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Background: Pay for performance (P4P) schemes provide financial incentives or facilities to health workers based on the achievement of predetermined performance goals. Various P4P programs have been implemented around the world. There is a question of which model is suitable for p4p implementation to achieve better results. The purpose of this study is to compare pay for performance models in different countries. Methods: This is a descriptive-comparative study comparing the P4P model in selected countries in 2022. Data for each country are collected from reliable databases and are tabulated to compare their payment models. the standard framework of the P4P model is used for data analysis. Results: we used the standard P4P model framework to compare pay for performance programs in the primary care sector of selected countries because this framework can demonstrate all the necessary features of payment programs, including performance domains and measures, basis for reward or penalty, nature of the reward or penalty, and data reporting. The results of this study show that although the principles of P4P are almost similar in the selected countries, the biggest difference is in the definition of performance domains and measures. Conclusions: Designing an effective P4P program is very complex, and its success depends on a variety of factors, from the socioeconomic and cultural context and the healthcare goals of governments to the personal characteristics of the healthcare provider. considering these factors and the general framework of the features of P4P programs are critical to the success of the p4p design and implementation. [ABSTRACT FROM AUTHOR]

Purpose: The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods: Mono‐delivery and co‐delivery of SRL and CsA by NLCs (S‐NLCs, C‐NLCs, and S‐C‐NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results: Well‐designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co‐delivery by NLCs. Following S‐NLCs and C‐NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro‐inflammatory cytokines (IFN‐γ, TNF‐α, IL‐17, and IL‐21) and their regulators (T‐bet and RORγt), as well as a lower level of an anti‐inflammatory cytokine (IL‐10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S‐C‐NLCs intervention. Conclusions: S‐C‐NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance. [ABSTRACT FROM AUTHOR]

Background: Recently, biosensors have become popular analytical tools for small analytes due to their high sensitivity and wide analytical range. In the present work, development of a novel biosensing method based on tungsten disulfide quantum dots (WS2 QDs)-Au for rapidly and selectively detecting c-Met protein is introduced. As a proof of concept, M13 bacteriophage-based biosensors were used for the electrochemical detection of c-Met protein as a colon cancer biomarker. Method: The M13 bacteriophage (virus), as the biorecognition element, was immobilized on glassy carbon electrodes which were modified by WS2 QDs-functionalized gold nanoparticles. The stepwise presence of the WS2 QDs, gold nanoparticles, and immobilized phage on glassy carbon electrodes were confirmed by scanning electron microscope (SEM) and square wave voltammetry (SWV) technique. Results: The designed biosensor was applied to measure the amount of c-Met protein in standard solutions, and consequently the desirable detection limit of 1 pg was obtained. Finally, as a proof of concept, the developed platform was used for the evaluation of c-Met protein in serum samples of colon cancer-suffering patients and the results were compared with the results of the common Elisa kit. Conclusions: As an interesting part of this study, some concentrations of the c-Met protein in colon cancer serum samples which could not be determined by Elisa, were easily analyzed by the developed bioassay system. The developed bioassay system has great potential to application in biomedical laboratories. [ABSTRACT FROM AUTHOR]

Background: Nurses play a very important role in caring for patients with coronavirus disease-19 (COVID-19). They are on the frontline fighting COVID-19. The objective was to explore the experiences of nurses in the surgical and infectious wards about caring for patients with COVID-19 in a large and tertiary care hospital in Iran. Materials and Methods: This was a qualitative study. Semi-structured qualitative interviews were conducted with 18 nurses in the Imam Reza Hospital Complex from April to May 2020, Mashhad, Iran. Data analysis was performed using the method proposed by Lundman and Granheim. The Maxqda10 software was used. Results: The experiences were summarized into three categories: (1) experiencing new feelings and relationships with colleagues and patients, (2) viewpoints about managers' performance, and (3) concern about getting infected with COVID-19. Findings reflected similar experiences on personal protective equipment between nurses in the surgical and infectious wards. Experiencing new feelings and relationships with colleagues and patients and concern about getting infected and spreading the COVID-19 were mostly expressed by infectious nurses and surgical nurses, respectively. Conclusions: This research results provide evidence of the experiences of infectious and non-infectious disease nurses who are currently caring for COVID-19 patients. Due to some differences between the experiences of these two groups in COVID-19, it is suggested to pay more attention to the needs and required skills in the staff mix during a crisis. [ABSTRACT FROM AUTHOR]

As the largest organ of the body, human skin is multifunctional and enjoys two layers, the epidermis and the dermis, the separation of which is performed by a basement membrane zone. Skin protects the body against mechanical forces and infections. Skin wounds represent large and growing challenges to the healthcare systems globally. Skin wound healing, as a protective shield for the body against the external environment, includes interactions among cell types, the neurovascular system, cytokines, and matrix remodeling. Growth factors (GFs) affect the microenvironment of the wound, and cause rises in cell differentiation, proliferation, and migration. Administrating exogenous GFs has revealed potential in enhancing wound healing outcomes. The use of human GFs in the field of wound healing is becoming gradually more interesting, because of the low-invasive techniques required for their use. Reviewed here are the literatures on the healing of skin wounds with emphasize on the role of GFs and their future prospects, containing profits, and probable long-standing side effects accompanied with their use. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase‐related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T‐cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types. Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus‐specific memory CD8+ T‐cells differentiation and homeostasis in a T‐cell‐intrinsic manner. The mTOR signaling pathway also plays a critical role in dictating the outcome of regulatory T cells (Treg), T helper 17 (Th17) cells, and natural killer (NK) cells proliferation and maturation, as well as the effector functions and cytotoxic properties of NK cells. Manipulation of mTOR activity is a critical therapeutic approach for pharmacological agents that seek to inhibit mTOR. This approach should enhance specific memory CD8 + T‐cells responses and induce fully functional effector properties of NK cells to provoke their antitumor and antiviral activities. [ABSTRACT FROM AUTHOR]

A 60‐year‐old man was referred to hospital for loss of consciousness. Her late‐onset Wilson disease was diagnosed with elevated serum bilirubin, hepatic copper concentration, and urinary copper excretion. Zinc sulfate administration decreased the majority of clinical symptoms. [ABSTRACT FROM AUTHOR]

