PAPipe: A Pipeline for Comprehensive Population Genetic Analysis.

Advancements in next-generation sequencing (NGS) technologies have led to a substantial increase in the availability of population genetic variant data, thus prompting the development of various population analysis tools to enhance our understanding of population structure and evolution. The tools that are currently used to analyze population genetic variant data generally require different environments, parameters, and formats of the input data, which can act as a barrier preventing the wide-spread usage of such tools by general researchers who may not be familiar with bioinformatics. To address this problem, we have developed an automated and comprehensive pipeline called PAPipe to perform nine widely used population genetic analyses using population NGS data. PAPipe seamlessly interconnects and serializes multiple steps, such as read trimming and mapping, genetic variant calling, data filtering, and format converting, along with nine population genetic analyses such as principal component analysis, phylogenetic analysis, population tree analysis, population structure analysis, linkage disequilibrium decay analysis, selective sweep analysis, population admixture analysis, sequentially Markovian coalescent analysis, and fixation index analysis. PAPipe also provides an easy-to-use web interface that allows for the parameters to be set and the analysis results to be browsed in intuitive manner. PAPipe can be used to generate extensive results that provide insights that can help enhance user convenience and data usability. PAPipe is freely available at https://github.com/jkimlab/PAPipe.

Lactiplantibacillus plantarum HY7718 Improves Intestinal Integrity in a DSS-Induced Ulcerative Colitis Mouse Model by Suppressing Inflammation through Modulation of the Gut Microbiota.

Inflammatory bowel disease (IBD), a chronic condition that causes persistent inflammation in the digestive system, is closely associated with the intestinal microbiome. Here, we evaluated the effects of Lactiplantibacillus plantarum HY7718 (HY7718) on IBD symptoms in mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration of HY7718 led to significant improvement in the disease activity index score and the histological index, as well as preventing weight loss, in model mice. HY7718 upregulated the expression of intestinal tight junction (TJ)-related genes and downregulated the expression of genes encoding pro-inflammatory cytokines and genes involved in the TLR/MyD88/NF-κB signaling pathway. Additionally, HY7718 reduced the blood levels of pro-inflammatory cytokines, as well as reversing DSS-induced changes to the composition of the intestinal microbiome. HY7718 also increased the percentage of beneficial bacteria (Lactiplantibacillus and Bifidobacterium), which correlated positively with the expression of intestinal TJ-related genes. Finally, HY7718 decreased the population of pathogens such as Escherichia, which correlated with IBD symptoms. The data suggest that HY7718 improves intestinal integrity in colitis model mice by regulating the expression of TJ proteins and inflammatory cytokines, as well as the composition of the intestinal microflora. Thus, L. plantarum HY7718 may be suitable as a functional supplement that improves IBD symptoms and gut health.

Effects of TiO2 Nanotubes and Reduced Graphene Oxide on Streptococcus mutans and Preosteoblastic Cells at an Early Stage.

The effects of TiO2 nanotube (TNT) and reduced graphene oxide (rGO) deposition onto titanium, which is widely used in dental implants, on Streptococcus mutans (S. mutans) and preosteoblastic cells were evaluated. TNTs were formed through anodic oxidation on pure titanium, and rGO was deposited using an atmospheric plasma generator. The specimens used were divided into a control group of titanium specimens and three experimental groups: Group N (specimens with TNT formation), Group G (rGO-deposited specimens), and Group NG (specimens under rGO deposition after TNT formation). Adhesion of S. mutans to the surface was assessed after 24 h of culture using a crystal violet assay, while adhesion and proliferation of MC3T3-E1 cells, a mouse preosteoblastic cell line, were evaluated after 24 and 72 h through a water-soluble tetrazolium salt assay. TNT formation and rGO deposition on titanium decreased S. mutans adhesion (p < 0.05) and increased MC3T3-E1 cell adhesion and proliferation (p < 0.0083). In Group NG, S. mutans adhesion was the lowest (p < 0.05), while MC3T3-E1 cell proliferation was the highest (p < 0.0083). In this study, TNT formation and rGO deposition on a pure titanium surface inhibited the adhesion of S. mutans at an early stage and increased the initial adhesion and proliferation of preosteoblastic cells.

