Evaluation of pea/rice and amylopectin/chromium as an alternative protein source to improve muscle protein synthesis in rats.

BACKGROUND: A preclinical study reported that the combination of an amylopectin/chromium complex (ACr) of branched-chain amino acids (BCAA) significantly enhanced muscle protein synthesis (MPS). This study was conducted to determine the effects of the addition of ACr complex to a pea/rice (PR) protein on MPS, insulin, muslin levels, and the mTOR pathway in exercised rats. METHODS: Twenty-four rats were divided into three groups: (i) exercise (Ex); (ii) Ex + PR 1:1 blend (0.465 g/kg BW); (iii) Ex + PR + ACr (0.155 g/kg BW). On the day of single-dose administration, after the animals were exercised at 26/m/min for 2 h, the supplement was given by oral gavage. The rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of deuterium-labeled phenylalanine to determine the protein fractional synthesis rate (FSR) one h after consuming the study product. RESULTS: The combination of PR and ACr enhanced MPS by 42.55% compared to the Ex group, while Ex + PR alone increased MPS by 30.2% over the Ex group (p < 0.0001) in exercised rats. Ex + PR plus ACr significantly enhanced phosphorylation of mTOR and S6K1 (p < 0.0001), and 4E-BP1 (p < 0.001) compared to the Ex (p < 0.0001). PR to ACr also significantly increased insulin and musclin levels (p < 0.0001) in exercised rats. Additionally, compared to Ex + PR alone, Ex + PR + ACr enhanced mTOR (p < 0.0001) and S6K1 (p < 0.0001) levels. CONCLUSION: These data suggested that PR + ACr may provide an alternative to animal proteins for remodeling and repairing muscle by stimulating MPS and mTOR signaling pathways in post-exercised rats. More preclinical and clinical human studies on combining pea/rice and amylopectin/chromium complex are required.

The effect of different boron compounds on nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism.

BACKGROUND: Gastrointestinal health is essential for maintaining a healthy lifestyle. Improving nutrient absorption and energy metabolism are the critical targets for intestinal health. This study aimed to determine the effects of different boron (B) derivatives on nutrient digestibility, intestinal nutrient transporters, and lipid metabolism in rats. METHODS: Twenty-one rats were allocated to three groups (n = 7) as follows: (i) Control, (ii) Sodium pentaborate pentahydrate (SPP), and (iii) boric acid (BA). The rats were fed a chow diet (AIN-93M) and supplemented with 8 mg/kg elemental B from SPP (45.2 mg/kg BW) and BA (42.7 mg/kg BW) via oral gavage every other day for 12 weeks. The nutrient digestibility of rats in each group was measured using the indigestible indicator (chromium oxide, Cr2 O3, 0.20%). At the end of the experiment, animals were decapitated by cervical dislocation and jejunum, and liver samples were taken from each animal. The nutrient transporters and lipid-regulated transcription factors were determined by RT-PCR. RESULTS: The nutrient digestibility (except for ash) was increased by SPP and BA supplementation (p < 0.05). SPP and BA-supplemented rats had higher jejunal glucose transporter 1 (GLUT1), GLUT2, GLUT5, sodium-dependent glucose transporter 1 (SGLT1), fatty acid transport protein-1 (FATP1), and FATP4 mRNA expression levels compared to nonsupplemented rats (p < 0.0001). BA-supplemented rats had remarkably higher peroxisome proliferator-activated receptor gamma (PPARγ) levels than nonsupplemented rats (p < 0.0001). In contrast, sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptor alpha (LxR-α), and fatty acid synthase (FAS) levels decreased by SPP supplementation compared to other groups (p < 0.05). DISCUSSION: SPP and BA administration enhanced nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism in rats.

The Effect of Residual Gastric Volume on Body Mass Index, Excess Weight Loss Rate and Metabolic Response after Sleeve Gastrectomy.

BACKGROUND/AIM: To investigate the metabolic response and body mass index reduction according to the remaining stomach volume between 6-12 months after the operation in patients who underwent sleeve gastrectomy surgery for obesity and to determine the relationship between the remaining stomach volume and metabolic improvement. Materials and Methods: Patients underwent sleeve gastrectomy in a single center by the same team and with the same standardized method. Residual gastric volumes were calculated from three-dimensional computed tomography images obtained 6-12 months postoperatively. BMI, excess weight loss (EWL), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), triglyceride, hemoglobin A1c (HbA1c), total protein, albumin values were recorded preoperatively and at the time of residual volume measurement. Results: There were 49 subjects with a mean SD preoperative BMI of 47.26+-6.21 kg/m2 and mean age 37.51+-10.88 years. Mean residual volume was 155.36+-56.71 cc. Residual volume was associated with postoperative mean BMI (28.44+-3.23 kg/m2; p 0.001) and postperative mean EWL%(29.27+-7.66; p=0.001). Residual gastric volume was also negative correlated with postoperative mean HbA1c (p=0.004). HbA1c (p=0.828), LDL (p=0.661), HDL (p=0.848), triglycerides (p=0.641), VLDL (p=0.794), total protein relation (p=0.539) and albumin (p=0.824) were analyzed before and after surgery and were not correlated with residual gastric volume. CONCLUSION: The smaller the residual gastric volume after laparoscopic sleeve gastrectomy, the higher the %EWL and the greater the decrease in HbA1c. This study show that laparoscopic sleeve gastrectomy is an effective surgical procedure in patients with Type 2 diabetes mellitus.

Marine Phytoplankton Improves Exercise Recovery in Humans and Activates Repair Mechanisms in Rats.

This study investigated the effects of marine phytoplankton supplementation on 1) perceived recovery and ground reaction forces in humans following a non-functional overreaching resistance-training program and 2) myogenic molecular markers associated with muscle cell recovery in a rat model. In the human trial, a 5-week resistance-training program with intentional overreaching on weeks 2 and 5 was implemented. Results indicate that marine phytoplankton prompted positive changes in perceived recovery at post-testing and, while both marine phytoplankton and placebo conditions demonstrated decreased peak and mean rate of force development following the overreaching weeks, placebo remained decreased at post-testing while marine phytoplankton returned to baseline levels. In the rat model, rats were divided into four conditions: (i) control, (ii) exercise, (iii) exercise + marine phytoplankton 2.55 mg·d-1, or (iv) exercise+marine phytoplankton 5.1 mg·d-1. Rats in exercising conditions performed treadmill exercise 5 d·wk-1 for 6 weeks. Marine phytoplankton in exercising rats increased positive and decrease negative myogenic factors regulating satellite cell proliferation. Taken together, marine phytoplankton improved perceptual and functional indices of exercise recovery in an overreaching human model and, mechanistically, this could be driven through cell cycle regulation and a potential to improve protein turnover.

Allyl isothiocyanate attenuates LED light-induced retinal damage in rats: exploration for the potential molecular mechanisms.

PURPOSE: Environmental light pollution due to artificial light may increase the rate and severity of retinal diseases, and plant-based nutritional interventions with antioxidant properties have the potential to reverse this phenomenon. We aimed to investigate the potential effects of allyl isothiocyanate (AITC) against white light-emitting diode (LED)-induced retinal degeneration (RD) in the rats. METHODS: Twenty-eight male rats were allocated as: (i) Control, (ii) LED, (iii) LED + AITC (10 mg/kg BW), (iv) LED + AITC (20 mg/kg BW). Rats were administered with AITC for 28 days, followed by two days of intense environmental LED light (750 Lux) exposure to the eyes. Animals were sacrificed immediately at the end of the study, then the blood and eyeballs were taken for the biochemical, western blotting, and histopathology examinations. RESULTS: AITC lowered the serum and retina malondialdehyde (MDA) levels while significantly (p < 0.05) improving the retinal antioxidant enzyme activities in a dose-dependent manner. AITC improved retinal and outer nuclear layer (ONL) thickness as compared to the LED group (p < 0.05). AITC increased the levels of Bax, caspase-3, HO-1, GAP43, and VEGF, while decreasing IL-1ß, IL-6, NF-κB, Bcl-2, GFAP, Grp78, activating ATF4 and ATF6 as compared to the LED group (p < 0.05). CONCLUSION: In conclusion, four weeks of AITC administration to the rats showed specific protective effects against two days of intense LED light-induced retinal damage; through antiinflammatory, antioxidant, anti-apoptotic, and modulating mitochondrial metabolic pathways.

Determination and molecular analysis of antibiotic resistance in Gram-negative enteric bacteria isolated from Pelophylax sp. in the Eastern Black Sea Region.