Problem: Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg‐related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. Methods: Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real‐time polymerase chain reaction (PCR). Enzyme‐linked immunosorbent assay (ELISA) was used to test the interleukin (IL)‐17, IL‐23, IL‐6, and IL‐10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. Results: PE patients exhibited a decreased number of Treg cells (p = 0.006), while Th17 cells were increased (p = 0.004). Forkhead box P3 and IL‐10 mRNA expressions were reduced (p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor‐related orphan nuclear receptor γt, IL‐17, IL‐23, and IL‐6 were enhanced (p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL‐6, IL‐17, and IL‐23 (p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL‐10 in the supernatant of PBMCs of PE patients compared with control group (p = 0.0011). There was significant upregulation of miR‐106b and miR‐326 (p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. Conclusions: These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto‐maternal immune cross‐talk. Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17/regulatory T cells is thought to play considerable roles in preeclampsia. [ABSTRACT FROM AUTHOR]

Impaired inflammatory immune cells have been implicated in the pathogenesis of Behcet's disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real‐time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme‐linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)‐10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL‐17, IL‐23, and retinoic acid‐related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17‐associated cytokines in the supernatant was found to be elevated in BD patients. T‐cell‐associated miRNA expression levels, miR‐25, miR‐106b, miR‐326, and miR‐93 were significantly upregulated, while miR‐146a and miR‐155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD. Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD. [ABSTRACT FROM AUTHOR]

Background: Approximately 20 million individuals are afflicted with cancer worldwide. Gastric cancer is the fourth leading cause of death in the world today. The aim of this study was to evaluate the direct medical care costs of gastric cancer patients in a tertiary teaching hospital in Iran.--- Methods: The present study is descriptive-analytical, carried out in two main stages. In the first stage we designed a form based on valid international guidelines. The second step identified the costs of diagnosis and treatment of gastric cancer. To analyze the cost data, descriptive statistics such as mean and standard deviation were utilized. We used nonparametric statistical tests such as Mann-Whitney, Wilcoxon in SPSS 16 software for data analysis. Results: In this study, the records of 449 gastric cancer patients who had referred to Omid tertiary teaching hospital of Mashhad between the years 2005 and 2015 were studied. According to the results, the highest average costs were related to patient hospitalization costs. Based on the significance level of the Mann Whitney test, no remarkable difference could be seen in the total costs of metastatic and non-metastatic patients (P-value: P> 0.05). Conclusion: Organizations such as: insurance agencies, charities and financial institutions need to adopt new policies to reduce patients' expenditures, remove financial barriers and prevent patients from facing catastrophic costs. [ABSTRACT FROM AUTHOR]

Background: One of the most significant problems in the treatment of leukemia is the expansion of resistance to chemotherapeutic agents. Therefore, assessing the drug resistance and especially the drug resistance genes of leukemic cells is important in any treatment. The impact of Mesenchymal Stem Cells (MSCs) and hypoxic condition have been observed in the biological performance of majority of leukemic cells. Methods: MOLT-4 cells were co-cultured with MSCs in the hypoxic condition induced by Cobalt Chloride (CoCl2) for 6 and 24 hr. Then, apoptosis of cells was analyzed using annexin-V/PI staining and expression of the drug resistance genes including MDR1, MRP, and BCRP along with apoptotic and anti-apoptotic genes, including BAX and BCL2, was evaluated by real-time PCR. Results: The hypoxic condition for MOLT-4 cells co-cultured with MSCs could signifi- cantly increase the expression of MDR1 and BCRP genes (p<0.05) which are involved in drug resistance. Also, the results indicated that this condition significantly increases the expression of BCL2 (p<0.05) and reduces the apoptosis in MOLT-4 cells co-cultured with MSCs in the hypoxic condition. Conclusion: These effects can demonstrate the important role of hypoxia and MSCs on the biological behavior of Acute Lymphoblastic Leukemia (ALL) cells that may lead to particular treatment outcomes. [ABSTRACT FROM AUTHOR]

Oryzatensin (ORZ) can reduce potentially IFN-γ secretion by natural killer (NK) cells. Therefore, current study was designed to evaluate the effects of ORZ treatment on peripheral blood mono-nuclear cells (PBMCs) cytokine secretion, proliferation and also to evaluate vascular endothelial growth factor (VEGF) and Matrix Metalloproteinase 9 (MMP-9) expression in HEP-G2 cell line after culture with ORZ-stimulated PBMCs. In this ex-vivo study, PBMCs from apparently healthy male volunteers (n=25) aged 20-30 were isolated by ficoll density gradient. Tetrazolium colorimetric test (MTT assay), ELISA test and real time PCR were performed to evaluate PBMCs proliferation, PBMCs cytokine secretion and the genes expression accordingly. The results of MTT assay showed that ORZ significantly stimulated proliferation of the isolated PBMCs. The results also indicated that ORZ treatment significantly decrease and increase IFN-γ and IL-4 secretion by isolated PBMCs, respectively. Also, VEGF and MMP-9 expression significantly increased in HEP-G2 cells after culture with ORZstimulated PBMCs. The previous studies have introduced ORZ-like peptide for pharmacological purpose and in this study we get to the conclusion that the administration of this peptide may change the immune system response and sensitize target populations to cancer. [ABSTRACT FROM AUTHOR]

Tetanus is a highly fatal disease caused by tetanus neurotoxin (TeNT) and remains a major threat to human and animal health, despite preventive strategies. TeNT is composed of heavy and light chain linked by a disulfide bond. The antibody response to TeNT is polyclonal and directed to multiple epitopes within both the light and heavy chains, leading to toxin neutralization. This study was undertaken to localize and compare neutralizing epitopes recognized by human and mouse TeNT-specific antibodies at a clonal level. In the present study, 22 murine hybridoma clones and 50 human lymphoblastoid cell lines secreting monoclonal antibodies (mAb) were generated against TeNT. The specificity of these mAb was determined using different recombinant fragments of tetanus toxin. Moreover, this study investigated thein vitrotoxin neutralizing activity of these mAb by a ganglioside GT1b assay. The results showed that tetanus toxoid immunization in humans and BALB/c mice induced a vigorous humoral immune response against different fragments of TeNT, particularly the carboxyl-terminal fragment of the heavy chain (known as fragment C). The fragment C-specific human and mouse mAb could largely neutralize TeNT. However, while all fragment C-specific human mAb reacted with the carboxyl-terminal part of this fragment (HCC), the majority of the mouse mAb failed to recognize this region. These results suggested that fragment C is the major target for the TeNT neutralizing antibodies, although different epitopes seem to be targeted by human and mouse antibodies. [ABSTRACT FROM AUTHOR]

