Search Results (775)

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article

Transforming growth factor-β (TGF-β) is a key protein family member that includes activins, inhibins, and bone morphogenetic proteins (BMPs). It is essential in numerous biological processes, such as chemotaxis, apoptosis, differentiation, growth, and cell migration. TGF-β receptors initiate signaling through two primary pathways: the canonical pathway involving Smad proteins and non-canonical pathways that utilize alternative signaling mechanisms. When TGF-β signaling is disrupted, it has been shown to contribute to the development of various diseases, including cancer. Initially, TGF-β effectively inhibits the cell cycle and promotes apoptosis. However, its role can transition to facilitating tumor growth and metastasis as the disease progresses. Moreover, TGF-β drives cancer progression through epithelial–mesenchymal transition (EMT), modulation of factor expression, and evasion of immune responses. This complexity establishes the need for further research, particularly into pharmacological agents targeting TGF-β, which are emerging as promising therapeutic options. Current clinical and preclinical studies are making significant strides toward mitigating the adverse effects of TGF-β. This underscores the critical importance of understanding its underlying mechanisms to enhance treatment effectiveness and improve survival rates for cancer patients. Full article

Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, including CCK-8, Alizarin Red S staining, Quantitative Real-Time PCR (qRT-PCR), and Western blot analysis. The results demonstrated that Osteolforte significantly enhanced osteogenic differentiation in hBMSCs. Alizarin Red S staining revealed increased mineralization, indicating elevated calcium deposition. Gene expression analysis showed an upregulation of key osteogenic markers, including runt-related transcription factor-2 (RUNX-2), collagen type I (COL-1), and bone morphogenetic protein-2 (BMP-2), supporting the role of Osteolforte in promoting osteoblastic activity. In particular, the elevated expression of RUNX-2—a master transcription factor in osteoblast differentiation along with COL-1, a major bone matrix component, and BMP-2, a key bone morphogenetic protein—highlights the compound’s osteogenic potential. In conclusion, Osteolforte enhances early-stage osteogenesis and mineralization in hBMSCs and represents a promising candidate for bone regeneration. Full article

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients. Full article

The transforming growth factor beta (TGF-$\mathsf{\beta }$) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-$\mathsf{\beta }$ family genes based on the genome sequence in Tupaia belangeri, which were classified into the TGF-$\mathsf{\beta }$, bone morphogenetic protein (BMP), growth differentiation factor (GDF), glial cell-derived neurotrophic factor (GDNF), and Activin/Inhibin subfamilies. A phylogenetic analysis revealed the evolutionary relationships among members of the TGF-$\mathsf{\beta }$ family in T. belangeri and their homologous genes in Homo sapiens, Mus musculus, and Pan troglodytes, indicating a high degree of conservation throughout evolution. A chromosomal distribution and collinearity analysis demonstrated the localization of these genes within the genome of T. belangeri and their collinearity with genes from other species. A gene structure and motif analysis further illustrated the conservation and diversity among TGF-$\mathsf{\beta }$ family members. A protein interaction network analysis highlighted the central roles of TGFB1, TGFB3, BMP7, and BMP2 in signal transduction. A functional enrichment analysis underscored the significance of the TGF-$\mathsf{\beta }$ signaling pathway in the biological processes of T. belangeri, particularly in cell proliferation, differentiation, and apoptosis. We assessed the impact of cold acclimation treatment on the expression of TGF-$\mathsf{\beta }$ family proteins in the adipose tissue (white adipose tissue [WAT] and brown adipose tissue [BAT]) of T. belangeri using ELISA technology, finding that protein expression levels in the experimental group were significantly higher than those of in the control group. These results suggested that cold acclimation may enhance the adaptability of T. belangeri to cold environments by modulating the expression of TGF-$\mathsf{\beta }$ family genes. This study offers new insights into the role of the TGF-$\mathsf{\beta }$ family in the cold acclimation adaptation of T. belangeri, providing a scientific foundation for future genetic improvements and strategies for cold acclimation. Full article

The reconstruction of a severely resorbed alveolar bone is a significant challenge in dental implantology and maxillofacial surgery. Traditional bone grafting materials, including autogenous, allogeneic, xenogeneic, and alloplastic materials, have limitations such as donor site morbidity, limited availability, and prolonged maturation periods. To address these challenges, recombinant human bone morphogenetic protein-2 (rhBMP-2) has emerged as a potent osteoinductive factor that facilitates bone regeneration without the need for additional donor site surgery. This study introduces a box technique which combines rhBMP-2 (CowellBMP^®, Cowellmedi, Busan, Republic of Korea) with a 3D-preformed titanium mesh (3D-PFTM), utilizing a mixture of allografts and xenografts for horizontal and vertical alveolar ridge augmentation. The technique leverages the structural stability provided by the OssBuilder^® (Osstem, Seoul, Republic of Korea), a preformed titanium mesh, that allows for simultaneous implant placement and vertical ridge augmentation. This technique not only reduces the treatment time compared to traditional methods but also minimizes post-operative discomfort by eliminating the need for autogenous bone harvesting. Clinical outcomes from this technique demonstrate successful bone regeneration within a shorter period than previously reported techniques, with excellent bone quality and implant stability being observed just four months after vertical augmentation. In conclusion, the so called BOXAM (BMP-2, Oss-builder, Xenograft, Allograft, Maintenance) technique presents a promising therapeutic strategy for alveolar bone reconstruction, particularly in cases of severe bone resorption. Further studies are needed to evaluate the long-term outcomes and potential limitations of this approach, especially in scenarios where the inferior alveolar nerve proximity poses challenges for fixture placement. Full article

