Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence.

PURPOSE: The safety and efficacy of the several types of COVID-19 vaccines, including mRNA-based, viral vector-based, and inactivated vaccines, have been approved by WHO. The vaccines can confer protection against severe SARS-CoV-2 infection through induction of the anti-spike protein neutralizing antibodies. However, SARS-CoV-2 vaccines have been associated with very rare complications, such as thyroid disorders. This review was conducted to highlight main features of thyroid abnormalities following COVID-19 vaccination. METHODS: A comprehensive search within electronic databases was performed to collect reports of thyroid disorders after vaccination with COVID-19 vaccines. RESULTS: Among 83 reported cases including in this review, the most cases of thyroid abnormalities were observed after vaccination with mRNA-based vaccines (68.7%), followed by viral vector vaccines (15.7%) and 14.5% cases following inactivated vaccines. Subacute thyroiditis (SAT) was the most common COVID-19 vaccination-related thyroid disease, accounting for 60.2% of all cases, followed by Graves' disease (GD) with 25.3%. Moreover, some cases with focal painful thyroiditis (3.6%), silent thyroiditis (3.6%), concurrent GD and SAT (2.4%), thyroid eye disease (1.2%), overt hypothyroidism (1.2%), atypical subacute thyroiditis (1.2%), and painless thyroiditis with TPP (1.2%) were also reported. Overall, in 58.0% of SAT cases and in 61.9% of GD cases, the onset of the symptoms occurred following the first vaccine dose with a median of 10.0 days (ranged: 3-21 days) and 10.0 days (ranged: 1-60 days) after vaccination, respectively. Moreover, 40.0% of SAT patients and 38.1% of GD patients developed the symptoms after the second dose with a median of 10.5 days (ranged: 0.5-37 days) and 14.0 days (ranged: 2-35 days) after vaccination, respectively. CONCLUSION: Fortunately, almost all cases with COVID-19 vaccination-associated thyroid dysfunctions had a favorable outcome following therapy. The benefits of COVID-19 vaccinations in terms of terminating the pandemic and/or reducing mortality rates can exceed any risk of infrequent complications such as a transient thyroid malfunction.

Humoral and T cell-mediated immune response against trichomoniasis.

Trichomonas vaginalis (T. vaginalis) infection leads to the synthesis of specific antibodies in the serum and local secretions. The profile of T. vaginalis-specific antibodies and T cell-mediated immune responses may influence the outcome of infection, towards parasite elimination, persistence or pathological reactions. Studies have indicated that Th1-, Th17- and Th22 cell-related cytokines may be protective or pathogenic, whereas Th2- and Treg cell-related cytokines can exert anti-inflammatory effects during T. vaginalis infection. A number of T. vaginalis-related components such as lipophosphoglycan (TvLPG), α-actinin, migration inhibitory factor (TvMIF), pyruvate:ferredoxin oxidoreductase (PFO), legumain-1 (TvLEGU-1), adhesins and cysteine proteases lead to the induction of specific antibodies. T. vaginalis has acquired several strategies to evade the humoral immune responses such as degradation of immunoglobulins by cysteine proteases, antigenic variation and killing of antibody-producing B cells. The characterization of the T. vaginalis-specific antibodies to significant immunogenic molecules and formulation of strategies to promote their induction in vaginal mucosa may reveal their potential protective effects against trichomoniasis. In this review, we discuss the current understanding of antibody and T cell-mediated immune responses to T. vaginalis and highlight novel insights into the possible role of immune responses in protection against parasite.

Regulatory effects of the novel synthesized Indole-3-carbaldehyde on expression of cell cycle genes: A study on Cyclin D and P21 expression by acute promylocytic leukemia cell line (NB4)

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Higher circulating levels of chemokines CXCL10, CCL20 and CCL22 in patients with ischemic heart disease.

