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BackgroundTotal oxygen consumption has been found to be reduced under deep neuromuscular blockade due to a lower rate of metabolism of skeletal muscles. However, the magnitude of this effect in individual muscles has not been investigated. Thus the aim of this study was to compare the oxygenation of paralyzed versus non-paralyzed forearm muscle under tourniquet-provoked ischemia.MethodsAfter ethics approval and written informed consent, 30 patients scheduled for elective hand and wrist surgery were included. Ischemia was provoked by inflation of bilateral upper arm tourniquets and muscle relaxation was achieved via intravenous administration of rocuronium 0.9 mg/kg. Bilateral tourniquets were applied to both upper arms before induction of anesthesia and near infrared spectrometry (NIRS) electrodes applied on both forearms. Muscular ischemia in an isolated (= non-paralyzed, NP) as well as a paralyzed forearm (P) was created by sequential inflation of both tourniquets before and after intravenous administration of rocuronium. Muscle oxygen saturations (SmO2) of NIRS in both forearms and their changes were determined and compared.ResultsData of 30 patients (15 male, 15 female; 41.8 ± 14.7 years) were analyzed. The speed of SmO2 decrease (50% decrease of SmO2 from baseline (median [percentiles]: NP 210 s [180/480s] vs. P 180 [180/300]) as well as the maximum decrease in SmO2 (minimum SmO2 in % (median [percentiles]: NP 20 [19/24] vs. P 21 [19/28]) were not significantly affected by neuromuscular paralysis.ConclusionsNo significant effect of muscle relaxation on NIRS-assessed muscle oxygenation under tourniquet-induced ischemia was found in human forearm muscles.

ABSTRACT: This study investigated the preventive effects of whey protein fermented with Lactobacillus gasseri IM13 (F-WP) against dexamethasone (DEX)-induced muscle atrophy. C2C12 muscle cells were treated with F-WP followed by DEX treatment. Dexamethasone treatment inhibited myotube formation and the expression of myogenic regulatory factors; however, pretreatment with F-WP attenuated DEX-induced damage. The F-WP significantly activated the phosphorylation of the IGF-1/PI3K/AKT pathway and improved muscle homeostasis suppressed by DEX. Moreover, F-WP alleviated the phosphorylation of mTOR, S6K1, and 4E-BP1 and enhanced muscle protein synthesis. Muscle-specific ubiquitin ligases and autophagy lysosomes, which were activated by the dephosphorylation of FOXO3a by DEX treatment, were significantly attenuated by F-WP pretreatment of myotubes. For peptidomic analysis, F-WP was fractionated using preparative HPLC (prep-HPLC), and the AA sequences of 11 peptides were identified using MALDI-TOF/MS/MS. In conclusion, fermentation of whey protein by the specific probiotic strain IM13 produced bioactive peptides with high antioxidant and anti-sarcopenic-sarcopenic effects, which markedly enhanced myogenesis and muscle protein synthesis while diminishing muscle protein degradation compared with intact whey protein.

Abstract We present a transmon qubit fabrication technique that yields systematic improvements in T 1 relaxation times. We encapsulate the surface of niobium and prevent the formation of its lossy surface oxide. By maintaining the same superconducting metal and only varying the surface, this comparative investigation examining different capping materials, such as tantalum, aluminum, titanium nitride, and gold, as well as substrates across different qubit foundries demonstrates the detrimental impact that niobium oxides have on coherence times of superconducting qubits, compared to native oxides of tantalum, aluminum or titanium nitride. Our surface-encapsulated niobium qubit devices exhibit T 1 relaxation times 2–5 times longer than baseline qubit devices with native niobium oxides. When capping niobium with tantalum, we obtain median qubit lifetimes above 300 μs, with maximum values up to 600 μs. Our comparative structural and chemical analysis provides insight into why amorphous niobium oxides may induce higher losses compared to other amorphous oxides.

Abstract DNA damage is a critical threat that poses significant challenges to all cells. To address this issue, cells have evolved a sophisticated molecular and cellular process known as the DNA damage response (DDR). Among the various cell types, mammalian oocytes, which remain dormant in the ovary for extended periods, are particularly susceptible to DNA damage. The occurrence of DNA damage in oocytes can result in genetic abnormalities, potentially leading to infertility, birth defects, and even abortion. Therefore, understanding how oocytes detect and repair DNA damage is of paramount importance in maintaining oocyte quality and preserving fertility. Although the fundamental concept of the DDR is conserved across various cell types, an emerging body of evidence reveals striking distinctions in the DDR between mammalian oocytes and somatic cells. In this review, we highlight the distinctive characteristics of the DDR in oocytes and discuss the clinical implications of DNA damage in oocytes.