The aim of this study was to evaluate the prevalence and types of antimicrobial resistance among Gram-negative enteric bacteria isolated from Pelophylax sp. Fifty-four frogs were collected from six provinces in the Eastern Black Sea Region of Turkey. In the cloacal swab cultures, bacteria from 160 different colonies were identified by biochemical tests, automated systems, and matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The antimicrobial susceptibility tests were performed by the disk diffusion method. The observed drug resistance rate was the highest to ampicillin and cefazolin, while the lowest against ciprofloxacin and tetracycline. In the molecular assays, bla TEM (8 Citrobacter spp.), bla SHV (2 Escherichia coli, 1 Hafnia alvei, and a Serratia liquefaciens), tetA genes (E. coli and Klebsiella spp.) and a class 1 integron without any gene cassette (E. coli) were detected. Among the strains, no plasmid-mediated quinolone resistance [qnrA, qnrB, qnrS, qepA and aac (6 ')-Ib-cr] was found. However, two of three quinolone-resistant Klebsiella strains showed the novel amino acid substitution in the gyrA gene resulting in Ser83Asp and Asp87Glu.The clonality between E. coli isolates was also examined by pulsed-field gel electrophoresis. We consider that multidrug-resistant Gram-negative enteric bacteria in the intestinal microbiota of a cosmopolitan frog species might be a reservoir for antibiotic resistance genes.

Influence of dietary genistein and polyunsaturated fatty acids on lipid peroxidation and fatty acid composition of meat in quail exposed to heat stress.

This experiment was conducted to investigate the effects of polyunsaturated fatty acids (PUFA) and genistein on performance and meat fatty acid profiles in quail exposed to heat stress. A total of 360 Japanese quail were divided into 12 groups in a 2 × 2 × 3 factorial design; each group comprised 30 quail with five replicates and were kept either at 22 ± 2 °C for 24 h/day (Thermoneutral, TN) or 34 ± 2 °C for 8 h/day (08:00 to 17:00 h) followed by 22 °C for 16 h (heat stress, HS) conditions. The diet contained either two levels of PUFA at 15 or 45% of total fat or three levels of genistein at 0, 400, or 800 mg/kg. Bodyweight gain, feed intake, and feed efficiency were lower (p ≥ 0.01) for quail reared under heat stress and fed low PUFA. Increasing dietary genistein in a linear manner improved the productive performance (p < 0.001). Heat stress caused increases in serum and thigh meat malondialdehyde (MDA) concentrations and decreases in genistein and vitamin E and A concentrations in serum and thigh meat (p < 0.001). High PUFA (PUFA45) in the diet of quail caused greater 18:2, 18:3 ALA, EPA, DHA, n-6, and n-3 PUFA as well as total PUFA and total USFA percentages (p < 0.001) in the thigh muscle, some of which decreased with heat stress (p ≥ 0.006) with no regard to genistein supplementation. This study revealed that genistein with greater doses along with greater PUFA inclusion to the diet of quail reared under heat stress is recommended for alleviating adverse effects of heat stress and for yielding healthier meat for human consumption.

Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats

Background/aim: This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats. Materials and methods: Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results: Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (p < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group. Conclusion: These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.

Wnt signaling pathway activities may be altered in primary Sjogren's syndrome

Background/aim: Sjögren's syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/ß-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS. Materials and methods: This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically. Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group. Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/ß-catenin pathway activities may be altered in case of glandular inflammation.

Genistein suppresses the inflammation and GSK-3 pathway in an animal model of spontaneous ovarian cancer

Background/aim: Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer. Materials and methods: A total of 300 laying hens were distributed into three groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively. Results: Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL- 6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (p < 0.001). Moreover, it upregulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but downregulated GSK-3α and ß after treatment. It acts in a dose-dependent manner. Conclusion: Genistein exhibited an anticancer effect by reducing proinflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. It is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.

Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine levels in an experimental arthritis model.

Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.

Effects of taurine supplementation on productive performance, nutrient digestibility and gene expression of nutrient transporters in quails reared under heat stress.

This study was conducted to examine the effects of dietary taurine supplementation on productive performance, nutrient digestibility, antioxidant status, and the gene expression of ileal nutrient transporters in laying quails reared under heat stress (HS). One hundred and eighty laying Japanese quails (Coturnix coturnix japonica) were fed a basal diet or basal diet supplemented with either 2.5 or 5 g of taurine per kg of diet, and reared at either 22 ± 2 °C for 24 h/d (thermoneutral, TN) or 34 ± 2 °C for 8 h/d (HS) for 12 weeks. The quails reared under HS consumed less feed, produced less egg, and had lower dry matter, organic matter and crude protein apparent digestibilities compared with the quails reared under the TN condition (P = 0.001). However, increasing taurine concentrations in the diet improved feed intake and egg production (P = 0.001), but also the apparent digestibilities (P ≤ 0.027) in quails reared under HS. The greater doses (5 g/kg) of taurine resulted in more responses. The quails reared under HS had greater serum and liver MDA concentrations (P = 0.0001) which decreased with dietary taurine supplementations, particularly greater doses. The gene expressions of ileal PEPT1, EAAT3, CAT1, CAT2, SGLT1, SGLT5, GLUT2, and GLUT5 decreased under HS conditions (P = 0.001). However, supplementing taurine, in a dose-dependent fashion, to the diet of quails reared under HS resulted in increases in the gene expressions of the transporters (P < 0.05) except for CAT1. The results of the present work showed that taurine supplementation, particularly with greater doses (5 g/kg), to the diet of laying quails kept under HS acts as alleviating negative effects of HS, resulting in improvements in productive performance and nutrient digestion, and also upregulation of ileal nutrient transporters.

