Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update.

BACKGROUND: We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. METHODS: A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted. RESULTS: There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92). CONCLUSIONS: Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.

Mesenchymal stem cells (MSCs) and MSC-derived exosomes in animal models of central nervous system diseases: Targeting the NLRP3 inflammasome.

The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is a multimeric protein complex that is engaged in the innate immune system and plays a vital role in inflammatory reactions. Activation of the NLRP3 inflammasome and subsequent release of proinflammatory cytokines can be triggered by microbial infection or cellular injury. The NLRP3 inflammasome has been implicated in the pathogenesis of many disorders affecting the central nervous system (CNS), ranging from stroke, traumatic brain injury, and spinal cord injury to Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, and depression. Furthermore, emerging evidence has suggested that mesenchymal stem cells (MSCs) and their exosomes may modulate NLRP3 inflammasome activation in a way that might be promising for the therapeutic management of CNS diseases. In the present review, particular focus is placed on highlighting and discussing recent scientific evidence regarding the regulatory effects of MSC-based therapies on the NLRP3 inflammasome activation and their potential to counteract proinflammatory responses and pyroptotic cell death in the CNS, thereby achieving neuroprotective impacts and improvement in behavioral impairments.

Bacillus subtilis supernatant improves the efficacy of radiation therapy in rat intestinal epithelial cells by upregulation of bax and caspase-3 genes.

BACKGROUND: Colorectal Cancer (CC) is among the most prevalent cancers in elderly persons. Radiotherapy is usually prescribed as CC develops, however, radiation beams indiscriminately affect normal cells. Previous studies nominated that probiotics and their metabolites can be used to minimize the side effects of radiotherapy. Hereby, the aim of this study was to investigate the probable correlation between cell-free supernatant of Bacillus subtilis and radiation response in normal and cancerous cell lines. METHODS AND RESULTS: IEC-18 and SW-48 cells were treated with different concentrations of B. subtilis supernatant. To evaluate the effect of probiotic treatments under radiation and the normal situation, the cytotoxicity of the treatments was measured using the MTT method. The cell cycle status was analyzed by flow cytometry. The expression levels of Bax, Bcl-2, and Caspase 3 genes were also determined by real-time (RT) PCR. B. subtilis supernatant increased the viability of normal cells under radiation treatment, although this effect was not significant. 40% v/v of this mixture could amplify the lethal effect of radiation and decreased the viability of cancer cells. SW-48 cells that received 40% v/v of the supernatant had a significantly higher rate of apoptosis. Probiotic supernatant effectively induced the expression of proapoptotic Bax and Caspase 3 genes. CONCLUSION: Presented results confirmed that the supernatant of B. subtilis can be supposed as a clue to improve the efficacy of radiation therapy in CC patients as it increased the sensitivity of cancerous cells and protected normal epithelial cells from detrimental effects of radiation.

Evaluation of a novel Echinococcus granulosus recombinant fusion B-EpC1 antigen for the diagnosis of human cystic echinococcosis using indirect ELISA in comparison with a commercial diagnostic ELISA kit.

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by the metacestode of Echinococcus granulosus sensu lato (s.l.). A large proportion of the patients are asymptomatic at the early and late stages of the disease. CE diagnosis is mainly based on imaging techniques. Laboratory diagnosis including antibody-antigen (recombinant or fusion recombinant) can be used for the diagnosis and follow up of CE and alveolar echinococcosis (AE), but need optimization and standardization. This study aimed to evaluate the efficacy of a recombinant B-EpC1 (rB-EpC1) fusion antigen comprising B1, B2, B4, and EpC1 antigens of E. granulosus using indirect ELISA in comparison with a commercial ELISA kit for the serodiagnosis of CE. The recombinant protein was expressed in the expression host, E. coli BL21, and purified. This recombinant antigen was then evaluated by indirect ELISA and compared to the commercial CE diagnostic kit (Vircell, Spain). The study samples included 124 human sera consisting of 62 sera of patients with CE, and 62 sera of individuals without clinical evidences of CE and specific anti-CE antibodies in routine indirect ELISA. The diagnostic sensitivity and specificity of the indirect rB-EpC1-ELISA test for detection of specific anti-hydatid cyst antibodies in human CE were 95.2% and 96.8%, respectively. Also, the diagnostic sensitivity and specificity of the commercial ELISA test were 96.8% in this study. Initial evaluation of the recombinant fusion antigen (B-EpC1) was promising for the detection of CE by ELISA in clinical settings. Standardization and evaluation of recombinant fusion protein require further studies.

