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1.
J Reprod Immunol ; 163: 104218, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38422808

ABSTRACT

This study aimed to evaluate the effectiveness of the endometrial receptivity array (ERA), endometrial immune profiling, and a combination of both in improving the pregnancy outcomes for multiple implantation failure patients. According to patients' willingness, 1429 women who incurred at least two or more consecutive implantation failures in IVF/ICSI treatment opted for frozen embryo transfer and were divided into four groups: 'No test', 'Immune Profiling', 'ERA' and 'ERA+ Immune Profiling'. Women in three test groups underwent timed endometrial biopsy for ERA, immune profiling, a combination of both. We observed the overall incidence rates of the displaced window of implantation (WOI) and endometrial immune dysregulation were 75.14% and 79.29%, respectively. After 1:1 propensity score matching (PSM), our data revealed that the 'ERA' and 'ERA + Immune Profiling' groups demonstrated significantly higher rates of biochemical, clinical, ongoing pregnancy, and implantation compared to the 'No test' group (p < 0.01). The 'Immune Profiling' group showed a higher implantation rate compared to 'No test' group (p < 0.05). Furthermore, when comparing three test groups, the 'ERA + Immune Profiling' group exhibited notably higher rates of clinical and ongoing pregnancy compared to the 'Immune Profiling' group (p < 0.017). However, there was no association between endometrial immune profiling and ERA phases, and their results did not differ between embryo implantation and non-implantation in these patients. Our findings underline the increased implantation rates by use of ERA and endometrial immune profiling in patients with multiple implantation failure, either individually or corporately. Moreover, a combination of both could improve their pregnancy outcomes significantly.


Subject(s)
Embryo Implantation , Embryo Transfer , Endometrium , Fertilization in Vitro , Propensity Score , Humans , Female , Endometrium/immunology , Endometrium/pathology , Pregnancy , Embryo Implantation/immunology , Adult , Retrospective Studies , Embryo Transfer/methods , Fertilization in Vitro/methods , Pregnancy Outcome , Pregnancy Rate
2.
Int Immunopharmacol ; 110: 108930, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35764020

ABSTRACT

Unexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions in the reproductive field, and macrophage M1/M2 polarization disorder is involved in URSA pathogenesis, although the relevant mechanisms are undefined. miR-146a-5p possesses an immunoregulatory role and is expressed in decidual immune cells, and this study aims to investigate its effect on decidual macrophage polarization and therapeutic prospects in URSA, which has never been reported. The levels of M1/M2 markers in the deciduae and the miR-146a-5p expression in the decidual macrophages of URSA and healthy pregnant women were first detected and analyzed. Then, the in vitro effect of miR-146a-5p on the M1/M2 polarization and the secretion of inflammatory cytokines was investigated in Tamm-Horsfall protein-1 (THP-1)-induced macrophages. Finally, the in vivo immunotherapeutic effect of miR-146a-5p on embryo survival and the potential mechanisms were evaluated in a murine model of immune-based URSA. As a result, the abnormal M1/M2 polarization, which showed a shift towards the M1 phenotype and correlated with the decreased expression of miR-146a-5p, was verified in human URSA decidual macrophages. miR-146a-5p could inhibit M1 polarization, promote M2 polarization, and result in an anti-inflammatory microenvironment in THP-1-induced macrophages. The intravenous injection of exogenous miR-146a-5p in the first trimester of pregnant URSA mice significantly reduced the embryo resorption rate and promoted the M2 polarization of decidual macrophages. In conclusion, miR-146a-5p enhances embryo survival in URSA by promoting decidual macrophage polarization toward an M2 phenotype, giving new ideas and potential targets for subsequent research on the pathogenesis and immunotherapeutic strategies of URSA.


