Evaluation of the effects of temperature and centrifugation time on elimination of uncured resin from 3D-printed dental aligners.

The study investigated the effects of temperature and centrifugation time on the efficacy of removing uncured resin from 3D-printed clear aligners. Using a photo-polymerizable polyurethane resin (Tera Harz TC-85, Graphy Inc., Seoul, Korea), aligners were printed and subjected to cleaning processes using isopropyl alcohol (IPA) or centrifugation (g-force 27.95g) at room temperature (RT, 23 °C) and high temperature (HT, 55 °C) for 2, 4, and 6 min. The control group received no treatment (NT). Cleaning efficiency was assessed through rheological analysis, weight measurement, transparency evaluation, SEM imaging, 3D geometry evaluation, stress relaxation, and cell viability tests. Results showed increased temperature and longer centrifugation times significantly reduced aligner viscosity, weight (P < 0.05), and transmittance. IPA-cleaned aligners exhibited significantly lower transparency and rougher surfaces in SEM images. All groups met ISO biocompatibility standards in cytotoxicity tests. The NT group had higher root mean square (RMS) values, indicating greater deviation from the original design. Stress relaxation tests revealed over 95% recovery in all groups after 60 min. The findings suggest that a 2-min HT centrifugation process effectively removes uncured resin without significantly impacting the aligners' physical and optical properties, making it a clinically viable option.

Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Efficacy Assessment of Five Policosanol Brands and Damage to Vital Organs in Hyperlipidemic Zebrafish by Six-Week Supplementation: Highlighting the Toxicity of Red Yeast Rice and Safety of Cuban Policosanol (Raydel®).

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt/wt) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt/wt). The results revealed that policosanol brands (PCO1-PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD's elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1-PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD's elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2-PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products.

Chloroplast Genomes of Vitis flexuosa and Vitis amurensis: Molecular Structure, Phylogenetic, and Comparative Analyses for Wild Plant Conservation.

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis L. species, V. flexuosa Thunb. and V. amurensis Rupr., contributing valuable data to the Korea Crop Wild Relatives inventory. Through exhaustive specimen collection spanning diverse ecological niches across South Korea, we ensured comprehensive representation of genetic diversity. Our analysis, which included rigorous codon usage bias assessment and repeat analysis, provides valuable insights into amino acid preferences and facilitates the identification of potential molecular markers. The assembled chloroplast genomes were subjected to meticulous annotation, revealing divergence hotspots enriched with nucleotide diversity, thereby presenting promising candidates for DNA barcodes. Additionally, phylogenetic analysis reaffirmed intra-genus relationships and identified related crops, shedding light on evolutionary patterns within the genus. Comparative examination with chloroplast genomes of other crops uncovered conserved sequences and variable regions, offering critical insights into genetic evolution and adaptation. Our study advances the understanding of chloroplast genomes, genetic diversity, and phylogenetic relationships within Vitis species, thereby laying a foundation for enhancing grapevine genetic diversity and resilience to environmental challenges.

Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.

BACKGROUND AND HYPOTHESIS: End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. METHODS: We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. RESULTS: Out of 69 368 incident dialysis patients, 22 326, 5020, 2853, and 39 169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and ≥ 6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. CONCLUSIONS: Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.

Chronic kidney disease in postmenopausal women is associated with tooth loss.

OBJECTIVE: Menopause is characterized by changes in reproductive hormone levels that can negatively affect bone. Chronic kidney disease (CKD) and tooth loss are also important and common health issues after menopause. This study aimed to evaluate the association between CKD and tooth loss in postmenopausal women. METHODS: The study evaluated 64,971 participants who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010-2018, including postmenopausal women, aged 40 to 79 years. Participants were divided into two groups based on the number of teeth in their dentition (≥20 and <20). MAIN OUTCOME MEASURES: The association between CKD and tooth loss was analyzed using multivariate logistic regression. Age, income, education, smoking, alcohol intake, body mass index, hypertension, diabetes, annual oral examination, toothbrushing, and the use of oral care products were considered. Subgroup analyses were further conducted according to age (40-65 yr and 66-79 yr). RESULTS: After adjusting for covariates, CKD and estimated glomerular filtration rate were significantly associated with having ≥20 teeth (PT20; CKD: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.04-1.90; estimated glomerular filtration rate (10 mL/min/1.73 m2): OR 0.90, 95% CI 0.86-0.94). Importantly, the association between CKD and PT20 was significant in postmenopausal women, aged 66 to 79 years (OR 1.45, 95% CI 1.05-2.01). CONCLUSIONS: In postmenopausal women, CKD and tooth loss may be associated. The association is significant in postmenopausal women, aged 66 to 79 years.

