Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Background: Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer’s disease and Parkinson’s disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR) assays were performed. Results: We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. Conclusions These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.

Purpose: The aim of this study was to evaluate the relationship between the patient's occlusion and a cracked tooth by using T-scan occlusal analysis and a quantitative light-induced fluorescence (QLF) technology. Materials and Methods: This study was carried out on 51 patients having cracked teeth between January, 2019 and December, 2020. The tooth crack was determined with a Q-ray pen and QLF parameters (ΔFmax and ΔRmax) were obtained by a Q-ray software. T-scan tests were conducted to all subjects and then, the occlusal force and disclosing time were analyzed. Mann-Whitney U test was performed to compare the occlusal force and disclosing time between cracked teeth groups and contra-lateral normal teeth groups (α = .05). Mann-Whitney U test was performed to compare ΔFmax and ΔRmax according to the results of cold/bite tests (α = .05). A Spearman correlation analysis was run to determine the relationship between ΔFmax or ΔRmax and occlusal force or disclosing time (α=.05). Results: The mean occlusal force and disclosing time were significantly higher on cracked teeth than on normal teeth (P < .05). The ΔFmax or ΔRmax were not significantly different according to the results of cold/bite tests (P > .05). There was no correlation between ΔFmax or ΔRmax and occlusal force or disclosing time (P > .05). Conclusion There was a significant relationship between occlusion and cracked tooth syndrome. QLF has the potential to be a valuable tool for the diagnosis of tooth crack in clinical practice.

OBJECTIVE: To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE, changes in proteins related to apoptosis, and pathological changes in tumors in mouse. METHODS: Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose, with 5 in each group. AGS gastric carcinoma cells (1 × 10 RESULTS: High performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10-85 µ g/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (P<0.05, P<0.01). The annexin V & dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G CONCLUSION ZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Female ; Mice ; Mice, Inbred BALB C ; Plant Extracts/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Tumor Suppressor Protein p53/metabolism* ; Zanthoxylum/metabolism*

BACKGROUND: Sufficient blood supply through neo-vasculature is a major challenge in cell therapy and tissue engineering in order to support the growth, function, and viability of implanted cells. However, depending on the implant size and cell types, the natural process of angiogenesis may not provide enough blood supply for long term survival of the implants, requiring supplementary strategy to prevent local ischemia. Many researchers have reported the methodologies to form pre-vasculatures that mimic in vivo microvessels for implantation to promote angiogenesis. These approaches successfully showed significant enhancement in long-term survival and regenerative functions of implanted cells, yet there remains room for improvement. METHODS: This paper suggests a proof-of-concept strategy to utilize novel scaffolds of dimpled/hollow electrospun fibers that enable the formation of highly mature pre-vasculatures with adequate dimensions and fast degrading in the tissue.RESULT: Higher surface roughness improved the maturity of endothelial cells mediated by increased cell-scaffold affinity. The degradation of scaffold material for functional restoration of the neo-vasculatures was also expedited by employing the hollow scaffold design based on co-axial electrospinning techniques. CONCLUSION This unique scaffold-based pre-vasculature can hold implanted cells and tissue constructs for a prolonged time while minimizing the cellular loss, manifesting as a gold standard design for transplantable scaffolds.

Purpose: The aim of this study was to evaluate the relationship between the patient's occlusion and a cracked tooth by using T-scan occlusal analysis and a quantitative light-induced fluorescence (QLF) technology. Materials and Methods: This study was carried out on 51 patients having cracked teeth between January, 2019 and December, 2020. The tooth crack was determined with a Q-ray pen and QLF parameters (ΔFmax and ΔRmax) were obtained by a Q-ray software. T-scan tests were conducted to all subjects and then, the occlusal force and disclosing time were analyzed. Mann-Whitney U test was performed to compare the occlusal force and disclosing time between cracked teeth groups and contra-lateral normal teeth groups (α = .05). Mann-Whitney U test was performed to compare ΔFmax and ΔRmax according to the results of cold/bite tests (α = .05). A Spearman correlation analysis was run to determine the relationship between ΔFmax or ΔRmax and occlusal force or disclosing time (α=.05). Results: The mean occlusal force and disclosing time were significantly higher on cracked teeth than on normal teeth (P < .05). The ΔFmax or ΔRmax were not significantly different according to the results of cold/bite tests (P > .05). There was no correlation between ΔFmax or ΔRmax and occlusal force or disclosing time (P > .05). Conclusion There was a significant relationship between occlusion and cracked tooth syndrome. QLF has the potential to be a valuable tool for the diagnosis of tooth crack in clinical practice.

