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Zinc is an essential mineral that is required for normal skeletal growth and bone homeostasis. Furthermore, zinc appears to be able to promote bone regeneration. However, the cellular and molecular pathways through which zinc promotes bone growth, homeostasis, and regeneration are poorly understood. Zinc can positively affect chondrocyte and osteoblast functions, while inhibiting osteoclast activity, consistent with a beneficial role for zinc in bone homeostasis and regeneration. Based on the effects of zinc on skeletal cell populations and the role of zinc in skeletal growth, therapeutic approaches using zinc to improve bone regeneration are being developed. This review focuses on the role of zinc in bone growth, homeostasis, and regeneration while providing an overview of the existing studies that use zinc as a bone regeneration therapeutic.

Here, we report on the development of a cost-effective, well-characterized three-dimensional (3D) model of bone homeostasis derived from commonly available stocks of immortalized murine cell lines and laboratory reagents. This 3D murine-cell-derived bone organoid model (3D-mcBOM) is adaptable to a range of contexts and can be used in conjunction with surrogates of osteoblast and osteoclast function to study cellular and molecular mechanisms that affect bone homeostasis in vitro or to augment in vivo models of physiology or disease. The 3D-mcBOM was established using a pre-osteoblast murine cell line, which was seeded into a hydrogel extracellular matrix (ECM) and differentiated into functional osteoblasts (OBs). The OBs mineralized the hydrogel ECM, leading to the deposition and consolidation of hydroxyapatite into bone-like organoids. Fourier-transform infrared (FTIR) spectroscopy confirmed that the mineralized matrix formed in the 3D-mcBOM was bone. The histological staining of 3D-mcBOM samples indicated a consistent rate of ECM mineralization. Type I collagen C-telopeptide (CTX1) analysis was used to evaluate the dynamics of OC differentiation and activity. Reliable 3D models of bone formation and homeostasis align with current ethical trends to reduce the use of animal models. This functional model of bone homeostasis provides a cost-effective model system using immortalized cell lines and easily procured supplemental compounds, which can be assessed by measuring surrogates of OB and OC function to study the effects of various stimuli in future experimental evaluations of bone homeostasis.

Osteoblastogenesis plays a critical role in bone repair. Insulin and insulin-mimetic compounds, such as vanadium (IV) oxide acetylacetonate (VAC), have been reported to enhance bone healing in various models. This study aimed to evaluate the effects of vanadium compounds, VAC and vanadium (IV) oxide sulfate (VOSO4), on osteoblast proliferation and function. MC3T3-E1 pre-osteoblast cells were treated with insulin, ascorbic acid, and varying concentrations of VAC or VOSO4, and samples were collected at multiple time points over 21 days. We assessed cell proliferation, functional markers, and gene and protein expression. Our findings demonstrate that both VAC and VOSO4 stimulate MC3T3-E1 proliferation, increase calcium and proteoglycan deposition, and enhance phosphorylation of Protein Kinase B (Akt) over time. Gene expression analysis revealed that VAC treatment upregulated RUNX2, BGLAP, and TWIST2 at Day 7 compared to controls, with sustained expression patterns observed at Day 10. These results align with existing literature, supporting that VAC and VOSO4 promote osteoblastogenesis and may serve as effective adjuvants to accelerate bone regeneration during fracture healing.

Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Many of these immune evasion products expressed during infection antagonize cellular apoptotic pathways. Poxvirus products target multiple points in both the extrinsic and intrinsic apoptotic pathways, thereby mitigating apoptosis during infection. Interestingly, recent evidence indicates that poxviruses also hijack cellular means of eliminating apoptotic bodies as a means to spread cell to cell through a process called apoptotic mimicry. Poxviruses are the causative agent of many human and veterinary diseases. Further, there is substantial interest in developing these viruses as vectors for a variety of uses including vaccine delivery and as oncolytic viruses to treat certain human cancers. Therefore, an understanding of the molecular mechanisms through which poxviruses regulate the cellular apoptotic pathways remains a top research priority. In this review, we consider anti-apoptotic strategies of poxviruses focusing on three relevant poxvirus genera: Orthopoxvirus, Molluscipoxvirus, and Leporipoxvirus. All three genera express multiple products to inhibit both extrinsic and intrinsic apoptotic pathways with many of these products required for virulence.

