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1.
Iran J Immunol ; 21(2)2024 May 27.
Article in English | MEDLINE | ID: mdl-38800958

ABSTRACT

Background: 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. Objective: To explore the impacts of G. glabra extract on different parameters related to TH1 and Treg cells using a breast cancer (BC) model. Methods: 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-ß, and IL-12, and intra-tumoral expressions of granzyme-B, T-bet, and FOXP3 were assessed. Results: 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-ß 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. Conclusion: Treatment of mice with BC using G. glabra extract improved survival rate, reduced tumor growth, and modulated T cell-mediated immune responses.

2.
J Cancer Res Clin Oncol ; 150(3): 165, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546751

ABSTRACT

PURPOSE: Cancer testis antigens (CTAs) are a family of proteins typically expressed in male testicles but overexpressed in various cancer cell types. Transmembrane Phosphatase with Tensin homology (TPTE) is expressed only in the testis of healthy individuals and is a member of the family of CTAs. The current study, for the first time, examined the significance of TPTE expression in prostate cancer (PCa) tissues by generating a novel antibody marker targeting TPTE protein. METHODS: Polyclonal antibodies were prepared for TPTE-p1 and TPTE-p2 peptides, which are derived from the extracellular domains of TPTE. Anti-TPTE-p2 antibody was then used to study the extent and pattern of TPTE expression in 102 PCa and 48 benign prostatic hyperplasia (BPH) tissue samples by immunohistochemistry. The viability of cancer cell lines (PC-3 and MCF-7 cells) was also evaluated in the presence of anti-TPTE-p2 antibody using the MTT test. RESULTS: The immunohistochemical analysis demonstrated a significant increase in cytoplasmic and membrane TPTE expression in the PCa samples compared to the BPH group (both P < 0.0001). Cytoplasmic TPTE expression was positively correlated with Gleason score and PSA levels (P = 0.03 and P = 0.001, respectively). Significant correlations were identified between the levels of PSA and perineural invasion and the membrane expression (P = 0.01, P = 0.04, respectively). Moreover, anti-TPTE-p2 antibody inhibited PC-3 and MCF-7 cells proliferation compared to the control group for 24 h (P < 0.001 and P = 0.001, respectively) as well as for 48 h (P = 0.001 and P = 0.001, respectively). CONCLUSION: Our findings indicate that increased TPTE expression is associated with progression of disease. The ability of anti-TPTE-p2 antibody to recognize and target the TPTE protein makes it a potential biomarker to assess and/or target the PCa.


Subject(s)
Membrane Proteins , PTEN Phosphohydrolase , Prostatic Hyperplasia , Prostatic Neoplasms , Humans , Male , Antibodies , Biomarkers , MCF-7 Cells , Prostate-Specific Antigen , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/genetics , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , PTEN Phosphohydrolase/genetics , Membrane Proteins/genetics , PC-3 Cells
3.
Immunopharmacol Immunotoxicol ; 46(1): 73-85, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37647347

ABSTRACT

PURPOSE: In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers. MATERIALS AND METHODS: Tumors were established in mice by subcutaneously injecting 7 × 105 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-ß) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively. RESULTS: Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (p = .0002), increasing survival rate (p = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (p < .001) and TH1 cells (p < .01); promoted the production of IFN-γ (p < .0001) and IL-12 (p < .001) by splenocytes; enhanced the T-bet (p < .05) and Granzyme B (p < .001) expression, whereas decreased the TGF-ß and FOXP3 expression (p < .05). CONCLUSION: Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.