Abstract Background The maintenance of spindle pole integrity is essential for spindle assembly and chromosome segregation during mitosis. However, the underlying mechanisms governing spindle pole integrity remain unclear. Methods ENSA was inhibited by siRNA or MKI-2 treatment and its effect on cell cycle progression, chromosome alignment and microtubule alignment was observed by immunohistochemical staining and western blotting. PP2A-B55α knockdown by siRNA was performed to rescue the phenotype caused by ENSA inhibition. The interaction between ENSA and Aurora A was detected by in situ PLA. Furthermore, orthotopic implantation of 4Tl-luc cancer cells was conducted to confirm the consistency between the in vitro and in vivo relationship of the ENSA-Aurora A interaction. Results During mitosis, p-ENSA is localized at the spindle poles, and the inhibition of ENSA results in mitotic defects, such as misaligned chromosomes, multipolar spindles, asymmetric bipolar spindles, and centrosome defects, with a delay in mitotic progression. Although the mitotic delay caused by ENSA inhibition was rescued by PP2A-B55α depletion, spindle pole defects persisted. Notably, we observed a interaction between ENSA and Aurora A during mitosis, and inhibition of ENSA reduced Aurora A expression at the mitotic spindle poles. Injecting MKI-2-sensitized tumors led to increased chromosomal instability and downregulation of the MASTL-ENSA-Aurora A pathway in an orthotopic breast cancer mouse model. Conclusions These findings provide novel insights into the regulation of spindle pole integrity by the MASTL-ENSA-Aurora A pathway during mitosis, highlighting the significance of ENSA in recruiting Aurora A to the spindle pole, independent of PP2A-B55α.

ABSTRACT: This study investigated the preventive effects of peptides derived from milk fermented with the probiotic strain Lactobacillus gasseri 505 (505) against stress-related brain damage and anxiety-like behavior. The peptides MKPWIQPKTKVIPYVRYL (Pep14) and VYQHQKAMKPWIQPKTKVIPYVRYL (Pep21), which exhibit high antioxidant and anti-inflammatory activities, were administered to stressed mice. The results showed that the stress mechanism in the gut-brain axis was regulated by pretreatment with both peptides, leading to inhibition of neurodevelopment and neuroinflammation through the hypothalamic-pituitary-adrenal (HPA) axis, based on the expression of related mRNA and proteins. The expression of colonic inflammation-related mRNA and proteins was also reduced. Moreover, anxiety-like behavior was significantly reduced in mice treated with Pep14 and Pep21. These results indicate that the bioactive peptides Pep14 and Pep21, derived from milk fermented with 505, may prevent stress-induced brain damage and anxiety-like behavior via regulation of the HPA axis.

Abstract Background This randomized controlled clinical trial compared the effects of platelet-rich fibrin (PRF) and concentrated growth factor (CGF) on early bone healing after endodontic microsurgery. Methods Eighteen patients with an isolated periapical lesion 0.05). However, no significant difference was observed between the PRF and CGF groups. At the six-month follow-up, no significant differences were observed between the groups. Conclusions These results suggested that PRF and CGF promote early bone healing after endodontic microsurgery.

Lactobacillus johnsonii 7409N31 was isolated from the feces of a healthy 11-day-old Hanwoo calf from a farm in Geochang-gun, Gyeongsangnam-do, Korea. The genome of the strain was completely sequenced using the PacBio RSII sequencing system, and it was confirmed that it was composed of one circular chromosome. The size of the entire genome was 2,198,442 bp, and it had 35.01 mol% guanine + cytosine (G + C) content and 2,222 protein-coding sequences, 24 rRNA, 3 ncRNA, and 112 tRNA genes. Strain 7409N31 possessed genes encoding enzymes involved in the hydrolysis of both fibrous and non-fibrous carbohydrates. These data provide a comprehensive theoretical understanding for developing industrial probiotic feed additives that improve nutrient digestibility.

