Background: Despite advancements in laboratory animal facility management, pinworm infections remain a persistent issue in immunodeficient mouse colonies. Rapid diagnosis and treatment are crucial to mitigating potential scientific and economic consequences. Effective control requires both the administration of anthelmintic agents and rigorous environmental decontamination. However, the safety and efficacy of these treatments in genetically modified mouse models remains uncertain.Case presentation Aspiculuris tetraptera infestation was identified in multiple immunodeficient mouse models housed in a laboratory facility. Diagnosis was confirmed through fecal flotation for egg detection and necropsy for adult worm examination in the large intestines. Mice received three subcutaneous ivermectin injections at two-week intervals, coupled with environmental decontamination using ivermectin spray for four consecutive weeks. Following treatment, all colonies tested negative for A. tetraptera without any mortality. Conclusions A combination of subcutaneous ivermectin injection and environmental spray application effectively eradicated A. tetraptera infestation in immunodeficient mouse colonies. The treatment protocol led to the complete elimination of eggs and adult worms, offering a practical strategy for managing pinworm infections in genetically modified mouse models. Limitations include the small sample size, and the lack of a comprehensive evaluation of physiological and metabolic safety in immunodeficient mice. Further validation will be required to confirm the broader applicability of this approach.

Background: The effects of propofol, a commonly used intravenous anesthetic, on the breast cancer tumor microenvironment are not well understood. This study examined the influence of propofol on natural killer group 2, member D (NKG2D) ligand expression, matrix metalloproteinase (MMP)-mediated immune evasion, and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells. Methods: We studied three human breast cancer cell lines representing distinct receptor subtypes: MCF-7 (estrogen receptor - and progesterone receptor-positive), MDA-MB-453 (human epidermal growth factor receptor 2-positive), and HCC-70 (triple-negative). Cells were treated with propofol at concentrations of 0 μg/ml (control; C), 4 μg/ml (P4), or 8 μg/ml (P8). Assessments included mRNA and protein expression of NKG2D ligands, NK cell cytotoxicity, protein levels of MMP-1 and MMP-2, and concentrations of soluble NKG2D ligands. Results: In MCF-7 and HCC-70 cell lines, propofol upregulated the mRNA and protein expression of NKG2D ligands in a dose-dependent manner, enhancing NK cell-mediated lysis. In contrast, in MDA-MB-453 cell lines, propofol downregulated the mRNA and protein expression of NKG2D ligands, resulting in diminished NK cell-mediated lysis. Across all receptor subtypes, propofol did not affect the expression of MMP-1 or MMP-2 or the concentration of soluble NKG2D ligands. Conclusions Our results demonstrate that propofol exerts receptor subtype-dependent effects on NK cell-mediated immunosurveillance in breast cancer cell lines, potentially mediated by changes in the transcription of NKG2D ligands rather than by alterations in MMP expression or their proteolytic activity.

Induced pluripotent stem cells (iPSCs) are a promising cell source for regenerative medicine. Clinical applications require a large number of functional red blood cells (RBCs), making it essential to ensure the proliferation of actively dividing, nucleated erythroblasts derived from iPSCs. Small molecules can enhance the efficiency and frequency of iPSC-derived cell differentiation. Sirtuin 1, a key enzyme in multiple biological processes, has been implicated in enhancing iPSC-derived cell differentiation. However, the specific effects of Sirtuin 1 on erythroblast proliferation from iPSCs remain unclear. Here, we developed a protocol to examine the effects of Sirtuin 1 on erythroblasts after endothelial-to-hematopoietic transition (EHT). We found that Sirtuin 1 activation increased the frequency of CD71＋CD235a＋erythroblasts at the early stage after EHT, suggesting a role for Sirtuin 1 in the proliferation of these specified erythroblasts. These findings reveal that Sirtuin 1 activation benefits erythroblast proliferation and could be considered for translational application in large-scale RBC culture.

Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. Given Piezo2's widespread expression across diverse subpopulations of DPA neurons, this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels (VGSCs) and neuropeptide profiles. Using whole-cell patch-clamp recordings, we observed mechanically activated action potentials (APs) and classified AP waveforms based on the presence or absence of a hump during the repolarization phase. Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties, including tetrodotoxin-resistant VGSCs (Na_V1.8 and Na_V1.9) and TRPV1 expression. Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides-including two CGRP isoforms (α-CGRP and β-CGRP), Substance P, and Galanin-and the expression of Na_V1.8 and Na_V1.9, which were linked to defined AP subtypes. These molecular associations were further validated in Piezo2⁺ DPA neurons using fluorescence in situ hybridization. Together, these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
Ion Channels/physiology* ; Mechanotransduction, Cellular/physiology* ; Animals ; Neurons, Afferent/metabolism* ; Patch-Clamp Techniques ; Mice ; TRPV Cation Channels/metabolism* ; Action Potentials ; Rats

Compared with other treatments, surgical resection is an effective treatment method with the lowest local recurrence rate and the highest survival rate for hepatocellular carcinoma (HCC). To achieve excellent results after surgical treatment, it is essential to carefully select patients who are suitable for hepatic resection and minimize postoperative complications and liver function decline through standardized surgical methods and pre- and postoperative management. However, domestic and international treatment guidelines only broadly recommend the application of hepatic resection for HCC with a single tumor and good liver function. Hence, practical treatment guidelines are required that can be standardized and used according to the varying clinical environments, including indications for hepatic resection, preoperative evaluation, basic principles of hepatic resection, minimally invasive hepatic resection, pre- and postoperative patient management, surgical treatment considerations in specific infection situations, and follow-up after surgical resection. Accordingly, an expert group from the Korean Liver Cancer Association Research Committee has developed practical recommendations based on expert consensus regarding the surgical treatment of HCC through a Delphi study.

This study aimed to explore the participation experiences of patients with type 2 diabetes in an Automated Personalized Self-Care program, assess the changes in self-care behavior and glycemic control, and evaluate the stages of change and readiness to change using the transtheoretical model (TTM). Methods: We examined 16 patients with type 2 diabetes who participated in a diabetes self-care program using a mobile application. Purposive sampling continued until data saturation. Using a mixed method study, we analyzed the participants’ characteristics, self-care behavior, stage of change, and readiness to change quantitatively and analyzed the qualitative data using Elo and Kyngas’s content analysis method. Results: The compliance group (CG) showed improved self-care behavior and glycemic control. In the CG, the proportion of participants in the action stage was higher in the exercise and diet domains and lower in the blood glucose testing and medication domains than in the non-compliance group (NCG). Readiness to change, motivation for health behaviors, and social motivation were higher in the CG, whereas personal motivation was higher in the NCG. In this qualitative study, three categories and 11 subcategories were identified. The findings suggest the CG regarded their experience in the program more frequently as positive, whereas the NCG perceived greater barriers to using the mobile application in the program. Conclusion: Based on the differences identified between the CG and NCG, TTM-based strategies are needed to facilitate the progression of NCG to the action stage.

Background: Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. Methods: We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845–0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752–0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. Conclusions The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.

Purpose: Providing continuous self-care support to the growing diabetes population is challenging. Strategies are needed to enhance engagement in self-care, utilizing innovative technologies for personalized feedback. This study aimed to assess the feasibility of the Automated Personalized Self-Care program among type 2 diabetes patients and evaluate its preliminary effectiveness. Methods: A parallel randomized pilot trial with qualitative interviews occurred from May 3, 2022, to September 27, 2022. Participants aged 40e69 years with type 2 diabetes and HbA1c ! 7.0% were recruited. The three-month program involved automated personalized goal setting, education, monitoring, and feedback. Feasibility was measured by participants' engagement and intervention usability. Preliminary effectiveness was examined through self-care self-efficacy, self-care behaviors, and health outcomes. Qualitative interviews were conducted with the intervention group. Results: A total of 404 patients were screened. Out of the 61 eligible patients, 32 were enrolled, resulting in a recruitment rate of 52.5%. Retention rates at three months were 84.2% and 84.6% in the intervention and control groups, respectively. Among the intervention group, 81.3% satisfied adherence criteria.Mobile application's usability scored 66.25, and participants' satisfaction was 8.06. Intention-to-treat analysis showed improvements in self-measured blood glucose testing, grain intake, and HbA1c in the intervention group. Qualitative content analysis identified nine themes. Conclusion Feasibility of the program was verified. A larger randomized controlled trial is needed to determine its effectiveness in self-care self-efficacy, self-care behaviors, and health outcomes among type 2 diabetes patients. This study offers insights for optimizing future trials assessing clinical effectiveness.

Background/Aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression. Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo. Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice. Conclusions KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Background: Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury. Methods: We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station. Results: Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1β, and MCP-1 production after IR or hypoxia-reoxygenation injury. Conclusion PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury.