Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus.

Diabetes mellitus (DM) is a progressive, chronic metabolic disorder characterized by high oxidative stress, which can lead to cardiac damage. Methionine sulfoxylation (MetO) of proteins by excessive reactive oxygen species (ROS) can impair the basic functionality of essential cellular proteins, contributing to heart failure. Methionine sulfoxide reductase B2 (MsrB2) can reverse oxidation induced MetO in mitochondrial proteins, so we investigated its role in diabetic cardiomyopathy. We observed that DM-induced heart damage in diabetic mice model is characterized by increased ROS, increased protein MetO with mitochondria structural pathology, and cardiac fibrosis. In addition, MsrB2 was significantly increased in mouse DM cardiomyocytes, supporting the induction of a protective process. Further, MsrB2 directly induces Parkin and LC3 activation (mitophagy markers) in cardiomyocytes. In MsrB2, knockout mice displayed abnormal electrophysiological function, as determined by ECG analysis. Histological analysis confirmed increased cardiac fibrosis and disrupted cardiac tissue in MsrB2 knockout DM mice. We then corroborated our findings in human DM heart samples. Our study demonstrates that increased MsrB2 expression in the heart protects against diabetic cardiomyopathy.

Primary surgery versus pharmacotherapy for newly diagnosed ileocecal Crohn's disease: a hospital-based cohort study.

Background/Aims: Limited knowledge exists regarding the optimal timing and relative advantages of primary surgery compared to medical treatment in ileocecal Crohn's disease (CD). This study aimed to compare long-term outcomes between medication-based treatment versus surgery in newly diagnosed ileocecal CD patients in an Asian population. Methods: Among the 885 patients diagnosed with CD and enrolled in the study site hospital cohort between 1980 and 2013, 93 (10.5%) had ileocecal CD. Patients were categorized into either the surgical or medical remission group based on their initial management strategy that led to remission. The rates of relapse, hospitalization, and surgery after achieving remission were compared using Kaplan-Meier curves. Results: The numbers of patients assigned to surgical and medical remission groups were 15 (17.0%) and 73 (83.0%), respectively. The surgical remission group exhibited a lower relapse rate and longer maintenance of remission (10.7 vs. 3.7 yr; p = 0.017) during a median follow-up of 6.6 years. Hospitalization after the first remission tended to be lower in the surgical remission group (p = 0.054). No cases required repeated intestinal resection after the initial surgical remission, whereas a 23% surgery rate was reported at 5 years after initial medical treatment (p = 0.037). In the multivariable analysis, the initial medication-based treatment was significantly associated with relapse (hazard ratio = 3.23, p = 0.039). Conclusions: In selected cases of localized ileocecal CD, ileocolic resection might be a favorable alternative to medication- based treatment, as it demonstrates a lower relapse rate and longer maintenance of remission.

Intraoperative Normal Saline Administration and Acute Kidney Injury in Patients Undergoing Liver Transplantation.

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.

The impact of preoperative coronavirus disease 19 infection on early postoperative mortality during the vaccination era: a nationwide retrospective cohort study.

BACKGROUND: We aimed to investigate the optimal surgical timing in patients with preoperative coronavirus disease 2019 (COVID-19) infection to minimize postoperative morbidity and mortality during the COVID-19 vaccination era. METHODS: The Korean nationwide data on patients who underwent standard surgery under general anesthesia in 2021 were analyzed. Patients were categorized based on the time from COVID-19 diagnosis to surgery: 0-4, 5-8, > 8 weeks, and those without preoperative COVID-19 infection. Multivariable logistic regression analysis, considering preoperative COVID-19 vaccination status (fully vaccinated vs. unvaccinated or partially vaccinated), was performed to associate the preoperative COVID-19 infection timing with 30- and 90-day postoperative mortality and 30-day respiratory complications. RESULTS: Among the 750,175 included patients, 28.2% were preoperatively fully vaccinated. Compared with patients without prior COVID-19 infection, those who had surgery 0-4 weeks (adjusted odds ratio [OR]: 4.28, 95% CI [1.81, 10.13], P = 0.001) and 5-8 weeks (adjusted OR: 3.38, 95% CI [1.54, 7.44], P = 0.002) after COVID-19 infection had a significantly increased risk of 30-day mortality. Preoperative full vaccination was significantly associated with a decrease in 90-day mortality (adjusted OR: 0.93, 95% CI [0.89, 0.98], P = 0.007) and 30-day respiratory complications (adjusted OR: 0.85, 95% CI [0.82, 0.87], P < 0.001), but not with 30-day mortality (P = 0.916). CONCLUSIONS: COVID-19 infection eight weeks preoperatively was associated with an increased 30-day postoperative mortality. Preoperative full vaccination was not associated with 30-day mortality but was related to lower risk of 90-day mortality and 30-day respiratory complications.

Proteomic analysis reveals activation of platelet- and fibrosis-related pathways in hearts of ApoE-/- mice exposed to diesel exhaust particles.

Air pollution is an environmental risk factor linked to multiple human diseases including cardiovascular diseases (CVDs). While particulate matter (PM) emitted by diesel exhaust damages multiple organ systems, heart disease is one of the most severe pathologies affected by PM. However, the in vivo effects of diesel exhaust particles (DEP) on the heart and the molecular mechanisms of DEP-induced heart dysfunction have not been investigated. In the current study, we attempted to identify the proteomic signatures of heart fibrosis caused by diesel exhaust particles (DEP) in CVDs-prone apolipoprotein E knockout (ApoE-/-) mice model using tandem mass tag (TMT)-based quantitative proteomic analysis. DEP exposure induced mild heart fibrosis in ApoE-/- mice compared with severe heart fibrosis in ApoE-/- mice that were treated with CVDs-inducing peptide, angiotensin II. TMT-based quantitative proteomic analysis of heart tissues between PBS- and DEP-treated ApoE-/- mice revealed significant upregulation of proteins associated with platelet activation and TGFß-dependent pathways. Our data suggest that DEP exposure could induce heart fibrosis, potentially via platelet-related pathways and TGFß induction, causing cardiac fibrosis and dysfunction.

IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1α is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1α. In this study, we aimed to determine the effects of IDF-11774 on gastric cancer cell lines. Treatment with IDF-11774 was found to markedly decrease the proliferation, migration, and invasion of the gastric cancer cell lines. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, and Jun N-terminal kinase in the mitogen-activated protein kinase signaling pathways were markedly increased in a dose-dependent manner, ultimately promoting apoptosis via the induction of cell cycle arrest. Our findings indicate that HIF-1α inhibitors are potent drugs for the treatment of gastric cancer.