Adipose-derived stem cells promote diabetic wound healing via the recruitment and differentiation of endothelial progenitor cells into endothelial cells mediated by the VEGF-PLCγ-ERK pathway.

Adipose-derived stem cell (ADSC) therapy is a promising treatment strategy for wound healing; however, the mechanism underlying this effect remains unclear. In the present study, we aimed to explore the influence of ADSC-derived VEGF on diabetic wounds and its role in modulating endothelial progenitor cells. The effect of ADSCs and ADSC-derived VEGF in vivo was investigated using a diabetic wound healing model, and inflammatory factors, such as IL-6, IL-10, and TNF-α, were detected. RT-qPCR and western blot analysis were used to detect the expression of downstream targets. In addition, the role of ADSC-derived VEGF in modulating endothelial progenitor cells (EPCs) was investigated using EdU assay, CD-31 immunofluorescence, and Transwell assay in vitro. The results show that ADSCs accelerated diabetic wound tissue closure and decreased the expression of inflammatory factors, such as IL-6, IL-10, and TNF-α. Further molecular mechanism studies indicated that coculturing EPCs with ADSC--conditioned medium enhanced the proliferation, mobilization and differentiation of EPCs into endothelial cells. This enhancement was inhibited when the expression of the VEGF downstream signal molecules VEGFR2, PLCγ, and ERK1/ERK2 was blocked, indicating that ADSCs might accelerate diabetic wound healing through the recruitment and differentiation of EPCs mediated by VEGF. Overall, the results of the study revealed that ADSCs could promote diabetic wound healing through the recruitment and differentiation of EPCs via angiogenesis effects regulated by the VEGF-PLCγ-ERK1/ERK2 pathway and suppression of the inflammatory response. In addition, it will be helpful to establish further understanding of ADSC therapy for clinical application.

Effect of Cytochrome P450 7A1 (CYP7A1) Polymorphism on Lipid Responses to Simvastatin Treatment.

BACKGROUND: Identifying patients with high risk of low response to statin therapy is important for optimization of lipid-lowering therapy. Cholesterol 7α-hydroxylase, a rate-limiting enzyme encoded by cytochrome P450 7A1 (CYP7A1) gene, is considered to be associated with statin efficacy. This study aimed to investigate the association between a novel CYP7A1 single nucleotide polymorphism rs3824260 and statin treatment response for hypercholesteremic patients in Chinese Han population. METHODS: A total of 336 subjects were prescribed with simvastatin for 12 weeks after enrollment. Plasma lipid parameters were measured at enrollment and after 12-week simvastatin treatment separately. Subjects were classified into high- and low-response groups depending on their total cholesterol, low-density lipoprotein cholesterol (LDL-C) and TG changes and increase or reduction groups according to their high-density lipoprotein cholesterol (HDL-C) levels changing after simvastatin treatment. The CYP7A1 rs3824260 was genotyped from blood samples with a SNaPshot assay. RESULTS: At baseline, the LDL-C level and TG level were significantly higher in the AA genotype, while the HDL-C level was significantly higher in the GG genotype of CYP7A1 rs3824260. Patients carrying AA genotype are at an increased risk of low response for LDL-C reduction (odds ratio = 2.295, 95% confidence interval = 1.164-4.524, P = 0.016). Furthermore, the GG genotype of rs3824260 was significantly associated with a high risk of HDL-C reduction response after simvastatin therapy (odds ratio = 2.240, 95% confidence interval = 1.137-4.413, P = 0.025). CONCLUSIONS: The CYP7A1 gene polymorphism rs3824260 is related to inappropriate response of simvastatin treatment for hypercholesterolemia patients in Chinese Han population.

Association of lipoprotein-associated phospholipase A2 mass with asymptomatic cerebral artery stenosis.

