Parathyroid Hormone Synthesis Research Articles

Modulation of Serum Metabolic Profiles by Bifidobacterium breve BBr60 in Obesity: A Randomized Controlled Trial.

Obesity, a prevalent metabolic disorder in youth, leads to complications and economic strain. Gut dysbiosis significantly contributes to obesity and metabolic issues. Bifidobacterium breve, a probiotic strain, may help regulate gut dysbiosis and benefit obese individuals. However, more research is needed on its effect on serum metabolism. A total of 75 overweight or obese young adults (aged 19-45) participated in the current study, and were randomly divided into probiotic and placebo groups using a random number table. Both groups received dietary guidance and underwent twelve weeks of intervention with either oral Bifidobacterium breve BBr60 (BBr60) or a placebo. After the intervention, collection and analysis of fasting serum samples were conducted using mass spectrometry coupled with liquid chromatography. Analyses of associations were conducted in order to determine the correlations between key serum metabolites and clinical obesity indicators, aiming to understand the influence of BBr60. Due to 10 participants dropping out for personal reasons, the study included 32 and 33 participants in the placebo and the BBr60 groups, respectively. The BBr60 intervention significantly regulated 134 serum metabolites and influenced crucial metabolic pathways in obesity management (p < 0.05), including ascorbate and aldarate metabolism for oxidative stress reduction, cholesterol metabolism for lipid regulation, parathyroid hormone synthesis, secretion and action for the endocrine system, oxidative phosphorylation for enhanced energy efficiency, and glycolysis/gluconeogenesis for glucose metabolism. Analysis showed a positive relationship between fasting blood glucose (FBG), aspartate aminotransferase (AST), total protein (TP), and the content of 5-Methyl DL-glutamate (p < 0.05). Similarly, body mass index (BMI), weight, and body fat percentage (BFP) were positively linked to serum metabolites (1-Hydroxycyclohexyl) acetic acid, and 5-Oxooctanoic acid (p < 0.05). Significant associations of AST levels with key serum metabolites in cholesterol metabolism pathways further suggest BBr60's potential to improve liver function and overall metabolic health in overweight or obese individuals. These findings support BBr60's effectiveness in modulating serum metabolic profiles and suggest it may improve liver function and BMI in overweight or obese individuals by regulating key serum metabolites.

Multiple Machine Learning Identifies Key Gene PHLDA1 Suppressing NAFLD Progression.

Non-alcoholic fatty liver disease (NAFLD) poses a serious global health threat, with its progression mechanisms not yet fully understood. While several molecular markers for NAFLD have been developed in recent years, a lack of robust evidence hampers their clinical application. Therefore, identifying novel and potent biomarkers would directly aid in the prediction, prevention, and personalized treatment of NAFLD. We downloaded NAFLD-related datasets from the Gene Expression Omnibus (GEO). Differential expression analysis and functional analysis were initially conducted. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) and multiple machine learning strategies were employed to screen and identify key genes, and the diagnostic value was assessed using Receiver Operating Characteristic (ROC) analysis. We then explored the relationship between genes and immune cells using transcriptome data and single-cell RNA sequencing (scRNA-seq) data. Finally, we validated our findings in cell and mouse NAFLD models. We obtained 23 overlapping differentially expressed genes (DEGs) across three NAFLD datasets. Enrichment analysis revealed that DEGs were associated with Apoptosis, Parathyroid hormone synthesis, secretion and action, Colorectal cancer, p53 signaling pathway, and Biosynthesis of unsaturated fatty acids. After employing machine learning strategies, we identified one gene, pleckstrin homology like domain family A member 1 (PHLDA1), downregulated in NAFLD and showing high diagnostic accuracy. CIBERSORT analysis revealed significant associations of PHLDA1 with various immune cells. Single-cell data analysis demonstrated downregulation of PHLDA1 in NAFLD, with PHLDA1 exhibiting a significant negative correlation with macrophages. Furthermore, we found PHLDA1 to be downregulated in an in vitro hepatic steatosis cell model, and overexpression of PHLDA1 significantly reduced lipid accumulation, as well as the expression of key molecules involved in hepatic lipogenesis and fatty acid uptake, such as FASN, SCD-1, and CD36. Additionally, gene set enrichment analysis (GSEA) pathway enrichment analysis suggested that PHLDA1 may influence NAFLD progression through pathways such as Cytokine Cytokine Receptor Interaction, Ecm Receptor Interaction, Parkinson's Disease, and Ribosome pathways. Our conclusions were further validated in a mouse model of NAFLD. Our study reveals that PHLDA1 inhibits the progression of NAFLD, as overexpression of PHLDA1 significantly reduces lipid accumulation in cells and markedly decreases the expression of key molecules involved in liver lipogenesis and fatty acid uptake. Therefore, PHLDA1 may emerge as a novel potential target for future prediction, diagnosis, and targeted prevention of NAFLD.