Antioxidant and anti-apoptotic effects of selenium nanoparticles and Lactobacillus casei on mice testis after X-ray.

Radiation can lead to various damages in the process of spermatogenesis that lead to a decrease in the number of sperm, an increase in spermatogenesis disorders, and defective sperm function. Radioprotectors are considered a good approach to reducing the damage caused by radiation. The goal of this work was to study how X-ray radiation affects testicular tissue and the process of spermatogenesis, as well as the radioprotective effects of selenium nanoparticles (SeNPs) and Lactobacillus casei (L. casei) as probiotic compounds, given alone or together. This study included 64 adult Syrian male mice weighing approximately 20 ± 5 g and aged 10 ± 1 weeks. Animals were randomly divided into eight groups: control group, SeNPs, probiotic, SeNPs and probiotic, X-ray radiation, SeNPs (X-ray), probiotic (X-ray), and SeNPs and probiotic (X-ray). Histology parameters and levels of oxidative stress biomarkers such as catalase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were examined. In addition, the level of apoptosis was measured in testicular cells that had been treated with SeNPs and L. casei as a probiotic. The results showed that the administration of SeNPs or probiotic diminished the effects of X-ray radiation. These compounds induced a significant decreased in malondialdehyde, caspase 3, and caspase 9 gene levels and a remarkable increased in catalase, superoxide dismutase, and Catsper gene expression. SeNPs and probiotic exhibited a potent antioxidant effect and elevated the mean number of spermatogonia cells, sperm cell count, spermatogenesis percentage, and sperm motility percentage. The prescribed compound exhibited an ideal radioprotective effect with the ability to reduce the side effects of ionizing radiation and to protect normal tissues. SeNPs and probiotic inhibit testicular injury and improve the antioxidant state in male mice.

Targets for protection and mitigation of radiation injury.

Protection of normal tissues against toxic effects of ionizing radiation is a critical issue in clinical and environmental radiobiology. Investigations in recent decades have suggested potential targets that are involved in the protection against radiation-induced damages to normal tissues and can be proposed for mitigation of radiation injury. Emerging evidences have been shown to be in contrast to an old dogma in radiation biology; a major amount of reactive oxygen species (ROS) production and cell toxicity occur during some hours to years after exposure to ionizing radiation. This can be attributed to upregulation of inflammatory and fibrosis mediators, epigenetic changes and disruption of the normal metabolism of oxygen. In the current review, we explain the cellular and molecular changes following exposure of normal tissues to ionizing radiation. Furthermore, we review potential targets that can be proposed for protection and mitigation of radiation toxicity.

Increasing Angiogenesis Factors in Hypoxic Diabetic Wound Conditions by siRNA Delivery: Additive Effect of LbL-Gold Nanocarriers and Desloratadine-Induced Lysosomal Escape.

