Contemporaneous SARS-CoV-2-Neutralizing Antibodies Mediated by N-glycan Shields.

Mutations and the glycosylation of epitopes can convert immunogenic epitopes into non-immunogenic ones via natural selection or evolutionary pressure, thereby decreasing their sensitivity to neutralizing antibodies. Based on Thomas Francis's theory, memory B and T cells induced during primary infections or vaccination will freeze the new mutated epitopes specific to naïve B and T cells from the repertoire. On this basis, some researchers argue that the current vaccines derived from the previous strains of the SARS-CoV-2 virus do not increase immunity and may also prevent the immune response against new epitopes. However, evidence shows that even if the binding affinity is reduced, the previous antibodies or T cell receptors (TCRs) can still bind to this new epitope of the Beta, Gamma, and Delta variant if their concentration is high enough (from a booster injection) and neutralize the virus. This paper presents some convincing immunological reasons that may challenge this theory and argue for the continuation of universal vaccination to prevent further mutations of the SARS-CoV-2 virus. Simultaneously, the information presented can be used to develop vaccines that target novel epitopes or create new recombinant drugs that do not lose their effectiveness when the virus mutates.

Differential roles of regulatory T cells in Alzheimer's disease.

Regulatory T (Treg) cells interact with a variety of resident cells and infiltrated immune cells in the central nervous system (CNS) to modulate neuroinflammation and neurodegeneration. Extracellular amyloid-ß (Aß) peptide deposition and secondary persistent inflammation due to activation of microglia, astrocytes, and infiltrated immune cells contribute to Alzheimer's disease (AD)-related neurodegeneration. The majority of evidence supports the neuroprotective effects of Treg cells in AD. In the early stages of AD, appropriate Treg cell activity is required for the induction of microglia and astrocyte phagocytic activity in order to clear A deposits and prevent neuroinflammation. Such neuroprotective impacts were in part attributed to the ability of Treg cells to suppress deleterious and/or boost beneficial functions of microglia/astrocytes. In the later stages of AD, an effective Treg cell activity needs to prevent neurotoxicity and neurodegeneration. Treg cells can exert preventive effects on Th1-, and Th17 cell-related pathologic responses, whilst potentiating Th2-mediated protective activity. The impaired Treg cell-related immunomodulatory mechanisms have been described in AD patients and in related animal models which can contribute to the onset and progression of AD. This review aimed to provide a comprehensive figure regarding the role of Treg cells in AD while highlighting potential therapeutic approaches.

The correlation between humoral immune responses and severity of clinical symptoms in COVID-19 patients.

The SARS-CoV-2 pandemic persists with global repercussions. Initial COVID-19 symptoms encompass pneumonia, fever, myalgia, and fatigue. The human immune system produces IgM and IgG antibodies in response to SARS-CoV-2. Despite previous research, a comprehensive understanding of the interplay between clinical manifestations and humoral immune responses remains elusive. This study aims to scrutinize this association. 134 COVID-19 patients were enrolled, and stratified into mild, moderate, and severe symptom groups. Serum IgM and IgG levels were assessed thrice at one-month intervals using ELISA. The findings reveal significant elevation in serum IgG levels in moderate compared to mild cases (P < 0.001). Additionally, IgG production was significantly heightened in severe cases compared to both mild (P < 0.0001) and moderate (P < 0.05) groups. IgM and IgG levels peaked initially and diminished over time. While anti-SARS-CoV-2 antibodies are expected to confer protection, the direct correlation between IgG levels and symptom severity may arise from delayed immune activation, resulting in an intense antibody response in severe cases. Given evidence linking delayed immune function with a dysregulated innate immune response, comprehensive data collection should encompass not only serum IgG and IgM, but also early measurement of type I interferons at symptom onset. This could provide a more thorough understanding of COVID-19 progression.

Evaluation of the gene encoding carnitine transporter (OCTN2/SLC22A5) expression in human breast cancer and its association with clinicopathological characteristics.

