Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development. METHODS: Tcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2f/f). Alb-Cre;Tcf7l2f/f and their wild-type (Tcf7l2f/f) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology. RESULTS: Alb-Cre;Tcf7l2f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions. CONCLUSIONS/INTERPRETATION: In mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL. DATA AVAILABILITY: RNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449 ).

Characterization of terminal-ileal and colonic Crohn's disease in treatment-naïve paediatric patients based on transcriptomic profile using logistic regression.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder of the gastrointestinal tract and comprises ulcerative colitis (UC) and Crohn's disease (CD). Crohn's disease can affect any part of the gastrointestinal tract, but mainly the terminal ileum and colon. In the present study, we aimed to characterize terminal-ileal CD (ICD) and colonic CD (CCD) at the molecular level, which might enable a more optimized approach for the clinical care and scientific research of CD. METHODS: We analyzed differentially expressed genes in samples from 23 treatment-naïve paediatric patients with CD and 25 non-IBD controls, and compared the data with previously published RNA-Seq data using multi-statistical tests and confidence intervals. We implemented functional profiling and proposed statistical methods for feature selection using a logistic regression model to identify genes that are highly associated in ICD or CCD. We also validated our final candidate genes in independent paediatric and adult cohorts. RESULTS: We identified 550 genes specifically expressed in patients with CD compared with those in healthy controls (p < 0.05). Among these DEGs, 240 from patients with CCD were mainly involved in mitochondrial dysfunction, whereas 310 from patients with ICD were enriched in the ileum functions such as digestion, absorption, and metabolism. To choose the most effective gene set, we selected the most powerful genes (p-value ≤ 0.05, accuracy ≥ 0.8, and AUC ≥ 0.8) using logistic regression. Consequently, 33 genes were identified as useful for discriminating CD location; the accuracy and AUC were 0.86 and 0.83, respectively. We then validated the 33 genes with data from another independent paediatric cohort (accuracy = 0.93, AUC = 0.92) and adult cohort (accuracy = 0.88, AUC = 0.72). CONCLUSIONS: In summary, we identified DEGs that are specifically expressed in CCD and ICD compared with those in healthy controls and patients with UC. Based on the feature selection analysis, 33 genes were identified as useful for discriminating CCD and ICD with high accuracy and AUC, for not only paediatric patients but also independent cohorts. We propose that our approach and the final gene set are useful for the molecular classification of patients with CD, and it could be beneficial in treatments based on disease location.

ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones.

AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae. ClpL exists as a tetradecamer in solution in the presence of ATP. The cryo-EM structure of ClpL at 4.5 Å resolution reveals a striking tetradecameric arrangement. Solution structures of ClpL derived from small-angle X-ray scattering data suggest that the tetradecameric ClpL could assume a spiral conformation found in active hexameric/dodecameric AAA+ chaperone structures. Vertical positioning of the middle domain accounts for the head-to-head arrangement of two heptameric rings. Biochemical activity assays with site-directed mutagenesis confirmed the critical roles of residues both in the integrity of the tetradecameric arrangement and activities of ClpL. Non-conserved Q321 and R670 are crucial in the heptameric ring assembly of ClpL. These results establish that ClpL is a functionally active tetradecamer, clearly distinct from hexameric/dodecameric AAA+ chaperones.

Characterization of sexual size dimorphism and sex-biased genes expression profile in the olive flounder.

Sexual size dimorphism (SSD) is a widespread phenomenon in fish species, including in the olive flounder. Although it is well established that female olive flounders acquire more bone mass than males, the underlying mechanism and timing of this SSD remains controversial. Here, the gene expression profiles of adult male and female olive flounder fish were explored to better understand the SSD mechanisms. Using RNA sequencing, a total of 4784 sex-biased differentially expressed genes (DEGs) in the fin with asymptotic growth after maturity were identified, among which growth-related factors were found. Gene ontology and pathway enrichment studies were performed to predict potential SSD-related genes and their functions. According to functional analysis, negative regulation of cell proliferation was significantly enriched in males, and anabolism related genes were highly expressed in females. In addition, pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that five sexual dimorphism-related candidate genes (bambia, smurf1, dvl2, cul1a, and dvl3) were enriched in osteogenesis-contributing pathways. These results suggest that these five candidate genes may be relevant for skeletal development in olive flounders. Altogether, this study adds new knowledge for a better understanding of SSD-related growth traits in olive flounder, which can be used for enhancing aquaculture productivity with reduced production costs.

