COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives

COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

Rickets guidance: part I—diagnostic workup

Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in the growth plate. Its symptoms depend on the patients’ age, duration of disease, and underlying disorder. Common features include thickened wrists and ankles due to widened metaphyses, growth failure, bone pain, muscle weakness, waddling gait, and leg bowing. Affected infants often show delayed closure of the fontanelles, frontal bossing, and craniotabes. The diagnosis of rickets is based on the presence of these typical clinical symptoms and radiological findings on X-rays of the wrist or knee, showing metaphyseal fraying and widening of growth plates, in conjunction with elevated serum levels of alkaline phosphatase. Nutritional rickets due to vitamin D deficiency and/or dietary calcium deficiency is the most common cause of rickets. Currently, more than 20 acquired or hereditary causes of rickets are known. The latter are due to mutations in genes involved in vitamin D metabolism or action, renal phosphate reabsorption, or synthesis, or degradation of the phosphaturic hormone fibroblast growth factor 23 (FGF23). There is a substantial overlap in the clinical features between the various entities, requiring a thorough workup using biochemical analyses and, if necessary, genetic tests. Part I of this review focuses on the etiology, pathophysiology and clinical findings of rickets followed by the presentation of a diagnostic approach for correct diagnosis. Part II focuses on the management of rickets, including new therapeutic approaches based on recent clinical practice guidelines.

Silicon Mitigates Nutritional Stress of Nitrogen, Phosphorus, and Calcium Deficiency in Two Forages Plants

Forages are one of the most cultivated crops in the world. However nutritional deficiency is common, specifically in N, P and Ca in many forages growing regions. Silicon (Si) can attenuate the stress caused by nutritional deficiency, but studies on the effects of Si supply on in forages plants are still scarce. This research was carried out to evaluate whether the Si supply can mitigate the effects of N, P and Ca deficiencies of two forages and the physiological and nutritional mechanisms involved. Two experiments were carried out with two forage species (Urochloa brizantha cv. Marandu and Megathyrsus maximum cv. Massai). Was used nutrient solution under balanced nutrition conditions and nutritional stress due to the lack of N, P and Ca combined with the -Si and +Si. The deficiencies of N, P and Ca in both forages cultivation caused damage to physiological and nutritional variables, hence decreasing the plant dry matter. However, in both species forages the addition of Si to the nutrient solution decreased the extravasation of cellular electrolytes and increased the content of phenolic compounds, the green color index, the quantum efficiency of photosystem II, the efficiencies of use of N, P and Ca and the production of shoot dry mass. The beneficial effects of Si were evidenced in stressed and non-stressed plants. The research emphasized the advantage of using Si for the growth of U. brizantha and M. maximum under N, P and Ca deficiency, contributing to their sustainable cultivation.

Transcriptomics Reveals the ERF2-bHLH2-CML5 Module Responses to H2S and ROS in Postharvest Calcium Deficiency Apples

Calcium deficiency usually causes accelerated quality deterioration in postharvest fruit, whereas the underlining mechanism is still unclear. Here, we report that calcium deficiency induced the development of bitter pit on the surface of apple peels compared with the healthy appearance in control apples during postharvest storage. Physiological analysis indicates that calcium-deficient peels contained higher levels of superoxide anion (O2•−), malondialdehyde (MDA), total phenol, flavonoid contents and polyphenol oxidase (PPO) activity, and reduced calcium, H2S production, anthocyanin, soluble protein content, and peroxidase (POD) activity compared with those in calcium-sufficient peels. The principal component analysis (PCA) results show that calcium content, ROS, and H2S production were the main factors between calcium-deficient and calcium-sufficient apple peels. Transcriptome data indicated that four calmodulin-like proteins (CMLs), seven AP2/ERFs, and three bHLHs transcripts were significantly differentially expressed in calcium-deficient apple peels. RT-qPCR and correlation analyses further revealed that CML5 expression was significantly positively correlated with the expression of ERF2/17, bHLH2, and H2S production related genes. In addition, transcriptional co-activation of CML5 by ERF2 and bHLH2 was demonstrated by apple transient expression assays and dual-luciferase reporter system experiments. Therefore, these findings provide a basis for studying the molecular mechanism of postharvest quality decline in calcium-deficient apples and the potential interaction between Ca2+ and endogenous H2S.

Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant

Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R510stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G660R) that, surprisingly, does not affect the Ca2+ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G660R and R510stop mutants and combinations with wild type TRPV6. We show that both the G660R and R510stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases.