The anti-Müllerian hormone (amh) and its receptor, amhr2, along with the downstream bone morphogenetic protein receptors (bmprs), have been recognized as the central regulators in teleost sex determination (SD) and differentiation. However, their evolution and function in reproduction among diverse teleost lineages may represent species-specific patterns and still need more explanation. In this study, systematic investigations of amh signaling genes, including amh, amhy (Y-linked paralog of amh), amhr2, bmpr1, and bmpr2, were conducted among teleost species. The results revealed generally conserved gene copy number, phylogeny, structure, and synteny, among teleost amh signaling genes. Notably, significantly accelerated evolutionary rates (dN/dS) were found in teleost amhy compared to amh, and amh exhibited faster molecular evolution in amhy-SD teleosts than in non-amhy-SD teleosts, suggesting their enhanced evolutionary plasticity in teleosts. Expression profiling identified testis-biased expression of the most amh signaling genes in fish species with different SD genes and mechanisms, including Lateolabrax maculatus and Dicentrarchus labrax from Order Perciformes, Cynoglossus semilaevis and Paralichthys olivaceus from Order Pleuronectiformes, and Salmo salar and Oncorhynchus mykiss from Order Salmoniformes, with ovary-biased expression also found in Salmoniformes. A weighted gene co-expression network analysis further uncovered strong species-specific functional interactions between amh signaling components and genes of germ-cell development, the meiotic process, etc. Collectively, the integrated evidence from this study supports the hypothesis that amh signaling provides the key molecules governing sex differentiation in a species-specific manner in diverse teleost lineages, independent of its SD role, and interacts with functions of both testis and ovary development. Full article

Background: The bone morphogenetic protein (BMP) signaling pathway is essential for lung development. BMP4, a key regulator, binds to type I (BMPR1) and type II (BMPR2) receptors to initiate downstream signaling. While the inactivation of Bmpr1a and Bmpr1b leads to tracheoesophageal fistulae, the role of BMPR2 mutations in lung epithelial development remains unclear. Methods: We generated induced pluripotent stem cells (iPSCs) from a patient carrying a BMPR2 mutation (c.631C>T), and gene-corrected isogenic controls were created using CRISPR/Cas9. These iPSCs were differentiated into lung progenitor cells and subsequently cultured to generate alveolar and airway organoids. The differentiation efficiency and epithelial lineage specification were assessed using immunofluorescence, flow cytometry, and qRT-PCR. Results: BMPR2-mutant iPSCs showed no impairment in forming a definitive or anterior foregut endoderm. However, a significant reduction in lung progenitor cell differentiation was observed. Further, while alveolar epithelial differentiation remained largely unaffected, airway organoids derived from BMPR2-mutant cells exhibited impaired goblet and ciliated cell development, with an increase in basal and club cell markers, indicating skewing toward undifferentiated airway cell populations. Conclusions: BMPR2 dysfunction selectively impairs late-stage lung progenitor specification and disrupts airway epithelial maturation, providing new insights into the developmental impacts of BMPR2 mutations. Full article

Gene therapy has emerged as a promising therapeutic approach across various oral diseases. This review examines current applications and future prospects of gene therapy in dentistry, focusing on five key areas: oral cancer, cancer-related pain, xerostomia (dry mouth), dental caries, and periodontal disease. Recent advances in viral and non-viral vectors have enabled more efficient gene delivery systems, with particular success in cancer pain management through µ-opioid receptor gene transfer and xerostomia treatment using aquaporin-1 gene therapy. For periodontal applications, gene therapy strategies include both immunomodulation and tissue regeneration approaches using growth factors like platelet-derived growth factor and bone morphogenetic proteins. While significant progress has been made, particularly in treating radiation-induced xerostomia and oral cancer pain, challenges remain in vector optimization and delivery methods. Clinical trials, predominantly in Phase I, indicate both the potential and current limitations of gene therapy in oral healthcare. This review synthesizes current evidence and outlines future directions for gene therapy applications in oral medicine and dentistry. Full article

