Lacticaseibacillus paracsei HY7207 Alleviates Hepatic Steatosis, Inflammation, and Liver Fibrosis in Mice with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty acid disease (NAFLD) is caused by a build-up of fat in the liver, inducing local inflammation and fibrosis. We evaluated the effects of probiotic lactic acid-generating bacteria (LAB) derived from a traditional fermented beverage in a mouse model of NAFLD. The LAB isolated from this traditional Korean beverage were screened using the human hepatic cell line HepG2, and Lactocaseibacillus paracasei HY7207 (HY7207), which was the most effective inhibitor of fat accumulation, was selected for further study. HY7207 showed stable productivity in industrial-scale culture. Whole-genome sequencing of HY7207 revealed that the genome was 2.88 Mbp long, with 46.43% GC contents and 2778 predicted protein-coding DNA sequences (CDSs). HY7207 reduced the expression of lipogenesis and hepatic apoptosis-related genes in HepG2 cells treated with palmitic acid. Furthermore, the administration of 109 CFU/kg/day of HY7207 for 8 weeks to mice fed an NAFLD-inducing diet improved their physiologic and serum biochemical parameters and ameliorated their hepatic steatosis. In addition, HY7207 reduced the hepatic expression of genes important for lipogenesis (Srebp1c, Fasn, C/ebpa, Pparg, and Acaca), inflammation (Tnf, Il1b, and Ccl2), and fibrosis (Col1a1, Tgfb1, and Timp1). Finally, HY7207 affected the expression of the apoptosis-related genes Bax (encoding Bcl2 associated X, an apoptosis regulator) and Bcl2 (encoding B-cell lymphoma protein 2) in the liver. These data suggest that HY7207 consumption ameliorates NAFLD in mice through effects on liver steatosis, inflammation, fibrosis, and hepatic apoptosis. Thus, L. paracasei HY7207 may be suitable for use as a functional food supplement for patients with NAFLD.

Adiponectin receptor 1 regulates endometrial receptivity via the adenosine monophosphate­activated protein kinase/E­cadherin pathway.

Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95­2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95­2 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcription­quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid­secretory phase compared with that in the proliferative phase and in receptive RL95­2 cells compared with that in non­receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E­cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP­activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5­aminoimidazole­4­carboxamide ribonucleotide affected E­cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E­cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes.

Exosomal miR-196b secreted from bronchial epithelial cells chronically exposed to low-dose PM2.5 promotes invasiveness of adjacent and lung cancer cells.

Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5 µg/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2-5p, miR-3117-3p, miR-218-5p, and miR-497-5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.

Exosomal miR-205-5p Improves Endometrial Receptivity by Upregulating E-Cadherin Expression through ZEB1 Inhibition.

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

Emerging Roles of Using Small Extracellular Vesicles as an Anti-Cancer Drug.

Small extracellular vesicles (sEVs) are emerging as a novel therapeutic strategy for cancer therapy. Tumor-cell-derived sEVs contain biomolecules that can be utilized for cancer diagnosis. sEVs can directly exert tumor-killing effects or modulate the tumor microenvironment, leading to anti-cancer effects. In this review, the application of sEVs as a diagnostic tool, drug delivery system, and active pharmaceutical ingredient for cancer therapy will be highlighted. The therapeutic efficacies of sEVs will be compared to conventional immune checkpoint inhibitors. Additionally, this review will provide strategies for sEV engineering to enhance the therapeutic efficacies of sEVs. As a bench-to-bedside application, we will discuss approaches to encourage good-manufacturing-practice-compliant industrial-scale manufacturing and purification of sEVs.

Repeated ventricular bigeminy by trigeminocardiac reflex despite atropine administration during superficial upper lip surgery: A case report.

BACKGROUND: The trigeminocardiac reflex (TCR) is usually caused by an increased parasympathetic tone when pressure or traction is applied to the surrounding tissue of the trigeminal nerve. However, the inexperienced anesthesiologists may have challenges on the management of TCR patients. CASE SUMMARY: This is the case of an 18-year-old woman diagnosed with hemangioma of the upper lip. During the operation, about 1 h after surgery started, a constant 1:1 premature ventricular complex was detected, and blood pressure was decreased when approaching the deeper part with more strong traction for exposure of the part. Although the management of arrhythmias, such as lidocaine and atropine, was injected, arrhythmia induced by surgical stimulation could not be eliminated completely. As the traction repeated, bradycardia was also repeated, despite injecting additional atropine. Therefore, the anesthesiologist and the surgeon decided to perform the operation only to the extent that the vascular tissue was selectively removed only at the site without the reflex. CONCLUSION: With TCR, anesthesiologists should perform appropriate monitoring. In addition to proper drug administration, surgeons should be consulted to cope with stopping the surgery and setting the scope of the surgery even if the site is superficial.

The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway.

Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κΒ (NF-κΒ)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κΒ/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.

