فهرست مطالب abdollah jafarzadeh

It is well-known that TH1 and Treg cells exert anti- and pro-tumorigenic activity, respectively. Thus, TH1 cell suppression together with Treg cell hyperactivation contribute to tumor development. Glycyrrhiza glabra (G. glabra) has various immunomodulatory and anti-tumorigenic properties. To explore the impacts of G. glabra extract on different parameters related to TH1 and Treg cells using a breast cancer (BC) model. Four groups of Balb/C mice bearing 4T1 cell-induced BC were treated intraperitoneally with either saline or G. glabra extract at dosages of 50, 100 and 150 mg/kg (G. glabra-50, G. glabra-100, and G. glabra-150, respectively). After sacrificing animals on day 26, the frequency of splenic TH1 and Treg cells, the levels of serum IFN-γ, TGF-β, and IL-12, and intra-tumoral expressions of granzyme-B, T-bet, and FOXP3 were assessed. Compared to untreated tumor control (UTC) group, treatment with G. glabra-50, G. glabra-100, or G. glabra-150 increased the survival rate, percentage of TH1 cells, and T-bet expression. Conversely, they reduced the percentage of Treg cells, and serum TGF-β levels. In comparison to the UTC group, treatment with G. glabra-50 and G. glabra-150 increased the serum IL-12 levels. Treatment with G. glabra-100 and G. glabra-150 boosted granzyme-B expression. Treatment with G. glabra-150 elevated IFN-γ levels, while treatment with G. glabra-50 decreased the FOXP3 expression. IL-12 levels were higher in mice treated with G. glabra-150 compared to those treated with G. glabra-100. Treatment of mice with BC using G. glabra extract improved survival rate, reduced tumor growth, and modulated T cell-mediated immune responses.

The ABO/Rh blood groups were related to susceptibility to numerous infectious and non-infectious diseases. Here, the association of ABO/Rh groups with susceptibility to COVID-19 and disease severity was investigated in a population from southeast Iran.

 In this descriptive study, information regarding the clinical characteristics and ABO/Rh blood groups was collected from 524 patients with COVID-19 from March to October, 2020. The data of blood groups from patients were compared with those from 7365 healthy individuals during the same period. Data was analyzed using SPSS.

 No significant differences were found between COVID-19 patients and the healthy group regarding the proportions of A, B, and O blood groups. However, the proportion of the AB blood group was significantly higher in COVID-19 patients than that in healthy people (11.8% versus 8.2%, P <0.004). When the A group was considered as a reference, the AB blood group was associated to a greater risk of COVID-19 [OR: 1.45 (1.06-1.98), P<0.02]. No association was found between ABO blood groups and COVID-19 severity. The proportion of the Rh-positive blood group was slightly higher in COVID-19 patients than in the other group. The proportion of Rh-negative patients was greater in severe COVID-19 than in mild and moderate forms (P<0.001). In A, AB, and O blood groups, the proportions of Rh-negative patients were greater in severe COVID-19 than those with mild and moderate disease (P=0.05, P<0.05, and P<0.001, respectively).

 The AB blood group was associated with greater susceptibility to COVID-19, while Rh-negative status was positively associated with disease severity.

Multiple sclerosis (MS) as a complex neurological abnormality is marked with loss of myelin and axons due to chronic inflammatory and autoimmune responses. The modulatory properties of the low dose radiation (LDR) on inflammatory and immune responses have well known.

The current research aimed to assess the impacts of LDR on the disability in patients suffering from MS.

This experimental pilot study was done on 10 patients with secondary progressive multiple sclerosis (SPMS). After magnetic resonance imaging, the SPMS patients were treated by LDR at a daily dose of 2 Gray for 5 consecutive days (totally 10 Gray dose) using a linear accelerator. The extent of the disability was evaluated one week after the completion of radiotherapy using expanded disability status scale (EDSS).

After receiving radiotherapy, the patients had a feeling of wellbeing of some sort. The mean of EDSS was significantly reduced after radiotherapy compared with before irradiation (7.4±0.45 vs 6.35±1.18; P<0.017). EDSS more decreased in younger SPMS patients (P=0.0001), and in the women after LDR (P=0.027). 

Radiotherapy can reduce fatigue and EDSS in patients with SPMS. The age and gender of patients may influence the LDR efficacy.

Following bone trauma, several factors participate in making a balance between the activity of osteoblasts and osteoclasts. The receptor activator of nuclear factor kappa B ligand (RANKL), receptor activator of nuclear factor kappa B (RANK), and osteoprotegerin (OPG) molecules play critical roles in the healing process via regulation of osteoclasts function. Turmeric is suggested to have an anti-osteogenic potential; however, its effect on accelerating bone healing has not been adequately studied. Here, we used a rat model of femur fracture to explore the effect of treatment with turmeric extract on the bone repair and the expression of RANK, RANKL, and OPG molecules.

Eight rats were subjected to surgery, randomly divided into two groups, and treated orally with turmeric (200 mg/kg), or olive oil. Four oil-treated rats without bone fracture were used as control group. After six weeks of treatment, the femurs of animals were examined for radiological, histological, and gene expression analysis.

X-ray radiography showed thicker callus and a more obscure fracture line in the turmeric group. Furthermore, higher osteoblast percentages but no osteoclasts were observed in turmeric-treated animals, representing better repair of bone in the fracture site. Also, real-time analyses showed that treatment with turmeric reduced RANK and RANKL expression (p <0.0001) and lowered RANKL/OPG ratio (p=0.01) in femoral bone tissue.

Our findings indicated the turmeric ability to facilitate bone hemostasis and optimize the expression of key markers involved in the bone metabolism.

COVID-19 and malignancy can affect the susceptibility of one another. Clinically recovered COVID-19 individuals display immune abnormalities that persist several months after discharge. The lymphopenia-related immunosuppression, functional exhaustion of cytotoxic lymphocytes (such as CD8+ cytotoxic T-cells and natural killer cells), hyperinflammatory responses, oxidative stress, downregulation of interferon response, development of the myeloid-derived suppressor cells, downregulation of tumor suppressor proteins and perhaps reactivation of the latent oncogenic viruses may directly and/or indirectly play a role in the cancer development and recurrence in severe COVID-19 patients. SARS-CoV-2-infected malignant patients may be at higher risk of death of their cancer than SARS-CoV-2-uninfected patients with the same cancers. On the other side, the patients with some types of cancers may be more vulnerable to SARS-CoV-2 infection compared with the non-cancerous individuals, due to their immunocompromised state resulted from malignancy, chemotherapy, and other concomitant abnormalities as well as perhaps greater expression of angiotensin-converting enzyme 2. SARS-CoV-2-infected cancerous patients are unable to produce an effective anti-virus immune response and may exhibit more severe forms of COVID-19. This review described the possible impacts of SARS-CoV-2 infection on cancer development and recurrence, and the potential cancer impacts on COVID-19 development, while the possible interventions are highlighted.

Recent evidences revealed that some genetic factors strongly predict occurrence of lamotrigine (LTG)-related skin reactions. The present study aimed to assess the association between some human leukocyte antigen (HLA)-B alleles and risk of LTG-related skin reactions among a sample of epileptic patients. Totally, 36 epileptic patients expressing LTG-related skin reactions and 70 sex- and age-matched healthy individuals were enrolled into this case-control study. Blood samples were collected from all participants and genomic DNA was extracted by salting-out method. HLA-B alleles were determined using standard sequence specific primer-PCR (SSP-PCR) technique. Of the 31 HLA alleles assessed in our survey, the frequencies of HLA-B*38 and HLA-B*40 were significantly higher in epileptic patients with LTG-related skin reactions when compared to the control group. In term of gender, the frequency of HLA-B*40 allele was significantly higher in the epileptic men with LTG-related skin reactions, whereas the frequency of HLA-B*38 allele was significantly higher in the epileptic women with LTG-related skin reactions than controls with the same gender. Moreover, the frequency of HLA-B*38 allele in patients with high grade of LTG-related skin side effects was significantly higher than patients with low grade of LTG-related skin side effects. These results indicated possible association between HLA-B*40 and HLA-B*38 alleles and LTG-induced skin lesions in Iranian epileptic patients. HLA-B*40 and HLA-B*38 alleles might be differentially expressed in male and female epileptic patients with LTG-induced skin lesions.

A fundamental duty of the immune system is to defend against infectious agents. Significant abnormalities were reported in immune parameters of hypothyroid and hyperthyroid patients. In this study, we aim to assess various quantities of antibodies against the tetanus toxin (anti-TT) in hypothyroid and hyperthyroid patients. 

Anti-TT levels were measured in serum samples from 50 hypothyroid patients, 50 hyperthyroid patients, and 50 euthyroid individuals, using the ELISA method. Besides, the minimum protective quantity of anti-TT was considered 0.1 IU/mL.

Seroprotective rates against tetanus were 100, 80, and 96.0 % in euthyroid, hypothyroid, and hyperthyroid groups with the means of 3.52 ± 0.31, 1.62 ± 0.21, and 4.07 ± 0.32 IU/ml, respectively. Accordingly, hypothyroid patients exhibited lower anti-TT levels and seroprotective rates than the euthyroid group (P < 0.001 and P<0.004, respectively). Besides, in the hypothyroid group, anti-TT quantities and seroprotective rates were lower than those in hyperthyroid individuals (P < 0.001 and P < 0.03, respectively).

The findings demonstrated lower immunity and higher susceptibility to tetanus in patients with hypothyroidism. However, more studies are needed to be conducted in this field to provide more data to be considered in health programs.

The spread of the novel coronavirus seems mysterious enough to make us double-check the indices being used to predict its transmission. In this study, serological analysis was performed to assess some metric and epidemiological aspects of the infection and its transmissibility among people in contact with SARA-CoV-2 patients.   

A total of 453 contacts of 40 COVID-19 patients entered this contact tracing prospective cohort study. Accordingly, SARS-CoV-2 patients were diagnosed by the real-time polymerase chain reaction testing of nasopharyngeal samples. The infectiousness history was detected by the serological testing of IgG and IgM. Trained expert team completed two questionnaires, and blood samples were taken by experts in a laboratory. Data were analyzed using SPSS V21.0 and R software.

The mean ages of the SARS-CoV-2 patients and the contacts were 53.0±18.2 and 30.8±19.3 years, respectively. The overall R0 of the infection was 2.58. Household and non-household secondary attack rates (SAR) were 20% (95%CI; 12.7–27.3) and 11.3% (95%CI; 6.1-16.5), respectively. The transmission probability of each contact was 0.0205, and the serial interval was 6.4±4.6 (95% CI; 5.2–7.6) days. The SAR was higher among the contacts who were exposed to asymptomatic primary cases (28%, 95%CI; 10-46%) than (13.8%, 95%CI; 9.4-18.2) among those exposed to symptomatic patients. 

It is concluded that the herd immunity of 60 to 65% is needed in human communities, based on the amount of R0 estimated in our survey. The findings demonstrated the amount of the reduction in infection R0, which is predicted based on both clinical and public health interventions.

Metformin, cimetidine, and ibuprofen separately exhibit immunomodulatory and anti-tumorigenic effects. Herein, the impacts of metformin alone and in combination with cimetidine/ibuprofen on some Th1- and regulatory T (Treg) cell-related parameters were evaluated using a breast cancer (BC) model. For establishing the BC model, four groups of Balb/c mice were challenged with the carcinoma cell line. After 11-30 days post-induction, they were treated intraperitoneally (with metformin (200 mg/kg), "metformin plus cimetidine (20 mg/kg)"; "metformin plus ibuprofen (20 mg/kg)", or with all three drugs in mentioned doses. Untreated BC and without tumor mice were enrolled as control groups. On day 31, splenic Th1 and Treg cell frequencies, serum interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-β) concentration, and intra-tumoral T-bet, TGF-β, and forkhead box protein P3 (FOXP3) expression were measured; using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time-PCR, respectively. Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-γ concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-β concentration, and the expression of FOXP3 and TGF-β compared with un-treated BC mice. FOXP3 expression in the metformin-treated group was lower in mice who received combination therapy. Survival rate and body weight were increased, while tumor size and spleen index were reduced in mice treated with metformin alone and its combination with cimetidine and/or ibuprofen. No remarkable differences were found between metformin-treated mice and those who received combination therapies regarding Th1 and Treg cell percentages, TGF-β expression, body weight, tumor size, and spleen index. The benefits of combinational therapy may be largely attributed to metformin. Immunotherapeutic potentials of metformin in cancers need further considerations.

Anesthesiologists should obtain the best technique for cesarean section (CS). This study designed to compare the effect of general anesthesia (GA) and spinal anesthesia (SA) on immune system function in elective CS.

This descriptive study was performed on forty candidates for elective CS. They were randomly divided into GA and SA groups. The serum concentrations of interleukin (IL)‑4, IL‑6, IL‑10, and IL‑17 and interferon‑gamma (IFN‑γ) were measured using ELISA method prior to anesthesia (T0), immediately after the uterine incision (T1), 2 h post CS (T2), and 24 h post CS (T3). Data were analyzed using descriptive statistics and Chi‑square, independent t‑test, and repeated measures.

No significant differences were observed between the GA and SA groups regarding the serum levels of IL‑4, IL‑6, IL‑10, IL‑17, and IFN‑γ. The serum levels of transforming growth factor beta (TGF‑β) in the SA group were significantly (P = 0.003) more than that of the GA group at T3.

According to the angiogenesis properties of TGF‑β, it seems that SA probably affects the rate of recovery more than that of the GA.

 The imbalanced expression of chemokines plays critical role in the development of Helicobacter pylori-mediated complications.

 Our aim was to determine ginger extract (GE) effects on the expression of chemokines CCL17, CCL20, CCL22, and CXCL10, as well as CCR4, CCR6, and CXCR3 receptors by peripheral blood mononuclear cells (PBMCs) from H. pylori -infected patients with peptic ulcer (PU).

 Peripheral blood mononuclear cells were obtained from 20 patients with H. pylori-associated PU, 20 H. pylori-infected asymptomatic subjects (HAS), and 20 non-infected healthy subjects (NHS). The PBMCs were stimulated by 10 µg/mL of H. pylori-derived crude extract (HPCE) in the presence of 0, 10, 20, and 30 µg/mL of GE. After 36 hours, the supernatant and the RNA extracted from the cells were tested for chemokine concentration and chemokine receptor expression using ELISA and real-time PCR techniques, respectively.

 In PU patients, treating HPCE-stimulated PBMCs with 10, 20, or 30 µg/mL GE reduced the production of CXCL10 (1.47, 1.5, and 1.53 folds, respectively, P < 0.001 for all), CCL20 (1.44, 1.62, and 1.65 folds, respectively, P < 0.003), and treatment with 30 µg/mL GE increased CCL17 (1.28-fold, P < 0.001) and CCL22 (1.59-fold, P < 0.001) production compared with untreated HPCE-stimulated PBMCs. In PU patients, the HPCE-stimulated PBMCs treated with 10, 20, or 30 µg/mL GE expressed lower levels of CXCR3 (1.9, 3, and 3.5 folds, respectively, P < 0.001) and CCR6 (2.3, 2.7, and 2.8 folds, respectively, P < 0.002) while treating with 10 µg/mL GE upregulated CCR4 (1.7 fold, P = 0.003) compared with untreated HPCE-stimulated PBMCs.

 Ginger extract modulated the expression of chemokines and their receptors in the PBMCs derived from H. pylori-infected PU patients. The therapeutic potentials of ginger for treating HP-related complications need to be further explored.

Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel anti-inflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity. Blood specimens were collected from two groups including 23 newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores>5 were higher than those with WOMAC scores<40, and VAS scores<5 (p=0.026 and p=0.035, respectively). The IL-38 levels in OA patients with body mass index (BMI)<25 were also significantly higher than in patients with BMI>25 (p=0.05). According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner. The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.

Cesarean section (CS) is an important challenge for a pregnant woman and her newborn. The most common anesthesia techniques used for CS are general anesthesia (GA) and spinal anesthesia (SA). This study was designed to compare the modulation of genes whose expression level is indicative of the immune system following exposure to GA and SA. The present study was performed on 40 women who were scheduled for elective CS receiving GA or SA. The expression levels of the relative mRNA of Interleukin (IL)-4, IL-6, IL-10, IL-17, Interferon (IFN)-γ, and tumor growth factor (TGF)-β before anesthesia (T0) and 24 hours post-anesthesia (T1) were analyzed by real-time polymerase chain reaction (RT-PCR) technique.  Twenty-four hours post-anesthesia, the expression levels of IL-10, IL-17, and IFN-γ genes were decreased while the expressions of IL-4, IL-6, and TGF-β genes were upregulated in two groups, however, the differences were not significant. The mRNA level of IL-4 was increased in the SA group significantly. The post-CS mRNA levels of IL-4 in the SA group may indicate that SA is more appropriate than GA for the initiation of tissue repair pathways.

 According to the previous studies, general anesthesia influences the immune system. Evaluating such impacts on the immune system helps to improve the management of anesthesia.

The current review aimed to summarize the literature related to the effects of general anesthesia agents on the cytokines. Google Scholar, PubMed, and ISI/Web of Sciences databases were searched using the following keywords: cytokine, general anesthesia, immune response, intravenous anesthetics, volatile anesthetics, opioids, benzodiazepines, and controlled ventilation.

Long-term administration of general anesthesia drugs, due to their effects on cytokines, can lead to disease progression in patients with immune deficiency. Due to the conflicting results of various studies and the increasing number of patients with immune deficiency, the choice of the appropriate general anesthesia agents facilitates achieving the more favorable function of the cytokines.

It seems that the effect of general anesthesia on the immune system in healthy patients and short-term surgeries is not considerable and changes in the immune system are related to surgical trauma, particularly in major surgery.

COVID-19, a respiratory infection caused by the virus SARS-CoV-2, causes a variety of symptoms in infected people. We have recently addressed our concerns over unintentional “Directed Accelerated Evolution” of the SARS-CoV-2 and introduced a modified treatment method for ARDS associated with COVID-19. COVID-19 outbreak could last for a long time in communities. Due to growing requests for medical equipment such as ventilators and ICU beds, “flattening the epidemic curve” has been considered as an effective strategy to adjust the level of health care demand to potential capacity of the system. In this paper, we compare possible outcomes of “Without Precaution” and “With Precaution” epidemic models. When there are no precautions, a higher number of people would be infected. RNA viruses such as SARS-CoV-2 have extremely high mutation rates. Accordingly, the combination of a higher number of infected people and any effort for inactivation of the viruses is expected to exert a strong selective pressure on SARS-CoV-2 that can lead to more mutations. These mutations can be either pathogenicity attenuating mutations (PAMs) or pathogenicity promoting mutations (PPMs). On the other hand, when flattening strategy is used, the number of infected people will be lower than the previous model, but both type of mutations may occur, although with lower frequency. Although the occurrence of PAMs helps the development of herd immunity, possible occurrence of PPMs needs serious tracking, especially in patients with severe COVID-19, to prevent new endemic with more virulent mutant viruses.

Thymus vulgaris, or thyme belongs to the Lamiaceae family of aromatic plant species and has established antioxidant and anti-inflammatory properties. We examined the association between thyme extract treatment to recovered urinary levels of melatonin, a hormone with neuroprotective effects, in mice induced with EAE.

Eight B6 mice induced with EAE were randomized into two groups and exposed to either 50 mg/kg of thyme extract or PBS. After EAE induction, mice were injected i.p every other day from day 0 to 21. Four B6 mice without EAE were considered the healthy control group. Urine samples were collected consecutively for two 24 h periods on day 19 and 20. We examined whether thyme extract treatment modified urinary melatonin sulfate concentration (ng/mL) in EAE-induced mice using an ELISA.

The clinical score and body weight in thyme-treated EAE group were significantly lower in comparison to the EAE control group at indicated time points. The urinary melatonin concentration was significantly lower in the EAE control group compared to the healthy mice. There was no significant difference between thyme-treated and EAE groups regarding the urine melatonin concentration.

Our results show that exposing EAE mice to thyme extract improved their clinical symptoms, however, there was no significant effect on urinary melatonin concentration.

The severity of postoperative pain and hemodynamic changes during and post-cesarean section have a direct effect on the neonatal and maternal condition. This study aimed to compare pain severity, hemodynamic changes, and patient satisfaction following two anesthesia techniques in elective cesarean section. In this blinded study, 60 women who were candidate for cesarean section were allocated into two equal groups of general anesthesia (GA) and spinal anesthesia (SA). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and O2 Saturation at pre cesarean (T0), the uterine incision time (T1), end of surgery (T2), 6h (T3), 12h (T4), and 24 hours post-cesarean (T5) were measured. A Visual Analog Scale assessed post-cesarean pain, 6, 12, and 24 hours post-cesarean. Gender, birth weight, first- and fifth- minutes’ apgar score was recorded in the checklists. The VAS score was significantly higher in the GA group at 6h, 12h, and 24 hours post-cesarean (P=0.014, P=0.002, P=0.017, respectively). SBP and DBP at T1 in the GA group were significantly higher than in the S.A group (P<0.001). The heart rate at T0 and T1 in the GA group was lower than the SA group (P=0.001, P=0.045 respectively). The difference between the apgar scores of the two groups was not significant. SA for cesarean section was associated with lower postoperative pain, systolic and diastolic blood pressure. However, the two groups had no significant difference in terms of patients’ satisfaction and apgar scores.

Due to advances in surgical procedure, anesthesia techniques, blood transfusion and antibiotic therapy, the technique of cesarean section has been progressing over the time. However, cesarean section is still a risk-specific operation, with long-term and shortterm consequences for the mother and neonate. The rate of cesarean surgery is constantly growing due to both justifiable and nonjustifiable medical and non-medical reasons. There is evidence indicating that efforts are made in many countries to reduce the rate of cesarean delivery. In this review article, we try to assess the frequency of cesarean section in different countries, especially Iran. We searched several keywords, including cesarean section prevalence, cesarean section rate, world, delivery, Iran and health policies within the newest articles published in Google Scholar, PubMed, and ISI/Web of Sciences, as well as Iranian databases (Magiran, SID), from January 2017 to April 2019. The results show that there is still a high prevalence of C-section. In Iran, the highest rate of cesarean was in Tehran province (62.1%-72.1%) and the lowest was in Sistan and Baluchestan province (12%). It appears necessary to plan for effective interventions in terms of painless vaginal delivery, improving the quality of vaginal delivery services, proper culture and education.

Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ T as well as B cells), monocytes and macrophages occur into the central nervous sys tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of  DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review.

Semaphorins play prominent roles in physiological and pathological processes such as vascular development, tumor growth and immune responses. Semaphorins have different roles in various kinds of cancers, but there is no study concerning their expression in the chronic lymphocytic leukemia (CLL). This study aimed to assess the SEMA3A, SEMA4A and SEMA4D expression in patients with CLL. Peripheral blood specimens were collected from 30 newly-diagnosed untreated patients with CLL and 30 healthy subjects as a control group. The SEMA3A, SEMA4A and SEMA4D expression was determined by real-time PCR method. The fold change expression of SEMA3A and SEMA4D was 7.58 ± 2.66 and 3.20 ± 0.99 in patients with CLL, and was 1.01 ± 0.31 and 1.00 ± 0.27 in healthy subjects, respectively. The CLL patients expressed higher amounts of SEMA3A and SEMA4D in comparison with healthy subjects (P<0.02 and P<0.03, respectively). The fold change expression of SEMA3A in patients with stage II (11.12 ± 5.35) was also higher than patients with stage I (4.49 ± 1.61, P<0.05). No significant difference was also observed in the expression of SEMA4A and SEMA4D between patients with stage I and stage II CLL. In both CLL and control groups, the fold change expression of SEMA3A was higher in men than in women (P<0.03 and P<0.02, respectively). The results of the study indicated elevated expression of the SEMA3A and SEMA4D in patients with CLL. The SEMA3A expression was influenced by tumor stage and gender of participants.

The imbalance between Th2 and Treg cells plays fundamental role in the pathogenesis of allergic asthma. The current study aimed at assessing the expression of some Th2 and Treg cell-related parameters in patients with allergic asthma. Material and The serum and peripheral blood mononuclear cell (PBMC) samples were collected from 30 patients with asthma and 36 healthy subjects. The serum levels of transforming growth factor (TGF)-β,‎ interleukin (IL)-4, as well as the expression levels of GATA3 and FOXP3 genes in PBMCs were determined by the enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. The PBMCs were cultured for 48 hours with/without phytohemagglutinin (PHA) stimulation. The TGF-β‎ and IL-4 levels in supernatants were also determined. The serum levels of IL-4, the expression level of GATA3, and GATA3/FOXP3 ratio in patients with asthma were significantly higher than healthy subjects (P <0.002, P <0.001, and P <0.004, respectively). The FOXP3 expression did no differ between the two groups. The serum level of TGF-β‎ as well as its secretion profile in non-stimulated and stimulated PBMCs isolated from patients with asthma were significantly higher than those of the controls (P <0.03, P <0.001, and P <0.001, respectively). The serum TGF-β levels in severe asthma were significantly higher than moderate asthma; whereas the TGF-β ‎secretion by PHA-stimulated PBMCs isolated from moderate asthma was higher than that of severe pattern of the disease (P <0.001 and P <0.05, respectively). The GTAT3/FOXP3 expression ratio in moderate asthma was significantly higher than severe form (P <0.04). The results confirmed a Th2 cell-biased pattern and possible contribution of TGF-β in allergic asthma. TGF-β may have different expression patterns in moderate and severe asthma and the two forms of the disease may have differences in some main immunological parameters