Transcriptome analysis to explore the mechanism of downregulated TNIK influencing the effect of risperidone.

Risperidone is one of the most reliable and effective antipsychotics for schizophrenia treatment. However, the mechanism of action of risperidone is not yet fully understood. Traf2 and Nck-interacting protein kinase (TNIK), a schizophrenia susceptibility gene, is associated with risperidone treatment response. Our previous in vitro experiments confirmed that downregulated TNIK affected the effect of risperidone on downstream targets. However, the effect of downregulated TNIK on risperidone-induced molecular expression remains to be further explored. Transcriptome analysis was performed on U251 cells subjected to risperidone, TNIK siRNA, and no treatment, respectively. Compared to the no-treatment group, two groups of DEGs were screened out and then intersected with the schizophrenia-related genes to screen the cross-talk genes. Those DEGs were analyzed using GO and KEGG. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network for the cross-talk gene. The results showed that the parathyroid hormone synthesis, secretion, and action were significantly enriched after risperidone treatment. Downregulated TNIK could have an impact on the collagen-containing extracellular matrix, signaling receptor activator activity, and PI3K-Akt signaling pathway. Interestingly, bone mineralization function and calcium signaling pathway were enriched in the cross-talk genes. Additionally, FGFR2, FGF1, and FGFR might be the potential targets for TNIK affecting the effects of risperidone. The study indicated that risperidone primarily influences functions and/or pathways associated with bone metabolism, potentially contributing to the adverse effect of osteoporosis. Our study may offer a novel perspective on investigating the mechanisms underlying the adverse effects of risperidone.

Effects of Lactobacillus plantarum on Broiler Health: Integrated Microbial and Metabolomics Analysis.

Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinalmetabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.

Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS-based untargeted metabonomics.

Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics. In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia. In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis". The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.

Thyroid and parathyroid function disorders induced by short-term exposure of microplastics and nanoplastics: Exploration of toxic mechanisms and early warning biomarkers

Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs exposure on vertebrates are unclear. Here we used intratracheal instillation and intragastric infusion to establish mouse models for MNPs exposure to systematically investigate the toxic mechanisms of MNPs on endocrine organs. Results showed that MNPs induced endocrine disruptions in short-term exposure by both dietary and respiratory pathways. Microplastics (MPs) exposed through dietary route were more toxic to thyroid gland, whereas nanoplastics (NPs) exhibited the highest level of toxicity to parathyroid gland through respiration. The transcriptome and validation of related functional genes revealed that MNPs affected the synthesis of thyroglobulin by interfering with the expressions of PAX8 and CREB. MNPs also impacted the levels of thyroid stimulating hormone, further mediating the secretion of thyroid hormones. Moreover, MNPs modulate the expression of Mafb, thereby exerting regulatory effects on parathyroid hormone (PTH) synthesis and growth development in parathyroid cells. Meanwhile, MNPs interfered with the expression of IP3R in the calcium signaling pathway, indirectly affecting the secretion of PTH. This study reveals the effects and mechanisms of MNPs on thyroid and parathyroid and highlights the significance of early warning of MNPs exposure.

Secondary hyperparathyroidism: Update

Secondary hyperparathyroidism is a clinical condition characterized by an increase in the synthesis and secretion of parathyroid hormone (PTH). Its presentation will be conditioned by the development of stimuli such as hyperphosphatemia, hypocalcemia, vitamin D deficiency, and PTH resistance. The most common cause of secondary hyperparathyroidism is chronic kidney disease, a pathological condition in which all the afore mentioned stimuli converge. Secondary hyperparathyroidism is evidenced by an increase in the size of the parathyroid glands, favored by cellular hyperplasia and hypertrophy. At the bone level, there will be an increase in the quantity and activity of osteoblasts and osteoclasts, leading to bone with unusual structural characteristics. Symptoms related to the disease include itching, bone pain, concentration alteration, and depression. In the long term, patients have a higher risk of cardiovascular mortality. Therapeutic options include calcimimetics, phosphate binders, vitamin D supplements, and surgery.

Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5′-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Rare genetic disorders that impair parathyroid hormone synthesis, secretion, or bioactivity provide insights into the diagnostic utility of different parathyroid hormone assays.

Parathyroid hormone (PTH) is the major peptide hormone regulator of blood calcium homeostasis. Abnormal PTH levels can be observed in patients with various congenital and acquired disorders, including chronic kidney disease (CKD). This review will focus on rare human diseases caused by PTH mutations that have provided insights into the regulation of PTH synthesis and secretion as well as the diagnostic utility of different PTH assays. Over the past years, numerous diseases affecting calcium and phosphate homeostasis have been defined at the molecular level that are responsible for reduced or increased serum PTH levels. The underlying genetic mutations impair parathyroid gland development, involve the PTH gene itself, or alter function of the calcium-sensing receptor (CaSR) or its downstream signaling partners that contribute to regulation of PTH synthesis or secretion. Mutations in the pre sequence of the mature PTH peptide can, for instance, impair hormone synthesis or intracellular processing, while amino acid substitutions affecting the secreted PTH(1-84) impair PTH receptor (PTH1R) activation, or cause defective cleavage of the pro-sequence and thus secretion of a pro- PTH with much reduced biological activity. Mutations affecting the secreted hormone can alter detection by different PTH assays, thus requiring detailed knowledge of the utilized diagnostic test. Rare diseases affecting PTH synthesis and secretion have offered helpful insights into parathyroid biology and the diagnostic utility of commonly used PTH assays, which may have implications for the interpretation of PTH measurements in more common disorders such as CKD.

The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases

Parathyroid hormone (PTH) plays a key role in the regulation of calcium-phosphate metabolism. The secretion of PTH is regulated by calcium-sensing receptor (CaSR), which primarily expressed in the parathyroid glands and the renal tubules of the kidney. Increase of calcium concentration in extracellular matrix of cells is causing activation of the CaSR. Activated CaSR inhibits secretion of PTH and increases urinary calcium excretion. All CaSR effects leads to prevent development of hypercalcemia complications. Downregulation of the CASR expression and/or altered CaSR functioning leads to dysregulation of PTH synthesis. It may be the underlying cause of the development of primary and secondary hyperparathyroidism, as well as a number of hereditary diseases associated with loss- and gain-of-function mutations of the CaSR. In this paper we discusses the function of the CaSR in physiology and also the potential mechanisms that can impaired CaSR-induced signaling in various calcitropic diseases.

Bioinformatics analysis of a disease-specific lncRNA-miRNA-mRNA regulatory network in recurrent spontaneous abortion (RSA).

This study investigated the molecular mechanisms of long non-coding RNAs (lncRNAs) in RSA using the lncRNA-miRNA-mRNA regulatory network. The present study obtained expression datasets of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) from blood samples of individuals with unexplained recurrent spontaneous abortion (RSA) and healthy controls. Differentially expressed lncRNAs (DELs), mRNAs (DEMs), and miRNAs (DEmiRs) were identified. A regulatory network comprising lncRNA, miRNA, and mRNA was constructed, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEM. Also, a protein-protein interaction (PPI) network was made and key genes were identified. A total of 57 DELs, 212 DEmiRs, and 301 DEMs regarding RSA were identified. Later analysis revealed a lncRNA-miRNA-mRNA network comprising nine lncRNAs, 14 miRNAs, and 65 mRNAs. Then, the ceRNA network genes were subjected to functional enrichment and pathway analysis, which showed their association with various processes, such as cortisol and thyroid hormone synthesis and secretion, human cytomegalovirus infection, and parathyroid hormone synthesis. In addition, ten hub genes (ITGB3, GNAI2, GNAS, SRC, PLEC, CDC42, RHOA, RAC1, CTNND1, and FN1) were identified based on the PPI network results. In summary, the outcomes of our study provided some data regarding the alteration genes involved in RSA pathogenic mechanism via the lncRNA-miRNA-mRNA network and reveal the possibility of identifying new lncRNAs and miRNAs as promising molecular biomarkers.