Impaired wound healing in people with diabetes has multifactorial causes, with insufficient neovascularization being one of the most important. Hypoxia-inducible factor-1 (HIF-1) plays a central role in the hypoxia-induced response by activating angiogenesis factors. As its activity is under precise regulatory control of prolyl-hydroxylase domain 2 (PHD-2), downregulation of PHD-2 by small interfering RNA (siRNA) could stabilize HIF-1α and, therefore, upregulate the expression of pro-angiogenic factors as well. Intracellular delivery of siRNA can be achieved with nanocarriers that must fulfill several requirements, including high stability, low toxicity, and high transfection efficiency. Here, we designed and compared the performance of layer-by-layer self-assembled siRNA-loaded gold nanoparticles with two different outer layers-Chitosan (AuNP@CS) and Poly L-arginine (AuNP@PLA). Although both formulations have exactly the same core, we find that a PLA outer layer improves the endosomal escape of siRNA, and therefore, transfection efficiency, after endocytic uptake in NIH-3T3 cells. Furthermore, we found that endosomal escape of AuNP@PLA could be improved further when cells were additionally treated with desloratadine, thus outperforming commercial reagents such as Lipofectamine® and jetPRIME®. AuNP@PLA in combination with desloratadine was proven to induce PHD-2 silencing in fibroblasts, allowing upregulation of pro-angiogenic pathways. This finding in an in vitro context constitutes a first step towards improving diabetic wound healing with siRNA therapy.

TGF-ß in radiotherapy: Mechanisms of tumor resistance and normal tissues injury.

Emerging evidences show that changes in tumor stroma can adapt cancer cells to radiotherapy, thereby leading to a reduction in tumor response to treatment. On the other hand, radiotherapy is associated with severe reactions in normal tissues which limit the amount radiation dose received by tumor. These challenges open a window in radiobiology and radiation oncology to explore mechanisms for improving tumor response and also alleviate side effects of radiotherapy. Transforming growth factor beta (TGF-ß) is a well-known and multitasking cytokine that regulates a wide range of reactions and interactions within tumor and normal tissues. Within tumor microenvironment (TME), TGF-ß is the most potent suppressor of immune system activity against cancer cells. This effect is mediated through stimulation of CD4+ which differentiates to T regulatory cells (Tregs), infiltration of fibroblasts and differentiation into cancer associated fibroblasts (CAFs), and also polarization of macrophages to M2 cells. These changes lead to suppression of cytotoxic CD8 + T lymphocytes (CTLs) and natural killer (NK) cells to kill cancer cells. TGF-ß also plays a key role in the angiogenesis, invasion and DNA damage responses (DDR) in cancer cells. In normal tissues, TGF-ß triggers the expression of a wide range of pro-oxidant and pro-fibrosis genes, leading to fibrosis, genomic instability and some other side effects. These properties of TGF-ß make it a potential target to preserve normal tissues and sensitize tumor via its inhibition. In the current review, we aim to explain the mechanisms of upregulation of TGF-ß and its consequences in both tumor and normal tissues.

Mitigation of radiation-induced hematopoietic system injury by melatonin.

BACKGROUND: Increased risks of exposure to accidental radiation events are a concern in today's world. Radiation terror, nuclear explosion, as well as accidental exposure to radioactive sources in some industries pose a threat to the life of exposed persons. Studies have been conducted using some low-toxic agents to mitigate radiation toxicity and increase survival probability for exposed people. In the current study, we aimed to show the mitigation of radiation-induced mortality and bone marrow toxicity using postirradiation treatment with melatonin. METHOD: Mice whole bodies were exposed to 4 or 7 Gy radiation followed by treatment with melatonin after 24 hours. Survival of mice with or without melatonin, the levels of peripheral cells, transforming growth factor (TGF)-ß and 8-hydroxy-2' -deoxyguanosine (8-OHdG) in the bone marrow, as well as the expression of NADPH oxidase (NOX)2 and NOX4 in bone marrow cells were evaluated. RESULTS: Whole body irradiation led to mortality 30 days after irradiation. However, melatonin treatment reduced mortality. Irradiation also showed severe reduction of lymphocytes, platelets, and red blood cells. The expressions of NOX2 and NOX4, in addition to TGF-ß level, were increased after exposure to radiation. Melatonin ameliorated the increased levels of these factors and improved the number of blood cells. CONCLUSIONS: Melatonin showed ability to mitigate radiation-induced hematopoietic system toxicity and also increased survival rate. These results suggest that melatonin could be a potential mitigator for accidental radiation events.

Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy.

