Phosphorus Metabolism Research Articles

Etiopathogenesis of Calcium–Phosphorus Metabolism in Rabbits

In this article clinical signs, hematological indicators and photo morphological changes in bones of the etiopathogenesis of calcium–phosphorus metabolism in rabbits are described. Low–nutrition, poor–quality feeding of mother rabbits during the estrus period means that the needs of the mother rabbits’ body for vitamins and macro–microelements are not fully met. Disorders of calcium and phosphorus metabolism in rabbits are on average 53,3% during the gestation period and on average 73,3% during the postpartum period. It is accompanied by symptoms such as a decrease in response to external influences, swelling of the skin, a decrease in gloss, strong whitening of the mucous membranes, a decrease in body weight, accompanied by symptoms such as a change in appetite.

Influence of host genotype in establishing root associated microbiome of indica rice cultivars for plant growth promotion.

Rice plants display a unique root ecosystem comprising oxic-anoxic zones, harboring a plethora of metabolic interactions mediated by its root microbiome. Since agricultural land is limited, an increase in rice production will rely on novel methods of yield enhancement. The nascent concept of tailoring plant phenotype through the intervention of synthetic microbial communities (SynComs) is inspired by the genetics and ecology of core rhizobiome. In this direction, we have studied structural and functional variations in the root microbiome of 10 indica rice varieties. The studies on α and β-diversity indices of rhizospheric root microbiome with the host genotypes revealed variations in the structuring of root microbiome as well as a strong association with the host genotypes. Biomarker discovery, using machine learning, highlighted members of class Anaerolineae, α-Proteobacteria, and bacterial genera like Desulfobacteria, Ca. Entotheonella, Algoriphagus, etc. as the most important features of indica rice microbiota having a role in improving the plant's fitness. Metabolically, rice rhizobiomes showed an abundance of genes related to sulfur oxidation and reduction, biofilm production, nitrogen fixation, denitrification, and phosphorus metabolism. This comparative study of rhizobiomes has outlined the taxonomic composition and functional diversification of rice rhizobiome, laying the foundation for the development of next-generation microbiome-based technologies for yield enhancement in rice and other crops.

Assessing essentiality of nickel in growing Hariana heifers by determining its effect on performance, nitrogen and mineral metabolism, urease activity, and endocrine biomarkers

The objective of this study was to determine the effect of nickel (Ni) on growth performance, nutrient utilization, urease activity, and endocrine variables in growing cattle. Growing Hariana heifers (18) were randomly assigned into three groups (n=6), i.e. groups either without Ni supplementation (Ni0.0; control) or supplemented with 1.5 mg of Ni/kg DM (Ni1.5), and 3.0 mg of Ni/kg DM (Ni3.0). The experiment lasted for 90 days. Heifers supplemented with Ni showed higher nutrient intake and average daily gain (ADG) than control group. The nutrient digestibility was not affected by treatment, while the Ni supplemented animals showed higher intake, excretion, and nitrogen balance. The urease activity was comparable and higher in the Ni1.5 and Ni3.0 groups than in the control group. There was no effect of treatment on the metabolism of calcium (Ca), phosphorus (P), zinc (Zn), copper (Cu), and chromium (Cr). However, iron (Fe) retention showed a negative association with Ni levels. Plasma cortisol concentration was lower while the insulin like growth factor-1 (IGF-1) and tetraiodothyronine (T4) were higher in the Ni3.0 group compared to the Ni0.0 group, with Ni1.5 being intermediate. The plasma concentrations of triiodothyronine (T3) and thyroid stimulating hormone (TSH) were not affected by dietary treatment. Plasma Ni concentration showed a dose dependent increase whereas, plasma levels of other minerals were not affected by treatment. In conclusion, dietary Ni supplementation in growing Hariana heifers improves performance and nutrient utilization by modulating urease activity and endocrine growth biomarkers.

Transcription Analysis of Liver and Muscle Tissues from Landrace Finishing Pigs with Different Feed Conversion Ratios.

The efficiency of feed utilization determines the cost and economic benefits of pig production. In the present study, two pairs of full-sibling and two pairs of half-sibling female Landrace finishing pigs were selected, with each pair including individuals with different feed conversion rates, with liver and longissimus muscle tissue samples collected from each group for transcriptome analysis. A total of 561 differentially expressed genes (DEGs), among which 224 were up-regulated and 337 were down-regulated, were detected in the liver transcriptomes in the high-feed efficiency group compared to the low-feed efficiency group. The DEGs related to phosphorus and phosphate metabolism, arginine biosynthesis, chemical carcinogenesis, cytokine-cytokine receptor interaction, the biosynthesis of amino acids, and drug metabolism-cytochrome P450 in liver tissue were also associated with feed efficiency. In total, 215 DEGs were screened in the longissimus muscle tissue and were mainly related to disease and immune regulation, including complement and coagulation cascades, systemic lupus erythematosus, and prion diseases. The combination of gene expression and functional annotation results led to the identification of candidate feed efficiency-related biomarkers, such as ARG1, ARG2, GOT1, GPT2, ACAA2, ACADM, and ANGPTL4, members of cytochrome P450 family, and complement component family genes. Although the novel feed efficiency-related candidate genes need to be further evaluated by a larger sample size and functional studies, the present study identifies novel candidate biomarkers for the identification of functional SNPs underlying porcine feed efficiency.

Effects of Tebuconazole Application on Soil Microbiota and Enzymes.

Identification of pesticide impact on the soil microbiome is of the utmost significance today. Diagnosing the response of bacteria to tebuconazole, used for plant protection, may help isolate the most active bacteria applicable in the bioaugmentation of soils contaminated with this preparation. Bearing in mind the above, a study was undertaken to test the effect of tebuconazole on the diversity of bacteria at all taxonomic levels and on the activity of soil enzymes. It was conducted by means of standard and metagenomic methods. Its results showed that tebuconazole applied in doses falling within the ranges of good agricultural practice did not significantly disturb the biological homeostasis of soil and did not diminish its fertility. Tebuconazole was found to stimulate the proliferation of organotrophic bacteria and fungi, and also the activities of soil enzymes responsible for phosphorus, sulfur, and carbon metabolism. It did not impair the activity of urease responsible for urea hydrolysis, or cause any significant changes in the structure of bacterial communities. All analyzed soil samples were mainly populated by bacteria from the phylum Proteobacteria, Actinobacteria, Firmicutes, Gemmatimonadetes, Acidobacteria, Planctomycetes, and Chloroflexi. Bacteria from the genera Kaistobacter, Arthrobacter, and Streptomyces predominated in the soils contaminated with tebuconazole, whereas these from the Gemmata genus were inactivated by this preparation.

Exploring the Impacts of Full-Scale Distribution System Orthophosphate Corrosion Control Implementation on the Microbial Ecology of Hydrologically Connected Urban Streams.

Many cities across the nation are plagued by lead contamination in drinking water. As such, many drinking water utilities have undertaken lead service line (LSL) replacement to prevent further lead contamination. However, given the urgency of lead mitigation, and the socioeconomic challenges associated with LSL replacement, cities have used phosphate-based corrosion inhibitors (i.e., orthophosphate) alongside LSL replacement. While necessary to ensure public health protection from lead contamination, the addition of orthophosphate into an aging and leaking drinking water system may increase the concentration of phosphate leaching into urban streams characterized by century-old failing water infrastructure. Such increases in phosphate availability may cascade into nutrient and microbial community composition shifts. The purpose of this study was to determine how this occurs and to understand whether full-scale distribution system orthophosphate addition impacts the microbial ecology of urban streams. Through monthly collection of water samples from five urban streams before and after orthophosphate addition, significant changes in microbial community composition (16S rRNA amplicon sequencing) and in the relative abundance of typical freshwater taxa were observed. In addition, key microbial phosphorus and nitrogen metabolism genes (e.g., two component regulatory systems) were predicted to change via BugBase. No significant differences in the absolute abundances of total bacteria, Cyanobacteria, and "Candidatus Accumulibacter" were observed. Overall, the findings from this study provide further evidence that urban streams are compromised by unintentional hydrologic connections with drinking water infrastructure. Moreover, our results suggest that infiltration of phosphate-based corrosion inhibitors can impact urban streams and have important, as-yet-overlooked impacts on urban stream microbial communities. IMPORTANCE Elevated lead levels in drinking water supplies are a public health risk. As such, it is imperative for cities to urgently address lead contamination from aging drinking water supplies by way of lead service line replacements and corrosion control methods. However, when applying corrosion control methods, it is also important to consider the chemical and microbiological effects that can occur in natural settings, given that our water infrastructure is aging and more prone to leaks and breaks. Here, we examine the impacts on the microbial ecology of five urban stream systems before and after full-scale distribution system orthophosphate addition. Overall, the results suggest that infiltration of corrosion inhibitors may impact microbial communities; however, future work should be done to ascertain the true impact to protect both public and environmental health.