Subject(s)
Neoplasms , Vaccines , Mice , Animals , Lipopolysaccharides/pharmacology , Granzymes/metabolism , Leptin/metabolism , Immunity, Cellular , Transforming Growth Factor beta/metabolism , Interferon-gamma/metabolism , Models, Animal , Neoplasms/metabolism , Interleukin-12 , Vaccines/metabolism , Dendritic Cells , Forkhead Transcription Factors/metabolism
4.
Chronic Dis Transl Med ; 9(4): 277-287, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37915385

ABSTRACT

The prevalence of cancer, especially in industrial countries, is a major problem for health and treatment systems. Cancer can affect the quality of life of all family members and has many negative effects on the community. Despite many advances in cancer treatment, this disease is still a major worldwide problem. There is strong evidence that dietary habits are effective in protecting against cancer and even helping in the disease treatment progress. Nuts with various biologically-active compounds, such as vitamins, phytosterols, isoflavones, flavonoids, and polyphenols have been reported to possess anticarcinogenic properties. Accordingly, this review provides an insight into the association between nut consumption and the prevention of some cancers. We considered the cancers related to the urogenital and genital tract, gastrointestinal tract, as well as women-related cancers. Both cell culture examinations and experimental animal studies alongside observational epidemiological studies demonstrated that regular consumption of a nut-enriched diet is able to reduce the risk of these cancers.

5.
Chin Med Sci J ; 38(3): 250-256, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37643873

ABSTRACT

Kidney stone is a highly recurrent disease in the urinary tract system. Most kidney stones are calcium stones, usually consisting of either calcium oxalate or calcium phosphate. Supersaturation of soluble calcium, oxalate, phosphate, and citrate in the urine is the basis for calcium stone formation. Genetics, diet, low physical activity, and individual habits contribute to the formation of kidney stones. In this review, the associations of the risk of kidney stones with oxalate consumption and some individual habits, such as smoking, alcohol drinking, and opium consumption, are summarized.


Subject(s)
Calcium , Kidney Calculi , Humans , Calcium/urine , Oxalates , Kidney Calculi/etiology , Kidney Calculi/urine , Calcium Oxalate/urine , Habits
6.
Med Oncol ; 40(6): 179, 2023 May 15.
Article in English | MEDLINE | ID: mdl-37188900

ABSTRACT

Apelin/APJ axis plays a critical role in cancer progression, thus its targeting inhibits tumor growth. However, blocking of Apelin/APJ axis in combination with immunotherapeutic approaches may be more effective. This study aimed to investigate the effects of APJ antagonist ML221 in combination with a DC vaccine on angiogenic, metastatic and apoptotic-related factors in a breast cancer (BC) model. Four groups of female BALB/c mice with 4T1-induced BC were treated with PBS, APJ antagonist ML221, DC vaccine, and "ML221 + DC vaccine". After completion of the treatment, the mice were sacrificed and the serum levels of IL-9 and IL-35 as well as the mRNA expression of angiogenesis (including VEGF, FGF-2, and TGF-ß), metastasis (including MMP-2, MMP-9, CXCR4) and apoptosis-related markers (Bcl-2, Bax, Caspase-3) in tumor tissues were determined using ELISA and real-time PCR, respectively. Angiogenesis was also evaluated by co-immunostaining of tumor tissues with CD31 and DAPI. Primary tumor metastasis to the liver was analyzed using hematoxylin-eosin staining. The efficiency of combination therapy with "ML221 + DC vaccine" was remarkably higher than single therapies in preventing liver metastasis compared to the control group. In comparison with the control group, combination therapy could significantly reduce the expression of MMP-2, MMP-9, CXCR4, VEGF, FGF-2, and TGF-ß in tumor tissues (P < 0.05). It also decreased the serum level of IL-9 and IL-35 compared with the control group (P < 0.0001). Moreover, vascular density and vessel diameter were significantly reduced in the combination therapy group compared with the control group (P < 0.0001). Overall, our findings demonstrate that combination therapy using a blocker of the apelin/APJ axis and DC vaccine can be considered a promising therapeutic program in cancers.


