Inhibitory activity of Limosilactobacillus reuteri isolated from camel milk against Helicobacter pylori effects in human gastric epithelial cells.

This study aimed to evaluate anti-Helicobacter pylori effects of Limosilactobacillus reuteri 2892 (L. reuteri 2892) isolated from camel milk in GC cell lines (AGS and MKN). From 15 camel milk samples, 132 microbial strains were isolated. Based on microbial and biochemical analysis, 11 potential probiotic candidates were selected. The potential probiotic candidates were assayed for anti-H. pylori activity, and the strain with the highest anti-H. pylori activity was identified genotypically. Based on 16S rDNA sequencing, the selected strain with the best activity against H. pylori (inhibition zone = 15.5 ± 0.8) belonged to the Lactobacillus reuteri strain 2892. Cell treatment with H. pylori HC-113 inhibits gene expression of Claudin-4, ZO-1, MUC5AC, and MUC2 in gastric cells, which are attenuated by L. reuteri 2892. The simulative effects of H. pylori HC-113 on the cell migration and invasion of gastric cells were lost when cells were cotreated with L. reuteri 2892. Cell treatment with H. pylori HC-113 promoted cell death, whereas cotreatment with L. reuteri 2892 markedly decreased necrotic and late apoptotic cells. The present study demonstrates that L. reuteri 2892 has potent anti-H. pylori effects and thus can be considered as an alternative protective agent against inflammatory effects of H. pylori in gastric cells.

The Anti-Helicobacter pylori effects of Limosilactobacillus reuteri strain 2892 isolated from Camel milk in C57BL/6 mice.

Helicobacter pylori infection (H. pylori) is associated with chronic gastritis, peptic ulcers, and gastric cancer. The present study provides information on the protective effects of Limosilactobacillus reuteri strain 2892 (L. reuteri 2892) isolated from camel's milk against H. pylori-induced gastritis in the stomach tissue of animal models. Animal assays revealed that L. reuteri 2892 pretreatment significantly downregulated the virulence factor cagA gene expression. It upregulated the expression level of tight junction molecules [zona occludens (ZO-1), claudin-4] and suppressed metalloproteinase (MMP)-2 and MMP-9 expressions. L. reuteri 2892 exhibited immunomodulatory effects on cytokine profile, as it reduced the serum concentrations of pro-inflammatory cytokines interleukin (IL)-6, IL-1ß, and INF-γ and increased the anti-inflammatory cytokine, IL-10. In addition, L. reuteri 2892 showed anti-oxidative stress activity by regulating the levels of oxidative stress-associated markers [superoxide dismutase (SOD) and malondialdehyde (MDA)]. Our findings suggest that L. reuteri 2892 attenuates H. pylori-induced gastritis.

Heavy metal analysis in of indoor and outdoor dust extracts and cytotoxicity evaluation and inflammation factors on lung, gastric and skin cell lines.

Dust particles (DPs) are one of the most important public health concerns in the urban environment. The presence of heavy metals (HMs) on the surface of DPs might increase the health risk of exposure to the DPs. Accordingly, The purpose of this study was to examine the content of HMs in the outdoor and indoor DPs in Neyshabur city and assess the cytotoxic effects of DPs exposure on lung, gastric, and skin cell lines. To this end, the city was divided into three areas, high-traffic, medium-traffic, and low-traffic (rural). The average concentration of the HMs in the indoor DPs were as follows, 655.5 µg g-1 for Zn, 114.6 µg g-1 for Cu, 77.7 µg g-1 for Cr, 108.6 µg g-1 for Ni, 52 µg g-1 for Pb, 12 µg g-1 for Co, and 3.3 µg g-1 for Cd, while the average concentration of Zn, Cu, Cr, Ni, Pb, Co, Cd in the outdoor DPs were 293.7 µg g-1, 200.6 µg g-1, 100.7 µg g-1, 68.4 µg g-1, 44.7 µg g-1, 18.6 µg g-1, 0.25 µg g-1, respectively. A higher concentration of HMs, as well as cytotoxicity, were revealed in the indoor samples compared to outdoor ones. The degree of cytotoxicity of DPs collected from high-traffic areas was higher than that of low and medium-traffic ones. In addition, treatment of AGS and L929 cells with indoor dust samples induced the expression level of inflammatory agents such as TNFα, IL6, and, CYP1A1 genes more than in outdoor dust samples (P < 0.05). Briefly, a higher level of HMs concentration and cytotoxicity effect on the given cell lines was observed in the samples taken from indoor environments and high-traffic areas.