RORα contributes to the maintenance of genome ploidy in the liver of mice with diet-induced nonalcoholic steatohepatitis.

Hepatic polyploidization is closely linked to the progression of nonalcoholic fatty liver disease (NAFLD); however, the underlying molecular mechanism is not clearly understood. In this study, we demonstrated the role of retinoic acid-related orphan receptor α (RORα) in the maintenance of genomic integrity, particularly in the pathogenesis of NAFLD, using the high-fat diet (HFD)-fed liver-specific RORα knockout (RORα-LKO) mouse model. First, we observed that the loss of hepatic retinoic acid receptor-related orphan receptor α (RORα) accelerated hepatocyte nuclear polyploidization after HFD feeding. In 70% partial hepatectomy experiments, enrichment of hepatocyte polyploidy was more obvious in the RORα-LKO animals, which was accompanied by early progression to the S phase and blockade of the G2/M transition, suggesting a potential role of RORα in suppressing hepatocyte polyploidization in the regenerating liver. An analysis of a publicly available RNA sequencing (RNA-seq) and chromatin immunoprecipitation-seq dataset, together with the Search Tool of the Retrieval of Interacting Genes/Proteins database resource, revealed that DNA endoreplication was the top-enriched biological process Gene Ontology term. Furthermore, we found that E2f7 and E2f8, which encode key transcription factors for DNA endoreplication, were the downstream targets of RORα-induced transcriptional repression. Finally, we showed that the administration of JC1-40, an RORα activator (5 mg/kg body wt), significantly reduced hepatic nuclear polyploidization in the HFD-fed mice. Together, our observations suggest that the RORα-induced suppression of hepatic polyploidization may provide new insights into the pathological polyploidy of NAFLD and may contribute to the development of therapeutic strategies for the treatment of NAFLD.NEW & NOTEWORTHY It has been reported that hepatic polyploidization is closely linked to the progression of NAFLD. Here, we showed that the genetic depletion of hepatic RORα in mice accelerated hepatocyte polyploidization after high-fat diet feeding. The mechanism could be the RORα-mediated repression of E2f7 and E2f8, key transcription factors for DNA endoreplication. Thus, preservation of genome integrity by RORα could provide a new insight for developing therapeutics against the disease.

Lactobacillus paracasei HY7015 and Lycopus lucidus Turcz. Extract Promotes Human Dermal Papilla Cell Cytoprotective Effect and Hair Regrowth Rate in C57BL/6 Mice.

Hair loss is a disease that requires accurate diagnosis and type-specific medical treatment. Many hair loss treatments have some side effects, such as hormone-related effects, so there is a need for safe and effective hair loss treatment. In this study, we investigated the effects of Lactobacillus paracasei HY7015 (HY7015) and Lycopus lucidus Turcz. (LT) extract on hair regrowth and protection. In vitro experiments were conducted to assess the effects of HY7015 and/or LT extract on human follicle dermal papilla cells (HFDPC) of cytoprotective functions such as proliferations, antioxidants, anti-inflammatory, and growth factor expressions. In animal experiments, we investigated hair regrowth rate, hair follicle formation and secretion of growth factors in telogenic C57BL/6 mice. We confirmed the cytoprotective effects of HY7015 and LT through regulations of proliferation, SOD and IL-1ß in HFDPC. In mouse experiments, oral administration of HY7015 and LT promoted hair regrowth as well as hair follicle maturation in the dermal skin of C57BL/6 mice, and upregulated VEGF and IGF-1 growth factor levels in mouse serum. In summary, our data demonstrate that ingestions of HY7015 and LT can promote hair regrowth by enhancing cytoprotective effects and expressions of growth factors.

Dysregulation of murine immune functions on inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole, or propionic acid.