Siloxanes and synthetic musk compounds (SMCs) have been widely used as additives in household and personal care products. Humans are easily exposed to siloxanes and SMCs originating from these products through ingestion and dermal absorption of indoor dust. In the present study, indoor dust samples were analyzed for 19 siloxanes (cyclic and linear) and 12 SMCs (polycyclic, macrocyclic, and nitro musks) to assess their occurrence, time trends over time, source, and health risks. A total of 18 siloxanes and 10 SMCs were detected in all indoor dust samples obtained from 2011⎯2021, indicating widespread and long-term contamination. Higher detection frequencies and concentrations were associated with siloxanes and SMCs with higher use and strong resistance against degradation processes. Indoor dust samples were dominated by linear siloxanes (L11–L13), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB), musk ketone (MK), and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN). The frequent use of household and personal care products is likely an important source of siloxane and SMC contamination in indoor environments. The concentrations of siloxanes and SMCs in indoor dust increased from 2011 to 2021, particularly, those of linear siloxanes, reflecting the impact of regulatory actions addressing cyclic siloxanes. The profiles of siloxanes remained stable throughout the study period, whereas those of SMCs shifted from nitro to polycyclic musks. The estimated daily intakes (EDIs) of siloxanes and SMCs arising from ingestion were greater than from dermal absorption of indoor dust. The EDIs of siloxanes and SMCs associated with indoor dust indicated that children are exposed to these pollutants.

Niobium superconducting radiofrequency cavities enable applications in modern accelerators and quantum computers. However, the surface resistance significantly deteriorates the cavities’ performance. Nitrogen doping surface treatment can consistently increase cavity performance by reducing surface resistance, but the improvement mechanism is not fully understood. Herein, we employed transmission electron microscopy and spectroscopy to uncover the structural and chemical differences of the Nb/air interface between the non-doped and nitrogen-doped cavities. The results indicate that nitrogen doping passivates the Nb surface by introducing a compressive stress/strain close to the Nb/air interface, which impedes the diffusion of oxygen and hydrogen atoms and reduces surface oxide thickness.

The effects of solution concentration and pH on the formation and surface structure of 2-pyrimidinethiolate (2PymS) self-assembled monolayers (SAMs) on Au(111) via the adsorption of 2,2′-dipyrimidyl disulfide (DPymDS) were examined using scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS). STM observations revealed that the formation and structural order of 2PymS SAMs were markedly influenced by the solution concentration and pH. 2PymS SAMs formed in a 0.01 mM ethanol solution were mainly composed of a more uniform and ordered phase compared with those formed in 0.001 mM or 1 mM solutions. SAMs formed in a 0.01 mM solution at pH 2 were composed of a fully disordered phase with many irregular and bright aggregates, whereas SAMs formed at pH 7 had small ordered domains and many bright islands. As the solution pH increased from pH 7 to pH 12, the surface morphology of 2PymS SAMs remarkably changed from small ordered domains to large ordered domains, which can be described as a (4√2 × 3)R51° packing structure. XPS measurements clearly showed that the adsorption of DPymDS on Au(111) resulted in the formation of 2PymS (thiolate) SAMs via the cleavage of the disulfide (S-S) bond in DPymDS, and most N atoms in the pyrimidine rings existed in the deprotonated form. The results herein will provide a new insight into the molecular self-assembly behaviors and adsorption structures of DPymDS molecules on Au(111) depending on solution concentration and pH.

Free gingival graft (FGG) is the gold standard procedure for the reliable augmentation of lost keratinized mucosa (KM) around dental implants. This conventional surgical approach has its drawbacks, including limitations in manipulation, the requirement for suturing, postoperative discomfort, and pain. This case report aimed to evaluate the efficacy of a simplified free gingival graft (sFGG) in addressing the issue of inadequate keratinized mucosa around dental implants. Fixation tacks were used to perform the sFGG procedure. Initially, a partial-thickness flap was created and apically repositioned. The gingival graft was harvested from the palate with a narrow profile and securely affixed to the recipient site using 5 mm long fixation tacks. Significant gains in keratinized mucosa were achieved and successfully maintained within 1 year. Consequently, the sFGG technique emerges as a simple and reliable treatment approach for managing inadequate keratinized mucosa around dental implants.