Detection of infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in whiteleg shrimp (Penaeus vannamei) imported from Vietnam to South Korea.

In this study, whiteleg shrimp (Penaeus vannamei) imported from Vietnam were collected from South Korean markets, and examined for 2 viruses: infectious hypodermal and hematopoietic necrosis virus (IHHNV, recently classified as decapod penstyldensovirus-1), and white spot syndrome virus (WSSV). Among 58 samples, we detected IHHNV in 23 samples and WSSV in 2 samples, using polymerase chain reaction and sequencing analyses. This is the first report of IHHNV and WSSV detection in imported shrimp, suggesting that greater awareness and stricter quarantine policies regarding viruses infecting shrimp imported to South Korea are required.

Three-dimensional volumetric gray-scale uterine cervix histogram prediction of days to delivery in full term pregnancy.

OBJECTIVE: Our aim was to figure out whether volumetric gray-scale histogram difference between anterior and posterior cervix can indicate the extent of cervical consistency. METHODS: We collected data of 95 patients who were appropriate for vaginal delivery with 36th to 37th weeks of gestational age from September 2010 to October 2011 in the Department of Obstetrics and Gynecology, Korea University Ansan Hospital. Patients were excluded who had one of the followings: Cesarean section, labor induction, premature rupture of membrane. Thirty-four patients were finally enrolled. The patients underwent evaluation of the cervix through Bishop score, cervical length, cervical volume, three-dimensional (3D) cervical volumetric gray-scale histogram. The interval days from the cervix evaluation to the delivery day were counted. We compared to 3D cervical volumetric gray-scale histogram, Bishop score, cervical length, cervical volume with interval days from the evaluation of the cervix to the delivery. RESULTS: Gray-scale histogram difference between anterior and posterior cervix was significantly correlated to days to delivery. Its correlation coefficient (R) was 0.500 (P = 0.003). The cervical length was significantly related to the days to delivery. The correlation coefficient (R) and P-value between them were 0.421 and 0.013. However, anterior lip histogram, posterior lip histogram, total cervical volume, Bishop score were not associated with days to delivery (P >0.05). CONCLUSION: By using gray-scale histogram difference between anterior and posterior cervix and cervical length correlated with the days to delivery. These methods can be utilized to better help predict a cervical consistency.

Anti-inflammatory activity of Taraxacum officinale.

Taraxacum officinale has been widely used as a folkloric medicine for the treatment of diverse diseases. The dried plant was extracted with 70% ethanol to generate its ethanol extract (TEE). For some experiments, ethyl acetate (EA), n-butanol (BuOH) and aqueous (Aq) fractions were prepared in succession from TEE. TEE showed a scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, a diminishing effect on intracellular reactive oxygen species (ROS) level, and an anti-angiogenic activity in the chicken chorioallantoic (CAM) assay. In the carrageenan-induced air pouch model, TEE inhibited production of exudate, and significantly diminished nitric oxide (NO) and leukocyte levels in the exudate. It also possessed an inhibitory effect on acetic acid-induced vascular permeability and caused a dose-dependent inhibition on acetic acid-induced abdominal writhing in mice. Suppressive effects of TEE on the production of NO and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Among the fractions, the n-butanol fraction (BuOH) was identified to be most effective in the CAM assay. Collectively, Taraxacum officinale contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities through its inhibition of NO production and COX-2 expression and/or its antioxidative activity.

Anti-angiogenic activity of the methanol extract and its fractions of Ulmus davidiana var. japonica.

This study aimed to elucidate anti-angiogenic activity of Ulmus davidiana var. japonica that has been widely used in folk medicine. The methanol extract (UDE) of Ulmus davidiana var. japonica concentration-dependently displayed a strong inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. The n-butanol fraction of UDE and subsequent 30% MeOH subfraction were identified to be most responsible for the anti-angiogenic activity.

Anti-inflammatory and anti-angiogenic activities of Gastrodia elata Blume.

Gastrodia elata Blume rhizome has been traditionally used as a folk medicine for centuries in Oriental countries. Its ethanol extract (GEE) and subsequent fractions were used to evaluate anti-angiogenic, anti-inflammatory and related activities of Gastrodia elata. GEE potently inhibited angiogenesis in the chick chorioallantoic membrane assay, and its n-butanol fraction (BuOH) exerted the higher inhibitory effect. In a dose-dependent manner, GEE inhibited vascular permeability induced by acetic acid. GEE and its BuOH fraction exerted an inhibitory activity on exudate production, leukocyte migration and nitric oxide (NO) level in rat air-pouch model. GEE caused a dose-dependent inhibition of acetic acid-induced abdominal writhing in mice. In addition, GEE inhibited NO production and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) upon stimulation by lipopolysaccharide (LPS) in RAW264.7 macrophages. In summary, we demonstrate some novel pharmacological activities of Gastrodia elata, such as anti-angiogenic, anti-inflammatory and analgesic activities, and in vivo and in vitro inhibitory activity on NO production.