BACKGROUND: Fatty acid oxidation (FAO) is a major energy-generating process in the mitochondria and supports proliferation, growth, and survival of cancer cells. L-Carnitine is an essential co-factor for carrying long-chain fatty acids into the mitochondria. The entry of l-carnitine across cell membrane is regulated by OCTN2 (SLC22A5). Thus, it can plays a significant role in the mitochondrial fatty acid oxidation. This study aimed to evaluate the OCTN2 expression and its association with clinicopathological characteristics in breast cancer. METHODS: In this work, OCTN2 was examined in 54 pairs of fresh samples of breast cancer (BC) and adjacent noncancerous tissue using quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). The IHC approach was also used to investigate the expression of additional clinicopathological features. RESULTS: The present research findings revealed that the relative expression of OCTN2 in BC tissues was substantially higher than the adjacent normal tissues. This up-regulation was correlated positively with tumor size and Ki-67 and negatively with the progesterone receptor (PR) status, providing evidence of the opposite effects of OCTN2 and PR on tumor development. CONCLUSION: The study shows that the OCTN2 expression in BC patients may be used as a prognostic biomarker and a tumor oncogene. As a result, it could be considered a possible therapeutic target. Nevertheless, the significance of the findings needs to be confirmed by further studies.

Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models.

BACKGROUND: In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity. METHODS: SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1 +RBD, and SS1 +N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120 µg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry. RESULTS: The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120 µg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1 +RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed. CONCLUSION: These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.

Natural adjuvants (PC and G2) induce activated natural killer cells with NKG2D expression and cytotoxic properties in colorectal cancer.

Aim: This study aimed to investigate the effects of natural adjuvants (G2 and PC) to activate natural killer cells in colorectal cancer. Background: Natural killer (NK) cells are an element of the innate immune system that can recognize and kill cancer cells and provide hope for cancer therapy. One of the current methods in cancer immunotherapy is NK cell therapy. Immunotherapy with NK cells has been limited because of the low number and cytotoxicity level of NK cells. Natural adjuvants such as PC and G2 may stimulate the immune system. It seems that these adjuvants could increase cytotoxic NK cells. Methods: Twelve patients with colorectal cancer and six healthy individuals qualified for inclusion in this study. Peripheral blood mononuclear cells (PBMCs) from each patient with two distinctive concentrations (105and 5×104 cells/well) were treated with Interleukin2 (IL2), PC, and G2 adjuvant separately. The NK cell's surface markers, including CD16, CD56, and NKG2D, were evaluated by flow cytometry. The cytotoxicity effect of treated PBMCs as effector cells against NK sensitive cell line (K562) was assessed using the LDH assay method. Results: The results revealed a significant increase in the level of CD16+NKG2D+ NK cells in PBMCs treated with the G2 group compared with the control group in CRC PBMC (p<0.001) as well as the normal PBMC group (p < 0.01). In addition, the results indicated a significant increase in the level of CD56+NKG2D+ cells in the PBMC treated with PC (p < 0.05) and G2 (p < 0.001) groups compared with the PBMC group. The cytotoxicity result of PBMC from CRC patients in 10:1 ratio of the effector: target showed that the cells' cytotoxicity in the PBMCs treated with PC (p<0.01) and G2 (p<0.05) was significantly higher than the untreated PBMC. Conclusion: According to the result of this study, it can be stated that the PC and G2 adjuvants could be candidates for inducing cytotoxic natural killer cells.

HOTAIR Induces the Downregulation of miR-200 Family Members in Gastric Cancer Cell Lines