Hyperphosphatemia during nutrition recovery in patients with severe anorexia nervosa

IntroductionAnorexia nervosa (AN) is a disorder associated with many medical complications. Regarding phosphorus metabolism, the only recognized alteration is hypophosphatemia associated with refeeding syndrome. However, in our clinical practice, we have observed a high frequency of hyperphosphatemia in late phases of nutrition therapy in severely undernourished AN patients, which has barely been described. Materials and methodsWe carried out a retrospective study of patients with AN hospitalized for severe decompensation of the disease. ResultsEleven patients were included, all women, with a median age of 23 years [20−46] and a body mass index at admission of 12.2 kg/m2 [11.7−13.1]. Hyperphosphatemia was noted in 9 of the 11 cases (81.8%) with a median time to onset of 53 days [30−75]. The median peak serum phosphorus (P) level was 5.1 mg/dl [4.9−5.4]. An inverse relationship was found between the increase in P levels and phosphorus supplementation at the onset of admission. The magnitude of the P increase was associated with the body weight gain achieved during nutrition therapy. ConclusionLate hyperphosphatemia during nutrition therapy in severely undernourished AN patients affects more than 80% of cases. Body weight gain throughout nutrition therapy is a predictor of increased P levels.

The Effect of a Single High Dose of Vitamin D on Serum Levels of Its Metabolites in the Elderly.

Vitamin D is a dietary micronutrient responsible for calcium and phosphorus metabolism and multiple extraskeletal actions. The assessment of vitamin D status is commonly based on measurement of 25(OH)D total concentration in serum. However, the usage of liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique allows to reliably assess a panel of vitamin D metabolites in serum or plasma, which may help to investigate the metabolic paths of vitamin D, especially in populations at risk of deficiency. A randomized, two-arms, open study was conducted on 58 patients (28 female and 30 male; aged from 61 to 96 years old). The primary aim was to assess the effects of a single, high, oral dose of vitamin D3 (120,000 IU) on serum 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3/25(OH)D3 ratio, and 25(OH)D3/3-epi-25(OH)D3 ratio concentration (measured by LC-MS/MS) at baseline, 3 days and 7 days after administration, compared to control group. The secondary aim was assessment of influence of percentage of fat tissue on serum metabolites of vitamin D and their changes after bolus dose. 56.6% study group attained a serum 25(OH)D3 concentration >30 ng/mL. All subjects, except for one patient achieved a serum 25(OH)D3 concentration >20 ng/mL after administration. No one exceed reference value of vitamin D (30-50 ng/mL). Among participants who received vitamin D3 there were significant increase in 25(OH)D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3 on 3rd day after administration. 24,25(OH)2D3 concentration gradually grew, achieving the highest concentration on 7th day. The percentage increase of 25(OH)D3 was negatively correlated with baseline 25(OH)D3 (r = -0.688, p = 0.001). Positive correlation between percentage increase in 25(OH)D3 and a percentage increase serum concentration of 24,25(OH)2D3 (r = 0.954, p < 0.001), 3-epi-25(OH)D3 (r = 8.03, p < 0.001) and 1,25(OH)2D3 (r = 0.789, p <0.001) were found. None of the study participants developed hypercalcemia. The baseline concentration of analyzed metabolites of vitamin D in serum and their percentage increase were neither dependent on BMI nor percentage of fat tissue. High dose of vitamin D rapidly increases 25(OH)D3 concentration in the elderly patients. The response to the bolus of vitamin D includes activation of 3-epimerase, followed by production of 24,25(OH)2D3, which protects from excessive increase of active form of vitamin D.

