Low-Mineral Water Diminishes the Bone Benefits of Boron.

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35-40 °C, 70-80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits.

Potassium Intake and Bone Health: A Narrative Review.

Potassium is a cation involved in the resting phase of membrane potential. Diets rich in fresh fruit and vegetables, whole grains, dairy products, and coffee have high potassium content. The shift from a pre-agriculture diet to today's consumption has led to reduced potassium intake. Indeed, the Western diet pattern is characterized by a high daily intake of saturated fats, sugars, sodium, proteins from red meat, and refined carbohydrates with a low potassium intake. These reductions are also mirrored by high sodium intakes and a high consumption of acid-generating food, which promote a chronic state of low-grade metabolic acidosis. The low-grade metabolic acidosis is a cause of the bone-wasting effect. Therefore, a long-standing acidotic state brings into play the bone that contributes to the buffering process through an increase in osteoclastic resorption. In consideration of this background, we carried out a review that focused on the pathophysiological mechanisms of the relationship between dietary potassium intake and bone health, underlining the detrimental effects of the Western dietary patterns characterized by low potassium consumption.

Evaluating the efficacy of three Y-STRs commercial kits in degraded skeletal remains.

Y chromosome short tandem repeats (Y-STRs) typing is a useful tool in scenarios such as mass graves analysis or disaster victim identification and has become a routine analysis in many laboratories. Not many comparisons have been performed with the currently available commercial kits, much less with degraded skeletal remains. This research aims to evaluate the performance of three commercial Y-STR kits: Yfiler™ Plus, PowerPlex® Y23, and Investigator® Argus Y-28 in 63 degraded skeletal remains from mass graves. PowerPlex® Y23 yields more reportable markers and twice the RFU on average, while Yfiler™ Plus and Investigator® Argus Y-28 exhibited a similar behaviour. Additionally, Argus Y-28, which has not been tested with this kind of samples in literature before, showed a good performance. Finally, a predictive model was attempted to be developed from quantification and autosomal STR data. However, no acceptable model could be obtained. Nevertheless, good Y-STR typing results may be expected if at least 50 pg DNA input is used or 13 autosomal markers were previously obtained.

Differences in Bone Metabolism between Children with Prader-Willi Syndrome during Growth Hormone Treatment and Healthy Subjects: A Pilot Study.

Despite therapy with growth hormone (GH) in children with Prader-Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children with PWS undergoing GH therapy and a low-energy dietary intervention. Twenty-four children with PWS and 30 healthy children of the same age were included. Serum concentrations of bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), periostin, osteopontin, osteoprotegerin (OPG), sclerostin, C-terminal telopeptide of type I collagen (CTX-I), and insulin-like growth factor-I (IGF-I) were determined using immunoenzymatic methods. OC levels and the OC/CTX-I ratios were lower in children with PWS than in healthy children (p = 0.011, p = 0.006, respectively). Glu-OC concentrations were lower (p = 0.002), but Gla-OC and periostin concentrations were higher in patients with PWS compared with the controls (p = 0.005, p < 0.001, respectively). The relationships between IGF-I and OC (p = 0.013), Gla-OC (p = 0.042), and the OC/CTX-I ratio (p = 0.017) were significant after adjusting for age in children with PWS. Bone turnover disorders in children with PWS may result from impaired bone formation due to the lower concentrations of OC and the OC/CTX-I ratio. The altered profile of OC forms with elevated periostin concentrations may indicate more intensive carboxylation processes of VKDPs in these patients. The detailed relationships between the GH/IGF-I axis and bone metabolism markers, particularly VKDPs, in children with PWS requires further research.

A Review of Animal Models for Studying Bone Health in Type-2 Diabetes Mellitus (T2DM) and Obesity.

Preclinical research on diabetes and obesity has been carried out in various animal models over the years. These animal models are developed from genetic manipulation that affects their body metabolism, chemical-induced procedures, diet alteration/modifications, or combinations of the aforementioned approaches. The diabetic and obesity animal models have allowed researchers to not only study the pathological aspect of the diseases but also enable them to screen and explore potential therapeutic compounds. Besides several widely known complications such as macrovascular diseases, diabetic neuropathy, nephropathy and retinopathy, type 2 diabetes mellitus is also known to affect bone health. There is also evidence to suggest obesity affects bone health. Therefore, continuous research needs to be conducted to find a remedy or solution to this matter. Previous literature reported evidence of bone loss in animal models of diabetes and obesity. These findings, as highlighted in this review, further augment the suggestion of an inter-relationship between diabetes, obesity and bone loss.

