•Pemphigus is a rare autoimmune disease, affecting the skin and mucous membranes.•Cytokines could have a pathogenic and protective role in pemphigus.•Increased and decreased levels of different ...cytokines were reported in pemphigus patients.•Manipulation of cytokine levels could be used as the treatment of pemphigus.
Pemphigus is a rare and life-threatening group of blistering autoimmune diseases that affects the skin and mucous membranes. There are two major subtypes of pemphigus, including pemphigus vulgaris (PV) and pemphigus foliaceus (PF); each has different clinical manifestations. Pemphigus cannot be considered as a single disease and each patient may have a specific immunological profile. There are a lot of studies available regarding the role of different cytokines in the pathogenesis of pemphigus, although the data are not coherent between different studies. In this study, a systematic review from inception to December 25, 2019, through the MEDLINE/PubMed database had been performed to address several aspects of cytokines’ roles in PV and PF. As a result, 57 studies from 352 initially found records, containing 26 cytokines had met the inclusion criteria. We found different pieces of evidence in favor of increased levels of TNF-α, TGF-β, interleukin (IL)-8, IL-10, IL-12, IL-17, IL-21; while decreased levels of IL-2 and IL-23 in pemphigus patients. Regarding other cytokines, such as IFN-γ, IL-5, IL-15, IL-22, there are controversial results. Different studies suggested the association of TNF-α and IL-6 with disease activity and autoantibodies values. However, there is uncertainty regarding the role of IFN-γ, IL-2, IL-15, IL-27, and IL-33. Treatments with immunosuppressive agents may decrease IL-1, IL-6, IL-8, IFN-γ, IL-33, IL-17 levels. In conclusion, cytokines are deeply involved in PV and PF pathogenesis, and targeting specific cytokines may lead to development of more promising treatments for pemphigus.
Contrast agents are non-biologically active substances required for various diagnostic imaging procedures. Exposure to contrast materials, predispose some patients to renal disturbances entitled as ...contrast-associated acute kidney injury. Nephropathy of contrast medium is a deterioration of renal function which happens within 24 to 72 hours after iodinated contrast medium injection. Cancer individuals have several risk factors for contrast-associated acute renal failure, consisting of administration of chemotherapy regimen, which are mainly nephrotoxic, presence of diabetes or chronic renal failure, hypertension, taking of non-steroidal anti-inflammatory drugs, simultaneous use of nephrotoxic drugs, aminoglycosides, cisplatin, cyclosporine A or amphotericin B, increases the risk of contrast-associated acute renal failure. Similarly, age more than65 years old and anemia is an independent risk factor for contrast-associated acute kidney injury and also timing of CT within 45 days after last chemotherapy and low fluid intake, as the common risk factors in cancer individuals.
Many neurodegenerative diseases including frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD), multiple system atrophy (MSA), etc., show colocalized deposits of TDP-43 and α-synuclein ...(αS) aggregates. To understand whether these colocalizations are driven by specific molecular interactions between the two proteins, we previously showed that the prion-like C-terminal domain of TDP-43 (TDP-43PrLD) and αS synergistically interact to form neurotoxic heterotypic amyloids in homogeneous buffer conditions. However, it remains unclear if αS can modulate TDP-43 present within liquid droplets and biomolecular condensates called stress granules (SGs). Here, using cell culture and in vitro TDP-43PrLD - RNA liquid droplets as models along with microscopy, nanoscale AFM-IR spectroscopy, and biophysical analyses, we uncover the interactions of αS with phase-separated droplets. We learn that αS acts as a Pickering agent by forming clusters on the surface of TDP-43PrLD - RNA droplets. The aggregates of αS on these clusters emulsify the droplets by nucleating the formation of heterotypic TDP-43PrLD amyloid fibrils, structures of which are distinct from those derived from homogenous solutions. Together, these results reveal an intriguing property of αS to act as a Pickering agent while interacting with SGs and unmask the hitherto unknown role of αS in modulating TDP-43 proteinopathies.
The outbreak of 2019-novel coronavirus disease (COVID-19), caused by SARS-CoV-2, started in late 2019; in a short time, it has spread rapidly all over the world. Although some possible antiviral and ...anti-inflammatory medications are available, thousands of people are dying daily. Well-understanding of the SARS-CoV-2 genome is not only essential for the development of new treatments/vaccines, but it also can be used for improving the sensitivity and specificity of current approaches for virus detection. Accordingly, we reviewed the most critical findings related to the genetics of the SARS-CoV-2, with a specific focus on genetic diversity and reported mutations, molecular-based diagnosis assays, using interfering RNA technology for the treatment of patients, and genetic-related vaccination strategies. Additionally, considering the unanswered questions or uncertainties in these regards, different topics were discussed.