Subject(s)
Breast Neoplasms , Liver Neoplasms , Animals , Female , Mice , Apelin/genetics , Apelin/metabolism , Apelin Receptors/genetics , Apelin Receptors/metabolism , Breast Neoplasms/therapy , Dendritic Cells/metabolism , Fibroblast Growth Factor 2 , Interleukin-9 , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Transforming Growth Factor beta , Vaccine Efficacy , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
7.
Adv Med Sci ; 68(1): 157-168, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37003235

ABSTRACT

PURPOSE: Prostaglandin E2 (PGE2), a product of cyclooxygenase (COX) pathway of arachidonic acid, exerts inhibitory impacts on dendritic cell (DC) activity to repress anti-tumor immune responses. Therefore, targeting COX during DC vaccine generation may enhance DC-mediated antitumor responses. We aimed to investigate the impacts of DC vaccine treated with celecoxib (CXB), a selective COX2 inhibitor, on some T cell-related parameters. MATERIALS AND METHODS: Breast cancer (BC) was induced in BALB/c mice, and then they received DC vaccine treated with lipopolysaccharide (LPS-mDCs), LPS with a 5 â€‹µM dose of CXB (LPS/CXB5-mDCs) and LPS with a 10 â€‹µM dose of CXB (LPS/CXB10-mDCs). The frequency of splenic Th1 and Treg cells and amounts of IFN-γ, IL-12 and TGF-ß production by splenocytes, as well as, the expression of Granzyme-B, T-bet and FOXP3 in tumors were determined using flow cytometry, ELISA, and real-time PCR, respectively. RESULTS: Compared with untreated tumor group (T-control), treatment with LPS/CXB5-mDCs and LPS/CXB10-mDCs decreased tumor growth (P â€‹= â€‹0.009 and P â€‹< â€‹0.0001), escalated survival rate (P â€‹= â€‹0.002), increased the frequency of splenic Th1 cells (P â€‹= â€‹0.0872, and P â€‹= â€‹0.0155), increased the IFN-γ (P â€‹= â€‹0.0003 and P â€‹= â€‹0.0061) and IL-12 (P â€‹= â€‹0.001 and P â€‹= â€‹0.0009) production by splenocytes, upregulated T-bet (P â€‹= â€‹0.062 and P â€‹< â€‹0.0001) and Granzyme-B (P â€‹= â€‹0.0448 and P â€‹= â€‹0.4485), whereas decreased the number of Treg cells (P â€‹= â€‹0.0014, and P â€‹= â€‹0.0219), reduced the amounts of TGF-ß production by splenocytes (P â€‹= â€‹0.0535 and P â€‹= â€‹0.0169), and reduced the expression of FOXP3 (P â€‹= â€‹0.0006 and P â€‹= â€‹0.0057) in comparison with T-control group. CONCLUSIONS: Our findings show that LPS/CXB-treated DC vaccine potently modulated antitumor immune responses in a mouse BC model.


Subject(s)
Neoplasms , Vaccines , Animals , Mice , Celecoxib/pharmacology , Celecoxib/therapeutic use , Granzymes , Lipopolysaccharides , Interleukin-12 , Immunity, Cellular , Transforming Growth Factor beta , Dendritic Cells , Vaccination , Forkhead Transcription Factors
8.
Immunopharmacol Immunotoxicol ; 44(5): 773-785, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35620857

ABSTRACT

OBJECTIVE: Th9- and regulatory T (Treg) cells exert pro- and anti-allergic activity, respectively. Mesenchymal stem cell (MSC)-related immunomodulatory impacts can be enhanced by inflammatory cytokines. Here, the modulatory effects of IFN-γ/TNF-α-induced MSCs on Th9- and Treg cell-related parameters were investigated using an asthma model. METHODS: Allergic asthma was induced in BALB/c mice using sensitized and challenging with ovalbumin (OVA). The asthmatic groups were treated intraperitoneally with PBS, MSCs, IFN-γ-induced MSCs, TNF-α-induced MSCs and 'IFN-γ + TNF-α'-induced MSCs before the challenge phase. The mice were sacrificed 24 h after challenge. The serum IL-9 and IL-35 levels, as well as gene expression of IL-9, PU.1, IL-35-EBI3, and FOXP3 in the lung tissues were assessed using ELISA and real time-PCR, respectively. RESULTS: The differences of Th9 and Treg-related parameters were not significant between untreated asthmatic mice and those treated with non-induced MSCs. In comparison with untreated asthmatic group, treatment with IFN-γ-induced MSCs significantly reduced serum IL-9 levels, reduced lung expression of IL-9 and PU.1, while increasing serum IL-35 levels as well as lung expression of FOXP3; treatment with TNF-α-induced MSCs significantly reduced serum IL-9 levels as well as lung expression of IL-9, and treatment with 'IFN-γ + TNF-α'-induced MSCs, significantly modulated all investigated Th9 and Treg-related parameters. In comparison to mice treated with non-induced MSCs, serum IL-9 levels were remarkably decreased in mice treated with IFN-γ-induced and 'IFN-γ + TNF-α'-induced MSCs. CONCLUSIONS: IFN-γ-and 'IFN-γ + TNF-α' treated MSCs exerted almost comparable impacts, but were more efficient than TNF-α-exposed MSCs. Thus, IFN-γ alone can be sufficient to promote immunomodulatory effects of MSCs.


