Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line.

AIMS AND BACKGROUND: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake. MATERIAL METHODS: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting. RESULTS: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group. CONCLUSION: Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.

Electronic equipment and appliances in special wards of hospitals as a source of azole-resistant Aspergillus fumigatus: a multi-centre study from Iran.

BACKGROUND: Azole-resistant Aspergillus fumigatus (ARAf), reported as a global public health concern, has been unexpectedly observed in different countries. AIM: To identify ARAf and detect azole resistance related to the CYP51A mutation in different hospital environmental samples. METHODS: In this multi-centre study from Iran, surfaces of electronic equipment and appliances from different hospitals in Iran were sampled using cotton swabs. All samples were cultured using azole-containing agar plates (ACAPs). Recovered Aspergillus isolates were identified at the species level using partial DNA sequencing of the ß-tubulin gene. The azole susceptibility testing of A. fumigatus isolates was performed using the Clinical and Laboratory Standards Institute M38-A3 guideline. The sequencing of the CYP51A gene was also performed to detect mutations related to resistance. FINDINGS: Out of the 693 collected samples, 89 (12.8%) Aspergillus species were recovered from ACAPs. Aspergillus fumigatus (41.6%) was the most prevalent, followed by A. tubingensis (23.6%) and A. niger (15.6%). Among 37 isolates of A. fumigatus, 19 (51.3%) showed high minimum inhibitory concentration (MIC) values to at least one of the three azoles, voriconazole, itraconazole, and posaconazole. CYP51A polymorphisms were detected in all 19 isolates, of which 52.6% showed the TR34/L98H mutation. Other detected mutations were G432C, G448S, G54E/G138C, F46Y, and Y121F/M220I/D255E. T289F and G432C were the first reported mutations in ARAf. CONCLUSION: There was a considerable level of azole resistance in hospital environmental samples, a serious warning for patients vulnerable to aspergillosis. Our findings have also revealed a different mutation pattern in the CYP51A gene.

Comprehensive review of resveratrol as a feed additive in dairy cows: exploring its potential diverse effects and implications.

Heat stress and growing demand for dairy products in tropical regions exert metabolic pressure on dairy cows, leading to metabolic diseases and economic losses. Resveratrol (RSV) is known for its numerous beneficial health effects and can be used as a barrier against metabolic abnormalities and prevent economic losses. Several studies have investigated the effects of RSV in humans and various animal species. In this review, we attempted to investigate the effects of RSV from different aspects so that we could have a practical proposal for its utilization in dairy cows. RSV was found to have potential antioxidant, anti-inflammatory, anti-obesity, and antimicrobial effects, leading to improved reproductive performance. It is interesting that the effect of RSV on the microbial population leads to a significant decrease in methane emissions. However, high doses of RSV have been associated with possible adverse effects, underscoring the dose dependence of its efficacy. In conclusion, RSV polyphenol at optimal doses is a promising agent for the prevention and treatment of metabolic abnormalities in dairy cows, based on our literature review and study results.

Aspergillus fumigatus and aspergillosis: From basics to clinics.

The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP 51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP 51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.

Treatment-induced tumor cell apoptosis following high-intensity interval training and saffron aqueous extract in mice with breast cancer.

This study was to investigate whether high-intensity interval training (HIIT) and saffron aqueous extract (SAE) would provide a synergistic effect to improve tumor volume reduction and also modulate pro- and anti-apoptotic protein expression in tumor tissue of 4T1 breast cancer-bearing mice. Female mice following induction of breast cancer through injection of 4T1 cell lines were randomly divided into four groups: (1) HIIT, (2) SAE, (3) HIIT+ SAE, and (4) control. The tumor volume was significantly lower in the HIIT, SAE, and HIIT+SAE groups than in the controls. The protein level of caspase-3 in the HIIT and the SAE groups was higher than in the control and the HIIT+SAE groups. The Bax protein level in the SAE group was higher than in the control. The HIIT+SAE group showed a lower level of Bax than the HIIT and the SAE groups. The protein level of Bcl-2 was higher in the HIIT+SAE vs. both the HIIT and the SAE groups. Finally, the ratio of Bax/Bcl-2 was significantly higher in the HIIT and the SAE groups than in the HIIT+SAE and control groups. These findings indicate that a combination of HIIT and SAE interventions does not improve the apoptotic induction in tumor tissue, while both HIIT and SAE treatments may mediate apoptotic pathway as evinced by the elevated ratio of Bax/Bcl-2 and caspase-3 levels during tumor progression in breast cancer-bearing mice.

Iodine supplementation for pregnant women: a cross-sectional national interventional study.