Bioinformatic analysis of regulation of natural antisense transcripts by transposable elements in human mRNA.

Non-coding RNA is no longer considered to be "junk" DNA, based on evidence uncovered in recent decades. In particular, the important role played by natural antisense transcripts (NATs) in regulating the expression of genes is receiving increasing attention. However, the regulatory mechanisms of NATs remain incompletely understood. It is well-known that the insertion of transposable elements (TEs) can affect gene transcription. Using a bioinformatics approach, we identified NATs using human mRNA sequences from the UCSC Genome Browser Database. Our in silico analysis identified 1079 NATs and 700 sense-antisense gene pairs. We identified 179 NATs that showed evidence of having been affected by TEs during cellular gene expression. These findings may provide an understanding of the complex regulation mechanisms of NATs. If our understanding of NATs as modulators of gene expression is further enhanced, we can develop ways to control gene expression.

Effects of Granulocyte Macrophage Colony-Stimulating Factor Inhibition on the Skin/Nerve Cell Model In Vitro.

The present study is based on the concept of neuro-aging and how it may affect surrounding skin cells. It has been shown that many factors play a significant role in skin homeostasis by interfering with various cytokines, either through activation or inhibition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine, and our previous study has shown its effects on neuronal senescence after ultraviolet (UV) irradiation of skin cells. Following our previous work, this study was performed to investigate the neuroprotective effects of a GM-CSF antagonist, and how it may play an essential role in mediating anti-senescence and anti-inflammatory effects in the keratinocyte/nerve aging model. When human blastoma cells (SH-SY5Y) were treated with 10 ng/ml of GM-CSF, the levels of regulatory RNAs associated with aging, such as matrix metalloproteinase-9 (MMP9), nuclear factor NF-kappa-B p50 subunit (NFKB), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1ß) increased, whereas GM-CSF inhibition caused their expression to decrease. A decrease in the antioxidant, glutathione (GSH) was observed after SH-SY5Y cells were treated with GM-CSF. This study confirms that this GM-CSF antagonist may play an important role in neural senescence, where inhibition may be a new target in the skin/nerve aging model.

Highly Hydrophilic Polyurethane Foam Dressing Versus Early Hydrophilic Polyurethane Foam Dressing on Skin Graft Donor Site Healing in Patients with Diabetes: An Exploratory Clinical Trial.

OBJECTIVE: To compare the effects of early hydrophilic polyurethane (EHP) foam dressing and highly hydrophilic polyurethane (HHP) foam dressing on wound healing in patients with diabetes. METHODS: Twenty patients with diabetes with skin graft donor sites on the lateral thigh were enrolled in this study. Each donor site was divided into two equal-sized areas for the application of HHP or EHP foam dressing. The study endpoint was the time required for healing, defined as complete epithelialization of the donor site without discharge. All possible adverse events were also documented. MAIN RESULTS: Donor site healing was faster in 15 patients on the HHP half and 1 patient on the EHP half. In four patients, healing rates were the same between the HHP and EHP areas. Donor sites treated with HHP and EHP foam dressings healed in 17.2 ± 4.4 and 19.6 ± 3.7 days (P = .007), respectively. During the study period, no adverse event associated with the dressings occurred in either group. CONCLUSIONS: The HHP foam dressing might provide faster healing than EHP foam dressing for skin graft donor sites in patients with diabetes.

The Ancient Phosphatidylinositol 3-Kinase Signaling System Is a Master Regulator of Energy and Carbon Metabolism in Algae.

Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy and hyper-accumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and "omics" approaches to demonstrate that PI3K signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents. Lipid profiling of wild-type and PI3K KD lines showed significantly reduced membrane lipid breakdown under nitrogen starvation (-N) in the KD. RNA-seq and network analyses showed that under -N conditions, the KD line carried out lipogenesis rather than lipid hydrolysis by initiating de novo fatty acid biosynthesis, which was supported by tricarboxylic acid cycle down-regulation and via acetyl-CoA synthesis from glycolysis. Remarkably, autophagic responses did not have primacy over inositide signaling in algae, unlike in mammals and vascular plants. The mutant displayed a fundamental shift in intracellular energy flux, analogous to that in tumor cells. The high free fatty acid levels and reduced mitochondrial ATP generation led to decreased cell viability. These results indicate that the PI3K signal transduction pathway is the metabolic gatekeeper restraining biofuel yields, thus maintaining fitness and viability under stress in algae. This study demonstrates the existence of homeostasis between starch and lipid synthesis controlled by lipid signaling in algae and expands our understanding of such processes, with biotechnological and evolutionary implications.

Septorhinoplasty for Destructed Septal L-Strut in Patients with Previously Applied Porous High-Density Polyethylene Implants (Medpor®).

BACKGROUND: Porous high-density polyethylene implants (Medpor®) have been extensively used for septal extension grafts in Asian rhinoplasty. However, studies on the long-term complications associated with Medpor® have not been reported. Therefore, the purpose of this study was to evaluate the long-term complications of septal extension grafts using Medpor® and present a reconstructive strategy for destructed septal L-struts. METHODS: We conducted a 12-year retrospective medical chart review of 428 patients who visited our center for septorhinoplasty. Among 428 patients, 43 patients had Medpor® for septal extension grafts previously applied at other clinics. The quadrangular cartilage was devoid or destructed in the area where Medpor® was previously applied. Therefore, all patients underwent secondary septorhinoplasty using autogenous cartilage grafts. Patient outcome was assessed to evaluate satisfaction, hardness of nasal tip, functional nasal obstruction symptom evaluation (NOSE) scores, and pain scores. Anthropometric analyses were carried out with patients' photographs. Postoperative complications were also evaluated. RESULTS: After septal L-strut reconstruction, 87% of patients were satisfied with their aesthetic results. Hardness of nasal tip, NOSE scores, and pain scores also improved after reconstruction. Anthropometric analyses demonstrated that increased nasal length and decreased columellar-labial angle were achieved in patients with short nose deformities. No postoperative complications related to the reconstruction were recorded for any patient. CONCLUSIONS: The devastated destruction of nasal support lines was found after the use of Medpor® for septorhinoplasty. Therefore, the use of Medpor® should be reduced. Autogenous cartilage grafts are the last resort for reconstruction of destructed septal L-struts. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

HIF1A overexpression using cell-penetrating DNA-binding protein induces angiogenesis in vitro and in vivo.

Hypoxia-inducible factor-1 alpha (HIF1A) is an important transcription factor for angiogenesis. Recent studies have used the protein transduction domain (PTD) to deliver genes, but the PTD has not been used to induce the expression of HIF1A. This study aimed at using a novel PTD (Hph-1-GAL4; ARVRRRGPRR) to overexpress the HIF1A and identify the effects on angiogenesis in vitro and in vivo. Overexpression of HIF1A was induced using Hph-1-GAL4 in human umbilical vein/vascular endothelium cells (HUVEC). The expression levels of genes were analyzed by the quantitative real-time polymerase chain reaction (qPCR) after 2 and 4 days, respectively. An in vitro tube formation was performed using Diff-Quik staining. HIF1A and Hph-1-GAL4 were injected subcutaneously into the ventral area of each 5-week-old mouse. All of the plugs were retrieved after 1 week, and the gene expression levels were evaluated by qPCR. Each Matrigel plug was evaluated using the hemoglobin assay and hematoxylin and eosin (HE) staining. The expression levels of HIF1A and HIF1A target genes were significantly higher in HIF1A-transfected HUVEC than in control HUVEC in vitro. In the in vivo Matrigel plug assay, the amount of hemoglobin was significantly higher in the HIF1A-treatment group than in the PBS-treatment group. Blood vessels were identified in the HIF1A-treatment group. The expression levels of HIF1A, vascular endothelial growth factor (Vegf), and Cd31 were significantly higher in the HIF1A-treatment group than in the PBS-treatment group. These findings suggest that using Hph-1-G4D to overexpress HIF1A might be useful for transferring genes and regenerating tissues.

Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer.

BACKGROUND: Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear. AIMS: This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3' untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs). METHODS: RNA-sequencing and small RNA-sequencing were performed on AGS and MKN-45 cells with a stable ADAR1 knockdown. Changed frequencies of editing and mRNA and miRNA expression were then identified by bioinformatic analyses. Targets of RNA editing were further validated in patients' samples. RESULTS: In the Alu region of both gastric cell lines, editing was most commonly of the A-to-I type in 3'-UTR or intron. mRNA and protein levels of PHACTR4 increased in ADAR1 knockdown cells, because of the loss of seed sequences in 3'-UTR of PHACTR4 mRNA that are required for miRNA-196a-3p binding. Immunohistochemical analyses of tumor and paired normal samples from 16 gastric cancer patients showed that ADAR1 expression was higher in tumors than in normal tissues and inversely correlated with PHACTR4 staining. On the other hand, decreased miRNA-148a-3p expression in ADAR1 knockdown cells led to increased mRNA and protein expression of NFYA, demonstrating ADAR1's editing-independent function. CONCLUSIONS: ADAR1 regulates post-transcriptional gene expression in gastric cancer through both RNA editing-dependent and editing-independent mechanisms.

Profiling of the Major Phenolic Compounds and Their Biosynthesis Genes in Sophora flavescens Aiton.

Sophorae Radix (Sophora flavescens Aiton) has long been used in traditional medicine in East Asia due to the various biological activities of its secondary metabolites. Endogenous contents of phenolic compounds (phenolic acid, flavonol, and isoflavone) and the main bioactive compounds of Sophorae Radix were analyzed based on the qualitative HPLC analysis and evaluated in different organs and at different developmental stages. In total, 11 compounds were detected, and the composition of the roots and aerial parts (leaves, stems, and flowers) was significantly different. trans-Cinnamic acid and p-coumaric acid were observed only in the aerial parts. Large amounts of rutin and maackiain were detected in the roots. Four phenolic acid compounds (benzoic acid, caffeic acid, ferulic acid, and chlorogenic acid) and four flavonol compounds (kaempferol, catechin hydrate, epicatechin, and rutin) were higher in aerial parts than in roots. To identify putative genes involved in phenolic compounds biosynthesis, a total of 41 transcripts were investigated. Expression patterns of these selected genes, as well as the multiple isoforms for the genes, varied by organ and developmental stage, implying that they are involved in the biosynthesis of various phenolic compounds both spatially and temporally.

Predictive factors associated with failure of nonoperative treatment of superior labrum anterior-posterior tears.

BACKGROUND: Uncertainty remains in the natural course of superior labrum anterior-posterior (SLAP) tears treated conservatively with rehabilitation and activity modification. Our purpose was to evaluate clinical outcomes after nonoperative treatment of type II SLAP tear in young active patients and to identify factors related to negative outcomes. METHODS: We retrospectively reviewed 63 patients who initially underwent nonoperative treatment for isolated type II SLAP tear. Assessments were made at baseline and at 6 months, and telephone survey was used to evaluate the final outcome. All included patients underwent a consistent nonoperative treatment protocol, and patient-specific data on the outcome were assessed. Failure was defined as abandonment of nonoperative management for surgery at any time points, <20-point improvement in American Shoulder and Elbow Surgeons score at final follow-up, or inability to return to activities. RESULTS: At the average follow-up of 21 months, pain relief and function improved significantly (American Shoulder and Elbow Surgeons score, 54.2-86.4; Visual Analog Scale score, 4.6-1.7; P < .05) in 45 patients (71.4%) with successful nonoperative treatment. Eighteen patients (28.5%) were either dissatisfied with treatment or had arthroscopic surgery and were considered a failure group. Multivariate analysis showed that failure of nonoperative treatment is strongly linked with history of trauma, positive compression-rotation test result, and participation in overhead activities (P < .05). CONCLUSIONS: An initial trial of nonoperative management may be considered in young active patients with isolated SLAP tear. Patients with history of trauma, mechanical symptoms, and demand for overhead activities are less likely to succeed.

