Dietary supplementation with inosine-5′-monophosphate improves the functional, energetic, and antioxidant status of liver and muscle growth in pigs

Inosine 5′-monophosphate (5′-IMP) is an essential nucleotide for de novo nucleotide biosynthesis and metabolism of energy, proteins, and antioxidants. Nucleotides are conditionally essential, as they cannot be produced sufficiently rapidly to meet the needs of the body in situations of oxidative stress or rapid muscle growth. A deficient intake of nucleotides can result in decreased ATP and GTP synthesis and impaired metabolism. We demonstrated that supplementation of finishing pig diets with 5′-IMP reduces the relative weight of the liver, and increases oxygen consumption during mitochondrial respiration without changing the ADP/O ratio, indicating an increase in the respiratory efficiency of liver mitochondria. We also observed a reduction in liver lipid peroxidation and an increase in muscle creatine. Moreover, 5′IMP supplementation increases slaughter weight, lean meat yield, sarcomere length, and backfat thickness in finishing barrows, demonstrating influence on protein metabolism. We suggest that 5′-IMP supplementation increase the mitochondrial respiratory capacity when the liver metabolic activity is stimulated, enhances antioxidant defense, and promotes muscle growth in finishing barrows.

The epidemiology and importance of vitamin B12 screening in diabetic patients

Peripheral neuropathy is a commonly reported chronic adverse event among diabetes mellitus (DM) patients secondary to poor glycemic control. It might also result secondary to deficiency of vitamin B12, reportedly common among diabetic patients. Deficiency of vitamin B12 might result from prolonged metformin administration in patients with type II DM (T2DM). It might also result from reduced absorption and impaired metabolism-related events in type I DM (T1DM) patients. This occurs secondary to the presence of associated autoimmune disorders. Vitamin B12 deficiency is a commonly encountered condition among diabetic patients, both T1DM and T2DM, with variable etiologies. Our current study discussed the epidemiology and importance of screening of vitamin B12 in these patients. However, our findings show that screening is not commonly practiced in different settings. Therefore, awareness is low about the benefits and complications of this practice. Therefore, further research is encouraged to alleviate the quality of care in diabetic patients. Screening for vitamin B12 deficiency might intervene against any potential complications, including irreversible, painful, and potentially disabling nerve injury. Accordingly, it is recommended that screening should be initiated since the start of metformin administration and every year or when relevant clinical manifestations were reported.

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

Branched-chain amino acids (BCAAs) are critical for skeletal muscle and whole-body anabolism and energy homeostasis. They also serve as signaling molecules, for example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). This has implication for macronutrient metabolism. However, elevated circulating levels of BCAAs and of their ketoacids as well as impaired catabolism of these amino acids (AAs) are implicated in the development of insulin resistance and its sequelae, including type 2 diabetes, cardiovascular disease, and of some cancers, although other studies indicate supplements of these AAs may help in the management of some chronic diseases. Here, we first reviewed the catabolism of these AAs especially in skeletal muscle as this tissue contributes the most to whole body disposal of the BCAA. We then reviewed emerging mechanisms of control of enzymes involved in regulating BCAA catabolism. Such mechanisms include regulation of their abundance by microRNA and by post translational modifications such as phosphorylation, acetylation, and ubiquitination. We also reviewed implications of impaired metabolism of BCAA for muscle and whole-body metabolism. We comment on outstanding questions in the regulation of catabolism of these AAs, including regulation of the abundance and post-transcriptional/post-translational modification of enzymes that regulate BCAA catabolism, as well the impact of circadian rhythm, age and mTORC1 on these enzymes. Answers to such questions may facilitate emergence of treatment/management options that can help patients suffering from chronic diseases linked to impaired metabolism of the BCAAs.

Disorders of metabolism in lysosomes in oncopathology as marker of nutritional prognosis

With oncopathology, the role of Katepsin L in proteolysis is not sufficiently studied, in particular, its connection with the nutritional status and the nutritional forecast.The purpose of the study. To determine the effect of impaired metabolism in lysosomes and its connection with the development of nutritional failure.Material and methods. The study includes 156 patients (65 with pancreatic cancer, 69 with СP). In the serum, MMP-9, TIMP-1 and GC were determined by the ELISA method. Statistical analysis was carried out by the criterion of Mann–Whitney. The results were presented in the form of medians (intercomdlic range). The reliability of differences was considered essential at p < 0.05.Results. It was revealed that the dynamics of changes in the epidermal-mezenchymal transition markers indicates an increase in the level of cystatin C (inhibitor of cathepsins), a decrease in the level of RSB in relations with the Catencin L, which is subsequently reflected in the reduction of the level of prehalet (marker of somatic protein deficiency). Cathepsin L in the complex with RSB determines one of the mechanisms for the development of nutritional failure and can predict it.Conclusions. The definition in the colprix of the RSB, cathepsin L and prehaletbin can serve as an early prognostic marker of nutritional insufficiency.

Acute Angle-Closure—A Rare but Vision-Threatening Ocular Adverse Effect of Selective Serotonin Reuptake Inhibitors

Acute angle closure (AAC) is a relatively rare but serious ophthalmological condition in which early diagnosis and intraocular pressure (IOP) -lowering treatment play a key role in prognosis. The aim of this review is to present current understanding of the pathophysiology, symptoms, diagnosis, potential mechanisms as well as management of AAC associated with the use of selective serotonin reuptake inhibitors (SSRIs). In most cases, AAC in individuals receiving SSRIs occurs in the pupillary block mechanism, secondary to SSRI-induced mydriasis. However, SSRIs may also cause uveal effusion and, consequently, iridocorneal angle closure. Other factors such as impaired metabolism and elimination of SSRIs, individual genetic conditions, as well as inhibition of SSRIs metabolism due to the effects of other drugs used may also promote AAC.

The decrease of intraflagellar transport impairs sensory perception and metabolism in ageing

Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19/RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19/RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing.

Current conceptions and promising tools to prevent cataractogenesis

This paper highlights current pharmacotherapeutic modalities for various metabolic disorders which result in cataract. This therapy is preferable for the prevention and treatment of lens opacities due to less financial costs and ease of use. A novel strategy of the medical treatment for cataract was developed. Several compounds prevent the generation of lens protein aggregates and to contribute to their degradation. Oxidative stress, excessive quinoid substances, and activation of aldose reductase promote cataract progression. Quinoid theory suggests that quinones, which are produced because of impaired metabolism of aromatic amino acids (tryptophan, tyrosine etc.) are important for cataractogenesis. Lens opacity occurs when its water-soluble proteins denature and transform into dense compounds under the influence of quinones. Many studies clearly demonstrate that Catalin (pirenoxine) eye drops provide anti-cataract effect on all layers of the lens, in particular, cortex and posterior capsule. High therapeutic efficacy and long-term safety allow for recommending Catalin to slow the progression of cataract, in particular, early cataracts in patients under 59 years of age. Further studies are needed to assess the effects of pirenoxine in various cataracts and risk of cataracts. Cited published data best illustrate the crux of this issue. Keywords: lens, cataract, antioxidants, quinoid compounds, cataractogenesis, medical treatment, pirenoxine, oxidative stress. For citation: Kovalevskaya M.A., Vladimirova Yu.V., Filina L.A., Kokorev V.L. Current conceptions and promising tools to prevent cataractogenesis. Russian Journal of Clinical Ophthalmology. 2021;21(1):24–28. DOI: 10.32364/2311-7729-2021-21-1-24-28.