Recruitment of leukocytes is one of the earliest events in the pathogenesis of ischemic heart disease (IHD) and chemokines play an important role in the migration of these cells into the inflammation sites. The aim of this study was to evaluate the CXCL10, CCL20 and CCL22 levels and the single nucleotide polymorphisms (SNPs) rs4508917, rs6749704 and rs4359426 in chemokine genes in patients with IHD to clarify any association. A total of 300 patients with IHD as having acute myocardial infarction (AMI; n=100), stable angina (SA; n=100) or unstable angina (UA; n=100) and 100 healthy subjects as a control group were enrolled to study. Serum samples from all participants were tested for the CXCL10, CCL20 and CCL22 levels by using ELISA. The SNPs were determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method. The mean serum concentrations of CXCL10, CCL20 and CCL22 in AMI patients (395.97±21.20Pg/mL, 108.38±10.31Pg/mL and 1852.58±205.77Pg/mL), SA patients (405.48±27.36Pg/mL, 90.20±7.69Pg/mL and 2322.04±231.23Pg/mL) and UA patients (396.69±22.79Pg/mL, 141.87±18.10Pg/mL and 2754.89±211.70Pg/mL) were significantly higher than in the healthy group (179.38±8.85Pg/mL, 51.92±4.62Pg/mL and 451.82±23.76Pg/mL, respectively; P<0.001). Similarly, the serum levels of CXCL10, CCL20 and CCL22 in total IHD patients (399.38±13.77Pg/mL, 113.49±7.48Pg/mL and 2309.84±126.39Pg/mL, respectively) were also significantly higher as compared with healthy subjects (P<0.001). The serum levels of CCL20 and CCL22 in UA patients were significantly higher than those in SA and AMI patients, respectively (P<0.01 and P<0.003, respectively). The serum levels of CXCL10 and CCL20 in diabetic patients were significantly higher in comparison to non-diabetic patients (P<0.05 and P<0.02, respectively). The serum levels of CCL22 in dyslipidemic- and obese patients were also significantly higher in comparison with non-dyslipidemic- and non-obese patients, correspondingly (P<0.05 and P<0.01, respectively). There were no significant differences between men and women or between patients who treated with statin, aspirin, ß-blockers or angiotensin converting enzyme (ACE) inhibitors and patients without mentioned treatment regarding the levels of chemokines. The frequency of the GG genotype at SNP rs4508917 in CXCL10 gene was higher, whereas the frequency of the AA genotype at SNP rs4359426 in CCL22 gene was lower in total patients with IHD as compared with healthy subjects (P<0.04 and P<0.002, respectively). These results showed that the higher levels of CXCL10, CCL20 and CCL22 were associated with IHD. The serum levels of chemokines may influence by the certain traditional risk factors of IHD and some studied SNPs, but did not influence by treatment and gender of patients.

Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism.

The receptor for CCL22 is named CCR4 that preferentially is expressed on the regulatory T cells (Treg), and accordingly, CCL22 acts as a chemoattractant for the intratumoral Treg migration. The aim of this study was to evaluate the serum CCL22 levels and a single nucleotide polymorphism (SNP) in chemokine gene, [2030 G/C (rs223818)], in patients with breast cancer. Blood samples were collected from 100 women with breast cancer before receiving chemotherapy, radiotherapy, or immunotherapy and 100 age-matched healthy women as a control group. The serum CCL22 levels were measured by ELISA. The DNA extracted and the SNP rs223818 determined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The mean serum CCL22 levels in patients with breast cancer (2398.5 ± 123 Pg/mL) was significantly higher in comparison to healthy control group (974.2 ± 39.9 Pg/mL; P < 0.001). According to the tumor stages, the mean serum levels of CCL22 were 999.8 ± 85.0 Pg/mL in stage I, 1718.8 ± 82.3 Pg/mL in stage II, 2846.8 ± 118.0 Pg/mL in stage III, and 3954.5 ± 245.2 Pg/mL in stage IV. There was significant difference between tumor stages regarding the serum CCL22 levels (P < 0.001). In patients with breast cancer, the frequencies of CC genotype (63%) and C allele (79%) at rs223818 were significantly higher as compared to healthy controls (31 and 52%, respectively; P < 0.001). In both patients and control groups, the mean serum levels of CCL22 in subjects with CC genotype or C allele at rs223818 were also significantly higher as compared to subjects with GG genotype or G allele (P < 0.001). Higher serum CCL22 levels were observed in patients with breast cancer that is increased with advanced stages. These findings represent that the CCL22 may contribute in tumor development. The CC genotype and C allele at rs223818 were more frequent in breast cancer patients. The serum CCL22 levels were affected by genetic variations at SNP rs223818. Accordingly, SNP rs223818 may play a role in the susceptibility to breast cancer.