Phosphate-sensing mechanisms and functions of phosphate as a first messenger.

Bone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human body, and around 85% of phosphate is present in bone as a constituent of hydroxyapatite, Ca10(PO4)6(OH)2. Because hypophosphatemia induces rickets/osteomalacia, and hyperphosphatemia results in ectopic calcification, blood phosphate (inorganic form) level must be regulated in a narrow range (2.5 mg/dL to 4.5 me/dL in adults). However, as yet it is unknown how bone senses changes in blood phosphate level, and how bone regulates the production of FGF23. Our previous data indicated that high extracellular phosphate phosphorylates FGF receptor 1 (FGFR1) in an unliganded manner, and its downstream intracellular signaling pathway regulates the expression of GALNT3. Furthermore, the post-translational modification of FGF23 protein via a gene product of GALNT3 is the main regulatory mechanism of enhanced FGF23 production due to high dietary phosphate. Therefore, our research group proposes that FGFR1 works as a phosphate-sensing receptor at least in the regulation of FGF23 production and blood phosphate level, and phosphate behaves as a first messenger. Phosphate is involved in various effects, such as stimulation of parathyroid hormone (PTH) synthesis, vascular calcification, and renal dysfunction. Several of these responses to phosphate are considered as phosphate toxicity. However, it is not clear whether FGFR1 is involved in these responses to phosphate. The elucidation of phosphate-sensing mechanisms may lead to the identification of treatment strategies for patients with abnormal phosphate metabolism.

Expression and clinical significance of miR-8078 in patients with congenital heart disease-associated pulmonary arterial hypertension

ObjectivesThis study aimed to analyze the plasma levels of miR-8078 in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) and to explore the diagnostic value and potential mechanisms of miR-8078 in CHD-PAH. MethodsPlasma samples were collected from 110 patients with congenital heart disease. Subsequently, based on the mean pulmonary artery pressure (PAPm) measured via right heart catheterization, the patients were divided into three groups: no-PAH group (Group W, PAPm < 25 mmHg), mild group (Group M, 25 mmHg ≤ PAPm < 35 mmHg), and moderate-to-severe group (Group H, PAPm ≥ 35 mmHg). The study also involved a control group (Group C) comprised of 40 healthy individuals. The miR-8078 expression levels were determined by means of reverse transcription-polymerase chain reaction (RT-PCR). The target genes and biological functions of miR-8078 were predicted using TargetScan, PicTar, and miRDB software. Statistical analysis was performed to evaluate the correlation between miR-8078 and hemodynamic parameters in CHD-PAH, in addition to its diagnostic value. ResultsThe plasma miR-8078 expression levels were significantly higher in the moderate-to-severe group when compared with the control group, no-PAH group, and mild group (p < 0.05). Furthermore, the mild group and no-PAH group showed significantly higher miR-8078 expression levels when compared with the control group (p < 0.05). Both results were consistent with the high-throughput sequencing results. KEGG pathway analysis of the miR-8078 target genes revealed associations with morphine addiction, ubiquitin-mediated proteolysis, and parathyroid hormone synthesis and secretion. GO enrichment analysis indicated the involvement of miR-8078 in the regulation of transcription by RNA polymerase II, the positive regulation of stress-activated MAPK cascade, the transmembrane transport of CI- and K+ ions, chromatin organization, and atrioventricular valve morphogenesis. Correlation analysis showed that the miR-8078 expression levels were positively correlated with the pulmonary artery systolic pressure, mean pulmonary artery pressure, and pulmonary vascular resistance (correlation coefficients of 0.404, 0.397, and 0.283, respectively; all p < 0.05). Univariate and multivariate regression analyses revealed plasma miR-8078 (odds ratio: 1.475, 95 % confidence interval: 1.053–2.065, p < 0.05) to be an independent risk factor for CHD-PAH. Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) for miR-8078 alone and for B-type natriuretic peptide alone in diagnosing CHD-PAH was 0.686 and 0.851, respectively, while the AUC for a combined diagnosis was 0.874, which was higher than that associated with the individual diagnoses (p < 0.05). ConclusionThe findings of this study suggest that miR-8078 is upregulated in CHD-PAH, while the results of the bioinformatics analysis indicate its involvement in the pathogenesis of CHD-PAH, suggesting it to be a potential therapeutic target or biomarker.

