Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known.Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVAinduced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes.We sought to characterize the clinical characteristics of ATTR-CM in Asia. Methods: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). Results: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010–2013 vs. 22 [21.0%] during 2014–2017 vs. 75 [71.4%] during 2018–2021).Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010–2013 to 77% between 2018–2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan.Asp38Ala was the most common mutation. Conclusion A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Owing to donor-related issues, blood shortages and transfusion-related adverse reactions have become global issues of grave concern. In vitro manufactured red blood cells (RBCs) are promising substitutes for blood donation. In the United Kingdom, a clinical trial for allogeneic mini transfusion of cultured RBCs derived from primary hematopoietic stem cells has recently begun. However, current production quantities are limited and need improved before clinical use. New methods to enhance manufacturing efficiencies have been explored, including different cell sources, bioreactors, and 3-dimensional (3D) materials; however, further research is required. In this review, we discuss various cell sources for blood cell production, recent advances in bioreactor manufacturing processes, and the clinical applications of cultured blood.

Background: CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. Methods: KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. Results: CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). Conclusion Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype-phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.
Humans ; Phenotype ; Wnt Proteins

R, G186S, S219F) in hemagglutinin up to 15 passages when cultured in eggs.CONCLUSION: H3N2 influenza virus cultured in eggs could lead mutations in amino acid sequence of hemagglutinin, distinct from the corresponding virus cultured in cells for which no antigenic mutation was observed. These findings suggest that cell culture is a more stable and effective way of production with lower risk of antigenic mutations for the manufacture of influenza vaccines.]]>
Amino Acid Sequence ; Animals ; Cell Culture Techniques ; Cell Line ; Chickens ; Eggs ; Erythrocytes ; Guinea Pigs ; Hand ; Hemagglutination ; Hemagglutinins ; Humans ; Influenza Vaccines ; Influenza, Human ; Neuraminidase ; Orthomyxoviridae ; Ovum ; Sequence Analysis ; Specific Pathogen-Free Organisms

Contrast-enhanced ultrasound (CEUS) is a powerful technique for differentiating focal liver lesions (FLLs) without the risks of potential nephrotoxicity or ionizing radiation. In the diagnostic algorithm for FLLs on CEUS, washout is an important feature, as its presence is highly suggestive of malignancy and its characteristics are useful in distinguishing hepatocellular from non-hepatocellular malignancies. Interpreting washout on CEUS requires an understanding that microbubble contrast agents are strictly intravascular, unlike computed tomography or magnetic resonance imaging contrast agents. This review explains the definition and types of washout on CEUS in accordance with the 2017 version of the CEUS Liver Imaging Reporting and Data System and presents their applications to differential diagnosis with illustrative examples. Additionally, we propose potential mechanisms of rapid washout and describe the washout phenomenon in benign entities.
Carcinoma, Hepatocellular ; Contrast Media ; Diagnosis ; Diagnosis, Differential ; Information Systems ; Liver ; Magnetic Resonance Imaging ; Microbubbles ; Neoplasm Metastasis ; Radiation, Ionizing ; Ultrasonography

OBJECTIVE: The purpose of this study was to investigate factors influencing the success rate of orthodontic microimplants (OMIs) using panoramic radiographs (PRs). METHODS: We examined 160 OMIs inserted bilaterally in the maxillary buccal alveolar bone between the second premolars and first molars of 80 patients (51 women, 29 men; mean age, 18.0 ± 6.1 years) undergoing treatment for malocclusion. The angulation and position of OMIs, as well as other parameters, were measured on PRs. The correlation between each measurement and the OMI success rate was then evaluated. RESULTS: The overall success rate was 85.0% (136/160). Age was found to be a significant predictor of implant success (p < 0.05), while sex, side of placement, extraction, and position of the OMI tip were not significant predictors (p > 0.05). The highest success rate was observed for OMIs with tips positioned on the interradicular midline (IRML; central position). Univariate analyses revealed that the OMI success rate significantly increased with an increase in the OMI length and placement height of OMI (p = 0.001). However, in simultaneous analyses, only length remained significant (p = 0.027). Root proximity, distance between the OMI tip and IRML, interradicular distance, alveolar crest width, distance between the OMI head and IRML, and placement angle were not factors for success. Correlations between the placement angle and all other measurements except root proximity were statistically significant (p < 0.05). CONCLUSIONS Our findings suggest that OMIs positioned more apically with a lesser angulation, as observed on PRs, exhibit high success rates.