Subject(s)
Anti-Allergic Agents , Asthma , Mesenchymal Stem Cells , Animals , Anti-Allergic Agents/pharmacology , Asthma/drug therapy , Cytokines/metabolism , Disease Models, Animal , Forkhead Transcription Factors/metabolism , Interferon-gamma/metabolism , Interleukin-9/metabolism , Interleukin-9/pharmacology , Interleukin-9/therapeutic use , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred BALB C , Ovalbumin/pharmacology , T-Lymphocytes, Regulatory , Tumor Necrosis Factor-alpha/metabolism
9.
Iran J Microbiol ; 14(6): 874-880, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36721439

ABSTRACT

Background and Objectives: Few studies have considered potential benefits of probiotic bacteria and their derivatives on human and animal health. Nisin is an antimicrobial agent that is produced by lactobacilli and served as a preservative in foods. This study aims to investigate whether nisin suppresses or decreases the genes involved in the pathogenicity of methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). Materials and Methods: MSSA and MRSA strains were cultured at the », ½, and 1 × minimum inhibitory concentration (MIC) of nisin. Next, RNA extraction was performed at the mid-exponential stage of growth, and cDNA was synthesized. The expression of virulence factors was measured by qPCR, and the data were analyzed by the ΔΔCt formula. Results: Depending on the incubation times and the Lactobacillus species, the MIC of nisin on MRSA and MSSA observed in 800 and 1600 mg/l, respectively. The qPCR assay showed the expression level of the sea, agrA, and spa genes decreased and the level of the sae gene increased at the sub-MIC of nisin, and no antagonism was observed. Concerning MRSA, the maximum downregulation rate was observed in the sea gene (up to 5.9 folds) while in MSSA, the maximum downregulation rate was noticed in the agrA gene (up to 10 folds). Conclusion: Due to the high inhibitory effect of the sub-MIC of nisin on the expression of virulence factor genes in MRSA and MSSA, this compound could potentially reduce the virulence of S. aureus.

10.
J Pharm Pharm Sci ; 24: 363-380, 2021.
Article in English | MEDLINE | ID: mdl-34310275

ABSTRACT

Since the first production of monoclonal antibodies about 35 years ago, researchers have found them useful in the treatment and diagnosis of various diseases such as cancer. By developing different types of monoclonal antibodies such as humanized, drug conjugated, or bispecific ones, researchers, have achieved remarkable success in treating several complicated and challenging diseases, targeting specific antigens or receptors makes monoclonal antibodies the right choice to inhibit signaling pathways like programmed death-ligand 1 (PD-L1) or programmed death1 (PD-1) and changing cell behavior. As one of the most common types of malignancies among women, breast cancer is one of the most critical conditions which different types of monoclonal antibodies were designed and produced to treat. Therefore, we reviewed these antibodies in breast cancer, their targets, and their efficacy and toxicity, with more focus on recent PD-L1or PD-1 inhibitor antibodies in breast cancer and beyond.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Breast Neoplasms/drug therapy , Animals , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/pharmacology , B7-H1 Antigen/immunology , Breast Neoplasms/immunology , Female , Humans , Programmed Cell Death 1 Receptor/immunology
11.
Asian Pac J Cancer Prev ; 22(5): 1413-1419, 2021 May 01.
Article in English | MEDLINE | ID: mdl-34048169