Animal husbandry workers are exposed to various malodorous compounds in the workplace. Although these compounds cause severe nuisance, no systemic investigation of their effects on the immune system has been conducted. To address this issue, we evaluated the effects of inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole (3-MI), and propionic acid (PA), representing four major groups of malodorous compounds, on humoral and cellular immunity in mice. Mice were exposed to the substances (low dose: 10 µL and high dose: 200 µL) for 10 min/day for 4 weeks in a modified standard mouse cage. Neutrophil% and splenic cytotoxic T cell% were significantly lower in the high-dose ammonia group than in the vehicle control. Exposure to ammonia and 3-MI increased immature thymic T lymphocyte% relative to control and concomitantly decreased both mature helper and cytotoxic T-cell populations in the thymus. In the ammonia exposure group, levels of serum immunoglobulin E and immunoglobulin A were elevated, and the IgG2a:IgG1 ratio in the serum was reduced in a dose-dependent manner. Splenic natural killer cell activity was significantly less in the PA exposure group than in the control. Overall, our findings suggest that inhalational exposure to these malodorous substances disturbs immune homeostasis in vivo.

Rapid Access to Ordered Mesoporous Carbons for Chemical Hydrogen Storage.

Ordered mesoporous carbon materials offer robust network of organized pores for energy storage and catalysis applications, but suffer from time-consuming and intricate preparations hindering their widespread use. Here we report a new and rapid synthetic route for a N-doped ordered mesoporous carbon structure through a preferential heating of iron oxide nanoparticles by microwaves. A nanoporous covalent organic polymer is first formed in situ covering the hard templates of assembled nanoparticles, paving the way for a long-range order in a carbonaceous nanocomposite precursor. Upon removal of the template, a well-defined cubic mesoporous carbon structure was revealed. The ordered mesoporous carbon was used in solid state hydrogen storage as a host scaffold for NaAlH4 , where remarkable improvement in hydrogen desorption kinetics was observed. The state-of-the-art lowest activation energy of dehydrogenation as a single step was attributed to their ordered pore structure and N-doping effect.

Major environmental characteristics of swine husbandry that affect exposure to dust and airborne endotoxins.

Inhalation of organic dust or endotoxin in the dust is considered a major risk factor for occupational respiratory illnesses. Eighteen environmental characteristics associated with animal husbandry were surveyed at 36 swine farms in seven provinces throughout South Korea. Association of these factors with levels of indoor inhalable or respirable dust or endotoxin in each type of dust was analyzed using backward stepwise multiple linear regression models. Mean levels of inhalable and respirable dust were 0.5 ± 0.35 and 0.13 ± 0.12 mg/m3 air, respectively, and mean endotoxin levels were 676 ± 463 and 48.4 ± 68.2 EU/m3, respectively, in each dust. Factors negatively associated with inhalable dust levels included pig age, indoor farm temperature, number of pigs in the building, hr/week of indoor farm work, and partly slatted floor. Factors positively associated with inhalable dust levels included floor cleaning by manual scraping and slurry deposit duration. Factors negatively associated with the level of endotoxin in inhalable dust included pig age, temperature, number of pigs, hr/week of indoor farm work, and partly slatted floor. Factors negatively associated with respirable dust level included area of the confinement building, whereas factors positively associated with respirable dust level included the number of pigs and stocking density. Endotoxin levels in respirable dust were negatively associated with h/week of indoor farm work and partly slatted floor. Overall, data suggest that husbandry variables may be adjusted to control dust and airborne endotoxin levels in swine farms.

Prediction of the skin sensitization potential of polyhexamethylene guanidine phosphate, oligo(2-(2-ethoxy)ethoxyethyl) guanidinium chloride, triclosan, and mixtures of these compounds with the excipient propylene glycol through the local lymph node assay: BrdU-FCM.

The guanidine family of antimicrobial agents, which includes polyhexamethylene guanidine phosphate (PHMG) and oligo(2-(2-ethoxy)ethoxyethyl) guanidinium chloride (PGH), and chlorophenol biocidal chemicals such as 2,4,4'-trichloro-2'-hydroxydiphenyl ether (triclosan) are used in various occupational and environmental biocidal applications. The excipient propylene glycol (PG) is used to dissolve the active ingredients. The skin sensitization (SS) potential of these substances has not been systemically investigated and is still debated. Moreover, mixtures of PHMG, PGH, or triclosan with PG have not been evaluated for SS potency. An in vivo assay known as the local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) was recently adopted as an alternative testing method and was used to address these issues. Via the LLNA: BrdU-FCM, PHMG, PGH, and triclosan were predicted to be sensitizers, while PG was predicted to be a nonsensitizer. In addition, d-limonene, which is used as a flavoring in various consumer products, was also predicted to be a sensitizer, although no unanimous conclusion has been reached regarding its SS potential. Mixtures of PHMG, PGH, triclosan, or d-limonene with PG at ratios of 9:1, 4:1, and 1:4 (w/w) were all positive in terms of SS potential, indicating that the PG excipient does not influence the SS predictions of these chemicals. Since humans can be occupationally and environmentally exposed to mixtures of excipients with active ingredients, the present study may give insight into further investigations of the SS potentials of various chemical mixtures.

