The latest medical research on Clinical Immunology
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Request AccessExploring the Molecular Interaction Between NR2E3 and NR1D1 in Retinitis Pigmentosa: A Docking and Molecular Dynamics Study.
Clinical LaboratoryRetinitis pigmentosa (RP) is a hereditary retinal disorder that gradually leads to vision loss due to photoreceptor cell degeneration. This study aims to investigate the clinical features and genetic underpinnings of RP within a large Iranian family. Our focus centered on mutations in the NR2E3 gene, which plays a critical role in the development and maintenance of the retina.
Twenty-five family members showed symptoms of RP, and fourteen of them underwent clinical examinations conducted by geneticists and ophthalmologists. The DNA samples of five individuals diagnosed with RP from the family were subjected to whole-exome sequencing (WES) as part of the study. The candidate variant identified through WES was subsequently confirmed using bidirectional sequencing in additional family members. Additionally, in silico analysis, including molecular modeling, protein-protein docking, and molecular dynamics simulation (MD), was employed to assess potential pathogenic effects associated with the candidate variants.
Ophthalmic examination revealed night blindness, which is a common symptom among affected individuals. Genetic analysis identified a homozygous missense variant (c.934G>A/p.R311Q) in NR2E3 exon 6, which co-segregates with other affected family members. Furthermore, molecular docking analysis indicated potential disruption in the binding affinity between NR2E3 and NR1D1 proteins. In-depth, molecular dynamics analysis, considering parameters such as RMSD, RMSF, and hydrogen bonding, revealed notable differences between normal and mutant protein complexes.
Exploring the molecular interaction between NR2E3 and NR1D1 provides new insights into the pathogenic mechanism of the p.R311Q mutation in RP.
Cell Communications Between GCs and Macrophages Contribute to the Residence of Macrophage in Preovulatory Follicles.
American Journal ofThere were not only granulosa cells (GCs) but also immune cells in preovulatory follicular fluid. The objective of this study was to explore the interactions between macrophages and GCs via adhesion molecules in preovulatory follicles and the regulatory mechanisms of the interactions.
Flow cytometry and immunofluorescence were used to detect the expression of ITGB1 in macrophages and fibronectin (FN)1 in GCs in preovulatory follicles from 12 patients. The synthesis of FN1 protein in human ovarian GCs line (KGN) was detected by western blot. An adhesion experiment was performed to observe the changes of KGN cells adhesion to macrophages.
The progesterone levels 12 h after human chorionic gonadotropin (HCG) administration in the high proportion immune cells (high immune [HI]) group were significantly higher than that in the low proportion immune cells (low immune [LI]) group (p < 0.0001). The expression of ITGB1 in macrophages in the HI group was higher than in the LI group. The expression of FN1 in GCs in HI group was higher than in LI group (p < 0.01). Progesterone increased the synthesis of FN1 in KGN cells (p < 0.0001) and was suppressed by the elimination of PGR. The adhesion effect of KGN cells on macrophages was enhanced by progesterone (p < 0.0001).
After luteinizing hormone (LH)/HCG surge, progesterone promotes the expression of FN1 in GCs by acting on the receptor PGR, and then GCs enhance the adhesion of macrophages by FN1-ITGB1 interaction, further leading to the result that macrophages perform diverse functional activities to maintain tissue homeostasis during ovulation.
Impact of Omicron Variant Infection on Female Fertility and Laboratory Outcomes: A Self-Controlled Study.
American Journal ofInvestigating the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on female fertility and laboratory outcomes in patients undergoing assisted reproductive technology (ART) treatment who were initially uninfected but later became infected.
This self-controlled study included 197 patients who underwent repeated oocyte retrieval before and after SARS-CoV-2 infection between March 2021 and April 2023, of which 117 used the same ovarian stimulation protocol within a consistent age range. We evaluated the ovarian reserve, ovarian response, and laboratory outcomes in patients before and after SARS-CoV-2 infection.
The ovarian reserve (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estrogen [E2], anti-Müllerian hormone [AMH], antral follicle count [AFC]), ovarian response (total Gn dosage, duration of Gn administration, number of follicles ≥14 mm on trigger day, number of retrieved oocytes), and laboratory outcomes (cleavage stage good-quality embryo rate, blastocyst formation rate, and cycle freezing rate) showed no significant differences before and after SARS-CoV-2 infection in 117 patients (p > 0.05). When stratified by age, the ≤ 35 years group showed a higher two pronuclei (2PN) fertilization rate post-infection, while the >35 years group had increased mature metaphase II (MII) oocyte and blastocyst stage good-quality embryo rates. Additionally, upon stratified by the time interval between SARS-CoV-2 infection and ART treatment, in the ≤ 3 months group, there was an increased post-infection MII oocyte rate, 2PN fertilization rate, and blastocyst stage good-quality embryo rate. Meanwhile, no significant differences were found in any indicators when the interval exceeded three months.