ABSTRACT

OBJECTIVE: The present study aims to examine the effects of nisin on the survival and apoptosis of the hepatoma cell line HepG2 and to investigate possible apoptosis pathways activated by nisin. MATERIALS AND METHODS: For this purpose, viability and apoptosis of the cells were accomplished by the nisin treatment using the MTT assay and Annexin-V-fluorescein/propidium iodide (PI) double staining, respectively. Additionally, the human apoptosis PCR array was performed to determine pathways or genes activated by nisin during possible apoptosis. RESULTS: The results of the present study showed that nisin was able to decrease cell viability (IC50 ~ 40 µg/ml) in a dose-dependent manner and could induce apoptosis in HepG2 cells. PCR data indicated a considerable increase in the expression of genes, such as caspase and BCL2 families, involved in the induction of apoptosis. CONCLUSIONS: The data from this study showed that overexpression of genes involved in the intrinsic pathway of apoptosis, especially caspase-9 and BID, increased apoptosis in HepG2 cells treated by nisin, compared to the control group.


Subject(s)
Anti-Bacterial Agents/pharmacology , Apoptosis , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Gene Expression Regulation, Neoplastic/drug effects , Liver Neoplasms/pathology , Nisin/pharmacology , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Proliferation , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism
12.
Biotechnol Appl Biochem ; 68(2): 267-271, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32311159

ABSTRACT

The aims of this study were to compare mRNA levels of melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) in multiple sclerosis (MS) patients in comparison to the healthy controls as well as investigating the effects of IFN-ß 1a on the expression of these molecules. In this study, mRNA levels of MDA5 and RIG-1 in peripheral leukocytes of 30 new cases of MS patients and 35 healthy controls were evaluated using the real-time-PCR method. mRNA levels of MDA5 and RIG-1 were determined in the MS patients 6 months after treatment with standard doses of IFN-ß 1a. mRNA levels of MDA5 and RIG-1 were significantly decreased in the MS patients in comparison to the healthy controls. The analysis also revealed that IFN-ß 1a therapy leads to the upregulation of RIG-1, but not MDA5, in the total MS patients and the female group. MS patients suffer from insufficient expression of MDA5 and RIG-1, and IFN-ß 1a therapy results in the upregulation of RIG-1 in the patients, especially in the female patients. Thus, it seems that IFN-ß 1a not only decreased pathogenic inflammatory responses but also modulated the expression of RIG-1 to protect the patients from infectious diseases and upregulation of IFN-I in a positive feedback.


Subject(s)
DEAD Box Protein 58/biosynthesis , Gene Expression Regulation/drug effects , Interferon beta-1a/pharmacology , Interferon-Induced Helicase, IFIH1/biosynthesis , Leukocytes/metabolism , Multiple Sclerosis/metabolism , Receptors, Immunologic/biosynthesis , Female , Humans , Leukocytes/pathology , Male , Multiple Sclerosis/pathology
13.
J Conserv Dent ; 22(1): 12-16, 2019.
Article in English | MEDLINE | ID: mdl-30820076

ABSTRACT

INTRODUCTION: Inflammation is a risk factor for dental complications. Inflammasomes are a set of intracellular sensors which participate in the induction of inflammation. As the main factors involved in the induction of pulp inflammation in the carious teeth are yet to be clarified, this study was aimed to evaluate NLRP1 and NLRC4 expression levels in the inflamed and healthy pulps. MATERIALS AND METHODS: Fifty inflamed and fifty healthy pulps were evaluated regarding the multiRNA levels of NLRP1 and NLRC4 using real-time polymerase chain reaction technique. RESULTS: Results demonstrated that expression of NLRP1 (P = 0.985) and NLRC4 (P = 0.581) did not significantly differ in inflamed in comparison to healthy pulps. NLRP1 (P = 0.989) and NLRC4 (P = 0.170) did not change in males when compared with females in inflamed pulps. Furthermore, NLRP1 (P = 0.133) and NLRC4 (P = 0.642) were not altered in males in comparison to females in healthy pulps. CONCLUSION: Although NLRP1 and NLRC4 are the main inflammasomes, it appears that they are not the responsible molecules involved in the human pulp inflammation in the carious teeth.

