Circadian rhythms govern a remarkable variety of metabolic and physiological functions. Accumulating epidemiological and genetic evidence indicates that the disruption of circadian rhythms might be directly linked to cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with regulators of the cell cycle, and alterations in clock function could lead to aberrant cellular proliferation. In addition, connections between the circadian clock and cellular metabolism have been identified that are regulated by chromatin remodelling. This suggests that abnormal metabolism in cancer could also be a consequence of a disrupted circadian clock. Therefore, a comprehensive understanding of the molecular links that connect the circadian clock to the cell cycle and metabolism could provide therapeutic benefit against certain human neoplasias.
Nutrition counseling and dietary intervention are essential to obesity management because weight reduction is the consequence of negative energy balance. The first step of the nutrition counseling in patients with obesity is thorough evaluation of the nutritional status. During the nutritional evaluation, amount of energy consumption, dietary habits, and medical and socioeconomic factors influencing diets should be evaluated. Diet interventions including low calorie diet, low fat diet, low carbohydrate diet, and high protein diet are all effective in weight reduction as long as decrease in energy consumption is accompanied. Amount of energy restriction and choice of diet interventions should be individualized based the medical condition and characteristics of each patient.
Either the fasting during natural molting or the starvation in induced molting would be a severe metabolic stress to laying hens. The metabolic stress during starvation and subsequent refeeding syndrome could lead to unbalance of mineral homeostasis, including $Mg^{2+}$, $K^+$ and P required by ATP synthesis. Since $Mg^{2+}$ is a fundamental ion for normal metabolic processes and stress may not only increase in demands of $Mg^{2+}$ but also produce consequence of $Mg^{2+}$ deficiency, we investigated the changes of blood ionized and total ions related to starvation during molting in laying hens. We founded the significant decrease in blood $Mg^{2+}$ and $K^+$ accompanied by the changes of biochemical parameters relating to increased metabolic stress after molting. These results suggested that appropriate $Mg^{2+}$ and $K^+$ supplements to laying hens could have beneficial effects during molting and subsequent refeeding that could produce a severe hypomagnesemia and hypokalcemia.
Diabetes mellitus(DM) is a metabolic syndrome caused by deficiency of insulin secretion and a consequence of insulin resistance. Poor glycemic control is a common finding in children with Type 1 DM(T1DM). Approximately 60% of the young patients with T1DM develop abnormalities in the eyes and 15-20% in the kidney. Diabetic nephropathy (DN) is a serious metabolic complication of T1DM that leads to renal failure. Some clinical studies report that the duration of prepubertal diabetes may contribute less to the development of microvascular complications than pubertal and postpubertal duration. There have been few cases of DN in prepubertal patients with T1DM in Korea. Thus we report a case of a 12-year-old female with T1DM who had poor glycemic control and was diagnosed as DN in a prepubertal period. It was proven by renal biopsy after microscopic hematuria and proteinuria were detected through the mass school urinary screening program.
Budgets for water, nitrogen, and chemical oxygen demand (COD) were determined in two 0.012 ha earthy-bottom ponds stocked with Israeli strain common carp at an initial stocking density of $20\;fish/m^3$. Total ammonia nitrogen (TAN) concentrations increased continuously but later decreased in pond A as a consequence of high nitrification. COD concentrations increased during the experimental period due to the accumulation of feed input. Nutrient budgets showed that feed represented $94-95\%$ of nitrogen input and about 99% of organic matter input. Fish harvest accounted for $40\%$ of nitrogen and organic matter input. Seepage and water exchange removed $15-17\%$ of nitrogen input but only $1-2\%$ of organic matter. Draining of the ponds removed $20-26\%$ of input nitrogen, mostly in inorganic forms, but removed only minus organic matter. Fish and water column respiration accounted for $39\%$ of organic matter input, and benthic respiration accounted for $7-12\%$ of organic matter input. No significant change of nitrogen and organic matter in both pond bottoms were found during the three-month growth period. The unrecovered input nitrogen, about $6.3-13\%$, was lost through denitrification and ammonia volatilization. On a dry matter basis, fish growth removed $31\%$ of total feed input and left $69\%$ as metabolic wastes.
Sun, Je Young;Kim, Jong Woo;Yim, Sung-Vin;Oh, Miae;Kang, Won Sub
Korean Journal of Biological Psychiatry
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v.29
no.1
/
pp.9-14
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2022
Objectives Sleep is fundamental to maintaining homeostatic control and has behavioral and psychological effects on humans. To better understand the function and pathophysiology of sleep, specific gene expressions in reference to sleep deprivation have been studied. In this study, we investigated the gene expression of peripheral blood mononuclear cells after sleep deprivation to better understand the functional consequence of sleep. Methods In eight healthy men, 24 h sleep deprivation was induced. Blood was sampled at 14:00, before and after sleep deprivation. mRNA was isolated and analyzed via microarrays. cDNAs before and after sleep deprivation were coupled to Cy3 or Cy5, respectively, and normalized cDNAs were selected with a ratio greater than two as a significant gene. Results are expressed as mean. Results Among 41174 transcripts, 38852 genes were selected as reliable, and only a small minority (< 1%) of the genes were up-or down-regulated. Total six and eleven genes were selected as significant upregulated and downregulated genes, respectively. Protein tyrosine phosphatase receptor type O was most upregulated (6.9-fold), and low-density lipoprotein receptor-related protein 5-like protein showed the most substantial inhibition (0.06-fold). Conclusions This study showed significant associations between sleep deprivation and the immune system. Acute sleep deprivation affects pathways in proinflammatory cytokines as well as metabolic pathways of glutamate and purine, neurotransmitters related to sleep and wake cycle.