Fungicides are a type of pesticide used to protect plants and crops from pathogenic fungi. Azoxystrobin (AZO), a natural methoxyacrylate derived from strobilurin, is one of the most widely used fungicides in agriculture. AZO exerts its fungicidal activity by inhibiting mitochondrial respiration, but its cytotoxicity to mammalian oocytes has not been studied. In this study, we investigated the effect of AZO exposure on mouse oocyte maturation to elucidate the underlying mechanisms of its possible reproductive toxicity. We found that AZO exposure disturbed meiotic maturation by impairing spindle formation and chromosome alignment, which was associated with decreased microtubule organizing center (MTOC) integrity. Moreover, AZO exposure induced abnormal mitochondrial distribution and increased oxidative stress. The AZO-induced toxicity to oocytes was relieved by melatonin supplementation during meiotic maturation. Therefore, our results suggest that AZO exposure impairs oocyte maturation not only by increasing oxidative stress and mitochondrial dysfunction, but also by decreasing MTOC integrity and subsequent spindle formation and chromosome alignment.

Objective The objective of this study was to evaluate the antimicrobial effects of fermented Maillard reaction products made by milk proteins (FMRPs) on Clostridium perfringens (C. perfringens), and to elucidate antimicrobial modes of FMRPs on the bacteria, using physiological and morphological analyses. Methods Antimicrobial effects of FMRPs (whey protein plus galactose fermented by Lactobacillus rhamnosus [L. rhamnosus] 4B15 [Gal-4B15] or Lactobacillus gasseri 4M13 [Gal-4M13], and whey protein plus glucose fermented by L. rhamnosus 4B15 [Glc-4B15] or L. gasseri 4M13 [Glc-4M13]) on C. perfringens were tested by examining growth responses of the pathogen. Iron chelation activity analysis, propidium iodide uptake assay, and morphological analysis with field emission scanning electron microscope (FE-SEM) were conducted to elucidate the modes of antimicrobial activities of FMRPs. Results When C. perfringens were exposed to the FMRPs, C. perfringens cell counts were decreased (p

In this paper, a hybrid genetic algorithm (GA) is proposed for thinning a two-dimensional planar array by combining the conventional GA with moving least squares (MLS). This enhances the convergence rate and the global search performance. The MLS method is used to estimate local interpolation functions from non-uniform sample data (the population and the value of the objective function in the GA), and to find new and better populations from the interpolated functions. By incorporating these improved populations into the next generation, the MLS-GA achieves improved search performance of the global optimum and a faster convergence rate compared to conventional GA alone. Moreover, a nonlinear chirp function is used for an efficient thinning design. To verify the proposed MLS-GA, it is applied to a test function and the results are compared to that of the GA. The algorithm is then applied to thin an array with a rectangular grid and circular boundary. The design objectives are to minimize the peak side-lobe level and gain loss while satisfying a given thinning coefficient and to compare the results with the GA.

Lactobacillus amylovorus are known to exist in the intestinal flora of healthy cattle or pigs. The L. amylovorus strain 1394N20 was isolated from the feces of the Hanwoo calf (Bos taurus coreanae). The genome of strain 1394N20 consists of a single circular chromosome (2,176,326 bp) with overall guanine + cytosine content of 37.8 mol%. Moreover, 2,281 protein-coding sequences, 15 rRNAs, and 65 tRNAs genes were identified in the chromosome based on the results of annotation. The bacterium has a gene encoding endoglucanase, an enzyme that hydrolyzes the 1,4-β-D-glycosidic linkages in cellulose, hemicellulose, lichenin, and cereal β-D-glucans. Genomic sequencing of L. amylovorus strain 1394N20 reveals the immense potential of the strain as a probiotic with nutrient digestibility.

Infectious calf diarrhea is one of the most significant diseases of neonatal calves. This study is conducted to identify the prevalence of pathogens in calf diarrhea for 2 years. A total of 544 feces samples from Korean native beef calves were obtained to investigate selected seven pathogens causing calf diarrhea: bovine rotavirus, bovine coronavirus, Cryptosporidium parvum, bovine viral diarrhea virus, Eimeria species, Escherichia coli K99, and Salmonella species. The presence of diarrhea, the number and species of detected pathogens, and the calves’ ages were analyzed using various statistical methods depending on the case. Of the 544 calves, 340 calves (62.5%) had normal feces and 204 calves (37.5%) had diarrhea. The presence of pathogens was significantly associated with diarrhea (p < 0.01) and fecal scores and the number of detected pathogens showed a significant linear trend (p < 0.001). Of the 7 target pathogens, 6 were detected in samples, but only C. parvum (p = 0.001) and bovine rotavirus (p < 0.001) were found at significantly higher rates in diarrheic calves than in non-diarrheic calves. Only Eimeria spp. showed a significant linear trend between the detection rate of the pathogen and the age groups (p < 0.05).

