Predictive potential of various plasma inflammation-, angiogenesis-, and extracellular matrix remodeling-associated mediators for intra-amniotic inflammation and/or microbial invasion of the amniotic cavity in preterm labor.

PURPOSE: To determine whether various inflammatory-, angiogenic/anti-angiogenic-, and extracellular matrix remodeling-associated proteins in plasma, alone or in combination with conventional blood-based markers, can predict intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with spontaneous preterm labor (PTL). METHODS: A total of 193 singleton pregnant women with PTL (23-33 weeks) were included in this retrospective cohort study. Plasma samples were obtained at the time of amniocentesis. Amniotic fluid (AF) was cultured for microorganism detection and consequent MIAC diagnosis. IL-6 levels were determined in AF and used to identify IAI (AF IL-6 ≥ 2.6 ng/mL). Endostatin, haptoglobin, IGFBP-2/3, LBP, M-CSF, MMP-2/8, pentraxin 3, PlGF, S100A8/A9, and VEGFR-1 levels were assayed in plasma samples by ELISA. CRP levels and neutrophil-to-lymphocyte ratio (NLR) were measured. RESULTS: Plasma LBP, MMP-8, and S100A8/A9 levels, CRP levels, and NLR were significantly higher, and plasma IGFBP-2 and MMP-2 levels were significantly lower in women with IAI/MIAC than in those without this condition, whereas no baseline variables differed significantly between the two groups. Using a stepwise regression analysis, a noninvasive prediction model for IAI/MIAC was developed, which included plasma LBP, MMP-2, and MMP-8 levels (area under the curve [AUC], 0.785). The AUC for this prediction model was significantly or borderline greater than that of any single factor included in the model. CONCLUSIONS: IGFBP-2, LBP, MMP-2, MMP-8, and S100A8/A9 may represent valuable plasma biomarkers for predicting IAI/MIAC in women with PTL. Combination of LBP, MMP-2, and MMP-8 expression data can significantly improve the predictive potential for IAI/MIAC.

Serum Extracellular Vesicle Protein Profiling for Prediction of Corneal Transplant Rejection.

BACKGROUND: Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival. METHODS: In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex-mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation. RESULTS: Our time course study revealed a decrease in the number of serum EVs on day 1, followed by a gradual increase by day 7. A comparative analysis of proteomics profiles of EVs from transplant recipients with rejection (rejectors) and without rejection (nonrejectors) found a distinct enrichment of histocompatibility 2, Q region locus 2, which is a part of major histocompatibility complex-class I of donor C57BL/6 mice, in day 7 EVs of rejectors, compared with nonrejectors, syngeneic controls, or naïve mice. In contrast, serum amyloid A2, a protein induced in response to injury, was increased in day 7 EVs of nonrejectors. CONCLUSIONS: Our findings offer noninvasive EV-based potential biomarkers for predicting corneal allograft rejection or tolerance.

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.

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.

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.

Potential of plasma inflammatory and angiogenic mediators for predicting spontaneous preterm delivery, intraamniotic infection/inflammation, and composite neonatal morbidity/mortality in women with early preterm premature rupture of membranes.

PROBLEM: To assess the potential of five inflammatory and six angiogenic/antiangiogenic plasma proteins for predicting imminent spontaneous preterm delivery (SPTD; ≤14 days of sampling), microbial invasion of the amniotic cavity and/or intraamniotic inflammation (MIAC/IAI), and composite neonatal morbidity and mortality (CNMM) in women with early preterm premature rupture of membranes (PPROM). METHODS OF STUDY: This retrospective cohort study included 76 singleton pregnant women with early PPROM (23-30 weeks). Amniotic fluid obtained via amniocentesis was cultured for microorganism detection and assayed for interleukin-6 to define IAI (≥2.6 ng/mL). Plasma C4a, endoglin, endostatin, IGFBP-1, IGFBP-2, MMP-9, PlGF, S100A8, S100A9, S100 A8/A9, and VEGFR-1 levels were determined using ELISA. RESULTS: Multivariate logistic regression analyses revealed significant associations between (i) high levels of plasma S100A8/A9, SPTD ≤14 days after sampling, and shorter sampling-to-delivery intervals; (ii) elevated plasma MMP-9, S100A9, and S100A8/A9 levels and MIAC/IAI, and (iii) decreased plasma endoglin levels and increased CNMM risk, while adjusting for gestational age at sampling (or delivery) and tocolytic use. The area under the curves of the aforementioned proteins ranged from 0.655 to 0.731 for each outcome. Notably, the SPTD risk increased significantly with increasing plasma S100A8/A9 levels (P for trend < .05). CONCLUSIONS: Plasma S100A8/A9, MMP-9, S100A9, and endoglin may represent valuable biomarkers associated with SPTD, MIAC/IAI, and CNMM in women with early PPROM. Owing to their less invasive nature, repeatability, and fair-to-moderate diagnostic accuracy, these biomarkers may contribute to risk stratification of PPROM-related complications in the clinical setting.

Immersive virtual reality simulation training for cesarean section: a randomized controlled trial.

BACKGROUND: Caesarean section (CS) is a complex surgical procedure that involves many steps and requires careful precision. Virtual reality (VR) simulation has emerged as a promising tool for medical education and training, providing a realistic and immersive environment for learners to practice clinical skills and decision-making. This study aimed to evaluate the educational effectiveness of a VR simulation program in training the management of patients with premature rupture of membranes (PROM) and CS. MATERIALS AND METHODS: A two-arm parallel randomized controlled trial was conducted with 105 eligible participants randomly assigned to the VR group ( n =53) or the control group ( n =52) in a 1:1 ratio. The VR group received VR simulation training focused on PROM management and CS practice, while the control group watched a video presentation with narrative of clinical scenario and recording of CS. Both groups completed questionnaires assessing their prior experiences with VR, experience in managing patients with PROM and performing CS, as well as their confidence levels. These questionnaires were administered before and after the intervention, along with a mini-test quiz. RESULTS: Baseline characteristics and previous experiences were comparable between the two groups. After the intervention, the VR group had higher confidence scores in all four aspects, including managing patients with PROM, performing CS as an operator, and understanding the indications and complications of CS, compared to the control group. The VR group also achieved significantly higher scores on the mini-test quiz [median (interquartile range), 42 (37-48) in the VR group; 36 (32-40) in the control group, P <0.001]. CONCLUSION: VR simulation program can be an effective educational tool for improving participants' knowledge and confidence in managing patients with PROM and performing CS.

Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.

OBJECTIVE: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS: Meal intervention statistically significantly stabilized serum phosphorus level (ß = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.

Analysis of gastric fluid in preterm newborns supports the view that the amniotic cavity is sterile before the onset of parturition: a retrospective cohort study.

OBJECTIVES: To compare the frequency of Ureaplasma-positive gastric fluid (GF) cultures based on the cause and mode of delivery in preterm newborns. METHODS: This retrospective cohort study included women with a singleton pregnancy who delivered prematurely (between 23+0 and 32+0 weeks of gestation, n=464) at a single university hospital in South Korea. The newborns' GF was obtained on the day of birth via nasogastric intubation. The frequency of Ureaplasma spp. in GF cultures was measured and compared according to the cause and mode of delivery. RESULTS: Ureaplasma spp. was detected in 20.3 % of the GF samples. The presence of Ureaplasma spp. was significantly higher in the spontaneous preterm birth group than in the indicated preterm birth group (30.2 vs. 3.0 %; p<0.001). Additionally, Ureaplasma spp. was more frequently found in the vaginal delivery group than in the cesarean delivery group, irrespective of the cause of preterm delivery [indicated preterm birth group (22.2 vs. 1.9 %, p=0.023); spontaneous preterm birth group (37.7 vs. 24.2 %, p=0.015)]. CONCLUSIONS: Ureaplasma spp. were found in 20.3 % of the GFs. However, only 1.9 % of newborns in the indicated preterm birth group with cesarean delivery had a Ureaplasma-positive GF culture.

Effect of pelvic artery embolization for postpartum hemorrhage on subsequent pregnancies: a single-center retrospective cohort study.

OBJECTIVE: Pelvic artery embolization (PAE) is a uterus-saving treatment for postpartum hemorrhage (PPH); however, subfertility or abnormal placentation for subsequent pregnancy has been a concern in several previous reports. This study aimed to investigate the impact of PAE on subsequent pregnancies in women with a history of PPH. METHODS: A retrospective cohort study was conducted on women transferred to the tertiary center for PPH and delivered for the next pregnancy at the same center later. The study group was divided into two groups based on PAE application to treat previous PPH. RESULTS: Of the 62 women included, 66% (41/62) had received PAE for the previous PPH, while 21 had not. Pregnancy outcomes for subsequent pregnancies were compared between the PAE and non-PAE groups. The PAE group had a higher estimated blood loss volume for the present delivery than the non-PAE group (600 vs. 300 mL, p = 0.008). The PAE group also demonstrated a higher incidence of placenta previa (4.8% vs. 24.4%, p = 0.080) and placenta accreta (0% vs. 14.6%, p = 0.082) than the non-PAE group, although the difference was not statistically significant. CONCLUSION: These findings suggest that the use of PAE to treat PPH may increase the risk of bleeding, placenta previa, and placenta accreta spectrum in subsequent pregnancies.

Neonatal outcomes of early preterm births according to the delivery indications.

OBJECTIVE: To compare the neonatal outcomes of early preterm births according to delivery indications and determine the obstetric risk factors associated with adverse outcomes. METHODS: We retrospectively studied pregnancies delivered between 22 + 0 and 26 + 6 weeks at the tertiary center between April 2013 and April 2022. Stillbirths, elective termination of pregnancy, and multifetal pregnancies were excluded. Patients were classified into two groups according to delivery indications: spontaneous preterm birth (sPTB) due to premature rupture of membranes (PROM), preterm labor, or acute cervical insufficiency; and indicated preterm birth (iPTB). Obstetric and neonatal outcomes were compared between the groups. RESULTS: Of the 121 neonates, 73 % (88/121) underwent sPTB. The overall survival rates were 73 % and 49 % in the sPTB and iPTB groups, respectively (p = 0.017). Multivariate logistic regression analysis was performed with adjustment for gestational age at delivery, fetal growth restriction, cesarean section, histological chorioamnionitis, and funisitis. Moreover, in the 1-year follow-up, the proportion of body mass below the third percentile was significantly higher in the iPTB-group than in the sPTB-group (53 % vs. 20 %, p = 0.019). Furthermore, diagnoses of developmental delay and cerebral palsy were slightly higher in the iPTB-group (33 % and 20 %, respectively) than in the sPTB-group (27 % and 9 %, respectively); however, this difference was not statistically significant. CONCLUSIONS: In early preterm births, iPTB was associated with a higher neonatal mortality than sPTB.

Cytomegalovirus infection during pregnancy.

Cytomegalovirus (CMV) infection during pregnancy is a global silent problem. Additionally, it is the leading cause of congenital infections, non-genetic sensorineural hearing loss, and neurodevelopmental delays in infants. However, this has barely been recognized globally. This condition lacks adequate attention, which is further emphasized by the lack of awareness among healthcare workers and the general population. The impact of CMV infection is often overlooked because of the asymptomatic nature of its presentation in infected pregnant women and newborns, difficulty in diagnosis, and the perception that infants born to women with pre-existing antibodies against CMV have normal neonatal outcomes. This article highlights the latest information on the epidemiology, transmission, clinical manifestations, and development of CMV infection and its management. We reviewed the pathophysiology and clinical manifestations of CMV infection in pregnant women, diagnostic methods, including screening and prognostic markers, and updates in treatment modalities. Current advancements in research on vaccination and hyperimmunoglobulins with worldwide treatment protocols are highlighted.

Targeting HMG-CoA synthase 2 suppresses tamoxifen-resistant breast cancer growth by augmenting mitochondrial oxidative stress-mediated cell death.

AIMS: In this study, we aimed to investigate previously unrecognized lipid metabolic perturbations in tamoxifen-resistant breast cancer (BC) by conducting comprehensive metabolomics and transcriptomics analysis. We identified the role of 3-hydroxy-3-methylglutary-coenzyme-A-synthase 2 (HMGCS2), a key enzyme responsible for ketogenesis, in tamoxifen-resistant BC growth. MAIN METHODS: Comprehensive metabolomics (CE-TOFMS, LC-TOFMS) and transcriptiomics analysis were performed to characterize metabolic pathways in tamoxifen-resistant BC cells. The upregulation of HMGCS2 were verified thorugh immunohistochemistry (IHC) in clinical samples obtained from patients with recurrent BC. HMGCS2 inhibitor was discovered through surface plasmon resonance analysis, enzyme assay, and additional molecular docking studies. The effect of HMGCS2 suppression on tumor growth was studied thorugh BC xenograft model, and intratumoral lipid metabolites were analyzed via MALDI-TOFMS imaging. KEY FINDINGS: We revealed that the level of HMGCS2 was highly elevated in both tamoxifen-resistant T47D sublines (T47D/TR) and clinical refractory tumor specimens from patients with ER+ breast cancer, who had been treated with adjuvant tamoxifen. Suppression of HMGCS2 in T47D/TR resulted in the accumulation of mitochondrial reactive oxygen species (mtROS) and apoptotic cell death. Further, we identified alphitolic acid, a triterpenoid natural product, as a novel HMGCS2-specific inhibitor that elevated mtROS levels and drastically retarded the growth of T47D/TR in in vitro and in vivo experiments. SIGNIFICANCE: Enhanced ketogenesis with upregulation of HMGCS2 is a potential metabolic vulnerability of tamoxifen-resistant BC that offers a new therapeutic opportunity for treating patients with ER+ BC that are refractory to tamoxifen treatment.

Anti­tumor properties of FoxO1 in YD­9 oral squamous cell carcinoma cells.

Oral squamous cell carcinoma (OSCC) is a tumor with a poor prognosis and a high recurrence rate. Despite its high annual incidence worldwide, appropriate therapeutic strategies have not yet been developed. Consequently, the 5­year survival rate for OSCC is low when advanced stages or recurrence is diagnosed. Forkhead transcriptional factor O1 (FoxO1) is a key mediator for maintaining cellular homeostasis. FoxO1 can function as a tumor suppressor as well as an oncogene depending on the cancer type. Therefore, the precise molecular functions of FoxO1 need to be validated, considering intracellular factors and the extracellular environment. To the best of our knowledge, however, the roles of FoxO1 in OSCC have not yet been defined. The present study examined FoxO1 levels under pathological conditions (oral lichen planus and oral cancer) and selected an appropriate OSCC cell line (YD­9). Crispr/Cas9 was used to generate FoxO1­deficient YD­9 cells in which the protein levels of phospho ERK and phospho STAT3 were upregulated, promoting cancer proliferation and migration. In addition, FoxO1 reduction increased the levels of the cell proliferation markers phospho H3 (Ser10) and PCNA. FoxO1 loss significantly reduced cellular ROS levels and apoptosis in YD­9 cells. Collectively, the present study demonstrated that FoxO1 exerted an anti­tumor effect by suppressing proliferation and migration/invasion but promoting oxidative stress­linked cell death in YD­9 OSCC cells.

Proteomic analysis of plasma to identify novel biomarkers for intra-amniotic infection and/or inflammation in preterm premature rupture of membranes.

To identify potential plasma biomarkers associated with microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in women with preterm premature rupture of membranes (PPROM). This retrospective cohort study included 182 singleton pregnant women with PPROM (23-33 weeks) who underwent amniocentesis. Plasma samples; all subjects were chosen from these participants and were analyzed using label-free liquid chromatography-tandem mass spectrometry for proteome profiling using a nested case-control study design (cases with MIAC/IAI vs. non-MIAC/IAI controls [n = 9 each]). Three identified target molecules for MIAC/IAI were further verified by ELISA in the study cohort (n = 182). Shotgun proteomic analysis revealed 17 differentially expressed proteins (P < 0.05) in the plasma of MIAC/IAI cases. In particular, the levels of FCGR3A and haptoglobin, but not LRP1, were found to be increased in the plasma of patients with MIAC, IAI, and both MIAC/IAI compared with those without these conditions. Moreover, these differences remained significant after adjusting for gestational age at sampling. The area under the curves of plasma FCGR3A and haptoglobin ranged within 0.59-0.65 with respect to each of the three outcome measures. Plasma FCGR3A and haptoglobin were identified as potential independent biomarkers for less-invasively detecting MIAC/IAI in women with PPROM.

Lactobacillus helveticus HY7801 ameliorates bacterial vaginosis by inhibiting biofilm formation and epithelial cell adhesion of Gardnerella vaginalis.

Bacterial vaginosis (BV) is caused by a microbial imbalance in the vaginal ecosystem, which causes genital discomfort and a variety of potential complications in women. This study validated the potential of Lactobacillus helveticus HY7801 as a probiotic to benefit vaginal health. In vivo, HY7801 reduced the number of Gardnerella vaginalis (GV) and pro-inflammatory cytokines in the vagina of GV-induced BV mice and ameliorated vaginal histological changes. In vitro, HY7801 exhibited positive resistance to simulated gastrointestinal conditions, showed excellent adherence ability to the female genital epithelium, and had high lactic acid and H2O2 production capacity. Furthermore, it was found that HY7801 can alleviate BV because it can suppress the expression of virulence factor genes of GV involved in epithelial cell adhesion and biofilm formation along with antibacterial activity against GV. These results indicate that HY7801 can be used as a promising probiotic strain for the maintenance of a healthy vaginal physiological state. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01208-7.

Organic vegetable juice supplement alleviates hyperlipidemia in diet-induced obese mice and modulates microbial community in continuous colon simulation system.