Background: Gastric cancer (GC) is the fourth most common human malignancy and the second reason for cancer morbidity worldwide. Long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) has recently emerged as a promoter of metastasis in various cancer types, including GC, through the epithelial­mesenchymal transition (EMT) process. However, the exact mechanism of HOTAIR in promoting EMT is unknown. Aberrant expression of the miR-200 family has been linked to the occurrence and development of various types of malignant tumors. This study investigates the correlation between the HOTAIR and miR-200 family gene expression patterns in GC cell lines. We investigated the miR-200 and HOTAIR due to their common molecular features in the EMT process. Methods: AGS and MKN45 cell lines were transfected with si-HOTAIR, along with a negative control. The effect of HOTAIR knockdown was also analyzed on cell viability and also on the expression of miR-200 family members, including miR-200a, -200b, and -200c, in cell lines using qRT-PCR. Statistical analysis was performed to find the potential correlation between the expression level of HOTAIR and miRs. Results: Our results showed significant increased miR-200 family expression level in transfected AGS and MKN45 GC cells (fold changes > 2; p < 0.001). Moreover, a negative correlation was observed between HOTAIR and miR-200 expression levels in GC cell lines (p < 0.05). Conclusion: Our findings showed a significant association between miR-200 family and HOTAIR expression levels in GC cell lines. Taken together, the HOTAIR-miR-200 axis seems to play a vital role in human GC, suggesting a potential therapeutic target in future GC treatment.

Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor.

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.

Role of the mesenchymal stem cells derived from adipose tissue in changing the rate of breast cancer cell proliferation and autophagy, in vitro and in vivo.

OBJECTIVES: Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions. MATERIALS AND METHODS: In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue. RESULTS: In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues. CONCLUSION: The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation.

Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response.

Natural Killer (NK) cells are innate immune cells with the unique ability to recognize and kill virus-infected and cancer cells without prior immune sensitization. Due to their expression of the Fc receptor CD16, effector NK cells can kill tumor cells through antibody-dependent cytotoxicity, making them relevant players in antibody-based cancer therapies. The role of NK cells in other approved and experimental anti-cancer therapies is more elusive. Here, we review the possible role of NK cells in the efficacy of various anti-tumor therapies, including radiotherapy, chemotherapy, and immunotherapy, as well as the impact of these therapies on NK cell function.

An immunotherapeutic method for COVID-19 patients: a soluble ACE2-Anti-CD16 VHH to block SARS-CoV-2 Spike protein.

The third outbreak of coronavirus (CoV) infection (after SARS-CoV and MERS-CoV) caused by a novel CoV (SARS-CoV-2) of the genus Beta-coronavirus has become a global pandemic. CoVs are enveloped viruses whose proteins include spike (S), membrane (M), and envelope (E) which are embedded in the viral envelope. The glycosylated S protein, which forms homo-trimeric spikes on the surface of the viral particle, mediates viral entry into host cells. SARS-CoV-2, like SARS-CoV, uses the Angiotensin-Converting Enzyme 2 (ACE2) cell surface protein for cellular entry. An attractive anti-viral approach is targeting virus entry into cells, for which three strategies are suggested: 1) direct targeting of the viral glycoprotein; 2) targeting the viral receptor on the cell surface; and 3) using soluble (s) ACE2 that binds to S protein thereby neutralizing the virus. In this article, the advantages and disadvantages of these strategies are explained. Moreover, we propose that fusion of the sACE2 to anti-CD16 to produce a bi-specific molecule could be a promising anti-viral strategy.

Evaluation of long-chain acyl-coenzyme A synthetase 4 (ACSL4) expression in human breast cancer.

BACKGROUND AND PURPOSE: Breast cancer (BC) is one of the major causes of female cancer-related death. It has recently been demonstrated that metabolic reprogramming including alteration in lipid metabolism is indicated in various types of cancer. The enzymes of the acyl-coenzyme A synthetase long-chain family (ACSLs) are responsible for converting fatty acids to their corresponding fatty acyl-coenzyme A esters which are essential for some lipid metabolism pathways. ACSL4 is one of the isoforms of ACSLs and has a marked preference for arachidonic and eicosapentaenoic acids. The objective of this study was to evaluate ACSL4 expression, its prognostic significance, and its correlation with p53 tumor suppressor in BC patients. EXPERIMENTAL APPROACH: In this study 55 pairs of fresh samples of BC and adjacent non-cancerous tissue were used to analyze ACSL4 expression, using real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other studied variables was also examined using the IHC technique. FINDINGS / RESULTS: ACSL4 expression was significantly higher in BC tissues compared to the adjacent normal tissue. This upregulation was negatively correlated with Ki-67 and age, and positively correlated with p53 status. The correlation between ACSL4 and p53 may indicate the role of p53 in the regulation of lipid metabolism in cancer cells, in addition to its role in the regulation of ferroptosis cell death. CONCLUSION AND IMPLICATIONS: Our results indicated that the expression of ACSL4 may be considered as a prognostic indicator and potential therapeutic target in BC. However, further studies are needed to confirm the significance of these findings.