Cancer incidences are growing and cause millions of deaths worldwide. Cancer therapy is one of the most important challenges in medicine. Improving therapeutic outcomes from cancer therapy is necessary for increasing patients' survival and quality of life. Adjuvant therapy using various types of antibodies or immunomodulatory agents has suggested modulating tumor response. Resistance to apoptosis is the main reason for radioresistance and chemoresistance of most of the cancers, and also one of the pivotal targets for improving cancer therapy is the modulation of apoptosis signaling pathways. Apoptosis can be induced by intrinsic or extrinsic pathways via stimulation of several targets, such as membrane receptors of tumor necrosis factor-α and transforming growth factor-ß, and also mitochondria. Curcumin is a naturally derived agent that induces apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing reactive oxygen species (ROS) production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of NF-κB and COX-2, which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis PI3K signaling and increase the expression of MAPKs to induce endogenous production of ROS. In this paper, we aimed to review the molecular mechanisms of curcumin-induced apoptosis in cancer cells. This action of curcumin could be applicable for use as an adjuvant in combination with other modalities of cancer therapy including radiotherapy and chemotherapy.

Selenium as an adjuvant for modification of radiation response.

Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.

Identification of common vaginal Lactobacilli immunoreactive proteins by immunoproteomic techniques.

Lactobacilli are considered as the most important microorganisms in regulating immune system and maintaining vaginal health. The uses and benefits of Lactobacilli as probiotics, particularly the regulation of immune system, are dependent on the strain used and a comprehensive understanding of their effects on the host. Several factors have been identified in Lactobacilli that influence the immune response, such as exopolysaccharides and proteins. The current study was designed to investigate the serum immunoreactivity of healthy women against common vaginal Lactobacilli immunoreactive proteins. Three common vaginal Lactobacillus strains (L. crispatus L1, L. gasseri L9, and L. fermentum L2) were compared for immune response. The ELISA results showed that the levels of total immunoglobulin (Ig-total) antibody for L. crispatus L1, L. fermentum L2, and L. gasseri L9 were 47%, 45% and 29%, respectively. Regarding the lower prevalence of L. fermentum L2 in comparison with the other two strains, the approximately equal levels of Ig-total compared to L. crispatus L1 and more than L. gasseri L9 indicate that L. fermentum L2 has the greater antigenicity ability. Accordingly, the immunoreactive proteins of L. fermentum L2 were identified using MALDI-TOF-MS detected by SDS-PAGE and Western blotting. These proteins included 30s ribosomal protein S4 and 50s ribosomal protein L5. Antigenic epitopes on the 3D structure of these proteins was also predicted using bioinformatics analysis. The presence of antibody in serum of healthy pre-menopausal women indicates that Lactobacilli (normal flora) proteins can stimulate host immune response. Purification and further studies of the proteins may allow their potential use as an adjuvant to improve the efficacy of vaccines.

Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study.

Background and objectives: Pneumonitis and fibrosis are the most common consequences of lung exposure to a high dose of ionizing radiation during an accidental radiological or nuclear event, and may lead to death, after some months to years. So far, some anti-inflammatory and antioxidant agents have been used for mitigation of lung injury. In the present study, we aimed to detect possible mitigatory effects of melatonin and metformin on radiation-induced pneumonitis and lung fibrosis. Materials and methods: 40 male mice were divided into 4 groups (10 mice in each). For control group, mice did not receive radiation or drugs. In group 2, mice were irradiated to chest area with 18 Gy gamma rays. In groups 3 and 4, mice were first irradiated similar to group 2. After 24 h, treatment with melatonin as well as metformin began. Mice were sacrificed after 100 days for determination of mitigation of lung pneumonitis and fibrosis by melatonin or metformin. Results: Results showed that both melatonin and metformin are able to mitigate pneumonitis and fibrosis markers such as infiltration of inflammatory cells, edema, vascular and alveolar thickening, as well as collagen deposition. Conclusion: Melatonin and metformin may have some interesting properties for mitigation of radiation pneumonitis and fibrosis after an accidental radiation event.

Radiation-Induced Dual Oxidase Upregulation in Rat Heart Tissues: Protective Effect of Melatonin.

Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control; (2) melatonin treated (100 mg/kg); (3) radiation (15 Gy gamma rays); (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.

Protection Against Radiation-Induced Micronuclei in Rat Bone Marrow Erythrocytes by Curcumin and Selenium L-Methionine.

BACKGROUND: The search for potent radioprotective agents for the amelioration of radiation side effect is an important aim in radiobiology. The present study aimed to evaluate the effects of curcumin and seleno-L-methionine against radiation-induced micronucleus formation in rat bone marrow. METHODS: In total, 40 male rats were divided into 8 groups (n=5 each), including control, curcumin or seleno-L-methionine treated alone or in combination, 2 Gy irradiation, irradiation of treated groups with curcumin or seleno-L-methionine or their combination. Curcumin was administrated orally and seleno-L-methionine was injected intraperitoneally 24 hours before irradiation. The frequency of micronucleated normochromatic erythrocytes (MnNCEs) and micronucleated polychromatic erythrocytes (MnPCEs) was scored in 5,000 polychromatic erythrocytes (PCEs) and the cell proliferation ratio [(PCE/(PCE+NCE); NCE=normochromatic erythrocytes] was calculated for each treatment group. Data were analyzed by the SPSS software version 16.0 and P<0.05 was considered as statistically significant differences. RESULTS: Pretreatment with curcumin and seleno-L-methionine before irradiation reduced the frequency of MnPCEs and MnNCEs (P=0.01) and increased the cell proliferation ratio. Moreover, the results showed that this pretreatment reduced the frequency of MnPCEs with a protection factor (PF) of 1.2 and 1.6, respectively. The combination of curcumin and seleno-L-methionine in reducing MnPCEs and MnNCEs was not more effective than each agent alone, while improved cell proliferation ratio. CONCLUSION: Both curcumin and seleno-L-methionine showed potent protection against radiation induced MN in bone marrow cells. The combination of the two agents further ameliorates this activity, thus leading to improve bone marrow protection.

Comparative evaluation of probiotics effects on plasma glucose, lipid, and insulin levels in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes is a chronic disorder caused by the relative decrease in insulin production from the pancreas, tissue resistance to insulin, or both. Daily consumption of probiotics, particularly Lactobacilli, has been proposed as a new strategy for prevention or control of diabetes. METHODS: In the current study, the effects of various probiotics including Lactobacillus reuteri (L reuteri), Lactobacillus crispatus (L crispatus), and Bacillus subtilis on the levels of blood glucose, lipid, and insulin as well as haemoglobin A1c (HbA1c ) were investigated in rat models of streptozotocin (STZ)-induced diabetes and compared with metformin. In addition, GLUT-4 and PPAR-γ transcript levels have been analysed in adipose tissues. RESULTS: A significant decrease in plasma glucose and HbA1c levels and a dramatic increase in insulin levels have been detected after consumption of probiotics. Furthermore, lipid profiles have been improved. The expression of Glut-4 and Ppar-γ genes in adipose tissues also increased after treatment period. CONCLUSION: The results of this experiment showed that daily consumption of probiotics can be effective in control of STZ-induced diabetes and its complications.

Application of immuno-PCR assay for the detection of serum IgE specific to Bermuda allergen.

In vivo and in vitro tests are the two major ways of identifying the triggering allergens in sensitized individuals with allergic symptoms. Both methods are equally significant in terms of sensitivity and specificity. However, in certain circumstances, in vitro methods are highly preferred because they circumvent the use of sensitizing drugs in patients. In current study, we described a highly sensitive immuno-PCR (iPCR) assay for serum IgE specific to Bermuda allergens. Using oligonucleotide-labelled antibody, we used iPCR for the sensitive detection of serum IgE. The nucleotide sequence was amplified using conventional PCR and the bands were visualized on 2.5% agarose gel. Results demonstrated a 100-fold enhancement in sensitivity of iPCR over commercially available enzyme-linked immunosorbent assay (ELISA) kit. Our iPCR method was highly sensitive for Bermuda-specific serum IgE and could be beneficial in allergy clinics.

