Efficacy of nutritional selenium nanoparticles on growth performance, immune response, antioxidant capacity, expression of growth and immune-related genes, and post-stress recovery in juvenile Sobaity seabream (Sparidentex hasta).

This study evaluated the impacts of nano-Se on the growth, immunity, antioxidant capacity, physiological parameters, gene expression, and stress resistance of fingerling Sobaity seabream (Sparidentex hasta). The fish with an average weight of 21.5 ± 0.1 g were divided into four treatment groups in triplicates that received one of the test diets supplemented with varying levels of nano-Se: 0 (control), 0.5 (Se-0.5), 1 (Se-1), and 2 (Se-2) mg/Kg for 60 days. The results showed that final weight, weight gain rate, specific growth rate, feed intake, and feed conversion ratio improved with significant linear and quadratic trends (P < 0.05) in response to nano-Se-supplemented diets, and the best values were measured in the Se-2 group. Superoxide dismutase activity level remained unaffected among the four groups (P > 0.05). Catalase activity increased in nano-Se-supplemented groups, with the highest level measured in fish fed the Se-0.5 diet. Glutathione peroxidase activity levels were not significantly different between the control and nano-Se groups, but the lowest malondialdehyde concentration was detected in the Se-2 group. Nano-Se had no marked effect on total plasma Ig levels; however, the highest lysozyme activity and alternative complement activity (ACH50) were observed in the Se-0.5 and Se-2 groups, respectively. No significant differences (P > 0.05) were observed in plasma total protein, albumin, globulin, triglyceride, and thyroid hormone (T3 and T4) contents among the groups. However, the lowest cholesterol and low-density lipoprotein values and the highest high-density lipoprotein concentration were measured in the Se-2 group. The Se-0.5 and Se-1 groups exhibited significantly lower levels of aspartate aminotransferase activity, and the lowest alkaline phosphatase activity level was detected in the Se-1 group. The expression level of insulin-like growth factor I gene in all nano-Se-fed groups was significantly higher than the control. Also, the expression of interleukin-1ß and lysozyme genes was significantly upregulated in nano-Se-supplemented groups, with the highest values in the Se-2 group. Following acute crowding stress, plasma cortisol and lactate levels at all post-stress time intervals were not significantly different among the experimental groups. Fish fed the Se-0.5 and Se-2 diets tended to have lower plasma glucose concentrations than other groups. In conclusion, dietary nano-Se at 2 mg/kg is recommended to promote growth performance and enhance antioxidant and immune parameters in Sobaity juveniles.

Evaluation of the prevalence of Aeromonas spp., Campylobacter spp., and Clostridioides difficile in immunocompromised children with diarrhea.

AIM: Diarrhea is a common disease in immunocompromised patients and can be associated with greater morbidity and even mortality. Therefore, the present study was designed to determine the prevalence of Aeromonas spp., Campylobacter spp., and C. difficile among immunocompromised children. METHODS: This study was conducted on 130 stool samples from patients with diarrhea who had defects in the immune system and were referred to Hazrat Masoumeh Children's Hospital in Qom. Demographic information, clinical symptoms, immune status, and duration of chemotherapy were also recorded for each child. DNAs were extracted from the stool, and then direct PCR assays were done by specific primers for the detection of Aeromonas spp., Campylobacter spp., and toxigenic C. difficile, including tcdA/B and cdtA/B genes. Co-infection in patients was also evaluated. RESULTS: 60.8% and 39.2% were male and female, respectively, with a m ± SD age of 56.72 ± 40.49 months. Most cases of immunocompromised states were related to Acute Lymphocytic Leukemia (77.7%) and Non-Hodgkin Lymphoma (14.6%). 93.1% of patients were undergoing chemotherapy during the study. Among patients, most clinical symptoms were related to bloody diarrhea (98.5%) and fever (92.3%). Based on PCR, 14.6, 9.2, and 1.5% were positive for Aeromonas spp., C. difficile, and C. jejuni, respectively. Among the C. difficile-positive cases, the tcdA gene was only detected in one patient. In total, three co-infections were identified, which included Aeromonas spp./C. difficile (tcdA+), C. jejuni/C. difficile, and C. jejuni/Aeromonas spp. CONCLUSIONS: This is the first study in Iran to investigate the simultaneous prevalence of some pathogens in immunocompromised children with diarrhea. Because Aeromonas spp., Campylobacter spp., and C. difficile are not routinely detected in some laboratories, infections caused by them are underappreciated in the clinic. Our results showed that these pathogens are present in our region and can cause gastroenteritis in children, especially those with underlying diseases. Therefore, increasing the level of hygiene in some areas and controlling bacterial diarrheal diseases should be given more attention by health officials.

