Methotrexate/mifepristone-combined with embryo removal in the treatment of caesarean scar pregnancy.

OBJECTIVE: The aim of this study was to compare the effect of different administration modalities of methotrexate (MTX)/mifepristone in the initial medication stage, followed by embryo transfer in the treatment of caesarean scar pregnancy (CSP). PATIENTS AND METHODS: A retrospective analysis of 66 CSP patients who received treatment in our hospital from January 2015 to July 2021 was performed, and participants were divided into three groups: Group one (n=14) received mifepristone followed by embryo removal treatment, Group two (n=29) received MTX followed by embryo removal, and Group three (n=23) received a methotrexate/mifepristone combined treatment followed by embryo removal. The basic findings were analysed, along with the curative effects between the three groups. Risk factors predicting additional treatment after initial intervention failure were analysed. RESULTS: There were statistically significant differences in gestational age, hospitalization days, costs, myometrial thickness, cardiac activity, and mean sac diameter between groups (p<0.05) after grouping by eight weeks. The initial intervention success rates were 92.86%, 89.66%, and 65.22% in Group one, two, and three, respectively (p<0.05), while the complication rates were 14.29%, 6.90%, and 26.87%, respectively (p>0.05). After grouping according to eight weeks of gestational age, the difference in initial serum ß-hCG between Group two and three was statistically significant (p<0.05). Mean sac diameter was a risk factor for additional treatment after initial intervention failure, with an odds ratio of 1.113 (p<0.05). A cut-off of 22.75 mm was a preferable indicator. CONCLUSIONS: MTX/mifepristone followed by embryo removal is a reliable way to treat CSP. Mean sac diameter was a risk factor for additional treatment after initial intervention failure.

Effects of miR-32 targeting PTEN on proliferation and apoptosis of myeloma cells.

OBJECTIVE: To explore the effects of micro ribonucleic acid (miR)-32 on the proliferation and apoptosis of myeloma cells, and to verify whether it exerts its function by targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN). PATIENTS AND METHODS: The differentially expressed miRNAs were screened in healthy people and myeloma patients. The myeloma U266 cells transfected with negative control (NC) were used as control group, those transfected with miR-32 inhibitor as transfection group, and those transfected with miR-32 inhibitor and treated with PTEN inhibitor SF1670 as the transfection + inhibitor group. Then, the cell proliferation and apoptosis in each group were detected using the 5-Ethynyl-2'-deoxyuridine (EdU) kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. Finally, the expressions of apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2 homologous antagonist/killer (Bak), caspase-9, and survivin were detected. RESULTS: The expressions of some miRNAs and genes in myeloma patients were significantly different from those in healthy people. In myeloma patients, miR-32, miR-126, miR-123, and miR-183 were significantly highly expressed, while miR-5, miR-76, and miR-50 were remarkably lowly expressed. After myeloma U266 cells were transfected with the miR-32 inhibitor, the expression of miR-32 markedly declined. In addition, the mRNA expression of PTEN in myeloma cells rose after transfection with the miR-32 inhibitor, and declined after addition of the PTEN inhibitor SF1670, which were consistent with the results of Western blotting. Besides, the proliferation ability of myeloma cells was evidently weakened after transfection with the miR-32 inhibitor, while it was restored to a certain extent after addition of the PTEN inhibitor SF1670. Moreover, the number of apoptotic myeloma cells was remarkably larger after transfection with the miR-32 inhibitor, while it was remarkably smaller after addition of the PTEN inhibitor SF1670. The expressions of pro-apoptotic proteins Bak and caspase-9 in myeloma cells were significantly increased after transfection with the miR-32 inhibitor (p<0.05), and significantly decreased after addition of the PTEN inhibitor SF1670, while the expressions of anti-apoptotic proteins Bcl-2 and survivin were opposite to those of Bak and caspase-9. CONCLUSIONS: MiR-32 targeting PTEN will have certain effects on the proliferation and apoptosis of myeloma cells.

Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in Beta-lactoglobulin-induced allergic mice model

OBJECTIVES: Β-lactoglobulin (Β-Lg)-sensitized mice model was employed to investigate the correlation between Lactobacillus acidophilus KLDS 1.0738 (Lap KLDS 1.0738) modulating gut microbiota and inducting Toll-like receptors (TLRs) expression. METHODS: The alterations of mice fecal microbiota were analyzed by 16S rRNA gene sequencing. The serum cytokines production and TLR4/NF-κB mRNA expression in the colon tissues were measured by ELISA kit and quantitative RT-PCR, respectively. RESULTS: The results showed that Lap KLDS 1.0738 pretreatment attenuated Β-Lg-induced hypersensitivity, accompanied with a diminished expression of TLR4/NF-κB signaling. Moreover, oral administration of Lap KLDS 1.0738 improved the richness and diversity of fecal microbiota, which was characterized by fewer Proteobacteria phylum and Helicobacteraceae family, and higher Firmicutes phylum and Lachnospiraceae family than allergic group. Notably, TLR4/NF-κB expression was positively correlated with the family of Helicobacteraceae in allergic group, but negatively correlated with the family of Lachnospiraceae, Ruminococcaceae and anti-inflammatory cytokines level. A significant positive correlation was observed between TLR4/NF-κB expression and the production of histamine, total IgE and pro-inflammatory cytokines. CONCLUSIONS: Intake of Lap KLDS 1.0738 can influence the gut bacterial composition, which might result in recognizing TLRs signaling so as to inhibit allergic response

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Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in ß-lactoglobulin-induced allergic mice model.

OBJECTIVES: ß-lactoglobulin (ß-Lg)-sensitized mice model was employed to investigate the correlation between Lactobacillus acidophilus KLDS 1.0738 (Lap KLDS 1.0738) modulating gut microbiota and inducting Toll-like receptors (TLRs) expression. METHODS: The alterations of mice fecal microbiota were analyzed by 16S rRNA gene sequencing. The serum cytokines production and TLR4/NF-κB mRNA expression in the colon tissues were measured by ELISA kit and quantitative RT-PCR, respectively. RESULTS: The results showed that Lap KLDS 1.0738 pretreatment attenuated ß-Lg-induced hypersensitivity, accompanied with a diminished expression of TLR4/NF-κB signaling. Moreover, oral administration of Lap KLDS 1.0738 improved the richness and diversity of fecal microbiota, which was characterized by fewer Proteobacteria phylum and Helicobacteraceae family, and higher Firmicutes phylum and Lachnospiraceae family than allergic group. Notably, TLR4/NF-κB expression was positively correlated with the family of Helicobacteraceae in allergic group, but negatively correlated with the family of Lachnospiraceae, Ruminococcaceae and anti-inflammatory cytokines level. A significant positive correlation was observed between TLR4/NF-κB expression and the production of histamine, total IgE and pro-inflammatory cytokines. CONCLUSIONS: Intake of Lap KLDS 1.0738 can influence the gut bacterial composition, which might result in recognizing TLRs signaling so as to inhibit allergic response.

Immune efficacy of a porcine circovirus type 2 vaccine purified using Gram-positive enhancer matrix surface display technology.

AIMS: Purification of porcine circovirus type 2 (PCV2) using Gram-positive enhancer matrix (GEM) surface display technology and immunogenicity evaluation of the purified antigen. METHODS AND RESULTS: A recombinant bifunctional protein containing a protein anchor domain and a 'virus anchor' domain was designed as a protein linker (PL) between PCV2 and GEM particles. By incubating with PL and GEM particles sequentially, PCV2 could be purified and enriched through a simple centrifugation process with GEM surface display technology. Our data showed that one unit (2·5 × 109 particles) of GEM particles with 80 µg PL could purify 100 ml of PCV2-containing culture supernatant (viral titre: 106·5 TCID50 per ml-1 ) with a recovery rate up to 99·6%. The impurity removal efficiency of this method, calculated according to decreased total protein content during purification, was approximately 98%. Furthermore, in vivo experimentation showed that piglets immunized with purified PCV2 could elicit strong immune responses to prevent against PCV2 infection. CONCLUSION: Porcine circovirus type 2 could be efficiently purified and enriched with GEM display technology via a crucial PL, and the purified PCV2 could elicit effective immune responses against PCV2 infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The GEM-based purification method established here is cost-efficient and high-throughput, and may represent a promising large-scale purification method for PCV2 vaccine production.

