Impact of the intensive psychological intervention care on post-traumatic stress disorder and negative emotions of teenage female patients seeking an induced abortion.

Aim: This study aimed to investigate the effects of intensive psychological intervention care on adverse emotions and post-traumatic stress disorder (PTSD) symptoms in female teenage patients after induced abortion. Methods: This prospective cohort study included 100 teenage female patients seeking induced abortion who were randomly divided into two groups: the intervention group (n = 50) and the control group (n = 50). The intervention group received intensive psychological intervention care, while the control group received standard routine nursing. The scores of the PTSD checklist for DSM-5 (PCL-5), self-rating depression (SDS), and self-rating anxiety scale (SAS) were compared between the two groups at 1 month and 3 months after the operation. Results: The intervention group had lower risk of developing PTSD (24% vs. 44%), depression (10% vs. 32%), and anxiety (0% vs. 12%) symptoms at 1 month after the surgery. However, there were no significant differences observed between the two groups at 3 months after the surgery. Furthermore, the intervention group had significantly lower scores in PCL-5 (27.4 ± 5.4 vs. 31.8 ± 5.7; 20.5 ± 7.1 vs. 25.0 ± 7.5; p < 0.05), SDS (31.8 ± 5.4 vs. 37.8 ± 6.6; 26.8 ± 5.0 vs. 31.4 ± 7.2; p < 0.05), and SAS (32.7 ± 5.0 vs. 39.8 ± 6.9; 25.0 ± 2.7 vs. 27.5 ± 2.8; p < 0.05) at 1 month and 3 months after induced abortion. Conclusion: These findings suggest that intensive psychological intervention care can reduce the incidence and severity of depression, anxiety, and PTSD symptoms in teenage patients who undergo induced abortion. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=185200, identifier ChiCTR2300067531.

Organocatalytic Asymmetric Construction of Tetrasubstituted Carbon Stereocenters Bearing Three Heteroatoms via Intramolecular Cyclization of Vinylidene ortho-Quinone Methide with Imidates.

We report herein an organocatalytic asymmetric protocol for the construction of tetrasubstituted carbon stereocenters bearing three heteroatoms. The reaction proceeded via the enantioselective intramolecular cyclization reaction of vinylidene ortho-quinone methide (VQM) with imidates to form pentacyclic heterocycles. The formed tetrasubstituted carbon center was stable under a high temperature and the conditions for further transformations.

Manganese exposure caused reproductive toxicity of male mice involving activation of GnRH secretion in the hypothalamus by prostaglandin E2 receptors EP1 and EP2.

Exposure to manganese (Mn) can cause male reproductive damage and lead to abnormal secretion of sex hormones. Gonadotropin-releasing hormone (GnRH) plays an important role in the neuromodulation of vertebrate reproduction. Astrocytes can indirectly regulate the secretion of GnRH by binding paracrine prostaglandin E2 (PGE2) specifically to the EP1 and EP2 receptors on GnRH neurons. Prior studies assessed the abnormal secretion of GnRH caused by Mn exposure, but the specific mechanism has not been reported in detail. This study investigated the effects of Mn exposure on the reproductive system of male mice to clarify the role of PGE2 in the abnormal secretion of GnRH in the hypothalamus caused by exposure to Mn. Our data demonstrate that antagonizing the EP1 and EP2 receptors of PGE2 can restore abnormal levels of GnRH caused by Mn exposure. Mn exposure causes reduced sperm count and sperm shape deformities. These findings suggest that EP1 and EP2, the receptors of PGE2, may be the key to abnormal GnRH secretion caused by Mn exposure. Antagonizing the PGE2 receptors may reduce reproductive damage caused by Mn exposure.

Prepubertal overexposure to manganese induce precocious puberty through GABAA receptor/nitric oxide pathway in immature female rats.