Induction of apoptosis by pistachio (Pistacia vera L.) hull extract and its molecular mechanisms of action in human hepatoma cell line HepG2.

Several important Pistacia species such as P. vera have been traditionally used for treating a wide range of diseases (for instance, liver-related disorders). There is a relative lack of research into pharmacological aspects of pistachio hull. Hence, this study was aimed at investigating whether pistachio rosy hull (PRH) extract exerts apoptotic impacts on HepG2 liver cancer cell line. In order to evaluate cell viability and apoptosis in response to treatment with the extract, MTT assay and Annexin-V-fluorescein/propidium iodide (PI) double staining were performed, respectively. Moreover, molecular mechanism of apoptosis induced by the extract was determined using human apoptosis PCR array. Our findings showed that PRH extract treatment reduced cell viability (IC50 ~ 0.3 mg/ml) in a dose-dependent manner. Flow cytometric analysis revealed that the extract significantly induced apoptosis in HepG2 cells. In addition, quantitative PCR array results demonstrated the regulation of a considerable number of apoptosis-related genes belonging to the TNF, BCL2, IAP, TRAF, and caspase families. We observed altered expression of both pro-apoptotic and anti-apoptotic genes associated with the extrinsic and intrinsic apoptosis signaling pathways. These results suggest that the aqueous extract of PRH possesses apoptotic activity through cytotoxic and apoptosis-inducing effects on HepG2 cells.

Lower serum level of anti-tetanus toxin antibodies in patients with type 2 diabetes mellitus.

AIM: To evaluate the serum levels of anti-tetanus toxin antibodies (anti-TTA) in patients with type 2 diabetes mellitus (DM) and in a control group. METHODS: Totally, 100 patients with type 2 DM and 100 age- and sex-matched healthy individuals were enrolled to study. The presence of type 2 DM confirmed according to the clinical and para-clinical criteria such as fasting plasma glucose above 126 mg/dl. A peripheral blood sample was collected from all subjects. The serum samples of participants tested for the levels of anti-TTA by ELISA method. The serum antitoxin concentration 0.1 IU/mL was considered as a protective level of antibody. RESULTS: The seroprotective rate in healthy group was significantly higher than diabetic group (99% vs. 92%; p<0.02). The mean titer of anti-TTA in healthy group (5.32 ± 0.26 IU/ml) was also significantly higher than diabetic patients (3.46 ± 0.26 IU/ml; p>0.001). In diabetic men the mean titer of anti-TTA was significantly higher in comparison to diabetic women (3.94 ± 0.34 IU/ml vs 2.59 ± 0.36 IU/ml; p<0.01). In diabetic patients the seroprotective rate and the mean titer of anti-TTA in subjects with age >40 years was also lower in comparison to those with age <40 years (89.23% vs 97.14%; p<0.15 and 4.57 ± 0.38 IU/ml vs 2.86 ± 0.32 IU/ml; P<0.002, respectively). The mean titer of anti-TTA was significantly higher in patients with diabetes duration <5 years in comparison to patients with disease duration >5 years (3.91 ± 0.35 IU/ml vs 2.85 ± 0.38 IU/ml; p<0.04). CONCLUSION: these results showed lower levels of anti-TTA in patients with type 2 DM, in diabetic women, in patients aged >40 years and in diabetic patients with disease duration >5 years.

Total leukocyte counts and neutrophil-lymphocyte count ratios among Helicobacter pylori-infected patients with peptic ulcers: independent of bacterial CagA status.

Elevated leukocyte counts can be a marker of inflammation and infection. The aim of this study was to determine the total leukocyte count and neutrophil-lymphocyte count ratio (NLCR) among Helicobacter pylori-infected patients with peptic ulcer disease (PU) and among asymptomatic subjects (AS) and to evaluate if there is an association between these lab values and the presence of the H. pylori virulence factor cytotoxin-associated gene A (CagA). Sixty H. pylori-infected PU patients, 63 AS carriers and 32 healthy H. pylori-negative subjects (controls) were included in the study. The total white blood cell (WBC) counts and differentials were determined using standard hematological methods. The mean total WBC count, mean neutrophil count and NLCR were significantly higher among PU patients than in controls (p < 0.001, p < 0.001 and p < 0.001, respectively). Similarly, the mean WBC count, mean neutrophil count and NLCR were significantly higher among AS patients than in controls (p < 0.005, p < 0.001 and p < 0.02, respectively). The differences of mean WBC counts mean neutrophil counts and NLCR were also significantly different (p < 0.005, p < 0.001 and p < 0.001, respectively) between the PU and AS patients. There were no differences in the PU and AS patients in regard to anti-CagA positivity. These results show the CagA factor was not associated with the presence or absence of symptoms in H. pylori infected patients.

Serum levels of interleukin (IL)-27 in patients with ischemic heart disease.

OBJECTIVE: Cytokines, the key mediators of immune responses, play an important role in the pathogenesis of cardiovascular diseases. The aim of this study was to evaluate the serum levels of IL-27 in patients with ischemic heart disease (IHD) and also to clarify its association with traditional risk factors of the disease. METHODS: A total of 120 patients with IHD as having acute myocardial infarction (AMI; n=60) or unstable angina (UA; n=60) and 60 sex- and age-matched healthy subjects as a control group were enrolled in this cross-sectional, case-controlled study. Serum samples were collected from all participants (for AMI patients at 3-5 days after events and for UA at admission time) and tested for the levels of IL-27 by use of ELISA method. RESULTS: The mean serum levels of IL-27 in AMI group (38.00±14.38 Pg/ml) and UA group (35.77±18.93 Pg/ml) were significantly higher than those observed in the control group (24.91±14.96 Pg/ml; P<0.0001 and 0.001, respectively). The mean serum levels of IL-27 in IHD patients with or without a certain traditional risk factor including hypertension, dyslipidemia, diabetes smoking were significantly higher as compared to those in the control group. CONCLUSIONS: These results showed that the higher serum levels of IL-27 were associated with IHD. The presence or absence of certain traditional risk factors of IHD did not influence the serum levels of cytokine.

Serum concentrations of Helicobacter pylori IgG and the virulence factor CagA in patients with ischaemic heart disease.

To compare the serum concentrations of IgG to Helicobacter pylori and its virulence factor CagA in patients with ischaemic heart disease (IHD), we recruited 120 patients with IHD [acute myocardial infarction (AMI) (n = 60); unstable angina (UA) (n = 60)] and 60 sex- and age-matched healthy controls in this study. The seroprevalence of anti-H. pylori IgG was 86.7% in AMI, 91.7% in UA patients and 58.3% in the control group with mean titres of 33.2 U/ml [standard error (SE) 4.76], 57.96 U/ml (SE 7.54) and 25.72 U/ml (SE 4.01) respectively. The seroprevalence of anti-H. pylori in the patient groups was significantly higher than the control group. The mean levels of anti-H. pylori in the AMI and UA groups were also significantly higher than in the control group. The seroprevalence and mean titre of anti-CagA IgG did not differ significantly between patient and control groups.

Serum levels of high-sensitivity C-reactive protein (hs-CRP)in Helicobacter pylori-infected peptic ulcer patients and its association with bacterial CagA virulence factor.

OBJECTIVE: CRP is a marker of inflammation and infection of the gastric mucosa with Helicobacter pylori, which causes an inflammatory reaction. It has been reported that CagA(+) H. pylori strains induce more severe gastric inflammation and are also associated with higher risks of peptic ulcer and gastric cancer. The purpose of this study was to compare serum concentrations of hs-CRP in H. pylori-infected peptic ulcer (PU) patients, H. pylori infected asymptomatic (AS) carriers, and a healthy control group, and their association with bacterial virulence factor CagA. MATERIAL AND METHODS: A total of 60 H. pylori infected PU patients (30 patients were positive for anti-CagA antibody and 30 were negative for anti-CagA antibody), 53 H. pylori-infected AS carriers (25 subjects were positive for anti-CagA antibody and 28 were negative for anti-CagA antibody), and 22 healthy H. pylori-negative subjects (as a control group) were enrolled in the study. Serum concentrations of hs-CRP were measured by use of an ELISA method. RESULTS: The mean serum level of hs-CRP in all PU patients (124.9±32.4 µg/dl) was significantly higher than that in all AS subjects (18.6±2.6 µg/dl; P<0.001) and the healthy uninfected control group (10.7±2.9 µg/dl; P<0.0001). Moreover, the mean serum level of hs-CRP in the AS group was significantly higher than that observed in the uninfected control group (P<0.04). No significant difference was observed between mean serum levels of hs-CRP of PU patients with positive test for anti-CagA antibody (132.6±49.4 µg/dl) and PU patients with negative test for anti-CagA antibody (117.1±42.9 µg/dl). Moreover, mean serum levels of hs-CRP were similar in AS subjects with positive test for anti-CagA (18.4±3.1 µg/dl) and in those who were negative for anti-CagA antibody (18.9±4.1 µg/dl). CONCLUSION: The results of this study showed that mean serum concentrations of hs-CRP in PU patients and in H. pylori infected AS carriers were higher than in a healthy control group. Although H. pylori infection is associated with higher serum levels of hs-CRP, serum concentrations of this inflammatory marker were not affected by expression of bacterial CagA virulence factor.

Specific serum immunoglobulin G to H pylori and CagA in healthy children and adults (south-east of Iran).

AIM: To evaluate the serologic IgG response to H pylori and CagA across age groups and in healthy children and adults. METHODS: Totally, 386 children aged 1-15 years and 200 adults aged 20-60 years, were enrolled to study. The serum samples of participant were tested for presence of anti-H pylori and anti-CagA IgG by using ELISA method. RESULTS: The seroprevalence of H pylori in adults was significantly higher than that observed in children (67.5% vs 46.6%; P < 0.000003). In children, the seropositivity rate in males (51.9%) was significantly (P < 0.05) higher than that observed in females (41.7%). The prevalence of serum anti-CagA antibody was 72.8% and 67.4% in infected children and adults, respectively. The mean titer of serum anti-CagA antibodies was significantly higher among children in comparison to adults (64.1 Uarb/mL vs 30.7; P < 0.03). In infected children and adults the prevalence of serum anti-CagA antibody was higher in males compared to females (78.4% vs 66.3%; P = 0.07 and 75.6% vs 54.71%; P < 0.04, respectively). The age-specific prevalence of anti-H pylori and anti-CagA antibody (in infected subjects) was 37.6% and 59.57% at age 1-5 years, 46.9% and 75% at age 6-10 years, 54.9% and 79.45% at age 11-15, 59.01% and 83.33% at age 20-30 years, 66.6% and 60.52% at age 31-40 years, 73.46% and 63.88% at age 41-50 years and 75.75% and 60% at age 51-60 years with mean titer of anti-CagA antibody of 75.94, 63.32, 57.11, 52.06, 23.62, 21.52 and 21.80 Uarb/mL, respectively. There was significant difference between mean serum anti-CagA antibody in age subgroups (P < 0.001). CONCLUSION: These results showed that anti-H pylori and anti-CagA antibodies were common in the children and adults. The H pylori-specific antibodies influenced by age and sex of subjects. Moreover, it seems that males are more susceptible to infection with CagA(+) strains compared to females. The seroprevalence of anti-CagA antibody was increased with age, up to 30 years and then decreased. It was also found that the magnitude of the IgG response to CagA decreased with advanced age.

Immunomodulatory Effects of Adjuvants CPG, MPLA, and BCG on the Derp2-Induced Acute Asthma at Early Life in an Animal Model of BALB/c Mice.

The Th1- and Treg cell-related immune responses play key roles in the modulation of Th2 cell-related allergic disorders. The aim was to evaluate the effects of CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters in an animal model of asthma. BALB/c mice were divided into five groups and immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37. Blood samples were collected from the retro-orbital sinus, on days 0, 23, and 40. The serum levels of IL-4, IFN-γ, IgE, and IgG2a were measured using ELISA technique. The blood number of Th1 and Treg cells was determined using flow cytometry. At the sensitization phase, the number of Th1 and the serum levels of IFN-γ and IgG2a were significantly increased in the Derp2-sensitized group pretreated with CPG plus MPLA, and the number of Treg cells was significantly elevated in Derp2-sensitized mice pretreated with CPG or CPG plus MPLA as compared with that in Derp2-sensitized control mice. At the challenge phase, the number of Th1 was significantly elevated in Derp2-sensitized mice pretreated with CPG plus MPLA, CPG plus BCG, or CPG; the count of Treg cells was significantly increased in Derp2-sensitized mice pretreated with CPG plus BCG group; and the levels of IFN-γ and IgG2a were significantly enhanced in the Derp2-sensitized group pretreated with CPG plus MPLA in comparison with those in Derp2-sensitized control mice. The scores of inflammation and mucus secretion in the lung were significantly decreased in the Derp2-sensitized group pretreated with CPG, BCG, and CPG plus MPLA in comparison with those in the Derp2-sensitized control group. These results showed that BCG, MPLA, and CPG modulate Th1-, Th2-, and Treg-related parameters and ameliorate lung inflammatory parameters in a mouse model of asthma.

The association of the vitamin D status with the persistence of anti-HBs antibody at 20years after primary vaccination with recombinant hepatitis B vaccine in infancy.

BACKGROUND AND OBJECTIVE: Vitamin D has potent immunoregulatory effects due to the expression of its receptor on the majority of immune cells. The aim was to evaluate the association of the vitamin D status with the persistence of anti-HBs antibody and immune response to booster immunization at 20years after primary vaccination with hepatitis B (HB) vaccine. METHODS: Blood samples were collected from 300 adults 20years after completion of the primary HB vaccination in infancy. The serum levels of vitamin D and anti-HBs antibody were measured by ELISA. A single booster dose of a recombinant HB vaccine was administered to a total of 138 subjects, whose anti-HBs titer was<10IU/L. The sera of revaccinated subjects were re-tested for anti-HBs antibody, 4weeks after booster vaccination. RESULTS: At 20years after primary vaccination, the mean vitamin D concentrations were significantly higher in seroprotective subjects as compared to non-seroprotective individuals (P<0.01). The levels of anti-HBs were significantly increased with advanced concentrations of vitamin D (P<0.01). Overall, 125/138 (90.6%) of the revaccinated subjects showed an anamnestic response to booster vaccination. The concentrations of vitamin D were significantly higher in subjects with an anamnestic response to booster vaccination as compared with subjects without this response (P<0.01). CONCLUSION: Vitamin D status may influence the persistence of anti-HBs antibody and durability of protection after primary vaccination with a recombinant HB vaccine in infancy.

Higher circulating levels of chemokine CXCL10 in patients with breast cancer: Evaluation of the influences of tumor stage and chemokine gene polymorphism.

BACKGROUND: The CXCL10 receptor, CXCR3, is preferentially expressed on Th1 and NK cells. Therefore, CXCL10 acts as a chemoattractant for these cells. OBJECTIVE: The aim was to evaluate the CXCL10 levels and a single nucleotide polymorphism (SNP), rs4508917, in chemokine gene, in patients with breast cancer (BC). METHODS: A total of 200 subjects including 100 women with BC and 100 healthy women were enrolled into study. The serum CXCL10 levels were measured by ELISA and the SNP rs4508917 was determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). RESULTS: The CXCL10 levels were significantly higher in patients than control group (P< 0.0001). There was also significant difference between tumor stages regarding the CXCL10 levels (P< 0.0001). The frequencies of GG genotype and G allele at rs4508917 were significantly higher in patients than controls (P< 0.0001). The CXCL10 levels were higher in patients with GG genotype whereas they were lower in healthy subjects having GG genotype as compared with those having AA genotype at rs4508917 (P< 0.001). CONCLUSION: Higher CXCL10 levels in patients with BC represent that the chemokine may contributes in tumor development. The rs4508917 may play a role in the susceptibility to BC. Different association was also observed between rs4508917 and CXCL10 levels in patients with BC and healthy subjects.

Probiotic Yogurt Culture Bifidobacterium Animalis Subsp. Lactis BB-12 and Lactobacillus Acidophilus LA-5 Modulate the Cytokine Secretion by Peripheral Blood Mononuclear Cells from Patients with Ulcerative Colitis.