Prediction of the skin sensitization potential of didecyldimethylammonium chloride and 3,7-dimethyl-2,6-octadienal and mixtures of these compounds with the excipient ethylene glycol through the human Cell Line Activation Test and the Direct Peptide Reactivity Assay.

In commercial products such as household deodorants or biocides, didecyldimethylammonium chloride (DDAC) often serves as an antimicrobial agent, citral serves as a fragrance agent, and the excipient ethylene glycol (EG) is used to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances are still being debated. Moreover, mixtures of DDAC or citral with EG have not been evaluated for SS potency. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) and Direct Peptide Reactivity Assay (DPRA) served to address these issues. On three independent runs of h-CLAT, DDAC and citral were predicted to be sensitizers while EG was predicted to be a non-sensitizer and also by the DPRA. Mixtures of DDAC or citral with EG at ratios of 7:3 and 1:4 w/v were all positive by the h-CLAT in terms of SS potential but SS potency was mitigated as the proportion of EG increased. Citral and its EG mixtures were all positive but DDAC and its EG mixtures were all negative by the DPRA, indicating that the DPRA method is not suitable for chemicals with pro-hapten characteristics. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.

Induction of ER Stress-Mediated Apoptosis by the Major Component 5,7,4'-Trimethoxyflavone Isolated from Kaempferia parviflora Tea Infusion.

Kaempferia parviflora (KP) is a famous medicinal plant from Thailand, and is a rich source of various kinds of methoxyflavones (MFs). Many kinds of food products such as tea, capsule, and liquor are manufactured from the rhizomes of KP. In this study, KP infusions were prepared with different brewing conditions, and the amounts of three major methoxylflavones, 5,7-dimethoxyflavone (DMF), 5,7,4'-trimethoxyflavone (TMF), and 3,5,7,3',4'-pentamethoxyflavone (PMF), were analyzed. The antiproliferative activities of DMF, TMF, and PMF isolated from the brewed tea samples were evaluated. TMF was discovered to be significantly effective at inhibiting proliferation of SNU-16 human gastric cancer cells in a concentration dependent manner. TMF induced apoptosis, as evidenced by increments of sub-G1 phase, DNA fragmentation, annexin-V/PI staining, the Bax/Bcl-xL ratio, proteolytic activation of caspase-3,-7,-8, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Furthermore, it was found that TMF induced apoptosis via ER stress, verified by an increase in the level of C/EBP homologous protein (CHOP), glucose regulated protein 78 (GRP78), inositol-requiring enzyme 1 α (IRE1α), activating transcription factor-4 (ATF-4), and the splice isoform of X-box-binding protein-1 (XBP-1) mRNA.

Development of Liver Decellularized Extracellular Matrix Bioink for Three-Dimensional Cell Printing-Based Liver Tissue Engineering.

The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimized for 3D cell printing-based liver tissue engineering remains. Therefore, in this work, we developed a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D cell printing. We further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D cell printing-based liver tissue engineering.

Dual CLAVATA3 Peptides in Arabidopsis Shoot Stem Cell Signaling.