Lactiplantibacillus plantarum GL001 alleviates jejunal oxidative damage induced by intestinal ischemia-reperfusion injury by influencing jejunal tissue metabolism through the improvement of jejunal microbial composition

Intestinal ischemia-reperfusion (IIR) injury is associated with inflammation and oxidative stress, yet its precise mechanisms remain not fully understood. IIR injury is closely linked to the gut microbiota and its metabolites. The anti-inflammatory and antioxidant effects of Lactiplantibacillus plantarum are specific to IIR. In our study, we conducted a 30-day pre-treatment of SD rats with both a standard strain of Lactiplantibacillus plantarum and Lactiplantibacillus plantarum GL001. After a 7-day cessation of treatment, we induced an IIR injury model to investigate the mechanisms by which Lactiplantibacillus plantarum alleviates IIR damage. The results demonstrate that Lactiplantibacillus plantarum effectively mitigates the inflammatory and oxidative stress damage induced by IIR. Lactiplantibacillus plantarum GL001 can improve the gut microbiota by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. In IIR intestinal tissue, the levels of secondary bile acids are elevated. The content of the bacterial metabolite Calcimycin increases. Annotations of metabolic pathways suggest that Lactiplantibacillus plantarum GL001 can alleviate IIR damage by modulating calcium-phosphorus homeostasis through the regulation of parathyroid hormone synthesis, secretion, and action. Microbiota-metabolite correlation analysis reveals a significant negative correlation between calcimycin and Lactonacillus and a significant positive correlation between calcimycin and Shigella. There is also a significant positive correlation between calcimycin and secondary bile acids. Lactiplantibacillus plantarum GL001 can alleviate oxidative damage induced by IIR through improvements in gut microbiota and intestinal tissue metabolism.

Quality of life in patients with hyperparathyroidism before and after surgical treatment

BACKGROUND: Hyperparathyroidism (HPT) is a syndrome characterized by excessive synthesis of parathyroid hormone (PTH), an imbalance of phosphorus-calcium metabolism, and damage to target organs. Radical treatment of any clinical variant of HPT is surgical. In this regard, the assessment of the quality of life (QoL) of patients before and after surgery is an indicator that reflects the impact of the disease on the patient’s health and the effectiveness of the treatment.AIM: To study QoL of patients with various clinical variants of HPT before and after surgical treatment.MATERIALS AND METHODS: The single-center prospective study included patients operated on for primary (PHPT), secondary (SHPT) and tertiary HPT in 2019–2021. A comparison was made of preand postoperative QoL indicators with a sample comparable in sex and age from residents of the Irkutsk region.RESULTS: The study included 100 patients, of which 13 had multiple lesions of the parathyroid glands (PTG) and 51 with solitary lesions in PHPT, 34 with SHPT and 2 with SHPT. Indicators QoL of patients with HPT before surgery is statistically significantly lower than in the region. The greatest decrease in QoL was found in the group of patients with multiple PTG lesions in PHPT. Improvement in QoL was achieved in 90% of the studied patients. Despite the identified complications, there was an improvement in QoL after surgery in case of achieving remission of the disease. Persistence of the disease is an outcome that does not allow for a statistically significant improvement in QoL after surgery for any type of HPT. Deterioration of QoL according to some indicators was found in 10% of patients. In patients with solitary PTG lesions in PHPT, deterioration in QoL is associated with postoperative hypocalcemia against the background of the «hungry bones» syndrome, and in patients with SHPT with a decrease in parathyroid hormone below population indicators.CONCLUSION: The study demonstrates QoL of patients with various clinical variants of hyperparathyroidism before and after surgical treatment. The dynamics of QoL indicators depending on the nosology, volume, duration, outcome and complications of operations is shown.