Clostridium tetani causes a life-threatening infectious disease by production of tetanus neurotoxin (TeNT), a 150 kDa molecule composed of light (LC) and heavy chain (HC) polypeptides. The TeNT HC contains an N-terminal domain critical for LC translocation and a C-terminal toxin receptor-binding domain known as fragment C. Despite extensive investigations on epitope specificity of anti-TeNT antibodies, the immunodominant neutralizing epitopes of the toxin are poorly defined. This study describes the generation and characterization of four monoclonal antibodies (MAb) specific for TeNT. The characteristics of each MAb were explored in terms of isotype, specificity, affinity, and immuno-globulin heavy chain variable region (IGHV) gene usage using ELISA, Western blotting, and sequencing techniques. The toxin neutralizing activity of the MAbs was also investigated using the in vitro GT1b neutralizing assay. The data demonstrated that all MAbs bind to tetanus toxin and toxoid. Sub-fragments binding analysis showed that two MAbs react with fragment C, one with both fragment C and LC, and one with LC. Only the two fragment C-specific MAbs were able to neutralize the toxin. Sequencing of the expressed VH and VL genes revealed rearrangements of various VH and VL gene segments in all hybridoma clones. Clonality of the hybridomas was also confirmed by a competition assay that showed recognition of distinct epitopes by these MAbs. The results suggest the importance of TeNT fragment C in terms of immunogenicity and toxin neutralization activity. [ABSTRACT FROM AUTHOR]

Background and Aim: Managers are always looking for better ways to improve productivity of staff. The aim of this study was to introduce a model based on work and time measurement for Staff Management based on performance in hospital. Materials and Methods: This descriptive - practical study was conducted in ten steps for a medical documents expert’s in a general hospital. The main activities of employees were determined via interview and direct observation. Then expected time, tolerances, final coefficient and work units for each activity were calculated. Finally, the total working units were calculated. Results: Implementation of introduced model for a medical documents expert’s in a general hospital showed that the total work units which the staff was obliged to do in one month was 918 units and the remaining (1160-918) was the extra units. Conclusion: Using appropriate models for the performance management of hospital staff workloads, can help to improve the hospital productivity and staff satisfaction. [ABSTRACT FROM AUTHOR]

Background: Light chain (LC) and heavy chain carboxyterminal subdomain (Hcc) fragments are the most important parts of tetanus neurotoxin (TeNT) which play key roles in toxicity and binding of TeNT, respectively. In the present study, these two fragments were cloned and expressed in a prokaryotic system and their identity was confirmed using anti-TeNT specific polyclonal and monoclonal antibodies. Methods: LC and Hcc gene segments were amplified from Clostridium tetani genomic DNA by PCR, cloned into pET28b(+) cloning vector and transformed in Escherichia coli (E. coli) BL21(DE3) expression host. Recombinant proteins were then purified through His-tag using Nickel-based chromatography and characterized by SDS-PAGE, Western blotting and ELISA techniques. Results: Recombinant light chain and Hcc fragments were successfully cloned and expressed in (E. coli) BL21 (DE3). Optimization of the induction protocol resulted in production of high levels of Hcc (~35% of total bacterial protein) and to lesser extends of LC (~5%). Reactivity of the His-tag purified proteins with specific polyclonal and monoclonal antibodies confirmed their renatured structure and identity. Conclusion: Our results indicate successful cloning and production of recombinant LC and Hcc fragments of TeNT. These two recombinant proteins are potentially useful tools for screening and monitoring of anti-TeNT antibody response and vaccine production. [ABSTRACT FROM AUTHOR]

Little is known regarding the immunobiology of regulatory T (Treg) cells in hematopoietic malignancies, particularly in chronic lymphocytic leukemia (CLL). In the present study, we showed that the frequencies of CD8+ and CD4+ Treg cells were significantly increased in progressive as compared with indolent CLL patients and normal subjects. Enriched CD4+ Treg cells induced a similar level of inhibition in polyclonally activated B cells and effector T cells from CLL patients and normal subjects. Our results suggest that the increase in circulating Treg cells may result in downregulation of tumor-specific immune response, leading to tumor expansion and disease progression. [ABSTRACT FROM AUTHOR]

• This study was performed to investigate of using the plug weld of an inaccessible end of CSCs on the failure modes and flexural behavior in SCSbeams contrast to one-end welded ones. • The specimens were numerically modeled and verified to investigate parameters including the thickness of the concrete, the number of rows of CSCs, the type of connection of the CSCs, faceplates thickness, concrete thickness, CSCs width and thickness on structural behavior of SCS beams. • Based on the relationships of reinforced concrete beams, a modification factor was proposed to predict the final strength of SCS beams. An important weakness of the steel–concrete-steel (SCS) sandwich structure with corrugated-strip shear connectors (CSCs) is the lack of access to make two-end welding of CSCs to the steel faceplates. In the present study, the use of plug weld was proposed to weld an inaccessible end of the CSCs. To evaluate the partial two-end welded CSCs, the SCS flexural beams including one specimen with one-end welded and four specimens with two-end welded were fabricated and tested under concentrated quasi-static loading. Then, failure modes and force–displacement diagrams were analyzed by examining parameters including the thickness of the concrete core, the number of the rows of CSCs and the type of connection of the CSCs (one-end or two-end welded). To further investigate, numerical model of the experimental specimens were created and validated. Using numerical models, the effect of parameters of steel faceplates thickness, concrete core thickness, CSCs breadth and thickness was investigated. The results showed that the use of partial two-end welded CSCs with plug welding, in addition to increasing the ultimate strength by about 30%, also provided more energy absorption than samples with one-end welded CSCs. Also, in most samples with two-end welded CSCs, the flexural failure mode was dominant over the shear failure. Finally, based on the relationships of reinforced concrete beams, a correction factor was proposed to predict the ultimate strength of the samples, which was in acceptable agreement with the experimental and numerical results. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. The main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c. Method: In this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated. Results: The designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment. Conclusions: As far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients. [ABSTRACT FROM AUTHOR]