Gamma-aminobutyric acid (GABA) plays a critical role in regulation of gonadotropin-releasing hormone (GnRH) through GABAA receptor (GABAAR). Nitric oxide (NO) production has correlation with GABA and regulates GnRH secretion. This study was performed to examine the mechanisms by which manganese (Mn) accelerate puberty onset involves GABAAR/NO pathway in the preoptic area-anterior hypothalamus (POA-AH) in immature female rats. First, female rats received daily dose of MnCl2 0 (saline), 2.5, 5 and 10 mg/kg b.w by oral gavage during postnatal day (PND) 21-32. Animals administered with 10 mg/kg MnCl2 exhibited earlier puberty onset age and advanced ovary and uterus development than these in saline-treatment group. Furthermore, we found that decrease of GABAAR result in elevated production of nitric oxide synthase1 (NOS1), NO and GnRH in the POA-AH. Second, we recorded the neuronal spikes alternation after perfusion with GABAAR inhibitor bicuculline (BIC), GABAAR agonist isoguvacine (isog), and MnCl2 from the POA-AH in acute brain slices of PND21 rats. Spontaneous firing revealed a powerful GABAAR-mediated action on immature POA-AH and confirm that MnCl2 has a significant effect on GABAAR. Third, we revealed that decrease in NOS1 and NO production by treatment with isog-alone or isog+MnCl2 contribute to the decrease of GnRH in the POA-AH and a delayed puberty onset age compared to treatment with MnCl2-alone. Together, these results suggested that excessive exposure to MnCl2 stimulates NO production through decreased GABAAR in the POA-AH to advance puberty onset in immature female rats.

The effect of manganese exposure on GnRH secretion via Nrf2/mGluR5/COX-2/PGE2/signaling pathway.

There are limited studies focused on the precise mechanism of gonadotropin-releasing hormone (GnRH) secretion dysfunction after overexposure to manganese (Mn). The objective of the present study was to explore the mechanism of Mn disruption of GnRH synthesis via nuclear factor erythroid-2-related factor-2 (Nrf2)/metabotropic glutamate receptor-5 (mGluR5)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signaling pathway in vitro and in vivo. Primary astrocytes were cultured and treated with different doses of Mn, tert-butylhydroquinonet (tBHQ; Nrf2 agonists), 3-[(2-methyl-4-thaizolyl) ethynyl] pyridine (MTEP; mGluR5 inhibitor), and celecoxib (COX-2 inhibitor) to measure the levels of COX-2, mGluR5, Nrf2, and Nrf2 target genes. Mice were randomly divided into 11 groups, of which included the control group, 12.5-, 25-, and 50-mg/kg MnCl2 group, dimethyl sulfoxide (DMSO) group, tBHQ control group, tBHQ pretreatment group, MTEP control group, MTEP pretreatment group, celecoxib control group, and celecoxib pretreatment group. The injection was administered every day for 2 weeks. Then, levels of GnRH, PGE2, COX-2, mGluR5, Nrf2, Nrf2 target genes, and morphological changes in the hypothalamus of mice were measured. Mn reduced protein levels of Nrf2 and mRNA expression of Nrf2 target genes and increased mGluR5, COX-2, PGE2, and GnRH levels. Meanwhile, injury-related histomorphology changes in the hypothalamus of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GnRH secretion through Nrf2/mGluR5/COX-2/PGE2 signaling pathway.

Occupational manganese exposure, reproductive hormones, and semen quality in male workers: A cross-sectional study.

It has been found that exposure to manganese (Mn) could induce reproductive dysfunction, but its occupational risk in male workers is unclear. This study aims to assess the association of occupational Mn exposure with reproductive hormones and semen quality in a cross-sectional study. Urinary Mn, semen quality, and reproductive hormones were explored in 84 male workers occupationally exposed to Mn and 92 referents. Multiple linear regression analyses were used to assess the relationship. Urinary Mn levels in Mn-exposed workers ranged from 0.56 to 34.25 µg/L, and the average level was 15.92 ± 8.49 µg/L. Compared with the control group, gonadotropin-releasing hormone (GnRH) levels and luteinizing hormone (LH) levels increased significantly and the levels of testosterone (TSTO) decreased significantly in the Mn-exposed group. There was a significant positive linear association between urinary Mn and GnRH and LH, while the linear association between urinary Mn and TSTO was negative. Sperm progressive motility and total motility decreased significantly in the Mn-exposed group. There was a significantly negative linear association between urinary Mn and sperm progressive motility and total motility. In conclusion, occupational Mn exposure was inversely associated with reproductive health of male workers, resulting in the abnormality of hormones secretion and decrease of sperm motility.

Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice.

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.