Loss Of Glycogen Research Articles

Laporan Pendidikan Kesehatan Kebutuhan Nutrisi Untuk Proses Penyembuhan Luka Post OP di Bangsal Mawar RSUD Dr Soehadi Prijonegoro Sragen

: Background: Nutrients are obtained from food and fluids which are then assimilated by the body. Nutrition itself is one of the factors that can support the wound healing process, there are things that are no less important that must be considered as well, namely the nutrients from the food we eat during the wound healing process. Objective: The purpose of postoperative diet is to strive for the patient's nutritional status to return to normal immediately to accelerate the healing process and increase the patient's immune system, by providing basic needs (fluids, energy, protein), replacing the loss of protein, glycogen, iron, and other nutrients, correcting electrolyte and fluid imbalances, preventing and stopping bleeding. Methods: The media used in health education activities is leaflets. Through leaflets we hope that the delivery of material can be understood by participants and can be delivered well.Results: The results of observations from this health education activity, that the majority of participants are active in asking questions and answering questions given by the health education team and can explain the essence of the material that has been delivered by the speaker Conclusion: Of the 20 patient families who attended 15 people had understood the fulfillment of nutritional needs for the correct post op wound healing process.

Citrus p-Synephrine Improves Energy Homeostasis by Regulating Amino Acid Metabolism in HFD-Induced Mice.

p-Synephrine is a common alkaloid widely distributed in citrus fruits. However, the effects of p-synephrine on the metabolic profiles of individuals with energy abnormalities are still unclear. In the study, we investigated the effect of p-synephrine on energy homeostasis and metabolic profiles using a high fat diet (HFD)-induced mouse model. We found that p-synephrine inhibited the gain in body weight, liver weight and white adipose tissues weight induced by HFD. p-Synephrine supplementation also reduced levels of serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) but not to a statistically significant degree. Histological analysis showed that HFD induced excessive lipid accumulation and glycogen loss in the liver and adipocyte enlargement in perirenal fat tissue, while p-synephrine supplementation reversed the changes induced by HFD. Moreover, HFD feeding significantly increased mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and reduced the mRNA expression level of interleukin-10 (IL-10) compared to the control group, while p-synephrine supplementation significantly reversed these HFD-induced changes. Liver and serum metabolomic analysis showed that p-synephrine supplementation significantly altered small molecule metabolites in liver and serum in HFD mice and that the changes were closely associated with improvement of energy homeostasis. Notably, amino acid metabolism pathways, both in liver and serum samples, were significantly enriched. Our study suggests that p-synephrine improves energy homeostasis probably by regulating amino acid metabolism in HFD mice, which provides a novel insight into the action mechanism of p-synephrine modulating energy homeostasis.

Hydraulic retention time optimization achieved unexpectedly high nitrogen removal rate in pilot-scale anaerobic/aerobic/anoxic system for low-strength municipal wastewater treatment

Applications of post-denitrification processes are subjected to low reaction rates caused by a lack of carbon resources. To offer a solution for reaction rate promotion, this research found a pilot-scale anaerobic/aerobic/anoxic bioreactor treating 55–120 m3/d low-strength municipal wastewater for 273 days. A short hydraulic retention time (HRT, 5–6 h) and a high nitrogen removal rate (63.2 ± 9.3 g-N/m3·d) were achieved using HRT optimization. The effluent total nitrogen concentration was maintained at 5.8 ± 1.4 mg/L while operating at a high nitrogen loading rate of 86.2 ± 12.8 g-N/m3·d. The short aeration (1.25–1.5 h) minimized the Glycogen loss. The endogenous denitrification rate increased to above 1.0 mg/(g-VSS·h). The functional genus Ca. Competibacter enriched to 2.3 %, guaranteeing the efficient post-denitrification process. Dechloromonas rose to 1.1 %, aiding in the synchronous phosphorus removal. These findings offered fresh insights into AOA processes to achieve energy/cost-saving wastewater treatment.

Impaired cardiac glycolysis and glycogen depletion are linked to poor myocardial outcomes in juvenile male swine with metabolic syndrome and ischemia.