Artificial sensory system based on memristive devices.

In the biological nervous system, the integration and cooperation of parallel system of receptors, neurons, and synapses allow efficient detection and processing of intricate and disordered external information. Such systems acquire and process environmental data in real-time, efficiently handling complex tasks with minimal energy consumption. Memristors can mimic typical biological receptors, neurons, and synapses by implementing key features of neuronal signal-processing functions such as selective adaption in receptors, leaky integrate-and-fire in neurons, and synaptic plasticity in synapses. External stimuli are sensitively detected and filtered by "artificial receptors," encoded into spike signals via "artificial neurons," and integrated and stored through "artificial synapses." The high operational speed, low power consumption, and superior scalability of memristive devices make their integration with high-performance sensors a promising approach for creating integrated artificial sensory systems. These integrated systems can extract useful data from a large volume of raw data, facilitating real-time detection and processing of environmental information. This review explores the recent advances in memristor-based artificial sensory systems. The authors begin with the requirements of artificial sensory elements and then present an in-depth review of such elements demonstrated by memristive devices. Finally, the major challenges and opportunities in the development of memristor-based artificial sensory systems are discussed.

Oral Supplementation of Ozonated Sunflower Oil Augments Plasma Antioxidant and Anti-Inflammatory Abilities with Enhancement of High-Density Lipoproteins Functionality in Rats.

Research on ozonated sunflower oil (OSO) is mostly restricted to its topical application, whereas the functional and toxicological assessment of oral OSO consumption is yet to be solved. Herein, OSO was orally supplemented in rats to assess the impact on plasma antioxidant status, low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Also, the functionality of HDL from the OSO-supplemented rats (OSO-HDL) was tested against carboxymethyllysine (CML)- induced hyperinflammation in embryo and adult zebrafish. The results revealed that four weeks of OSO supplementation (3 g/kg BW/day) had no adverse effect on rats' hematological and blood biochemical profiles. Nonetheless, decreased interleukin (IL)-6, and LDL-C levels, along with enhanced ferric ion reduction ability (FRA) and sulfhydryl content, were observed in the plasma of OSO-supplemented rats compared to the control and sunflower oil (SO) supplemented group. In addition, OSO supplementation stabilized apoA-I/HDL and augmented HDL-allied paraoxonase (PON)-1 activity. The microinjection of OSO-HDL (10 nL, 2 mg/mL) efficiently prevented the CML (500 ng)-induced zebrafish embryo mortality and developmental deformities. Similarly, OSO-HDL thwarted CML-posed neurotoxicity and demonstrated a significant hepatoprotective effect against CML-induced fatty liver changes, hepatic inflammation, oxidative stress, and apoptosis, as well as exhibiting a noticeable influence to revert CML-induced dyslipidemia. Conclusively, OSO supplementation demonstrated no toxic effects on rats, ameliorated plasma antioxidant status, and positively influenced HDL stability and functionality, leading to a protective effect against CML-induced toxicity in zebrafish.

Cascade Sequence of Photooxygenation-Epoxidation for the Flow Synthesis of Epoxy Alcohols.

A photooxygenation-epoxidation cascade sequence converting alkenes to epoxy alcohols was developed and evaluated in batch and continuous-flow systems. In the batch system, the undesired interactions between the photooxygenation and epoxidation catalysts resulted in suboptimal yields, whereas the fine control of reaction parameters in the flow system allowed the allyl hydroperoxides produced through photooxygenation of alkenes to be rapidly converted to epoxy alcohols in yields of up to 93%. The developed procedure allows one to avoid an important synthetic bottleneck, works well where traditional batch synthesis fails, and can be scaled up to meet the needs of industrial production, thus presenting a valuable addition to the toolbox of practicing organic chemists.

B-Cell Lymphoma Arising From a Nasal Implant: A Brief Clinical Study.