Cerebral artery stenosis (CAS) is the most important causes of ischaemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays 2 diverse roles in atherosclerosis (pro-inflammatory and anti-inflammatory), and the association between Lp-PLA2 mass and cardiovascular or cerebrovascular events is inconsistent among previous studies. A cross-sectional study including 2012 North Chinese adults aged ≥40 years was performed in 2010-2011 to investigate whether Lp-PLA2 mass is associated with asymptomatic cerebral artery stenosis (ACAS). Serum Lp-PLA2 mass was determined by enzyme-linked immunosorbent assay (ELISA). All participants underwent transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS). The median serum Lp-PLA2 mass of the participants was 140.74 ng/mL (interquartile range: 131.79-158.07 ng/mL). The adjusted odds ratio (OR) when comparing the 4th quartile to the 1st quartile of Lp-PLA2 was 1.98 (95% confidence interval (CI): 1.42-2.78), 1.79 (95% CI: 1.08-2.94) and 1.87 (95% CI: 1.28-2.73) for the occurrence of ACAS, asymptomatic ECAS and asymptomatic ICAS, respectively, after controlling for vascular risk factors. These independently significant associations remained statistically significant in the male or elderly subgroups, but not in females or middle-aged participants. Lp-PLA2 mass is positively correlated with subclinical atherosclerosis determined by ACAS, ICAS and ECAS in North Chinese, particularly in male and older participants, suggesting that serum Lp-PLA2 mass might be potential biomarker for the detection of ACAS in the adults.

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis.

BACKGROUND: Myocardial infarction (MI) is an acute and fatal condition that threatens human health. Dl-3-n-butylphthalide (NBP) has been used for the treatment of acute ischemic stroke. Mitochondria may play a protective role in MI injury. However, there are few reports on the cardioprotective effect of NBP or the potential mitochondrial mechanism for the NBP-induced protection against cardiac ischemia injury. We investigated the therapeutic effects of NBP in an in vivo MI model and an in vitro oxidative stress model, as well as the potential mitochondrial mechanism. METHODS: This study comprised two different experiments. The aim of experiment 1 was to determine the protective effects of NBP on MI and the underlying mechanisms in vivo. In part 1, myocardial infarct size was measured by staining with 2,3,5-triphenyltetrazoliumchloride (TTC). Myocardial enzymes and mitochondrial enzymes were assayed. The aim of experiment 2 was to investigate the role of NBP in H2O2-induced myocardial ischemic injury in H9c2 cells and to determine the potential mechanism. In part 2, H9c2 cell viability was evaluated. ROS levels, mitochondrial morphology, and mitochondrial membrane potential of H9c2 cells were measured. ATP levels were evaluated using an assay kit; mitochondrial DNA (mtDNA), the expressions of NRF-1 and TFAM, and mitochondrial biogenesis factors were determined. RESULTS: NBP treatment significantly reduced the infarct ratio, as observed by TTC staining, decreased serum myocardial enzymes in MI, and restored heart mitochondrial enzymes (isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and a-ketoglutarate dehydrogenase (a-KGDH) activities after MI. Moreover, in in vitro studies, NBP significantly increased the viability of H9c2 cells in a dose-dependent manner, reduced cell apoptosis, protected mitochondrial functions, elevated the cellular ATP levels, and promoted H2O2-induced mitochondrial biogenesis in H9c2 cardiomyoblasts. CONCLUSION: Collectively, the results from both the in vivo and in vitro experiments suggested that NBP exerted a cardioprotective effect on cardiac ischemic injury via the regulation of mitochondrial function and biogenesis.

Leptin Attenuates the Contractile Function of Adult Rat Cardiomyocytes Involved in Oxidative Stress and Autophagy.

BACKGROUND: Leptin has been identified as an important protein involved in obesity. As a chronic metabolic disorder, obesity is associated with a high risk of developing cardiovascular and metabolic diseases, including heart failure. The aim of this paper was to investigate the effects and the mechanism of leptin on the contractile function of cardiomyocytes in the adult rat. METHODS: Isolated adult rat cardiomyocytes were exposed to leptin (1, 10, and 100 nmol/L) for 1 hour. The calcium transients and the contraction of adult rat cardiomyocytes were recorded with SoftEdge MyoCam system. Apocynin, tempol and rapamycin were added respectively, and Western blotting was employed to evaluate the expression of LC3B and Beclin-1. RESULTS: The peak shortening and maximal velocity of shortening/relengthening (± dL/dtmax) of cell shortening were significantly decreased, and the time to 50% relengthening was prolonged with leptin perfusion. Leptin also significantly reduced the baseline, peak and time to 50% baseline of calcium transient. Leptin attenuated autophagy as indicated by decreased LC3-II and Beclin-1. All of the abnormalities were significantly attenuated by apocynin, tempol or rapamycin. CONCLUSIONS: Our results indicated that leptin depressed the intracellular free calcium and myocardial systolic function via increasing oxidative stress and inhibiting autophagy.

