Everolimus treatment enhances inhibitory immune checkpoint molecules' expression in monocyte-derived dendritic cells.

BACKGROUND: Antigen-specific T-cell immunity is provided by dendritic cells (DCs), which are specialized antigen-presenting cells. Furthermore, they establish a link between innate and adaptive immune responses. Currently, DC modification is a new approach for the therapy of several disorders. During solid organ transplantation, Everolimus, which is a mammalian target of rapamycin (mTOR) inhibitor, was initially utilized to suppress the immune system's functionality. Due to the intervention of Everolimus in various signaling pathways in cells and its modulatory properties on the immune system, this study aims to investigate the effect of treatment with Everolimus on the maturation and expression of immune checkpoint genes in monocyte-derived DCs. METHODS: To isolate monocytes from PBMCs, the CD14 marker was used via the MACS method. Monocytes were cultured and induced to differentiate into monocyte-derived DCs by utilizing GM-CSF and IL-4 cytokines. On the fifth day, immature DCs were treated with Everolimus and incubated for 24 h. On the sixth day, the flow cytometry technique was used to investigate the effect of Everolimus on the phenotypic characteristics of DCs. In the end, the expression of immune checkpoint genes in both the Everolimus-treated and untreated DCs groups was assessed using the real-time PCR method. RESULTS: The findings of this research demonstrated that the administration of Everolimus to DCs led to a notable rise in human leukocyte antigen (HLA)-DR expression and a decrease in CD11c expression. Furthermore, there was a significant increase in the expression of immune checkpoint molecules, namely CTLA-4, VISTA, PD-L1, and BTLA, in DCs treated with Everolimus. CONCLUSION: The findings of this study show that Everolimus can target DCs and affect their phenotype and function in order to shift them toward a partially tolerogenic state. However, additional research is required to gain a comprehensive understanding of the precise impact of Everolimus on the activation status of DCs.

Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

BACKGROUND: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. METHODS AND RESULTS: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). CONCLUSIONS: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.

The role of neutrophils and neutrophil extracellular traps (NETs) in stages, outcomes and pregnancy complications.

Neutrophils are the main components of innate immunity to eliminate infectious pathogens. Neutrophils play a role in several stages of the reproductive cycle, and their presence in the female reproductive system is highly regulated, so their function may change during pregnancy. Emerging evidence suggests that neutrophils are important at all stages of pregnancy, from implantation, placentation, and connective tissue regeneration to birth, as well as birth itself. Neutrophil extracellular traps (NETs) are defined as extracellular strands of unfolded DNA together with histone complexes and neutrophil granule proteins. NET formation is a new mechanism of these cells for their defense function. These strands containing DNA and antimicrobial peptides were initially recognized as one of the defense mechanisms of neutrophils, but later it was explained that they are involved in a variety of non-infectious diseases. Since the source of inflammation and tissue damage is the irregular activity of neutrophils, it is not surprising that NETosis are associated with a number of inflammatory conditions and diseases. The overexpression of NET components or non-principled NET clearance is associated with the risk of production and activation of autoantibodies, which results in participation in autoinflammatory and autoimmune disorders (SLE, RA), fibrosis, sepsis and other disorders such as vascular diseases, for example, thrombosis and atherosclerosis. Recent published articles have shown the role of neutrophils and extracellular traps (NETs) in pregnancy, childbirth and pregnancy-related diseases. The aim of this study was to identify and investigate the role of neutrophils and neutrophil extracellular traps (NETs) in the stages of pregnancy, as well as the complications caused by these cells.

Current approaches in glioblastoma multiforme immunotherapy.

Glioblastoma multiform (GBM) is the most prevalent CNS (central nervous system) tumor in adults, with an average survival length shorter than 2 years and rare metastasis to organs other than CNS. Despite extensive attempts at surgical resecting, the inherently permeable nature of this disease has rendered relapse nearly unavoidable. Thus, immunotherapy is a feasible alternative, as stimulated immune cells can enter into the remote and inaccessible tumor cells. Immunotherapy has revolutionized patient upshots in various malignancies and might introduce different effective ways for GBM patients. Currently, researchers are exploring various immunotherapeutic strategies in patients with GBM to target both the innate and acquired immune responses. These approaches include reprogrammed tumor-associated macrophages, the use of specific antibodies to inhibit tumor progression and metastasis, modifying tumor-associated macrophages with antibodies, vaccines that utilize tumor-specific dendritic cells to activate anti-tumor T cells, immune checkpoint inhibitors, and enhanced T cells that function against tumor cells. Despite these findings, there is still room for improving the response faults of the many currently tested immunotherapies. This study aims to review the currently used immunotherapy approaches with their molecular mechanisms and clinical application in GBM.