Rose Petal Extract Ameliorates Obesity in High Fat Diet-Induced Obese Mice.

In Asia, Rosa spp. has been used in traditional medicine for the treatment of osteoarthritis, rheumatoid arthritis, and edema. In this study, we investigated the effect of rose petal extract (RPE) on high fat diet (HFD)-induced obesity in mice. C57BL/6J mice were fed with either an AIN-93G diet (normal control), a 60% HFD, or a HFD plus supplementation with RPE at 100 or 200 mg/kg body weight (HFD+R100, HFD+R200) for 14 weeks. The HFD increased the body weight gain, liver and fat weight, lipid profiles (total cholesterol, triglyceride, high density lipoprotein cholesterol, and low density lipoprotein cholesterol), and the serum aspartate aminotransferase and alanine aminotransferase levels of mice, while RPE supplementation significantly decreased these parameters compared with the HFD group. Furthermore, the HFD increased the protein expressions of adipogenesis- and lipogenesis-related factors and decreased the protein expression of lipolysis- and energy metabolism-related factors. Conversely, RPE supplementation significantly decreased the protein expression of adipogenesis- and lipogenesis-related factors and increased the protein expression of lipolysis- and energy metabolism-related factors compared to the HFD group. Taken together, the results provide preliminary evidence for the potential protective effects of the RPE against obesity.

Curcuma longa L. extract exhibits anti-inflammatory and cytoprotective functions in the articular cartilage of monoiodoacetate-injected rats.

Background: Osteoarthritis (OA), the most prevalent form of arthritis, is a degenerative joint disease marked by the progressive deterioration of articular cartilage, leading to clinical manifestations such as joint pain. Objective: This study investigated the effects of Curcuma longa L. extract (CL) containing curcumin, demethoxycurcumin, and bisdemethoxycurcumin on monosodium iodoacetate (MIA)-induced OA rats. Design: Sprague-Dawley rats with MIA-induced OA received CL supplementation at doses of 5, 25, and 40 mg/kg body weight. Results: CL extract administration suppressed mineralisation parameters and morphological modifications and decreased arachidonate5-lipoxygenase and leukotriene B4 levels in articular cartilage. Additionally, it decreased serum prostaglandin E2, NO, and glycosaminoglycanlevels as well as the protein expression of phosphorylated inhibitor kappa B-alpha, phosphorylated p65, cyclooxygenase-2, and inducible nitric oxide synthase in the cartilage of MIA-injected rats. Furthermore, it also reduced matrix metalloproteinases and elevated SMAD family member 3 phosphorylation, tissue inhibitor of metalloproteinases, aggrecan, collagen type I, and collagen type II levels in the articular cartilage of MIA-induced OA rats. Conclusions: This study's findings suggest that CL supplementation helps prevent OA development and is an effective therapy for OA.

Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids.

Three-dimensional human intestinal organoids (hIO) are widely used as a platform for biological and biomedical research. However, reproducibility and challenges for large-scale expansion limit their applicability. Here, we establish a human intestinal stem cell (ISC) culture method expanded under feeder-free and fully defined conditions through selective enrichment of ISC populations (ISC3D-hIO) within hIO derived from human pluripotent stem cells. The intrinsic self-organisation property of ISC3D-hIO, combined with air-liquid interface culture in a minimally defined medium, forces ISC3D-hIO to differentiate into the intestinal epithelium with cellular diversity, villus-like structure, and barrier integrity. Notably, ISC3D-hIO is an ideal cell source for gene editing to study ISC biology and transplantation for intestinal diseases. We demonstrate the intestinal epithelium differentiated from ISC3D-hIO as a model system to study severe acute respiratory syndrome coronavirus 2 viral infection. ISC3D-hIO culture technology provides a biological tool for use in regenerative medicine and disease modelling.