Plant shoot stem cell pool is constantly maintained by a negative feedback loop through peptide-receptor mediated signaling pathway. CLAVATA3 (CLV3) encode a 96 amino-acid protein which is processed to 12-amino-acid or arabinosylated 13-amino-acid peptides, acting as a ligand signal to regulate stem cell homeostasis in the shoot apical meristem (SAM). Although arabinosylated 13-amino-acid CLV3 peptide (CLV3p) shows more significant binding affinity to its receptors and biological activities in the SAM, the physiological function of two mature forms of CLV3p remained an unresolved puzzle in the past decade due to the technical difficulties of arabinosylation modification in the peptide synthesis. Here, we analyzed the role of two mature CLV3 peptides with newly synthesized arabinosylated peptide. Beside shoot meristem phenotypes, arabinosylated CLV3p showed the conventional trait of CLV2-dependent root growth inhibition. Moreover, both 12-amino-acid and arabinosylated 13-amino-acid CLV3 peptides have analogous activities in shoot stem cell signaling. Notably, we demonstrated that non-arabinosylated 12-amino acid CLV3p can affect shoot stem cell signaling at the physiological level unlike previously suggested (Ohyama et al., 2009; Shinohara and Matsubayashi, 2013; Shinohara and Matsubayashi, 2015). Therefore, these results support the physiological role of the 12-amino-acid CLV3p in shoot stem cell signaling in the deficient condition of arabinosylated 13-amino-acid CLV3p in Arabidopsis thaliana.

RORα-GABP-TFAM axis alleviates myosteatosis with fatty atrophy through reinforcement of mitochondrial capacity.

BACKGROUND: Fat infiltration in muscle, called 'myosteatosis', precedes muscle atrophy, which subsequently results in sarcopenia. Myosteatosis is frequently observed in patients with nonalcoholic fatty liver disease (NAFLD). We have previously reported that retinoic acid receptor-related orphan receptor-α (RORα) regulates mitochondrial dynamics and mitophagy in hepatocytes, resulting in an alleviation of NAFLD. In this study, we aimed to investigate the role of RORα in skeletal muscle and to understand molecular mechanisms by which RORα controls mitochondrial capacity, using an NAFLD-associated myosteatosis mouse model. METHODS: To establish a myosteatosis model, 7-week-old C57BL/6N mice were fed with high-fat diet (HFD). After 15 weeks of diet feeding, an adeno-associated virus vector encoding RORα (AAV-RORα) was injected to gastrocnemius (GA) muscles, or after 7 weeks of HFD feeding, JC1-40, an RORα agonistic ligand, was administered daily at a dose of 5 mg/kg/day by oral gavage for 5 weeks. Histological, biochemical and molecular analyses in various in vivo and in vitro experiments were performed. RESULTS: First, the number of oxidative MyHC2a fibres with intensive lipid infiltration increased by 3.8-fold in the red region of the GA of mice with myosteatosis (P < 0.001). RORα was expressed around MyHC2a fibres, and its level increased by 2.7-fold after HFD feeding (P < 0.01). Second, treatment of RORα ligands in C2C12 myoblasts, such as cholesterol sulfate and JC1-40, enhanced the number of oxidative fibres stained for MyHC1 and MyHC2a by two-fold to four-fold (P < 0.01), while it reduced the lipid levels in MyHC2a fibres by 20-50% (P < 0.001) in the presence of palmitic acids. Third, mitochondrial membrane potential (P < 0.01) and total area of mitochondria (P < 0.01) were enhanced by treatment of these ligands. Chromatin immunoprecipitation analysis showed that RORα bound the promoter of GA-binding protein α subunit gene that led to activation of mitochondrial transcription factor A (TFAM) in C2C12 myoblasts (P < 0.05). Finally, intramuscular transduction of AAV-RORα alleviated the HFD-induced myosteatosis with fatty atrophy; lipid contents in MyHC2a fibres decreased by 48% (P < 0.001), whereas the number of MyHC2b fibre increased by 22% (P < 0.001). Also, administration of JC1-40 improved the signs of myosteatosis in that it decreased the level of adipose differentiation-related protein (P < 0.01) but increased mitochondrial proteins such as cytochrome c oxidase 4 and TFAM in GA muscle (P < 0.01). CONCLUSIONS: RORα plays a versatile role in regulating the quantity of mitochondria and the oxidative capacity, ultimately leading to an improvement in myosteatosis symptoms.

An RORα agonist, ODH-08, inhibits fibrogenic activation of hepatic stellate cells via suppression of SMAD3.