Subject(s)
Abortion, Habitual , MicroRNAs , Abortion, Habitual/metabolism , Animals , Cytokines/metabolism , Female , Humans , Macrophage Activation/genetics , Macrophages , Mice , MicroRNAs/metabolism , Pregnancy
3.
Am J Reprod Immunol ; 87(3): e13513, 2022 03.
Article in English | MEDLINE | ID: mdl-34766396

ABSTRACT

PROBLEM: The clinical value of endometrial receptivity array (ERA), endometrial immune profiling, or a combination of both for multiple implantation failure patients is unclear. METHOD OF STUDY: One hundred and seventy-two women with a history of at least two or more consecutive implantation failures in IVF/ICSI treatment were included. According to patients' willingness, they were divided into four groups, 'no treatment', 'Immune Profiling', 'ERA' and 'ERA + Immune Profiling'. Endometrial biopsy was examined by ERA, immune profiling alone, or combination, and intention was adopted accordingly. Pregnancy outcomes were compared, and the association between ERA phases and endometrial immune profiling was also assessed. RESULTS: The overall incidence rate of the displaced window of implantation (WOI) and endometrial immune dysregulations were 84.9% and 75.3%, respectively. Implantation rate was significantly higher in the 'ERA + Immune Profiling' group than the 'no treatment' group (P = .007). Clinical pregnancy rate was somewhat improved in the three treatment groups but with a borderline significance (P = .071). After controlling for other confounders, 'ERA + Immune Profiling' treatment was associated with a higher pregnancy rate [aOR (95%CI)  = â€Š3.412 (1.387-8.395), P = .008]. There was no association between endometrial immune profiling and ERA phases. CONCLUSIONS: Our findings highlight the high incidence of displaced WOI and endometrial immune dysregulation in multiple implantation failure patients. The combination of ERA and endometrial immune profiling is more likely to have clinical value than ERA or immune profiling alone. These data suggested the unsubstitutability of ERA and endometrial immune profiling on the treatment outcome for multiple implantation failure patients.


Subject(s)
Embryo Transfer , Infertility, Female , Embryo Implantation , Embryo Transfer/methods , Endometrium/pathology , Female , Fertilization in Vitro/methods , Humans , Infertility, Female/pathology , Infertility, Female/therapy , Pregnancy , Pregnancy Rate
4.
Int Immunopharmacol ; 89(Pt B): 107066, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33059199

ABSTRACT

Spontaneous abortion (SA) is a common pregnancy failure, but the cause of numerous cases remains unexplained. Decidual immune cells (DICs)-mediated cytokine microenvironment is involved in pregnancy and regulated by many microRNAs, but whether microRNA-146a-5p (miR-146a) regulate the decidual cytokine microenvironment and the potential mechanisms in unexplained SA pathogenesis have rarely been reported. In this study, the levels of cytokines and miR-146a in healthy and unexplained SA deciduae were first investigated, and the correlation between them was analyzed. Then, the effect of miR-146a inhibitor on cytokines was assessed in healthy deciduae-derived DICs. Third, the downstream targets and related molecular mechanisms of miR-146a were analyzed by bioinformatics, and the levels of the predicted targets in deciduae were assessed, followed by the correlation analysis between the levels of miR-146a and the targets. Finally, the effect of miR-146a on the predicted targets and inflammatory cytokines was validated in unexplained SA deciduae-derived DICs. As a result, decreased miR-146a correlated with the cytokine disorder in unexplained SA deciduae, and inhibition of miR-146a promoted pro-inflammatory response in healthy deciduae-derived DICs. One hundred four target genes and related molecular mechanisms of miR-146a were predicted, among which the toll-like receptor (TLR) pathway might be associated with the decidual cytokine regulation. Upregulation of miR-146a inhibited the expression of the predicted molecules enriched in the TLR pathway and improved the cytokine disorder in unexplained SA deciduae-derived DICs. Collectively, miR-146a improves the decidual cytokine microenvironment by regulating the TLR pathway in unexplained SA, providing novel potential targets for further therapeutic research.