• In order to establish an optimal immune environment, for the semi-allogenic foetus, the maternal immune system undergoes functional changes. • Immune checkpoints and microRNAs play a role in establishing the appropriate local immune environment for successful pregnancy. • Further studies of the expression and function of ICPs in RPL women migwill potentially provide new opportunities in therapy and diagnosis. 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-β 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-β 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. [ABSTRACT FROM AUTHOR]

As one of the problems and diseases for women before 40 years, premature ovarian failure (POF) could be characterized by amenorrhea, low estrogen levels, infertility, high gonadotropin levels, and lack of mature follicles. Causes of the disease involve some genetic disorders, autoimmunity diseases, and environmental factors. Various approaches have been employed to treat POF, however with limited success. Today, stem cells are used to treat POF, since they have the potential to self-repair and regenerate, and are effective in treating ovarian failure and infertility. As mesenchymal stem cell (MSC) could simultaneously activate several mechanisms, many researchers consider MSC transplantation to be the best and most effective approach in cell therapy. A good source for mesenchymal stem cells is human umbilical cord (HUCMSC). Animal models with cyclophosphamide are required for stem cell treatment and performance of HUCMSC transplantation. Stem cell therapy could indicate the levels of ovarian markers and follicle-stimulating hormone receptor. It also increases ovarian weight, plasma E2 levels, and the amount of standard follicles. Herein, the causes of POF, effective treatment strategies, and the effect of HUCMSC transplantation for the treatment of premature ovarian failure are reviewed. Many studies have been conducted in this field, and the results have shown that stem cell treatment is an effective approach to treat infertility. [ABSTRACT FROM AUTHOR]

Abstract Introduction: A growing number of studies have thus far showed the association between type 2 diabetes mellitus (DM) and the intestinal microbiome homoeostasis. As reported, the gut microflora can be significantly different in patients with type 2 DM (T2DM) compared to those in healthy individuals. Methods: The authors collected the relevant articles published until 2022 and these are carefully selected from three scientific databases based on keywords. Discussion: This review highlights research on the anti-diabetic properties of berberine (BBR)-induced glucagon-like peptide-1 (GLP-1), as a glucose-lowering factor and a balance regulator in the microbial flora of the intestines, which plays an important role in adjusting the signalling pathways affecting insulin secretion. Results: Considering the anti-diabetic characteristics of the BBR-induced GLP-1, BBR makes a promising complementary treatment for reducing the clinical symptoms of DM by reducing the hyperglycaemia. Berberin might be a safe and effective drug for T2DM with little or no adverse effects. Highlights Berberine induces GLP-1 insulin secretion by PLC2 pathway in the intestinal Berberine-induced GLP-1 decreases mitochondrial stress and relocates cytochrome c out of the mitochondria. Berberine induces GLP-1 secretion in the intestine by altering the bacterial profile, thus could possibly lighten diabetes symptoms Berberine-induced SCFA production, SCFA causes GLP-1 secretion from the intestinal L-Cell. Preventing mitochondrial damage, reducing adipose tissue fat, and reducing oxidative stress are thus among the results of BBR-induced GLP-1. The lower costs of BBR, and its limited side effects and higher availability, make it a promising supplementary medicine for DM Berberine induces GLP-1 insulin secretion by PLC2 pathway in the intestinalBerberine-induced GLP-1 decreases mitochondrial stress and relocates cytochrome c out of the mitochondria.Berberine induces GLP-1 secretion in the intestine by altering the bacterial profile, thus could possibly lighten diabetes symptomsBerberine-induced SCFA production, SCFA causes GLP-1 secretion from the intestinal L-Cell.Preventing mitochondrial damage, reducing adipose tissue fat, and reducing oxidative stress are thus among the results of BBR-induced GLP-1.The lower costs of BBR, and its limited side effects and higher availability, make it a promising supplementary medicine for DM [ABSTRACT FROM AUTHOR]

Objectives: Thyroid autoimmunity is considered as the most prevalent autoimmune condition in women in fertility age. There are different clinical evidences indicating the association between thyroid autoimmunity and increased risk of RPL. This study aimed to analyze the association of Tregs and Th17 cells development factors and anti–thyroid peroxidase (anti-TPO) antibodies in RPL patients. Healthy controls (n = 36), TPO + controls (n = 25) and TPO + RPL (n = 32) participated in this study. After blood sampling, the frequency of Th17 and Tregs was evaluated using flow cytometry. Real-time PCR and ELISA was used to assess the status of Tregs and Th17 related transcription factors and cytokines in mRNA and protein level, respectively. Results: TPO + RPL group showed a higher Th17 frequency compared to healthy controls and TPO + controls groups (p = 0.0002 and p = 0.04, respectively). Additionally, mRNA expression levels of RORγT and IL-17 were significantly higher in TPO + RPL compared to healthy controls and TPO + controls groups. In contrast, Foxp3 and TGFβ expression was lower in TPO + RPL. ELISA findings also indicated a significantly higher IL-17 and lower TGFβ secretion in TPO + RPL compared to healthy controls and TPO + controls. Thyroid autoimmunity should intensely be controlled specially in patients with RPL history. [ABSTRACT FROM AUTHOR]

