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Hyun-Jin Kim,1,* Sung-Suk Suh,2,* Jeongwon Park,3 Min-Ji Shin,2 Man Hyung Koo,4 Suk Jun Lee,5 Young-Jun Jeon,6 Seongsoo Lee,3 Ui-Joung Youn,7 Sung-Hak Kim1 1Department of Animal Science, Chonnam National University, Gwangju, 61186, Korea; 2Department of Biosciences, Mokpo National University, Muan, 58554, Korea; 3Gwangju Center, Korea Basic Science Institute (KBSI), Gwangju, 61186, Korea; 4Research Unit of Cryogenic Novel Material, Korea Polar Research Institute, Incheon, 21990, Korea; 5Department of Biomedical Laboratory Science, College of Health & Medical Sciences, Cheongju University, Chungbuk, 28503, Korea; 6Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea; 7Division of Life Sciences, Korea Polar Research Institute (KOPRI), Incheon, 21990, Korea*These authors contributed equally to this workCorrespondence: Ui-Joung Youn, Division of Life Sciences, Korea Polar Research Institute (KOPRI), Incheon, 21990, Korea, Tel +82 32 760 5562, Email ujyoun@kopri.re.kr Sung-Hak Kim, Department of Animal Science, Chonnam National University, Gwangju, 61186, Korea, Tel +82 62 530 2115, Email sunghakkim@jnu.ac.krBackground: Glioma stem cells (GSCs) have been reported to contribute to tumor initiation and relapse, therapy resistance, and intra-tumoral heterogeneity of glioblastoma multiforme. Therefore, inhibiting GSCs presents a critical therapeutic tactic to suppress the aggressiveness of tumors.Methods: In this study, we examined the effects of 7β-22 dihydroxyhopane (AP 18), isolated from the sub-Antarctic lichen, Pseudocyphellaria freycinetii. The cytotoxic effect of AP 18 and its effects on cell proliferation were assessed by alamarBlue assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Real-time confluence analysis was performed with a Celloger automatic live cell imaging system. Western Blotting and 3-D optical diffraction tomography (ODT) imaging were performed to determine whether apoptosis was triggered by AP 18. A Limiting dilution assay and qRT-PCR were performed to investigate the impact of AP 18 on GSC stemness.Results: AP 18 significantly reduced GSCs viability and proliferation, inducing programmed cell death identified by Annexin V/PI staining and had effects on morphologic features determined by 3-D ODT. Interestingly, treatment with AP 18 suppressed stemness features.Conclusion: Taken together, our results suggest that AP 18 might be a potential therapeutic agent to target GSCs.Keywords: Glioblastoma, glioma, Pseudocyphellaria freycinetii, hopane triterpenoid

Development of an accessible method to routinely evaluate the clonality of strains is needed in microbiology laboratories. We compared the discriminatory power of the Fourier-transform infrared (FTIR) spectroscopy-based IR Biotyper (Bruker Daltonics GmbH, Bremen, Germany) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), using whole-genome sequencing (WGS) as the reference method.Eighty-three extended-spectrum β-lactamase-producingThe SDI (95% confidence interval) was 0.969 (0.952-0.985) for WGS, 0.865 (0.807-0.924) for MALDI-TOF MS, and 0.974 (0.965-0.983) for IR Biotyper. Compared with WGS, IR Biotyper showed compatible diversity, whereas MALDI-TOF MS did not. The concordance and aRI improved from 66.3% to 84.3% and from 0.173 to 0.538, respectively, for IR Biotyper versus MALDI-TOF MS with WGS as the reference method. IR Biotyper showed substantially improved performance in strain typing compared with MALDI-TOF MS.IR Biotyper is useful for diversity analysis with improved discriminatory power over MALDI-TOF MS in comparison with WGS as a reference method. IR Biotyper is an accessible method to evaluate the clonality of strains and could be applied in epidemiological analysis during an outbreak of a health care facility, as well as for research on the transmission of resistant bacteria in community settings.

Introduction: More than half of the results of axillary lymph node dissection followed by metastasis in sentinel lymph node(SLN) biopsy are negative. For deescalating axillary surgery, it is necessary to predict the non-SLN metastasis state, where metastasis was confirmed in the SLN biopsy. Method: Breast cancer patients with T1 and T2 stage were retrospectively reviewed from January 2008 to December 2016. A total of 818 patients underwent surgery as the primary treatment and the result of SLN biopsy was positive for metastasis. Patients who skipped SLN biopsy procedure and were proven metastatic axillary lymph nodes by needle-aspiration biopsy (NAB) were excluded. SLN was defined as lymph nodes detected by the dual method with hot-uptake by radioisotope and dyed by blue dye, or lymph nodes with palpable or suspected metastatic findings during SLN biopsy. Clinicopathological factors including and extra-nodal invasiveness were analyzed. Result: The median follow-up period was 73 months. Non-SLN metastasis was significantly seen in patients with older than 50 years, positive node metastases by preoperative NAB, high T stage, and extra-nodal invasion. In subgroup analysis, patients who underwent total mastectomy had the similar patterns of the increased risk of having non-SLN. Poor overall survival was observed in the patients with the presence of non-SLN metastasis. Conclusion: We confirmed predictive factors with a high probability of non-SLN metastasis. Axillary lymph node dissection cannot be overlooked in the patients proven the metastatic result of preoperative NAB. Citation Format: Jee Hyun Ahn, Suk Jun Lee, Jieon Go, Hyung Seok Park, Jee Ye Kim, Seung Il Kim, Byeong Woo Park, Seho Park. The clinical impact of preoperatively needle-aspiration biopsy for axillary lymph nodes in T1-T2 breast cancer patients with axillary lymph node metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-56.