Normocalcemic non-renal hyperparathyroidism

Parathyroid hormone (PTH) is produced by the parathyroid glands, which are the main regulators of calcium and phosphorus metabolism. Hyperparathyroidism is a clinical condition associated with an increase in serum PTH content. The state of parathyroid glands depends very much on the amount of vitaminD, magnesium and boron in the blood because, according to official data, substantiated by a number of scientific studies, the majority of the world population (80%) has a lack/deficiency of vitamin D. This fact explains the high prevalence of thyroid diseases (hyperplasia, adenoma, hyperparathyroidism) and associated pathology. Previous studies have shown that a deficiency/lack of vitaminD was found in 85–94% of Ukraine population. A deficiency/lack of vitamin D compensatorily stimulates an increase in PTH synthesis. Doctors very rarely determine the level of PTH, which prolongs the progression of hyperparathyroidism, and they detect it only with severe associated changes in other systems. Hyperparathyroidism occurs when one or more of the parathyroid glands become hyperactive, gradually leading to elevated serum parathyroid hormone levels and hypercalcemia. The diagnostic criteria for hyperparathyroid conditions are very vague, which is confusing and leads to unnecessary surgeries instead of simple vitamin D and boron therapy. Normocalcemic primary hyperparathyroidism is a diagnosis of exclusion, and it can be considered only after careful assessment of the causes of secondary hyperparathyroidism, including that associated with a lack of vitamin D. The most common form of hyperparathyroidism is normocalcemic non-renal hyperparathyroidism. Prophylactic use of vitamin D in the correct individualized doses (25(OH)D range of 100–150 nmol/l or 40–60 ng/ml) should reduce the risk of parathyroid pathology but only 10% of the population receives such therapy, others do not know that it is useful. The only way to eliminate the gradual progression of parathyroid disorders is to administer individual prophylactic or therapeutic doses of vitaminD.

Mycorrhizal Role in Phosphorus Metabolism

&#x0D; The roots of the plants are in contact with a substrate, and biotic and abiotic factors influence their functioning and development. The most known microorganisms associated with plant roots are soil fungi, which are adapted to the soil's living environment, called mycorrhizae. Arbuscular mycorrhizae are the most common of these associations. In agricultural ecosystems, the constant use of technologies has resulted in a progressive reduction of mycorrhizal diversity. Due to this phenomenon, soil presents a lower potential for the development of multi-level hyphal networks which implies reduced connections between all individuals of a single species. Mycorrhizas offer benefits for the host plant, including mineral nutrition, increased drought tolerance, and protection against pathogens. They play a significant role in acquiring the necessary nutrients (especially phosphorus and nitrogen) from soil to their host plants, as these nutrients may have low mobility in most soils. Plants take up phosphorus from soil indirectly through the hyphal network that can reach outside from the root depletion area. Mycorrhizal association increases the accumulation of nitrogen in the plant as a result of the competition of hyphae for the organic mineralized form of this element.&#x0D;

Comparison between liquid chromatography-tandem mass spectrometry and immunoassay methods for measurement of plasma 25 (OH) vitamin D