BACKGROUND: Sufficient blood supply through neo-vasculature is a major challenge in cell therapy and tissue engineering in order to support the growth, function, and viability of implanted cells. However, depending on the implant size and cell types, the natural process of angiogenesis may not provide enough blood supply for long term survival of the implants, requiring supplementary strategy to prevent local ischemia. Many researchers have reported the methodologies to form pre-vasculatures that mimic in vivo microvessels for implantation to promote angiogenesis. These approaches successfully showed significant enhancement in long-term survival and regenerative functions of implanted cells, yet there remains room for improvement. METHODS: This paper suggests a proof-of-concept strategy to utilize novel scaffolds of dimpled/hollow electrospun fibers that enable the formation of highly mature pre-vasculatures with adequate dimensions and fast degrading in the tissue.RESULT: Higher surface roughness improved the maturity of endothelial cells mediated by increased cell-scaffold affinity. The degradation of scaffold material for functional restoration of the neo-vasculatures was also expedited by employing the hollow scaffold design based on co-axial electrospinning techniques. CONCLUSION This unique scaffold-based pre-vasculature can hold implanted cells and tissue constructs for a prolonged time while minimizing the cellular loss, manifesting as a gold standard design for transplantable scaffolds.

Background: The study was planned to show the status of indoor microorganisms and the status of the reduction device in the military dog clinic. Methods: Airborne microbes were analyzed according to the number of daily patient canines. For identification of bacteria, sampled bacteria was identified using VITEK®2 and molecular method. The status of indoor microorganisms according to the operation of the ventilation system was analyzed. Results: Airborne bacteria and fungi concentrations were 1000.6 ± 800.7 CFU/m3 and 324.7 ± 245.8 CFU/m3. In the analysis using automated identification system, based on fluorescence biochemical test, VITEK®2, mainly human pathogenic bacteria were identified. The three most frequently isolated genera were Kocuria (26.6%), Staphylococcus (24.48%), and Granulicatella (12.7%). The results analyzed by molecular method were detected in the order of Kocuria (22.6%), followed by Macrococcus (18.1%), Glutamicibacter (11.1%), and so on. When the ventilation system was operated appropriately, the airborne bacteria and fungi level were significantly decreased. Conclusion Airborne bacteria in the clinic tend to increase with the number of canines. Human pathogenic bacteria were mainly detected in VITEK®2, and relatively various bacteria were detected in molecular analysis. A decrease in the level of bacteria and fungi was observed with proper operation of the ventilation system.

Genome editing has recently emerged as a powerful tool for generating mutant mice. Small deletions of nucleotides in the target genes are frequently found in CRISPR/Cas9 mediated mutant mice. However, there are very few reports analyzing the phenotypes in small deleted mutant mice generated by CRISPR/Cas9. In this study, we generated a mutant by microinjecting sgRNAs targeting the IL2 receptor γ gene and Cas9 protein, into the cytoplasm of IVF-derived NOD.CB17/Prkdcscid/JKrb (NOD/SCID) mice embryos, and further investigated whether a 2 bp deletion of the IL2 receptor γ gene affects severe deficiency of immune cells as seen in NOD/LtSz-scid IL2 receptor γ−/− (NSG) mice. Our results show that the thymus weight of mutant mice is significantly less than that of NOD/SCID mice, whereas the spleen weight was marginally less. T and B cells in the mutant mice were severely deficient, and NK cells were almost absent. In addition, tumor growth was exceedingly increased in the mutant mice transplanted with HepG2, Raji and A549 cells, but not in nude and NOD/SCID mice. These results suggest that the NOD/SCID mice with deletion of 2 bp in the IL2 receptor γ gene shows same phenotype as NSG mice. Taken together, our data indicates that small deletions by genome editing is sufficient to generate null mutant mice.

Background: The study was planned to show the status of indoor microorganisms and the status of the reduction device in the military dog clinic. Methods: Airborne microbes were analyzed according to the number of daily patient canines. For identification of bacteria, sampled bacteria was identified using VITEK®2 and molecular method. The status of indoor microorganisms according to the operation of the ventilation system was analyzed. Results: Airborne bacteria and fungi concentrations were 1000.6 ± 800.7 CFU/m3 and 324.7 ± 245.8 CFU/m3. In the analysis using automated identification system, based on fluorescence biochemical test, VITEK®2, mainly human pathogenic bacteria were identified. The three most frequently isolated genera were Kocuria (26.6%), Staphylococcus (24.48%), and Granulicatella (12.7%). The results analyzed by molecular method were detected in the order of Kocuria (22.6%), followed by Macrococcus (18.1%), Glutamicibacter (11.1%), and so on. When the ventilation system was operated appropriately, the airborne bacteria and fungi level were significantly decreased. Conclusion Airborne bacteria in the clinic tend to increase with the number of canines. Human pathogenic bacteria were mainly detected in VITEK®2, and relatively various bacteria were detected in molecular analysis. A decrease in the level of bacteria and fungi was observed with proper operation of the ventilation system.