Obesity continues to rise in the juveniles and obese children are more likely to develop metabolic syndrome (MetS) and related cardiovascular disease. Unfortunately, effective prevention and long-term treatment options remain limited. We determined the juvenile cardiac response to MetS in a swine model. Juvenile male swine were fed either an obesogenic diet, to induce MetS, or a lean diet, as a control (LD). Myocardial ischemia was induced with surgically placed ameroid constrictor on the left circumflex artery. Physiological data were recorded and at 22 weeks of age the animals underwent a terminal harvest procedure and myocardial tissue was extracted for total metabolic and proteomic LC/MS-MS, RNA-seq analysis, and data underwent nonnegative matrix factorization for metabolic signatures. Significantly altered in MetS versus. LD were the glycolysis-related metabolites and enzymes. In MetS compared with LD Glycogen synthase 1 (GYS1)-glycogen phosphorylases (PYGM/PYGL) expression disbalance resulted in a loss of myocardial glycogen. Our findings are consistent with the concept that transcriptionally driven myocardial changes in glycogen and glucose metabolism-related enzymes lead to a deficiency of their metabolite products in MetS. This abnormal energy metabolism provides insight into the pathogenesis of the juvenile heart in MetS. This study reveals that MetS and ischemia diminishes ATP availability in the myocardium via altering the glucose-G6P-pyruvate axis at the level of metabolites and gene expression of related enzymes. The observed severe glycogen depletion in MetS coincides with disbalance in expression of GYS1 and both PYGM and PYGL. This altered energy substrate metabolism is a potential target of pharmacological agents for improving juvenile myocardial function in MetS and ischemia.

Marantodes pumilum (Kacip Fatimah) Aqueous Extract Enhances Osteoblast and Suppresses Osteoclast Activities in Cancellous Bone of a Rat Model of Postmenopause.

Evidence pointed towards the benefits of Marantodes pumilum in treating osteoporosis after menopause; however, the detailed mechanisms still have not been explored. Therefore, this study aims to identify the molecular mechanisms underlying M. pumilum's bone-protective effect via the involvement of RANK/RANKL/OPG and Wnt/β-catenin signaling pathways. Ovariectomized adult female rats were given M. pumilum leaf aqueous extract (MPLA) (50 and 100mg/kg/day) and estrogen (positive control) orally for twenty-eight consecutive days. Following the treatment, rats were sacrificed, and femur bones were harvested. Blood was withdrawn for analysis of serum Ca2+, PO43-, and bone alkaline phosphatase (BALP) levels. The bone microarchitectural changes were observed by H&E and PAS staining and distribution and expression of RANK/RANKL/OPG and Wnt3a/β-catenin and its downstream proteins were determined by immunohistochemistry, immunofluorescence, Western blot, and real-time PCR. MPLA treatment increased serum Ca2+ and PO43- levels and reduced serum BALP levels (p < 0.05). Besides, deterioration in cancellous bone microarchitecture and the loss of bone glycogen and collagen content were mitigated by MPLA treatment. Levels of RANKL, Traf6, and NF-kB but not RANK in bone were decreased; however, levels of OPG, Wnt3a, LRP-5, Frizzled, Dvl, β-catenin, RUNX, and Bmp-2 in bone were increased following treatment with MPLA. In conclusion,MPLA helps to protect against bone deterioration in estrogen deficiency state and thus, this herb could potentially be used to ameliorate osteoporosis in women after menopause.

Does apocynin increase liver regeneration in the partial hepatectomy model?

Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Effects of Salinity and Dissolved Oxygen Concentration on the Tail-Flip Speed and Physiologic Response of Whiteleg Shrimp, Litopenaeus vannamei