BACKGROUND: Although Iran has been considered iodine replete since 2000, the first national survey of iodine intake among Iranian pregnant women in 2014 indicated that despite the adequate intake of iodine by the general population, this vulnerable group has moderate iodine deficiency. Therefore, in this national cross-sectional interventional study, we aimed to assess the iodine intake and thyroid function of Iranian pregnant women 2 years after implementing national iodine supplementation for this vulnerable group. MATERIALS AND METHODS: In this cross-sectional study, we conducted a national interventional survey of pregnant women. A total of 1200 pregnant women (400 women from each trimester) from 12 provinces of Iran were recruited from the antenatal care clinics from October 2018 to March 2019. The median urinary iodine concentration (MUIC), as an indicator of iodine status in three spot urine samples, was measured, along with the serum total T4 (TT4), thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPO-Ab), and iodine content of household salt. RESULTS: The mean age of the cohort was 28 ± 6.2 years, with the mean gestational age of 22.7 ± 13.0 weeks. The overall MUIC (IQR) of pregnant women was 188 µg/L (124.2-263 µg/L). Also, the MUICs in the three trimesters of pregnancy were 174 µg/L (110-254), 175 µg/L (116-251), and 165 µg/L (114-235), respectively. The MUICs ≥ 150, 100-149, and < 100 µg/L were found in 63, 19.8, and 16.2% of the subjects, respectively. The mean TT4 level was 12 ± 4.5 µg/dL, and the median (IQR) level of TSH was 2.37 mIU/L (1.66-3.18 mIU/L). According to our local reference range, 118 (10.5%) pregnant women had subclinical hypothyroidism, 6 (0.53%) women had isolated hypothyroxinemia, and 65 (5.7%) women were TPO-Ab positive. Also, the median (IQR) level of Tg was 10.08 µg/dL (5.7-20.4 µg/dL), and the median iodine content of household salt was 29.6 µg/g; the iodine content was ≥ 30 µg/g in 85% of household salt. The results showed that more than 95% of households were under iodized salt coverage. CONCLUSION: The results of this study indicated that iodine supplementation with at least 150 µg of iodine per day improved the iodine intake of pregnant women. Except for subclinical hypothyroidism, the prevalence of clinical hypothyroidism, clinical/subclinical thyrotoxicosis, TPO-Ab positivity, and isolated hypothyroxinemia decreased significantly, which emphasizes the importance of iodine supplementation during pregnancy.

Effect of potassium iodide supplementation and teat-dipping on iodine status in dairy cows and milk iodine levels.

Two experiments were designed to determine the effects of dietary iodine and teat-dipping on the iodine status of dairy cows and their milk. Eight mid-lactation Holstein dairy cows with an initial body weight of 642 ± 62 kg and 145 ± 21 d in milk were studied for 2 periods over 44 d. In period 1, all cows were fed a basal diet supplemented with potassium iodide (KI) (10 mg I/Kg DM) for 8 d with no teat-dipping. In period 2, a pre-milking teat-dipping was applied for 10 d followed by no teat-dipping before milking (udder wash without iodine) and then post-dipping treatment was applied for 5 d. Feeding KI increased concentrations of iodine in serum, urine, and milk (P < 0.05). Switching from the KI supplementation to no iodine addition resulted in an immediate decrease of iodine in serum, urine, and milk (P < 0.05). Post teat-dipping resulted in increased iodine levels in serum, urine, and milk (P < 0.05). However, pre-milking teat-dipping did not affect iodine concentration compared to post-dipping. A 250 mL cup of milk from the control and KI-supplemented diets would provide 29.4% and 68.4%, respectively, of the adult-recommended dietary allowance for iodine. In conclusion, milk iodine concentration could be effectively enhanced by KI supplementation and teat-dipping practices.

Effects of oral contraceptives on serum concentrations of adipokines and adiposity indices of women with polycystic ovary syndrome: a randomized controlled trial.

PURPOSE: To compare the effects of oral contraceptives (OCs) with different progestins, including Levonorgestrel (LNG), Desogestrel (DSG), Cyproterone Acetate (CPA), and Drospirenone (DRSP) on adipokines levels and adiposity indices in women with polycystic ovary syndrome (PCOS). METHODS: In this parallel randomized clinical trial, 120 women with PCOS randomly assigned to intervention with OCs containing LNG, DSG, CPA, or DRSP. Outcomes of interest, including serum concentrations of adiponectin, leptin, and resistin, and adiposity indices, i.e., body mass index (BMI), waist circumference (WC), obesity, central obesity, waist to hip ratio (WHR), waist to height ratio (WHtR), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI), and lipid profiles were assessed at baseline, and 6 months of treatment. RESULTS: This study showed no significant differences in serum concentrations of adipokines between the four study groups after 6 months of treatment. Our results also showed that patients treated with various compounds of OC for 6 months had no significant differences in their adiposity indices, except for LAP (p = 0.04), and VAI (p = 0.03). PCOS patients treated with OCs containing CPA had significantly a higher mean LAP, compared to those using products containing LNG. Besides, patients treated with OCs containing CPA had significantly a higher mean VAI, compared to those treated with OCs containing DRSP. CONCLUSION: This study demonstrated that OCs with low androgenic and antiandrogenic activities had identical effects on serum concentrations of adipokines, and adiposity indices, except LAP, and VAI parameters. REGISTRATION NUMBER: IRCT20080929001281N3.

Medullary thyroid cancer is associated with high serum vitamin D level and polymorphism of vitamin D receptors.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy. Studies have observed an anti-cancer effect for vitamin D and found that polymorphisms of vitamin D receptors can influence the prevalence of various cancers. The present study investigated the serum level of vitamin D and FokI, BsmI and Tru9I polymorphisms of vitamin D receptors. METHODS: Forty patients with medullary thyroid cancer and 40 healthy controls were investigated. The genomic DNA of the subjects was extracted using saturated salt/proteinase K and investigated by PCR sequencing. Serum levels of vitamin D were evaluated by ELISA. The results were analyzed in SPSS and GraphPad Prism 5 software. RESULTS: The genotypic and allelic frequencies of FokI and BsmI polymorphisms showed no significant differences between test and control groups. For Tru9I polymorphism, Tt genotype and t allelic frequency in the test group were significantly different from those of the control group. Also, we found Tt genotype and t allelic frequency to be significantly associated with medullary thyroid cancer (MTC) type and the agressiveness of the disease. The average serum vitamin D level was 23.32 ng/mL and 18.95 ng/mL for patients and controls, respectively, and the difference between the two groups was statistically significant. Moreover, we found high serum vitamin D level to be associated with t allelic frequency. CONCLUSIONS: Unexpectedly, the mean serum vitamin D level of the test group was significantly higher than that of the control group. Tru9I polymorphism was found to be significantly correlated with the prevalence of medullary thyroid carcinoma.