KoNA: Korean Nucleotide Archive as A New Data Repository for Nucleotide Sequence Data.

During the last decade, the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges, including access to human data, as well as transfer, storage, and sharing of enormous amounts of data. To promote data-driven biological research, the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station (K-BDS), which consists of multiple databases for individual data types. Here, we introduce the Korean Nucleotide Archive (KoNA), a repository of nucleotide sequence data. As of July 2022, the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome projects. To ensure data quality and prepare for international alignment, a standard operating procedure was adopted, which is similar to that of the International Nucleotide Sequence Database Collaboration. The standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline, followed by manual examination. To ensure fast and stable data transfer, a high-speed transmission system called GBox is used in KoNA. Furthermore, the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called Bio-Express. This seamless coupling of KoNA, GBox, and Bio-Express enhances the data experience, including submission, access, and analysis of raw nucleotide sequences. KoNA not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in genomics. The KoNA is available at https://www.kobic.re.kr/kona/.

The bone-protective benefits of amino-conjugated calcium in an ovariectomized (OVX) rat model.

Low bone density, fragility, and microarchitectural disintegration are the symptoms of osteoporosis. An imbalance between bone growth and resorption can lead to osteoporosis. This study evaluated the effects of amino-calcium (AC) on bone protection in ovariectomized control group (NC) rats. Amino-calcium (AC) was characterized using Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), and nuclear magnetic resonance spectroscopy analyses (NMR). After determining the biocompatibility of amino-calcium (AC) with MC3T3-E1 cells, alkaline phosphatase staining revealed significant changes on day 7. Three of the four groups underwent ovariectomy, whereas one group received a placebo. On micro-computed tomography, in vivo, data showed increased bone volume fraction in the femoral head and shaft areas in the amino-calcium (AC) group. Hematoxylin and eosin staining showed a bone mass and architectural protection in the amino-calcium (AC) group compared with the calcium carbonate and OVX control group. RNA sequencing analysis revealed high expression of osteogenesis-related genes in MC3T3-E1 cells. RNA sequencing revealed a significant fold change in the expression of integrin-binding sialoprotein (IBSP), bone gamma-carboxyglutamate proteins 1 and 2(BGLAP1 and BGLAP2), and periostin (POSTN). The study concluded that supplementing the OVX rats with calcium enhanced bone protection.

Gly-Pro-Val-Gly-Pro-Ser Peptide Fish Collagen Improves Skin Moisture and Wrinkles with Ameliorated the Oxidative Stress and Pro-inflammatory Factors in Skin Photoaging Mimic Models.

This study aimed to investigate whether low molecular fish collagen peptide (FC) from Oreochromis niloticus had protective effects on skin of photoaging mimic models. We observed that FC supplementation improved antioxidant enzymes activities and regulated the pro-inflammatory cytokines [e.g., tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6] by reducing the protein expressions of pro-inflammatory factors IκBα, p65, and cyclooxygenase-2 in ultraviolet-B (UV-B) irradiated in vitro and in vivo. Furthermore, FC increased hyaluronic acid, sphingomyelin, and skin hydration by reg-ulating the mRNA expression of hyaluronic acid synthases 1∼3, serine palmitoyltransferase 1, delta 4-desaturase, sphingolipid 1, and protein expressions of ceramide synthase 4, matrix metalloproteinase (MMP)-1, -2, and -9. In UV-B irradiated in vitro and in vivo, FC down-regulated the protein expression of the c-Jun N-terminal kinase, c-Fos, c-Jun, and MMP pathways and up-reg-ulated that of the transforming growth factor-ß receptor I, collagen type I, procollagen type I, and small mothers against decapentaplegic homolog pathways. Our results suggest that FC can be effective against UV-B induced skin photoaging by improving skin dryness and wrinkle formation through antioxidant and anti-inflammatory properties.