Jaw defects can have a variety of causes, including tumors, trauma, and osteomyelitis. The reconstruction of jaw defects has been improved with the free flap technique and sophisticated microvascular techniques. A deep circumflex iliac artery (DCIA) flap provides a large amount of bone for the reconstruction of the mandible. However, various complications and side effects, such as abnormal hip contour, hernia, severe bleeding tendency, gait disturbance, and hypoesthesia, can occur. Iliac bone fracture is not a common complication after DCIA flap harvesting, because the anterior superior iliac spine (ASIS) can include the harvested flap. If an iliac avulsion fracture occurs, various treatment options exist. If severe dislocation of the bone fragment exists, open reduction and internal fixation are required. At this time, orthopedic implants composed of various materials can be used. Among these, when using a 3D-fabricated implant using a Ti6Al4V alloy, the accuracy of the size and shape is excellent, and it can have mechanical–biocompatible advantages. In this study, we report cases of iliac bone fracture after reconstruction of the jaw with a DCIA flap and the treatment modality using a 3D-printed, patient-specific titanium implant.

Background: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/ sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs. Materials and Methods: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed. Results: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months. Conclusion: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial. [ABSTRACT FROM AUTHOR]

Bovine coronavirus (BCoV) is associated with severe diarrhea, dehydration, and depression, which result in significant economic damages in the dairy and beef cattle industries worldwide. However, differences in the gut microbiota structure and their correlations with differing physiological parameters between BCoV-infected calves with diarrhea and recovered calves are not well understood. In this study, fecal specimens were collected from 10 post-weaned calves, before and after 2 months of fluid therapy, and the samples were used for microbiota analysis. Following recovery, the alpha-diversity profiles (observed operational taxonomic units [OTUs], and Chao1, Shannon, and Simpson indices) changed significantly when compared with those of calves with diarrhea. Beta-diversity analysis exhibited significant differences in gut microbiota compositions between calves with diarrhea and those in the recovered state. The abundances of eight phyla and thirteen genera in feces changed markedly after restoration of BCoV diarrhea. In addition, our correlation study clearly revealed that increased abundances of the genera Caproiciproducens, Pseudoflavonifractor, and Oscillibacter negatively correlated with serum glucose, and phosphorus levels, but positively correlated with serum chloride in calves with diarrhea, whereas increased abundances of the genera Peptostreptococcaceae;Clostridium (Clostridium cluster XI), Intestinibacter, Cellulosilyticum, Ruminococcus, Romboutsia, Paeniclostridium, Clostridiaceae;Clostridium and Turicibacter in recovered calves showed the opposite pattern. These results suggest that structural changes of the gut microbiota after recovery from BCoV infection correlate with changes in physiological parameters. In conclusion, our data provide evidence of gut microbiota-composition changes and their correlations with the physical profiles of post-weaned calves, before and after fluid therapy for BCoV-related diarrhea.

This study aimed to investigate the effects of glycated milk casein (Gc) fermented with Lactobacillus rhamnosus 4B15 (FGc) on the intestinal microbiota and physiological and behavioral properties in mice under chronic stress. Mice were administered Gc or FGc for 10 weeks and then exposed to unpredictable chronic mild stress (UCMS) for 7 weeks. FGc administration restored alterations of gut microbiota induced by UCMS. Moreover, FGc significantly reduced the stress-induced increase in serum corticosterone and decrease in serotonin levels. Anxiety-like behaviors induced by UCMS were also significantly decreased in the FGc group. UCMS-induced dysregulation of gene and protein expression related to neuroendocrine function, neuronal development, and inflammation, and gut-blood-brain barrier function was controlled by FGc pre-treatment. These results strongly suggest the protective effects of FGc targeting of intestinal microbiota for abnormal brain activity, which is consistent with the view that FGc plays an important role in regulating stress-related gut-brain axis disorders.