Molecular examination for Coxiella burnetii and Brucella spp. infections in Iranian women experiencing spontaneous miscarriage.

BACKGROUND: Spontaneous miscarriage, a leading health concern globally, often occurs due to various factors, including infections. Among these, Coxiella burnetii and Brucella spp. may have adverse effects on pregnancy outcomes. While previous research has established a link between infections and spontaneous miscarriage, our study aimed specifically to investigate the presence of these two pathogens in abortion samples from women who experienced spontaneous miscarriages in Iran. Our study can add to the existing knowledge by focusing on Iran, a region with a high prevalence of C. burnetii and Brucella spp. As a result, it could provide a better understanding and unique insights into the relationship of these pathogens with spontaneous miscarriages in endemic regions. METHODS: From March 2021 to March 2022, a total of 728 abortion samples (including placenta and cotyledon) were collected from 409 women who had experienced spontaneous miscarriages in the provinces of Tehran, Fars, and West Azerbaijan in Iran. The specimens included 467 Formalin-Fixed Paraffin-Embedded (FFPE) and 261 fresh frozen samples. After DNA extraction from abortion samples, the quantitative real-time PCR (qPCR) assay targeted a specific fragment of the IS1111 and IS711 elements for molecular identification of C. burnetii and Brucella spp., respectively. Furthermore, the qPCR assay employing specific primers for different species was used to determine the species of Brucella. RESULTS: Among the studied women, 1 out of 409 (0.24%) samples tested positive for Brucella spp., specifically Brucella melitensis. There were no positive specimens for C. burnetii. CONCLUSIONS: Our study contributes to understanding the potential involvement of Brucella species in spontaneous infectious abortion within endemic regions. The identification of B. melitensis in this study highlights the need for further research in this area. However, while our results suggest a relatively low or zero identification of these pathogens in our sample population, this does not rule out the possibility of undetected infections. Therefore, it is critical to acknowledge the limitations of the molecular techniques used (qPCR), which may have potential limitations such as sensitivity and specificity. Moreover, because 64.15% of our samples were FFPE, the sensitivity of the qPCR test may be reduced. These raise concerns about the accuracy of the reported prevalence rates and the potential for false positives or negatives.

Myrtenol Ameliorates Recognition Memories' Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats.

INTRODUCTION: Asthma is related to neurochemical alterations which affect brain functions and lead to anxiety and cognitive dysfunctions. Myrtenol has sparked considerable interest due to its pharmacological effects, especially for the remediation of chronic disorders. Thus, the present research was designed to evaluate the impacts of myrtenol on anxiety-like behaviors, cognitive declines, inflammation, and oxidative stress in the hippocampus of asthmatic rats. METHODS: Rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Asthma was elicited in the rats by ovalbumin, and the animals were then exposed to myrtenol inhalation. Anxiety-like behavior and memory were assessed by elevated plus maze (EPM) and novel object and location recognition tests. Interleukins (interleukin-6, -17, and -10), tumor necrosis factor α (TNF-α), and oxidative stress biomarkers such as malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in the hippocampus were assessed by the ELISA method. RESULTS: The levels of IL-6, IL-17, TNF-α, and MDA decreased, but GPX, SOD, and TAC levels increased in the hippocampus of asthmatic animals due to myrtenol inhalation. CONCLUSION: Myrtenol diminished asthma-induced anxiety-like behaviors and cognitive deficits in asthmatic rats; these effects might have been typically mediated by a reduction in inflammation and oxidative stress.

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.

Morphine upregulates Toll-like receptor 4 expression and promotes melanomas in mice.