Mechanical compression upregulates MMP9 through SMAD3 but not SMAD2 modulation in hypertrophic scar fibroblasts.

PURPOSE: Activation of transforming growth factor-ß (TGF-ß) signaling and matrix metalloproteinases are involved in hypertrophic scar (HS) formation. Compression therapy is known to be an effective approach for the treatment of hypertrophic scarring; however, the underlying molecular mechanisms remain poorly understood. We investigated the relationship between TGF-ß signaling activation and matrix metalloproteinases in HS fibroblasts during mechanical compressive stress. MATERIALS AND METHODS: Two groups of skin tissue from HS and the nearby normal tissue were obtained from surgical patients and analyzed. Primary fibroblasts from the HS tissue and normal fibroblasts were isolated. Pressure therapy was recapitulated in an in vitro three-dimensional culture model, using mechanical stress produced with the Flexcell FX-4000C Compression Plus System. Quantitative real-time PCR (qPCR) was used to analyze the gene expression profiles in skin tissue and cultured primary cells exposed to compressive stress. Knockdown of SMAD2 and SMAD3 was performed using their specific siRNA in HS and normal fibroblasts subjected to compressive stress, and gene expression was examined by qPCR and Western blot. RESULTS: There was a significant upregulation of the mRNA expression of matrix metalloproteinase-2 (MMP2) and MMP9 in primary HS fibroblasts in response to mechanical stress. In contrast, the mRNA levels of collagen I and collagen III were downregulated in primary HS fibroblasts compared with those in the control cells. SiRNA-mediated knockdown of SMAD3 in the primary fibroblasts exposed to mechanical stress resulted in a decrease in the expression of MMP9 compared to control cells. CONCLUSION: These results demonstrate that compressive stress upregulates MMP9 by SMAD3 but not by SMAD2.

[Effects of rosuvastatin on arterial stiffness in hyperlipidemia patients].

OBJECTIVE: To evaluate the effects of rosuvastatin on arterial stiffness in hyperlipidemia patient without hypertension. METHODS: A total of 60 patients without hypertension received rosuvastatin (10 mg, n = 60) daily for 12 weeks while another 60 subjects used no statins. Brachial-ankle pulse wave velocity (ba-PWV), radial artery augmentation index of reflected wave (rAI) and metabolic index were measured before and after treatment. RESULTS: There were no significant change before and after non-statin treatment. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels decreased dramatically after resuvastin treatment [TC: (4.0 ± 1.0) vs (5.8 ± 1.1) mmol/L; LDL-C: (2.1 ± 0.7) vs (3.8 ± 0.7) mmol/L, both P < 0.01]. In rosuvastatin group, ba-PWV and rAI decreased significantly [ba-PWV: (1 340 ± 177) vs (1 477 ± 159) cm/s; rAI: (44 ± 13) % vs (57 ± 15) %, P < 0.01 and P < 0.05). CONCLUSION: Atherosclerosis may be improved by rosuvastatin treatment in hyerlipidemia patient without hypertension.

Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory.

The long-lasting humoral immunity induced by viral infections or vaccinations depends on memory B cells with greatly increased affinity to viral antigens, which are evolved from germinal center (GC) responses. However, it is unclear whether antiviral memory B cells represent a distinct subset among the highly heterogeneous memory B cell population. Here, we examined memory B cells induced by a virus-mimicking antigen at both transcriptome and epigenetic levels and found unexpectedly that antiviral memory B cells exhibit an enhanced innate immune response, which appeared to be facilitated by the epigenetic memory that is established through the memory B cell development. In addition, T-bet is associated with the altered chromatin architecture and is required for the formation of the antiviral memory B cells. Thus, antiviral memory B cells are distinct from other GC-derived memory B cells in both physiological functions and epigenetic landmarks.

Digital measurement of deciduous tooth dimensions in China: A cross-sectional survey.