This study investigated the effects of a synbiotic combination (Syn) of Lactobacillus gasseri 505 (505) and Cudrania tricuspidata leaf extract (CT) on the hypothalamic-pituitary-gonadal axis in mice under chronic stress. Unpredictable chronic mild stress (UCMS) significantly increased the serum levels of corticosterone, however, treatment with Syn suppressed UCMS-induced increases. Histopathological analysis of the testes showed that these organs experienced some damage during UCMS, but this was repaired following treatment with Syn. Similarly, the transcription levels of gonadotropin-releasing hormone (GnRH), GnRH receptor, and gonadotropins, moreover, testicular development (i.e., Adam5, Adam29, and Spam1) - and steroidogenesis (i.e., Lhr, Egfr, and StAR) -related genes were significantly downregulated by UCMS. These UCMS-induced changes were inhibited by the administration of Syn, which was confirmed by the results of in situ hybridization analysis. These results suggest that the administration of Syn could attenuate the testicular dysfunctions induced by UCMS.

In eukaryotic chromosomes, the centromere and telomere are two specialized structures that are essential for chromosome stability and segregation. Although centromeres and telomeres often are located in close proximity to form telocentric chromosomes in mice, it remained unclear whether these two structures influence each other. Here we show that TRF1 is required for inner centromere and kinetochore assembly in addition to its role in telomere protection in mouse oocytes. TRF1 depletion caused premature chromosome segregation by abrogating the spindle assembly checkpoint (SAC) and impairing kinetochore-microtubule (kMT) attachment, which increased the incidence of aneuploidy. Notably, TRF1 depletion disturbed the localization of Survivin and Ndc80/Hec1 at inner centromeres and kinetochores, respectively. Moreover, SMC3 and SMC4 levels significantly decreased after TRF1 depletion, suggesting that TRF1 is involved in chromosome cohesion and condensation. Importantly, inhibition of inner centromere or kinetochore function led to a significant decrease in TRF1 level and telomere shortening. Therefore, our results suggest that telomere integrity is required to preserve inner centromere and kinetochore architectures, and vice versa, suggesting mutual regulation between telomeres and centromeres.

The purpose of this study is to analyze the clinical results of the implant rehabilitation for a jaw reconstructed by the deep circumflex iliac artery (DCIA) flap. A total of 13 patients were included in this study from 2010 to 2020. Medical records were collected retrospectively and analyzed. The mandible was involved in 10 cases and the maxilla was in 3 cases. The average width of the DCIA flap was 8.6 mm, and the height was 20.65 mm. A total of 41 dental implants with a diameter of 3.9–5.0 mm and a length of 10.0–11.5 mm were placed at an average of 12.3 months after the reconstruction. The average follow-up period after delivering a permanent prosthesis was 15 months (range, 2 to 51 months) and the overall mean follow-up period was 48 months. In all, 3 implants of the total 41 implants were removed. The DCIA flap is the most suitable for reproducing the original contour of the original jawbone compared with the fibular flap. In addition, the height and width of the reconstructed bone is appropriate for implant placement, which is advantageous for the rehabilitation of oral function and aesthetics using the implant.

The polycyclic aromatic hydrocarbon quinone derivative 9,10-phenanthrenequinone (9,10-PQ) is one of the most abundant and toxic components found in diesel exhaust particles (DEPs). These DEPs are created during diesel fuel combustion and are considered the main source of urban air pollution. As 9,10-PQ can produce excessive reactive oxygen species (ROS) through redox cycling, it has been shown to exert potent cytotoxic effects against various cell types. However, the mechanisms underlying this cytotoxicity remain unclear. In this study, we showed that 9,10-PQ exerts cytotoxicity by impairing mitotic progression and spindle assembly in HeLa cells. Exposure to 9,10-PQ impaired spindle assembly and chromosome alignment, resulting in delayed mitotic entry and progression in HeLa cells. Furthermore, 9,10-PQ exposure decreased the CEP192 and p-Aurora A levels at the spindle poles. Notably, these mitotic defects induced by 9,10-PQ were not rescued by scavenging ROS, implying the ROS-independent activity of 9,10-PQ. Therefore, our results provide the first evidence that 9,10-PQ exerts its cytotoxicity through specific inhibition of mitotic progression and spindle assembly, independent of ROS.

