The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor positive metastatic breast cancer.

We aimed to evaluate the feasibility and preliminary efficacy of trauma-focused group psychotherapy in adolescents who experienced traumatic events in Korea. Participants were assigned and recruited from two sites in Korea. Children in Disaster: Evaluation and Recovery (CIDER) V1.0 is a trauma-focused group psychotherapy approach consisting of psychoeducation, normalization, stabilization, and techniques of managing the traumatic memory. The CIDER intervention consists of eight 50-minute-long sessions. The effectiveness of the intervention was evaluated using the Korean version of the Children’s Response to Traumatic Events Scale-Revised (K-CRTES-R), the Beck Depression Inventory (BDI), the State Anxiety Inventory for Children (SAIC), and the Pediatric Quality of Life Inventory (PedQL). Data were analyzed by Wilcoxon signed-rank test. We recruited 22 traumatized adolescents (mean age 16 years; SD 1.43; range 13–18 years old; 71.4% boys) in this pilot study. The K-CRTES-R scores were significantly improved (Z = −2.85, p < 0.01). The BDI demonstrated the effectiveness of the therapy (Z = −2.35, p < 0.05). The assessment of the PedQL supported the effect of CIDER (Z = −3.08, p < 0.01). However, there was no statistically significant differences in the SAIC scores (Z = −1.90, p > 0.05). The results show that there is preliminary evidence that CIDER intervention reduces post-traumatic stress and depressive symptoms and improves quality of life. Our findings indicate that CIDER is feasible for treating adolescents exposed to traumatic events. Larger controlled trials are needed to establish the efficacy of this trauma-focused group psychotherapy and examine its impact on post-traumatic stress disorder.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass &lt;0.789 in men and &lt;0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

We investigated the potential genetic variants using whole exome sequencing (WES) and evalu-ated the disease course using T cell receptor (TCR) repertoire analysis in rheumatoid arthritis (RA). Fourteen patients with RA and five healthy controls (HCs) were enrolled. For patients with RA, only naïve patients were recruited before treatment, and data were collected at baseline and 6 and 12 months after the initiation of disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using Shannon-Weiner diversity. Some variants were detected by WES, but their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in patients with RA was lower than that in HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively cor-related with laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified and the clinical significance of TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Ecklonia cava (E.cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.

Tobacco smoke is an environmental mixture including polycyclic aromatic hydrocarbons and may interfere in endocrine system as an EDC in aging. Thus, we performed a molecular epidemiological approach with in-depth biological monitoring of combustible cigarette smoking among adolescents and adults in South Korea (N=620) with exposure biomarkers, i.e., exhaled CO, urinary cotinine, t,t-muconic acid (TTMA), malondialdehyde (MDA), and obtained information of their lifestyle and tobacco addiction status. We also diagnosed the genetic polymorphisms on the 96 SNPs for tobacco-metabolism, -addiction, and expression differences and compared mtDNA abnormalities in buccal and blood cells. As results, there were positive associations among the above tobacco exposure biomarkers. Man or youth smokers showed high frequency in some of mtDNA alteration, such as ‘SNPs for inconsistent bases between buccal and blood cells’. Among the SNPs, the polymorphisms on SULT1A1, DRD2, and ADH1B were related to multi-exposure biomarkers. Interestingly, youth showed similar levels of urinary TTMA and MDA to adults, although their pack-year was approx. 1/6 volume of that of adults. We also observed the negative association between urinary MDA levels and the growth rate in the adolescents (p<0.05). In conclusion, the present biological monitoring provides high susceptible population, i.e., adolescents rather than adults, and reliable genetic factors affecting tobacco exposure. The inferred environment-gene-gene interaction suggests tobacco smoking accelerats aging in adolescents as an EDC.

A new compound containing a triene, a tetrahydropyran ring and glycine ester functionalities, restricticin B (1), together with four known compounds (2-5) were obtained from the EtOAc extract of the marine fungus Penicillium janthinellum. The planar structure of 1 was determined by detailed analyses of MS, 1D and 2D NMR data. The relative and absolute configurations of 1 were established via analyses of NOESY spectroscopy data, comparison of optical rotation values with those of restricticin derivatives reported and electronic circular dichroism (ECD). All the compounds were screened for their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglia cells. Restricticin B (1) and N-acetyl restricticin (2) exhibited anti-neuroinflammatory effects by suppressing the production of pro-inflammatory mediators in activated microglial cells.