OBJECTIVE: Crown dimensions data of deciduous teeth hold anthropological, forensic, and archaeological value. However, such information remains scarce for the Chinese population. This multi-center study aimed to collect a large sample of deciduous crown data from Chinese children using three-dimensional measurement methods and to analyze their dimensions. DESIGN: A total of 1592 children's deciduous dentition samples were included, and the sample size was distributed according to Northeast, North, East, Northwest, Southwest and South China. Digital dental models were reconstructed from plaster dental models. Independent sample t test, paired t test, principal component analysis (PCA), and factor analysis (FA) were used to analyze the tooth crown dimensions. RESULT: 18,318 deciduous teeth from 1592 children were included. Males exhibited slightly larger values than females. The range of sexual dimorphism percentages for each measurement was as follows: mesiodistal diameter (0.40-2.08), buccolingual diameter (0.13-2.24), and maxillogingival diameter (0.48-3.37). The FA results showed that the main trend of crown dimensions changes was the simultaneous increase or decrease in mesiodistal diameter, buccolingual diameter and maxillogingival diameter in three directions. CONCLUSION: This is the first large-scale survey of deciduous tooth crown dimensions in China, which supplements the data of deciduous tooth measurement and provides a reference for clinical application.

Dramatic response and acquired resistance to savolitinib in advanced intrahepatic cholangiocarcinoma with MET amplification: a case report and literature review.

Background: Cholangiocarcinoma (CCA) is an aggressive disease with limited treatment options. Despite substantial efforts to explore better regimens, gemcitabine-based chemotherapy has been the standard first-line treatment for decades. With the growing field of precision medicine, biomarker-guided treatments are gaining popularity. MET alteration is a frequent occurrence in various cancer types, making it a promising target. Case presentation: A 53-year-old man visited our hospital with a complaint of upper abdominal pain. Advanced CCA was diagnosed based on the biopsy of the metastatic lymph nodes and immunohistochemistry. Next-generation sequencing revealed MET amplification. As the patient was intolerant to traditional chemotherapy, savolitinib (a c-MET inhibitor) was administered. Partial response was achieved, and the treatment was well tolerated. After 1 year, the patient developed progressive disease, to which the emergence of epidermal growth factor receptor amplification may have contributed. Conclusion: Our study verified the therapeutic value of a c-MET inhibitor in advanced CCA-harboring MET amplification and provides an alternative strategy for patients who are intolerant to chemotherapy.

Icaritin inhibits endometrial carcinoma cells by suppressing O-GlcNAcylation of FOXC1.

BACKGROUND: Icaritin has a wide range of pharmacological activities, including significant an-titumor activity. However, the mechanism of action of icaritin in endometrial cancer (UCEC) remains unknown. FOX proteins are a highly conserved transcription factor superfamily that play important roles in epithelial cell differentiation, tumor metastasis, angiogenesis, and cell cycle regulation. FOXC1 is an important member of the FOX protein family. FOXC1 is aberrantly expressed in endometrial cancer and may play a role in the migration and invasion of endometrial cancer; however, its mechanism of action has not yet been reported. O-GlcNAc glycosylation is a common post-translational modification. In endometrial cancer, high levels of O-GlcNAcylation promote cell proliferation, migration, and invasion. Cancer development is often accompanied by O-GlcNAc modification of proteins; however, O-GlcNAc modification of the transcription factor FOXC1 has not been reported to date. PURPOSE: To investigate the inhibitory effects of icaritin on RL95-2 and Ishikawa endometrial cancer cells in vitro and in vivo and to elucidate the possible molecular mechanisms. METHODS/STUDY DESIGN: CCK8, colony formation, migration, and invasion assays were used to determine the inhibitory effects of icaritin on endometrial cancer cells in vitro. Cell cycle regulation was assayed by flow cytometry. Protein levels were measured based on western blotting. The level of FOXC1 expression in endometrial cancer tissues was determined by immunohistochemistry. To assess whether icaritin also has activity in vivo, its effect on tumor xenografts was evaluated. RESULTS: Immunohistochemical analysis of clinical samples revealed that FOXC1 expression was significantly higher in endometrial cancer tissues than in normal tissues. Downregulation of FOXC1 inhibited the proliferative, colony formation, migration, and invasive abilities of RL95-2 and Ishikawa endometrial cancer cells. Icaritin inhibited the proliferation, colony formation, migration, and invasion of endometrial cancer cells and blocked the cell cycle in S phase. Icaritin affected O-GlcNAc modification of FOXC1 and thus the stability of FOXC1, which subsequently triggered the inhibition of endometrial cancer cell proliferation. CONCLUSION: The anti-endometrial cancer effect of icaritin is related to the inhibition of abnormal O-GlcNAc modification of FOXC1, which may provide an important theoretical foundation for the use of icaritin against endometrial cancer.

Signalling in pancreatic cancer: from pathways to therapy.