Prognostic Significance of Tripartite Motif Containing 16 Expression in Patients with Gastric Cancer.

BACKGROUND AND AIM: Tripartite Motif Containing 16 (TRIM16) is a member of the TRIM protein family which is known to play a suppressor role in development of numerous tumor types. However, a positive correlation between TRIM16 expression and gastric cancer (GC) progress has created a controversial situation that need to be fully delineated.  The aim of this study was to assess the expression level of TRIM16 mRNA and its relationship with ß-catenin, CyclinD, and BCL2 expression in Iranian GC patients and to investigate its possible association with patients' overall survival.  Materials and Methods: The expression level of TRIM16 of fresh primary tumor and adjacent normal tissues in 40 GC patients was evaluated by real-time quantitative PCR method. Moreover, patients were subdivided into high or low expression subgroups based on the TRIM16 expression levels. The relationship between TRIM16 expression level, ß-catenin, Cyclin D, BCL2, some clinicopathological data and prognosis of GC patients was also analyzed. RESULTS: qPCR analysis showed a lower level of TRIM16 in GC tissues (fold change=0.351) in comparison to their matched adjacent noncancerous tissues (p <0.001). Contrary to this, the expression levels of ß-catenin, Cyclin D, and BCL2 genes were up-regulated in cancerous samples. This may explain the tumor suppressive function of TRIM16 in GC; as reduction in TRIM16 expression leads to the accumulation of mRNAs from ß-catenin, Cyclin D, and BCL2 genes and eventually cancer progression. We did not observe any significant correlation between TRIM16 expression and patients' overall survival. Univariate Cox regression analysis indicated that anemia, weight loss, bleeding, stomach ache, and smoking are statistically associated with overall survival; while, multivariate analysis did not support any correlation.  Conclusions: In sum, this study suggests a tumor suppressive role for TRIM16 in gastric cancer and proposes it as a potential candidate for GC prognosis.
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Anticancer Potential of Doxorubicin in Combination with Green-Synthesized Silver Nanoparticle and its Cytotoxicity Effects on Cardio-Myoblast Normal Cells.

BACKGROUND: The use of DOX as an anticancer agent is associated with serious side effects on normal cells especially in cardiovascular tissue. OBJECTIVE: Here, it is proposed that the combination of a low dose of DOX with AgNPs provides ideal cytotoxicity against cancer cells and decreases side effects on normal human cells. This study evaluates the cytotoxic effects of green-synthetized AgNPs (GS-AgNPs) in combination with DOX in cancerous cells (MCF7) and investigates its influences on cell growth and apoptosis in a normal cell line of the heart (H9c2). METHODS: We used coffee extracts, as a reducing and stabilizing agent for the green-synthesis of AgNPs. GSAgNPs were characterized by using various analytical methods. MTT assay was used for cell toxicity analysis in cancerous and normal cells. Moreover, Annexin-V /PI staining and mRNA expression of Bax, Bcl2 and p53 were performed for apoptosis measurement in heart normal cell line. RESULTS: GS-AgNPs showed more biocompatibility for normal cells and higher cytotoxicity for cancerous cells compared to that reported for chemically synthesized nanoparticles. Our results also demonstrated that a selected combination of DOX and AgNPs, 20 µM AgNPs / 0.3 µM DOX, had a suitable cytotoxic effect against cancerous cells with a minimum toxic effect on normal cells. So, no significant alteration was observed in cell migration capacity, apoptosis and gene expression of BAX, Bcl-2 and P53 when H9c2 cells were treated with 20 µM AgNPs / 0.3 µM DOX relative to the non-treated control. CONCLUSION: Finally, it seems that the combination of GS-AgNPs and DOX could be a potent strategy to combat cancer.