Therapeutic and diagnostic algorithm for preoperative prediction of sporadic multigland parathyroid disease

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrinological disease that is characterized by autonomic increased synthesis of parathyroid hormone (PTH) with elevated or upper-normal levels of blood calcium [1]. In 80–85% of cases, the cause of sporadic PHPT is an adenoma of one parathyroid gland (PTG) (sigle-gland parathyroid disease), in 20–25% — a lesion of a larger number of PTGs (hyperplasia of all glands or double adenomas — multigland parathyroid disease) [2]. The complexity of clinical and laboratory prediction, low sensitivity of imaging methods, poor assessment of the radicalness of the operation by intraoperative monitoring of intact PTH (IMiPTH) are the components of the problem of multiple lesions in PHPT. Therefore, the improvement of existing and the development of new methods for diagnosing and treating this variant of the disease are urgent tasks of modern endocrine surgery.AIM: To develop an algorithm for the diagnosis and treatment of PHPT, aimed at preoperative detection of multigland parathyroid disease.MATERIALS AND METHODS: The study was based on a study of a continuous sample of 208 patients, of which 34 with multigland parathyroid disease in PHPT, 95 with single-gland parathyroid disease in PHPT, 69 with secondary hyperparathyroidism on renal replacement therapy (RRT) with hemodialysis, and 10 with tertiary hyperparathyroidism on RRT of LT. The work was performed on the basis of clinical, laboratory, instrumental, morphological and immunohistochemical studies. The nature of the expression of the calcium-sensitive receptor and the vitamin D receptor in the studied groups was studied as a pathogenetic substantiation of the proposed algorithm [3]. Based on the study of clinical and laboratory parameters and the results of preoperative imaging methods, predictors of multigland parathyroid disease in PHPT [4,5] were established, and a method for differential diagnosis of PTG lesions in PHPT was developed [6]. In addition, the results of surgical treatment of patients with multiple PTG lesions in various clinical variants of hyperparathyroidism were studied [7]. RESULTS: The proposed algorithm is used when the diagnosis of PHPT is already established and there are indications for surgical treatment. First of all, the level of GFR (CKD-EPI) is assessed in conjunction with the results of the “gold standard” preoperative imaging methods (ultrasound and scintigraphy), with an assessment of the number of localized increased PTG and the consistency of the results of preoperative methods.At a GFR level of more than 73 ml/min/1.73 m2, an increase of only 1 PTG according to the results of 2 imaging methods, provided that they are consistent, the PHPT variant is defined as a sigle-gland parathyroid disease. If there is an inconsistency between the 2 methods of preoperative imaging, we recommend calculating the scores according to the differential diagnosis scale for multiple lesions in PHPT [6]. At a GFR level of less than 73 ml/min/1.73 m2, an increase of &gt;1 PTG according to the results of 2 imaging methods, we recommend calculating points according to the proposed scale [6].With the established variant of PHPT — sigle-gland parathyroid disease, the patient undergoes selective parathyroidectomy (PTE) with IMiPTH. When iPTH drops to reference values, the test is considered positive, and the operation ends there. If the test result is negative, a second test is required after 10 minutes. In the event that the repeated test is also negative, then the patient is shown a bilateral neck exploration (BNE) in accordance with the tactics for multigland parathyroid disease (see below).With the established variant of PHPT — multigland parathyroid disease, the following tactics are used:BNE with obligatory exploration of all four PTGs;Macroscopic assessment of the PTG found.When making a decision about 2 pathologically changed enlarged PTG, and 2 others are intact and not enlarged, a double PTE with IMiPTH is performed. If after the removal of 2 pathologically altered PTGs, the IMiPTH test is negative, then a second one is necessary after 10 minutes. In the event that the repeated test is negative, then from the 2 recognized intact ones, the least altered is determined and the scope of the operation is expanded to subtotal PTE (3.5 PTG), leaving ½ of the least altered PTG. The operation ends here.When deciding that 3 or more PTG are pathologically changed and enlarged, a subtotal PTE with IMiPTH is performed. In case of a negative IMiPTH test, the places of possible ectopic location of the PTG are examined: thyrothymic ligaments, upper thymus horns, fatty tissue along the carotid arteries. If there are no ectopically located PTGs in the indicated places, the operation is completed.CONCLUSION: The proposed treatment and diagnostic algorithm is pathogenetically substantiated, aimed at preoperative detection of multiple PTG lesions in PHPT and will improve the quality of life of this group of patients by reducing the persistence of the disease.

