HFD Feeding for Seven Months Abolishes STING Disruption-driven but not Female Sex-based Protection against Hepatic Steatosis and Inflammation in Mice: HFD feeding alters MASLD.

Stimulator of interferon genes (STING) is positively correlated with the degrees of liver inflammation in human metabolic dysfunction-associated steatotic liver disease (MASLD). In addition, STING disruption alleviates MASLD in mice fed a high-fat diet (HFD) for 3 months (3-m-HFD). Here we investigated the role of the duration of dietary feeding in regulating MASLD in mice and explored the involvement of STING in sex differences in MASLD. Both male and female STING-disrupted (STINGgt) and wild-type C57BL/6J mice were fed an HFD for 3 or 7 months (7-m-HFD). Additionally, female STINGgt mice upon ovariectomy (OVX) and 3-m-HFD were analyzed for MASLD. Upon 3-m-HFD, STINGgt mice exhibited decreased severity of MASLD compared to control. However, upon 7-m-HFD, STINGgt mice were comparable with wild-type mice in body weight, fat mass, and MASLD. Regarding regulating the liver RNA transcriptome, 7-m-HFD increased the expression of genes indicating proinflammatory activation of various liver cells. Interestingly, the severity of MASLD in female mice was much lighter than in male mice, regardless of STING disruption. Upon OVX, female STINGgt mice showed significantly increased severity of MASLD relative to sham control but were comparable with male STINGgt mice. Upon treatment with 17-beta estradiol (E2), hepatocytes revealed decreased fat deposition while macrophages displayed decreases in lipopolysaccharide-induced phosphorylation of Nfkb p65 and Jnk p46 independent of STING. These results suggest that 7-m-HFD, without altering female sex-based protection, abolishes STING disruption-driven protection of MASLD, likely through causing proinflammatory activation of multiple types of liver cells to offset the effect of STING disruption.

The impact of the COVID-19 pandemic on infant obesity: A nationwide retrospective cohort study.

BACKGROUND: Lifestyle changes, such as those related to the COVID-19 pandemic, including alterations in physical activity and dietary habits, are known to affect pregnancy outcomes. In particular, suboptimal intrauterine conditions during pregnancy are known to influence not only fetal growth but also growth during infancy. However, research on the impact of the environmental changes caused by the COVID-19 pandemic on the growth of infants and children during their early years is lacking. To address this issue, this study evaluated the effect of the COVID-19 pandemic on obesity in infants. METHODS: This retrospective cohort study used the data collected from the Korea National Health Insurance (KNHI) claims database. The data of 1985,678 women who delivered infants between 2015 and 2021 were collected. Women who delivered during the pandemic and those who delivered during the pre-pandemic period were matched in a 1:1 frequency-matched pair procedure for factors such as age, hypertension, diabetes mellitus, preeclampsia, gestational diabetes mellitus, mode of delivery, gestational age at delivery, offspring sex, and birth weight. Finally, 197,580 women were enrolled. The weight and head circumference of infants (4-6 months of age) of the COVID-19 pandemic group were compared with those of the pre-pandemic group. RESULTS: The COVID-19 pandemic group infants exhibited significantly higher weight and prevalence of obesity at 4-6 months of age compared to infants in the pre-pandemic group. After adjustment for covariates, pandemic group infants had a higher risk of obesity (odds ratio: 1.54, 95% confidence interval: 1.51-1.57) compared to the pre-pandemic group infants. CONCLUSION: The COVID-19 pandemic has had a notable impact on the weight of infants aged 4-6 months. This suggests that pandemic conditions may influence the growth of newborns, underscoring the importance of monitoring and assessing trends in the growth of infants born during such crises.

Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study.

BACKGROUND: We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults. METHODS: The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616). RESULTS: During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up. CONCLUSION: Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

The risk of cardiovascular disease and stroke in survivors of head and neck cancer in Korea.

BACKGROUND: Head and neck cancer (HNCA) survivors have a high risk of developing cardiovascular disease (CVD) or stroke because of sharing risk factors of disease. Therefore, we investigated the risk of CVD or stroke occurrence among HNCA survivors in Korea based on the Health Insurance Review and Assessment (HIRA) Service claims database. METHODS: We retrieved claims data of patients who were diagnosed with HNCA in 2014-2015 using ICD-10 code and followed up data until 2018. Patients with newly diagnosed with CVD or stroke after HNCA diagnosis during the follow-up period were detected. We analyzed the characteristics of patients with HNCA who were subsequently diagnosed with CVD or stroke. In addition, the risk factors of CVD or stroke occurrence were investigated using Cox proportional hazard regression analysis. RESULTS: Among the 8288 patients with HNCA, 477 and 404 patients were diagnosed with new-onset CVD and stroke, respectively. Patients with hypertension, diabetes mellitus (DM), and hyperlipidemia had a 3.25-fold higher risk of CVD comparing to patients without any underlying disease (95% confidence index [CI], 2.38-4.45) Patients with three underlying diseases had a 2.92-fold higher risk of stroke compared to patients without any underlying disease (95% CI 2.03-4.21). CONCLUSIONS: HNCA survivors with hypertension, DM, and hyperlipidemia should be cautious of the risks of CVD and stroke.

Herceptin-conjugated temperature-sensitive immunoliposomes encapsulating gemcitabine for breast cancer.

Gemcitabine (2',2'-difluorodeoxycytidine, GCT) is an analog of deoxycytidine with cytotoxicity for breast cancer cells. However, because of its hepatotoxicity and other side effects, an efficient drug delivery system is needed for better therapeutic outcomes. A temperature-sensitive PEGylated immunoliposome (TSL) with trastuzumab (or Herceptin) attached encapsulating GCT (Her-PEG-TSL-GCT) was prepared. The mean diameter of the liposome was about 200 nm and the prepared immunoliposome showed the capacity to deliver the payload to the hyperthermic environment. The actual number of antibody molecules attached to one single liposome is about 19, with the GCT encapsulation efficiency of 54.6 ± 3.50 %. This immunoliposome shows a temperature-dependent drug release at around 41-43 °C. Anticancer activity of Her-PEG-TSL-GCT was determined using HER-2 expressing breast cancer cells, SK-BR-3, in vitro and resulted in increased cytotoxicity compared to free GCT (IC20 11.7 nM) or conventional liposome lacking the targeting antibody. In conclusion, these data show that improved delivery of GCT to breast cancer cells can be achieved by Her-PEG-TSL-GCT in vitro, and this strategy could be used for breast cancer therapy with further studies.