Search results for: Liver X receptor (LXR)

Authors: Ionelia Taranu, Gina Cecilia Pistol, Mihai Alexandru Gras, Mihai Laurentiu Palade, Mariana Stancu, Veronica Sanda Chedea

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In the last decade bioactive compounds from grape waste are investigated as new therapeutic agents for the inhibition of carcinogenesis and other diseases. The objective of this study was to characterize several bioactive compounds (polyphenols and polyunsaturated fatty acids) of a dried grape pomace (GP) derived from a Romanian winery and further to evaluate their effect on inflammation and oxidative markers in liver of pig used as animal model. The total polyphenol concentration of pomace was 36.2g gallic acid equiv /100g. The pomace was rich in polyphenols from the flavonoids group, the main class being flavanols (epicatechins, catechin, epigallocatechin, procyanidins) and antocyanins (Malvidin 3-O-glucoside). The highest concentration was recorded for epicatechin (51.96g/100g) and procyanidin dimer (22.79g/100g). A high concentration of total polyunsaturated fatty acids (PUFA) especially ω-6 fatty acids (59.82 g/100g fat) was found in grape pomace. 20 crossbred TOPIG hybrid fattening pigs were randomly assigned (n = 10) to two experimental treatments: a normal diet (control group) and a diet included 5% grape pomace (GP group) for 24 days. The GP diet lowered the gene expression and protein concentration of IL-1β, IL-8, TNF-α and IFN-γ cytokines in liver suggesting an anti-inflammatory effect of GP diet. Concentration of hepatic TBARS also decreased, but the total antioxidant capacity (liver TEAC) and activity and gene expression of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) did not differ between the GP and control diet. The results showed that GP diet exerted an anti-inflammatory effect, but the 5% dietary inclusion modulated only partially the oxidative stress.

Keywords: animal model, inflammation, grape waste, immune organs

Procedia PDF Downloads 339

Authors: N. Nwachoko, E. B. Essien, E. O. Ayalogu

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Owing to the outbreak of different diseases and microbial resistance to some available drugs, proper identification, and evaluation of plants have been encouraged. There have been claims worldwide by the traditional system that some plants possessed medicinal properties. Plants and their components have been said to be source of large amount of drugs which comprise of distinct groups such as antispasmodics, anticancer and antimicrobials. Researchers have reported that chemicals in plants are responsible for the medicinal uses of plants. Thus this study evaluated the protective effect of Aframomun chrysanthum seed aqueous extract in acetaminophen-induced liver toxicity in rats. A suspension of 750 mg/kg acetaminophen was administered once every 72 hours to induce toxicity in the rats. Oral administration of 500, 1000 and 2000 mg/kg body weight of the extract and 100 mg/kg of silymarin (reference drug) were administered for 10 days. Biochemical analysis showed significant (p < 0.05) increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT)and alkaline phosphatase (ALP)as well as the concentrations of albumin (ALB) and total bilirubin (T.B.) levels in rats administered with acetaminophen only. The levels of these parameters were significantly (p < 0.05) decreased in the groups pretreated with the extract.

Keywords: Aframomun chrysanthum, silymarin, hepatoprotective, toxicity

Procedia PDF Downloads 397

Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad

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COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.

Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy

Procedia PDF Downloads 144

Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

Abstract:

Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

Procedia PDF Downloads 307

Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

Abstract:

A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

Procedia PDF Downloads 104

Authors: F. Haddadj, S. Hamdi, A. Milla, S. Zenia, A. Smai, H. Saadi, F. Marniche, B. Doumandji-Mitiche

Abstract:

The use of a biopesticide based on a microorganism scale requires particular care including safety against the useful auxiliary fauna and mammals among other human beings. Due to its persistence in soil and its apparent human and animal safety, Beauveria bassiana is a cryptogram used for controlling pests organizations, particularly in the locust where its effectiveness has been proven. This fungus is also called for greater respect for biotic communities and the environment. Indeed, biopesticides have several environmental benefits: biodegradability, their activity and selectivity decrease unintended non-target species effects, decreased resistance to some of them. It is in this sense that we contribute by presenting our work on the safety of B. bassiana against mammals. For this we conducted a toxicological study of this fungus strain on Wistar rats Rattus norvegicus, first its effect on weight gain. In a second time were performed histological target organ is the liver. After 20 days of treatment, the results of the toxicological studies have shown that B. bassiana caused no change in the physiological state of rats or weight gain, behavior and diet. On cuts in liver histology revealed no disturbance on the organ.

