Candidate MicroRNA Biomarkers in Lupus Nephritis: A Meta-analysis of Profiling Studies in Kidney, Blood and Urine Samples.

CONTEXT: Lupus nephritis (LN) is a kidney disease caused by systemic lupus erythematosus in which kidneys are attacked by the immune system. So far, various investigations have reported altered miRNA expression profiles in LN patients and different miRNAs have been introduced as biomarkers and/or therapeutic targets in LN. The aim of this study was to introduce a consensus panel of potential miRNA biomarkers by performing a meta-analysis of miRNA profiles in the LN patients. MATERIALS AND METHODS: A comprehensive literature review approach was performed to find LN-related miRNA expression profiles in renal tissues, blood, and urine samples. After selecting the eligible studies and performing the data extraction, meta-analysis was done based on the vote-counting rank strategy as well as meta-analysis of p-values. The meta-miRNAs and their related genes were subjected to functional enrichment analyses and network construction. RESULTS: The results of the meta-analysis of 41 studies were three lists of consensus miRNAs with altered expression profiles in the various tissue samples of LN patients (meta-analysis of p-values < 0.05). Of the 13 studies on kidney tissue, the meta-miRNAs were let-7a, miR-198, let-7e, miR-145, and miR-26a. In addition, meta-miRNAs of miR-199a, miR-21, miR-423, miR-1260b, miR-589, miR-150, miR-155, miR-146a, and miR-183 from 21 studies on blood samples, and miR-146a, miR-204, miR-30c, miR-3201, and miR-1273e from 11 studies on urine samples can be considered as non-invasive biomarker panels for LN. Functional enrichment analysis on the meta-miRNA lists confirmed the involvement of their target genes in nephropathy-related signaling pathways. CONCLUSION: Using a meta-analytical approach, our study proposes three meta-miRNA panels that could be the target of further research to assess their potential as therapeutic targets/biomarkers in LN disease.

Unexpected Positive Effects of Rituximab and Corticosteroids on COVID-19 in a Patient Suffering from Granulomatosis with Polyangiitis.

The COVID-19 pandemic has raised concerns among physicians and patients with autoimmune disorders about how this viral infection affects the patients receiving immunosuppressive drugs. There are speculations about a higher incidence and severity of COVID-19 in patients receiving a variety of immunosuppressant drugs. However, we reported the rapid recovery from COVID-19 in a 67-year-old male with granulomatosis with polyangiitis who did not experience severe symptoms of the COVID-19 as expected, despite having a history of serious lung involvement due to the autoimmune disease. He received conventional medications to treat COVID-19, though he had been receiving rituximab and corticosteroids before the onset of COVID-19 symptoms. Prevention of the cytokine storm caused by SARS-CoV-2 infection owing to taking the immunosuppressive drugs (rituximab and corticosteroids) could be a reason for these unexpected observations. Therefore, this case showed that taking immunosuppressive drugs is unlikely to be directly related to the increased severity of COVID-19.

Anti-cancer immunoprotective effects of immunization with hydatid cyst wall antigens in a non-immunogenic and metastatic triple-negative murine mammary carcinoma model.

Cancer vaccines have gained lots of attention as the future of cancer treatment. However, poor immunogenicity of tumor-associated antigens often fails to induce an efficient immune response against the tumor. Strange anti-tumor immune responses at the parasite-infected patients due to cross-reactivity have been reported in various studies. Therefore, parasite antigens with significant immunogenicity and high epitope homology with cancer antigens may activate a strong immune response against cancer cells. Herein, the sera of immunized rabbits with the hydatid cyst wall (HCW) antigens were incubated with 4 T1 mammary carcinoma cells to investigate cross-reactivity between the HCW antigens antisera and surface antigens of the breast cancer cells. Also, the SDS-PAGE profile of HCW antigens was prepared and incubated with the breast cancer patients' sera and considerable reactivity was observed between their sera and a specific band (~27/28 kDa) according to Western blotting analyzes. Then, the protein bands with cross-reactivity with breast cancer patients' sera were utilized for prophylactic immunizations of Balb/c mice. The immunoprotective effect of immunization with the HCW antigens caused significant inhibition of 4 T1 breast tumor growth, decrease of metastasis, and enlargement of the tumor-bearing mice survival time in comparison with PBS and pure immune adjuvant injected groups. Mass spectrometry analysis showed that the ~ 27/28 kDa band has numbers of proteins/polypeptides with a high degree of homology with cancer cells antigens which can be the reason for this cross-reactivity and anti-tumor immune response. Taking together, immunization with HCW antigens would be a promising approach in cancer immunotherapy after further investigations.

TNF-α Blockers Showed Prophylactic Effects in Preventing COVID-19 in Patients with Rheumatoid Arthritis and Seronegative Spondyloarthropathies: A Case-Control Study.

INTRODUCTION: The interaction between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 is a crucial factor in the viral infections leading to the release of inflammatory proteins, such as TNF-α. Thus, it is hypothesized that TNF-α blockers can prevent either COVID-19 incidence or its serious symptoms. TNF-α blockers are prescribed to treat various autoimmune disorders, including rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA). Therefore, the objective of this work was to examine this hypothesis that TNF-α blockers can prevent COVID-19 incidence in patients with RA or SpA. METHODS: A case-control study was conducted through interviews based on a structured questionnaire to investigate the frequency of COVID-19 incidence in 254 eligible patients with RA or SpA about whom 45% were under treatment with one type of TNF-α blockers including infliximab, adalimumab, and etanercept at least for 3 months during the COVID-19 pandemic. Interviews were carried out twice, at the beginning and the end of the study (June-December 2020). Patients with COVID-19 during the study or before that were considered as cases. The control group was patients without COVID-19 experience. Data were analyzed using descriptive statistics, and logistic regression was used to determine the relationships between COVID-19 incidence and independent variables. RESULTS: A small percentage of patients treated with TNF-α blockers (5.22%, 6/115) experienced COVID-19, while a large percentage of patients with COVID-19 did not receive TNF-α blockers (27.34%, 38/139). According to odds ratio, adalimumab, infliximab, and etanercept decreased significantly the risk of developing COVID-19 up to 96.8, 95, and 80.3% (p < 0.05), respectively. Therefore, TNF-α blockers could probably decrease the chances of the COVID-19 incidence in patients with RA or SpA. CONCLUSIONS: A direct and positive correlation between the use of TNF-α blockers and a reduction in the incidence of COVID-19 could suggest the prophylactic role of these drugs in preventing COVID-19 in patients with RA and SpA.

TNF-α Blockers Showed Prophylactic Effects in Preventing COVID-19 in Patients with Rheumatoid Arthritis and Seronegative Spondyloarthropathies: A Case-Control Study.

INTRODUCTION: The interaction between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 is a crucial factor in the viral infections leading to the release of inflammatory proteins, such as TNF-α. Thus, it is hypothesized that TNF-α blockers can prevent either COVID-19 incidence or its serious symptoms. TNF-α blockers are prescribed to treat various autoimmune disorders, including rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA). Therefore, the objective of this work was to examine this hypothesis that TNF-α blockers can prevent COVID-19 incidence in patients with RA or SpA. METHODS: A case-control study was conducted through interviews based on a structured questionnaire to investigate the frequency of COVID-19 incidence in 254 eligible patients with RA or SpA about whom 45% were under treatment with one type of TNF-α blockers including infliximab, adalimumab, and etanercept at least for 3 months during the COVID-19 pandemic. Interviews were carried out twice, at the beginning and the end of the study (June-December 2020). Patients with COVID-19 during the study or before that were considered as cases. The control group was patients without COVID-19 experience. Data were analyzed using descriptive statistics, and logistic regression was used to determine the relationships between COVID-19 incidence and independent variables. RESULTS: A small percentage of patients treated with TNF-α blockers (5.22%, 6/115) experienced COVID-19, while a large percentage of patients with COVID-19 did not receive TNF-α blockers (27.34%, 38/139). According to odds ratio, adalimumab, infliximab, and etanercept decreased significantly the risk of developing COVID-19 up to 96.8, 95, and 80.3% (p < 0.05), respectively. Therefore, TNF-α blockers could probably decrease the chances of the COVID-19 incidence in patients with RA or SpA. CONCLUSIONS: A direct and positive correlation between the use of TNF-α blockers and a reduction in the incidence of COVID-19 could suggest the prophylactic role of these drugs in preventing COVID-19 in patients with RA and SpA.

Efficacy of synbiotic supplementation in improving rheumatoid arthritis.

BACKGROUND AND PURPOSE: Today, improving rheumatoid arthritis (RA) as a chronic inflammatory disease is attributed to the proper status of the gut microbiota. Although some supplements containing beneficial live microorganisms (probiotics) can reduce inflammation by altering the bacterial composition of the gut, there is limited information on the effect of synbiotic (probiotics mixed with prebiotics) supplements on RA. Therefore, this study aimed to evaluate the anti-inflammatory effects of a synbiotic supplement as an adjuvant therapy in rheumatic patients. Moreover, for the first time, it was attempted to investigate whether addition of a synbiotic (1000 mg/day) to the combination of methotrexate and prednisolone increases the effectiveness of these antirheumatic drugs. EXPERIMENTAL APPROACH: Eligible patients (186 subjects) were randomly divided into two groups. Both groups received their standard routine antirheumatic drugs, methotrexate and prednisolone. Moreover, the first group received a daily oral synbiotic supplement (1000 mg) for 3 months while the second group received a placebo. Various parameters indicating RA status were evaluated at baseline (time 0) and 3 months after the treatment. FINDINGS / RESULTS: The results showed the changes in the level of RA indicators, including tender joint count with a range of 0 to 28 joints, swollen joint count with a range of 0 to 28 joints, visual analog scale, erythrocyte sedimentation rate, CRP, and disease activity score based on 28 joints, after 3 months. CONCLUSION AND IMPLICATIONS: Overall, no significant differences in the measured parameters were observed between synbiotic and placebo groups probably due to the short duration of the treatment period, and it is suggested to extend the treatment period to six months.

Immunization with Hydatid Cyst Wall Antigens Can Inhibit Breast Cancer through Changes in Serum Levels of Th1/Th2 Cytokines.

BACKGROUND: Hydatid cysts are the larval stage of Echinococcus granulosus, which lead to humoral and cellular immune responses in hosts. Such immune responses play a key role in the inhibition of tumor growth and cancers. To test this hypothesis, it was attempted not only to examine the changes in serum level of some Th1 and Th2 cytokines but also to find relationships between the cytokines and cancer in 4T1 breast cancer-bearing mice immunized with hydatid cyst wall (HCW) antigens. METHODS: Six to eight-week-old Balb/c female mice were immunized with alum, PBS and HCW antigens, including crude extract of HCW (laminated layer) 28 and 27 kDa protein bands (upper and lower bands) and then challenged with 4T1 breast cancer cells. The amounts of IL2, TNF-α, IFN-γ (Th1 cytokines), and IL4 (Th2 cytokine) were estimated using ELISA. Correlations between these cytokines and cancer parameters (tumor growth, metastasis, and survival) were determined by Pearson's correlation coefficients. RESULTS: Overall, HCW antigens increased the amounts of IL2, TNF-α, IFN-γ, and IL4. Pearson's correlation coefficients indicated reverse relationships between changes in amounts of these cytokines and tumor growth/metastasis. However, except for IL-4, all cytokines had a direct relationship with mouse survival. CONCLUSIONS: The results of this study indicated that the inhibition of breast tumor growth and metastasis and improvement of survival in 4T1 mice immunized with HCW antigens, especially laminated layer and 27 kDa protein band can occur through a rise in the levels of cytokines.

Characterization of PP2A-A3 mRNA expression and growth patterns in Arabidopsis thaliana under drought stress and abscisic acid.

Phosphoprotein phosphatase 2A (PP2A) plays a crucial role in cellular processes via reversible dephosphorylation of proteins. The activity of this enzyme depends on its subunits. There is little information about mRNA expression of each subunit and the relationship between these gene expressions and the growth patterns under stress conditions and hormones. Here, mRNA expression of subunit A3 of PP2A and its relationship with growth patterns under different levels of drought stress and abscisic acid (ABA) concentration were analyzed in Arabidopsis thaliana. The mRNA expression profiles showed different levels of the up- and down-regulation of PP2AA3 in roots and shoots of A. thaliana under drought conditions and ABA treatments. The results demonstrated that the regulation of PP2AA3 expression under the mentioned conditions could indirectly modulate growth patterns such that seedlings grown under severe drought stress and those grown under 4 µM ABA had the maximum number of lateral roots and the shortest primary roots. In contrast, the minimum number of lateral roots and the longest primary roots were observed under mild drought stress and 0.5 µM ABA. Differences in PP2AA3 mRNA expression showed that mechanisms involved in the regulation of this gene under drought conditions would probably be different from those that regulate the PP2AA3 expression under ABA. Co-expression of PP2AA3 with each of PIN1-4,7 (PP2A activity targets) depends on the organ type and different levels of drought stress and ABA concentration. Furthermore, fluctuations in the PP2AA3 expression proved that this gene cannot be suitable as a reference gene although PP2AA3 is widely used as a reference gene.