Pancreatic cancer (PC) is a common malignant tumour in the digestive system. Due to the lack of sensitive diagnostic markers, strong metastasis ability, and resistance to anti-cancer drugs, the prognosis of PC is inferior. In the past decades, increasing evidence has indicated that the development of PC is closely related to various signalling pathways. With the exploration of RAS-driven, epidermal growth factor receptor, Hedgehog, NF-κB, TGF-ß, and NOTCH signalling pathways, breakthroughs have been made to explore the mechanism of pancreatic carcinogenesis, as well as the novel therapies. In this review, we discussed the signalling pathways involved in PC and summarised current targeted agents in the treatment of PC. Furthermore, opportunities and challenges in the exploration of potential therapies targeting signalling pathways were also highlighted.

Visual Sensing of ß-Glucosidase From Intestinal Fungus in the Generation of Cytotoxic Icarisid II.

ß-Glucosidase (ß-Glc) is an enzyme capable of the selective hydrolysis of the ß-glycosidic bond of glycosides and glycans containing glucose. ß-Glc expressed by intestinal microbiota has attracted increasing levels of interest, due to their important roles for the metabolism of exogenous substances in the gut. Using the 2-((6-hydroxy-2,3-dihydro-1H-xanthen-4-yl)methylene)malononitrile fluorophore (DXM-OH, λem 636 nm) and the recognition group ß-Glucose, an enzymatic activatable turn-on fluorescent probe (DXM-Glc) was developed for the selective and sensitive sensing of ß-Glc. In addition, DXM-Glc could be used to sense endogenous ß-Glc in living fungal cells. Using DXM-Glc, Pichia terricola M2 was identified as a functional intestinal fungus with ß-Glc expression. P. terricola M2 could transform the flavone glycoside Icariin to Icariside Ⅱ efficiently, which confirmed the metabolism of glycosides in the gut mediated by fungi. Furthermore, Icariside Ⅱ could inhibit the proliferation of human endometrial cancer cells (RL 95-2 and ishikawa) significantly, suggesting the metabolic activation of Icariin by intestinal fungi in vivo. Therefore, DXM-Glc as a probe for ß-Glc provided a novel technique for the investigation of the metabolism of bioactive substances by intestinal microbiota.

Progress in traditional Chinese medicine and natural extracts for the treatment of lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease with multiple system involvement and is also one of the most serious forms of organ damage in systemic lupus erythematosus (SLE), which is mainly caused by the formation and deposition of immune complexes in glomeruli. More than 50% of SLE patients have clinical manifestations of renal damage. At present, the treatment of lupus nephritis is mainly based on glucocorticoids and immunosuppressants. However, due to adverse drug reactions and frequent recurrence or aggravation after drug reduction or withdrawal, the prognosis remains poor; thus, it is still one of the most important causes of end-stage renal failure. Therefore, new treatment strategies are urgently needed. This article aims to review the application of traditional Chinese medicine and natural extracts in the treatment of lupus nephritis to provide the basic mechanisms of treatment and a new treatment strategy with clear effects and high safety performance.

Improved antitumor activity and IgE/IgG-binding ability of α-Lactalbumin/ß-lactoglobulin induced by ultrasonication prior to binding with oleic acid.

Bovine α-lactalbumin (α-La)/ß-lactoglobulin (ß-Lg) was pretreated through ultrasonic treatment and subsequently binding with oleic acid (OA) by heat treatment. And, the antitumor activity, IgE/IgG-binding ability, and structural modifications were investigated. After α-La/ß-Lg were treated by ultrasonic prior to binding with OA, the treated α-La/ß-Lg showed high antitumor activity and IgE/IgG-binding ability, and significantly affected the structural modifications, which reflected by the reduction in α-helix content, the increase of molecular weight, intrinsic fluorescence intensity, and surface hydrophobicity. Molecular docking studies indicated that OA bound to α-La/ß-Lg by hydrogen bonds and hydrophobic interaction. Therefore, ultrasonic prior to binding with OA could improve antitumor activity and IgE/IgG-binding ability of α-La/ß-Lg as a result of structural modifications. And, ultrasonic prior to binding with fatty acid processing of milk products alone may increase the antitumor activity, this change may enhance the risk of an allergenic reaction in milk allergy patients to some extent. PRACTICAL APPLICATIONS: Fatty acids, natural ligands associated with the bovine milk proteins, and milk protein-fatty acid complex has a variety of functional applications in the food industry. This study revealed that antitumor activity, IgE/IgG-binding ability, and structural modifications of α-La/ß-Lg induced by ultrasonic prior to binding with oleic acid. It will be beneficial to understand the mechanism of the functional changes of protein. Ultrasonic prior to binding with oleic acid will be more likely to develop a practical technology to improve the functional characteristics of milk protein and design the optimal nutritional performance of milk food.