In this study, we investigated the effects of organic vegetable juice (OVJ) supplementation on modulating the microbial community, and how its consumption ameliorated blood-lipid profiles in diet-induced obese mice. Here, we studied the alleviating effect of hyperlipidemia via animal experiments using diet-induced obese mice and analyzed the effect of OVJ on the microbial community in continuous colon simulation system. OVJ consumption did not have a significant effect on weight loss but helped reduce the weight of the epididymis fat tissue and adipocytes. Additionally, blood-lipid profiles, such as triglyceride, high-density lipoprotein, and glucose, were improved in the OVJ-fed group. Expression levels of genes related to lipid synthesis, including SREBP-1, PPARγ, C/EBPα, and FAS, were significantly decreased. In addition, OVJ treatment significantly reduced inflammatory cytokines and oxidative stress. OVJ supplement influenced intestinal bacterial composition from phylum to genus level, including decreased Proteobacteria in the ascending colon in the phylum. At the family level, Akkermansia, which are associated with obesity, were significantly augmented in the transverse colon and descending colon compared to the control juice group. In addition, treatment with OVJ affected predicted lipid-metabolism-function genes related to lipid synthesis. These results suggest that OVJ supplementation may modulate gut microbial community and reduce the potential symptom of hyperlipidemia in diet-obese mice.

Expression of inflammatory, angiogenic, and extracellular matrix-related mediators in the cervicovaginal fluid of women with preterm premature rupture of membranes: Relationship with acute histological chorioamnionitis.

PROBLEM: To investigate whether altered expression of various inflammation-, angiogenesis-, and extracellular matrix-related mediators in cervicovaginal fluid (CVF) could be independently associated with acute histological chorioamnionitis (HCA), microbial-associated HCA, and funisitis in women with preterm premature rupture of membranes (PPROM). METHOD OF STUDY: Clinical data of 102 consecutive singleton pregnant women with PPROM at 23+0 to 34+0 weeks were retrospectively analyzed. CVF samples were collected upon admission. Levels of APRIL, DKK-3, IGFBP-1/2, IL-6/8, lipocalin-2, M-CSF, MIP-1α, MMP-8/9, S100A8A9, TGFBI, TIMP-1, TNFR2, uPA, and VDBP were determined by ELISA. Placentas were histologically examined after birth. RESULTS: Multivariate logistic regression analyses showed that: (1) elevated CVF levels of IL-8 and TNFR2 were independently associated with acute HCA; (2) elevated CVF levels of IL-6, IL-8, M-CSF, MMP-8, and TNFR2 were independently associated with microbial-associated HCA; and (3) elevated CVF IL-8 and MMP-8 levels were independently associated with funisitis when adjusted for gestational age. Areas under the curves of the aforementioned CVF biomarkers ranged within 0.61-0.77, thereby demonstrating poor to fair diagnostic capacity for these clinical endpoints. HCA risk significantly increased as the CVF levels of each inflammatory mediator increased (P for trend < 0.05). CONCLUSIONS: Herein, we identified several inflammatory biomarkers (IL-6/8, M-CSF, MMP-8, and TNFR2) in the CVF that are independently associated with acute HCA, microbial-associated HCA, and funisitis in women with PPROM. Furthermore, the degree of inflammatory response in the CVF, based on the levels of these proteins, demonstrated a direct relationship with HCA risk (especially risk severity).

Comprehensive characterization of maternal, fetal, and neonatal microbiomes supports prenatal colonization of the gastrointestinal tract.

In this study, we aimed to comprehensively characterize the microbiomes of various samples from pregnant women and their neonates, and to explore the similarities and associations between mother-neonate pairs, sample collection sites, and obstetrical factors. We collected samples from vaginal discharge and amniotic fluid in pregnant women and umbilical cord blood, gastric liquid, and meconium from neonates. We identified 19,597,239 bacterial sequences from 641 samples of 141 pregnant women and 178 neonates. By applying rigorous filtering criteria to remove contaminants, we found evidence of microbial colonization in traditionally considered sterile intrauterine environments and the fetal gastrointestinal track. The microbiome distribution was strongly grouped by sample collection site, rather than the mother-neonate pairs. The distinct bacterial composition in meconium, the first stool passed by newborns, supports that microbial colonization occurs during normal pregnancy. The microbiome in neonatal gastric liquid was similar, but not identical, to that in maternal amnionic fluid, as expected since fetuses swallow amnionic fluid in utero and their urine returns to the fluid under normal physiological conditions. Establishing a microbiome library from various samples formed only during pregnancy is crucial for understanding human development and identifying microbiome modifications in obstetrical complications.