Abstract Objectives Vitamin D is one of the major hormones involved in the metabolism of calcium (Ca) and phosphorus (P). In the present study, we aimed to determine the analytical performance of the immunoassay method used for determining plasma 25-hydroxyvitamin D [25(OH)D] levels in routine clinical practice in laboratories. Methods Venous blood samples were collected from 156 patients for the comparisons and were analyzed with Siemens ADVIA Centaur XPT, the Roche Cobas 6,000’s module e601, Abbott Architect i2000, and the liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results The four methods were analyzed and compared through the Passing-Bablok regression for 25(OH)D, and the highest correlation was found at LC-MS/MS and Cobas 6,000’s module e601 (r=0.799), LC-MS/MS/Abbott Architect i2000, and LC-MS/MS/Siemens ADVIA Centaur XPT as r=0.736, 0.721, respectively. The correlation coefficient was found between Abbott Architect i2000 with Roche Cobas e601 and Siemens ADVIA Centaur XPT as r=0.934 and r=0.907, respectively. Also, the correlation coefficient was found between Roche Cobas e601 and Siemens ADVIA Centaur XPT as r=0.906. Conclusions The Roche Cobas assay showed better performance, compared with the other assays. Based on our findings, the chemiluminescence methods in automated systems seem to be expedient.

Oyster culture changed the phosphorus speciation in sediments through biodeposition

Phosphorus speciation in the sediments is regulated by a series of physicochemical and microbial processes, and directly affects water phosphorus pool. However, the influence of culture activities and microbial metabolism on the sedimentary phosphorus speciation is poorly studied. In this study, we compared the abundance of distinguishable phosphorus phases and other physicochemical properties of sediments from oyster-farming areas and reference areas. The Geochip 5.0 technique was introduced to reveal the microbiological mechanisms of phosphorus metabolic alteration. The results showed that oyster culture enhanced the bioavailability of phosphorus in sediments. The free organic phosphorus was reduced significantly, whereas the free inorganic phosphorus and iron-bound phosphorus greatly increased in the oyster culture area (P ≤ 0.05). Moreover, the results of Geochip showed that the oyster culture reshaped the microbial network structure in sediments, with typical phosphate-solubilizing and phosphorus-accumulating microbes being enriched by 17.76% and 10.60%. The abundance of functional genes related to the main phosphorus cycle pathways were also significantly increased (P ≤ 0.05) in the culture area compared to the reference area. This work suggested that oyster culture can greatly improve the microbial phosphorus metabolism and provided insights into the environmental recovery and reconstruction from marine aquaculture activities.

Metagenomic insights into the functional genes across transects in a typical estuarine marsh

Salt marshes are potentially one of the most efficient carbon (C) sinks worldwide and perform important ecosystem functions, but sea level rise alters marsh sediments properties and thus threatens microbial roles in ecosystem functioning. Yet, the mechanisms of interactions of biochemical processes with microorganisms and their functions are still not fully understood. Here, this study investigated metagenomic taxonomic and functional profiling from the water-land conjugation up to about 300 m, 1000 m, and 2500 m in three parallel transects, respectively, in Hangzhou Bay, China. The results showed that soil physicochemical factors drove metagenomic taxonomic and functional genes in the 2500-m transect significantly different from other sites. The 2500-m transect had a greater abundance of Chloroflexi and Acidobacteria but lower in Proteobacteria. The metagenomic functional genes related to Phosphorus Metabolism (PHO) and Potassium Metabolism (POT) increased in the 2500 m. Additionally, nutrient-cycling functions and the genera of Anaeromyxobacter, Roseiflexus, and Geobacter related to PHO, POT at 2500 m were significantly greater than those of other transects. Carbon cycling functions within Carbohydrates (CHO) also differed significantly across transects. These research results demonstrated that the relative abundance of metagenomic microorganisms and their functional genes were significantly separated across the three transects. The vegetation type, salinity, and soil properties might be among the influencing factors.

Does Vitamin D Have a Role in Diabetes?