Keywords: B. bassiana, entomopathogenic fungus, histology, Rattus norvegicus

Procedia PDF Downloads 238

Authors: R. Stevens, W.L. Bryden

Abstract:

The objective of this study was to determine the efficacy of zeolite in preventing the adverse effects of aflatoxin B1 (AFB1) in broilers. A total of 540 one-day-old Ross chicks were randomly divided into nine treatments, with four replicate pens per treatment and 15 chicks per pen. The treatments included 3 Levels of AFB1 (0,1and 2 mg/kg diet) and 3 levels of zeolite (0, 1.5 and 3 %) in a 3 ×3 factorial arrangement. The experimental treatments commenced on d 7 post-hatch. A starter diet was provided from d 1 to 14, a grower diet from d 15 to 28 and a finisher diet from d 29 to d 49. Diets were based on corn and soybeans and formulated to meet the bird's requirements. The evaluated parameters were as follows: Bodyweight, daily gain, feed intake (FI), feed conversion (FC), relative weights of organs (carcass, liver, heart and abdominal fat) and clinical biochemistry parameters: alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Bodyweight, daily gain and FC were significantly (P<0.05) impaired by aflatoxin. Relative weights of the liver and heart were also affected. The addition of zeolite (1.5 and 3 %) to the contaminated diets ameliorated the effects of aflatoxin, especially at the higher level of inclusion. These data demonstrate that this specific sorbent (zeolite) can protect against the toxicity of AFB1in young broiler chicks.

Keywords: aflatoxin, broiler, toxicity, zeolite

Procedia PDF Downloads 157

Authors: Aliyu Maje Bello, Yaowaluck Maprang Roshorm

Abstract:

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection affecting mostly infants and children. Although the Enterovirus A71 (EV71) is usually the major causative agent of HFMD, other enteroviruses such as coxsackievirus A16, A10, and A6 are also found in some of the recent outbreaks. The commercially available vaccines have demonstrated their effectiveness against only EV71 infection but no protection against other enteroviruses. To address the limitation of the monovalent EV71 vaccine, the present study thus designed a tetravalent vaccine against the four major enteroviruses causing HFMD and primarily evaluated the designed vaccine using an immunoinformatics approach. The immunogen was designed to contain the EV71 VP1 protein and multiple reported epitopes from all four distinct enteroviruses and thus designated a tetravalent vaccine. The 3D structure of the designed tetravalent vaccine was modeled, refined, and validated. Epitope screening showed the presence of B-cell, CTL, CD4 T cell, and IFN epitopes with vast application among the Asian population. Docking analysis confirmed the stable and strong binding interactions between the immunogen and immune receptor B-cell receptor (BCR). In silico cloning and immune simulation analyses guaranteed high efficiency and sufficient expression of the vaccine candidate in humans. Overall, the promising results obtained from the in-silico studies of the proposed tetravalent vaccine make it a potential candidate worth further experimental validation.

Keywords: enteroviruses, coxsackieviruses, hand foot and mouth disease, immunoinformatics, tetravalent vaccine