Previously, a synbiotic combination of probiotic Lactobacillus gasseri 505 (LG) and a new prebiotic, Cudrania tricuspidata leaf extract (CT) in fermented milk, designated FCT, showed an in vitro immunomodulatory effect and antioxidant activity. Although synbiotic combination might have cancer-protective effects, these activities have not been fully validated in vivo. Ten-week treatment of LG, CT, or FCT to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colorectal cancer (CAC) mouse model reduced both the incidence of colonic tumors and damage to the colonic mucosa effectively, suggesting a cancer-protective effect. To understand these, biomarkers associated with inflammation, colon barrier, apoptosis, and cancer cell proliferation were monitored in AOM/DSS group versus LG/CT/FCT groups. A synbiotic combination (FCT) down-regulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) and inflammation-associated enzymes (iNOS and COX-2), and up-regulated anti-inflammatory cytokines (IL-4 and IL-10). In addition, colon barrier experiment revealed that biomarkers of mucus layer (MUC-2 and TFF3) and tight junction (occludin and ZO-1) were up-regulated. Subsequent apoptosis experiment showed that pro-apoptotic factors (p53, p21, and Bax) were up-regulated and anti-apoptotic factors (Bcl-2 and Bcl-xL) were down-regulated. Furthermore, comparative metagenome analysis of gut microbiota revealed that Staphylococcus decreased but Lactobacillus, Bifidobacterium, and Akkermansia increased, supporting their protective effects, accompanied by increased short-chain fatty acids (SCFAs). Taken together, the FCT administration showed cancer-protective effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Consequently, the synbiotic combination (FCT) could be a novel potential health-protective natural agent against CAC.

The objective of this study was to evaluate the effects of peptides derived from synbiotics on improving inflammatory bowel disease (IBD). Five-week-old male C57BL/6 mice were administered with dextran sulfate sodium (DSS) via drinking water for seven days to induce IBD (IBD group). The mice in the IBD group were orally administered with PBS (IBD-PBS-positive control), Lactobacillus gasseri 505 (IBD-Pro), fermented powder of CT extract with L. gasseri 505 (IBD-Syn), β-casein: LSQSKVLPVPQKAVPYPQRDMP (IBD-Pep 1), or αs2-casein: VYQHQKAMKPWIQPKTKVIPYVRYL (IBD-Pep 2) (both peptides are present in the synbiotics) for four more days while inducing IBD. To confirm IBD induction, the weights of the animals and the disease activity index (DAI) scores were evaluated once every two days. Following treatment of probiotics, synbiotics, or peptides for 11 days, the mice were sacrificed. The length of the small and large intestines was measured. The expression of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and COX-2 in the large intestine was measured. Large intestine tissue was fixed in 10% formalin and stained with hematoxylin and eosin for histopathological analysis. The body weights decreased and DAI scores increased in the IBD group, but the DAI scores were lower in the IBD-Pep 2 group than those in the IBD group treated with PBS, Pro, Syn, or Pep 1. The lengths of the small and large intestines were shorter in the IBD group than in the group without IBD, and the expression levels of the proinflammatory cytokines were lower (p

The aim of the presented study was to investigate the synbiotic effects of L. rhamnosus 4B15 and C. tricuspidata extract administration on the gut microbiota and obesity-associated metabolic parameters in diet-induced obese mice. Thirty-one 6-week-old male C57BL/N6 mice were divided into five diet groups: normal diet (ND, n = 7) group; high-fat diet (HFD, n = 6) group; probiotic (PRO, n = 5) group; prebiotic (PRE, n = 7) group; and synbiotic (SYN, n = 6) group. After 10 weeks, the percent of fat mass, serum triglyceride, and ALT levels were significantly reduced in SYN-fed obese mice, compared with other treatments. SYN treatment also modulated the abundance of Desulfovibrio, Dorea, Adlercreutzia, Allobaculum, Coprococcus, unclassified Clostridiaceae, Lactobacillus, Helicobacter, Flexispira, Odoribacter, Ruminococcus, unclassified Erysipelotrichaceae, and unclassified Desulfovibrionaceae. These taxa showed a strong correlation with obesity-associated indices. Lastly, the SYN-supplemented diet upregulated metabolic pathways known to improve metabolic health. Further investigations are needed to understand the mechanisms driving the synbiotic effect of C. tricuspidata and L. rhamnosus 4B15.