Lactobacillus bulgaricus and Lactobacillus plantarum improve diabetic wound healing through modulating inflammatory factors.

Probiotics are nonpathogenic bacterial strains that exert beneficial effects on the host. Previous studies have shown that topical use of some strains of probiotic bacteria have good effects on the healing of cutaneous wounds. In the current study, the wound healing potentials of bacterial probiotics on diabetic cutaneous wounds were evaluated. The effects of probiotics on migration, the viability of fibroblasts, and macrophage proliferation were measured through using wound healing assay, methylthiazol tetrazolium assay, and bromodeoxyuridine, respectively. In this regard, in vivo diabetic wound healing experiments in Wistar rats following treatment with nontoxic concentrations of Lactobacillus bulgaricus and Lactobacillus plantarum were conducted. The histopathological and gene expression analyses were performed following removal of wound sites 3, 7, and 14 days postwounding. Results showed that treatment with probiotics accelerated the healing process of diabetic wounds and modulated the inflammatory cells in wound sites during a 14-day period postwounding. The altered mRNA levels of inflammatory cytokines were observed in wound sites following treatment with probiotics. The findings of the current study reveal that L. bulgaricus and L. plantarum could improve the healing of diabetic wounds via regulation of inflammation.

Dietary fats promote inflammation in Wistar rats as well as induce proliferation, invasion of SKOV3 ovarian cancer cells.

The role of high fat diet (HFD) in ovarian cancer and its underlying mechanisms are poorly known. In current investigation, we investigated inflammatory and oncogenic effect of dietary fats in female Wistar rats and ovarian cancer cell line (SKOV3). The ELISA kits were used for adipokines and inflammatory factors analyses in sera collected from rats fed with high fat diet (SR-HFD). Cell growth, proliferation, apoptosis, migration, and invasion were measured in SKOV3 cells treated with the SR-HFD and FA mix. IL6, IL1ß, TNFα, NF-kß, and p53 expression were measured in cells incubated with the mentioned treatments. Leptin and inflammatory factors increased, while adiponectin decreased in SR-HFD. Moreover, FA mix significantly induced proliferation, migration, and invasion, promoted the expression of inflammatory factors and NF-κB and inhibited apoptosis markers in SKOV3 cells. Taken together, our findings revealed that diet might be a crucial factor in ovarian cancer progression through altering the inflammatory factors. PRACTICAL APPLICATIONS: The HFD-mediated obesity promotes cancer progression in various tissues. This study highlights the progression of inflammation in female Wistar rats and the growth of ovarian cancer cells by dietary fats. Thus, dietary factors can be considered as key factors for the prevention of ovarian cancer.

The cross-talk between adipokines and miRNAs in health and obesity-mediated diseases.

BACKGROUND: Multiple studies have revealed a direct correlation between obesity and the development of multiple comorbidities, including metabolic diseases, cardiovascular disorders, chronic inflammatory disease, and cancers. However, the molecular mechanism underlying the link between obesity and the progression of these diseases is not completely understood. Adipokines are factors that are secreted by adipocytes and play a key role in whole body homeostasis. Collaboratively, miRNAs are suggested to have key functions in the development of obesity and obesity-related disorders. Based on recently emerging evidence, obesity leads to the dysregulation of both adipokines and obesity-related miRNAs. In the present study, we described the correlations between obesity and its related diseases that are mediated by the mutual regulatory effects of adipokines and miRNAs. METHODS: We reviewed current knowledge of the modulatory effects of adipokines on miRNAs activity and their relevant functions in pathological conditions and vice versa. RESULTS: Our research reveals the ability of adipokines and miRNAs to control the expression and activity of the other class of molecules, and their effects on obesity-related diseases. CONCLUSIONS: This study may help researchers develop a roadmap for future investigations and provide opportunities to develop new therapeutic and diagnostic methods for treating obesity-related diseases.

Estrogen-independent role of ERα in ovarian cancer progression induced by leptin/Ob-Rb axis.