Vitamin D, a fat-soluble vitamin, acts in the calcium and phosphorus metabolism in its active form (1,25-dihydroxy vitamin D). It may help prevent and treat autoimmune diseases, including diabetes mellitus. Diabetes has become a significant global health issue with a rising incidence and prevalence. A recent focus has been on vitamin D supplementation as part of efforts to discover novel ways to prevent and treat diabetes. Most evidence points to the vitamin D receptors (VDRS) gene in both types of diabetes. The main objective of this study is to analyze how vitamin D affects both type 1 and type 2 diabetes. In this literature review, we searched the PubMed and Google Scholar databases to collect related articles from 13 papers of different study designs. We found a significant association between vitamin D deficiency and type 1 and type 2 diabetes development. It has been shown that vitamin D supplements have a promising effect in reducing glycated hemoglobin (HbA1c) in patients with type 1 diabetes, with no significant impact on the incidence or improvement of type 2 diabetes. Patients with diabetes and people at high risk of diabetes need the appropriate amount of vitamin D; therefore, regular testing and vitamin D supplementation are advised for the management and prevention of diabetes. Additional randomized studies with bigger sample sizes and longer-term trials are required to fully explore the benefits of vitamin D supplementation in patients with type 1 and type 2 diabetes.

Morinda officinalis Polysaccharides Ameliorates Bone Growth by Attenuating Oxidative Stress and Regulating the Gut Microbiota in Thiram-Induced Tibial Dyschondroplasia Chickens.

Tibial dyschondroplasia (TD) occurs in chickens and other fast-growing birds, affecting their cartilage growth and leading to reduced meat quality in broilers. Morinda officinalis polysaccharide (MOP) is one of the chief active components of Morinda officinalis, which promotes bone formation, inhibiting bone loss and having anti-oxidant and anti-inflammatory properties. A total of 120 AA chickens were randomly divided into the CON group (basal diet), TD group (100 mg/kg thiram + basal diet), and MOP group (100 mg/kg thiram + basal diet + water with 500 mg/kg MOP). The experiment lasted 21 days. The results showed that MOP could alleviates broiler lameness caused by TD, restore the morphological structure of tibial growth plate (TGP), increase tibial weight (p < 0.05), balance the disorder of calcium and phosphorus metabolism, and promote bone formation by increasing the expression of BMP-2, Smad4, and Runx2 genes In addition, MOP supplementation stimulated the secretion of plasma antioxidant enzymes (T-SOD and GSH-Px) by regulating the expression of SOD and GPX-1 genes, thereby enhancing the antioxidant capacity of TD broilers. Interestingly, we observed MOP can also improve gut microbiota by increasing the beneficial bacteria count and decreasing the harmful bacteria count. These findings indicated that MOP can regulate bone formation through the BMP/Smads signaling pathway, attenuating oxidative stress and regulating the gut microbiota of TD broilers, so as to achieve the effect of treating TD. This suggests that MOP might be a potential novel drug in the treatment of TD in chickens.

IMPACT OF VITAMIN D DEFICIENCY DURING PREGNANCY

Vitamin D deficiency (vdd) is a public health problem. 50% of the world population have inadequate levels of vitamin D. Vitamin D is necessary for the absorption and metabolism of calcium and phosphorus. More than 90% of pregnant women had vitamin D insufficiency. According to the vitamin D council, pregnancy is a known risk factor for vitamin D deficiency. Vitamin D deficiency during pregnancy increases the risk of pre‐eclampsia, gestational diabetes, preterm birth, and low birthweight. Pregnant mothers who are deficient in vitamin D should be treated with cholecalciferol or ergocalciferol. Supplementing pregnant women with vitamin D reduces the risk of pre-eclampsia, gestational diabetes, low birthweight and the risk of severe postpartum haemorrhage.