An electrochemical immunosensing platform was developed for the detection of receptor tyrosine kinase-orphan receptor-2 (ROR2) at a glassy carbon electrode (GCE) modified with the electrospun nanofiber containing polyvinylpyrrolidone (PVP), soy, and Au nanoparticles (AuNPs). The PVP/soy/AuNP nanofiber exhibited good electrochemical behavior due to synergistic effects between PVP, soy, and AuNPs. The PVP/soy in the modified film provided good mechanical strength, high porosity, flexible structures, and high specific surface area. On the other hand, the presence of AuNPs effectively improved conductivity, as well as the immobilization of anti-ROR2 on the modified GCE, leading to enhanced sensitivity. Various characterization approaches such as FE-SEM, FTIR, and EDS were used for investigating the morphological and structural features, and the elemental composition. The designed immunosensor performance was investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). Under optimum conditions with a working potential range from −0.2 to 0.6 V (vs. SCE), sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R2) were acquired at 122.26 μA/cm2 dec, 0.01–1000 pg/mL, 3.39 fg/mL, and 0.9974, respectively. Furthermore, the determination of ROR2 in human plasma samples using the designed immunosensing platform was examined and exhibited satisfactory results including good selectivity against other proteins, reproducibility, and cyclic stability. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive brain disorder characterized by the ongoing decline of brain functions. Studies have revealed the detrimental effects of hyperphosphorylated tau (p-tau) protein fibrils in AD pathogenesis, highlighting the importance of this factor in the early-stage detection of AD conditions. We designed an electrochemical immunosensor for quantitative detection of the cis conformation of the p-tau protein (cis-p-tau) employing platinum nanoparticles (Pt NPs) supported on zeolitic imidazolate frameworks (ZIF) for modifying the glassy carbon electrode (GCE) surface. Under optimum conditions, the immunosensor selectively and sensitively detected cis-p-tau within the broad linear range of 1 fg mL−1 to 10 ng mL−1 and the low limit of detection (LOD) of 1 fg mL−1 with desired reproducibility and stability. Furthermore, the fabricated immunosensor's performance was examined for the cis-p-tau analysis in the serum of AD patients, indicating its accuracy and feasibility for real-sample analysis. Notably, this is the first application of Pt@ZIF-8 nanocomposite in fabricating a valid immunosensor for selective cis-p-tau detection, even in the presence of trans-p-tau. It is worth mentioning that the enzyme-linked immunosorbent assay (ELISA) reference technique is not able to evaluate pico- or femtomolar concentrations of cis-p-tau, making the fabricated immunosensor superior for early-stage measurement and screening of AD. [ABSTRACT FROM AUTHOR]

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, [ABSTRACT FROM AUTHOR]

Biallelic mutations in the ITK gene cause a T-cell primary immunodeficiency with Epstein-Barr virus (EBV)–lymphoproliferative disorders. We describe a novel association of a homozygous ITK mutation with β–human papillomavirus (HPV)–positive epidermodysplasia verruciformis. Thus, loss of function in ITK can result in broad dysregulation of T-cell responses to oncogenic viruses, including β-HPV and EBV. [ABSTRACT FROM AUTHOR]

Autologous platelet-rich plasma (PRP) and platelet lysate (PL) are nowadays promising candidates in the treatment of articular cartilage lesions. We aimed to compare PRP and PL injection effectiveness in patients with knee osteoarthritis (KOA). A total of fifty women with KOA were included in the study. Patients were treated with intra-articular injections of PRP and PL. Clinical outcomes were evaluated using the comparison of VAS, WOMAC, and ROM scores. The concentration levels of growth factors and cytokines were measured by ELISA. All patients showed significant improvements in pain and function following treatment of KOA with PL and PRP compared to baseline. Moreover, PL's concentration of growth factors was significantly higher than PRP. A significant increase was also observed in all of the aforementioned mediators in both PRP and PL products compared to control. These results can introduce PL as a promising and alternative option for KOA therapy in the future. [ABSTRACT FROM AUTHOR]

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into Tregs from patients with COVID-19. Exosomes were isolated from adipose derived -- tissue MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127- Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo--treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of Tregs, potentiating its therapeutic effects in COVID-19. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is a main organism of tooth infections including tooth decay and periodontitis. The aim of this study was to assess the influence of sucrose and starch on biofilm formation and proteome profile of S. mutans ATCC 35668 strain. The biofilm formation was assessed by microtiter plating method. Changes in bacterial proteins after exposure to sucrose and starch carbohydrates were analyzed using matrix‐assisted laser desorption/ionization mass spectrometry. The biofilm formation of S. mutans was increased to 391.76% in 1% sucrose concentration, 165.76% in 1% starch, and 264.27% in the 0.5% sucrose plus 0.5% starch in comparison to biofilm formation in the media without sugars. The abundance of glutamines, adenylate kinase, and 50S ribosomal protein L29 was increased under exposure to sucrose. Upregulation of lactate utilization protein C, 5‐hydroxybenzimidazole synthase BzaA, and 50S ribosomal protein L16 was formed under starch exposure. Ribosome‐recycling factor, peptide chain release factor 1, and peptide methionine sulfoxide reductase MsrB were upregulated under exposure to sucrose in combination with starch. The results demonstrated that the carbohydrates increase microbial pathogenicity. In addition, sucrose and starch carbohydrates can induce biofilm formation of S. mutans via various mechanisms such as changes in the expression of special proteins. [ABSTRACT FROM AUTHOR]