Protective Effects of Alpha-lipoic Acid, Resveratrol, and Apigenin against Oxidative Damages, Histopathological Changes, and Mortality Induced by Lung Irradiation in Rats.

AIM: This study investigated the protective effects of three antioxidants on radiationinduced lung injury. BACKGROUND: Oxidative stress is one of the key outcomes of radiotherapy in normal tissues. It can induce severe injuries in lung tissue, which may lead to pneumonitis and fibrosis. Recently, interest in natural chemicals as possible radioprotectors has increased due to their reduced toxicity, cheaper price, and other advantages. OBJECTIVE: The present study was undertaken to evaluate the radioprotective effect of Alpha-lipoic Acid (LA), Resveratrol (RVT), and Apigenin (APG) against histopathological changes and oxidative damage and survival induced by ionizing radiation (IR) in the lung tissues of rats. METHODS: First, the lung tissue of 50 mature male Wistar rats underwent an 18 Gy gamma irradiation. Next, the rats were sacrificed and transverse sections were obtained from the lung tissues and stained with hematoxylin and eosin (H and E) and Mason trichrome (MTC) for histopathological evaluation. Then, the activity of Glutathione peroxidase (GPx), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) was measured by an ELISA reader at 340, 405, and 550 nm. RESULTS: Based on the results of this study, IR led to a remarkable increase in morphological changes in the lung. However, APG, RVT, and LA could ameliorate the deleterious effects of IR in lung tissue. IR causes an increase in GPX level, and APG+IR administration causes a decrease in the level of GPX compared to the control group. Also, the results of this study showed that RVT has significant effects in reducing MDA levels in the short term. In addition, compared to the control group, IR and RVT+IR decrease the activity of SOD in the long term in the lung tissues of rats. Also, the analysis of results showed that weight changes in IR, LA+IR, APG+IR, and control groups were statistically significant. CONCLUSION: APG and RVT could prevent tissue damage induced by radiation effects in rat lung tissues. Hence, APG, LA, and RVT could provide a novel preventive action with their potential antioxidant anti-inflammatory properties, as well as their great safety characteristic.

Immunosuppressive Effects of Two Probiotics, Lactobacillus paracasei DSM 13434 and Lactobacillus plantarum DSM 15312, on CD4+ T Cells of Multiple Sclerosis Patients.

T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor ß (TGF-ß), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-ß and IFN-γ were not significantly different among any of the study groups.  Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.

Inhibition of HIV and HSV infection by vaginal lactobacilli in vitro and in vivo.

BACKGROUND AND THE PURPOSE OF THE STUDY: The cervico-vaginal mucosa which is populated with microflora (mostly includes lactobacilli) is the portal of entry for sexually transmitted pathogens. METHODS: The in vitro anti-viral effect of vaginal and non-vaginal lactobacillus was evaluated using single cycle HIV-1 replication and HSV-2 plaque reduction assays. The XTT proliferation assay was used to monitor the cellular toxicity. The in vivo anti-HSV-1 activity was evaluated in BALB/c mouse model by monitoring skin lesion and immune response development. RESULTS AND MAJOR CONCLUSION: DMEM culture supernatant of L. Gasseri and L. fermentum (PH 7.3) did not show toxic effect but inhibited 50% of HIV replication at 12 and 31% concentrations, respectively. Co-culture of L. gasseri (1000 CFU/ target cell) showed mild cytotoxicity but inhibited 68% of HIV replication. The supernatant of L. crispatus inhibited 50% of HSV replication at 4% and also co-culture of L. gasseri, L. rhamnosus and L. crispatus revokes almost all of the HSV multiplication. Culture supernatants of L. gasseri and L. crispatus had significant virucidal effect against the HIV and HSV and inhibited HSV infection in a stage before viral entry to the target cells. Alive L. gasseri cells showed high potential for inhibiting HSV-1 infection in vivo condition. Current data indicates that lactobacilli supernatant encompasses components with neutralizing activity against HIV and HSV and it would be a determinant factor for viral diseases transmission and promising lead for anti-viral probiotic design.