One of the most important limiting factors affecting the efficacy of treatment using monoclonal antibodies (mAbs) is their immunogenicity to the patients that may influence the diagnostic and therapeutic process. This study determined the unwanted immunologic response to the presence of antibody against some theraputic agents made following taking mAbs in patients with malignancy. Blood samples were collected from patients with cancer, including 32 patients with lymphoma or leukemia, 43 patients with breast cancer, and 23 patients with adenocarcinoma (colon or ovarian cancer) while receiving treatment with Rituximab, Trastuzumab, and Bevacizumab, respectively. Serum levels of human antibodies against the mentioned mAbs were determined by the standard sandwich ELISA method designed in the research. The presence of human antibodies against the mentioned mAbs was detected in 4 out of 32 (12.5%) Rituximab-treated patients and 7 out of 43 (16.3%) Trastuzumab-treated patients with a mean ± SD titer of 2.33 ± 0.37 AU/mL and 1.2 ± 0.21 AU/mL, respectively. The probability for the presence of anti-mAb in patients treated with Rituximab alone was significantly higher than patients, who took concomitantly Rituximab and once or more chemotherapeutic agents (26.6% vs. 0.0%; P < 0.02). None of Bevacizumab-treated patients, as was anticipated, developed antibody against the administrated mAb. The results of this study indicates the production of antibody against therapeutic mAbs Rituximab and Trastuzumab in a number of treated patients and this may influence their efficacy of treatment. The production of the human anti-mAb may be suppressed by chemotherapeutic drugs in Rituximab-treated patients and this phenomenon may be considered as a bonus effect during treatment. Bevacizumab did not show immunogenicity in the treated patients.

  Multiple Sclerosis (MS) is an inflammatory disorder caused by self-reactive Th1 lymphocytes, while Th2 cells may confer protection. The Th1 and Th2 cell differentiation are regulated by specific transcription factors, especially T-bet and GATA-3, respectively. This investigation aimed to measure the T-bet and GATA-3 expression by Peripheral Blood Mononuclear Cells (PBMCs) obtained from MS patients after specific and non-specific in vitro stimulation. The PBMCs were separated from 22 patients with MS and 20 healthy individuals. They were cultured at 37°C for 24 h in the absence of a stimulator or in the presence of Myelin oligodendrocyte Glycoprotein (MOG) or Phytohemagglutinin (PHA) at a concentration of 10 μg/mL. Then the T-bet and GATA-3 expression was measured by real time-PCR. The T-bet expression was enhanced, while the GATA-3 expression diminished. Therefore the expression of T-bet/GATA-3 ratio diminished in not-stimulated, MOG-stimulated and PHA-stimulated PBMCs from MS patients compared with equal cultures from the healthy individuals (P<0.01, P<0.01 and P<0.01, for T-bet; P<0.03, P<0.01 and P<0.02, for GATA-3; P<0.01, P<0.001 and P<0.01 for T-bet/GATA-3 ratio, respectively). The not-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from men with MS expressed higher amounts of GATA-3 than equal cells from MS women (P<0.05, P<0.05 and P<0.01, respectively). These results probably indicate an imbalance in Th1/Th2 cells in the level of transcription factors with a tendency toward Th1 cells in MS. The clinical utilization of the transcription factors as novel biomarkers of MS should be evaluated in further studies.

Background & objective The immunoregulatory effects of transforming growth factor (TGF)-βand interleukin-12 (IL-12) and immunomodulatory actions of vitamin D (VD) were reported in several studies. This study aims to evaluate VD effects on IL-12 and TGF-β expression in experimental autoimmune encephalomyelitis (EAE).
EAE was induced in three groups of C57BL/6 mice by immunization with MOG and administered intra-peritoneally 200 ngVD, PBS or olive oil (OO) from day to . One group was also considered as healthy control group. At day 31, cytokines expression in the spinal cord and their serum levels were determined using real time-PCR and ELISA, respectively.
IL-12 gene expression and its serum levels in PBS-injected- or OO-administrated EAE groups were significantly higher than healthy group. IL-12 gene expression in EAE group treated with VD was significantly decreased compared to PBS-injected- or OO-administrated EAE groups (P
VD modulates the expression of IL-12 and TGF-β in spinal cord and serum of EAE mice.