Data-Driven identification of chemopreventive agents for breast cancer

Preclinical animal models of breast cancer provide the opportunity to identify chemopreventive drugs with single-agent activity as well as effective multi-modality regimens for primary as well as secondary prevention in high-risk persons. Our group has used the 7,12-dimethylbenz(a)anthracene (DMBA) mouse model of carcinogen-induced breast cancer to explore the clinical potential of two tyrosine kinase inhibitors and a nucleoside analog as chemopreventive agents. All three agents exhibited promising preclinical activity both as monotherapy and as components of combination therapy with the standard chemotherapy drug paclitaxel. The tumors developing despite chemoprevention were not only small and grew slowly, but they also displayed a uniquely more pro-apoptotic protein expression profile. Hence, our experimental chemopreventive drugs were capable of preventing the development of aggressive mammary gland tumors with an apoptosis-resistant protein expression profile.

Mango ginger (curcuma amada) inhibits collagen-induced arthritis by modulating inflammatory cytokine levels in rats

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis. Materials and methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund's adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed. Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws. Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.

Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats.

BACKGROUND: Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. METHODS: Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/8hD, 24hL/0hD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-κB), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. RESULTS: L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IGF1, Nrf2, and HO-1 levels. However, the levels of NF-κB and GFAP levels were decreased by administration of L/Zi. CONCLUSIONS: According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress.

Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice.

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood-brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1ß (IL1ß) and interleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-κB were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC, when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies.

(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers.

PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. RESULTS: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), Gα Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-κB (NF- κB) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. CONCLUSIONS: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.

Effects of supplementation of chromium histidinate on glucose, lipid metabolism and oxidative stress in cats.

In recent years, two meta-analyses of chromium (Cr) supplementation have shown beneficial effects on glucose metabolism. Chromium histidinate (CrHis) reduces serum glucose levels in rats fed a high-fat diet but no study has been conducted on cats until now. The aim of this study was to examine the effects of CrHis on glucose and lipid metabolism in cats. To challenge the glucose metabolism, 16 cats were fed a high-carbohydrate high-fat diet for three months. One group (n = 8) received 800 ug CrHis per day for two months, while the other group (n = 8) served as control group. An oral glucose tolerance test was conducted, blood samples were taken, and biochemical parameters and oxidative stress were measured. CrHis serum levels were significantly increased (p = 0.027) in the treatment group, while fructosamine levels were significantly lower (p = 0.029) in the control group. In both groups, glucose (p < 0.01), b-hydroxy-butyrate (p = 0.024) and 8-hydroxy-deoxyguanosine (p = 0.028) levels decreased significantly and cholesterol levels increased significantly (p < 0.01). In conclusion, CrHis did not improve glucose or lipid metabolism and did not affect oxidative stress in healthy cats.

Determining the insulin secretion potential for certain specific G-protein coupled receptors in MIN6 pancreatic beta cells

Background/aim: The polypeptide hormone insulin is essential for the maintenance of whole-body fuel homeostasis, and defects in insulin secretion and/or action are associated with the development of type 1 and type 2 diabetes. The aim of this study was to assess the role of some G-protein coupled receptors (GPCRs), GPR54, GPR56, and GPR75, and cannabinoid receptors CB1R and CB2R, in the regulation of pancreatic ß-cell function. Materials and methods: Insulin secretion from mouse insulinoma ß-cell line (MIN6) monolayers was assessed via insulin radioimmu-noassay (RIA). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the expression of some specific GPCRs and the other receptors by MIN6 pancreatic ß-cells. Results: The agonists were not found to be toxic for the MIN6 pancreatic ß-cells within the range of the doses used in this study, whereas insulin secretion altered depending on the ligands and receptors. In addition, arachidonyl-2'-chloroethylamide (ACEA), carbachol, chemokine (C-C motif ) ligand-5 (CCL5), and exendin as well as phorbol myristate acetate (PMA) ligands showed significant increases in the insulin secretion of MIN6 pancreatic ß-cells. Conclusion: Understanding the normal ß-cell function and identifying the defects in ß-cell function that lead to the development of diabetes will generate new therapeutic targets

LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice.

The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-ß-hydroxy-ß-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.