Sodium para-aminosalicylic acid attenuates combined manganese/iron-induced cortical synaptic damage in rats.

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Factors associated with the efficacy of mature oocyte production after dual-trigger controlled ovarian stimulation using a GnRH antagonist protocol.

BACKGROUND: The number of mature oocytes retrieved plays a significant role in determining embryo development and pregnancy outcomes of in vitro fertilization (IVF). However, studies investigating factors predictive of the efficacy of mature oocyte production (EMOP) after dual-trigger controlled ovarian stimulation (COS) are rare. This study aims to identify key predictors of EMOP during dual-trigger COS with a gonadotropin-releasing hormone (GnRH) antagonist protocol for IVF. METHODS: This retrospective cohort study included 359 first-time IVF patients undergoing dual-trigger COS with a GnRH antagonist protocol. EMOP was defined as the ratio of metaphase II (MII) oocyte count to antral follicle count (AFC). Based on EMOP results, patients were divided into two groups: group A (EMOP <70%; n = 232) and group B (EMOP ≥70%; n = 127). RESULTS: Multivariate logistic regression analysis revealed that day-2 follicle-stimulating hormone (FSH), stimulation duration, and total oocyte count were the most significant predictors of EMOP ( p < 0.05; odds ratios: 1.637, 3.400, and 1.530, respectively). Receiver operating characteristic analysis demonstrated that total oocyte count <9.5 (area under the curve [AUC], 0.782; sensitivity, 76.2%; specificity, 69.2%; p < 0.001) and stimulation duration <9.5 days (AUC, 0.725; sensitivity, 63.5%; specificity, 66.7%; p < 0.001) significantly predicted EMOP <70%. Stimulation duration combined with total oocyte count exhibited the highest power in predicting EMOP <70% (AUC, 0.767; sensitivity, 92.3%; specificity, 42.4%). CONCLUSION: Stimulation duration combined with total oocyte count was identified as the most important factor associated with the EMOP during dual-trigger COS in IVF using a GnRH antagonist protocol.

Nomogram incorporating potent inflammatory indicators for overall survival estimation of patients with primary oral squamous cell carcinoma.

Background: Inflammation has been recognized to be a factor that substantially influences tumorigenesis and tumor prognosis. Hence, this study was aimed to investigate an inflammatory marker with the most potent prognostic ability and to evaluate the survival estimation capability of dynamic change in this marker for patients suffered from oral squamous cell carcinoma (OSCC). Methods: 469 patients' inflammatory indicators including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory response index (SIRI), were calculated. Their predictive abilities for overall survival (OS) were evaluated by Kaplan-Meier curves to screen for the one with the most potent prognostic value. The predictive ability of dynamic changes in this marker was verified and a predictive nomogram incorporating inflammatory indicators was developed. Results: A high LMR was identified to be an indicator of a satisfactory survival rate. Compared with that of other inflammatory markers, area under the receiver operating characteristics (ROC) curve (AUC) of LMR for 1-year and 3-year OS was significantly larger (P<0.001). Dynamic LMR change remained an significant parameter for predicting OS (OR: 2.492, 95% CI: 1.246-4.981, p = 0.010). The nomogram incorporating LMR exhibited a superior prognostic significance than the TNM system, as suggested by the C-index (0.776 vs 0.651 in primary cohort; 0.800 vs 0.707 in validation cohort, P<0.001) and AUC. Conclusions: LMR was demonstrated to possess a more potent survival estimation capability than the other three inflammatory parameters. Dynamic changes in LMR serves as a significant parameter for overall survival estimation of primary OSCC patients. The established nomogram incorporating inflammatory markers showed more accuracy and sensitivity for survival estimation of primary OSCC patients.

Protective Effects of Sodium Para-Aminosalicylic Acid on Lead and Cadmium Co-Exposure in SH-SY5Y Cells.

BACKGROUND: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. METHODS: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. RESULTS: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 µmol/L lead, 0.25 µmol/L cadmium, and 1-fold Pb-Cd mixture (1 µmol/L Pb + 0.25 µmol/L Cd), while 10-fold Pb-Cd combined exposure (10 µmol/L Pb + 2.5 µmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 µmol/L Pb + 2.5 µmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. CONCLUSION: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.

Endometrial L-selectin ligand is downregulated in the mid-secretory phase during the menstrual cycle in women with adenomyosis.

OBJECTIVE: Defects in L-selectin ligand (LSL) expression have been reported to cause implantation failure, but little is known about LSL expression in adenomyosis. This study evaluates LSL expression throughout the menstrual cycle in women with adenomyosis. MATERIALS AND METHODS: Endometrial samples were obtained from reproductive-aged women with adenomyosis who underwent hysterectomy. A total of 42 endometrial biopsies were included. There were 12 women in proliferative phase, 10 in early-secretory phase, 9 in mid-secretory phase, and 11 in late-secretory phase. Immunohistochemistry, western blotting, and RT-PCR were performed to evaluate LSL expression. A non-parametric Kruskal-Wallis one-way analysis of variance with multiple comparisons was performed to examine differences among menstrual phases. RESULTS: Immunohistochemistry analysis with MECA-79 shows that LSL is expressed with weak intensity in the endometrium in all phases. In the luminal epithelium, MECA-79 reactivity increased from the proliferative to the late-secretory phase but decreased in the mid-secretory phase. There were significant differences in the mean histological scores (HSCOREs) among the proliferative, early-secretory, and late-secretory phases (p < 0.05). Five LSL genes were detected in the adenomyotic endometria: PODXL, EMCN, CD300LG, GLYCAM1, and CD34. The mRNA expression of LSL genes occurred differentially among phases. Moreover, PODXL differed significantly among phases (p < 0.05). CONCLUSIONS: LSL expressions were downregulated in the luminal epithelium of adenomyotic endometria in the mid-secretory phase. The mRNA expressions of LSL genes also had differential expression patterns throughout the menstrual cycle, especially for PODXL. Our study showed that adenomyosis may cause abnormalities of LSL production in the mid-secretory phase, which may contribute to impaired endometrial receptivity and implantation failure.