Journal of The Korean Society of Inherited Metabolic disease
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v.23
no.2
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pp.39-44
/
2023
Hereditary tyrosinemia type 1 (HT-1) is a metabolic disorder caused by biallelic pathogenic variants in the fumarylacetoacetate hydrolase (FAH) gene, which impairs the function of the FAH enzyme, resulting in the accumulation of tyrosine's toxic metabolites in hepatocytes and renal tubular cells. As a consequence, individuals with HT-1 exhibit symptomatic manifestations. Rapid diagnosis and treatment of HT-1 can prevent short-term death and long-term complications. A 15-day-old boy presented to the outpatient department with elevated levels of tyrosine on his newborn screening tests conducted at the age of 3 and 10 days, respectively. Further blood tests revealed increased levels of alpha-fetoprotein and amino acids including tyrosine and threonine. Urine organic acid tests indicated a significant elevation in tyrosine metabolites, as well as the presence of succinylacetone (SA), which led to the diagnosis of HT-1. Two pathogenic and likely pathogenic variants of FAH compatible with HT-1 were also detected. He began a tyrosine-restricted diet at one month old and received nitisinone (NTBC) at two months old. With continued treatment, the patient's initially elevated AFP level, detection of SA in the urine, and mild hepatomegaly showed improvement. During four years and seven months of treatment, there were no exceptional complications apart from an increase in tyrosine levels and a delay in speech. We report a case of tyrosinemia type 1 detected through newborn screening, treated with dietary restriction and NTBC, with a good prognosis.
Ryu, Kyungguk;Seo, Go Hun;Kim, Yoon-Myung;Choi, Jin-Ho;Yoo, Han-Wook;Lee, Beom Hee
Journal of The Korean Society of Inherited Metabolic disease
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v.17
no.1
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pp.24-30
/
2017
Gorham-Stout disease is a rare disorder characterized by lymphovascular proliferation and destruction of osseous matrix. The etiology of this condition remains poorly understood. Chylothorax as a consequence of lymphatic leakage in thoracic cage may cause a severe life-threatening complication, accompanying respiratory difficulty. Currently, there is no standard management for this extremely rare condition. Here we describe a patient affected by Gorham-Stout disease successfully managed by the combined treatment of mTOR inhibitor and beta-blocker. A previously healthy 11-year-old female developed dyspnea and chest pain with a massive pleural effusion. The ligation of right thoracic duct and bilateral pleurodesis temporarily decreased her pleural effusion, which was aggravated repetitively and required frequent admission and tube thoracotomies. Along with bilateral pleural adhesiolysis with thoracotomy, the combined treatment of oral beta-blocker and mTOR inhibitor was commenced. After 1 month of oral medication, her pleural effusion was not increased and she was free of respiratory difficulty on room air without chest tubes. Over eleven months of treatment, no serious adverse reaction was noted and her condition has been stable with no further admission required.
Proceedings of the Korean Society for Applied Microbiology Conference
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2002.10a
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pp.18-25
/
2002
The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.
Reis de Souza, T.C.;Aumaitre, A.;Mourot, J.;Peiniau, J.
Asian-Australasian Journal of Animal Sciences
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v.13
no.4
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pp.497-505
/
2000
Thirty piglets weaned at 24.5 d of age ($6.9{\pm}0.5kg$) randomly alloted to 3 treatments were used to investigate the effect of dietary tallow on average performance, digestibility of nutrients, metabolic utilization of energy and body composition at 25 kg. Weaned piglets respond to increasing levels of dietary tallow from 0 to 4% and 8% by digestive and metabolic adaptation. Apparent fecal digestibility of fat (AFDf) was highly correlated with the level of dietary tallow (X as % of fat extracted after HCl hydrolysis) by the following curvilinear equation of regression: $AFDf=33.8+6.9X-0.3X^2$. Feed intake expressed as DE was only significantly increased at the higher inclusion level of tallow. But neither average daily gain, nor feed conversion was affected by the addition of fat. On the other hand, body composition at 25 kg was equally affected, by both levels of supplementary fat; dry matter and energy content in the body were significantly higher (p<0.01) in piglets receiving tallow. As a consequence, the energy cost of the live weight gain was also increased from 23 to 24.7 MJ DE/kg (p<0.02) and the efficiency of energy deposition was decreased from 3.2 to 2.8 MJ DE/MJ deposited energy (p<0.01) in the presence of dietary tallow. An increase in the level of fat stimulated the activity of pancreatic lipase up to a constant value of $22{\pm}1.4IU/mg$ protein but conversely depressed the activity of amylase from 300 to 100 IU/mg of protein. The activity of liver acetyl CoA carboxylase and malic enzyme in the perirenal fat were low lind not affected by dietary fat; the activity of glucose-6-phosphate dehydrogenase was high. Opposite to that, the activity of acetyl CoA carboxylase and malic enzyme in the perirenal and backfat were higher than in the liver and both were significantly reduced by the inclusion of fat in the diet. A direct deposition of dietary fat has been demonstrated by increasing the energy and lipid content of the empty body weight gain between 7 and 25 kg of live weight, and decreasing the efficiency of digestible energy utilization.
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