Continuous exposure to foreign substances initiates a sustained inflammatory reaction in the body, and subsequent chronic inflammation is recognized as one of the causes of lymphoma. Most lymphomas caused by foreign bodies are composed of 2 major phenotypes. Diffuse large B-cell lymphoma arising from metallic prosthesis, also called metallic implant-associated lymphoma and T-cell phenotype anaplastic large cell lymphoma, commonly associated with breast implants. Augmentation rhinoplasty is often performed to improve the esthetics of the nasal dorsum and various synthetic materials have been used as implants. The occurrence of lymphoma originating from a nasal implant is scarcely documented, and even more uncommon is its manifestation as epstein-barr virus (EBV)-negative extranodal marginal zone lymphoma. Here, the authors describe a rare case of B-cell lymphoma of the nose and nasolacrimal duct in a 49-year-old woman who underwent rhinoplasty with a silicone implant 20 years ago.

Mitochondrial SIRT3 as a protective factor against cyclosporine A-induced nephrotoxicity.

Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.

Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Cuban Policosanol (Raydel®) Exerts Higher Antioxidant and Anti-Glycation Activities than Chinese Policosanol (BOC Sciences) in Reconstituted High-Density Lipoproteins: In Vivo Anti-Inflammatory Activities in Zebrafish and Its Embryos.

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel®) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and 1-tetratriacotanol (C34). After synthesizing rHDL with apolipoprotein A-I (apoA-I), the two policosanols bound well with phospholipid and apoA-I to form the discoidal rHDL. Notably, rHDL-1, containing Cuban policosanol, displayed the largest particle diameter at approximately 78 ± 3 nm. In contrast, both control rHDL (rHDL-0) and rHDL containing Chinese policosanol (rHDL-2) exhibited smaller particles, with diameters of approximately 58 ± 3 nm and 61 ± 2 nm, respectively. Furthermore, rHDL-1 demonstrated enhanced anti-glycation activity, safeguarding apoA-I from degradation within HDL, and displayed the antioxidant ability to inhibit LDL oxidation. A microinjection of each rHDL into zebrafish embryos in the presence of carboxymethyllysine (CML) revealed rHDL-1 to have the strongest antioxidant activity with the highest embryo survivability and normal developmental morphology. Dermal application to recover the wound revealed rHDL-1 to have the highest wound-healing activity (75%) and survivability (92%) in the cutaneous wound area in the presence of CML. In adult zebrafish, injecting CML (250 µg) caused acute death and hyperinflammation, marked by heightened neutrophil infiltration and interleukin (IL)-6 production in liver. However, co-administering rHDL-1 notably increased survival (85%) and exhibited strong anti-inflammatory properties, reducing IL-6 production while improving the blood lipid profile. However, a co-injection of rHDL-2 resulted in the lowest survivability (47%) with more hepatic inflammation. In conclusion, Cuban policosanol (Raydel®) has more desirable properties for the in vitro synthesis of rHDL with stronger anti-glycation and antioxidant activities than those of Chinese policosanol (BOC Sciences). Moreover, Raydel-policosanol-integrated rHDL demonstrates a noteworthy effect on accelerated wound healing and robust anti-inflammatory properties, leading to increased survivability in zebrafish embryos and adults by effectively suppressing CML-induced hyperinflammation.

Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea.

Purpose: The rate of interval colorectal cancer (iCRC) is now accepted as a key performance indicator of organized colorectal cancer (CRC) screening programs. We aimed to examine the association between endoscopist volumes and the rate of iCRC among individuals with a positive fecal immunochemical test (FIT) within a nationwide population-based CRC screening program. Materials and Methods: Individuals aged ≥50 years who underwent colonoscopy after a positive FIT from January 1, 2019 until December 31, 2020 in the Korean National Cancer Screening Program (KNCSP) were enrolled. We converted the data into per-endoscopist screening results, calculated the iCRC rates per endoscopist, and compared them to the previous year's annual volume that was divided into five groups (V1, 1-9; V2, 10-29; V3, 30-59; V4, 60-119; V5, ≥120). Results: A total of 10,412 endoscopists performed 216,907 colonoscopies. Overall, the average rate of iCRC per endoscopist was 8.46 per 1,000 examinations. Compared with the group with the highest volume (V5 group), the rate of iCRC was 2.21 times higher in the V1 group. Similar trends were observed in the other groups (V2: Relative risks [RR], 2.15; 95% Confidence Interval [CI], 1.57-2.94; V3: RR, 1.56, 95% CI, 1.15-2.13; V4: RR, 1.18; 95% CI, 0.83-1.67). Conclusion: The findings emphasize that endoscopists with lower procedure volumes have higher risks of interval cancer being missed or undetected. To maximize the preventative impact of colonoscopy for colorectal cancer, this issue should be addressed by monitoring endoscopist volumes and variations in performances.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

Background/Aims: : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

Clinicopathologic and Endosonographic Characteristics of Colon Subepithelial Tumors Discovered Incidentally.