The swimming ability of shrimp is important for their survival and growth, which directly affects their avoidance of enemies and uncomfortable environment, search and capture of food, reproductive behavior, and distribution. The knowledge concerning the swimming ability of shrimp can be widely used in the conservation of fishery resources, improving capture efficiency and stock enhancement. As one of the edible marine organisms, Litopenaeus vannamei is a traditional fishery resource and an important economic aquaculture species in China. Dissolved oxygen (DO) concentration and salinity are considered to play crucial roles in the swimming ability of L. vannamei. The tail-flip speed (Stf) of whiteleg shrimp L. vannamei (79.90 ± 0.41 mm, 5.76 ± 0.10 g) that were exposed to various salinities (20‰, 25‰, 30‰, 35‰, and 40‰) and DO concentrations (1.9, 3.8, 6.8, and 13.6 mg/L) was determined under laboratory conditions. Metabolite concentrations in the hemolymph, hepatopancreas, and abdominal muscles were measured before and after tail-flip fatigue to evaluate the physiologic effects of fatigue in L. vannamei. The results showed that salinity and DO significantly affected the Stf of L. vannamei. The Stf increased and subsequently decreased with the increase in salinity from 20‰ to 40‰. The relationship between Stf and salinity (s, ‰) can be expressed by the quadratic model as Stf = −0.2386s2 + 15.528s − 145.12, R2 = 0.9693. The optimum salinity and corresponding maximum Stf were 32.54‰ and 107.52 cm/s, respectively. The Stf increased as the DO concentration increased from 1.9 mg/L to 13.6 mg/L. The relationship between Stf and DO (mg/L) can be expressed by the power model as Stf = 75.621 DO0.1753, R2 = 0.9981. The different salinities and DO concentrations directly affected the physiology of the shrimp, inducing changes in hepatopancreas total protein, plasma total protein, abdominal muscle lactate, plasma lactate, plasma glucose, hepatopancreas glycogen, and abdominal muscle glycogen concentration. Fatigue from tail-flip led to severe loss of hepatopancreas glycogen under 20‰ salinity and plasma glucose under 25‰, 30‰, and 35‰ salinity. The triglyceride and lactate in the plasma concentration increased significantly in a range of salinities. In the DO concentration experiment, fatigue from tail-flip led to a severe loss of plasma glucose under 1.9 mg/L and 3.8 mg/L DO concentrations. The plasma lactate concentration increased significantly in all DO groups. The results suggested that the inappropriate salinity and DO significantly limited the tail-flip speed of shrimp, which was due to the accumulation of metabolites. The proper salinity and DO accelerated the elimination of metabolites, reduced the energy consumption of shrimp, and thus, improved the exercise ability of shrimp. This conclusion is of particular value in evaluating the swimming ability of shrimp and understanding its ecological processes to improve capture and rearing techniques.

The effects of experimental temperature increase on gametogenesis and heat stress parameters in oysters: Comparison of a temperate-introduced species (Crassostrea gigas) and a native tropical species (Crassostrea corteziensis)

The effect of thermal stress during reproduction was experimentally evaluated in the oyster Crassostrea gigas, a temperate species, and in the tropical oyster Crassostrea corteziensis. The temperature was gradually increased (1 °C day−1) from 20 °C to 34 °C for two weeks. As expected, C. gigas was the species most affected by heat stress, with the highest mortality rate (P < 0.05) starting at 28 °C, while mortality in C. corteziensis was significant only at 34 °C. The reproductive effort at higher temperatures was reflected in C. gigas as the highest index of mature oocytes and the largest rate of atresic and degenerated oocytes. C. corteziensis showed significant increases in the proliferation of early-developing oocytes at maximum temperatures. Lipid peroxidation and lipofuscin accumulation significantly increased in both species at maximum temperatures, with levels in C. gigas being 8-fold higher than in C. corteziensis. A significant loss of biomass and glycogen reserves stored in gonads was found in C. gigas at 34 °C. The mRNA signal of Hsp70 was detected in gonadic tissues from both oysters after thermal stress for in situ hybridization (ISH), with a temperature increase in both species; the cover area of Hsp70 was significantly higher in C. gigas during the experiment. Hemocyte infiltration significantly increased with increasing temperature in both oyster species, and apoptosis was strongly correlated with Hsp70 in both species (r = 0.93; P < 0.05). These results could explain the high tolerance that C. corteziensis has to thermal stress compared to C. gigas and could be used to adapt aquaculture strategies to the use of native species in subtropical climates to reduce summer mortality events.

Short term magnesium supplementation to reduce dark cutting in pasture finished beef cattle

This study assessed the capacity of magnesium supplementation to reduce muscle glycogen loss, ultimate pH and increase plasma magnesium in pasture fed slaughter cattle. Beef cattle (n = 1075) from 14 farms were supplemented with or without magnesium pellets for 7–14 days prior to slaughter. Magnesium was allocated at 9.83 g of elemental magnesium per head per day, while the control diet was balanced to be isoenergetic and isonitrogenous, but contained no added magnesium. Groups of cattle (n = 44) were slaughtered at the same processing plant over two consecutive seasons, from August – September 2016 to May – July 2017.Magnesium supplementation increased muscle glycogen (P < 0.01) in cattle supplied from 2 of 14 farms, and increased plasma magnesium in 4 of 14 farms (P < 0.01). Magnesium supplementation had no effect on overall incidence of ultimate pH between the magnesium and control supplementation groups. The benefits of short term magnesium supplementation prior to slaughter was inconsistent for protecting muscle glycogen.