•Although a large number of variants have been reported for SARS-CoV-2, at least there are 17 frequently reported mutations.•PCR-based and CRISPR/Cas-based approaches are the most reliable and sensitive tests for detection of SARS-CoV-2, respectively.•RNA-interference (RNAi) approaches are novel and probably effective options for the treatment of COVID-19 patients.
Chemotherapy has been accepted as the most common choice for cancer treatment. However, chemotherapy-induced toxicity and chemotherapy resistance are the two challenging barriers to the treatment. ...Metformin is a safe, inexpensive, and the first line drug to treat type II diabetes. It has also a significant anti-tumor effect with a selective cytotoxic efficacy on cancer stem cells. It also has renoprotective efficacy. The current study contributes to incorporating metformin to chemotherapeutic agents to develop treatment efficiency and reduce the chemotherapy-induced side-effects (such as toxicity and resistance) and also to benefit the nephroprotective impact of this drug.
Background and Aims:The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem.Here,a systematic review and meta-analysis were conducted to evaluate the evidence ...regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine,telbivudine (LdT),and tenofovir (TDF).Methods:A PubMed and Scopus search resulted in 1,076 records,which were reduced to 36,containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria.The latest search was in August 2019.Results:Treatment with LdT,but not lamivudine and TDF,could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) =0.37) in infants;it also led to higher rates of hepatitis B e antigen loss (OR =12.14),hepatitis B e antigen seroconversion (OR =8.93),and alanine aminotransferase normalization in mothers (OR =1.49).Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR =0.19) and mother-to-child-transmission of HBV (total OR =0.15),and to cause higher rates of HBV DNA suppression in mothers (total OR =25.53).However,nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR =7.48).In contrast,no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births,congenital malformation,low birth weight,and abortion or fetal/infant death.The results suggested LdT's high capability of preventing mother-to-childtransmission.However,TDF failed to show significant associations to a reduced risk of mother-to-child-transmission,probably due to the low number of patients included.Conclusions:Although using either lamivudine,LdT,orTDF could lead to more favorable maternal/fetal outcomes,LdT seemed to show more potential in resolving certain infant-and maternal-related outcomes.More studies on the safety profile of such treatments are required.
Background: Glioblastoma (GBM) is the most common and aggressive brain tumor, which has a poor prognosis despite the advent of different therapeutic strategies. There are numerous molecular ...biomarkers to contribute diagnosis, prognosis, and prediction of response to the current therapy in GBM. One of the most important markers that are potentially valuable is immortalization-specific or immortalization-associated marker named "hTERT messenger ribonucleic acid (mRNA)" the key subunit of telomerase enzyme, which is expressed in more than 85% of cancer cells, in spite of the majority of normal somatic cells. In this study, we investigated the effects of resveratrol (RSV) on this mRNA marker level, leading to cancer progression. Materials and Methods: U-87MG cell line was obtained from Pasteur Institute of Iran and treated with various concentrations of 0- 160 μg/mL of RSV and at different time points (24, 48, and 72 h). To evaluate viability of U-87MG cells, standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. Real-time polymerase chain reaction (RT-PCR) was used for comparative and quantitative assessment of human telomerase reverse transcriptase (hTERT) mRNA copy number versus control- untreated group. Results: The results of our investigation suggested that RSV effectively inhibited cell growth and caused cell death in dose-dependent (P < 0.05) and not in time-dependent manner (P > 0.05), in vitro. Interestingly, quantitative RT-PCR analysis demonstrated that at half inhibition concentration, RSV dramatically decreased mRNA expression of hTERT, the catalytic subunit of telomerase enzyme, which leads to prevention of cell division and tumor progression. Conclusion: With regard to downregulation of this immortalization-associated marker, RSV may potentially be used as a therapeutic agent against GBM.
Pemphigus vulgaris (PV) is a rare autoimmune blistering disorder, which could affect both skin and mucosal surfaces. There is increasing evidence that genetics plays a critical role in PV ...development, severity and prognosis. Single‐nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people and have been widely evaluated in most diseases. However, there are few studies regarding the roles of SNPs in the PV. Here, we reviewed both pathogenic and protective roles of the SNPs in non‐HLA genes regarding the PV. Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population‐specific manner. Moreover, SNPs in glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, including rs11745958, rs17209237, rs33388, rs7701443 as well as rs116855232 at NUDT15, seem to be associated with therapeutic outcomes in PV patients. Additionally, variations in the other genes involved in the drugs' metabolisms, pharmacokinetics and pharmacodynamics such as rs396991 in FCGR3A gene could be used for the prediction of clinical response to drugs and side effects. Taken together, SNPs seem to be valuable tools for better management of PV patients. Further studies need to be conducted to evaluate SNPs in genes that control immune responses and apoptosis.
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