Comparative Physiological and Transcriptomic Analysis Reveal MdWRKY75 Associated With Sucrose Accumulation in Postharvest Apples With Bitter Pits

Background: Calcium (Ca) deficiency can cause apple bitter pits, reduce the quality and shelf life. WRKY Transcription factors play essential role in plant response to multiple diseases. However, the underlying mechanisms causing bitter pits in apple fruit due to Ca deficiency during storage is extremely limited. Results: In the present study, the nutritional metabolites and reactive oxygen species (ROS) were compared in Ca-deficient and healthy apple fruit (CK) during storage. Results showed that Ca-deficient apples sustained significantly higher production of ROS, PPO activity, flavonoids, total phenol, total soluble solids (TSS), and sucrose contents, but the contents of Ca, H2O2, titratable acids (TA), glucose and fructose were significantly lower than those of CK during storage. Principal component analysis (PCA) showed that TSS, •O2−­, PPO, MDA and Ca were the main factors, and TSS had a positive correlation with sucrose. Furthermore, transcriptome analysis revealed that WRKYs were co-expressed with sucrose metabolism-related enzymes (SWEETs, SS, SPS). RT-qPCR and correlation analysis indicated that MdWRKY75 were significantly positively correlated with MdSWEET1. Moreover, transient overexpression of MdWRKY75 could significantly increase the sucrose content and promote the expression of MdSWEET1 in apple fruit.Conclusions: Calcium deficiency could decrease antioxidant capacity, accelerate nutritional metabolism and up-regulate the expression of WRKYs in apple with bitter pits. Overexpression of MdWRKY75 significantly increased sucrose accumulation and the expression of MdSWEET1. These findings further strengthened knowledge of the basic molecular mechanisms in calcium-deficient apple flesh and contributed to improving the nutritional quality of apple fruit.

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of osteoporosis and bone fractures

Background Non-alcoholic fatty liver disease (NAFLD) and osteoporosis are common diseases with a rising incidence worldwide. Both diseases occur in similar patient populations, however, data on their mutual influence are conflicting. Here, we aimed to evaluate the impact of NAFLD on the incidence of osteoporosis and fractures by using the Disease Analyzer database featuring data on diagnoses, prescriptions, and demographic aspects of 7.49 million cases followed in general practices in Germany. Methods A total of 50,689 patients with NAFLD diagnosed between 2000 and 2015 were matched by age, sex, index year, and 3 comorbidities (obesity, diabetes mellitus, and vitamin D/calcium deficiency) to a cohort of equal size without NAFLD. Incidence of osteoporosis and bone fractures were compared between both groups within 10 years from the index date. Results Within the observation period, the incidence of osteoporosis was significantly higher in the NAFLD group (6.4%) compared to patients without NAFLD (5.1%; log-rank, p < 0.001). Similar results were observed for bone fractures (12.6 vs. 10.3 %; log-rank p < 0.001). The difference was more pronounced in women compared to men and observed in all age groups >50 years of age. Conclusion Our data show that NAFLD is significantly associated with osteoporosis as well as bone fractures in a large cohort of patients followed in German general practices. This finding suggests that NAFLD patients might benefit from improved monitoring for the occurrence of bone demineralization and osteoporosis, which in turn could trigger preventive therapeutic measures.

Vitamin D Receptor Binding with DNA in Duodenal Crypt, Duodenal Villi, and Colonic Epithelial Cells of Mice

Vitamin D receptor (VDR) is a transcription factor that mediates calcium absorption by intestinal epithelial cells. Although calcium absorption is ca-nonically thought to occur only in the small intestine, recent studies have shown that VDR activity in the co-lon alone is sufficient to prevent calcium deficiency in mice. Here, we further investigate VDR activity in the colon. We assess VDR-DNA binding in mouse duodenal crypt, duodenal villi, and colonic epithelial cells using Chromatin Immunoprecipitation se-quencing (ChIP-seq). We find that most VDR-respon-sive elements are common to all intestinal epithelial cells, though some VDR-responsive elements are re-gionally-enriched and exhibit greater VDR-binding affinity in either duodenal epithelial cells or colonic epithelial cells. We also assess chromatin accessibil-ity in the same three cell types using Assay for Trans-posase-Accessible Chromatin sequencing (ATAC-seq). By integrating the VDR ChIP-seq and ATAC-seq data, we find that regionally-enriched VDR-re-sponsive elements exhibit greater chromatin acces-sibility in the region of their enrichment. Finally, we assess the transcription factor motifs present in VDR-responsive elements. We find that duodenum- and colon-enriched VDR-responsive elements exhibit different sets of transcription factor motifs other than VDR, suggesting that VDR may act together with dif-ferent partner transcription factors in the two re-gions. Our work is the first investigation of VDR-DNA binding in the colon and provides a basis for further investigations of VDR activity in the colon.

Pharmaceutico-analytical study of Praval Bhasma (Coral calax) with two different herbs

Introduction: In the present study, Praval is used as a raw material to form Praval Bhasma. Praval (Coral) is the calcareous skeleton of the minute marine organism called Anthezoa polypus and belongs to phylum coelenterate. It is a natural source of rich calcium widely used in Deepan, Pachan, Amlapitta Raktapitta, Yakshma, Kasa, Netra Roga and Hridaya Roga (1)and Calcium deficiency diseases etc. it is administered in the form of Bhasma and Pishti. Method: Shodhan of Praval is done in Sarjika kshara. The Pravala bhasma is prepared by two different method by triturating it with Kumari Swaras and Guduchi Kashay and incineration in Muffle furnace. physico-chemical tests like Total Ash, Acid Insoluble Ash, Loss on Drying, and Qualitative analysis of praval bhasma by NPST (Namburi Phased Spot Test) are done. Result & conclusion: Praval bhasma prepared by two different medicines shows potency, efficacy for further clinical use.