Narrative review of glycogen storage disorder type III with a focus on neuromuscular, cardiac and therapeutic aspects.

Glycogen storage disorder type III (GSDIII) is a rare inborn error of metabolism due to loss of glycogen debranching enzyme activity, causing inability to fully mobilize glycogen stores and its consequent accumulation in various tissues, notably liver, cardiac and skeletal muscle. In the pediatric population, it classically presents as hepatomegaly with or without ketotic hypoglycemia and failure to thrive. In the adult population, it should also be considered in the differential diagnosis of left ventricular hypertrophy or hypertrophic cardiomyopathy, myopathy, exercise intolerance, as well as liver cirrhosis or fibrosis with subsequent liver failure. In this review article, we first present an overview of the biochemical and clinical aspects of GSDIII. We then focus on the recent findings regarding cardiac and neuromuscular impairment associated with the disease. We review new insights into the pathophysiology and clinical picture of this disorder, including symptomatology, imaging and electrophysiology. Finally, we discuss current and upcoming treatment strategies such as gene therapy aimed at the replacement of the malfunctioning enzyme to provide a stable and long-term therapeutic option for this debilitating disease.

Sex and death.

Sexual interactions negatively impact health and longevity in many species across the animal kingdom. C. elegans has been established as a good model to study how mating and intense sexual interactions influence longevity of the individuals. In this chapter, we review the most recent discoveries in this field. We first describe the phenotypes caused by intense mating, including shrinking, fat loss, and glycogen loss. We then describe three major mechanisms underlying mating-induced killing: germline activation, seminal fluid transfer, and male pheromone-mediated toxicity. Next, we summarize the current knowledge of genetic pathways involved in regulating mating-induced death, including DAF-9/DAF-12 steroid signaling, Insulin/IGF-1 signaling (IIS), and TOR signaling. Finally, we discuss the possible fitness benefits of mating-induced death. Throughout this review, we compare and contrast mating-induced death between the sexes and among different species in an effort to discuss this phenomenon and underlying mechanisms from the evolutionary perspective. Further investigation using mated C. elegans will improve our understanding of sexual antagonism, as well as the coordination between reproduction and somatic longevity in response to various external signals. Due to the evolutionary conservation in many aspects of mating-induced death, what we learn from a short-lived mated worm could provide new strategies to improve our own fitness and longevity.

Renal injury and hepatic effects from the methylimidazolium ionic liquid M8OI in mouse

The ionic liquid 1-octyl-3-methylimidazolium (M8OI) has been found in the environment and identified as a hazard for triggering the liver disease primary biliary cholangitis (PBC). Given limited toxicity data for M8OI and other structurally-related ionic liquids, target organs for M8OI toxicity were examined. Adult male C57Bl6 mice were acutely exposed to 0–10 mg/kg body weight M8OI via 2 intraperitoneal injections (time zero and 18 h) and effects examined at 24 h. At termination, tissue histopathology, serum and urinary endpoints were examined. No overt pathological changes were observed in the heart and brain. In contrast, focal and mild to multifocal and moderate degeneration with a general trend for an increase in severity with increased dose was observed in the kidney. These changes were accompanied by a dose-dependent increased expression of Kim1 in kidney tissue, marked elevations in urinary Kim1 protein and a dose-dependent increase in serum creatinine. Hepatic changes were limited to a significant dose-dependent loss of hepatic glycogen and a mild but significant increase in portal tract inflammatory recruitment and/or fibroblastic proliferation accompanied by a focal fibrotic change. Cultured mouse tissue slices reflected these in vivo effects in that dose-dependent injury was observed in kidney slices but not in the liver. Kidney slices accumulated higher levels of M8OI than liver slices (e.g. at 10 μM, greater than 4 fold) and liver slices where markedly more active in the metabolism of M8OI. These data indicate that the kidney is a target organ for the toxic effects of M8OI accompanied by mild cholangiopathic changes in the liver after intraperitoneal administration.