The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of Lithospermum erythrorhizon (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.

Although microtubule-associated serine/threonine kinase-like (MASTL) is a promising target for selective anticancer treatment, MASTL inhibitors with nano range potency and antitumor efficacy have not been reported. Here, we report a novel potent and selective MASTL inhibitor MASTL kinase inhibitor-2 (MKI-2) identified in silico through a drug discovery program. Our data showed that MKI-2 inhibited recombinant MASTL activity and cellular MASTL activity with IC50 values of 37.44 nM and 142.7 nM, respectively, in breast cancer cells. In addition, MKI-2 inhibited MASTL kinase rather than other AGC kinases, such as ROCK1, AKT1, PKACα, and p70S6K. Furthermore, MKI-2 exerted various antitumor activities by inducing mitotic catastrophe resulting from the modulation of the MASTL-PP2A axis in breast cancer cells. The MKI-2 treatment showed phenocopies with MASTL-null oocyte in mouse oocytes, which were used as a model to validate MKI-2 activity. Therefore, our study provided a new potent and selective MASTL inhibitor MKI-2 targeting the oncogenic MAST-PP2A axis in breast cancer cells.

The medicinal plant noni (Morinda citrifolia) is widely dispersed throughout Southeast Asia, the Caribbean, and Australia. We previously reported that fermented Noni could alleviate atopic dermatitis (AD) by recovering Th1/Th2 immune balance and enhancing skin barrier function induced by 2,4-dinitrochlorobenzene. Noni has a high deacetylasperulosidic acid (DAA) content, whose concentration further increased in fermented noni as an iridoid constituent. This study aimed to determine the anti-AD effects and mechanisms of DAA on HaCaT, HMC-1, and EOL-1 cells. DAA inhibited the gene expression and secretion of AD-related cytokines and chemokines including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-25, IL-33, thymic stromal lymphopoietin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation, normal T cell expressed and secreted, in all cells, and inhibited histamine release in HMC-1 cells. DAA controlled mitogen-activated protein kinase phosphorylation levels and the translocation of nuclear factor-kappa light chain enhancer of activated B cells into the nucleus by inhibiting IκBα decomposition in all the cells. Furthermore, DAA increased the expression of proteins involved in skin barrier functions such as filaggrin and involucrin in HaCaT cells. These results confirmed that DAA could relieve AD by controlling immune balance and recovering skin barrier function.

Purpose: The purpose of this study was to compare changes in the physicochemical and biologic characteristics of titanium surfaces through short-term re-hydrophobization for 24 hours and ultraviolet (UV) re-irradiation for 24 hours. Materials and Methods: Photofunctionalization was performed with four 15-W bactericidal lamps at an intensity of 5.0 mW/cm2 (wavelength = 254 ± 20 nm) on sandblasted, large-grit, acid-etched (SLA)-treated titanium surfaces, which were stored in sterilized sealed containers for 8 weeks to allow enough biologic aging. The duration of the UV irradiation was as follows: irradiation group--UV irradiated for 24 hours; re-hydrophobization group--UV irradiated for 24 hours and then stored in an ambient sterilized medium; and re-irradiation group--UV irradiated for 24 hours followed by storing for 24 hours in an ambient sterilized medium and then UV re-irradiated for 24 hours. The surface characteristics were evaluated with field emission scanning electron microscopy, x-ray photoelectron spectroscopy (XPS), and water contact angle. Cell viability and morphology were measured using fluorescence staining. Alkaline phosphatase (ALP) assay and alizarin red S staining were performed to evaluate the differentiation of osteogenic cells and mineralization capability. Results: Macroroughness and superimposed microroughness were observed on the disk surfaces in all groups as typically seen on SLA surfaces. The water contact angles were measured to be 1.85, 1.48, and 1.18 degrees for the irradiation group, rehydrophobization group, and re-irradiation group, respectively, indicating superhydrophilicity. There was no difference in the surface elemental ratio or the spectra of XPS, cell viability, or ALP activity. Although the re-irradiation group had the highest total amount of calcium deposition, there was no statistical significance. Conclusion: Within the limitations of this study, improved superhydrophilicity and bioactivity after UV irradiation were maintained during short-term rehydrophobization and repeated re-irradiation without changing the topography of SLA titanium surfaces. [ABSTRACT FROM AUTHOR]