The disturbance of maternofetal immune tolerance is identified as one of the important issues in the pathology of preeclampsia (PE). PE exosomes are believed to possess significant roles in immune abnormalities. In this study, to assess the possible effects of PE exosomes in the pathophysiology of preeclampsia patients, exosomes were isolated from the serum of PE patients and incubated with peripheral blood mononuclear cells (PBMCs) of healthy pregnant women. Also, exosomes from healthy pregnant women were utilized as the control. Th17/Treg ratio in PE and healthy pregnant women and the effects of PE exosomes on expression level of Th17 and Treg transcription factors, as well as their related cytokines in PBMCs of healthy pregnant women, were evaluated. A significant decrease in Treg cell number and increase in Th17 cells and Th17/Treg ratio were observed in PE patients. Following PE-exosome intervention, a significant increase in mRNA expression level of RORγt, IL-17, IL-23, IL-1β, and IL-6, and significant decrease in IL-10 and TGFβ were evident. On the other hand, no significant difference in FoxP3 level was detected. Additionally, increased IL-6, IL-17, IL-23, and IL-1β levels and decreased IL-10 level in the supernatant of cultured PBMCs from healthy pregnant women following PE-exosome intervention were exhibited. However, TGF-β level did not change significantly. Based on our findings, PE exosomes are able to alter the activity of Th17 and Treg cells as well as their related gene expression and cytokine profiles. These findings support the probable role of PE exosomes in PE pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is proven to have anti-apoptotic effects in several malignancies. In addition, HO-1 is reported to cause chemoresistance and increase cell survival. Growing evidence indicates that HO-1 contributes to the course of hematological malignancies as well. Here, the expression pattern, prognostic value, and the effect of HO-1 targeting in HMs are discussed. Main body: According to the recent literature, it was discovered that HO-1 is overexpressed in myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), acute myeloblastic leukemia (AML), and acute lymphoblastic leukemia (ALL) cells and is associated with high-risk disease. Furthermore, in addition to HO-1 expression by leukemic and MDS cells, CML, AML, and ALL leukemic stem cells express this protein as well, making it a potential target for eliminating minimal residual disease (MRD). Moreover, it was concluded that HO-1 induces tumor progression and prevents apoptosis through various pathways. Conclusion: HO-1 has great potential in determining the prognosis of leukemia and MDS patients. HO-1 induces resistance to several chemotherapeutic agents as well as tyrosine kinase inhibitors and following its inhibition, chemo-sensitivity increases. Moreover, the exact role of HO-1 in Chronic Lymphocytic Leukemia (CLL) is yet unknown. While findings illustrate that MDS and other leukemic patients could benefit from HO-1 targeting. Future studies can help broaden our knowledge regarding the role of HO-1 in MDS and leukemia. C7s1tZ_Vi-gUBcV-QiSC3w Video abstract [ABSTRACT FROM AUTHOR]

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre‐eclampsia are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid‐derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications. [ABSTRACT FROM AUTHOR]

Interleukin 17 (IL17)-expressing CD4+ T cells and IL-17/IL-23 pathway play a key role in the pathogenesis of axial spondyloarthritis (axSpA). Synbiotics have been suggested due to their immunomodulatory effects in the treatment of autoimmune diseases. This randomized double-blind, placebo-controlled trial was designed to assess the effects of synbiotic supplement on IL-17/IL-23 pathway and disease activity in patients with axSpA. Forty-eight axSpA patients were randomly allocated to use one synbiotic capsule or placebo daily for 12 weeks. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASAS-endorsed disease activity score-C-reactive protein (ASDAS-CRP). The secondary outcome was proportion of IL17-expressing CD4+ T cells, IL-17 and IL-23 gene expression, and supernatant levels of IL-17 and IL-23, which were measured at the baseline and end of the trial. A total of 48 patients were randomized into the synbiotic and placebo groups. Thirty-eight patients completed the study. Synbiotic supplementation significantly reduced the proportion of IL17-expressing CD4+ T cells (4.88 ± 2.47 vs. 2.16 ± 1.25), gene expression of IL-17 (1.03 ± 0.24 vs. 0.65 ± 0.26) and IL-23 (1.01 ± 0.13 vs. 0.68 ± 0.24) and serum IL-17 (38.22 ± 14.40 vs. 24.38 ± 11.68) and IL-23 (51.77 ± 17.40 vs. 32.16 ± 12.46) compared with baseline. Significant differences between groups were noticed only in the proportion of IL17-expressing CD4+ T cells, and IL-17 and IL-23 gene expression. Synbiotic supplementation did not significantly alter BASDAI and ASDAS-CRP compared with baseline and placebo group at the end of trial. Present study indicated beneficial effect of synbiotic supplement on IL-17/IL-23 pathway without improving disease activity in axSpApatients. Synbiotic supplementation reduced IL17-expressing CD4+ T cells proportion in axSpA. Synbiotic supplementation decreased IL-17 and IL-23 gene expression in axSpA. Synbiotic supplementation did not change disease activity score in axSpA. [ABSTRACT FROM AUTHOR]

Linezolid, an oxazolidinone antimicrobial agent that acts by inhibiting protein synthesis in a unique fashion, is used in the treatment of community-acquired pneumonia, skin and soft-tissue infections and other infections caused by Gram-positive bacteria including VRE and methicillin-resistant staphylococci. Currently, linezolid resistance among these pathogens remains low, commonly <1.0%, although the prevalence of antibiotic resistance is increasing in many countries. Therefore, the development of resistance by clinical isolates should prompt increased attention of clinical laboratories to routinely perform linezolid susceptibility testing for this important agent and should be taken into account when considering its therapeutic use. Considering the importance of linezolid in the treatment of infections caused by Gram-positive bacteria, this review was undertaken to optimize the clinical use of this antibiotic. [ABSTRACT FROM AUTHOR]

The oral cavity is inhibited by many of the bacterial species. Some of them have a key role in the development of oral disease. Interrelationships between oral microbiome and systemic conditions such as head-and-neck cancer have become increasingly appreciated in recent years. Emerging evidence also suggests a link between periodontal disease and oral cancer, and the explanation being that chronic inflammation could be a major factor in both diseases. Squamous cell carcinoma is that the most frequently occurring malignancy of the oral cavity and adjacent sites, representing over 90% of all cancers. The incidence of oral cancer is increasing, significantly among young people and women. Worldwide there are 350,000–400,000 new cases diagnosed every year. Bacteria, viruses, and fungi are strongly implicated as etiological factors in certain cancers. In this review we will discuss the association between the development of oral cancer in potentially malignant oral lesions with chronic periodontitis, chronic Porphyromonas gingivalis , Fusobacterium nucleatum , candida, other microbes and described mechanisms which may be involved in these carcinoma. [ABSTRACT FROM AUTHOR]