Abstract IA19: Role of autophagy in cancer metabolism

Abstract Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and enable survival in starvation. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect manifested by starvation intolerance and gradual loss of white adipose tissue, liver glycogen, and muscle mass. Cancer cells benefit from autophagy as deletion of essential autophagy genes impairs spontaneous tumor growth in autochthonous cancer models. Tumor cell autonomous autophagy is required to recycle macromolecules to sustain mitochondrial substrate supply and thereby energy and nucleotide pools essential for survival during nutrient limitation. In addition to promoting tumor cell survival, autophagy in the host also promotes tumorigenesis. Host-specific Atg7 or Atg5 deletion impairs growth of multiple different allografted tumors, by preventing the release of Arginase 1 from hepatocytes. Arginase 1 degrades circulating arginine that is essential for the growth of tumors, most of which are auxotrophic for arginine. Thus, autophagy sustains both tumor cell and host metabolism to enable tumor growth. In tumors with a high neoantigen load that can be recognized and killed by T cells, autophagy suppresses an antitumor T-cell response. Autophagy prevents tumor killing by T cells by suppressing production of interferon gamma in a T cell-dependent manner. Thus, autophagy promotes tumorigenesis by promoting intrinsic and extrinsic tumor metabolism and by suppressing the ability of the immune system to eliminate tumors. This suggests that autophagy inhibitors may be especially useful for cancer therapy when combined with immunotherapy. To better understand the toxicity of autophagy inhibition to normal tissues, we have examined the functional consequence of conditional Atg7 or Atg5 deletion in adult mice. Whereas Atg7 deletion causes neurodegeneration in 2-3 months, Atg5 deletion causes very specific loss of telocytes and stem cells in the ileum part of the intestine and rapid death due to a more abrupt loss of autophagy function. This indicates that there is a difference in the sensitivity of cell types and tissues to the loss of autophagy and that there are discrete functional dependencies on different ATGs. Citation Format: Eileen P. White. Role of autophagy in cancer metabolism [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA19.

Secondhand Smoke Induces Liver Steatosis through Deregulation of Genes Involved in Hepatic Lipid Metabolism.

We investigated the role of secondhand smoke (SHS) exposure, independently of diet, in the development of chronic liver disease. Standard diet-fed mice were exposed to SHS (5 h/day, 5 days/week for 4 months). Genome-wide gene expression analysis, together with molecular pathways and gene network analyses, and histological examination for lipid accumulation, inflammation, fibrosis, and glycogen deposition were performed on the liver of SHS-exposed mice and controls, upon termination of exposure and after one-month recovery in clean air. Aberrantly expressed transcripts were found in the liver of SHS-exposed mice both pre- and post-recovery in clean air (n = 473 vs. 222). The persistent deregulated transcripts (n = 210) predominantly affected genes and functional networks involved in lipid metabolism as well as in the regulation of the endoplasmic reticulum where manufacturing of lipids occurs. Significant hepatic fat accumulation (steatosis) was observed in the SHS-exposed mice, which progressively increased as the animals underwent recovery in clean air. Moderate increases in lobular inflammation infiltrates and collagen deposition as well as loss of glycogen were also detectable in the liver of SHS-exposed mice. A more pronounced phenotype, manifested as a disrupted cord-like architecture with foci of necrosis, apoptosis, inflammation, and macrovesicular steatosis, was observed in the liver of SHS-exposed mice post-recovery. The progressive accumulation of hepatic fat and other adverse histological changes in the SHS-exposed mice are highly consistent with the perturbation of key lipid genes and associated pathways in the corresponding animals. Our data support a role for SHS in the genesis and progression of metabolic liver disease through deregulation of genes and molecular pathways and functional networks involved in lipid homeostasis.

The stress-responsive geneGDPGP1/mcp-1regulates neuronal glycogen metabolism and survival

Maladaptive responses to stress might play a role in the sensitivity of neurons to stress. To identify novel cellular responses to stress, we performed transcriptional analysis in acutely stressed mouse neurons, followed by functional characterization in Caenorhabditis elegans. In both contexts, we found that the gene GDPGP1/mcp-1 is down-regulated by a variety of stresses. Functionally, the enzyme GDPGP1/mcp-1 protects against stress. Knockdown of GDPGP1 in mouse neurons leads to widespread neuronal cell death. Loss of mcp-1, the single homologue of GDPGP1 in C. elegans, leads to increased degeneration of GABA neurons as well as reduced survival of animals following environmental stress. Overexpression of mcp-1 in neurons enhances survival under hypoxia and protects against neurodegeneration in a tauopathy model. GDPGP1/mcp-1 regulates neuronal glycogen levels, indicating a key role for this metabolite in neuronal stress resistance. Together, our data indicate that down-regulation of GDPGP1/mcp-1 and consequent loss of neuronal glycogen is a maladaptive response that limits neuronal stress resistance and reduces survival.