AIMS: Hepatic fibrosis is a dynamic process characterized by the net accumulation of an extracellular matrix resulting from chronic liver injury such as nonalcoholic steatohepatitis. Activation of hepatic stellate cells (HSCs) plays a role in transdifferentiation of quiescent cells into fibrogenic myofibroblasts. We aimed to examine the function of retinoic acid receptor-related orphan receptor alpha (RORα) and its novel agonistic ligand, 1-(4-benzyloxybenzyl)-3-(2-dimethylaminoethyl)-thiourea (ODH-08) against activation of HSCs using hepatic fibrosis mouse models. MAIN METHODS: Chemical synthesis, a reporter gene assay, surface plasmon resonance analysis, and a docking study were performed to evaluate ODH-08 as a ligand of RORα. In vivo experiments with mice fed a Western diet were performed to evaluate the effect of ODH-08. The human HSC line, Lx-2, and primary mouse HSCs were employed to identify the molecular mechanisms underlying the antifibrogenic effect of ODH-08. KEY FINDINGS: A novel RORα-selective ligand, ODH-08, was developed based on modification of JC1-40, an analog of N-methylthiourea. Administration of ODH-08 to the Western diet-fed mice reduced hepatic collagen deposition and expression levels of fibrogenic markers such as α-smooth muscle actin and collagen type I alpha 1 chain. Activation of RORα-either by transient overexpression of RORα or treatment with ODH-08-suppressed the expression of fibrogenic proteins in HSCs. The activation of RORα suppressed the activity of SMAD2 and 3, which are the primary downstream proteins of transforming growth factor ß. SIGNIFICANCE: RORα and its agonist ODH-08 have a potent antifibrotic effect, which could provide a novel antifibrotic strategy against hepatic fibrosis.

Comparative profiling by data-independent acquisition mass spectrometry reveals featured plasma proteins in breast cancer: a pilot study.

Purpose: Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers. Methods: This pilot study was conducted using bioresources from Seoul National University Bundang Hospital's Human Bioresource Center. Serum samples from 10 breast cancer patients and 10 healthy controls were obtained. Liquid chromatography-mass spectrometry analysis was performed to identify differentially expressed proteins. Results: We identified 891 proteins; 805 were expressed in the breast cancer group and 882 in the control group. Gene set enrichment and differential expression analysis identified 30 upregulated and 100 downregulated proteins in breast cancer. Among these, 10 proteins were selected as potential biomarkers. Three proteins were upregulated in breast cancer patients, including cluster of differentiation 44, eukaryotic translation initiation factor 2-α kinase 3, and fibronectin 1. Seven proteins downregulated in breast cancer patients were also selected: glyceraldehyde-3-phosphate dehydrogenase, α-enolase, heat shock protein member 8, integrin-linked kinase, tissue inhibitor of metalloproteinases-1, vasodilator-stimulated phosphoprotein, and 14-3-3 protein gamma. All proteins had been previously reported to be related to tumor development and progression. Conclusion: The findings suggest that plasma proteome profiling can reveal potential diagnostic biomarkers for breast cancer and may contribute to early detection and personalized treatment strategies. A further validation study with a larger sample cohort of breast cancer patients is planned.

Recent Progress in Fabrication of Electrospun Nanofiber Membranes for Developing Physiological In Vitro Organ/Tissue Models.

Nanofiber membranes (NFMs), which have an extracellular matrix-mimicking structure and unique physical properties, have garnered great attention as biomimetic materials for developing physiologically relevant in vitro organ/tissue models. Recent progress in NFM fabrication techniques immensely contributes to the development of NFM-based cell culture platforms for constructing physiological organ/tissue models. However, despite the significance of the NFM fabrication technique, an in-depth discussion of the fabrication technique and its future aspect is insufficient. This review provides an overview of the current state-of-the-art of NFM fabrication techniques from electrospinning techniques to postprocessing techniques for the fabrication of various types of NFM-based cell culture platforms. Moreover, the advantages of the NFM-based culture platforms in the construction of organ/tissue models are discussed especially for tissue barrier models, spheroids/organoids, and biomimetic organ/tissue constructs. Finally, the review concludes with perspectives on challenges and future directions for fabrication and utilization of NFMs.

Extracellular matrix-based sticky sealants for scar-free corneal tissue reconstruction.