The evaluation of PD-1 and Tim-3 expression besides their related miRNAs in PBMCs of women with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is a multifactorial disorder, associated with immunologic abnormalities. During pregnancy, the maternal immune system uses different tolerance mechanisms to deal with a semi-allogenic fetus. The expression of immune checkpoints and their related miRNAs in immune cells can ensure pregnancy at the feto-maternal interface by modulating immune responses. This study aims to evaluate the expression of the immune checkpoint molecules PD-1 and Tim-3 on circulating T cells by flow cytometry, that of mir-138 and mir-155 in PBMCs by Real-time PCR, and the concentrations of TGF-ß and IP-10 in the sera of women suffering from RPL as well as of gestational age-matched healthy pregnant women by ELISA. The percentage of PD-1 or Tim-3 expressing CD8+ T cells was significantly lower in RPL patients compared to the controls, while there was no significant difference in Tim-3 expression of CD4+ T cells between the two groups. The mRNA of both the PD-1 and Tim-3 genes were downregulated in PBMCs of RPL patients compared to controls, however, the difference was not statistically significant for Tim-3. The concentration of TGF-ß was significantly lower and that of IP-10 was significantly higher in the sera of RPL patients than in those of the controls. The relative expression of mir-138 and miR-155 were significantly lower, in PBMCs of RPL patients than in those of healthy pregnant women. These data confirm that by affecting cytokine production, immune checkpoints, and microRNAs play a role in establishing the appropriate local immune environment for successful pregnancy. The wider analysis of immune checkpoints may also yield new biomarkers for the diagnosis and prevention of RPL.

Diagnostic performance of CT scan-based radiomics for prediction of lymph node metastasis in gastric cancer: a systematic review and meta-analysis.

Objective: The purpose of this study was to evaluate the diagnostic performance of computed tomography (CT) scan-based radiomics in prediction of lymph node metastasis (LNM) in gastric cancer (GC) patients. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for original studies published until 10 November 2022, and the studies satisfying the inclusion criteria were included. Characteristics of included studies and radiomics approach and data for constructing 2 × 2 tables were extracted. The radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) were utilized for the quality assessment of included studies. Overall sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to assess diagnostic accuracy. The subgroup analysis and Spearman's correlation coefficient was done for exploration of heterogeneity sources. Results: Fifteen studies with 7,010 GC patients were included. We conducted analyses on both radiomics signature and combined (based on signature and clinical features) models. The pooled sensitivity, specificity, DOR, and AUC of radiomics models compared to combined models were 0.75 (95% CI, 0.67-0.82) versus 0.81 (95% CI, 0.75-0.86), 0.80 (95% CI, 0.73-0.86) versus 0.85 (95% CI, 0.79-0.89), 13 (95% CI, 7-23) versus 23 (95% CI, 13-42), and 0.85 (95% CI, 0.81-0.86) versus 0.90 (95% CI, 0.87-0.92), respectively. The meta-analysis indicated a significant heterogeneity among studies. The subgroup analysis revealed that arterial phase CT scan, tumoral and nodal regions of interest (ROIs), automatic segmentation, and two-dimensional (2D) ROI could improve diagnostic accuracy compared to venous phase CT scan, tumoral-only ROI, manual segmentation, and 3D ROI, respectively. Overall, the quality of studies was quite acceptable based on both QUADAS-2 and RQS tools. Conclusion: CT scan-based radiomics approach has a promising potential for the prediction of LNM in GC patients preoperatively as a non-invasive diagnostic tool. Methodological heterogeneity is the main limitation of the included studies. Systematic review registration: https://www.crd.york.ac.uk/Prospero/display_record.php?RecordID=287676, identifier CRD42022287676.

Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.

Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of autoimmune disease, particularly multiple sclerosis (MS), have garnered considerable attention and hold great potential for developing effective therapeutic strategies. Given the well-established immunoregulatory role of ICPs in maintaining a balance between stimulatory and inhibitory signaling pathways to promote immune tolerance to self-antigens, a dysregulated expression pattern of ICPs has been observed in a significant proportion of patients with MS and its animal model called experimental autoimmune encephalomyelitis (EAE), which is associated with autoreactivity towards myelin and neurodegeneration. Consequently, there is a rationale for developing immunotherapeutic strategies to induce inhibitory ICPs while suppressing stimulatory ICPs, including engineering immune cells to overexpress ligands for inhibitory ICP receptors, such as program death-1 (PD-1), or designing fusion proteins, namely abatacept, to bind and inhibit the co-stimulatory pathways involved in overactivated T-cell mediated autoimmunity, and other strategies that will be discussed in-depth in the current review. Video Abstract.