BACKGROUND: Morphine and other opioids are used to manage cancer-related pain; however, the role of these drugs in cancer progression remains controversial. Emerging evidence indicates that morphine can activate Toll-like receptor 4 (TLR4) and its signaling pathways, by the way the activation and expression of TLR4 can promote melanoma. In this study, we investigated the effects of morphine on the expression of TLR4 and promotion of melanoma in mice. METHODS: Mice melanoma cells (B16F10) were cultured with morphine (0.1, 1 and 10 µM) for 24 h. In the other experiment, cells were treated with morphine with or without TLR4 agonist (LPS) or antagonist (TAK-242). In in-vivo model, B16F10 cells were subcutaneously injected to C57BL/6 mice, and morphine was administrated in three different treatment protocols after developing palpable tumors (acute treatment, chronic daily injections, escalating doses of morphine). In another set of experiments, B16F10 cells were pretreated with LPS (5 µg/ml) 24 h before injection into mice. Control group received normal saline. We measured cell proliferation, the expression level of Tlr4, Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (Nf-κb1) genes, TLR4 protein expression, and tumor volume. RESULTS: Chronic, acute, and escalating doses of morphine increased tumor. Morphine increased the expression of Tlr4 and Nf-κb1 regardless of the treatment protocol used. CONCLUSION: Morphine increases the progression of melanoma cancer and may be related to the increased expression of TLR4. Our results suggest that morphine should be used with caution in patients with melanoma.HighlightsMorphine increases the expression of TLR4 in melanoma.Morphine increases melanoma progression.These effects are mostly observed with chronic and escalating morphine administration.

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.

Multicenter Study of Antibody Seroprevalence against COVID-19 in Patients Presenting to Iranian Cancer Centers after One Year of the COVID-19 Pandemic.

Patients with cancer are at significantly greater risk of COVID-19 and its complications than the general population. Since IgG antibodies remain detectable well after infection with the SARS-CoV-2 virus, seroprevalence can be used to estimate the proportion of the cancer population previously infected and potentially immune to SARS-CoV-2. The current study is a multi-center, prospective observational study to assess the seroprevalence of SARS-CoV-2 IgG antibody in a cancer population referred for vaccination between April and June 2021. Of a total of 270 adult patients with cancer accrued, 16% reported a history of COVID-19 more than four weeks previously confirmed by PCR. At the same time, serologic positivity for SARSCoV2 IgG was found in 29% of patients prior to vaccination including nearly 20% of patients without a history of confirmed COVID-19. Seropositivity was significantly greater in females consistent with higher rates in patients with breast cancer and gynecologic cancers. A seroconversion rate of 79.5% was observed in cancer patients with a history of PCR confirmed COVID-19, less than observed in the general population. In multivariable analysis, gender and prior history of COVID-19 were both independently associated with seropositivity prior to vaccination. Follow-up is continuing of this cohort of patients with cancer following vaccination to assess antibody and clinical outcomes.

Effects of dietary taurine amino acid on growth performance, mucosal and immune response, gene expression and antioxidant defence of asian seabass (Lates calcarifer).

BACKGROUND: The enhancement of fish immune system and growth performance throughout the administration of bio-friendly agents such as diet supplements (taurine) is considered a promising alternative in farmed aquatic species. MATERIALS AND METHODS: The present study was aimed to examine the effect of supplementation of dietary taurine (0, 5 g-TAU5 and 10 g-TAU10) in crystalline form (99% purity) in L. calcarifer juveniles, taking into account growth performance, general health indices and immune related-genes mRNA transcript abundance. RESULTS: The results confirmed that the supplementation of taurine enhances significantly all the growth parameters and a better flesh quality. While the blood biochemical and immunological factors didn't present any significant differences, the expression of growth-related genes showed that IGF-1 was almost 3 times higher in fishes fed diet Tau 5 and Tau 10 compared to the control group. CONCLUSIONS: Finally, it can be concluded that at the maximum dose tested (10 g) the treatment was effective for Asian seabass. In addition, Tau inclusion in an FM-based diet can increase the productivity parameters along with raising the antioxidant status.

Metabolic Syndrome and Body Composition Among People Aged 50 Years and Over: Results from The Neyshabur Longitudinal Study on Ageing (NeLSA).

