March 2009 to January 2012. RESULTS: VASLND was successfully performed in all 26 PTC patients. The mean operative time was 46 min (range 26-75 min) on VASLND. No major complications occurred. Average postoperative hospital stay was 3.6 days (range 2-8 days). The mean number of removed nodes was 7.3 (range 4-12) in central neck and 8.3 (range 3-21) in lateral compartment. Positive yield amounted to a mean value of 2.6 (range 0-5) and 3 (range 0-6), respectively. No persistent or recurrent disease was observed in any patient during a follow-up period. The cosmetic result was excellent. CONCLUSIONS: Our initial experience demonstrates that VASLND is feasible and safe for selected PTCs, with superior appearance and less pain. Nevertheless, larger series and comparative studies with longer follow-up could be necessary to confirm its oncological effectiveness.

A meta-analysis comparing lightweight meshes with heavyweight meshes in Lichtenstein inguinal hernia repair.

BACKGROUND: To evaluate the influence of lightweight and heavyweight mesh on postoperative recovery in Lichtenstein inguinal hernia repair. METHODS: PubMed, EMBASE, and the Cochrane library were used to search for published clinical randomized controlled trials (RCTs), which compared lightweight meshes with heavyweight meshes in Lichtenstein inguinal hernia repair. Two independent reviewers assessed the trials for eligibility and quality, and all the related data matching our standards were abstracted for meta-analysis by RevMan 5.0 software. The evaluation criteria included recurrence, pain, seroma, hematoma, the sensation of a foreign body, wound infection, urine retention, and testicular atrophy. RESULTS: A total of 2231 hernias from 11 RCTs were included. Compared with a heavyweight polypropylene mesh, the lightweight mesh led to less postoperative chronic pain (odds ratio [OR] = 0.64, 95% confidence interval (CI) = 0.51-0.82; P < .05) and less sensation of a foreign body (OR = 0.56; 95% CI = 0.40-0.78; P < .05), regardless of whether the mesh was made of partially absorbable or nonabsorbable material. There was no significant difference in postoperative recurrence, seroma, hematoma, wound infection, urine retention, and testicular atrophy. CONCLUSION: Current evidence suggests that the use of a lightweight mesh is associated with less postoperative pain and less sensation of a foreign body, without increasing the incidence of recurrence. Further high-quality, long-term follow-up RCTs are needed to provide more reliable evidence.

Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study.

BACKGROUND: Adiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography. RESULTS: The results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E' (correlation coefficient (r) = -0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and -0.626 for E/E', p = 0.002, respectively) while positively correlated with E/A and E'/A' (r = 0.683 for E/A, p = 0.001, 0.671 for E'/A', p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found. CONCLUSION: Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.