The transforming growth factor-beta (TGF-β) superfamily plays a crucial role in regulating female reproductive traits, particularly litter size, in small ruminants, such as sheep and goats. This review comprehensively examines the molecular mechanisms through which TGF-β superfamily members—including bone morphogenetic proteins (BMPs), growth differentiation factor 9 (GDF9), inhibin (INHA and INHB), and associated signaling genes—influence ovarian follicular development, ovulation rate, and ultimately, litter size. We synthesize recent findings on polymorphisms in key genes, such as BMPR1B, BMP15, GDF9, inhibins and SMADs family genes, across diverse sheep and goat breeds worldwide. The manuscript highlights how specific mutations in these genes create an intricate signaling network that modulates granulosa cell proliferation, follicular sensitivity to FSH, and the prevention of dominant follicle selection. These molecular interactions result in increased ovulation rates and larger litter sizes in prolific breeds. The gene dosage effects observed in heterozygous versus homozygous mutation carriers further illuminate the complex nature of these reproductive regulations. This improved the understanding of the genetic basis for prolificacy provides valuable insights for marker-assisted selection strategies aimed at enhancing reproductive efficiency in small ruminant breeding programs, with significant implications for improving livestock productivity and economic outcomes. Full article

Background/Objectives: Endplate lesions of the lumbar spine are often asymptomatic and frequently observed incidentally by radiological assessment. Variants in the vitamin D receptor gene (VDR) and an increase in some biochemical markers related to the osteo-cartilaginous metabolism were found in patients with endplate lesions. The aim of this study was to identify biochemical and genetic markers putatively associated with the presence of endplate lesions of the lumbar spine. Methods: Quantification of circulating bone remodeling proteins was obtained from 10 patients with endplate lesions and compared with age- and sex-matched controls. Whole exome sequencing (WES) was performed on patient genomic DNA using the Novaseq 6000 platform (Illumina, San Diego, CA, USA), obtaining a median read depth of 117×–200×, with ≥98% of regions covering at least 20×. The sequencing product was aligned to the reference genome (GRCh38.p13-hg38) and analyzed with Geneyx software. Results: We observed modifications in the levels of circulating proteins involved in bone remodeling and angiogenesis. We identified variants of interest in aggrecan (ACAN), bone morphogenetic protein 4 (BMP4), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), GLI family zinc finger 2 (GLI2), heparan sulfate proteoglycan 2 (HSPG2), and mesoderm posterior bHLH transcription factor 2 (MESP2). VDR polymorphism (rs2228570) was present in nine patients, with the homozygotic ones having more severe endplate lesions and higher levels of the analyzed circulating markers in comparison with heterozygotic patients. Conclusions: These data represent interesting evidence of genetic variants, particularly in VDR, and altered levels of circulating markers of bone remodeling associated with endplate lesions, which should be confirmed in a larger population. The hypothesis suggested by our results is that the endplate lesions could be the consequence of an altered ossification mechanism at the vertebral level. Full article

Rosavin, a glycoside isolated from Rhodiola rosea, exhibits various biological activities, including potential modulation of metabolic pathways. Despite promising findings in animal models, its effects on many human bone cells remain unexplored. This study aimed to investigate, for the first time, the in vitro effects of rosavin on human osteoblasts (HOBs), focusing on BMP-2 expression, cell morphology, and culture confluence as indicators of osteogenic activity. HOB cultures were treated with 50 µM or 100 µM rosavin for 21 days. BMP-2 expression was measured by ELISA, collagen production was assessed via Sirius Red staining, and cell morphology and confluence were evaluated using phase-contrast microscopy. A significant increase in BMP-2 expression was observed in the 100 µM rosavin group compared to the mineralization control (p < 0.05), particularly on days 14 and 21. Both rosavin-treated groups exhibited higher confluence than controls, with the 50 µM group showing unexpectedly greater confluence than the 100 µM group. Rosavin at 50 µM also promoted a cuboidal morphology characteristic of active HOBs. The presence of collagen validated both the successful progression of the mineralization process and the correct implementation of the experimental protocol. Rosavin enhances BMP-2 expression and supports HOB proliferation and morphological maturation in vitro. These findings suggest its potential as a supportive agent in the prevention or treatment of metabolic bone diseases. Further research is necessary to determine its bioavailability, safety profile, and therapeutic relevance in clinical settings. Full article

Large segmental bone defects present significant challenges due to the insufficient vascularization of implanted grafts, necessitating advances in vascularized bone tissue engineering. Recent innovations focus primarily on enhancing graft vascularization through advanced biomaterial scaffolds, precise three-dimensional (3D) bioprinting technologies, biochemical interventions, and co-culture techniques. Biomaterial scaffolds featuring microchannels and high-surface-area architectures facilitate endothelial cell infiltration and subsequent vessel formation. Concurrently, sophisticated 3D-bioprinting methods, including inkjet, extrusion, and laser-assisted approaches, enable the precise placement of endothelial and osteogenic cells, promoting anatomically accurate vascular networks. