TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-κB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients.

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-ß, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikßα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses. MATERIALS AND METHODS: Ten OA patients' synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-ß, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikßα and pIkßα. RESULTS: The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-ß, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikßα which was increased by LPS treatment. CONCLUSION: According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.

Interferon-γ Induces Interleukin-6 Production and Alpha-smooth Muscle Actin Expression in Systemic Sclerosis Fibroblasts.

Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc.

Determination of IL-23 receptor expression and gene polymorphism (rs1884444) in Iranian patients with ankylosing spondylitis.

BACKGROUND: Through investigating genetic variations, it has been demonstrated that single nucleotide polymorphisms (SNPs) in the IL-23 receptor (IL23R) gene have a critical role in the pathophysiology of ankylosing spondylitis (AS). Here, we investigated whether the IL23R variant (rs1884444) is associated with AS in the Iranian population. METHODS AND MATERIAL: In this research, we analyzed rs1884444 in a group of 425 patients with AS and 400 matched controls. For DNA extraction, the phenol/chloroform technique was utilized. Peripheral blood mononuclear cells (PBMCs) were obtained from the whole blood of 39 patients and 43 healthy controls and total RNA was extracted. Genotyping was performed by amplification-refractory mutation system (ARMS)-PCR method. Afterward, the expression level of IL23R was analyzed by the real-time quantitative (Q)-PCR method. RESULTS: We observed no significant association between the distribution of alleles and genotypes of rs1884444 and susceptibility to AS. In addition, the expression level of IL23R did not differ between PBMCs from AS patients compared to the control group (P = 0.167). Furthermore, the relative expression level of IL23R was positively correlated with the BASDAI (P < 0.01) and BASFI (P < 0.05) scores of the patients. CONCLUSION: It appears that IL23R polymorphism (rs1884444) and the level of gene expression might not contribute to the susceptibility to AS in the Iranian population. The correlation of IL23R expression with the level of BASDAI and BASFI scores in patients may be due to the role of the IL-23/IL-23R signaling cascade in inflammation and exert a critical role in the development of AS.

The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients. METHOD: One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes. RESULTS: The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1Asn80 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls. CONCLUSION: Our results suggest that the presence HLA-C1Asn80 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.

Characterization of a novel TiF4 inclusion complex and its in vitro evaluation on inhibiting enamel demineralization.

Titanium tetrafluoride (TiF4) is an anticariogenic agent with high remineralizing potential. However, the acidic pH of TiF4 solution can limit its clinical application. Dendrimers have been reported to show promising remineralizing potentials. Thus, the present study aimed to prepare and characterize a new TiF4 dendrimer inclusion complex and evaluate its ability to inhibit enamel demineralization under pH cycling conditions. PEG-citrate dendrimer and TiF4-dendrimer inclusion complex were synthesized and their molecular structures were evaluated using FTIR, H NMR, and LC-MS tests. Forty-eight enamel samples were prepared randomly and divided into four groups: distilled water (negative control), TiF4 solution (T), dendrimer solution (D), and TiF4-dendrimer solution (TD). The microhardness of the samples was measured initially. Next, the samples underwent pH-cycling, were exposed to the solutions, the microhardness was measured again, and microhardness loss was calculated. EDX analysis was performed on the surface and cross-sectional segments of the samples. The microhardness loss was significantly higher in control (-65.1± 6.0) compared to other groups. No significant difference was observed between T (-47.9± 5.6) and D (-41.7± 12.0), and also D and TD (-40.5± 9.4) in this regard. Microhardness loss was significantly higher in T compared to TD group. The T+D samples showed similar fluoride and titanium content in both surface and subsurface regions, while the T group had higher concentrations in the surface region. Moreover, the DT solution had a higher pH of 3.4 compared to the T solution's pH of 1.1. TiF4-dendrimer solution showed similar efficacy in inhibiting demineralization comparable to TiF4 solution, with the added advantage of having a higher pH.

Potential Roles for B cells and Autoantibodies in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that predominantly affects young males. AS is a condition in which the spine and sacroiliac joints become inflamed. More specifically, most AS patients experience spine malformations over time, resulting in functional incapability. The etiopathogenesis of AS is a complex combination of genetic predisposition and environmental factors. Extensive studies on AS have revealed the central role of genetics and immune reactions in its etiology. However, an utmost agreement has yet to be created. The available evidence suggests that both autoinflammation and T-cell-mediated autoimmune processes have significant roles in the disease process of AS. So far, B cells have obtained moderately little attention in AS pathogenesis, primarily because of the absence of disease-defining autoantibodies. However, against general dogma, evidence is mounting showing B cell involvement. Disruptions depict this in circulating B cell populations, the increased expression of immunoglobulin (Ig)G, IgA, and IgM, and B cell infiltration within the axial skeleton of AS patients. Meanwhile, compared to many other inflammatory autoimmune disorders, AS has no disease-specific autoantibodies that help disease diagnosis. This study has provided an overview of the B lymphocytes and antibodies' role in AS pathogenesis. It also introduces autoantibodies that can be the prognosis and diagnosis biomarkers of AS.

Highly efficient removal of trace heavy metals by high surface area ordered dithiocarbamate-functionalized magnetic mesoporous silica.

The study describes synthesizing and characterizing a novel dithiocarbamate-functionalized magnetic nanocomposite. This nanocomposite exhibits several desirable properties, including a large pore diameter of 2.55 nm, a high surface area of 1149 m2/g, and excellent capturing capabilities. The synthesis process involves the preparation of highly porous magnetic nanocomposites, followed by functionalization with dithiocarbamate functional groups through a reaction with carbon disulfide and amine. The synthesized nanocomposite was thoroughly characterized using various techniques, including X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The performance of the mesoporous nanocomposite as an adsorbent for removing Pb(II), Cd(II), and Cu(II) cations from contaminated water was evaluated. The study finds that the maximum removal efficiency for Pb(II), Cd(II), and Cu(II) cations is achieved at pH values above 4. The optimal contact time for achieving 100% removal efficiency of the mentioned cations ranged between 60 and 120 min. Within this time range, the adsorbent exhibited efficient capture of the heavy metal cations from contaminated water. Additionally, the appropriate amount of adsorbent required for complete elimination of the heavy metal cations is determined. For Cd(II), the optimal dosage was found to be 50 mg of the adsorbent. For Cu(II), the optimal dosage was determined to be 40 mg. Finally, for Pb(II), the optimal dosage was 30 mg. The adsorbent's regeneration capability was demonstrated, showing that it could be reused for five consecutive runs.

Streamlining efficient and selective synthesis of benzoxanthenones and xanthenes with dual catalysts on a single support.

Using two catalysts on a single support can improve reaction efficiency, higher yields, improved selectivity, and simplified reaction conditions, making it a valuable approach for industrial transformation. Herein, we describe the development of a novel and effective heterogeneous catalyst, WCl6/CuCl2, supported on graphitic carbon nitride (W/Cu@g-C3N4), which was synthesized under hydrothermal conditions. The structure and morphology properties of the W/Cu@g-C3N4 were characterized using various spectroscopic techniques, including FTIR, XRD, TEM, TGA, EDX, and SEM. The W/Cu@g-C3N4 support material enabled the rapid and efficient synthesis of benzoxanthenones and xanthenes derivatives in high yields under mild reaction conditions and short reaction times. The W/Cu@g-C3N4 catalyst was also found to be easily recyclable, and its catalytic performance did not significantly decrease after five times use. The findings suggest that W/Cu@g-C3N4 is a promising chemical synthesis catalyst with significant implications for sustainable and cost-effective organic synthesis.

Altered expression of apoptosis-related genes in rheumatoid arthritis peripheral blood mononuclear cell and related miRNA regulation.

AIM: Impaired apoptosis and proliferation resulted in autoreactive lymphocyte development and inflammation in Rheumatoid arthritis (RA). TP53, BAX, FOXO1, and RB1 are related genes in cell survival, proliferation, and inflammation which could be important in RA development and disease severity. Here we investigated their expression in peripheral blood mononuclear cells (PBMCs) from RA patients in comparison to healthy controls. METHODS: Fifty healthy controls and 50 RA patients were selected. The quantitative real-time polymerase chain reaction was used to assess the gene expression level in PBMCs. RESULTS: The mRNA expression of TP53 (FC = 0.65, p = .000), BAX (FC = 0.76, p = .008), FOXO1 (FC = 0.59, p = .000) and RB1 (FC = 0.50, p = .000) were significantly reduced in RA PBMCs. TP53 expression was negatively correlated with miR-16-5p (p = .032) and FOXO1 expression was negatively correlated with miR-335-5p (p = .005) and miR-34a-5p (p = .014). A positive correlation was seen between TP53 expression and its downstream gene, BAX (p = .001). FOXO1 expression was also negatively correlated with disease activity, DAS28 (p = .021). CONCLUSION: All selected genes have downregulated expression in RA PBMCs which could be correlated with RA pathogenesis by regulating apoptosis, cell survival, inflammatory mediator production, and proliferation. Due to the correlation of miR-16-5p, miR-34a-5p, and miR-335-5p with TP53 and FOXO1 expression in RA PBMCs, they could be used as future therapeutic targets.

Effect of curcumin on the expression of NOD2 receptor and pro-inflammatory cytokines in fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients.

BACKGROUND: Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural anti-inflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. METHODS: Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 µM curcumin alone or in combination with 20.3 µM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1ß. RESULTS: The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1ß in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. CONCLUSION: This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

Ras family signaling pathway in immunopathogenesis of inflammatory rheumatic diseases.

The Ras (rat sarcoma virus) is a GTP-binding protein that is considered one of the important members of the Ras-GTPase superfamily. The Ras involves several pathways in the cell that include proliferation, migration, survival, differentiation, and fibrosis. Abnormalities in the expression level and activation of the Ras family signaling pathway and its downstream kinases such as Raf/MEK/ERK1-2 contribute to the pathogenic mechanisms of rheumatic diseases including immune system dysregulation, inflammation, and fibrosis in systemic sclerosis (SSc); destruction and inflammation of synovial tissue in rheumatoid arthritis (RA); and autoantibody production and immune complexes formation in systemic lupus erythematosus (SLE); and enhance osteoblast differentiation and ossification during skeletal formation in ankylosing spondylitis (AS). In this review, the basic biology, signaling of Ras, and abnormalities in this pathway in rheumatic diseases including SSc, RA, AS, and SLE will be discussed.

Association of Killer Cell Immunoglobulin-like Receptor (KIR) Genes and their HLA Ligands with Susceptibility to Takayasu Arteritis in the Iranian Population.

Takayasu arteritis (TA) is a chronic inflammatory disorder characterized by vascular damage and fibrosis in the intima that commonly occurs in the aorta. In many damaged sites in TA patients, natural killer (NK) cells have been shown to be hyperactivated and produce inflammatory cytokines and toxic components. Killer cell immunoglobulin-like receptors (KIRs) are found on NK cells and interact with human leukocyte antigen (HLA) class I ligands to activate or suppress NK cells. The present study assessed the possible role of KIR and their HLA ligand genes in susceptibility to TA in Iranian patients. This case-control study included 50 TA patients and 50 healthy subjects. DNA was extracted from whole peripheral blood samples, and polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed to recognize the presence or absence of polymorphism in 17 KIR genes and 5 HLA class I ligands in each participant. Among the KIR and HLA genes, a significant decrease was detected in the frequency of 2DS4 (full allele) in TA patients (38%) compared with healthy controls (82%) (OR=0.13, 95% CI=0.05-0.34). However, none of the KIR and HLA genotypes or the interactions between these genes were associated with susceptibility to TA. The KIR2DS4 gene might be involved in the regulation of activation as well as the production of cytotoxic mediators of NK cells in patients with TA.

Blood regulatory T cells in inflammatory bowel disease, a systematic review, and meta-analysis.

INTRODUCTION: Inflammatory bowel disease (IBD) is an autoimmune disease involving various parts of the gastrointestinal (GI) tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). Due to the contradictory results regarding the percentage of peripheral blood (PB) regulatory T cells (Tregs) in IBD patients, this meta-analysis aimed to determine the Tregs frequency in IBD patients. METHOD: We searched PubMed, Web of Science, SCOPUS, and Google Scholar databases for relevant observational articles that analyzed and reported the frequency of PB Tregs in IBD patients and healthy control groups. After choosing the related articles by two reviewers, the data regarding the definition of Tregs and their frequencies in different groups were recorded. RESULT: In 22 studies, the results showed a nonsignificant difference in the frequency of PB Tregs between IBD cases and control subjects (SMD: -0.27, 95 % CI: -0.78, 0.23). However, the frequency of CD4+CD25+CD127- (SMD: -0.89, 95 % CI: -1.52, -0.26) and CD4+CD25+FoxP3+ (SMD: -1.32, 95 % CI: -2.37, -0.26) Tregs were significantly lower in IBD cases, compared to healthy subjects. Also, UC cases and active IBD cases showed a significantly lower frequency of Treg cells, compared to controls and remission IBD cases, respectively (SMD: -0.68, 95 % CI: -1.24, -0.11 and SMD: -0.60, 95 % CI: -0.93, -0.27). CONCLUSION: Our study highlighted a probable decrease of Tregs in IBD patients, especially the patients with active states of the disease. The decrease of Treg cells might cause an imbalance in the immune system and the over-activation of auto-immune responses against the digestive tract.

Upregulation of KAT2B and ESCO2 gene expression level in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune condition that causes progressive inflammation. It seems that alternations in epigenetic modifications contribute to RA development. The present study aimed to assess the expression pattern of K (lysine) acetyltransferase 1 (KAT1; HAT1) and lysine acetyltransferase 2B (KAT2B; PCAF), and the establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) in peripheral blood mononuclear cells (PBMCs) from RA patients. METHOD AND MATERIAL: In this case-control study, we studied 50 cases with RA in comparison to 50 age- and gender-matched healthy subjects. Separation of PBMCs samples from whole blood, extraction of RNA, and reverse transcription were performed. Gene transcript levels of KAT1, KAT2B, and ESCO2 were determined using SYBR green real-time quantitative PCR. RESULTS: Our results exhibited a significant upregulation in the expression levels of ESCO2 and KAT2B genes in patients with RA compared to normal individuals (P-value < 0.0001). Similarly, we observed higher expression of KAT1 in the patients' group when compared to the healthy controls, although the difference in expression level failed to show any significant changes (P-value = 0.485). Also, we found a positive correlation between ESCO2 and the level of erythrocyte sedimentation rate (ESR) in patients. CONCLUSION: Collectively, our results suggest that upregulated expression of KAT2B and ESCO2 genes may be correlated to RA development. Further studies with larger sample sizes are required for understanding the potential contribution of these enzymes in the pathology of RA. Key Points • Dysregulated expression level of epigenetics enzymes was observed in PBMCs from RA patients. • The expression of KAT2B was 2.44 times higher in the PBMCs of RA patients than in the healthy subjects. • The expression of ESCO2 was upregulated (2.75 times) in the PBMCs of RA patients compared to the control group. • There was a positive correlation between ESCO2 expression and the ESR level in patients.

Anti-inflammatory effects of PRIMA-1MET (mutant p53 reactivator) induced by inhibition of nuclear factor-κB on rheumatoid arthritis fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLSs), the main pathological cells in rheumatoid arthritis (RA), display tumor-like phenotype, including hyper-proliferation, apoptosis resistance, and aggressive phenotype. Excessive proliferation and insufficient apoptosis of RA-FLSs can lead to hyperplastic synovial pannus tissue, excess production of inflammatory mediators, and destruction of joints. In this article, we investigate the effect of PRIMA-1MET on the apoptosis induction and inhibition of pro-inflammatory cytokines in RA-FLSs. Synovial tissue samples were obtained from 10 patients with RA. The FLSs were treated with different concentrations of PRIMA-1MET. The rate of apoptosis and cell survival was assessed by flow cytometry and MTT assay and Real-time quantitative PCR was performed to evaluate the transcription of p53, IL-6, IL-1ß, TNF-α, Noxa, p21, PUMA, Bax, Survivin, and XIAP in treated RA-FLSs. The protein level of p53, IκBα, and phospho-IκBα were measured using Western blotting. The results showed that PRIMA-1MET induced apoptosis in RA-FLSs and increased significantly the expression of Noxa, and decreased significantly IL-6, IL-1ß, p53, and phospho-IκBα expression. PRIMA-1MET can induce apoptosis in RA-FLSs through induction of Noxa expression while p53 was downregulated. Furthermore, PRIMA-1MET treatment results in the suppression of pro-inflammatory cytokine production and NF-κB inhibition. Given the role of p53 and NF-κB in RA-FLSs, PRIMA-1MET can be considered as a new therapeutic strategy for rheumatoid arthritis.

Analysis of semen parameters, and hormonal changes of FSH, LH, testosterone, and libido following bariatric surgery.

Introduction: Although studies have shown that bariatric surgery can have a positive effect on the patient's sexual function, there are still disagreements and contradictions in this regard. The present study is aimed to evaluate semen parameters, hormonal changes of FSH, LH, testosterone, and libido following bariatric surgery. Methods: The present research as a prospective study was performed on 20 male candidates for bariatric surgery referred to Golestan and Aria hospitals in Ahvaz in 2021. Semen parameters (volume, count, motility, and the percentage of sperm with normal morphology), hormonal profile (including FSH, LH test hormones), and sexual function were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire before and 6 months after the surgery. Results: The results of this study indicated that semen parameters did not change significantly 6 months after surgery in comparison with before the surgery (P < 0.05). After the operation, just the total level of testosterone increased significantly (2.23 nmol/L vs. 2.74, P = 0.009). However, LH and FSH levels did not change significantly six months after surgery (P = 0.858 and P = 0.287). The results indicated significant improvement in IIEF score after the operation (P = 0.011). Conclusion: The findings of the present study indicated that the decrement of weight as a result of bariatric surgery had a favorable effect on the levels of serum testosterone and sexual performance, while semen parameters did not improve after surgery.

Comparing the occurrence rate of gestational hypertension during pregnancy with frozen embryo transfer and natural pregnancy.

Introduction: Recent researches have indicated that pregnancies with frozen embryo transfer are associated with the increment of risk of maternal and neonatal complications, especially hypertension during pregnancy. The present study aimed to compare the occurrence rate of gestational hypertension in pregnancy with frozen embryo transfer and normal pregnancy. Materials and Methods: This research, as a retrospective cross-sectional study, was performed on pregnant women with frozen embryo transfer (n = 97) and women with normal pregnancies (n = 164) referring to medical centers under the supervision of Ahvaz University of Medical Sciences in 2021. Women aged 18-35 were included in the study after week 20th of pregnancy. Maternal and neonatal outcomes including hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia), preterm birth (before the week 37th), low birth weight (lower than 2500 g), neonatal asphyxia (Apgar score >7 in minute 5th), intrauterine growth restriction (IUGR) and bleeding in the first trimester of pregnancy were evaluated. The association between frozen embryo transfer and pregnancy outcomes was evaluated using multiple logistic regressions. Results: The findings of this study indicated that pregnancy hypertension was observed in 23 people (23.7%) from the frozen embryo transfer group vs. 18 people (11.0%) from the normal pregnancy group (P = 0.006). Frozen embryo transfer pregnancy has a higher risk of gestational hypertension (OR = 2.521, 95% CI: 1.281-4.962; P = 0.007), preterm birth (OR = 2.264, 95% CI: 1.335-3.840; P = 0.002), and low birth weight (OR = 2.017, 95% CI: 1.178-3.455; P = 0.011). However, the incidence of birth asphyxia (P = 0.850), intrauterine growth restriction (P = 0.068), first-trimester bleeding (P = 0.809), and placenta accreta (P = 0.143) did not show a significant difference between two types of normal pregnancy and frozen embryo transfer pregnancy. Conclusion: Frozen embryo transfer pregnancy was associated with a higher risk of maternal and neonatal complications, hypertension, preterm birth, and low birth weight compared to natural and spontaneous pregnancies.

Effect of curcumin on the expression of NOD2 receptor and pro-inflammatory cytokines in fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients

Abstract Background Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural antiinflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. Methods Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 μM curcumin alone or in combination with 20.3 μM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1β. Results The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1β in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. Conclusion This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

Increased catalytic activity through ZnMo7O24/g-C3N4 heterostructured assemblies for greener indole condensation reaction at room temperature.

As an economical conjugated polymer, graphitic carbon nitride (g-C3N4) has recently attracted much attention due to its exciting chemical and thermal stability and easy availability. Herein, we constructed a metal-coordinated graphitic carbon nitride (M-g-C3N4) catalyst through simple impregnation and calcination methods and used it as a new heterogeneous catalyst for the efficient synthesis of bis (indolyl) methanes and trisindolines under mild conditions. This reaction is performed efficiently in water as an environmentally friendly solvent at ambient conditions. The ZnMo7O24/g-C3N4 nanocomposite was synthesized by a simple method by immobilizing Mo7O24(NH4)6·4H2O and ZnCl2 on the surface of g-C3N4 under hydrothermal conditions. It was characterized by FT-IR, EDS, and electronic scanning microscopy (SEM). The metal doping of Mo and Zn on the surface of graphitic carbon nitride leads to the formation of a green catalyst that gives good to excellent yields of products in short reaction times with an easy working procedure. In addition, the ZnMo7O24/g-C3N4 catalyst could be reused at least five runs without apparent loss of efficiency.

MicroRNA-211-5p Overexpression Effect on Endoplasmic Reticulum Stress and Apoptotic Genes in Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA). Endoplasmic reticulum (ER) stress and dysregulation of unfolded protein response are involved in the resistance to apoptosis of FLSs in RA (RA-FLSs). MicroRNA (MiR)-211 plays an important role in controlling ER stress and apoptotic genes in a PKR-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-dependent manner. We investigated the effect of miR-211-5p overexpression on ER stress and apoptotic genes in RA-FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients. MiR-211-5p and mRNA expression of the selected genes involved in the PERK pathway and apoptosis regulation were measured in RA, trauma, and thapsigargin (Tg)-treated RA-FLSs. Afterward, Tg-treated RA-FLSs following miR-211-5p overexpression were evaluated for miR-211-5p and mRNA levels of the study genes. The expression of miR-211-5p, PERK, BAX, and BCL2 showed no differences between RA and trauma. However, the expression of ATF4 and BCL-XL showed a significant increase in trauma. In addition, the levels of C/EBP homologous protein (CHOP) and MCL1 indicated a significant increase in RA-FLSs. Tg treatment significantly increased the expression of PERK, ATF4, and CHOP in RA-FLSs with no effect on miR-211-5p, BAX, BCL2, BCL-XL, and MCL1. Furthermore, Tg treatment following miR-211-5p overexpression in RA-FLSs showed a significant increase in levels of miR-211-5p with no changes in apoptotic genes. MiR-211-5p overexpression in stimulated RA-FLSs did not alter the levels of selected genes involved in apoptosis regulation. However, more investigations are necessary to determine the ER stress role in apoptosis regulation in RA-FLSs.