Our study suggested that undergoing IVF/ICSI treatment after recovering from COVID-19 may not adversely affect female fertility and laboratory outcomes.
Impact of Overweight on Renal Prognosis in Malignant Hypertension Patients With Thrombotic Microangiopathy.
Clinical LaboratoryOverweight and obesity is a risk factor for hypertension. Malignant hypertension (MHT) is the most severe form of hypertension, and thrombotic microangiopathy (TMA), one of its complications, has been linked to significant renal outcomes. However, the impact of overweight and obesity on renal prognosis in MHT patients with TMA is not well understood.
This was a prospective cohort enrolled 288 MHT patients with renal TMA from 2008 to 2023. The clinical and histopathological characteristics were recorded based on body mass index (BMI, < 25 and ≥ 25 kg/m2). The outcome was the incidence of kidney failure. The associations of BMI with kidney failure were examined in logistic regression models.
Among 288 patients, 180 (62.5%) progressed to kidney failure, including 113 (68.5%) patients with BMI < 25 kg/m2. Participants with obesity had higher levels of hemoglobin, estimated glomerular filtration rate and C3, but lower levels of serum creatinine and IgA nephropathy. BMI ≥ 25 kg/m2 was associated with a better outcome of kidney failure in MHT patients with TMA (odd ratios [ORs]: 0.49 [95% confidence interval (CI): 0.27-0.91], p = 0.025). Male, uric acid, onion skin lesions, and global sclerosis ratio were correlated with higher risk of kidney failure; serum albumin and treatment with renin-angiotensin system blockers were related to lower risk of kidney failure.
In MHT patients with renal TMA, normal-weight rather than overweight was found to associate with a worse renal prognosis. Management efforts for MHT may be directed toward controlling body weight within a reasonable range for patients.
Immune Thrombocytopenic Purpura and Maternal and Neonatal Outcomes During Pregnancy: A Systematic Review and Meta-Analysis.
American Journal ofImmune thrombocytopenic purpura (ITP) affects 1-3 out of every 10 000 pregnancies, posing significant risks to both mothers and newborns. The condi...
Pregnancy Outcomes in Grand Multiparity Women With Antiphospholipid Antibodies.
American Journal ofIn recent years antiphospholipid syndrome (APS) as well as antiphospholipid antibodies (aPL) prevalence has demonstrated an upward trend in women during reproductive age. There is a lack of data concerning its effects on women with grand multiparity (GMP) (parity ≥5). Hence, this study aimed to assess pregnancy outcomes among GMP aPL/APS patients.
We retrospectively assembled the births of GMP women with aPL/APS, between 2017 and 2022 in the Sheba Medical Center. We compared their deliveries with those of two control groups: (1) the "aPL/APS-controls"-of pregnant women with aPL/APS and parity <5. (2) The "GMP-controls"- parity ≥5 without aPL/APS. We examined demographics, aPL characteristics, pregnancy, and neonatal outcomes between the groups.
In total, 42 deliveries in the study group were compared to 461 deliveries in the "aPL/APS-controls" group and 84 deliveries of the "GMP-controls." Most parameters were similar across groups. However, the study group had a higher rate of obstetric APS diagnosis (64.64% vs. 83.33%, p < 0.01) and showed significant differences such as older maternal age, higher BMI, more polyhydramnios cases, and larger babies compared to controls (33.91 vs. 36.19, p = 0.05; 23.2 vs. 28.89, p = 0.02; 3.68 vs. 11.9, p = 0.01; and 2.17 vs. 14.28, p < 0.01, respectively).
Our findings reveal that perinatal outcomes in aPL/APS GMP women are comparable and not inferior to those in aPL/APS women with <5 pregnancies or in comparison to the general GMP population. The minor differences observed may all be related to GMP women's older age and higher BMI.
SR-16234, a Unique Selective Estrogen Receptor Modulator, Suppressed Proliferation and Pain-Related Factor Expression by Inhibition of the Nuclear Factor-kappa B Pathway in Endometriotic Stromal Cells.
American Journal ofWhat is the effect of SR-16234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?
Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)-α. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST-8 assay. The gene expressions of inflammatory and pain-related factors, including interleukin (IL)-6, IL-8, cyclooxygenase (COX)-2, transient receptor potential vanilloid (TRPV)1, ESR1, and ESR2, were evaluated by real-time RT-PCR. The phosphorylation of Inhibitor κBα (IκBα), extracellular signal-regulated kinase (ERK)1/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.