Expression and clinicopathological significance of lipin-1 in human breast cancer and its association with p53 tumor suppressor gene.

Breast cancer (BC) is an important cause of female cancer-related death. It has recently been demonstrated that metabolic disorders including lipid metabolism are a hallmark of cancer cells. Lipin-1 is an enzyme that displays phosphatidate phosphatase activity and regulates the rate-limiting step in the pathway of triglycerides and phospholipids synthesis. The objective of this study was to evaluate lipin-1 expression, its prognostic significance, and its correlation with p53 tumor suppressor in patients with BC. In this study, 55 pairs of fresh samples of BC and adjacent noncancerous tissue were used to analyze lipin-1, using quantitative real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other clinicopathological variables and p53 was also examined using IHC technique. The cell migration was studied in MCF-7 and MDA-MB231 cells following the inhibition of lipin-1 by propranolol. Our results show that the relative expression of lipin-1 messenger RNA was significantly higher in BC tissues compared with the adjacent normal tissue and its inhibition reduced cell migration in cancer cells. This upregulation was negatively correlated with histological grade of tumor and p53 status (p = .001 and p = .034) respectively and positively correlated with the tumor size (p = .006). Our results also seem to indicate that the high lipin-1 expression is related to a good prognosis in patients with BC. The expression of lipin-1 may be considered as a novel independent prognostic factor. The inhibition of lipin-1 may also have therapeutic significance for patients with BC. The correlation between lipin-1 and p53 confirms the role of p53 in the regulation of lipid metabolism in cancer cells.

Sugarcane molasses enhances TGF-ß secretion and FOXP3 gene expression by Bifidobacterium Animalis Subsp. Lactis stimulated PBMCs of Ulcerative Colitis patients.

Ulcerative colitis (UC) is one of the inflammatory diseases of the gut with frequent bloody diarrhea leads to increased rates of anemia. Evidences indicate the immunomodulation disorders in the response to intestinal microbiota in UC. Although sugarcane molasses, rich in necessary minerals and vitamins, could be a good support nutrient but its effect on immune system of UC patients is unknown. To determine how the immune system of UC patients responds to molasses this study was planned. Bifidobacterium lactis were cultivated on MRS broth. PBMCs of 12 UC patients were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria and/or molasses in RPMI-1640 plus 10 % FCS. The gene expression of FoxP3 was measured by real-time PCR. TGF-ß and TNF-α were measured in supernatant of PBMCs by ELISA. Sugarcane molasses and B. lactis significantly augmented TGF-ß compared to control (p < 0.01 and p < 0.001 respectively). The secretion levels of TGF-ß by B. lactis plus molasses compared to B. lactis stimulated PBMCs was significantly higher (p < 0.05) but the level of TNF-α by PBMCs after 2/4/12 h incubation with B. lactis plus molasses compared to B. lactis alone was not changed (p > 0.2). The level of FOXP3 expression after treatment with molasses was increased significantly (p < 0.05). These data show that if sugarcane molasses added to B. lactis, not only do not increase the pro-inflammatory cytokine, TNF-α, but also augments the anti-inflammatory cytokine, TGF-ß by PBMCs. Therefore, these results pave the way for further investigation to show sugarcane molasses as a safe support to compensate the lost nutrients in UC patients.

Prevalence of Anaerobic Bacteria (P.gingivalis) as Major Microbial Agent in the Incidence Periodontal Diseases by Meta-analysis.