14.
Curr Drug Discov Technol ; 16(3): 265-271, 2019.
Article in English | MEDLINE | ID: mdl-29766814

ABSTRACT

OBJECTIVE: This research aimed to study the anti-aging and anti-inflammatory effects of low and high doses of the ß-D-mannuronic (M2000) on gene expression of enzymes involved in oxidative stress (including SOD2, GST, GPX1, CAT, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy donors under in vitro conditions. METHODS: The PBMCs were separated and the RNAs were then extracted and the cDNAs synthesized, and expression levels of the mentioned genes were detected by qRT-PCR. RESULTS: Our results indicated that the high dose of this drug could significantly reduce the expression level of the SOD2 gene compared to the lipopolysaccharide (LPS) group (p < 0.0001). Moreover, it was found that the high dose of this drug could significantly decrease the expression level of the GST gene compared to the LPS group (p < 0.0001). However, no significant reductions were observed in expression levels of the CAT and GPX1 genes compared to the LPS group. Furthermore, our data revealed that the level of iNOS and MPO gene expression was significantly reduced, in both doses of M2000, respectively, compared to the LPS group (p < 0.0001). CONCLUSION: This research showed that M2000 as a novel NSAID with immunosuppressive properties could modify oxidative stress through lowering expression levels of the SOD2, GST, iNOS, and MPO genes compared to the healthy expression levels, with a probable reduction of the risk of developing inflammatory diseases related to age and aging.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Hexuronic Acids/pharmacology , Immunosuppressive Agents/pharmacology , Leukocytes, Mononuclear/drug effects , Adult , Aging , Catalase/genetics , Gene Expression Regulation/drug effects , Glutathione Peroxidase/genetics , Glutathione Transferase/genetics , Humans , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/pharmacology , Middle Aged , Nitric Oxide Synthase Type II/genetics , Oxidative Stress/drug effects , Peroxidase/genetics , RNA, Messenger/metabolism , Superoxide Dismutase/genetics , Glutathione Peroxidase GPX1
15.
Asian Pac J Cancer Prev ; 19(8): 2217-2222, 2018 Aug 24.
Article in English | MEDLINE | ID: mdl-30139228

ABSTRACT

Background: Nisin is a member of the group of anti-microbial peptides which are considered as bacteriocins, but it possesses a vast range of activities. Astrocytoma is among the most prevalent types of brain tumor globally. Considering all facts about this peptide, the aim of the present study was the evaluation of any impact of nisin on proliferation and apoptosis of an astrocytoma cell line (SW1088). Methods: The SW1088 cell line was purchased from the Pasteur Institute of Iran and treated with various concentrations of Nisin. Nisin-induced cell toxicity and apoptosis were detected by both MTT assay and annexin V-FITC /propidium iodide (PI) staining. Result: In current study we observed that the cell death and apoptosis were significantly increased following nisin treatment, as compared to the control group. Conclusion: These results open a new window for establishment promising approaches with the concept of anti-cancer therapy by nisin in the future.