Time-Series Expression Analysis of Epidermal Stem Cells from High Fat Diet Mice.

We aimed to identify differentially expressed genes (DEGs) in epidermal stem cells (epiSCs) in response to high fat diet (HFD). DEGs were identified by time-series analysis of the gene expression profile (GSE84510) in Gene Expression Omnibus (GEO) database. Functions and pathways affected by HFD were identified by functional annotation of DEGs. Key factors responding to HFD was identified by protein-protein interaction (PPI) network analysis. Two groups of genes with the same tendency in response to HFD were identified. ECM-related processes and PI3K pathway were altered in the early stage of obesity. A PPI network was constructed to delineate the interactions among proteins encoded by DEGs and ICAM1 and RELA were key epiSC factors respond to HFD. Our studies may provide valuable insights into the molecular mechanisms underlying how obesity affects the functions of epiSC.

[Effect of oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on vaginal Group B Streptococcus colonization and vaginal microbiome in late pregnancy].

OBJECTIVE: To explore the effects of intervention with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on vaginal Group B Streptococcus (GBS) colonization, pregnancy outcome and vaginal microbiome in GBS-positive women in the third trimester of pregnancy. METHODS: This study were conducted among 155 women in the third trimester of pregnancy with positive results of GBS culture in the Outpatient Department of Zhujiang Hospital from March to November, 2019. After excluding 32 patients who received lactobacillus intervention for less than 2 weeks or underwent postpartum GBS retesting, the women were divided into oral probiotics intervention group (60 cases) and non-intervention group (63 cases). According to the results of GBS retesting, the 60 women in the intervention group were divided into GBS-negative group (18 cases) and persistent GBS-positive group (42 cases). At the end of the intervention, the rates of negative GBS culture result were calculated and the pregnancy outcomes were compared. From 5 women randomly selected from the intervention group, samples of vaginal secretions were collected before and after the intervention for amplicon sequencing and bioinformatics analysis. RESULTS: At the end of the intervention, the GBS-negative rate in the intervention group was 30% (18/60), as compared with 23% (3/13) in the non-intervention group. Probiotic intervention significantly reduced the incidence of premature rupture of membranes (P < 0.05) and reduced the use of antibiotics during pregnancy (P < 0.05). OTU analysis of the vaginal secretions suggested probiotic intervention decreased the total sequence number and GBS sequence number, increased the species composition, and significantly decreased GBS abundance (P < 0.05). Probiotics intervention also significantly decreased the species abundance of Enterococcus, Staphylococcus and Streptococcus in the vaginal flora (P < 0.05). CONCLUSIONS: Intervention with oral probiotics can reduce vaginal GBS colonization in late pregnancy and improve the pregnancy outcome. Lactobacillus is capable of reducing the abundance of GBS and other pathogenic bacteria to improve the microbiome of vaginal flora.

Investigation of optimal pathways for preeclampsia using network-based guilt by association algorithm.

This study investigated optimal pathways for preeclampsia (PE) utilizing the network-based guilt by association (GBA) algorithm. The inference method consisted of four steps: preparing differentially expressed genes (DEGs) between PE patients and normal controls from gene expression data; constructing co-expression network (CEN) for DEGs utilizing Spearman's correlation coefficient (SCC) method; and predicting optimal pathways by network-based GBA algorithm of which the area under the receiver operating characteristics curve (AUROC) was gained for each pathway. There were 351 DEGs and 61,425 edges in the CEN for PE. Subsequently, 53 pathways were obtained with a good classification performance (AUROC >0.5). AUROC for 9 was >0.9 and defined as optimal pathways, especially microRNAs in cancer (AUROC=0.9966), gap junction (AUROC=0.9922), and pathogenic Escherichia coli infection (AUROC=0.9888). Nine optimal pathways were identified through comprehensive analysis of data from PE patients, which might shed new light on uncovering molecular and pathological mechanism of PE.