Lack of regulation of microRNAs (miRNAs) expression has been observed in some autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. G2013, as a novel non-steroidal anti-inflammatory drug (NSAID) with the immunomodulatory property, has been shown the positive effects in multiple sclerosis and anti-ageing experimental models. This research aimed to study the inhibitory effect of G2013 on miR-155 gene expression using HEK-Blue hTLR4 and Null2 cell lines. Total RNA was extracted from the treated and control cells. cDNA was made for miRNA and expression levels of miR-155 were detected by quantitative Real-time PCR using a specific primer together with U6 as the internal reference gene. A non-significant reduction was observed in the gene expression level of miR-155 in the HEK-Blue hTLR4 and Null2 cell lines under the influence of a low dose of G2013. In contrast, adding lipopolysaccharide (LPS) to the mentioned cells led to a significant increase in miR-155 expression, whereas addition of LPS four hours after exposing the cells with G2013 could not increase the expression level of this miRNA (P < 0.05). Collectively, this research showed that G2013, as a novel NSAID with immunomodulatory property is able to significantly decrease the gene expression of miR-155 following stimulation by LPS. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is considered one of the most infectious diseases in the world. In this study, we intended to examine the epidemiology of tuberculosis by MIRU-VNTR to define the changes that occur in the transmission of tuberculosis in the region during the COVID-19 era. A total of 120 Mycobacterium tuberculosis isolates were collected from sputum samples of patients referred to East Azerbaijan Center TB from December 2020 to August 2021. Demographic information such as age, sex, place of birth, previous TB history, and relevant medical data was collected. The proportion method was performed for drug susceptibility testing, and the PCR-based MIRU-VNTR method was applied to identify molecular epidemiology relationships. Results: The isolates were collected from 78 male (65%) and 39 female (32.5%) Iranian patients and 3 (2.5%) Azerbaijani patients. Ninety-three distinct patterns were identified including 15 clustered patterns and 36 unique patterns. The largest cluster was composed of seven isolates. Furthermore, one cluster with 5 members, four clusters with 3 members, and nine clusters with 2 members. In MIRU-VNTR typing, 75 clusters belonged to the Tabriz region and just 3 to the Republic of Azerbaijan. All isolates were sensitive to rifampin, isoniazid, and ethambutol. Conclusions: Results of the current study showed COVID-19 pandemic had a direct effect on the transmission and diagnosis of tuberculosis. Less diagnosis and less clustering can indicate public controls and hygiene, and the use of masks had a direct effect on the transmission and diagnosis of tuberculosis. However, misidentification and less focus on other respiratory infections are expected during the pandemic. Studies on the co-infection of COVID-19 and tuberculosis and the role of mask and sanitization against TB are strongly recommended. [ABSTRACT FROM AUTHOR]

Premature ovarian failure is a to some extent unknown and intricate problem with diverse causes and clinical manifestations. The lack of ovarian sex hormones presumably is effective in the occurrence of ovarian failure. Our progress in this field has been very little despite undertaken scientific research endeavors; scholars still are trying to understand the explanation of this dilemmatic medical condition. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Very recently Scientists have investigated the regulating effects of small RNA molecules on steroidogenesis apoptosis, ovulation, gonadal, and corpus luteum development of ovaries. In this literature review, we tried to talk over the mechanisms of miRNAs in regulating gene expression after transcription in the ovary. 9nPs_Ypm2yRV7ZYy5cg5NU Video abstract [ABSTRACT FROM AUTHOR]

Objectives: From the ancient, medicinal benefits of Hyssop (Hyssopus officinalis L.) have been implicated for respiratory and digestive diseases despite the effects of Hyssop on viral infections have not been mechanistically investigated. In this study, we examined whether the Hyssop extract activated anti-viral innate immunity, as a sentinel for immune system, through activation of endosomal TLRs recognizing nucleic acids and their downstream signaling. The Hyssop herb extracts was prepared and co-cultured with healthy individual's peripheral blood mononuclear cells (PBMCs). After viability assay, gene expression levels of TLR3,7,8,9, as well as MyD88 and NF-κB, were evaluated in treated PBMCs using Real-time PCR. Next, the secretion level of immune related cytokines was quantified via ELISA. Results: Post 24 h, 40 µg/ml of the extract significantly inhibited the viability of less than 50% of cells compared to the control and had a maximum effect on cellular function. The Hyssop-treated PBMCs demonstrated an elevated expression of endosomal TLRs genes, as well as MyD88 and NF-κB. Moreover, the release of INF-α and β notably enhanced in cell culture supernatant, while the content of inflammatory cytokines remarkably diminished (P < 0.05). The Hyssop extract was capable of inducing antiviral innate immune responses so can be promising in antiviral drug strategies. [ABSTRACT FROM AUTHOR]

The concept of reduced maternal immune responsiveness in pregnancy emerged when some studies demonstrated that the immune response to particular antigens is decreased throughout pregnancy. Manifold substances are stated to be immunomodulatory or immunosuppressive, such as the components of the seminal fluid as well as several regulatory and inhibitory molecules. Slight changes take place in the maternal immune competence in pregnancy, which makes sense since a generalized immunosuppression would probably result in the loss of fetus. Supposedly, enhancement of the immune system and the following immunomodulation in mother are the operative mechanism throughout pregnancy. Conceivably, the overall response of the immune system during pregnancy could be the net result of interactions which operate for ensuring the survival of the antigenically alien fetus and simultaneously prevent an excessive immunosuppression state. Therefore, such dynamic homeostatic mechanisms seem to be significant for a successful pregnancy. [ABSTRACT FROM AUTHOR]

After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody‐dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs) transplantation is considered a suitable treatment for malignant or nonmalignant hematological diseases. This study aims to investigate the HSCs homing factors in bone marrow (BM) donors of acute lymphoblastic leukemia (ALL) patients following granulocyte colony‐stimulating factor (G‐CSF) injection, as well as the G‐CSF effects on BM transplantation quality in these patients. To mobilize HSCs into peripheral blood, G‐CSF was used for ALL patient's BM donors. For HSCs counting, CD34+ cells were evaluated in analogous and autologous donors using flow cytometry. The expression of stem cell homing factors in CD34+ cells and peripheral blood mononuclear cells (PBMCs) were investigated using a real‐time polymerase chain reaction. Finally, hematological factors after BM transplantation in ALL patients were assessed. According to our results, after G‐CSF injection, the level of CD34+ HSCs was statistically increased. Besides, autologous donors showed a higher level of CD34+ cells compared to analogous donors before and after G‐CSF injection. Additionally, a higher number of CD34+ HSCs was achieved in the autologous samples following G‐CSF injection. Furthermore, after G‐CSF injection, the expression of matrix metalloproteinase (MMP)‐2, MMP‐9 was increased; while, stromal cell‐derived factor 1, intercellular adhesion molecule‐1, and vascular cell adhesion molecule‐1 expression were decreased. Moreover, the expression of C‐X‐C chemokine receptor type 4, lymphocyte function‐associated antigen 1, and very late antigen‐4 in CD34+ cells and PBMCs were decreased. BM transplantation on Day 90 also caused an increased level of white blood cells, red blood cells, and platelets as compared to the first day; however, no statistical differences were observed in hemoglobin level. In conclusion, G‐CSF by altering the expression of HSCs homing factors in ALL donors improves BM transplantation quality in ALL patients. [ABSTRACT FROM AUTHOR]