Glioblastoma multiforme (GBM) is the most lethal form of brain cancer in humans, with a grim prognosis and a median overall survival rate of less than 15 months. Recently, glioma stem cells (GSCs) have been identified as a crucial factor in both tumor initiation and therapy resistance in GBM. Analysis of datasets and direct differentiation experiments on GSCs have both confirmed that CREB5 is expressed more highly in GSCs than in differentiated GSCs. Furthermore, studies on loss of function have shown that CREB5 promotes the proliferation and self-renewal ability of GSCs, while also reducing their tumor-forming ability in vivo. RNA-sequencing, Luciferase reporter assay, and ChIP assay have demonstrated a direct association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

Background Considering the effect of the gut microbiome on human physiology and aging, the gut microbiome may affect muscle strength in the same way as the host's own genes. Previous research has shown that the gut microbiome can have both positive and negative effects on muscle strength, suggesting the presence of two different types of gut microbiome. In this study, we demonstrate that the gut microbiome can contribute differently to muscle strength. Results We remodelled the original gut microbiome of mice through fecal microbiome transplant (FMT) using human feces, and compared the changes in muscle strength of the same mice before and three months after FMT. We found that FMT affected muscle strength in three different ways: positive, none, and negative. Analysis of the phylogenesis, α-diversities, and β-diversities on the gut microbiome in the three groups showed that a more diverse group of intestinal microbes was established after FMT in each of the three groups, indicating that the human gut microbiome is more diverse than that of mice. The remodelled gut microbiome by FMT in each group was also different from each other. Fold change and linear correlation analyses identified Phocaeicola barnesiae, Eisenbergiella massiliensis, and Anaeroplasma abactoclasticum in the gut microbiome as positive contributors to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense were found to have negative effects. Conclusions This study not only confirms the presence of gut microbiomes that contribute differently to muscle strength, but also explains the mixed results in previous research on the association between the gut microbiome and muscle strength.

Until now, studies on nail diseases have been performed through microscopic diagnosis and microscopic computed tomography (micro-CT). However, these kinds of conventional methods have some limitations. Firstly, the microscopic method is considered the gold standard for medical diagnosis. However, due to the use of fluorescent materials, the sample is damaged and it takes a long time to get results. Secondly, while micro-CT is a noninvasive method to get inner structure images of the sample with high resolution, the penetration and spatial resolution are insufficient for studying the microstructures of the sample, such as the sponge bone and the muscle fibers. In contrast, synchrotron radiation (SR) X-ray imaging technology has the advantage of very vividly demonstrating the anatomic structure of the sample with high penetration, sensitivity and resolution. In this study, we compared the optical microscopic method using hematoxylin and eosin staining and SR imaging to analyze the nail tissue in a mouse model. The results showed that SR could depict the inner structures of a mouse nail without any physical damage. Additionally, we could divide the important anatomical structures of the nail unit into three parts with three-dimensional (3D) images: the nail bed, nail matrix and hyponychium. The images showed that SR could be used for analyzing nails by visualizing the relatively clear and medically semantic structures in a 3D section. We expect that the results of this study will be applied to study nail diseases and conduct pharmaceutical research on their treatment.

Glioblastoma multiforme (GBM) is the most aggressive type of human brain tumor, with a poor prognosis and a median overall survival of fewer than 15 months. Glioma stem cells (GSCs) have recently been identified as a key player in tumor initiation and therapeutic resistance in GBM. ADAMTS family of metalloproteinases is known to cleave a wide range of extracellular matrix substrates and has been linked to tissue remodeling events in tumor development. Here, we investigate that ADAMTS3 regulates GSC proliferation and self-renewal activities, and tumorigenesis in orthotopic xenograft models.ADAMTS3 mRNA expression levels in normal human astrocyte (NHA), glioma, and GSCs cell lines were compared. After knockdown of ADAMTS3, alamarBlue assay, in vitro limiting dilution, and orthotopic xenograft assays were performed. To investigate the tumor-associated roles of ADAMTS3, several statistical assays were conducted using publicly available datasets.ADAMTS3 level was remarkably higher in GSCs than in NHA, glioma cell lines, and their matched differentiated tumor cells. Interestingly, knockdown of ADAMTS3 disrupted GSC's proliferation, self-renewal activity, and tumor formation in vivo. Furthermore, ADAMTS3 could be used as an independent predictor of malignancy progression in GBM.We identified ADAMTS3 as a potential therapeutic target for GBM.

