The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.

Kim ES, et al. J Korean Med Sci. 2021 Sep;36(39):e260. https://doi.org/10.3346/jkms.2021.36.e260

The objective of this systematic review and meta-analysis was to summarize the effects of early initiation and achievement of a high dose of parenteral lipids (≥1.5 g/kg/day reached within the first 24 h of birth) on growth and adverse outcomes in preterm infants. PubMed, EMBASE, and Cochrane databases were utilized to search for publications for this meta-analysis. Randomized controlled trials were eligible if data on growth or clinical outcome was available. The search returned nine studies. The mean proportion of postnatal weight loss (%) was lower (mean difference [MD]: −2.73; 95% confidence interval [CI]: −3.69, −1.78), and the mean head circumference near the term equivalent age (cm) was higher in the early high lipid treatment group (MD: 0.67; 95% CI: 0.25, 1.09). There was a favorable association of early high lipid administration with the incidence of extrauterine growth restriction (relative risk [RR]: 0.27; 95% CI: 0.15, 0.48). Generally, there were no differences in morbidities or adverse outcomes with early high lipid administration. Early initiation of parenteral lipids and high dose achieved within the first 24 h of life appear to be safe and endurable and offer benefits in terms of growth.

The government of South Korea implemented social distancing measures to control the coronavirus disease 2019 (COVID-19) outbreak. This study aimed to compare the composite preterm (PT) or low birth weight (LBW) birth rates during the COVID-19 pandemic period in South Korea to those during the prior decade, and to find out the associations of childbirth during the pandemic period with PT or LBW births. Over a ten-year period, this retrospective cohort study was performed in a single hospital in the Seoul metropolitan city. The COVID-19 period was defined as running from 22 March 2020, to 31 October 2020, and the pre-COVID-19 period as the sum of parallel periods from 2011 to 2019. Trends in composite birth rates were investigated, and logistic regression analysis was conducted to investigate independent factors associated with composite births. There were 246 and 2765 singleton deliveries during the COVID-19 period and the pre-COVID-19 period, respectively. The composite birth rate decreased from 16.5% to 9.8%. Childbirth during the pandemic was independently associated with a decreased composite birth rate (adjusted odds ratio, 0.563; 95% confidence interval, 0.355−0.844, p = 0.015). These findings suggested that the COVID-19 pandemic might provide an opportunity to find out preventive factors for PT or LBW births.

This study aimed to identify the independent association of handgrip strength and current smoking with cardiometabolic risk in adolescents. Data of 1806 adolescents (12–18 years) from the Korea National Health and Nutrition Examination Surveys were analyzed by complex samples logistic regression analyses. Handgrip strength was normalized by body weight into relative handgrip strength. A cardiometabolic risk index score was calculated from the z-scores of the following components: waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and blood pressure. Relative handgrip strength showed an inverse association with high cardiometabolic risk, with an adjusted odds ratio of 8.5 (95% confidence interval [CI], 3.7–19.3) for boys and 5.7 (95% CI, 2.9–11.2) for girls on comparing the lowest and the highest age-and sex-specific quartiles of relative handgrip strength. The adjusted odds ratios for high cardiometabolic risk on comparing the second quartile and the highest quartile of relative handgrip strength were 3.9 (95% CI, 1.7–8.9) in boys and 2.6 (95% CI, 1.3–5.3) in girls. Current smoking was independently associated with high cardiometabolic risk in boys aged 15–18 years. These findings suggest the need to increase muscle strength in adolescents and reduce smoking in older boys to promote cardiometabolic health.

Objective To evaluate the effects of direct swallowing training (DST) alone and combined with oral sensorimotor stimulation (OSMS) on oral feeding ability in very preterm infants. Design Blinded, parallel group, randomised controlled trial (1:1:1). Setting Neonatal intensive care unit of a South Korean tertiary hospital. Participants Preterm infants born at <32 weeks of gestation who achieved full tube feeding. Interventions Two sessions per day were provided according to the randomly assigned groups (control: two times per day sham intervention; DST: DST and sham interventions, each once a day; DST+OSMS: DST and OSMS interventions, each once a day). Primary outcome Time from start to independent oral feeding (IOF). Results Analyses were conducted in 186 participants based on modified intention-to-treat (63 control; 63 DST; 60 DST+OSMS). The mean time from start to IOF differed significantly between the control, DST and DST+OSMS groups (21.1, 17.2 and 14.8 days, respectively, p=0.02). Compared with non-intervention, DST+OSMS significantly shortened the time from start to IOF (effect size: −0.49; 95% CI: −0.86 to –0.14; p=0.02), whereas DST did not. The proportion of feeding volume taken during the initial 5 min, an index of infants’ actual feeding ability when fatigue is minimal, increased earlier in the DST+OSMS than in the DST. Conclusions In very preterm infants, DST+OSMS led to the accelerated attainment of IOF compared with non-intervention, whereas DST alone did not. The effect of DST+OSMS on oral feeding ability appeared earlier than that of DST alone. Trial registration number ClinicalTrials.gov Registry (NCT02508571).