Gene expression of human endometrial L-selectin ligand in relation to the phases of the natural menstrual cycle.

This study investigates peptide components of L-selectin ligand (LSL) and their gene expressions in human endometrium during the natural menstrual cycle. We recruited 41 endometrial samples from reproductive-aged women with leiomyoma and undergoing hysterectomy and 11 endometrial samples from menopausal women as controls. Immunohistochemistry revealed strong MECA-79 expression from the early through the mid-secretory phase and low expression in menopausal endometrium. Five peptide components of LSL were detected in reproductive and menopausal endometrium by one-step quantitative RT-PCR: podocalyxin, endomucin, nepmucin, GlyCAM-1, and CD34. Endomucin differed significantly between the proliferative and early-secretory phases. CHST2 and CHST4 genes (which are involved in the generation of LSL epitopes) were expressed without significant differences among phases. The gene expression of progesterone receptor decreased from the proliferative to the late-secretory phase, and the difference was significant. However, estrogen receptor α expression showed stability among phases. The significant expression of endomucin between the proliferative and early-secretory phases might play a vital role in endometrial receptivity. Further studies are needed to investigate the factors that regulate the expression of endomucin and other LSL peptide components in different phases of the menstrual cycle.

[Effects of Different AM Fungi on Quantity and Enzyme Activity of Rhizosphere Soil Microorganism of Paris polyphylla var. yunnanensis].

Objective: To investigate the rhizosphere soil microorganism and enzyme activity after Paris polyphylla var. yunnanensis inoculated Arbuscular Mycorrhizal( AM) fungi,which provide the technological condition for artificial cultivation of Paris polyphylla var. yunnanensis. Methods: By the method of combining the greenhouse pot inoculation trials with laboratory analysis, The effects of inoculation with 28 AM fungi on rhizosphere soil microorganism and soil enzyme activities of Paris polyphylla var. yunnanensis under sterilized soil conditions were observed. Results: There were certain mutualistic selection between Paris polyphylla var. yunnanensis and AM fungi. After induction treatment with AM fungi, different AM fungi had various effects on the quantity, microbial biomass carbon and soil enzyme activities of rhizosphere soil microorganism of Paris polyphylla var. yunnanensis. With application of AM fungi,the amount of culturable fungi from rhizosphere soil of Paris polyphylla var. yunnanensis were decreased,while the culturable bacteria and actinomycetes showed a rising trend,and increased the diversity index,the content of biomass carbon and protease,urease,phosphatase,catalase and invertase activities of rhizosphere soil microorganism. Conclusion: Applying AM fungi when artificial cultivate Paris polyphylla var. yunnanensis,by which can impel rhizosphere microorganism of Paris polyphylla var. yunnanensis to transform from low-fertile"fungus types"to high-fertile"bacterial forms",and raise fungi diversity and enzymatic activity of rhizosphere soil microorganism,it is helpful to maintain the stability and harmoniousness of microecosystem on rhizosphere of Paris polyphylla var. yunnanensis,which certify the efficiency and the possibility of spreading AM inoculum during artificial cultivation in the field.

Study on temporary resolution for offshore marine oil spill emergencies based on remote sensing system.

Time is particularly critical for an oil spill occurring in the ocean as wind and current can rapidly spread the oil over a large area in a short time. Using the features of sensor surveillance system and mathematical trajectory models, the cooperation of surveillance and trajectory under oil spill emergency response is presented in this paper. Based on integration of equation simulating an oil spill trajectory, the method for remote-sensing application time (Te) has been described, and optimization of processing time described in the application time equation has been proposed. This contribution, which is integrated with remote-sensing and mathematical models, is expected to be a powerful tool for real-time contingency planning in the Dalian Xingang oil spill. According to these findings, the method allowed spills emergency alerts to make the best decision for choosing remote-sensing data, considering effective temporary resolution.

Luminescent 2D bismuth-cadmium-organic frameworks with tunable and white light emission by doping different lanthanide ions.

The first luminescent Bi-Cd-organic framework, Bi2Cd(2,6-pdc)4(H2O)2·H2O (2,6-H2pdc = pyridine-2,6-dicarboxylate), has been synthesized by using bismuth (Bi) oxides and cadmium (Cd) salts as metal sources under hydrothermal conditions. Tunable and white light luminescence was obtained through the doping of different Ln(3+) ions into the Bi-Cd-organic framework.