Evaluating the Efficacy of Fish Proteins for the Amelioration of Extreme Exercise-induced Fatigue Leading to Death in Mice

Extreme exercise-induced fatigue leads to an altered metabolic state resulting in compromised central nervous system and muscle functions. Therefore, possible nutritional management of this metabolic state is of great interest, particularly in sports training and sports competitions. Herein, using a mouse model of extreme exercise-induced fatigue leading to death, we have evaluated the effects of fish protein hydrolysates on extreme exercise that led to a decrease in liver glycogen and an increase in blood lactic acid. The results show that treatments with fish protein hydrolysates resulted in increased swim time and decreased fatigue. These changes were associated with a decrease in glycogen loss and an accumulation of lactic acid.

Autophagy maintains tumour growth through circulating arginine.

Autophagy captures intracellular components and delivers them to lysosomes where they are degraded and recycled to sustain metabolism and to enable survival in starvation1–5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect manifested by starvation intolerance and gradual loss of white adipose tissue (WAT), liver glycogen, and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumors in autochthonous cancer models6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of Kras-driven cancers than tumor-specific autophagy deletion, suggesting a role for host autophagy in promoting tumor growth1,8. Here we show that host-specific Atg7 deletion impairs growth of multiple different allografted tumors, although not all tumor lines were sensitive to host autophagy status. Host autophagy loss was associated with reduction in circulating arginine and the sensitive tumor cells lines were arginine auxotrophs due to lack of expression of the enzyme argininosuccinate synthase (ASS1). Serum proteomic analysis identified the arginine-degrading enzyme Arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated degradation of serum arginine to ornithine. ARG1 is predominantly expressed in liver and can be released from hepatocytes into the circulation. Liver-specific Atg7 deletion produced circulating ARG1, and reduced serum arginine and tumor growth. Deletion of Atg5 in the host similarly regulated circulating arginine and tumorigenesis, demonstrating specificity to autophagy function. Dietary supplementation of Atg7-deficient hosts with arginine partially restored circulating arginine levels and tumor growth. Thus, defective host autophagy leads to release of ARG1 from liver and degradation of circulating arginine essential for tumor growth, identifying a novel metabolic vulnerability of cancer.

Protective effect of dexpanthenol against cisplatin-induced hepatotoxicity.

The aim of the present study was to investigate the protective effect of dexpanthenol (Dexp) against cisplatin (Cis)-induced hepatotoxicity. Thirty-two Sprague Dawley rats were divided into four groups: Control group (n=8), Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp), Cis group (n=8, 7 mg/kg/ip/single dose Cis) and Cis+Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp +7 mg/kg/ip/single dose Cis). MDA, CAT, GSH, GSH-Px, TOS, TAS, OSI, Total Nitrit, IL-1β, IL-6 and TNF-α levels were analyzed in liver tissue samples. After paraffinization of liver tissue samples, histopathological (congestion, loss of glycogen, number of Kupffer cells) and immunohistochemical (caspase-3 expression) parameters were assessed on the paraffinized liver sections. GSH, TAS, TOS, OSI, Tot Nit, L-Arginine, ADMA and SDMA levels were measured in the serum samples. Statistically significant differences were found between the groups in terms of all liver tissue biochemical parameters, with the exception of IL-1β and TNF-α levels. GSH, CAT, GSH-Px, TAS and Tot Nit levels were significantly higher in the Cis+Dexp group compared to the Cis group, whereas MDA, TOS, OSI and IL-6 levels were higher in the Cis group. Similarly, serum GSH, TAS, Tot Nit levels were higher in the Cis+Dexp group whereas TOS, L-Arginine, ADMA and SDMA levels were higher in Cis group. There were statistically significant differences between Control and Cis groups in terms of congestion increase, increase of glycogen loss, increase of Kupffer cell number and increase of caspase-3 expression (P<0.001). There was a statistically significant difference between the Cis and the Cis+Dexp groups in terms of histopathologic parameters, with the exception of congestion (P<0.001). To conclude, histopathological, immunohistochemical, and biochemical results of this study demonstrated that Dexp has a protective effect against Cis-induced hepatotoxicity.

Iodine in excess in the alterations of carbohydrate and lipid metabolic pattern as well as histomorphometric changes in associated organs.