Procedia PDF Downloads 72

Authors: Azza A. Ali, Toqa M. Elnahhas, Abeer I. Abd El-Fattah, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Environmental pollution with the different aluminium (Al) containing compounds especially those in industrial waste water exposes people to higher than normal levels of Al that represents an environmental risk factor. Cosmetics, Al ware, and containers are also sources of Al besides some foods and food additives. In addition to its known neurotoxicity, Al affects other body structures like skeletal system, blood cells, liver and kidney. Accumulation of Al in kidney and liver induces nephrotoxicity and hepatotoxicity. Coenzyme Q10 (CoQ10) is a pseudo-vitamin substance primarily present in the mitochondria. It is a powerful antioxidant and acts as radical scavenger. Wheat grass is a natural product that contains carbohydrates, proteins, vitamins, minerals, enzymes and has antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Cocoa is an excellent source of iron, potent antioxidants and can protect against many diseases. Vinpocetine is an antioxidant and anti inflammatory while zinc is an essential trace element involved in cell division and its deficiency is observed in many types of liver disease. Objective: To evaluate and compare the potency of different drugs (CoQ10, wheatgrass, cocoa, vinpocetine and zinc) against nephro- and hepato-toxicity induced by Al in rats. Methods: Rats were divided to seven groups and received daily for three weeks either saline for control group or AlCl3 (70 mg/kg, IP) for Al-toxicity model groups. Five groups of Al-toxicity model (treated groups) were orally received together with Al each of the following; CoQ10 (200mg/kg), wheat grass (100mg/kg), cocoa powder (24mg/kg), vinpocetine (20mg/kg) or zinc (32mg/kg). Biochemical changes in the serum level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea were measured. Liver and kidney specimens from all groups were also collected for the assessment of hepatic and nephrotic level of inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3, oxidative parameters (MDA, SOD, TAC, NO) and DNA fragmentation. Histopathological changes in liver and kidney were also evaluated. Results: Three weeks of AlCl3 (70 mg/kg, IP) exposure induced nephro- and hepato-toxicity in rats. Treatment by the all used drugs showed protection against hazards of AlCl3. The protective effects were indicated by the significant decrease in ALT, AST, ALP, LDH as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels which were increased by Al. Liver and kidney of the treated groups showed decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation which were increased by Al, together with significant increase in total proteins, SOD and TAC which were decreased by Al. The protection against both nephro- and hepato-toxicity was more pronounced especially with CoQ10 and wheat grass than the other used drugs. Histopathological examinations confirmed the biochemical results of toxicity and of protection. Conclusion: Protection from nephrotoxicity, hepatotoxicity and the consequent degenerations induced by Al can be achieved by using different drugs as CoQ10, wheatgrass, cocoa, vinpocetine and zinc, but CoQ10 as well as wheat grass possesses the most superior protection.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, coenzyme Q10, wheatgrass, cocoa, vinpocetine, zinc

Procedia PDF Downloads 338

Authors: Mahdeb Nadia, Ghadjati Nadhra, Bettihi Sara, Daamouche Z. El Youm, Bouzidi Abdelouahab

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The effects of subacute administration of total alkaloids of seeds Peganum harmala were studied in female Albino-Wistar rats. After intraperitoneal administration of dose 50 mg/kg for 10 days and 40 mg/kg for 7 days of total alkaloids to the seeds of Peganum harmala (animal treatment lasted 17 days), there were remarkable changes in general appearance and deaths occurred in experimental group. After 17 days a significant reduction was observed in the surviving animals treated with total alkaloid seeds.The Red Blood Cells (RBC), Hematocrit (HCT), Hemoglobin (HGB) and White blood cells (WBCs), show significant reduction in the treated groups. There were no statistical differences in Glutamic-Oxaloacetic Transaminase (GOT), Glutamic-pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP), total protein, glucose and creatinine observed between groups. However the urea was significantly higher in the treated female rats than the control group. Histological examination of liver showed no histopathological changes. Alkaloids of Peganum harmala showed significant toxicity in female rats.

Keywords: Peganum harmala, rat, liver, kidney, alkaloids, toxicity

Procedia PDF Downloads 439

Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

Abstract:

This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

Procedia PDF Downloads 161

Authors: Xi Chen, King-Yip Cheng

Abstract:

Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

Procedia PDF Downloads 67

Authors: Philippa Saunders, Claire Fletcher

Abstract:

INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

Procedia PDF Downloads 143

Authors: Areej Ali Baeshen, Hanaa Kamal Galal, Batoul Mohamed Abdullatif

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In the present study, the allelopathic effects of Eruca sativa, Mentha peprinta, and Coriandrum sativum aqueous extracts, prepared by 25 gm and 50 gm of fresh leaves dissolved in 100 ml of double distilled water in addition to the crude extract (100%). The final concentrations were 100 %, 50%, 25% and 0% as control. The extracts were tested for their allelopathic effects on seed germination and other growth parameters of Phaseolous vulgaris. Laboratory experiments were conducted in sterilizes Petri dishes with 5 and 10 day time interval for seed germination and 24 h, 48 h and 72 h for radicle length on an average of 25°C. The effects of different concentrations of aqueous extract were compared to distilled water (0%). 25% and 50% aqueous extracts of Eruca sativa and Coriandrum sativum caused a pronounced inhibitory effect on seed germination and the tested growth parameters of the receptor plant. The inhibitory effect was proportional to the concentration of the extract. Mentha peprinta extracts, on the other hand, caused an increase in germination percentage and other growth parameters in Phaseolous vulgaris. Hence, it could be concluded that the aqueous extracts of Eruca sativa and Coriandrum sativum might contain water-soluble allelochemicals, which could inhibit the seed germination and reduce radicle length of Phaseolous vulgaris. Mentha peprinta has beneficial allelopathic effects on the receptor plant.