Molecular diagnosis, phylogenetic analysis, and antifungal susceptibility profiles of Candida species isolated from neutropenic oncological patients.

BACKGROUND: Neutropenia is the most important cause of life-threatening invasive fungal infections (IFIs). Here, we studied the frequency and antifungal susceptibility profiles of Candida species that colonized or caused infections among neutropenic patients with solid or hematological malignancies. METHODS: A total of 362 clinical samples were collected from 138 patients. After initial isolation using a mix of mycological methods, isolates were screened using chromogenic culture media. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied for molecular identification. Positive or suspected cases were confirmed using the reference method of sequencing. Antifungal susceptibility testing for voriconazole and caspofungin was carried out using the microbroth dilution method. An in-silico assay was applied for phylogenetic analysis. RESULTS: Thirty-four Candida strains were isolated. C. albicans (47.06%) and C. glabrata (29.41%) were the most frequent strains. Antifungal treatment reduced the chance of Candida colonization by almost 76% in neutropenic patients (OR: 1.759; 95% CI: 1.349 to 2.390; p value: 0.000). An unusual and non-resistant strain, C. lambica, was reported from the bloodstream of a 56-year-old man with hematologic malignancy (HM). Eight isolates were non-susceptible, and one isolate was resistant to voriconazole. Also, four isolates were non-susceptible to caspofungin. CONCLUSION: We can conclude that there is a cause-and-effect relationship between neutropenia, HM background, and Candida species separated from neutropenic patients, which can lead to possible infections. Further and repetitive studies are recommended using different molecular methods for better prediction and management of fungal infections in neutropenic patients.

MRI-Based Radiomics Methods for Predicting Ki-67 Expression in Breast Cancer: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: The purpose of this systematic review and meta-analysis was to assess the quality and diagnostic accuracy of MRI-based radiomics for predicting Ki-67 expression in breast cancer. MATERIALS AND METHODS: A systematic literature search was performed to find relevant studies published in different databases, including PubMed, Web of Science, and Embase up until March 10, 2023. All papers were independently evaluated for eligibility by two reviewers. Studies that matched research questions and provided sufficient data for quantitative synthesis were included in the systematic review and meta-analysis, respectively. The quality of the articles was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS) tools. The predictive value of MRI-based radiomics for Ki-67 antigen in patients with breast cancer was assessed using pooled sensitivity (SEN), specificity, and area under the curve (AUC). Meta-regression was performed to explore the cause of heterogeneity. Different covariates were used for subgroup analysis. RESULTS: 31 studies were included in the systematic review; among them, 21 reported sufficient data for meta-analysis. 20 training cohorts and five validation cohorts were pooled separately. The pooled sensitivity, specificity, and AUC of MRI-based radiomics for predicting Ki-67 expression in training cohorts were 0.80 [95% CI, 0.73-0.86], 0.82 [95% CI, 0.78-0.86], and 0.88 [95%CI, 0.85-0.91], respectively. The corresponding values for validation cohorts were 0.81 [95% CI, 0.72-0.87], 0.73 [95% CI, 0.62-0.82], and 0.84 [95%CI, 0.80-0.87], respectively. Based on QUADAS-2, some risks of bias were detected for reference standard and flow and timing domains. However, the quality of the included article was acceptable. The mean RQS score of the included articles was close to 6, corresponding to 16.6% of the maximum possible score. Significant heterogeneity was observed in pooled sensitivity and specificity of training cohorts (I2 > 75%). We found that using deep learning radiomic methods, magnetic field strength (3 T vs. 1.5 T), scanner manufacturer, region of interest structure (2D vs. 3D), route of tissue sampling, Ki-67 cut-off, logistic regression for model construction, and LASSO for feature reduction as well as PyRadiomics software for feature extraction had a great impact on heterogeneity according to our joint model analysis. Diagnostic performance in studies that used deep learning-based radiomics and multiple MRI sequences (e.g., DWI+DCE) was slightly higher. In addition, radiomic features derived from DWI sequences performed better than contrast-enhanced sequences in terms of specificity and sensitivity. No publication bias was found based on Deeks' funnel plot. Sensitivity analysis showed that eliminating every study one by one does not impact overall results. CONCLUSION: This meta-analysis showed that MRI-based radiomics has a good diagnostic accuracy in differentiating breast cancer patients with high Ki-67 expression from low-expressing groups. However, the sensitivity and specificity of these methods still do not surpass 90%, restricting them from being used as a supplement to current pathological assessments (e.g., biopsy or surgery) to predict Ki-67 expression accurately.