There are few studies regarding body composition and metabolic syndrome (MetS) association in older adults. To evaluate the association between MetS and body composition indices in a large-scale population of subjects with an age of 50 and up. This study was based on the data from Neyshabur Longitudinal Study on Ageing (NeLSA) in a total of 7462 people of Neyshabur city in IRAN. The best cut-off scores and AUC value of body composition variables for having association with likelihood of MetS were determined by using a receiver operating curve analysis. Each unit increase in the Waist/Hip ratio, the odds of having MetS increase 3-6 times (OR: 4.937, 95%CI: 3.930, 6.203 in men; OR: 3.322, 95%CI: 2.259, 4.884 in women). In addition, in the case of BMI (OR: 1.256, 95% Cl: 1.226, 1.286 in men; OR: 1.104, 95% Cl: 1.086, 1.121 in women) and BFM (OR: 1.119, 95% Cl: 1.105, 1.133 in men; OR: 1.050, 95% Cl: 1.041, 1.060 in women), the chance of having MetS increases with increasing these variables. Totally, BMI and BFM showed the best AUC values. The optimal cut-off values for BMI in men was 26.45 and in women was 27.35 and for BFM in men was 23.35 and in women was 26.85. These results suggest that adiposity measures such as BMI and BFM are associated with likelihood of having MetS in subjects with an age of 50 and up, and that avoiding high adiposity is important to prevent MetS incidence.

Francisella tularensis human infections in a village of northwest Iran.

BACKGROUND: Recent seroepidemiological studies have suggested that tularemia could be an endemic bacterial zoonosis in Iran. METHODS: From January 2016 to June 2018, disease cases characterized by fever, cervical lymphadenopathy and ocular involvement were reported in Youzband Village of Kaleybar County, in the East Azerbaijan Province, northwestern Iran. Diagnostic tests included Francisella tularensis serology (including tube agglutination test and ELISA), PCR, and culture. RESULTS: Among 11 examined case-patients, the tularemia tube agglutination test was positive in ten and borderline in one. PCR detected the F. tularensis ISFtu2 elements and fopA gene in one rodent and a spring water sample from the same geographic area. CONCLUSIONS: Based on the clinical manifestations of the disease suggesting an oropharyngeal form of tularemia, serology results in case patients, and F. tularensis detection in the local fauna and aquatic environment, the water supply of the village was the likely source of the tularemia outbreak. Intervention such as dredging and chlorination of the main water storage tank of the village and training of villagers and health care workers in preventive measures and treatment of the illness helped control the infection.

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.

Effects of salinity on gills' chloride cells, stress indices, and gene expression of Asian seabass (Lates calcarifer, Bloch, 1790).

A 2-week research was carried out to assess water salinity (WS) effects including 0, 15, 35, and 50‰ on osmoregulatory mechanisms and stress indices in Asian sea bass (34.4 g) juveniles. Except for fish reared at 50‰, in the other treatments, it gradually decreased to the prescribed WS during a 10-day period (- 5‰ a day). After a 10-day acclimation period, fish were reared at the prescribed WS for 2 weeks. Fish reared at 15 and 35‰ had higher chloride cell (CC) counts in the interlamellar region. The number of CC in the interlamellar region elevated with increment of WS up to 35‰, but they were pronouncedly reduced in 50‰ group. The diameter of CC in the interlamellar region was not affected by WS. The smallest nucleus diameter of CC in the interlamellar region was observed in fish reared at 15‰ (P < 0.05). The largest and the smallest amounts of serum aspartate aminotransferase were observed in fish reared at freshwater and 15‰, respectively. Fish reared at 35‰ had the highest serum sodium and potassium contents. Serum chloride content and total osmolality increased with increment of WS (P < 0.05). Serum cortisol and glucose contents gradually increased with elevation of WS up to 35‰; then, their contents remarkably decreased. The relative expression of insulin like growth factor-1 in the liver of fish reared at 35‰ was strikingly higher than that in the other groups. The relative expression of HSP70 gene in fresh water group was pronouncedly elevated compared to other treatments. The relative expression of interleukin-1ß in 15 and 35‰ groups was higher than that in the other groups; however, the relative expression of lysozyme gene in the liver of fish reared at fresh water was pronouncedly lower than that in the other treatments. The results of this study suggested rearing L. calcarifer at 15‰ closer to the isosmotic point and better provide its welfare.