Replacing dietary sodium selenite with biogenic selenium nanoparticles improves the growth performance and gut health of early-weaned piglets

Selenium nanoparticles (SeNPs) are proposed as a safer and more effective selenium delivery system than sodium selenite (Na2SeO3). Here, we investigated the effects of replacing dietary Na2SeO3 with SeNPs synthesized by Lactobacillus casei ATCC 393 on the growth performance and gut health of early-weaned piglets. Seventy-two piglets (Duroc × Landrace × Large Yorkshire) weaned at 21 d of age were divided into the control group (basal diet containing 0.3 mg Se/kg from Na2SeO3) and SeNPs group (basal diet containing 0.3 mg Se/kg from SeNPs) during a 14-d feeding period. The results revealed that SeNPs supplementation increased the average daily gain (P = 0.022) and average daily feed intake (P = 0.033), reduced (P = 0.056) the diarrhea incidence, and improved (P = 0.013) the feed conversion ratio compared with Na2SeO3. Additionally, SeNPs increased jejunal microvilli height (P = 0.006) and alleviated the intestinal barrier dysfunction by upregulating (P < 0.05) the expression levels of mucin 2 and tight junction proteins, increasing (P < 0.05) Se availability, and maintaining mitochondrial structure and function, thereby improving antioxidant capacity and immunity. Furthermore, metabolomics showed that SeNPs can regulate lipid metabolism and participate in the synthesis, secretion and action of parathyroid hormone, proximal tubule bicarbonate reclamation and tricarboxylic acid cycle. Moreover, SeNPs increased (P < 0.05) the abundance of Holdemanella and the levels of acetate and propionate. Correlation analysis suggested that Holdemanella was closely associated with the regulatory effects of SeNPs on early-weaned piglets through participating in lipid metabolism. Overall, replacing dietary Na2SeO3 with biogenic SeNPs could be a potential nutritional intervention strategy to prevent early-weaning syndrome in piglets.

Interactions of vitamin D with parathyroid glands; an updated mini-review

Vitamin D is essential for regulating calcium and phosphate metabolism, and its deficiency or excess can significantly affect parathyroid function. The deficiency or insufficiency of vitamin D can lead to increased parathyroid hormone (PTH) production, resulting in secondary hyperparathyroidism. Conversely, adequate vitamin D levels suppress PTH synthesis and maintain normal calcium levels. Dysregulation of this delicate balance can contribute to various disorders such as osteoporosis, renal stones, and skeletal abnormalities. Hence, understanding the complex interactions between vitamin D and the parathyroid glands is important for diagnosing and managing disorders such as primary and secondary hyperparathyroidism.

Association of parathyroid hormone with plasma magnesium in health and disease; a review

Parathyroid hormone (PTH) is a hormone produced by the parathyroid glands that regulates calcium and phosphate metabolism in the body. Magnesium is an essential mineral that plays a role in many cellular processes, including nerve and muscle function, DNA synthesis, and bone health. This review aims to examine the association between PTH and magnesium in health and disease states. Several studies have shown that lower levels of magnesium in the blood are associated with higher levels of PTH. This association has been observed in both healthy individuals and those with chronic kidney disease, primary hyperparathyroidism, and vitamin D deficiency. The mechanism by which magnesium regulates PTH synthesis is not yet fully understood but appears to involve magnesium’s role in the calcium-sensing receptor (CaSR) and cellular signaling pathways. In conclusion, the evidence suggests a clear and significant association between PTH and magnesium, with lower serum magnesium levels associated with elevated PTH levels. Further research is needed to understand clinical practice’s underlying mechanisms and implications.

Lithium-induced parathyroid disease; an updated mini-review

Lithium is a medication commonly used to treat bipolar disorder and other psychiatric conditions. However, long-term use of lithium can lead to parathyroid dysfunction, known as lithium-induced parathyroid disease. The exact mechanism underlying lithium-induced parathyroid disease is not fully understood. Still, it is believed that lithium interferes with the normal function of the parathyroid gland by inhibiting the synthesis and secretion of parathyroid hormone (PTH) and impairing the sensitivity of the parathyroid gland to calcium. The management of lithium-induced parathyroid disease depends on the type and severity of parathyroid dysfunction. In patients with hypoparathyroidism, treatment involves the replacement of calcium and vitamin D supplements. In severe cases, intravenous calcium may be necessary. In patients with hyperparathyroidism, treatment consists in discontinuing lithium therapy and monitoring serum calcium and PTH levels. In situations where hyperparathyroidism persists, or complications like kidney stones or osteoporosis arise, surgery may become necessary.