STATs signaling pathways in dendritic cells: As potential therapeutic targets?

Dendritic cells (DCs) are professional antigen-presenting cells (APCs), including heterogenous populations with phenotypic and functional diversity that coordinate bridging innate and adaptive immunity. Signal transducer and activator of transcriptions (STAT) factors as key proteins in cytokine signaling were shown to play distinct roles in the maturation and antigen presentation of DCs and play a pivotal role in modulating immune responses mediated by DCs such as differentiation of T cells to T helper (Th) 1, Th2 or regulatory T (Treg) cells. This review sheds light on the importance of STAT transcription factors' signaling pathways in different subtypes of DCs and highlights their targeting potential usages for improving DC-based immunotherapies for patients who suffer from cancer or diverse autoimmune conditions according to the type of the STAT transcription factor and its specific activating or inhibitory agent.

What is the context?Multiple disorders, including different infectious and autoimmune diseases and cancers, have affected many individuals all around the world. One of the main methods for combating such diseases is immunotherapy based on the dendritic cell (DC) vaccine. DCs are the most potent antigen-presenting cells for developing T lymphocytes' potential to eliminate external and internal harmful factors. Manipulating DCs' different signaling pathways, such as activating or blocking inhibitory or activatory pathways, based on our purpose is a great method for achieving efficient DC vaccines. The signal transducer and activator of transcription (STAT) is a protein with six subtypes that exists in DCs and conducts specific signaling pathways. Changing the activity of each STAT via various methods and drugs can affect DCs differently. Furthermore, each DC-existing STAT can play a specific role in establishing a special kind of disease. Thus, STAT proteins and their related signaling pathways have attracted many scientists' attention.What does the review highlight?We provide a comprehensive overview of different STATs' roles in DC subsets. Moreover, we conducted this review to identify if DC-associated STATs have any role in starting a special kind of disease. The effects of different drugs on STATs in DCs were also investigated.What is the impact?Generalabsly, STAT1, STAT2, and STAT4 with activatory roles, STAT3 with inhibitory roles, and STAT5 and STAT6 with both inhibitory and activatory roles can affect DCs in different conditions. Targeting different STATs in DCs with specific drugs contributes to alleviating various disease symptoms.

Long-Term Effects of ART on the Health of the Offspring.

Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences.

Induction of TLR5, IRAK1, and NF-κB expression by Trichomonas vaginalis in cervical cancer cell (HeLa) and normal human vaginal epithelial cell (HVECs) lines.

INTRODUCTION: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. METHODOLOGY: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using ß-actin as a housekeeping control. RESULTS: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). CONCLUSIONS: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways.

Current status of skin cancers with a focus on immunology and immunotherapy.

Skin cancer is one of the most widespread cancers, with a significant global health effect. UV-induced DNA damage in skin cells triggers them to grow and proliferate out of control, resulting in cancer development. Two common types of skin cancer include melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Melanoma is the most lethal form of skin cancer, and NMSC includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and other forms. The incidence of skin cancer is increasing in part owing to a demographic shift toward an aging population, which is more prone to NMSC, imposing a considerable financial strain on public health services. The introduction of immunostimulatory approaches for cancer cell eradication has led to significant improvements in skin cancer treatment. Over the last three decades, monoclonal antibodies have been used as powerful human therapeutics besides scientific tools, and along with the development of monoclonal antibody production and design procedures from chimeric to humanized and then fully human monoclonal antibodies more than 6 monoclonal antibodies have been approved by the food and drug administration (FDA) and have been successful in skin cancer treatment. In this review, we will discuss the epidemiology, immunology, and therapeutic approaches of different types of skin cancer.

The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL).

In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.

SARS-CoV2 infection induce miR-155 expression and skewed Th17/Treg balance by changing SOCS1 level: A clinical study.

