Microcystin-LR prenatal exposure drives preeclampsia-like changes in mice by inhibiting the expression of TGF-ß and VEGFA.

Microcystin-leucine-arginine (MC-LR) is widespread in the water and food, which has suspected to be associated with adverse pregnancy outcomes. In the present study, we aim to assess the interaction between MC-LR exposure and preeclampsia development and elucidate the molecular events involved. After exposure to MC-LR during pregnancy, the mice developed hypertension and proteinuria, the typical symptoms of preeclampsia. This was associated with decreased invasiveness of placental trophoblast and vascular dysplasia caused by MC-LR through down-regulating VEGFA and TGF-ß expression via AKT/m-TOR/HIF-1α pathway. In addition, this conclusion has been confirmed in a case-control study. Significantly, the addition of Deferoxamine (DFM), a phosphorylated serine-threonine protein kinases (p-AKT) specific agonist, can antagonize the inhibitory effect of MC-LR on the expression of related proteins, which further ameliorate the migration and invasion ability of HTR-8/Svneo cells. To sum up, our study revealed the pathologic mechanism by which MC-LR lead to preeclampsia and emphasized the importance of pregnancy management.

Collagen Glycopeptides from Transglutaminase-Induced Glycosylation Exhibit a Significant Salt Taste-Enhancing Effect.

This study aimed to prepare collagen glycopeptides by transglutaminase-induced glycosylation and to explore their salt taste-enhancing effects and mechanism. Collagen glycopeptides were obtained by Flavourzyme-catalyzed hydrolysis, followed by transglutaminase-induced glycosylation. The salt taste-enhancing effects of collagen glycopeptides were evaluated by sensory evaluation and an electronic tongue. LC-MS/MS and molecular docking technologies were employed to investigate the underlying mechanism responsible for the salt taste-enhancing effect. The optimal conditions were 5 h for enzymatic hydrolysis, 3 h for enzymatic glycosylation, and 1.0% (E/S, w/w) for transglutaminase. The grafting degree of collagen glycopeptides was 26.9 mg/g, and the salt taste-enhancing rate was 59.0%. LC-MS/MS analysis revealed that Gln was the glycosylation modification site. Molecular docking confirmed that collagen glycopeptides can bind to salt taste receptors epithelial sodium channel protein and transient receptor potential vanilloid 1 through hydrogen bonds and hydrophobic interaction. Overall, collagen glycopeptides have a significant salt taste-enhancing effect, which contributes to the application of collagen glycopeptides for salt reduction without compromising taste in the food industry.

Microcystin-LR inhibits early pregnancy by impairing the vascular network of luteum: Involvement of the MEK/ERK/SP1/VEGFR2 axis.

Microcystin-leucine-arginine (MC-LR) reduces the fertility of female mice, but the mechanism is unknown. We studied the effect of MC-LR on early pregnancy and elucidated its possible mechanism. The number of embryo beds and embryo volume decreased in pregnant mice at 6 or 8 days after fertilization after acute exposure to MC-LR. The corpus luteum secretes estrogen and progesterone, which are involved in embryo implantation and maintenance of early pregnancy. MC-LR exposure reduced luteal blood vessel branches and inhibited hormone synthesis. Functional blood vessels are essential to the maintenance of luteal structure and function. Reduced migration and tube-forming were also detected in human umbilical vascular endothelial cells (HUVECs) treated with MC-LR. MC-LR significantly decreased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in vivo and in vitro, which was responsible for the inhibited construction of the vascular network. The MEK/ERK/SP1 signal pathway mediated the decrease in VEGFR2 expression, and the agonists of phosphorylated extracellular regulated protein kinases (p-ERK) alleviated the anti-angiogenic effect of MC-LR. In conclusion, we demonstrated the toxicity of MC-LR on construction of vascular network in corpus luteum, which could provide a new perspective on female infertility or miscarriage caused by environmental factors.

Microcystin-leucine arginine (MC-LR) induces mouse ovarian inflammation by promoting granulosa cells to produce inflammatory cytokine via activation of cGAS-STING signaling.