Subject(s)
Anti-Bacterial Agents/pharmacology , Apoptosis/drug effects , Astrocytoma/pathology , Cell Proliferation/drug effects , Nisin/pharmacology , Astrocytoma/drug therapy , Humans , Tumor Cells, Cultured
16.
J Investig Clin Dent ; 9(1)2018 Feb.
Article in English | MEDLINE | ID: mdl-28834384

ABSTRACT

AIM: S100 calcium-binding protein A1 (S100A12) is a pro-inflammatory molecule which is secreted during inflammation and induces chemotaxis and the production of pro-inflammatory cytokines via interaction with receptor for advanced glycation endproducts (RAGE) and subsequent, activation of nuclear factor-κB (NF-κB). The present study was designed to determine the expression levels of S100A12, RAGE, and NF-κB in the inflamed pulp of carried teeth. METHODS: In the present study, mRNA from 50 inflamed pulp and 50 healthy pulp were used for expression studies using real-time polymerase chain reaction. The expression levels of S100A12, RAGE, and NF-κB were compared between inflamed and healthy tissues. RESULTS: The results revealed that the expression of S100A12, but not of RAGE or NF-κB, was significantly decreased in inflamed pulp when compared to healthy pulp. mRNA levels of RAGE were also increased in the inflamed pulp taken from men when compared with women. CONCLUSION: The results suggest that S100A12 does not participate in the induction of inflammation in dental pulp. However, RAGE can participate in the inflammation in the pulp of males.


Subject(s)
Antigens, Neoplasm/biosynthesis , Dental Caries/metabolism , Dental Pulp Diseases/metabolism , Mitogen-Activated Protein Kinases/biosynthesis , NF-kappa B/biosynthesis , Periodontitis/metabolism , S100A12 Protein/biosynthesis , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Cross-Sectional Studies , Cytokines/genetics , Cytokines/metabolism , Dental Caries/pathology , Dental Pulp Diseases/pathology , Female , Gene Expression , Humans , Male , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Periodontitis/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , S100A12 Protein/genetics , S100A12 Protein/metabolism , Sex Factors , Young Adult
17.
Article in English | MEDLINE | ID: mdl-28504091

ABSTRACT

Chlamydia species are obligate intracellular pathogens causing different infectious diseases particularly asymptomatic genital infections and are also responsible for a wide range of complications. Previous studies showed that there are different immune responses to Chlamydia species and their infections are limited to some cases. Moreover, Chlamydia species are able to alter immune responses through modulating the expression of some immune system related molecules including cytokines. Toll like receptors (TLRs) belonge to pathogen recognition receptors (PRRs) and play vital roles in recognition of microbes and stimulation of appropriate immune responses. Therefore, it appears that TLRs may be considered as important sensors for recognition of Chlamydia and promotion of immune responses against these bacterial infections. Accordingly, TLR4 detects several microbial PAMPs such as bacterial lipopolysacharide (LPS) and subsequently activates transcription from pro-inflammatory cytokines in both MYD88 and TRIF pathways dependent manner. The purpose of this review is to provide the recent data about the status and major roles played by TLR4 in Chlamydia species recognition and promotion of immune responses against these infections and also the relationship between TLR4 activities and pathogenesis of Chlamydia infections.


Subject(s)
Chlamydia Infections/immunology , Chlamydia/immunology , Toll-Like Receptor 4/immunology , Adaptor Proteins, Vesicular Transport/immunology , Animals , Chlamydia Infections/microbiology , Cytokines , Humans , Mice , Myeloid Differentiation Factor 88/immunology , Signal Transduction
18.
Viral Immunol ; 29(9): 496-501, 2016 11.
Article in English | MEDLINE | ID: mdl-27750030

ABSTRACT

Nucleotide-binding domain leucine repeats (NLRs) are required for the recognition of various molecules that are expressed within microbes and are able to actuate appropriate immune responses via activation of cytokines. The current study evaluates the expression levels of NLRP1 and NLRC4, which are components of inflammasomes, in chronic hepatitis B (CHB) virus-infected patients. This study recruited two series of CHB patients (each contained 60 patients) and 60 healthy controls. Real-time polymerase chain reaction (PCR) was employed to evaluate mRNA expression levels of NLRP1, NLRP3, and NLRC4 as well as hepatitis B virus (HBV)-DNA copy number. Serum levels of liver markers were also used to evaluate the patients. Hepatitis B envelope antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were also examined in all patients to evaluate infection. The data showed that expression levels of NLRC4 and NLRP1 were not significantly different in circulating monocytes of CHB patients when compared with those of healthy controls. Furthermore, the data indicate that mRNA levels of NLRP1, NLRP3, and NLRC4 were also not altered in CHB patients regardless of HBV-DNA copy numbers/mL and HBeAg status. The data revealed that mRNA expression levels of NLRP1 and NLRC4 were not altered in CHB patients, suggesting that these genes are not responsible for the impaired immune responses against HBV observed in these patients.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , CARD Signaling Adaptor Proteins/metabolism , Calcium-Binding Proteins/metabolism , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers , Case-Control Studies , DNA, Viral/blood , Female , Hepatitis B e Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/virology , Humans , Inflammasomes/blood , Inflammasomes/immunology , Liver/pathology , Liver Function Tests , Male , Monocytes/metabolism , NLR Proteins , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Viral Load
19.
Inflammation ; 39(3): 1253-67, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26861136