STATEMENT OF THE PROBLEM: Periodontal diseases are complex oral diseases characterized by bacterial-induced inflammatory destruction of tooth-supporting tissues. Porphyromonas gingivalis (P. gingivalis) is a common gram-negative anaerobic oral bacteria strongly associated with periodontal disease. PURPOSE: The present study was conducted to estimate prevalence of P. gingivalis in patients with periodontal diseases by using meta-analysis method. MARTIALS AND METHOD: Different databases including PubMed, EmBase, Scopus, the Institute for Scientific Information (ISI) Web of Science, and the Cochrane Library were searched to identify original English-language studies addressing prevalence of P. gingivalis in periodontal diseases up to December 2014. The random effects model was applied in the meta-analysis and the heterogeneity between studies was assessed using a Cochran test and the I2 index. Funnel plots and Egger test were used to examine publication bias. Statistical analyses were performed using STATA version 12. RESULTS: Forty-two eligible studies published during 1993- 2016 were selected for meta-analysis. Considering all the included studies, the total sample size was 5,884 individuals containing 2,576 healthy people with a mean age of 37.21±7.45 years and 3,308 periodontal patients with a mean age of 44.16±8.35 years. Overall, the prevalence of P. gingivalis was 78% [95% CI: 74-81] in periodontal diseases group and 34% [95% CI: 26-41] in healthy individuals. There was a significantly higher prevalence of P.gingivalis in individuals with periodontal diseases compared to healthy subjects [78% versus 34%, respectively]. CONCLUSION: This study indicates that P. gingivalis is highly present in subjects with periodontal diseases and it also appears in periodontally healthy people, although to a lesser extent. Thus, the presence of P. gingivalis increases the chance of periodontal disease and it can be considered as a main potential risk factor.

Apoptosis induction in acute promyelocytic leukemia cells through upregulation of CEBPα by miR-182 blockage.

MicroRNAs (miRNAs) involved in regulation of the genes. The CCAAT/enhancer-binding protein-α (CEBPα) is a crucial transcription factor for normal hematopoiesis and cell cycle that frequently disrupted in human acute myeloid leukemia (AML). The miR-182 up-regulation in several malignant diseases such as AML was reported, in the other hand bioinformatics analysis revealed CEBPα targeted by miR-182.miR-182-5p inhibition in human acute promyelocytic leukemia (APL) cell line was performed by using locked nucleic acid (LNA) and subsequently miR-182-5p and CEBPα expression, apoptosis, necrosis and cell proliferation were measured. After LNA-anti-miR-182-5p transfection to cells at different time points, miR-182-5p down regulation and CEBPα overexpression was revealed in the LNA-anti-miR group compared to the control groups. The cell viability was meaningfully varied between LNA-anti-miR and control groups. Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia.

The Effect of Differentially Designed Fusion Proteins to Elicit Efficient Anti-human Thyroid Stimulating Hormone Immune Responses.

The production of human thyroid stimulating hormone (hTSH) immunoassays requires specific antibodies against hTSH which is a cumbersome process. Therefore, producing specific polyclonal antibodies against engineered recombinant fusion hTSH antigens would be of great significance. The best immunogenic region of the hTSH was selected based on in silico analyses and equipped with two different fusions. Standard methods were used for protein expression, purification, verification, structural evaluation, and immunizations of the white New Zealand rabbits. Ultimately, immunized serums were used for antibody titration, purification and characterization (specificity, sensitivity and cross reactivity). The desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. Structural analyses indicated that only the bigger antigen has showed changed 2 dimensional (2D) and 3D structural properties in comparison to the smaller antigen. The raised polyclonal antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum and negligible. The fusion which was solely composed of the tetanus toxin epitopes led to better protein folding and was capable of immunizing the host animals resulting into high titer antibody. Therefore, the minimal fusion sequences seem to be more effective in eliciting specific antibody responses.

Kefir: a powerful probiotics with anticancer properties.

