A-kinase anchoring protein 12 (AKAP12) is a key scaffolding protein that regulates cellular signaling by anchoring protein kinase A (PKA) and other signaling molecules. While recent studies suggest an important role for AKAP12 in the brain, including cognitive functions, its role in middle-aged mice and potential sex differences are not fully understood. Therefore, this study investigated the effects of AKAP12 on cognitive and exploratory behavior in middle-aged mice, focusing on sex differences. Cognitive function was assessed using the spontaneous Y-maze test and the novel object recognition test (NORT). No significant sex differences in cognitive function were found in middle-aged C57BL/6J mice; however, female mice showed greater exploratory behavior during the NORT. In addition, both middle-aged male and female Akap12 knockout (KO) mice performed similarly to wild-type (WT) mice in the Y-maze test, but had lower discrimination indices in the NORT, suggesting a potential role for AKAP12 in short-term memory. Notably, exploratory behavior was suppressed in female Akap12 KO mice compared to WT mice, whereas male Akap12 KO mice did not show this effect. There were no significant differences in movement distance and velocity during the Y-maze test and NORT between WT and KO mice of either sex. These results indicate that AKAP12 affects cognitive function and exploratory behavior in middle-aged mice and that these effects differ between sexes.

Distinct physical phenotypes observed in obese frailty are primarily attributable to the effect of obesity, with further impairment of muscle function resulting from the combined effects of frailty syndromes and obesity. Pure frailty and obese frailty share overlapping biological phenotypes, particularly in the regulation of muscle protein synthesis. Moreover, the interaction between obesity and frailty syndromes gives rise to both overlapping and distinct biological phenotypes, especially in the regulation of specific degradation signaling proteins.

A-kinase anchoring protein 12 (AKAP12) is a key scaffolding protein that regulates cellular signaling by anchoring protein kinase A (PKA) and other signaling molecules. While recent studies suggest an important role for AKAP12 in the brain, including cognitive functions, its role in middle-aged mice and potential sex differences are not fully understood. Therefore, this study investigated the effects of AKAP12 on cognitive and exploratory behavior in middle-aged mice, focusing on sex differences. Cognitive function was assessed using the spontaneous Y-maze test and the novel object recognition test (NORT). No significant sex differences in cognitive function were found in middle-aged C57BL/6J mice; however, female mice showed greater exploratory behavior during the NORT. In addition, both middle-aged male and female Akap12 knockout (KO) mice performed similarly to wild-type (WT) mice in the Y-maze test, but had lower discrimination indices in the NORT, suggesting a potential role for AKAP12 in short-term memory. Notably, exploratory behavior was suppressed in female Akap12 KO mice compared to WT mice, whereas male Akap12 KO mice did not show this effect. There were no significant differences in movement distance and velocity during the Y-maze test and NORT between WT and KO mice of either sex. These results indicate that AKAP12 affects cognitive function and exploratory behavior in middle-aged mice and that these effects differ between sexes.

Distinct physical phenotypes observed in obese frailty are primarily attributable to the effect of obesity, with further impairment of muscle function resulting from the combined effects of frailty syndromes and obesity. Pure frailty and obese frailty share overlapping biological phenotypes, particularly in the regulation of muscle protein synthesis. Moreover, the interaction between obesity and frailty syndromes gives rise to both overlapping and distinct biological phenotypes, especially in the regulation of specific degradation signaling proteins.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can diminish the quality of life of both children and adults in academic, occupational, and social contexts. The kynurenine pathway (KP) contains a set of enzymatic reactions involved in tryptophan (TRP) degradation. It is known to be associated with the risk of developing ADHD. This review will address the KP and underlying mechanism of inflammation in ADHD. Potential inflammatory biomarkers reported in the most recent studies are summarized. Although a strong neuroimmunological basis has been established due to the advances of recent neurobiological research, the pathophysiology of ADHD remains unclear.