ABSTRACT

Investigations revealed substantial parts accomplished by chemokines specifically eotaxins and their specific receptors. They are functionally involved in the modulation of the pathologic state of tissue inflammation which is as a result of allergic reactions. Chemokines as small proteins with approximately 8-10 kDa molecular weight are considered and fit in the bigger family of cytokines, containing basic heparin-binding polypeptide mediators. Chemokines actively interfere in the processes of selective, oriented leukocyte (including eosinophil) recruitment. As eminent from their name, more specifically, eotaxins are specialized for eosinophils' oriented locomotion toward allergic inflamed regions. To date, three members are defined for eotaxin subfamily as follows: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), all of them bind to and activate CCR3 but have a low level of homology and appear to exhibit different physiological potentials. Allergy is described as a clinical state in which a pathologic hypersensitivity reaction is always initiated throughout an immunologic mechanism; similar to other immunologic reactions, an allergic reaction could also either be antibody or cell mediated. This type of allergic reactions occurs in all age groups and damages several different organs, having a significant impact on the emotional and social health of patients and their families and relatives. Concerning introductory comments introduced above, the authors of the present review attempted to collect and provide the latest evidences and information regarding the correlation between expression of eotaxin family members and allergy, in a wider extent, in two important allergic disorders: atopic asthma (AA) and atopic dermatitis (AD). Overall, concerning the most recent articles published within the database in the life sciences literature regarding the fundamental role(s) played by eotaxins in the pathogenesis of AA and AD, the authors of the current article propose that eotaxins (CCL11, CCL24, and CCL26) play key role(s) during symptomatic inflammatory responses raised in response to allergic crisis of these two clinical states.


Subject(s)
Chemokines/physiology , Food Hypersensitivity/etiology , Asthma/etiology , Asthma/pathology , Chemokine CCL11/physiology , Chemokine CCL24/physiology , Chemokine CCL26 , Chemokines, CC/physiology , Dermatitis, Atopic/etiology , Dermatitis, Atopic/pathology , Food Hypersensitivity/pathology , Humans , Inflammation
20.
Iran Red Crescent Med J ; 18(9): e25995, 2016 Sep.
Article in English | MEDLINE | ID: mdl-28144453

ABSTRACT

BACKGROUND: Multiple Sclerosis (MS) is a common autoimmune system disease which affects the central nervous system. It has been documented that interleukin-25 (IL-25) plays key roles in suppressing Th1 responses, which is increased during MS. OBJECTIVES: The aim of this study was to investigate the c424C/A polymorphism within the IL-25 gene in MS patients in comparison to healthy controls. PATIENTS AND METHODS: In this case-control study, 74 patients with MS and 75 healthy controls were selected. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used in order to determine c424C/A polymorphism within the IL-25 gene. RESULTS: The results showed that there was no statistical significant difference in distribution of genotype (AA, AC and CC) and allele (A and C) frequencies between MS patients and healthy controls (P = 0.901 and P = 0.728, respectively). CONCLUSIONS: In conclusion, it appears that the c424C/A polymorphism within the IL-25 gene has no significant relationship with MS, and this polymorphism is probably not associated with MS complications, its onset and gender distribution.

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