Subject(s)
Abortion, Spontaneous/metabolism , Cytokines/metabolism , Decidua/metabolism , Inflammation Mediators/metabolism , MicroRNAs/metabolism , Toll-Like Receptors/metabolism , Abortion, Spontaneous/genetics , Abortion, Spontaneous/immunology , Adult , Case-Control Studies , Cells, Cultured , Cellular Microenvironment , Cytokines/genetics , Decidua/immunology , Female , Gene Expression Regulation , Gene Regulatory Networks , Humans , MicroRNAs/genetics , Pregnancy , Protein Interaction Maps , Signal Transduction , Toll-Like Receptors/genetics
5.
Huan Jing Ke Xue ; 41(3): 1227-1235, 2020 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-32608624

ABSTRACT

To explore the effects of water quality improvement by artificial destratification and artificially-induced mixing, as well as realize the conditions of artificial mixing and natural mixing, the Lijiahe Reservoir was selected to monitor the indexes of water quality and hydrometeorology from June 2017 to April 2019 and to analyze the characteristics of variations in water temperature, dissolved oxygen, and pollutants during the natural and induced-mixing processes. The results demonstrated that:① The natural process had the features of a long period of thermal stratification and only a short period of mixing of about 2.5 months. Through the operation of water-lifting aerators (WLAs) during the induced-mixing process, the water body was completely mixed and entered the cooling period at the end of September, achieving the conditions of induced-natural mixing. The surface water temperature and average air temperature were 20.17℃ and 16.5℃, respectively, and the water body continued to be naturally mixed after the WLA system was shut down, which led to a natural mixing cycle of 5.5 months. ② During the natural-mixing process, the concentration of pollutants was relatively high in the whole period, and the concentration of surface pollutants in the mixing stage presented a trend of increasing first and then decreasing. The oxycline appeared with thermal stratification, and the anaerobic cycle in the bottom of water column reached 6 months. ③ Compared with the natural-mixing process, the hypolimnetic anaerobic condition was eliminated and the control effects of pollutants dominated during the induced-mixing process. Simultaneously, the concentrations of NH4+-N, TP, Fe, and Mn in the bottom of the water column were cut by 76.2%, 75.5%, 82.2%, and 82.1%, respectively, during the same period from October to March of the following year, and met the "Environmental Quality Standards for Surface Water". This study shows that the artificially-induced mixing process contributes to water quality improvement and mixing-period prolongation.

6.
Scand J Infect Dis ; 40(2): 121-6, 2008.
Article in English | MEDLINE | ID: mdl-17852901

ABSTRACT

The diagnosis of tuberculosis remains among public health concerns due to shortcomings of the purified protein derivative (PPD). Recombinant truncated 38 kDa protein (rTPA38) of Mycobacterium tuberculosis was evaluated to screen new tuberculosis-specific tuberculin. 539 patients, 1133 healthy controls, and 55 guinea pigs were recruited to assess their sensitivity and specificity to rTPA38; 221 healthy controls, with negative responses to rTPA38 and PPD, were vaccinated with M. bovis BCG to determine their cross-reactions with M. bovis BCG. The Mantoux technique was adopted to perform skin tests. No difference in the sensitivity of skin tests was detected between rTPA38 and PPD (78.2% vs 83.4%), but there was a significant difference in the specificity of skin tests between rTPA38 and PPD (75.2% vs 47.0%). Compared to PPD, rTPA38 elicited low positive responses for those recruitments vaccinated with M. bovis BCG. The rTPA38 had significant skin reactions in M. tuberculosis-sensitized guinea pigs, and the opposite was true for both M. fortuitum- and M. kansasii-sensitized guinea pigs. These findings indicate that rTPA38 may have potential as a tuberculosis-specific skin test antigen.


Subject(s)
Antigens, Bacterial/immunology , Lipoproteins/immunology , Mycobacterium bovis/immunology , Tuberculin Test/methods , Tuberculosis/diagnosis , Animals , Guinea Pigs , Humans , Nontuberculous Mycobacteria/immunology , Recombinant Proteins/immunology , Sensitivity and Specificity , Tuberculin/immunology , Tuberculosis/immunology
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