BACKGROUND/AIMS: Colonoscopy is commonly used for colorectal cancer screening; therefore, the detection of colon subepithelial tumors (SETs) has also increased. Several research studies have been undertaken to diagnose and treat stomach and rectal SETs. The purpose of this study was to determine a diagnostic point for colon SETs by comparing histological findings with the endoscopic characteristics of colon SETs discovered by chance. METHODS: A total 194 patients underwent an endoscopic ultrasound (EUS) for suspicious colon SETs during a colonoscopy from May 2014 to December 2021. A total of 105 colon SETs, which were histologically diagnosed, were finally included. Fisher's exact test was used to determine the factors associated with malignant SETs. RESULTS: Colon SETs were predominantly present in the right colon (n = 73, 69.5%), particularly in the transverse colon (n = 32, 30.5%). The majority were smaller than 10 mm (n = 88, 83.8%), and they had hard consistencies (n = 84, 80%) and exhibited no surface changes (n = 96, 91.4%). Most of them were found in the submucosal layers (n = 54, 51.4%) and had a hypoechoic pattern (n = 56, 53.3%) in the EUS. Of the histologically confirmed cases, only three (3/105, 2.9%) were malignant. Most benign lesions were lipomas, suspected parasitic infections, or lesions caused by various inflammatory reactions, including fibrous/fibrocalcific lesions and necrotic nodules. All soft lesions were benign. Two of the three malignant lesions were adenocarcinomas, and the other was lymphoma. For the malignant SETs, there was a statistically significant alteration in the surface of the tumors (p < 0.001), and they were located where the muscularis mucosa layer was included (p = 0.008). The potential malignant SETs, granular cell tumors, and neuroendocrine tumors (NETs) had similar features, such as yellowish hypoechoic masses. Colon NETs were only found in the rectosigmoid junction. Parasitic infections and lesions, resulting in various inflammatory reactions, were observed as pale and hard SETs and mostly revealed as mixed echogenic masses located in the muscularis mucosa, submucosa, or multi-layers in the EUS. CONCLUSION: This study showed that small colon SETs were mostly benign lesions. Despite its rarity, pathological confirmation is crucial in cases where the SET has surface changes and has been located in a position where the muscularis mucosa layer was included on the EUS, due to the risk of malignancy.

Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.

PHD finger protein 7 (Phf7) is a member of the PHF family proteins, which plays important roles in spermiogenesis. Phf7 is expressed in the adult testes and its deficiency causes male infertility. In this study, we tried to find the causal relationship between Phf7 deficiency and reduced growth retardation which were found in null knock-out (Phf7-/-) mice. Phf7-/- mice were born normally in the Mendelian ratio. However, the Phf7-/- males showed decreased body weight gain, bone mineral density, and bone mineral content compared to those in wild-type (WT) mice. Histological analysis for tibia revealed increased number of osteoclast cells in Phf7-/- mice compared with that in WT mice. When we analyzed the expressions for marker genes for the initial stage of osteoclastogenesis, such as receptor activator of nuclear factor kappa B (Rank) in tibia, there was no difference in the mRNA levels between Phf7-/- and WT mice. However, the expression of tartrate-resistant acid phosphatase (Trap), a mature stage marker gene, was significantly higher in Phf7-/- mice than in WT mice. In addition, the levels of testosterone and dihydrotestosterone (DHT), more potent and active form of testosterone, were significantly reduced in the testes of Phf7-/- mice compared to those in WT mice. Furthermore, testicular mRNA levels for steroidogenesis marker genes, namely Star, Cyp11a1, Cyp17a1 and 17ß-hsd, were significantly lower in Phf7-/- mice than in WT mice. In conclusion, these results suggest that Phf7 deficiency reduces the production of male sex hormones and thereby impairs associated bone remodeling.

Long-Term Supplementation of Royal Jelly (Raydel®) Improves Zebrafish Growth, Embryo Production and Survivability, Blood Lipid Profile and Functionality of Vital Organs: A 72-Weeks' Consumption Study.