Background: While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a cornerstone of therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC), resistance remains a major clinical challenge. The genomic landscape of early-stage (ES) EGFR-mutant NSCLC and its evolution to advanced-stage (AS) disease is not fully understood. This study aimed to characterize the molecular disparities between ES and AS EGFR-mutant NSCLC and to identify genomic alterations associated with EGFR-TKI treatment outcomes. Methods: We have collected and profiled the complex genomes of 121 ES and 74 AS NSCLCs to determine their molecular and clinical disparities. Furthermore, we analyzed 84 EGFR-mutant NSCLC patients who were treated with EGFR-TKIs to identify potential molecular correlates that could predict the treatment response within the clinic. Patients were stratified by progression-free survival (PFS) and overall response rate (ORR), and hazard ratio analyses were performed. Results: In the study, significant enrichment of mutations in MTOR, ATRX, STAG2, ABL1, and SPEN was observed in AS tumors, whereas ES tumors predominantly exhibited mutations activating JAK2, ERBB2, and FGFR4. In the EGFR-TKI cohort, poor responders harbored frequent mutations in TP53, KIT, and ALK, and these were associated with worse clinical outcomes. Conversely, favorable responders showed enrichment of MTOR, ATM, EP300, and PIK3R1 mutations. ALK and FANCA were linked to increased hazard, while EP300 and PIK3R1 mutations correlated with improved prognosis. Conclusions: Given the growing importance of biomarker-driven treatment in the field of oncology, our results collectively open up new therapeutic opportunities for ES NSCLC patients.

Lower birth weight, treated patent ductus arteriosus, serum glucose levels, and higher intravenous lipid levels are significant risk factors for HTG. Adjusting the lipid dose aids in triglyceride normalization and reducing severe retinopathy of prematurity risk. Careful monitoring and management of intravenous lipid emulsion infusion rates are crucial to prevent HTG.

The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.

A-kinase anchor protein 12 (AKAP12), a scaffold protein, has been implicated in the central nervous system, including blood-brain barrier (BBB) function. Although its expression level in the corpus callosum is higher than in other brain regions, such as the cerebral cortex, the role of AKAP12 in the corpus callosum remains unclear. In this study, we investigate the impact of AKAP12 deficiency by transcriptome analysis using RNA-sequencing (RNA-seq) on the corpus callosum of AKAP12 knockout (KO) mice. We observed minimal changes, with only 13 genes showing differential expression, including <i>Akap12</i> itself. Notably, <i>Klf2</i> and <i>Sgk1</i>, genes potentially involved in BBB function, were downregulated in AKAP12 KO mice and expressed in vascular cells similar to <i>Akap12</i>. These changes in gene expression may affect important biological pathways that may be associated with neurological disorders. Our findings provide an additional data set for future research on the role of AKAP12 in the central nervous system.

Seoyeon Chin, Hyoyoung Kim, Yesul Kim, Chaewon Heo, Bo-young Kwon, Boyoon Choi, Bobae Lee, Jiye Lee, Chae-Eun Kwon, Yeongdo Mun, Kaveesha Fernando, and Ji Hyun Park. Korean J Clin Pharm 2023;33:153-67. https://doi.org/10.24304/kjcp.2023.33.3.153

For the past 10 years, immunotherapy has emerged as a promising approach to combat advanced stages of cancers. The ability of immune system to detect foreign matters and produce proteins (antibodies) against them is one of the essential means by which the body protect itself against diseases. In a similar vein, delivering substantial amount of antibodies targeting the tumor complex has been considered as a potentially effective approach to treat cancer. Monoclonal antibody (mAb) have demonstrated to be a useful addition to the armamentarium for many types of cancer. Pertuzumab, panitumumab, trastuzumab, and cetuximab, mAbs that are directly binding to the receptors of the epidermal growth factor family, result in the diminished function of subsequent signaling pathways. 1) In addition to signaling interruption, some of these mAbs can also activate antibody-dependent cellular cytotoxicity (ADCC) to cancer cells. 2)