Probiotics and fermented milk products have attracted the attention of scientists from various fields, such as health care, industry and pharmacy. In recent years, reports have shown that dietary probiotics such as kefir have a great potential for cancer prevention and treatment. Kefir is fermented milk with Caucasian and Tibet origin, made from the incubation of kefir grains with raw milk or water. Kefir grains are a mixture of yeast and bacteria, living in a symbiotic association. Antibacterial, antifungal, anti-allergic and anti-inflammatory effects are some of the health beneficial properties of kefir grains. Furthermore, it is suggested that some of the bioactive compounds of kefir such as polysaccharides and peptides have great potential for inhibition of proliferation and induction of apoptosis in tumor cells. Many studies revealed that kefir acts on different cancers such as colorectal cancer, malignant T lymphocytes, breast cancer and lung carcinoma. In this review, we have focused on anticancer properties of kefir.

Lactobacilus Delbrueckii subsp. Bulgaricus Modulates the Secretion of Th1/Th2 and Treg Cell-Related Cytokines by PBMCs from Patients with Atopic Dermatitis.

Background Atopic dermatitis (AD) is an inflammatory skin disease which may be due to the imbalance between Th1-, Th2 and Treg cell-related immune responses. Evidences suggest that appropriate stimulation with probiotics may correct the skewed immune response in children with AD. The aim was to determine the effects of the yogurt culture lactobacillus Bulgaricus on the secretion of Th1/Th2/Treg type cytokines by PBMCs from children with AD. MethodsL. Bulgaricus was cultivated on MRS broth. The PBMCs from 20 children with AD were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria in RPMI-1640 plus 10% FCS for 48/72 h. The levels of IL-10, IL-4, IL-12 and IFN-γ were measured in supernatant of PBMCs by ELISA. ResultsL. Bulgaricus significantly up-regulated the secretion of IL-10, IL-12 and IFN-γ, whereas decreased the secretion of IL-4 by PBMCs at both incubation times 48 h/72 h and both bacteria:PBMCs ratios 100:1/50:1, compared to control (p<0.05). There were no significant differences between incubation times 48 h and 72 h regarding the secretion levels of IL-12, IFN-γ and IL-4. However, the secretion of IL-10 by L. Bulgaricus-stimulated PBMCs at incubation time 72 h and in the presence of bacteria:PBMCs ratio 100:1 was significantly higher than in incubation time 48 h and in the presence of bacteria:PBMCs ratio 50:1 (P<0.000 and P<0.00, respectively). Conclusion These data show that L. Bulgaricus may modulate the secretion of Th1-, Th2-Treg-related cytokines in AD patients. Therefore, the possible potential therapeutic of L. Bulgaricus for treatment of AD should be consider in further investigation.

Circulating concentrations of interleukin (IL)-17 in patients with multiple sclerosis: Evaluation of the effects of gender, treatment, disease patterns and IL-23 receptor gene polymorphisms.

Background: Interleukin (IL)-17/IL-23 axis performs a prominent role in the pathogenesis of several autoimmune disorders. This study aimed to investigate the concentrations of IL-17 in patients with multiple sclerosis (MS) and its relationship with gender, medication, disease forms and single nucleotide polymorphisms (SNP) in IL-23R gene, including rs11209026 and rs1004819. Methods: The blood specimens were obtained from 135 healthy individuals and 135 MS patients. The patients exhibited relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 19), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) MS. The DNA was analyzed for SNPs using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and IL-17 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: We have observed elevated serum IL-17 concentrations in MS patients compared with healthy individuals (P < 0.001). The men with MS had higher IL-17 concentrations than women patients (P < 0.050). Untreated patients had significantly higher IL-17 concentrations than healthy individuals and treated patients (P < 0.001 and P < 0.010, respectively). The IL-17 concentrations were significantly decreased in patients treated with interferon-ß (IFN-ß), methylprednisolone or both drugs as compared with untreated MS patients (P < 0.050, P < 0.020 and P < 0.050, respectively). The IL-17 concentrations were also significantly higher in patients with RRMS and PRMS compared with healthy individuals (P < 0.005 and P < 0.010, respectively). The genetic variations at SNPs rs11209026 and rs1004819 were not significantly different between healthy individuals and patients. The IL-17 concentrations were not influenced by genetic variations at investigated SNPs. Conclusion: These results indicated higher levels of IL-17 in MS patients that may be influenced by disease patterns, medication and gender. No association was observed between investigated SNPs and MS.