Background Iodine is a nonpareil constituent of thyroid hormones (THs) and a prime regulator of thyroid gland functioning. Although essential at recommended levels for the prevention of iodine deficiency disorders (IDDs), exposure to excess iodine reportedly causes hypothyroidism, hyperthyroidism, and several other emerging deleterious impacts. The objective of the present study is to explore the influence of excess iodide exposure on carbohydrate and lipid metabolism along with the histoarchitecture of certain associated organs such as the pancreas, liver, kidney, and skeletal and cardiac muscle because information on those aspects was found to be scanty. Methods Twelve rats were taken, six were fed with iodine through gavage at a dose of 3.5 mg potassium iodide (KI)/100-g body weight, which corresponded to 500 times of the physiological daily dosage of iodide for a period of 60 days, while the other six formed the control group. Results KI-treated rats presented high body weight and urinary iodine with low TH levels, suggesting a primary thyroid dysfunction. There was an increase in blood glucose, cholesterol, triglycerides, low density lipoprotein (LDL), and very low density lipoprotein (VLDL), while high density lipoprotein (HDL) levels decreased. Tissue glycogen content in the liver and skeletal muscle was decreased and was increased in the heart and kidney. Histological sections of the pancreas showed a complete disruption with hardly recognizable histoarchistructure. Treated liver sections displayed the broadened central vein with degenerated hepatocytes, while skeletal muscle sections showed dissolution of muscle fibre cells linked with loss of glycogen from these organs. Histological changes in the heart include features similar to those of a fatty heart with cardiac muscles mutilation, while that of the kidney shows an increase in glomerular tuft size and Bowman's space expansion with general deterioration. Conclusions It may thus be concluded that excess iodine exposure for a long duration causes the development of a biochemical state of hypothyroidism. The developed hypothyroidism was found responsible for the hyperglycaemic and hypercholestromic status evident by high blood glucose and cholesterol levels and the depletion of glycogen at its storage sites in the liver and skeletal muscle but the extra deposition in the cardiac muscle and kidney; histomicrophotographs showed severe destruction of the pancreatic structure. All these alterations are conducive for the pathogenesis of cardiovascular and kidney diseases.

Protective Effect of Casperome®, an Orally Bioavailable Frankincense Extract, on Lipopolysaccharide- Induced Systemic Inflammation in Mice.

Introduction: Despite recent advances in critical care, sepsis remains a crucial cause of morbidity and mortality in intensive care units. Therefore, the identification of new therapeutic strategies is of great importance. Since ancient times, frankincense is used in traditional medicine for the treatment of chronic inflammatory disorders such as rheumatoid arthritis. Thus, the present study intends to evaluate if Casperome® (Casp), an orally bioavailable soy lecithin-based formulation of standardized frankincense extract, is able to ameliorate systemic effects and organ damages induced by severe systemic inflammation using a murine model of sepsis, i.e., intraperitoneal administration of lipopolysaccharides (LPS).Methods: Male 60-day-old mice were assigned to six treatment groups: (1) control, (2) LPS, (3) soy lecithin (blank lecithin without frankincense extract), (4) Casp, (5) soy lecithin plus LPS, or (6) Casp plus LPS. Soy lecithin and Casp were given 3 h prior to LPS treatment; 24 h after LPS administration, animals were sacrificed and health status and serum cytokine levels were evaluated. Additionally, parameters representing liver damage or liver function and indicating oxidative stress in different organs were determined. Furthermore, markers for apoptosis and immune cell redistribution were assessed by immunohistochemistry in liver and spleen.Results: LPS treatment caused a decrease in body temperature, blood glucose levels, liver glycogen content, and biotransformation capacity along with an increase in serum cytokine levels and oxidative stress in various organs. Additionally, apoptotic processes were increased in spleen besides a pronounced immune cell infiltration in both liver and spleen. Pretreatment with Casp significantly improved health status, blood glucose values, and body temperature of the animals, while serum levels of pro-inflammatory cytokines and oxidative stress in all organs tested were significantly diminished. Finally, apoptotic processes in spleen, liver glycogen loss, and immune cell infiltration in liver and spleen were distinctly reduced. Casp also appears to induce various cytochromeP450 isoforms, thus causing re-establishment of liver biotransformation capacity in LPS-treated mice.Conclusion: Casp displayed anti-inflammatory, anti-oxidative, and hepatoprotective effects. Thus, orally bioavailable frankincense extracts may serve as a new supportive treatment option in acute systemic inflammation and accompanied liver dysfunction.