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters. [ABSTRACT FROM AUTHOR]

Numerous treatment strategies have so far been proposed for treating refractory thin endometrium either without or with the Asherman syndrome. Inconsistency in the improvement of endometrial thickness is a common limitation of such therapies including tamoxifen citrate as an ovulation induction agent, acupuncture, long-term pentoxifylline and tocopherol or tocopherol only, low-dose human chorionic gonadotropin during endometrial preparation, aspirin, luteal gonadotropin-releasing hormone agonist supplementation, and extended estrogen therapy. Recently, cell therapy has been proposed as an ideal alternative for endometrium regeneration, including the employment of stem cells, platelet-rich plasma, and growth factors as therapeutic agents. The mechanisms of action of cell therapy include the cytokine induction, growth factor production, natural killer cell activity reduction, Th17 and Th1 decrease, and Treg cell and Th2 increase. Since cell therapy is personalized, dynamic, interactive, and specific and could be an effective strategy. Despite its promising nature, further research is required for improving the procedure and the safety of this strategy. These methods and their results are discussed in this article. [ABSTRACT FROM AUTHOR]

During SARS-CoV-2 infection, an effective immune response provides the first line of defense; however, excessive inflammatory innate immunity and impaired adaptive immunity may harm tissues. Soluble immune mediators are involved in the dynamic interaction of ligands with membrane-bound receptors to maintain and restore health after pathological events. In some cases, the dysregulation of their expression can lead to disease pathology. In this literature review, we described current knowledge of the basic features of soluble immune mediators and their dysregulation during SARS-CoV-2 infections and highlighted their contribution to disease severity and mortality. DXiAWb3TC5e1Uu4oQZrWWj Video Abstract [ABSTRACT FROM AUTHOR]

Objective: As a progressive chronic condition, osteoarthritis (OA) causes substantial pain and impairment. Secrete proinflammatory cytokines are essential mediators involved in the pathophysiology of OA. In this regard, the clinical effectiveness of autologous conditioned serum (ASC) has been shown through its injection into OA tissues. This study aimed to assess the effectiveness and concentration level of ACS components produced by Nano-carbon glass beads. Intravenous whole blood was obtained from each New Zealand male rabbit by 10-ml syringes, comprising 33 medical-grade Nano carbon-coated glass beads. Serum retrieving was performed after 6–8 h incubation (37 C, 5% Co2), and then centrifuged. The ACS was then injected into OA rabbits to assess its function. Results: Glass beads-prepared ACS coated with Nano-carbon, induced a huge amount of cytokines and growth factors production. The concentration level of anti-inflammatory cytokines and proinflammatory cytokines was improved throughout Nano-carbon coated glass beads stimulation. ACS also shortened the recovery time and improved the function and mobility of OA rabbits. We showed that ACS improved the function and mobility of OA rabbits, as well as shortened the recovery time. It is suggested that further studies evaluate this effectiveness. [ABSTRACT FROM AUTHOR]

Objectives: Osteoporosis is a common skeletal disorder attributed to age and is defined as a systematic degradation of bone mass and the microarchitecture leading to bone fractures. Exosomes have been reported in almost all biological fluids and during the failure of bone remodeling. 20 ml of blood samples were obtained from osteoporotic and non-osteoporotic postmenopausal women. After the isolation of peripheral blood mononuclear cells (PBMCs), T cells were separated via the magnetic-activated cell sorting (MACS) technique. Exosomes were driven from T cells of non-osteoporotic and osteoporotic volunteers. Subsequently, normal osteoblasts were treated with obtained T cell exosomes to assess osteoblastic function and gene expression. Results: Runx2, type I collagen, osteopontin, and osteocalcin expression decreased in osteoblasts treated by osteoporotic T cell exosomes. In contrast, an increased expression of the mentioned genes was observed following non-osteoporotic T cell exosome treatment. Additionally, osteoblast alkaline phosphatase (ALP) activity treated with non-osteoporotic T cell exosomes increased. However, this activity decreased in another group. Our data demonstrated that T cell exosomes obtained from osteoporotic and non-osteoporotic individuals could alter the osteoblastic function and gene expression by affecting the genes essential for bone remodeling. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T -cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T -cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation. [ABSTRACT FROM AUTHOR]

In this work, citric acid-based quantum dots (CA-QDs) as a novel and safe crosslinked agent was applied in different feeding ratios (5–15 wt%) to synthesize carboxymethyl cellulose/polyvinyl alcohol (CMC/PVA) nanofibers (NFs) for the first time. Colistin (CL) as an antibacterial agent was also loaded (2 w/w%) during the synthesizing process of CMC/PVA electrospun NFs to trigger antimicrobial properties. The morphological, hydrophilic, and mechanical properties of the prepared NFs were fully investigated with different techniques. The electrospun NFs with crosslinking ratios of 10 wt% CA-QDs revealed appropriate mechanical properties. According to cell culture data, the prepared NFs demonstrated good cytocompatibility against HFF-1 cells (over 80% cell viability). Remarkably, CL-loaded NFs showed desired antibacterial efficacy against S. aureus , E. coli , K. pneumoniae , and P. aeruginosa with 1.0–1.4, 1.3–1.4, 0.8–1.0, and 1.3–1.5 cm inhibition zones, respectively. These outcomes suggested that the fabricated NFs can be useful as wound healing scaffolds. [Display omitted] [ABSTRACT FROM AUTHOR]