BACKGROUND: There are some evidences for the immunomodulation disorders in the response to intestinal microbiota in inflammatory bowel disease. Yogurt is a fermented milk product made with a starter culture consisting of different probiotics which could be colonized in intestine. However, the role of probiotics in the aetiopathogenesis of ulcerative colitis (UC) has not been clarified. To determine how the immune system responds to these bacteria this study was planned. METHODS: Bifidobacterium lactis BB-12 (B. lactis) and Lactobacillus acidophilus LA-5 (L. acidophilus) were cultivated on MRS broth. PBMCs of 36 UC patients were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria in RPMI-1 640 plus 10% FCS for 48/72 h. IL-10, TGF-ß, IFN-γ and TNF-α were measured in supernatant of PBMCs by ELISA. RESULTS: Both bacteria significantly augmented IL-10, TGF-ß, IFN-γ and TNF-α compared to control (p<0.001). The secretion levels of IL-10 and TGF-ß by B. lactis- compared to L. acidophilus-stimulated PBMCs were significantly higher (p<0.05, p<0.01 respectively). The secretion levels of TNF-α and IFN-γ by PBMCs after 72 h were significantly lower compared to 48 h stimulation by B. lactis (p<0.001, p<0.035 respectively). CONCLUSION: These data show that both probiotics may trigger the pro- and anti-inflammatory immune response of UC patients. It seems that IL-10/TGF-ß uprising by B. lactis could be the reason of TNF-α/IFN-γ reduction. Therefore albeit B. lactis still stimulates the effector Th cells but because of more stimulatory effect on Tregs, it could be a good potential therapeutic candidate for further investigation.

Circulating levels of interleukin-35 in patients with multiple sclerosis: evaluation of the influences of FOXP3 gene polymorphism and treatment program.

The regulatory T (Treg) cells play a major role in the control of the autoimmunity and inflammation, and IL-35 has been described as an immunosuppressive cytokine that is mainly produced by CD4(+)FOXP3(+) Treg cells. The aim of this study was to evaluate the serum levels of IL-35 and a single nucleotide polymorphism (SNP), rs3761548, in FOXP3 gene in patients with multiple sclerosis. The blood samples were collected from 140 multiple sclerosis (MS) patients (including 51 untreated and 89 treated patients) and 140 healthy subjects as a control group. The serum levels of IL-35 were measured by ELISA. The DNA was analyzed for SNP rs3761548 in FOXP3 gene using SSP-PCR. There was no significant difference between untreated MS patients and control group regarding the mean serum levels of IL-35, although this parameter was higher in untreated patients. However, the mean serum level of IL-35 in treated MS patients was significantly higher than that in the control group (P < 0.008). The mean serum levels of IL-35 in patients who were treated with interferon-ß, methylprednisolone, or with the both interferon-ß and methylprednisolone were significantly higher than that in the healthy group (P < 0.01, P < 0.01, and P < 0.2, respectively). The frequencies of AA and AC genotypes at rs3761548 in the FOXP3 gene were significantly higher in MS group as compared with healthy subjects (P < 0.05). The frequency of CC genotype at rs3761548 was significantly lower in the MS group in comparison with healthy control subjects (P < 0.001). Moreover, the frequency of A allele was significantly higher whereas the frequency of C allele was significantly lower in MS patients in comparison to healthy subjects (P < 0.001). The mean serum level of IL-35 was significantly lower in MS patients or healthy subjects with AA genotype as compared with those with CC genotype at rs3761548 in FOXP3 gene (P < 0.01 and P < 0.001, respectively). These results showed higher serum levels of IL-35 in treated MS patients representing that the benefit effects of treatment may in part performed through the upregulation of the IL-35 production. The SNP rs3761548 may influence the susceptibility to MS disease and the serum levels of IL-35.

Augmenting the expression of NKp44 molecule and the natural killer activity in peripheral blood mononuclear cells from patients with malignant colorectal carcinoma.

OBJECTIVE: NKp44 and NKG2D are of the main NK activating receptors involved in recognition and killing of tumors. Here we studied the stimulatory effects of PHA and/or K562 cell line on induction of NKp44 and NKG2D expression and the NK activity of PBMCs from patients with colorectal carcinoma (CRC). MATERIALS AND METHODS: Peripheral blood samples were collected from 10 patients with CRC. The peripheral blood mononuclear cells (PBMCs) from each patient received a single stimulation with PHA or double stimulation with PHA and irradiated K562 cell line (iK562). The expression of CD56, NKG2D and NKp44 were detected by flowcytometry. The NK activity of PBMCs against a colorectal carcinoma cell line named as SW742 was determined with 51Cr-release assay. RESULTS: Double stimulation of PBMCs with PHA+iK562 significantly augmented the number CD56(+) cells compared to PHA alone and non-stimulated PBMCs (P<0.000, P<0.0000; respectively). A single stimulation of PBMCs with PHA resulted in an enhancement in NKG2D and NKp44 expression from 16.6±3.3% (for non-stimulated PBMCs) to 42±5.6% and 48.1±3.8% respectively (p<0.05). Double stimulation of PBMCs augmented the NKp44 expression significantly in comparison with single stimulation with PHA (73.6±12%, p<0.05). Double stimulation of PBMCs significantly enhanced the NK activity against SW742 target cells compared to single stimulation with PHA (p<0.05). DISCUSSION AND CONCLUSION: Our results demonstrated that the mitogen and iK562 exposure to PBMCs can significantly improve NK activity which is co-related to the higher expression of NKp44 and NKG2D. These data may help to improve cancer immunotherapy protocols.