BACKGROUND: One of the regulators in severe acute respiratory syndrome coronavirus2 (SARS-CoV2) infection is miRNAs. In COVID-19 patients, immunological responses to SARS-CoV2 infection may be impacted by miR-155, a miRNA associated to inflammation. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 50 confirmed COVID-19 patients /Healthy Controls (HCs) was isolated by Ficoll. The frequency of T helper 17 and regulatory T cells was analyzed by flowcytometry. The RNA was extracted from each sample and after synthesis of c-DNA, the relative expression of miR-155, suppressor of cytokine signaling (SOCS-1), Signal transducer and activator of transcription 3(STAT3), and Fork Head Box Protein 3 (FoxP3) was evaluated by real-time PCR. The protein level of STAT3, FoxP3 and RORγT in the isolated PBMCs measured by western blotting. The serum level of IL-10, TGF-ß, IL-17 and IL21 was assessed by ELISA method. RESULTS: The population of Th17 cells showed a significant rise, whereas Treg cells reduced in COVID-19 cases. The master transcription factor of Treg (FoxP3) and Th17 (RORγT) relative expression showed the same pattern as flowcytometry. STAT3 level of expression at RNA and protein level increased in COVID-19 cases. FOXP3 and SOCS-1 proteins were down-regulated. The relative expression of miR-155, up-regulated in PBMC of COVID-19 patients and revealed a negative correlation with SOCS-1. The serum cytokine profile showed a reduction in TGF-ß, on the other hand an increase was seen in IL-17, IL-21 and IL-10 in COVID-19 cases toward control group. CONCLUSION: Based on the studies conducted in this field, it can be suggested that Th17/Treg in covid-19 patients can be affected by miR-155 and it can be considered a valuable diagnostic and prognostic factor in this disease.

Autophagy-mediated immune system regulation in reproductive system and pregnancy-associated complications.

Autophagy lysosomal degradation is the main cell mechanism in cellular, tissue and organismal homeostasis and is controlled by autophagy-related genes (ATG). Autophagy has important effects in cellular physiology, including adaptation to metabolic stress, removal of dangerous cargo (such as protein aggregates, damaged organelles, and intracellular pathogens), regeneration during differentiation and development, and prevention of genomic damage in general. Also, it has been found that autophagy is essential for pre-implantation, development, and maintaining embryo survival in mammals. Under certain conditions, autophagy may be detrimental through pro-survival effects such as cancer progression or through possible cell death-promoting effects. Hormonal changes and environmental stress can initiate autophagy in reproductive physiology. The activity of autophagy can be upregulated under conditions like a lack of nutrients, inflammation, hypoxia, and infections. In this regard the dysregulation of autophagy involved in some pregnancy complications such as preeclampsia (PE) and pregnancy loss, and has a major impact on reproductive outcomes. Therefore, we aimed to discuss the relationship between autophagy and the female reproductive system, with a special focus on the immune system, and its role in fetal and maternal health.

A critical review of novel antibiotic resistance prevention approaches with a focus on postbiotics.

Antibiotic resistance is a significant public health issue, causing illnesses that were once easily treatable with antibiotics to develop into dangerous infections, leading to substantial disability and even death. To help fight this growing threat, scientists are developing new methods and techniques that play a crucial role in treating infections and preventing the inappropriate use of antibiotics. These effective therapeutic methods include phage therapies, quorum-sensing inhibitors, immunotherapeutics, predatory bacteria, antimicrobial adjuvants, haemofiltration, nanoantibiotics, microbiota transplantation, plant-derived antimicrobials, RNA therapy, vaccine development, and probiotics. As a result of the activity of probiotics in the intestine, compounds derived from the structure and metabolism of these bacteria are obtained, called postbiotics, which include multiple agents with various therapeutic applications, especially antimicrobial effects, by using different mechanisms. These compounds have been chosen in particular because they don't promote the spread of antibiotic resistance and don't include substances that can increase antibiotic resistance. This manuscript provides an overview of the novel approaches to preventing antibiotic resistance with emphasis on the various postbiotic metabolites derived from the gut beneficial microbes, their activities, recent related progressions in the food and medical fields, as well as concisely giving an insight into the new concept of postbiotics as "hyperpostbiotic".

The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies.

The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.

Association of IL-17 serum levels with clinical findings and systemic lupus erythematosus disease activity index.

The current study aims to investigate the relationship betweSen serum IL-17 (IL-17) levels and systemic lupus erythematosus disease activity index (SLE-DAEI) in systemic lupus erythematosus (SLE) patients. In this case-control study, 36 patients with SLE and 40 healthy individuals matched for age and sex were included as the control group. The study measured serum IL-17 in both groups. The correlation between serum IL-17 with disease activity (as per SLE-DAI) and organ involvement in SLE patients. The case group in this study consisted of 4 males and 32 females with a mean age of 35 (17-54) years old, and the control group included six males and 34 females with a mean age of 37 (25-53) years old (p = .35). Serum IL-17 was higher in the cases than in the controls (536 pg/mL vs. 110 pg/mL; p < .001). There was a positive correlation between the serum levels of IL-17 and disease activity index (p < .001, rho = 0.93) among cases. Additionally, the serum levels of IL-17 were higher in patients with renal (p = .003) or central nervous system involvement (p < .001) than in patients without such involvement. Serum Il-17 is associated with SLE, and its serum levels correlate positively with the disease activity and renal and nervous system involvement.