Differences in the Renal Accumulation of Radiogallium-Labeled (Glu)14 Peptides Containing Different Optical Isomers of Glutamic Acid.

Acidic amino acid peptides have a high affinity for bone. Previously, we demonstrated that radiogallium complex-conjugated oligo-acidic amino acids possess promising properties as bone-seeking radiopharmaceuticals. Here, to elucidate the effect of stereoisomers of Glu in Glu-containing peptides [(Glu)14] on their accumulation in the kidney, the biodistributions of [67Ga]Ga-N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid-conjugated (l-Glu)14 ([67Ga]Ga-HBED-CC-(l-Glu)14), [67Ga]Ga-HBED-CC-(d-Glu)14, [67Ga]Ga-HBED-CC-(dl-Glu)14, and [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [67Ga]Ga-HBED-CC-(d-Glu-l-Glu)7 exhibiting the lowest level of kidney accumulation among these compounds. Repeated d- and l-peptides may be a useful method for reducing renal accumulation in some cases.

Efficient Hydroxyapatite Extraction from Salmon Bone Waste: An Improved Lab-Scaled Physico-Chemico-Biological Process.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods-alkaline hydrolysis, calcination, and NaOH hydrolysis-to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis-calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications.

The people behind the papers - Yukiko Kuroda and Koichi Matsuo.

Developing bones can adapt their shape in response to mechanical stresses from neighbouring growing organs. In a new study, Koichi Matsuo and colleagues examine how bone-forming osteoblasts and bone-resorbing osteoclasts coordinate growth in the mouse fibula. They describe the process called 'endo-forming trans-pairing', where bone resorption by osteoclasts in the outer periosteum is paired with bone formation by osteoblasts in the inner endosteum to shape the growing bone. To learn more about the story behind the paper, we caught up with first author Yukiko Kuroda and the corresponding author Koichi Matsuo, Professor at the School of Medicine, Keio University, Japan.

Effect of PSMA PET/CT on the Use of Bone Scintigraphy for Prostate Cancer at a University Hospital System.

We observed at our university-based imaging centers that when prostate-specific membrane antigen (PSMA) PET/CT became available for staging and restaging prostate cancer, the volume of bone scanning on patients with prostate cancer (BS-P) markedly decreased. We aimed to study use patterns of PSMA PET/CT and BS-P at our imaging centers during the 4-y period around U.S. Food and Drug Administration approval of PSMA PET/CT in December 2020. We tested the hypothesis that the rate of decline of BS-P accelerated after U.S. Food and Drug Administration approval, as physicians planned for use of PSMA PET/CT in their patients. Methods: Our clinical report system was searched for BS-P and PSMA PET/CT scans from January 2019 through June 2023. Numbers of scans were tabulated by quarter and year. Quantitative and statistical analyses were performed. Results: Annualized average monthly BS-P peaked at 53.7 scans/mo in 2021 and then decreased over time. There were 552 BS-Ps performed in 2019, 503 in 2020, 614 in 2021, 481 in 2022, and 152 in the first half of 2023. BS-P monthly averages declined by 22% from 2021 to 2022 and by 36% from 2022 to 2023, whereas monthly PSMA PET/CT scan averages increased by 1,416% from 2021 to 2022 and by 69% from 2022 to 2023. There was a significantly greater decline in BS-Ps from 2022 to 2023 than from 2021 to 2022 (36% vs. 22%, P < 0.0001). There were 30 PSMA PET/CT scans performed in 2021, 455 in 2022, and 384 in the first half of 2023. The greatest quarterly increase in these scans (400%) occurred at the outset of PSMA PET/CT implementation in quarter 4 of 2021. In quarter 2 of 2023, the percentage of total studies was higher for PSMA PET/CT than for BS-P (74% vs. 26%, P < 0.0001). Conclusion: At our university-based imaging centers, use of BS-P has declined in correlation with the timing of U.S. Food and Drug Administration approval and implementation of PSMA PET/CT. This study illustrates one instance of workflow changes that occur in the nuclear medicine clinic when new agents are introduced and affect clinical management options.

Apoptotic metabolites ameliorate bone aging phenotypes via TCOF1/FLVCR1-mediated mitochondrial homeostasis.

Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.

A whole-body micro-CT scan library that captures the skeletal diversity of Lake Malawi cichlid fishes.