The COVID-19 pandemic introduced profound and rapid disruptions to family life, particularly affecting parents through altered routines, economic instability, and reduced access to childcare and social support. This study investigates the cascading effects of these stressors on parent–child relationships and their influence on children’s mental and physical well-being. Drawing on a U.S. based national sample, findings reveal that parental daily routine disruptions were significantly associated with adverse child outcomes. The quality of the parent–child relationship emerged as a central mediating factor, fully mediating mental health outcomes and partially mediating physical health impacts. While parental anxiety was a factor, its mediating impact was less pronounced. After peaking in 2020, modest improvements were observed by the end of 2022, yet residual stress and incomplete recovery highlight the enduring psychological impact of the pandemic. These results underscore the importance of strengthening parent–child relationships and alleviating parental burdens during public health crises. Effective policy responses should integrate mental health resources, flexible employment options, and parenting-focused programs that reinforce family stability and developmental outcomes.

Parkinson's disease (PD) is a neurodegenerative condition that is characterized by a progressive decline of neural pathways, and its pathology is associated with alpha-synuclein abnormalities. Currently, infertility affects about 10% of individuals of fertile age within the USA. Interestingly, an increased length of fertility is associated with a decreased incidence of PD. Our study utilized QIAGEN's Ingenuity Pathway Analysis (IPA) to identify and analyze molecular pathways that affect the underlying connection between alpha-synuclein (SNCA)-associated Parkinson's disease (PD) and infertility condition (IC). Furthermore, we explored nicotine's potential as a therapeutic in preventing the exacerbation of IC in terms of SNCA. Although the connection between SNCA-related PD and IC is not well explored, the Qiagen Knowledge Base (QKB) showed an overlap of 12 distinct molecules between SNCA and IC. These molecular pathways were established by adding SNCA and IC to \"Pathway Explorer\" and establishing connections to distinct molecules including transcription regulators, cytokines, and other enzymes/proteins. The Molecule-Activity-Predictor (MAP) tool predicted that SNCA activation would lead to an exacerbation of PD and IC with the potential involvement of dihydrotestosterone (DHT) and caspases. Specifically, it was found that SNCA decreased MAPK8 expression, which led to a downstream upregulation of IC. Activation of nicotine within this overarching molecular network resulted in a downregulation in both PD pathology and IC. Together, these findings reveal a possible connection between infertility condition and genes regularly associated with alpha-synuclein-related Parkinson's disease while identifying nicotine as a potential therapeutic application.

Category: Diabetes; Basic Sciences/Biologics; Trauma Introduction/Purpose: Prophylactic vancomycin treatment decreases the rates of surgical site and deep infections by >70% for diabetic patients undergoing reconstructive foot and ankle surgery. We aimed to identify whether local vancomycin at a clinically relevant dose impaired fracture healing in diabetic rats. Our hypothesis was that local vancomycin powder to the fracture site would not affect long term healing outcomes, but continuous exposure of vancomycin would inhibit differentiation of osteoblast precursor cells and their osteogenic activity in vitro. The 25 mg/kg vancomycin was a modest increase to routine surgical site vancomycin application of 1-2 grams for a 70 kg. adult (21.42 mg/kg). Determining how vancomycin affects diabetic fracture healing is of clinical interest, particularly considering its prophylactic use in foot and ankle patients. Methods: Following induction of a femur fracture in male BB Wistar type 1 diabetic rats, a longitudinal incision was made in the lateral aspect of the femur. Powdered vancomycin (25mg/kg) was administered to fracture site of treated (n=5), and Sham surgery (n=6) control rats. Femurs harvested at 6 weeks after fracture, were X-ray scored, µCT scanned and tested to failure in torsion. Bone marrow and periosteal cells isolated from diabetic bones and MC3T3 cells were plated for MTT survival and osteogenic assays. After 4 days, beta glycerol phosphate, ascorbic acid and either 0, 50, 500, or 5,000 µg/mL vancomycin were added to the media (n=3 per group). Cells were fixed at 7 and 14 days for alkaline phosphatase (ALP) staining and at 28 days for Alizarin Red S staining. Parametric data were analyzed using student t-tests. Non-parametric data were analyzed using a Kruskal-Wallis ANOVA on RANKs and Tukey post-hoc tests. Results: Radiographic scoring did not show differences between the control (2.28+-1.57) and treatment (3.67+-0.75) groups (p=0.093). BV/TV was similar between the control (61.2+-8.4 %) and treatment (56.5+-5.2 %) groups (p=0.081). Mechanical testing found similar values in normalized torque to failure (69.56+-36.80 vs 50.05+-28.82 %N*mm, p=0.356), and torsional rigidity (105.97+-103.62 vs 48.68+-32.95 %Nmm2, p=0.291), for control and treatment groups, respectively. ALP staining was comparable between groups at either 7 (p=0.809) or 14 days (p=0.343) in bone marrow or MC3T3 cells. Alizarin Red S staining found dose- dependent decreases in mineralized nodule formation between the untreated (10.16+-5.01 nodules per 3.8cm2), and 500µg/mL vancomycin (3.16+-2.26 nodules per 3.8cm2) bone marrow groups at 28 days (p=0.026). Periosteal and MC3T3 cell viability were only impaired at the 5000µg/mL vancomycin dose (p=0.001). Conclusion: Our study argues that local application of vancomycin does not affect diabetic fracture healing at clinically relevant doses. We studied a nearly 2-fold higher vancomycin dose than the 'standard' dose of 14.3mg/kg and less than the 143.5mg/kg dose that did not impair rat spine fusion. Although in vitro vancomycin did not affect cell viability and osteogenic staining in periosteal and MC3T3 cells, mineralized nodule formation was dose-dependently inhibited at day 28 in bone marrow cells. Our results bring novel insight into the effects of vancomycin in diabetic fracture healing and the how long-term dosing impacts cell viability and osteoblastogenesis.

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts.

The diversity of bacterial species in the oral cavity makes it a key site for research. The close proximity of the oral cavity to the brain and the blood brain barrier enhances the interest to study this site. Changes in the oral microbiome are linked to multiple systemic diseases. Alcohol is shown to cause a shift in the microbiome composition. This change, particularly in the oral cavity, may lead to neurological diseases. Alzheimer’s disease (AD) is a common neurodegenerative disorder that may cause irreversible memory loss. This study uses the meta-analysis method to establish the link between binge drinking, the oral microbiome and AD. The QIAGEN Ingenuity Pathway Analysis (IPA) shows that high levels of ethanol in binge drinkers cause a shift in the microbiome that leads to the development of AD through the activation of eIF2, regulation of eIF4 and p70S6K signaling, and mTOR signaling pathways. The pathways associated with both binge drinkers and AD are also analyzed. This study provides a foundation that shows how binge drinking and the oral microbiome dysbiosis lead to permeability changes in the blood brain barrier (BBB), which may eventually result in the pathogenesis of AD.

The COVID-19 pandemic continues to affect the world. Wuhan, the epicenter of the outbreak, underwent a 76-day lockdown. Research has indicated that the lockdown negatively impacted the quality of life of older individuals, but little is known about their specific experiences during the confinement period. Qualitative interviews were conducted with 20 elderly residents of Wuhan, aged 65 to 85, who experienced mandatory isolation throughout the pandemic. The interviews centered around three stages of experiences: the Early Lockdown stage (the first week of lockdown after the government implemented the lockdown policy in January 2020), Infection During Lockdown stage (from February to April 2020 when participants were affected by the lockdown), and the Post-Lockdown stage (after April 2020 when the government lifted the lockdown policy). We found that older adults experienced different core themes during each lockdown stage. In the Early Lockdown stage, they felt nervousness and fear while searching for information. During the Lockdown and Infection Stage, they relied on reciprocal support and adjusted to new lifestyles. In the Post-Lockdown stage, they expressed cautions, trust, and gratitude. The finding highlights the evolving emotions and coping strategies of older adults throughout the lockdown phases. This study has yielded valuable insights into the adaptations of behavior and the importance of social interactions, specifically emphasizing the significance of healthcare among the elderly population.