Positive effect of vitamin D supplementation on weight loss in obese patients treated with glucagon-like peptide 1 and lifestyle interventions

Background. Obesity, prediabetes and type 2 diabetes mellitus (T2DM) are global diseases affecting the population of Ukraine, with an annual increase in morbidity. Insulin resistance occurs in up to 90% of obese patients, contributing to the accumulation of white adipose tissue, and has a risk for the further development of prediabetes and T2DM. However, other factors also play a negative role in the development of obesity, particularly cholecalciferol (vitamin D) deficiency. Vitamin D is a steroid hormone the main function of which is to regulate calcium and phosphorus metabolism, but this molecule also exhibits various properties, including the effects on carbohydrate metabolism. The purpose of this study was to identify and evaluate the role of vitaminD elevation in patients receiving glucagon-like peptide-1 agonists (GLP-1a) in combination with lifestyle interventions for the treatment of obesity and to compare its effectiveness with that in patients treating with metformin and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Materials and methods. A prospective study included 155 obese patients, and follow-up data were available for 49 of them. The study group consisted of 30 patients receiving combination therapy with GLP-1a liraglutide at a dose of 1.2 to 3.0 mg per day. The control group included 19 patients receiving combination therapy with metformin in daily doses of 500 to 2,000 mg, and SGLT2i in daily doses of 10 to 12.5 mg. Treatment of vitamin D deficiency was performed with cholecalciferol at a dose of 4,000 IU/day. Results. In study group GLP-1a, 25 (83.3%) patients had vitamin D insufficiency, which is statistically similar to control group (p&gt;0.05)— 17 (89.5%) cases. All patients with vitamin D insufficiency received 4,000 IU of cholecalciferol daily during the follow-up period. In study group GLP-1a, the mean body mass before the treatment was 104.6 kg, after treatment— 96.36 kg (p=0.000007), the mean weight lost was 7.8% (range is 1–23.71%) of the initial level. Mean body mass index (BMI) before treatment was 37.1 kg/m2, after treatment— 34.11 kg/m2 (p=0.000006). In the control group, the mean weight before the treatment was 99.4 kg, after treatment— 91.74 kg (p=0.000196), the mean weight lost was 7.73% (range is 0–16.9%) of the initial level. BMI before treatment averaged 35.6 kg/m2, after treatment— 34.11 kg/m2 (p=0.000196). The analysis of carbohydrate metabolism parameters showed a significantly lower blood glucose level— 5.75 mmol/l in the study group GLP-1a compared to 8.42 mmol/l in the control group (p=0.00024). It should be noted that a similar clinical picture was also observed after treatment, despite the compensation of T2DM in all patients: a significantly lower blood glucose level— 5.03 mmol/l in the study group GLP-1a compared to 5.99 mmol/l in controls (p=0.002453). However, significantly higher levels of insulin were detected in the study group GLP-1a before treatment— 27.02 mU/L compared to 18.59mU/L in control patients (p=0.003286). After treatment, a similar situation was observed in terms of significantly higher levels of insulin: 19.41 mU/l in patients of the study group GLP-1a compared to 14.42mU/l in controls (p=0.0024). Corresponding changes were also observed for the HOMA index. Conclusions. Our results suggest high effectiveness of increasing the level of vitamin D in case of its insufficiency as a part of measures for the treatment of obese patients with liraglutide, metformin or SGLT2i.

GALNT3 protects against phosphate-induced calcification in vascular smooth muscle cells by enhancing active FGF23 and inhibiting the wnt/β-catenin signaling pathway

Vascular calcification (VC) acts as a notable risk factor in the cardiovascular system. Disorder of phosphorus (Pi) metabolism promotes VC. Recent findings show that polypeptide N-acetylgalactosaminyltransferase 3(GALNT3) is Pi responsive and with potent effects on Pi homeostasis. However, whether GALNT3 is involved in high Pi-induced VC remains unclear. The present study investigated the potential role of GALNT3 as a novel regulator of VC. In vitro, human aortic smooth muscle cells (HASMCs) calcification was induced by inorganic Pi, while in vivo, C57BL/6 J mice were used to determine the effects of GALNT3 on Vitamin D3-induced medial arterial calcification. Alizarin red staining, Von Kossa staining, calcium and alkaline phosphatase (ALP) activity were performed to test VC. We showed that expression of GALNT3 was increased in the calcified HASMCs and aortas of the calcified mice.In vitro, overexpression of GALNT3 increased the levels of active full-length FGF23, accompanied by suppression of the osteoblast-related factors (Runx2 and BMP2), and further inhibited the formation of calcified nodules. Moreover, the protein levels of Wnt3a and active β-catenin were determined and it was found that GALNT3 significantly inhibited their expression. LiCl, a Wnt/β-catenin signaling activator, was observed to reverse the protective effect of GALNT3 overexpression. The opposite results were observed in the GALNT3 knockdown cells. In vivo, overexpression of GALNT3 by adeno-associated virus decreased the serum Pi and slowed the formation of aortic calcification in the calcified mice. In conclusion, our results indicate that GALNT3 counteracts high Pi-induced osteoblastic differentiation of VSMCs and protects against the initiation and progression of VC by inhibiting the Wnt/β-catenin signaling pathway.