Keywords: Phaseolus vulgaris, Eruca sativa, Mentha peperinta, Coriandrum sativum, medicinal plants, seed germination

Procedia PDF Downloads 406

Authors: Abdolreza Esmaeilzadeh, Maryam Erfanmanesh, Sousan Ghasemi, Farzaneh Mohammadi

Abstract:

Background: Hepatitis C Virus (HCV), a public health problem, is an enveloped, single-stranded RNA virus and a member of the Hepacivirus genus of the Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the outcomes of chronic infection with HCV. HCV isolates show significant heterogeneity in genetics around the world. Therefore, determining HCV genotypes is a vital step in determining prognosis and planning therapeutic strategies. Materials and Methods: Serum samples of 136 patients were collected and analyzed for anti-HCV antibodies using ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were exposed to RT-PCR, which was performed under standard condition. Afterwards, they investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype 2.0 line probe assay (LiPA). Results: Samples indicated 216 bp bands on 2% agarose gel. Analyses of the results demonstrated that the most dominant subtype was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b, 1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively. The frequency of unknown HCV genotypes was 4.41%. Conclusions: According to the results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a. Analysis of the results provides identification of certain HCV genotypes, and these valuable findings could affect the type and duration of the treatment.

Keywords: anti-HCV antibody, Hepatitis C Virus (HCV), genotype, RT-PCR, AS-PCR

Procedia PDF Downloads 489

Authors: F. Haddadj, S. Hamdi, M. Khames, A. Kadi, S. Zenia, A. Smai, H. Saadi, B. Doumandji-Mitiche

Abstract:

The use of a biopesticide based on a microorganism scale requires particular care including safety against the useful auxiliary fauna and mammals among other human beings. Due to its persistence in soil and its apparent human and animal safety, Beauveria bassiana is a cryptogram used for controlling pests organizations, particularly in the locust where its effectiveness has been proven by several highly studies. This fungus is also called for greater respect for biotic communities and the environment. Indeed, biopesticides have several environmental benefits: biodegradability, their activity and selectivity decrease unintended non-target species effects, decreased resistance to some of them. It is in this sense that we contribute by presenting our work on the safety of B. bassiana against mammals. For this we conducted a toxicological study of this fungus strain on Wistar rats Rattus norvegicus, first its effect on weight gain. In a second time were performed histological target organ is the liver. After 20 days of treatment, the results of the toxicological studies have shown that B. bassiana caused no change in the physiological state of rats or weight gain, behavior and diet. On cuts in liver histology revealed no disturbance on the organ.

Keywords: entomopathogenic fungus, B. bassiana, Rattus norvegicus, toxicological study, environment

Procedia PDF Downloads 314

Authors: Nurjannatul Naim Kamaruddin, Tengku Sifziuzl Tengku Muhammad, Aina Farahiyah Abdul Manan, Habsah Mohamad