Collision cross section predictions using 2-dimensional molecular descriptors.

Traditional methods for deriving computationally-generated collision cross sections for comparisons with ion mobility-mass spectrometry data require 3-dimensional energy-minimized structures and are often time consuming, preventing high throughput implementation. Here, we introduce a method to predict ion mobility collision cross sections of lipids and peptide analogs important in prebiotic chemistry and other fields. Using less than 100 2-D molecular descriptors this approach resulted in prediction errors of less than 2%.

Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced impairments of synaptic plasticity in hippocampal dentate gyrus area of the anesthetized rats in vivo.

Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The common chelating agents have many adverse effects and are incapable of alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo-8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore with low affinity for metal ions, has yielded some promising results in animal models and clinical trials related to dysfunctions of metal ions. In addition, CQ-associated side effects are believed to be overcome with vitamin B12 (VB12) supplementation. To determine whether CQ treatment could rescue impairments of synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anesthetized rat in vivo by recording field potentials and measured hippocampal Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the lead-induced impairments of synaptic plasticity in hippocampal DG area of the anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments of LTP; however the co-administration of CQ and VB12 totally rescues these impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co-administration are specific to the lead-exposed animals.

Two new triterpenoid saponins from Symplocos chinensis.

Two new triterpenoid saponins, symplocososides X (1) and Y (2) have been isolated from the roots of Symplocos chinensis, and their structures elucidated as 21beta-O- cinnamoyl-22alpha-O-(2-methylbutanoyl)-15alpha, 16alpha, 28-trihydroxyolean-12-ene-3beta-O-[beta-D-glucopyranosyl (1 --> 2)]-alpha-L-arabinofuranosyl (1 --> 4)-beta-D-glucuronopyranoside (1) and 21beta-O-cinnamoyl-22alpha-O-(2-methylbutanoyl)-15alpha, 16alpha, 28-trihydroxyolean-12-ene-3beta-O-(3-O-acetyl)-[beta-D-glucopyranosyl (1 --> 2)]-alpha-L-arabinofuranosyl (1 --> 4)-beta-D-glucuronopyranoside (2) by spectral and chemical methods. Their antitumor activities have also been tested.

p38 kinase mediates nitric oxide-induced apoptosis of chondrocytes through the inhibition of protein kinase C zeta by blocking autophosphorylation.

This study investigated the molecular mechanisms underlying inhibition of protein kinase C (PKC) zeta by p38 kinase during nitric oxide (NO)-induced apoptosis of chondrocytes. Coimmunoprecipitation experiments showed that activation of p38 kinase following addition of an NO donor resulted in a physical association between PKCzeta and p38 kinase. Direct interaction of p38 kinase with PKCzeta was confirmed in vitro using p38 kinase and PKCzeta recombinant proteins. p38 kinase interacts with the regulatory domain of PKCzeta and its association blocked PKCzeta autophosphorylation. Micro LC-MS/MS analysis using recombinant proteins indicated that the interaction of p38 kinase with PKCzeta blocked autophosphorylation of PKCzeta on Thr-560, which is required for PKCzeta activation. Collectively, our results demonstrate a novel mechanism of PKCzeta regulation: following activation by the production of NO, p38 kinase binds directly to the PKCzeta regulatory domain, preventing PKCzeta autophosphorylation on Thr-560, thereby inhibiting PKCzeta activation.

New Quinoid Glycosides from Forsythia suspensa

Three novel compounds, suspenolic acid (1), forsythenside A (2), and forsythenside B (3), have been isolated from the fruits of Forsythia suspensa. Their structures were elucidated by spectral methods and chemical reactions.