Therapeutic inhibition of microRNA-21 (miR-21) using locked-nucleic acid (LNA)-anti-miR and its effects on the biological behaviors of melanoma cancer cells in preclinical studies.

BACKGROUND: Melanoma is a cancer that has a high mortality rate in the absence of targeted therapy. Conventional therapies such as surgery, chemotherapy, and radiotherapy are associated with poor prognosis. The expression of miR-21 appears to be of clinical importance, and the regulation of its expression appears to be an opportunity for treatment. METHODS: In this current study, we aimed to evaluate the effects of miR-21 inhibition in- vitro and in-vivo. In-vitro studies have investigated LNA-anti-miR-21 in mouse melanoma cells (B16F10), and in-vivo studies have proposed a model of melanoma in male C57BL/6 mice. To evaluate the anticancer effects of LNA-anti-miR-21, a QRT-PCR analysis was performed using the 2-ΔΔCT method to determine the degree of inhibition of oncomiR-21. The MTT test, propidium iodide/AnnexinV in-vitro, and tumor volume measurement using the QRT-PCR test with the 2-ΔΔCT method were used to estimate the inhibition of miR-21 and the expression of downstream genes including: SNAI1, Nestin (Nes), Oct-4, and NF-kB following miR-21 inhibition. Finally, immunohistochemistry was conducted for an in-vivo animal study. RESULTS: MiR-21 expression was inhibited by 80% after 24 h of B16F10 cell line transfection with LNA-anti-miR-21. The MTT test showed a significant reduction in the number of transfected cells with LNA-anti-miR-21. The transfected cells showed a significant increase in apoptosis in comparison with the control and scrambled LNA groups. According to our in vivo findings, anti-miR-21 could reduce tumor growth and volume in mice receiving intraperitoneal anti-miR after 9 days. The expression of the SNAI1gene was significantly reduced compared to the controls. Immunohistochemical analysis showed no change in CD133 and NF-kB markers. CONCLUSION: Our findings suggest LNA-anti-miR-21 can be potentially used as an anticancer agent for the treatment of melanoma.

Protective effects of doxepin cream on radiation dermatitis in breast cancer: A single arm double-blind randomized clinical trial.

AIMS: Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. METHODS: A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (1:1 ratio) to receive either doxepin (5%) or placebo cream for 7 days. RESULTS: There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). CONCLUSION: Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation.

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.

Epidemiological survey of tularemia in Ilam Province, west of Iran.

BACKGROUND: Francisella tularensis is the causative agent of tularemia in humans and a large number of animal species. Considering recent evidence of the circulation of this bacterium in different parts of Iran, especially in the western provinces, the aim of current study was to determine the tularemia seroprevalence in the human population living in Ilam Province. METHODS: In 2015, 360 serum samples were collected from five groups of people: ranchers (n = 112), farmers (n = 79), butchers and slaughterhouse workers (n = 61), Nature Conservation Officers (n = 34), and referents of medical diagnostic laboratories (n = 74). These samples were tested for the presence of anti- F. tularensis IgG antibodies using the ELISA method. RESULTS: According to the ELISA manufacturer cutoffs, we found that 10 (2.78%) and 9 (2.5%) sera, respectively, were positive or borderline for F. tularensis IgG antibodies. The highest tularemia seroprevalence was observed among farmers (7.59%). CONCLUSIONS: Our results strongly support the circulation of tularemia in Ilam Province. Because no human tularemia case has been reported so far in this province, we recommend specific education programs to increase knowledge of local health care professionals about this important zoonotic disease.

Design, Synthesis and Molecular Docking Studies of Some Tetrahydropyrimidine Derivatives as Possible Fascin Inhibitors.