Here we describe a dataset of freely available, readily processed, whole-body µCT-scans of 56 species (116 specimens) of Lake Malawi cichlid fishes that captures a considerable majority of the morphological variation present in this remarkable adaptive radiation. We contextualise the scanned specimens within a discussion of their respective ecomorphological groupings and suggest possible macroevolutionary studies that could be conducted with these data. In addition, we describe a methodology to efficiently µCT-scan (on average) 23 specimens per hour, limiting scanning time and alleviating the financial cost whilst maintaining high resolution. We demonstrate the utility of this method by reconstructing 3D models of multiple bones from multiple specimens within the dataset. We hope this dataset will enable further morphological study of this fascinating system and permit wider-scale comparisons with other cichlid adaptive radiations.

Impact of anti-fracture medications on bone material and strength properties: a systematic review and meta-analysis.

Background and aims: Reduced bone mineral density (BMD) and microarchitectural deterioration contribute to increased fracture risk. Although the effects of anti-fracture medications (AFMs) on BMD are well-documented, their impact on bone material properties (BMPs) remains poorly characterized. Accordingly, we conducted a systematic review and meta-analysis to evaluate the effects of AFMs on BMPs. Based on data availability, we further categorized AFMs into anti-resorptives, bisphosphonates alone, and strontium ranelate subgroups to perform additional analyses of BMPs in osteoporotic patients. Methods: We did a comprehensive search of three databases, namely, PubMed, Web of Science, and Google Scholar, using various permutation combinations, and used Comprehensive Meta-Analysis software to analyze the extracted data. Results: The 15 eligible studies (randomized and non-randomized) compared the following: (1) 301 AFM-treated patients with 225 on placebo; (2) 191 patients treated with anti-resorptives with 131 on placebo; (3) 86 bisphosphonate-treated patients with 66 on placebo; and (4) 84 strontium ranelate-treated patients with 70 on placebo. Pooled analysis showed that AFMs significantly decreased cortical bone crystallinity [standardized difference in means (SDM) -1.394] and collagen maturity [SDM -0.855], and collagen maturity in cancellous bone [SDM -0.631]. Additionally, anti-resorptives (bisphosphonates and denosumab) significantly increased crystallinity [SDM 0.387], mineral-matrix ratio [SDM 0.771], microhardness [SDM 0.858], and contact hardness [SDM 0.952] of cortical bone. Anti-resorptives increased mineral-matrix ratio [SDM 0.543] and microhardness [SDM 0.864] and decreased collagen maturity [SDM -0.539] in cancellous bone. Restricted analysis of only bisphosphonate-treated studies showed a significant decrease in collagen maturity [SDM -0.650] in cancellous bone and an increase in true hardness [SDM 1.277] in cortical bone. In strontium ranelate-treated patients, there was no difference in BMPs compared to placebo. Conclusion: Collectively, our study suggests that AFMs improve bone quality, which explains their anti-fracture ability that is not fully accounted for by increased BMD in osteoporosis patients.

The balance between helper T 17 and regulatory T cells in osteoimmunology and relevant research progress on bone tissue engineering.

BACKGROUND: Bone regeneration is a well-regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process. OBJECTIVE: This review aims to summarize the role of the T-helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering. RESULTS: The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano-structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration. CONCLUSION: Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.

[Challenges in Understanding the Biological and Pharmacological Responses Based on Emergent Complexity in Biological Systems: From Bone Metabolism to General Physiology].

Biological systems are complex, and although researchers strive to understand them, the accumulated knowledge often complicates integrative comprehension. Consolidating this knowledge can provide insights into the landscape of specific biological events. Our study on bone metabolism, focusing on the behavior of the receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) highlighted the challenges in understanding its role across different cell types. At the same time, the study underscores the importance of exploring interactions between various players (cell types and genes/proteins) in complex systems, which is a core focus of systems biology. Analysis by mathematical models is a potentially powerful tool for describing the dynamic behavior of components in the interaction networks. However, such model-based analyses are limited by parameter availability and reliability. To address this, we proposed two approaches, i.e., sequential simulation and system-wide behavior constraints. Sequential simulation of small dynamic models offers potential in reproducing behavior in larger networks, as seen in toxicity analysis of sunitinib-related adverse effects. System-wide constraints derived from "homeostasis" help reduce the parameter search space in large-scale models, as demonstrated in model-based analysis of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the arachidonic acid pathway. These analytical approaches offer insights into biological system dynamics and can enhance our understanding of pharmacological effects that result from perturbations in complexities of biological systems.

Multi-method dating reveals 200 ka of Middle Palaeolithic occupation at Maras rock shelter, Rhône Valley, France.

The emergence of the Middle Palaeolithic, and its variability over time and space are key questions in the field of prehistoric archaeology. Many sites have been documented in the south-eastern margins of the Massif central and the middle Rhône valley, a migration path that connects Northern Europe with the Mediterranean. Well-dated, long stratigraphic sequences are essential to understand Neanderthals dynamics and demise, and potential interactions with Homo sapiens in the area, such as the one displayed at the Maras rock shelter ("Abri du Maras"). The site is characterised by exceptional preservation of archaeological remains, including bones dated using radiocarbon (14C) and teeth using electron spin resonance combined with uranium series (ESR/U-series). Optically stimulated luminescence was used to date the sedimentary deposits. By combining the new ages with previous ones using Bayesian modelling, we are able to clarify the occupation time over a period spanning 200,000 years. Between ca. 250 and 40 ka, the site has been used as a long-term residence by Neanderthals, specifically during three interglacial periods: first during marine isotopic stage (MIS) 7, between 247 ± 34 and 223 ± 33 ka, and then recurrently during MIS 5 (between 127 ± 17 and 90 ± 9 ka) and MIS 3 (up to 39,280 cal BP).

Bone scaffolds-based localized drugs delivery for osteosarcoma: current status and future perspective.

A common malignant bone neoplasm in teenagers is Osteosarcoma. Chemotherapy, surgical therapy, and radiation therapy together comprise the usual clinical course of treatment for Osteosarcoma. While Osteosarcoma and other bone tumors are typically treated surgically, however, surgical resection frequently fails to completely eradicate tumors, and in turn becomes the primary reason for postoperative recurrence and metastasis, ultimately leading to a high rate of mortality. Patients still require radiation and/or chemotherapy after surgery to stop the spread of the tumor and its metastases, and both treatments have an adverse influence on the body's organ systems. In the postoperative management of osteosarcoma, bone scaffolds can load cargos (growth factors or drugs) and function as drug delivery systems (DDSs). This review describes the different kinds of bone scaffolds that are currently available and highlights key studies that use scaffolds as DDSs for the treatment of osteosarcomas. The discussion also includes difficulties and perspectives regarding the use of scaffold-based DDSs. The study may serve as a source for outlining efficient and secure postoperative osteosarcoma treatment plans.

An open dataset for oracle bone character recognition and decipherment.

Oracle bone script, one of the earliest known forms of ancient Chinese writing, presents invaluable research materials for scholars studying the humanities and geography of the Shang Dynasty, dating back 3,000 years. The immense historical and cultural significance of these writings cannot be overstated. However, the passage of time has obscured much of their meaning, presenting a significant challenge in deciphering these ancient texts. With the advent of Artificial Intelligence (AI), employing AI to assist in deciphering Oracle Bone Characters (OBCs) has become a feasible option. Yet, progress in this area has been hindered by a lack of high-quality datasets. To address this issue, this paper details the creation of the HUST-OBC dataset. This dataset encompasses 77,064 images of 1,588 individual deciphered characters and 62,989 images of 9,411 undeciphered characters, with a total of 140,053 images, compiled from diverse sources. The hope is that this dataset could inspire and assist future research in deciphering those unknown OBCs. All the codes and datasets are available at https://github.com/Pengjie-W/HUST-OBC .

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop new systems for treating bone related diseases and even repurposing current drug therapies. In this review, we shall summarise the latest progress in this area and present a perspective for future development in the field. We will focus on calcium-based nanoparticle systems that modulate calcium metabolism and consequently, the bone microenvironment to inhibit disease progression (including cancer). We shall also review the bone affinity drug family, bisphosphonates, as both a nano-drug and nano-delivery system for bone targeted therapy. The ability to target and release the drug in a controlled manner at the disease site represents a promising safe therapy to treat bone diseases in the future.

[Research progress of electrospinning polyurethane fiber in the field of biomedical tissue engineering].

Polyurethane materials have good biocompatibility, blood compatibility, mechanical properties, fatigue resistance and processability, and have always been highly valued as medical materials. Polyurethane fibers prepared by electrostatic spinning technology can better mimic the structure of natural extracellular matrices (ECMs), and seed cells can adhere and proliferate better to meet the requirements of tissue repair and reconstruction. The purpose of this review is to present the research progress of electrostatically spun polyurethane fibers in bone tissue engineering, skin tissue engineering, neural tissue engineering, vascular tissue engineering and cardiac tissue engineering, so that researchers can understand the practical applications of electrostatically spun polyurethane fibers in tissue engineering and regenerative medicine.