Early experimental studies have demonstrated that microcystin-leucine arginine (MC-LR) is able to induce multiple organ damage. Female reproductive disorders caused by MC-LR have attracted increased attention in recent years. However, the underlying mechanisms of female reproductive malfunctions are not yet fully understood. Our previous study confirmed that MC-LR could enter mice ovary, induce apoptosis of ovarian granulosa cell and lead to follicular atresia. Research shows that ovary inflammation is positively related to the decline of female reproductive function. This study was aimed to find out the relationship between inflammation response and ovarian injury caused by MC-LR. MC-LR were administrated at 0, 7.5, 22.5 and 45 µg/kg for two weeks by intraperitoneal injection in female BALB/c mice. Histopathological analysis of ovary was performed. We found that MC-LR exposure induced inflammation response and fibrosis in ovary. In the present study, we observed that MC-LR could enter ovary and was mainly distributed in mGCs (mouse ovarian granulosa cells), but not in the theca-interstitial cells. We isolated and cultured mGCs with different concentrations of MC-LR at 0, 0.01, 0.1, 1 and 10 µM. MC-LR exposure caused mitochondrial DNA (mtDNA) leakage which was detected by qPCR andimmunofluorescence staining. Subsequently, mtDNA leakage activated cGAS-STING signaling, leading to elevated production of inflammatory cytokines TNF-α in mGCs.Diffusion of TNF-α in ovary resulted in inflammatory cell infiltration and interstitial cell proliferation. Ovarian inflammation provides a new perspective to explore the underlying mechanisms associated with MC-LR-induced female reproductive dysfunction.

The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Epidemiological study of Trichosporon asahii infections over the past 23 years.

Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. In vitro susceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment of T. asahii infection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of T. asahii infection.

Rapid and sensitive detection of malachite green in aquaculture water by electrochemical preconcentration and surface-enhanced Raman scattering.

A highly sensitive and rapid method of in-situ surface-enhanced Raman spectroscopy (SERS) combining with electrochemical preconcentration (EP) in detecting malachite green (MG) in aquaculture water was established. Ag nanoparticles (AgNPs) were synthesized and spread onto the surface of gold electrodes after centrifuging to produce SERS-active substrates. After optimizing the pH values, preconcentration potentials and times, in-situ EP-SERS detection was carried out. A sensitive and rapid analysis of the low-concentration MG was accomplished within 200s and the limit of detection was 2.4 × 10-16M.

Molar Range Detection Based on Sideband Differential Absorption Spectroscopy with a Concentrated Reference.

Conventional absorption spectroscopy (CAS) with a blank reference has only a slight capacity to detect high concentrations at characteristic wavelengths owing to the corresponding large molar absorption coefficient (ε) on the scale of 103 or 104 cm-1 M-1. To monitor concentrated analytes as high as the molar range in a plating bath and on a chemical production line, we propose a new approach using sideband differential absorption spectroscopy (SDAS). SDAS is obtained by subtracting the absorption spectra of the samples, A(λ,Cx), from that of a reference containing a concentrated standard analyte, A(λ,Cref>Cx), resulting in concave spectra with peaks at the sideband of conventional spectra with generally low ε values on the scale of 100 cm-1 M-1 or less. The negative absorbance changes linearly with the sample concentration at a certain peak wavelength, obeying Lambert-Beer's law. In this work, SDAS was obtained and verified using inorganic and organic substances, such as chromate potassium, rhodamine B, and paracetamol.

[The expression of tumor related macrophages and matrix solution element in laryngeal squamous carcinoma tissue and the relationship with tumor microvascular density].

OBJECTIVE: To study the expression of CD68 antibody marked tumor associated macrophage TAMs and matrix solution element MMP-7 in laryngeal squamous carcinoma tissue and the relationship with clinicopathological parameters, so that to explore the relationship between the expression of the two molecular markers and laryngeal cancer tissue microvascular density (MVD). METHOD: Immunohistochemical method was employed to detect the expression of CD68 and MMP-7 in 65 cases (laryngeal squamous carcinoma tissue in 45 cases; peritumoral nontumor tissue in 20 cases) and CD 34 antibody marked MVD expression. RESULT: CD68 positive rate in squamous carcinoma tissue (82.2%, 37/45) is obviously higher than that in the peritumoral tissue (15%, 3/20) (P < 0.05), and MMP-7 positive rate in squamous carcinoma tissue is significantly different from that in peritumoral tissue (71.1%; 25%) (P < 0.05). The expression rate of CD34-MVD in laryngeal squamous carcinoma tissue( 26.52 +/- 6.36 )is higher than that in peritumoral tissue (12.23 +/- 4.01) (P < 0.05). In lymph node metastasis group, the positive expression rates of CD68 and MMP-7 are higher than those in the group without lymph node metastasis. MMP-7 showed no correlation with cancer stage, and CD68 was related with cancer stage; CD68, MMP-7 and CD34- MVD have positive correlation. CONCLUSION: The high level of expression of TAMs and MMP-7 in laryngeal cancer tissue and the positive correlation with MVD illustrate that both of the markers play important roles in promoting laryngeal squamous carcinoma tissue metastasis and angiogenesis, which can be used as important markers to evaluate the invasion and metastasis of laryngeal cancer.