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Atherosclerosis which leads to cardiovascular diseases such as myocardial infarction, unstable angina (ischemic heart pain), sudden cardiac death and stroke is the principal cause of death worldwide. It has been a very critical issue as current common drug treatment, statin therapy has left bad side effects like rhabdomyolysis, atrial fibrillation, liver disease, abdominal and chest pain. Interestingly, the discoveries of proprotein convertase subtilisin-kexin type 9 have paved a new way in the treatment of atherosclerosis. This serine protease is believed to involve in the regulation of LDL- uptake by LDL-receptor. Therefore, this study was conducted to evaluate the potential of Acanthaster plancii fractions to reduce the transcriptional activity of the PCSK9 promoter. In this study, the marine organism which is Acanthaster plancii has been used as the source for marine compounds in inhibiting PCSK9. The cytotoxicity activity of ten fractions from the methanol extracts of Acanthaster plancii was investigated on HepG2 cell lines using MTS assay and dual glo luciferase assay was carried out later to analyses the effects of the samples in reducing the transcriptional activity of the PCSK9 promoter. Both assays used fractions with five different concentrations, 3.13µg/mL, 6.25µg/mL, 12.5µg/mL, 25µg/mL, and 50µg/mL. MTS assay indicated that the fractions are non-cytotoxic towards HepG2 cell lines as their IC50 value is greater than 30µg/mL. Whilst, for the dual glo luciferase assay, among all the fractions, Enhance Fraction 2 (EF2) showed the best potential in reducing the transcriptional activity of the PCSK9 promoter. The results indicated that this EF2 gave the lowest PCSK9 promoter expression at low concentration which is 0.2 fold change at 6.25µg/mL. This finding suggested that further analysis should be done to validate the potential of Acanthaster plancii as the source of anti-atherosclerotic agent.

Keywords: Acanthaster plancii, atherosclerosis, luciferase assay, PCSK9

Procedia PDF Downloads 147

Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

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Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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Authors: Chiung-Man Tsai, Chia-Jui Weng

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Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The present case-control study aimed to examine the effects of single nucleotide polymorphisms (SNPs) of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma (OSCC). The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. All of The three genetic polymorphisms exhibited insignificant (P > .05) effects on the risk to have oral cancer. However, the patients with polymorphic allele of LEP -2548 have a significant low risk for the development of clinical stage (A/G, AOR = 0.670, 95% CI = 0.454–0.988, P < .05; A/G+G/G, AOR = 0.676, 95% CI = 0.467–0.978, P < .05) compared to patients with ancestral homozygous A/A genotype. Additionally, an interesting result was found that the impact of LEP -2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption (A/G, AOR=2.078, 95% CI: 1.161-3.720, p=0.014; A/G+G/G, AOR=2.002, 95% CI: 1.143-3.505, p=0.015) is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated with the susceptibility of oral cancer; SNP in LEP -2548 G/A showed a poor clinicopathological development of oral cancer; Population without tobacco consumption and with polymorphic LEP -2548 G/A gene may significantly increase the risk to have oral cancer.

Keywords: carcinogen, leptin, leptin receptor, oral squamous cell carcinoma, single nucleotide polymorphism

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Authors: Ae Ra Han, Taek Hoo Lee, Sun Zoo Kim, Hwa Young Lee

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Introduction: Ovarian endometrioma is one of the important causes of poor ovarian reserve and up to half of them have recurred. However, the treatment for recurrence prevention has limited efficiency and repeated surgical management makes worsen the ovarian reserve. To find better management for recurrence prevention, we investigated risk factors and biomarkers for the recurrence of ovarian endometrioma. Methods: The medical records of women with the history of surgical dissection for ovarian endometrioma were collected. After exclusion of the cases with concurrent hysterectomy, been menopaused during follow-up, incomplete medical record, and loss of follow-up, a total of 134 women were enrolled. Immunohistochemical staining for progesterone receptor isoform B (PR-B) and nuclear factor kappa B (NFκB) was done with the fixed tissue blocks of their endometriomas which were collected at the time of surgery. Results: Severity of dysmenorrhea and co-existence of adenomyosis had significant correlation with recurrence of endometrioma. Increased PR-B (P = .041) and decreased NFκB (P = .036) immunoreactivity were found in recurrent group. Serum CA-125 level at the time of recurrence was higher than the highest level of CA-125 during follow-up in unrecurred group (55.6 vs. 21.3 U/mL, P = .014). Conclusion: We found that the severity of dysmenorrhea and coexistence of adenomyosis are risk factors for recurrence of ovarian endometrioma, and serial follow-up of CA-125 is effective to detect and prevent the recurrence. However, to determine the possibility of immunoreactivity of PR-B and NFκB as biomarkers for ovarian endometrioma, further studies of various races and large numbers with prospective design are needed.

Keywords: endometriosis, recurrence, biomarker, risk factor

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Authors: Wooseok Byon, Eunyoung Kim, Junseong Kwon, Byung Joo Song, Chan Heun Park

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Purpose: 18F Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a noninvasive imaging modality that can identify nodal metastases in women with primary breast cancer. The aim of this study was to compare the accuracy of FDG-PET with MRI and sonography scanning to determine axillary lymph node status in patients with breast cancer undergoing sentinel lymph node biopsy or axillary lymph node dissection. Patients and Methods: Between January and December 2012, ninety-nine patients with breast cancer and clinically negative axillary nodes were evaluated. All patients underwent FDG-PET, MRI, ultrasound followed by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Results: Using axillary lymph node assessment as the gold standard, the sensitivity and specificity of FDG-PET were 51.4% (95% CI, 41.3% to 65.6%) and 92.2% (95% CI, 82.7% to 97.4%) respectively. The sensitivity and specificity of MRI and ultrasound were 57.1% (95% CI, 39.4% to 73.7%), 67.2% (95% CI, 54.3% to 78.4%) and 42.86% (95% CI, 26.3% to 60.7%), 92.2% (95% CI, 82.7% to 97.4%). Stratification according to hormone receptor status showed an increase in specificity when negative (FDG-PET: 42.3% to 77.8%, MRI 50% to 77.8%, ultrasound 34.6% to 66.7%). Also, positive HER2 status was associated with an increase in specificity (FDG-PET: 42.9% to 85.7%, MRI 50% to 85.7%, ultrasound 35.7% to 71.4%). Conclusions: The sensitivity and specificity of FDG-PET compared with MRI and ultrasound was high. However, FDG-PET is not sufficiently accurate to appropriately identify lymph node metastases. This study suggests that FDG-PET scanning cannot replace histologic staging in early-stage breast cancer, but might have a role in evaluating axillary lymph node status in hormone receptor negative or HER-2 overexpressing subtypes.

Keywords: axillary lymph node metastasis, FDG-PET, MRI, ultrasound

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Authors: Mohamed El Horri, Amine Mouden, Reda Messaoudi, Mohamed Chekkal, Driss Benlaldj, Malika Baghdadi, Lahcene Benmahdi, Fatima Seghier

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Background/aim: Recently, the Von Willebrand factor antigen (vWF-Ag)has been identified as a new marker of portal hypertension (PH) and its complications. Few studies talked about its role in the prediction of esophageal varices. VWF-Ag is considered a non-invasive approach, In order to avoid the endoscopic burden, cost, drawbacks, unpleasant and repeated examinations to the patients. In our study, we aimed to evaluate the ability of this marker in the prediction of another complication of portal hypertension, which is portal hypertensive gastropathy (PHG), the one that is diagnosed also by endoscopic tools. Patients and methods: It is about a prospective study, which include 124 cirrhotic patients with no history of bleeding who underwent screening endoscopy for PH-related complications like esophageal varices (EVs) and PHG. Routine biological tests were performed as well as the VWF-Ag testing by both ELFA and Immunoturbidimetric techniques. The diagnostic performance of our marker was assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and receiver operating characteristic curves. Results: 124 patients were enrolled in this study, with a mean age of 58 years [CI: 55 – 60 years] and a sex ratio of 1.17. Viral etiologies were found in 50% of patients. Screening endoscopy revealed the presence of PHG in 20.2% of cases, while for EVsthey were found in 83.1% of cases. VWF-Ag levels, were significantly increased in patients with PHG compared to those who have not: 441% [CI: 375 – 506], versus 279% [CI: 253 – 304], respectively (p <0.0001). Using the area under the receiver operating characteristic curve (AUC), vWF-Ag was a good predictor for the presence of PHG. With a value higher than 320% and an AUC of 0.824, VWF-Ag had an 84% sensitivity, 74% specificity, 44.7% positive predictive value, 94.8% negative predictive value, and 75.8% diagnostic accuracy. Conclusion: VWF-Ag is a good non-invasive low coast marker for excluding the presence of PHG in patients with liver cirrhosis. Using this marker as part of a selective screening strategy might reduce the need for endoscopic screening and the coast of the management of these kinds of patients.

Keywords: von willebrand factor, portal hypertensive gastropathy, prediction, liver cirrhosis

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Authors: Chih-Hung Liang, Jung-Jung Chen, Shen-Shih Chiang

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Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health, which are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Cordyceps militaris (CM) is a well-known traditional medicine in Asian countries and a rich source of biologically active components. Black rice (Oryza sativa L.) is a special cultivar of rice that contains rich anthocyanins and regarded as a health-promoting food in China and other Eastern. The aim of this study was to investigate the anti-obesity effect of Cordyceps militaris fermented black rice (CB) on HFD-induced BALB/c mice model. The results indicated that administration of low and high dosage of CB powder significantly reduced the body weights (7.38% and 7.78%), body fat ratio (2.37% and 2.78%), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels compared to the HF group (p<0.05). Histopathological analysis showed that the score of fatty liver in HF group (5.0) was significantly higher than CB groups (2.1 and 3.6) (p<0.05). In conclusion, Cordyceps militaris fermented black rice can reduce the body weight via inhibition of the fat accumulation in liver and body and possess the anti-obesity potency.

Keywords: Cordyceps militaris, black rice, obesity, HFD-induced mice

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Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

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Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

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Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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Authors: Bopit Puyati, Anchittha Kaewchana, Nuntita Ruksachat

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In January 2018, a male wild elephant, approximately 2 years old, was found dead in Phu Luang Wildlife Sanctuary, Loei province. The elephant was likely to die around 2 weeks earlier. The carcass was decayed without any signs of attack or bullet. No organs were removed. A deadly viral disease was suspected. Different organs including lung, liver, intestine and tongue were collected and submitted to the veterinary research and development center, Surin province for viral detection. The samples were then examined with real-time PCR for detecting U41 Major DNA binding protein (MDBP) gene and with conventional PCR for the presence of specific polymerase gene. We used tumor necrosis factor (TNF) gene as the internal control. In our real-time PCR, elephant endotheliotropic herpesvirus (EEHV) was recovered from lung, liver, and tongue whereas only tongue provided a positive result in the conventional PCR. All samples were positive with TNF gene detection. To our knowledge, this is the first report of EEHV detection in wild elephant in Thailand. EEHV surveillance in this wild population is strongly suggested. Linkage between EEHV in wild and domestic elephants should be further explored.

Keywords: elephant endotheliotropic herpes virus, PCR, Thailand, wild Asian elephant

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Authors: Kanchan Yadav, Ai-Chuan Chou, Rajesh Kumar Ulaganathan, Hua-De Gao, Hsien-Ming Lee, Chien-Yuan Pan, Yit-Tsong Chen

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Optogenetics is an innovative technology now widely adopted by researchers in different fields of the biological sciences. However, due to the weak tissue penetration capability of the short wavelengths used to activate light-sensitive proteins, an invasive light guide has been used in animal studies for photoexcitation of target tissues. Upconverting nanoparticles (UCNPs), which transform near-infrared (NIR) light to short-wavelength emissions, can help address this issue. To improve optogenetic performance, we enhance the target selectivity for optogenetic controls by specifically conjugating the UCNPs with light-sensitive proteins at a molecular level, which shortens the distance as well as enhances the efficiency of energy transfer. We tagged V5 and Lumio epitopes to the extracellular N-terminal of channelrhodopsin-2 with an mCherry conjugated at the intracellular C-terminal (VL-ChR2m) and then bound NeutrAvidin-functionalized UCNPs (NAv-UCNPs) to the VL-ChR2m via a biotinylated antibody against V5 (bV5-Ab). We observed an apparent energy transfer from the excited UCNP (donor) to the bound VL-ChR2m (receptor) by measuring emission-intensity changes at the donor-receptor complex. The successful patch-clamp electrophysiological test and an intracellular Ca2+ elevation observed in the designed UCNP-ChR2 system under optogenetic manipulation confirmed the practical employment of UCNP-assisted NIR-optogenetic functionality. This work represents a significant step toward improving therapeutic optogenetics.