Royal jelly is a honeybee product with substantial pharmacological and health promotional activities. Nevertheless, the health implications associated with the prolonged dietary supplementation of royal jelly have yet to be elucidated extensively. Herein, 72 weeks of dietary supplementation of royal jelly at 5% and 10% (w/w) were investigated to assess the impact on zebrafish survivability, body weight, liver, testis, ovary functionality, and blood lipid profile. The results revealed no adverse effect of 72 weeks of royal jelly supplementation on zebrafish survivability. Conversely, a noteworthy enhancement in the zebrafish body weight was observed in royal-jelly-supplemented zebrafish in a concentration-dependent manner [5% and 10% (w/w)]. Interestingly, female zebrafish were found to be more biased, with a significant 17% (p < 0.001) and 23% (p < 0.001) higher body weight enhancement after 72 weeks of consumption of 5% and 10% (w/w) royal jelly, compared to the male zebrafish. The histological outcome revealed no sign of hepatotoxicity; moreover, diminished reactive oxygen species (ROS) and apoptosis were observed in the hepatic tissue of the royal-jelly-supplemented group. Consistent with the histological outcomes, the liver function biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), exhibited a significant decrease of 1.9-fold (p = 0.006) and 1.4-fold (p = 0.003) in zebrafish supplemented with royal jelly compared to those on a normal diet (ND) and zebrafish given supplements. Also, no sign of ovary and testis-related toxicity was observed in the royal-jelly-supplemented group during the 72-week period. Furthermore, the 10% (w/w) royal-jelly-consuming zebrafish exhibited a notable 2.1-fold increase (p = 0.018) in egg-laying ability compared to the ND-supplemented zebrafish. The 10% (w/w) royal jelly supplementation also effectively maintained the blood lipid profile by curtailing serum triglycerides (TG) and elevating high-density lipoprotein cholesterol (HDL-C). Conclusively, royal jelly dietary supplementation for a prolonged time found royal jelly to be safe to consume, to efficiently improve hepatic function, reproduction, and sexual health, and to augment the serum HDL-C level.

Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.

BACKGROUND: Patients with fibro-calcific aortic valve disease (FCAVD) have lipid depositions in their aortic valve that engender a proinflammatory impetus toward fibrosis and calcification and ultimately valve leaflet stenosis. Although the lipoprotein(a)-autotaxin (ATX)-lysophosphatidic acid axis has been suggested as a potential therapeutic target to prevent the development of FCAVD, supportive evidence using ATX inhibitors is lacking. We here evaluated the therapeutic potency of an ATX inhibitor to attenuate valvular calcification in the FCAVD animal models. METHODS: ATX level and activity in healthy participants and patients with FCAVD were analyzed using a bioinformatics approach using the Gene Expression Omnibus datasets, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and western blotting. To evaluate the efficacy of ATX inhibitor, interleukin-1 receptor antagonist-deficient (Il1rn-/-) mice and cholesterol-enriched diet-induced rabbits were used as the FCAVD models, and primary human valvular interstitial cells (VICs) from patients with calcification were employed. RESULTS: The global gene expression profiles of the aortic valve tissue of patients with severe FCAVD demonstrated that ATX gene expression was significantly upregulated and correlated with lipid retention (r = 0.96) or fibro-calcific remodeling-related genes (r = 0.77) in comparison to age-matched non-FCAVD controls. Orally available ATX inhibitor, BBT-877, markedly ameliorated the osteogenic differentiation and further mineralization of primary human VICs in vitro. Additionally, ATX inhibition significantly attenuated fibrosis-related factors' production, with a detectable reduction of osteogenesis-related factors, in human VICs. Mechanistically, ATX inhibitor prohibited fibrotic changes in human VICs via both canonical and non-canonical TGF-ß signaling, and subsequent induction of CTGF, a key factor in tissue fibrosis. In the in vivo FCAVD model system, ATX inhibitor exposure markedly reduced calcific lesion formation in interleukin-1 receptor antagonist-deficient mice (Il1rn-/-, P = 0.0210). This inhibition ameliorated the rate of change in the aortic valve area (P = 0.0287) and mean pressure gradient (P = 0.0249) in the FCAVD rabbit model. Moreover, transaortic maximal velocity (Vmax) was diminished with ATX inhibitor administration (mean Vmax = 1.082) compared to vehicle control (mean Vmax = 1.508, P = 0.0221). Importantly, ATX inhibitor administration suppressed the effects of a high-cholesterol diet and vitamin D2-driven fibrosis, in association with a reduction in macrophage infiltration and calcific deposition, in the aortic valves of this rabbit model. CONCLUSIONS: ATX inhibition attenuates the development of FCAVD while protecting against fibrosis and calcification in VICs, suggesting the potential of using ATX inhibitors to treat FCAVD.