Leptin induces ovarian cancer cell invasion via overexpression of MMP7, MMP9, and upA. In addition, the key role of ERα in leptin-increased cell growth was indicated. However, the influence of ER on leptin-mediated cell invasion remains still unknown. The present study was designed to evaluate the E2-independent effect of ERα/ß on leptin-mediated cell invasion and cell proliferation in ovarian cancer. We utilized SKOV3 cancer (expressing OB-Rb and ERα/ß, insensitive to estrogen) and OVCAR3 (expressing OB-Rb) cell lines to show the involvement of ER in leptin-mediated effects in an E2-independent manner. MTT, BrdU, and BD matrigel invasion assays were applied to analyze cell growth, proliferation, and invasion. The siRNA approach was used to confirm the role of ERα/ß in leptin effects. Moreover, western blotting and Real-time PCR were employed to detect the OB-Rb, ER, MMP9/7, and upA proteins and mRNAs. Leptin, in the absence of E2, increased ERα expression in SKOV3 cells, which was attenuated using knockdown of OB-Rb gene by siRNA. The effect of leptin on the cell growth was promoted in the presence of PPT, but not in the presence of DNP and E2, which was lost when OB-Rb siRNA was transfected. Furthermore, ERα gene silencing and/or pre-incubation with ER antagonist (ICI 182,780, 10 nM) significantly reduced cell invasion and MMP9 expression stimulated by leptin. In conclusion, our findings demonstrated that ERα, but not ERß, is involved in leptin-induced ovarian cancer in an E2-independent manner, providing new evidence for cancer progression in obesity-associated ovarian cancer.

Leptin-induced signaling pathways in cancer cell migration and invasion.

BACKGROUND: Increasing evidence indicates that obesity is associated with tumor development and progression. Leptin is an adipocyte-related hormone with a key role in energy metabolism and whose circulating levels are elevated in obesity. The effect of leptin on cancer progression and metastasis and its underlying mechanisms are still unclear. Leptin can impact various steps in tumor metastasis, including epithelial-mesenchymal transition, cell adhesion to the extracellular matrix (ECM), and proteolysis of ECM components. To do so, leptin binds to its receptor (OB-Rb) to activate signaling pathways and downstream effectors that participate in tumor cell invasion as well as distant metastasis. CONCLUSIONS: In this review, we describe metastasis steps in detail and characterize metastasis-related molecules activated by leptin, which may help to develop a roadmap that guides future work. In addition, we conclude that a profound understanding of the fundamental molecular processes that contribute to leptin-induced metastasis may pave the way for the development of new prognostic molecules and appropriate approaches to the treatment of obesity-related cancers.

Therapeutic effects of aqueous extracts of Petroselinum sativum on ethylene glycol-induced kidney calculi in rats.

PURPOSE: To investigate the therapeutic effects of the aqueous extract of Petroselinum Sativum aerial parts and roots on kidney calculi. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly assigned into 6 groups and treated for 30 days. Group A served as normal control and group B received 1% ethylene glycol in drinking water. Groups C, D, E, and F received 1% ethylene glycol from day 0 and were used as the treatment subjects. Rats in groups C and D received 200 and 600 mg/kg body weight of aerial parts aqueous extract, respectively, and those in groups E and F received 200 and 600 mg/kg body weight of root aqueous extract in drinking water, respectively, from the 14th day of the experiment. RESULTS: On the 14th and 30th days of the experiment, serum level of magnesium (1.71 ± 0.12 and 3.81 ± 0.25, respectively) decreased significantly while serum level of calcium (10.45 ± 0.26 and 11.33 ± 0.18, respectively) increased significantly in group B compared with the control group (14th day: magnesium = 2.87 ± 0.17 and calcium = 8.80 ± 0.00 and 30th day: magnesium = 6.01 ± 0.00 and calcium = 8.30 ± 0.22; P < .001). In the treatment groups of C, D, E, and F, the number of deposits decreased significantly compared with group B on the 30th day (P < .001). The weight of the kidneys increased significantly in group B (2.01 ± 0.17) compared with the control group (1.52 ± 0.07) and decreased significantly in treatment groups (P < .05). CONCLUSION: Petroselinum Sativum has a therapeutic effect on calcium oxalate stones in rats with nephrolithiasis and reduces the number of calcium oxalate deposits.