A novel FGF23 mutation in hyperphosphatemic familial tumoral calcinosis and its deleterious effect on protein O-glycosylation.

BackgroundHyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and ectopic calcification, predominantly at periarticular locations. This study was performed to characterize the clinical profile of tumoral calcinosis and to identify gene mutations associated with HFTC and elucidated its pathogenic role.MethodsThe three subjects (two male and one female) were aged 30, 25 and 15 years, respectively. The clinical features, histopathological findings, and outcomes of three subjects with HFTC were retrospectively reviewed. The three subjects were analyzed for FGF23, GALNT3 and KL mutations. Function of mutant gene was analyzed by western blotting and wheat germ agglutinin affinity chromatography.ResultsAll subjects had hyperphosphatemia and elevated calcium-phosphorus product. Calcinosis positions included the left shoulder, left index finger, and right hip. Bone and joint damage were present in two cases and multiple foci influenced body growth in one case. The histopathological features were firm, rubbery masses comprising multiple nodules of calcified material bordered by the proliferation of mononuclear or multinuclear macrophages, osteoclastic-like giant cells, fibroblasts, and chronic inflammatory cells. The novel mutation c.484A>G (p.N162D) in exon 3 of FGF23 was identified in one subject and his family members. Measurement of circulating FGF23 in the subject confirmed low intact FGF23 and increased C-terminal fragment. In vitro experiments showed that the mutant FGF23 proteins had defective O-glycosylation and impaired protein proteolysis protection.ConclusionWe identified a novel FGF23 missense mutation, and confirmed its damaging role in FGF23 protein O-glycosylation. Our findings expand the current spectrum of FGF23 variations that influence phosphorus metabolism.

Regulatory Effect of Thyroxine on Calcium and Phosphorus Metabolism in Tissues of Common Indian Toad

Thyroxine (T4) plays a vital role in the metabolic processes of animals. It influences the storage and mobilisation of minerals and their utilisation according to the requirement of the body. It is also involved in the early development of vertebrates, especially in amphibian metamorphosis. It has shown anabolic and catabolic effects at a lower dose and higher dose, respectively. The present study aims to identify the role of thyroxine in regulating calcium and phosphorous metabolism in the blood, muscle and bone tissues of Bufo melanostictus. Toads of various sizes and different age groups were chosen, showing a positive correlation between body weight and snout to vent length, indicating overall continuous growth as observed for a large number of poikilothermic animals. As per an earlier report, thyroxine has been shown to have a direct catabolic effect on bone mineral homeostasis leading to an increase in bone mineral resorption and calcium loss through the kidney. Results of the present study indicate that thyroxine treatment in Bufo melanostictus caused depletion of calcium and phosphorous in muscle and bone, while their level increased in the serum at both doses (0.5 μg/gm and 2 μg/gm) during short term i.e. a one-day T4 treatment. Such results are very much consistent with many of the earlier obscurations that, T4 causes an increase in serum calcium and phosphorous levels, while their level in muscle and bone decreased. When the level of these two minerals falls in the serum due to any other condition, the bone resorption under the influence of thyroxine maintains the concentration in serum, consequently, there is a loss in bone density due to resorption and in muscle due to utilisation. However, if the exogenous supply is adequate, the loss caused as above is compensated for, in both bone and muscle.