Higher circulating levels of chemokine CCL20 in patients with multiple sclerosis: evaluation of the influences of chemokine gene polymorphism, gender, treatment and disease pattern.

Chemokines play an important role in the autoimmune diseases. The aim of this study was to investigate the levels of CCL20 and a polymorphism [-786C > T (rs6749704)] in the chemokine gene in patients with multiple sclerosis (MS). The blood samples were collected from 135 MS patients and 135 healthy subjects as a control group. The patients have relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 47), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) patterns. The serum levels of CCL20 were measured by ELISA. The DNA was analyzed for CCL20 polymorphism using PCR-RLFP. The mean serum levels of CCL20 in the MS group were significantly higher than in the healthy group (P < 0.001). In patients with a SPMS pattern, the frequency of CT genotype at rs6749704 (24.3 %) was significantly lower as compared to patients with other patterns (42.8 %; P < 0.04). No significant differences were observed between subjects with different genotypes in rs6749704 regarding the CCL20 levels. The mean serum levels of CCL20 in both newly diagnosed and previously diagnosed patients was significantly higher than in the healthy group (P < 0.05 and 0.001, respectively). The mean serum levels of CCL20 in patients with RRMS, SPMS and PPMS patterns were significantly higher than in the healthy group (P < 0.004, P < 0.04, and 0.05, respectively). The levels of CCL20 in untreated patients and in patients who received interferon-ß, methylprednisolone or the combination of interferon-ß plus methylprednisolone were higher as compared to the control group (P < 0.05, P < 0.03, P < 0.005, and P < 0.05, respectively). These results showed higher levels of CCL20 in patients that represent that the chemokine may play an important role in the pathogenesis of MS. The rs6749704 polymorphism was an associated SPMS pattern. The levels of CCL20 were not influenced by gender, disease pattern and treatment.

Lower serum levels of Th2-related chemokine CCL22 in women patients with multiple sclerosis: a comparison between patients and healthy women.

Chemokines play a major role in autoimmune diseases such as multiple sclerosis (MS). Gender also affects the susceptibility and course of MS. The aim of this study was to investigate the serum levels of the macrophage-derived chemokine (CCL22) in women and men patients with MS. Blood samples were collected from 135 healthy subjects (35 men and 100 women) and 135 MS patients (29 men and 136 women; 47 newly diagnosed and 88 treated patients and have relapsing-remitting (RRMS; n = 65), secondary progressive (SPMS; n = 37), primary progressive (PPMS; n = 19), or progressive relapsing (PRMS; n = 14) patterns). The serum levels of CCL22 were measured by ELISA. The difference of the mean serum levels of CCL22 between the newly diagnosed MS men and healthy men was not significant, but in newly diagnosed MS women, the mean serum levels of CCL22 were significantly lower than those in treated MS women and healthy women (P < 0.006 and P < 0.0001, respectively). The differences of the mean CCL22 levels between men patients with different treatment programs were not significant, but the mean CCL22 levels were significantly higher in women treated with interferon-ß or the combination of interferon-ß plus methylprednisolone as compared to untreated women patients (P < 0.01 and P < 0.05, respectively). The CCL22 levels were also significantly higher in women with RRMS and PRMS patterns in comparison to healthy women (P < 0.05 and P < 0.01, respectively). These results showed lower levels of CCL22 in women patients which represents that the reduction in CCL22 levels may play an important role in the pathogenesis of the disease in women. In women patients, the levels of CCL22 were influenced by disease pattern and treatment.