Keywords: Channelrhodopsin-2, near infrared, optogenetics, upconverting nanoparticles

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Authors: Pejman Taghibeikzadehbadr

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Muscle contraction stimulates a transient change of myogenic factors, partly related to the mode of contractions. Here, we assessed the response of Insulin-like growth factor 1Ea (IGF-1Ea), Insulin-like growth factor 1Eb (IGF-1Eb), Insulin-like growth factor 1Ec (IGF-1Ec), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α-1), Peroxisome proliferator-activated receptor gamma coactivator 4-alpha (PGC1α-4), and myostatin to the eccentric Vs the concentric contraction in human skeletal muscle. Ten healthy males were performed an acute eccentric and concentric exercise bout (n = 5 per group). For each contraction type, participants performed 12 sets of 10 repetitions knee extension by the dominant leg. Baseline and post-exercise muscle biopsy were taken 4 weeks before and immediately after experimental sessions from Vastus Lateralis muscle. Genes expression was measured by real-time PCR technique. There was a significant increase in PGC1α-1, PGC1α-4, IGF-1Ea and, IGF-1Eb mRNA after concentric contraction (p ≤ 0.05), while the PGC1α-4 and IGF-1Ec significantly increased after eccentric contraction (p ≤ 0.05). It is intriguing to highlight that; no significant differences between groups were evident for changes in any variables following exercise bouts (p ≥ 0.05). Our results found that concentric and eccentric contractions presented different responses in PGC1α-1, IGF-1Ea, IGF-1Eb, and IGF-1Ec mRNA. However, a similar significant increase in mRNA content was observed in PGC1α-4. Further, no apparent differences could be found between the response of genes to eccentric and concentric contraction.

Keywords: eccentric contraction, concentric contraction, gene expression, PGC-1 alpha, IGF-1 Myostatin

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Authors: Sourabh Jain, Vikas Jain, Dharmendar Kumar

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The present study investigated the antidiabetic potential of Cedrus deodara heart wood aqueous extract. Aqueous extract of Cedrus deodara was found to reduce blood sugar level in alloxan induced diabetic rats. Reduction in blood sugar could be seen from 5th day after continuous administration of the extract and on 21st day sugar levels were found to be reduced by 40.20%. Oxidative stress produced by alloxan was found to be significantly lowered by the administration of Cedrus deodara aqueous extract (500 mg/kg). This was evident from a significant decrease in lipid per oxidation level in liver induced by alloxan. The level of Glutathione, Catalase, Superoxide dismutase and Glutathione-S-Transferase in liver, kidney and pancreas tissue were found to be increased significantly after drug administration. The results obtained in the present study suggest that the Cedrus deodara aqueous extract effectively and significantly reduced the oxidative stress induced by alloxan and produced a reduction in blood sugar level.

Keywords: Cedrus deodara, heartwood, antioxidant, anti-diabetic, anti-inflammatory

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Authors: Boris Bajer, Andrea Havranova, Miroslav Vlcek, Richard Imrich, Adela Penesova

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Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, and also prevent cardiovascular diseases, as it showed many studies (the Finnish Diabetes Prevention Study, Diabetes Prevention Program (DPP), . the China Da Qing Diabetes Prevention Study, etc.) Therefore the aim of our study was to compare the effect of intensified lifestyle intervention on cardiometabolic parameters. Methods: It is an ongoing randomized interventional clinical study (NCT02325804) focused on the reduction of body weight/fat. Intervention: hypocaloric diet (30% restriction of calories) and physical activity 150 minutes/week. Before and after 8 weeks of intervention all patients underwent complete medical examination (measurement of physical fitness, resting metabolic rate (RMR), body composition analysis, oral glucose tolerance test, parameters of lipid metabolism, and other cardiometabolic risk factors. Results: So far 39 patients finished the intervention. The average reduction of body weight was 6,8 + 4,9 kg (0-15 kg; p=0,0006), accompanied with significant reduction of body fat percentage (p ≤ 0,0001), amount of fat mass (p=0,03), waist circumference (p=0.02). Amount of lean mass and RMR remained unchanged. Heart rate (p=0,02), systolic and diastolic blood pressure was reduced (p=0,01 p=0,02 resp.) as well as insulin sensitivity was improved. Lipid parameters also changed - cholesterol, LDL decreased (p=0,05, p=0,04 resp.), while triglycerides showed tendency to decrease (p=0,055). Liver function improved, alanine aminotrasnferase (ALT) were reduced (p=0,01). Physical fitness significantly improved (as measure VO2 max (p=0,02). Conclusion: Results of our study are in line with previous results about the beneficial effect of intensive lifestyle changes on the reduction of cardiometabolic risk factors and improvement of liver function. Supported by grants APVV 15-0228; VEGA 2/0161/16

Keywords: obesity, weight loss, diet lipids, blood pressure, liver enzymes

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