Regenerative medicine requires both tissue restoration and ease of compliance for clinical application. Considering this, sticky tissue sealants have been shown to have great potentials over surgical suturing and wound treatment. However, tissue sealants currently used pose challenges such as uncontrollable adhesion formation, mechanical mismatch, and lack of tissue restoration. A new sticky sealant based on gelatinized cornea-derived extracellular matrix (GelCodE) with a visible light-activating system is firstly being introduced in this study. De novo tissue regeneration relies on the matrisome in charge of tissue-organization and development within GelCodE while visible light-based photopolymerization with ruthenium/sodium persulfate rapidly induces covalent bonds with the adjacent tissues. The ease of not only in vivo application, biocompatibility, and biointegration, but also exceptional de novo tissue formation is demonstrated in this study. Interestingly, newly regenerated tissues were shown to have normal tissue-like matrices with little scar formation. Hence, this work presents a promising strategy to meet clinical demands for scar-free tissue recovery with superior ease of clinical application.

Probiotic Properties and Safety Evaluation of Lactobacillus plantarum HY7718 with Superior Storage Stability Isolated from Fermented Squid.

The aim of this study was to identify new potential probiotics with improved storage stability and to evaluate their efficacy and safety. Sixty lactic acid bacteria strains were isolated from Korean traditional fermented foods, and their survival was tested under extreme conditions. Lactobacillus plantarum HY7718 (HY7718) showed the greatest stability during storage. HY7718 also showed a stable growth curve under industrial conditions. Whole genome sequencing revealed that the HY7718 genome comprises 3.26 Mbp, with 44.5% G + C content, and 3056 annotated Protein-coding DNA sequences (CDSs). HY7718 adhered to intestinal epithelial cells and was tolerant to gastric fluids. Additionally, HY7718 exhibited no hemolytic activity and was not resistant to antibiotics, confirming that it has probiotic properties and is safe for consumption. Additionally, we evaluated its effects on intestinal health using TNF-induced Caco-2 cells. HY7718 restored the expression of tight junction proteins such as zonular occludens (ZO-1, ZO-2), occludin (OCLN), and claudins (CLDN1, CLDN4), and regulated the expression of myosin light-chain kinase (MLCK), Elk-1, and nuclear factor kappa B subunit 1 (NFKB1). Moreover, HY7718 reduced the secretion of proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8, as well as reducing the levels of peroxide-induced reactive oxygen species. In conclusion, HY7718 has probiotic properties, is safe, is stable under extreme storage conditions, and exerts positive effects on intestinal cells. These results suggest that L. plantarum HY7718 is a potential probiotic for use as a functional supplement in the food industry.

Lactobacillus helveticus Isolated from Raw Milk Improves Liver Function, Hepatic Steatosis, and Lipid Metabolism in Non-Alcoholic Fatty Liver Disease Mouse Model.

Here, we show that Lactiplantibacillus plantarum LP158 (LP158), Lactobacillus helveticus HY7804 (HY7804), and Lacticaseibacillus paracasei LPC226 (LPC226) isolated from raw milk alleviate non-alcoholic fatty acid disease (NAFLD) in a C57BL/6 mouse model. Lactic acid bacteria (LAB) were screened for their ability to inhibit fatty acid accumulation in palmitic acid (PA)-treated HepG2 cells, and three strains were selected based on the results. We also investigated hemolytic activity and antibiotic resistance of the three strains. LP158, HY7804, and LPC226 suppressed expression of mRNA encoding genes related to lipogenesis, and increased expression of genes related to ß-oxidation, in a PA-induced HepG2 cell model. Moreover, when LP158, HY7804, and LPC226 were administered at 109 CFU/kg/day for 8 weeks to mice with dietary-induced NAFLD, they all modulated blood biochemistry markers and reduced steatosis in liver tissue. Also, all three strains significantly reduced expression of mRNA encoding lipogenesis genes (Fasn, Acaca, and Srebp-1c) and inflammatory factors (Tnfα and Ccl-2) and fibrosis factors, and increased expression of a ß-oxidation gene (Acox1) in the liver. In particular, HY7804 showed the strongest effects both in vitro and in vivo. Therefore, HY7804, LP158, and LPC226 can be proposed as potential supplements that can improve NAFLD through anti-steatosis, anti-inflammatory, and anti-fibrotic effects.