SR treatment repressed TNF-α-induced proliferation by 20% in ESCs but not NESCs. SR also reduced IL-6, IL-8, COX-2, TRPV1, ESR1, and ESR2 mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only TRPV1 mRNA expression was decreased. SR suppressed TNF-α-induced phosphorylated IκBα levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF-α in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1/2.
SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.
Vaginal Microbiome and the Risk of Preterm Birth in Women Living With HIV: A Scoping Review.
American Journal ofThere are sparse data on the role of the vaginal microbiome (VMB) in pregnancy among pregnant women living with HIV (PWLWH) and its association wit...
Altered Endometrial Microbiota Profile Is Associated With Poor Endometrial Receptivity of Repeated Implantation Failure.
American Journal ofTo gain insight into the endometrial pathophysiology of unexplained repeated implantation failure (RIF), we examined the characteristics of genital tract microbiota and explored the correlation between the microbiota and endometrial receptivity.
Vaginal secretion (VS) and endometrial biopsy (EB) samples were collected from patients with RIF (RIF group, n = 32) and those with infertility who had achieved pregnancy during their initial embryo transfer cycle (control group, n = 18). 16S ribosomal RNA sequencing and quantitative PCR were performed to characterize the microbiota of the two groups. Spearman's correlation analysis was performed to determine the relationship between endometrial receptivity markers and endometrial microbiota.
Endometrial microbiota exhibited distinct characteristics from vaginal microbiota, with a higher alpha-diversity. Alpha-diversity of the endometrial microbiota was higher in the RIF group than in the control group. Compared with the control group, the RIF group had a significant decrease in endometrial Lactobacillus abundance and an increase in Gardnerella and Acinetobacter abundances. The expression levels of endometrial receptivity markers, including homeobox A11, integrin αvβ3, leukemia inhibitor factor, matrix metalloproteinase-9, and vascular endothelial growth factor, were lower in the RIF group than in the control group. Moreover, the expression levels of these markers were correlated with endometrial Lactobacillus, Gardnerella, and Acinetobacter abundances.
RIF is characterized by endometrial microbiota dysbiosis and poor endometrial receptivity. Moreover, abnormal endometrial microbiota is associated with impaired endometrial receptivity, which may be a potential cause of unexplained RIF.
Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies.
American Journal ofAntiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs.
The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared.
The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6% vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4% vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance.
The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs.
Protein Modifications During Early Embryo Development.
American Journal ofInfertility is a global reproductive health burden. Assisted reproductive technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop to the blastocyst stage with ARTs, leading to relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including reproductive processes. The aim of this study was to explore the characteristics of protein modifications during embryonic development.
Proteomic data from humans and mice were acquired from the integrated proteome resources (iProX) of ProteomeXchange (PXD024267) and a tandem mass tag (TMT)-mass spectrometry dataset. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for functional annotation. Protein-protein interactions (PPIs) of the modification-related genes were revealed by the STRING database. Modified proteins during mouse embryogenesis were visualized through heatmaps of hierarchically clustering using k-means.
We identified modification-related proteins in human embryo development and characterized them through heatmaps, GO analysis, KEGG analysis, and PPI network analysis. We found that the 4-cell stage to the 8-cell stage might be the demarcation period for modification-related protein expression patterns during embryo development. Using quantitative mass spectrometry, we elucidated the methylation, acetylation, and ubiquitination events that occur during mouse embryogenesis to validate our findings in human embryonic development to some extent.
The results of our study suggest that the posttranslational modifications (PTMs) of human preimplantation embryos might exhibit the same trends as those in mice to exert synergistic and fine-tuned regulatory effects during embryonic development.
Autoimmune Condition Diagnosis Following Recurrent Pregnancy Loss.
American Journal ofResearch has suggested a link between recurrent pregnancy loss (RPL) and cell-mediated immunity dysregulation. We aimed to determine if a history of RPL is associated with diagnosis of a cell-mediated autoimmune condition (AIC).
A retrospective cohort study was conducted using the TriNetX research network. The RPL group had ≥3 spontaneous or missed abortions. Controls had at least one pregnancy but no diagnosis of RPL. Propensity score matching was used for age, race, and ethnicity. Z-test and relative risk analysis investigated the relationship between RPL and subsequent AIC diagnoses.
One hundred twenty-eight thousand three hundred seventy-six patients were included in each cohort. RPL was associated with an increased risk for an AIC composite (RR 1.60, 95% CI [1.51, 1.69]), Crohn's disease, Graves' disease, Hashimoto's thyroiditis, multiple sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and ulcerative colitis, but not psoriatic arthritis.
Using a large research database of patients with RPL, we were able to demonstrate that an antecedent diagnosis of RPL is associated with increased risk of subsequent diagnosis of an AIC, often between 1 and 10 years after RPL.