This study was aimed to investigate the inhibitory effects of Porphyra dentata (P. dentata) extract on the adipogenesis of 3T3-L1 cells and evaluate its anti-obesity effect. The proliferation of 3T3-L1 cells and differentiation of adipocytes under treatment of P. dentata extract was examined by measuring the cell viability using alamarBlue assay and lipid droplets by Oil Red O staining. Results showed that P. dentata extract has no cytotoxicity effect and lipid droplets formation decreased in a concentration-dependent manner in 3T3-L1 cells. It has been confirmed that transcription factors affecting lipid accumulation and anti-adipogenic effects during cell differentiation are linked to P. dentata extract. We observed that P. dentata shows lowering the mRNA expression of peroxisome proliferator-activated receptor γ2 (PPARγ2), CCAAT/enhancer binding protein α (C/EBPα) that adipogenesis-associated key transcription factors and inhibiting adipogenesis in the early stages of differentiation. Treating the cells with P. dentata did not only suppressed PPARγ2 and C/EBPα but also significantly decreased the mRNA expression of adiponectin, Leptin, fatty acid synthase, adipocyte protein 2, and Acetyl-coA carboxylase 1. Overall, the P. dentata extract demonstrated inhibitory property in adipogenesis, which has a potential effect in anti-obesity in 3T3-L1 cells.

Damage to lower limb muscles requires accurate analysis of the muscular condition via objective microscopic diagnosis. However, microscopic tissue analysis may cause deformation of the tissue structure due to injury induced by external factors during tissue sectioning. To substantiate these muscle injuries, we used synchrotron X-ray imaging technology to project extremely small objects, provide three-dimensional microstructural analysis as extracted samples. In this study, we used mice as experimental animals to create soleus muscle models with various nerve injuries. We morphologically analyzed and quantified the damaged Section and Crush muscles, respectively, via three-dimensional visualization using synchrotron radiation X-ray imaging to diagnose muscle injury. Results of this study can also be used as basic data in the medical imaging field.

The timely mobilization of hematopoietic stem and progenitor cells (HSPCs) is essential for maintaining hematopoietic and tissue leukocyte homeostasis. Understanding how HSPCs migrate between bone marrow (BM) and peripheral tissues is of great significance in the clinical setting, where therapeutic strategies for modulating their migration capacity determine the clinical outcome. Here, we identify an epigenetic regulator, Phc2, as a critical modulator of HSPC trafficking. The genetic ablation of Phc2 in mice causes a severe defect in HSPC mobilization through the derepression of Vcam1 in bone marrow stromal cells (BMSCs), ultimately leading to a systemic immunodeficiency. Moreover, the pharmacological inhibition of VCAM-1 in Phc2-deficient mice reverses the symptoms. We further determine that Phc2-dependent Vcam1 repression in BMSCs is mediated by the epigenetic regulation of H3K27me3 and H2AK119ub. Together, our data demonstrate a cell-extrinsic role for Phc2 in controlling the mobilization of HSPCs by finely tuning their bone marrow niche., Mobilization of hematopoietic stem and progenitor cells (HSPCs) into the circulation is essential for maintaining homeostasis. Here, the authors show that Phc2 in bone marrow stromal cells represses the cell adhesion molecule Vcam1 and facilitates mobilization of HSPCs through regulation of epigenetic marks.

If intra-cerebral hemorrhage (ICH) rehabilitation animal model studies had included processes related to imaging diagnosis, not only interim evaluation of treatment effects but also the objectification of treatment effects would have been possible. The purpose of this study was to examine the rehabilitation treatment effect on biomarkers identified on magnetic resonance imaging/spectroscopy in an animal intra-cerebral hemorrhage model. Two groups of rats were used in this study: (1) the rehabilitation treatment group, 12 6-week-old Sprague–Dawley rats with experimental hemorrhage that received rehabilitation; and (2) the control group of 12 rats with experimental hemorrhage that received no intervention. Training rehabilitation was implemented 15 min daily for 2 weeks with 55–85% of the VO2 max. We conducted MRI/MRS scans before and after ICH rat modeling to evaluate brain metabolite concentration changes. The signal intensity of T2WI was measured at the site of ICH and in a similarly sized area on the opposite side. Integration of the areas under the peaks was conducted to measure cerebral metabolite concentrations. Differences in the mean T2WI-SI ratios measured 2 weeks after ICH induction were not statistically significant (p = 0.514) between the control group and the experimental group. However, the brain tCho/tCr metabolite ratio in the control group was significantly lower than in the experimental group 2 weeks after ICH induction (0.243 ± 0.044 vs. 0.326 ± 0.061, p = 0.007). The tCho/tCr ratio might be used as a biomarker to evaluate the effect of rehabilitation treatment for ICH.

To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant.Five client-owned dogs with glaucoma (five eyes).Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at20 mmHg.The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007).To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.