Eight derivatives of tetrahydropyrimidine scaffold were designed and prepared as hybrid compounds possessing the structural features of both monastrol as an anticancer drug and nifedipine as a fascin blocking agent. All of the compounds were evaluated for their cytotoxic potency and the ability to inhibit 4T1 breast cancer cells migration. Then, they were investigated in silico for their ability to inhibit the fascin protein using molecular docking simulation. The most potent compound was 4d and the weakest one was 4a according to the in vitro cytotoxicity assay. The corresponding IC50 values were 193.70 and 248.75 µm, respectively. The least cytotoxic compound (4a) was one of the strongest ones in binding to the fascin binding site according to the molecular docking results. 4a and 4e inhibited the 4T1 cells migration better than other compounds. They were more potent than nifedipine in inhibiting the migration process. In silico studies proved 4h to be the most potent fascin inhibitor in terms of ΔGbind although it was not inhibiting migration. The controversy between the in vitro and in silico results may cancel the theory of the involvement of the fascin inhibition in the migration inhibition. However, the considerable antimigratory effects of some of the synthesized compounds encourage performing further in vivo experiments to introduce novel tumor metastasis inhibitors.

Leptin induces matrix metalloproteinase 7 expression to promote ovarian cancer cell invasion by activating ERK and JNK pathways.

Leptin, an adipokine secreted by adipose tissue, induces cell invasion and metastasis. MMP7 is a member of the matrix metalloproteinase family that plays an important role in cell invasion. Here we evaluate the possible role and underlying mechanism of MMP7 in the leptin-mediated cell invasion in ovarian cancer cell lines. All experiments were carried out in cultured SKOV3, OVCAR3, and CaoV-3 ovarian cell lines. MMP7 expression was determined using the Western blot following treatment to various concentrations of leptin for defined time intervals. The activation of ERK, JNK, and P38 MAP kinases were determined using Western blotting. Wound healing and BD matrigel invasion assays were used to measure cell migration and invasion. The siRNA approach and pharmacological inhibitors of ERK and JNK pathway were used to confirm the receptor-dependent effect of leptin and a role for ERK and JNK pathway. Zymography assay was employed to determine MMP2 and MMP9 activation. Results show that leptin induces ERK1/2 and JNK1/2 activation and subsequently promotes MMP7 expression in SKOV3 (4.8 ± 0.14 fold of control, P < 0.01) and OVCAR3 (3.1 ± 0.19 fold of control, P < 0.01) ovarian cancer cell lines. These effects was reversed by knockdown of OB-Rb and/or pre-incubation with PD98059 (ERK1/2 inhibitor), SP600125 (JNK1/2 inhibitor). Gelatin zymography showed that MMP7 gene silencing attenuated leptin-induced MMP9 activation in SKOV3 cell line. Taken together, our results suggest new evidences for a modulatory effect of leptin in regulation of ovarian cancer cell invasion by stimulating MMP7 expression via ERK and JNK pathways.

A new ultrasound sign in the diagnosis of pediatric maxillary sinusitis.

Background: Computed tomography scans (CT scan) and X-rays are used to diagnose paediatric maxillary sinusitis. This study aimed at exploring the diagnostic value of the conventional and colour Doppler ultrasounds and their specific findings in cases of paediatric sinusitis. Methods: A total of 60 children diagnosed with sinusitis were included in this study. The conventional and colour Doppler ultrasounds of the sinus were performed on each of them. The symptoms that suggested increased blood flow to the sinuses were interpreted as positive findings on the colour Doppler ultrasound and were named "Ghasemi signs" for the purpose of this study. Such symptoms included unilateral artery bumps on the front artery, reduction of arterial resistive index (RI) to less than 0.5, and diameter of 2 mm or above for maxillary arteries. Sensitivity, specificity, and positive and negative predictive values, and accuracy of the conventional and colour Doppler ultrasounds were also calculated. Results: Compared to CT scan, the conventional ultrasound showed sensitivity and specificity of 73.4% and 100%, respectively. Sensitivity and specificity for the colour Doppler ultrasound were 89.36% and 100%, respectively. The maxillary artery diameter in normal and affected maxillary sinuses were, respectively, 2.4 mm (2.1-2.6, 95% CI) and 1.7 mm (1.6-1.9, 95% CI), with p<0.001. The RI of the affected sinuses were 0.47 (0.45-0.49, 95% CI), and those of the normal sinuses were 0.58 (0.54-0.61, 95% CI), with p<0.001. Conclusion: The findings of this study revealed that the conventional ultrasound agrees with the CT scans in the diagnosis of paediatric maxillary sinusitis. This diagnostic modality becomes even more valuable when the colour Doppler is used, particularly when considering the specific symptoms (Ghasemi signs) suggested by this study.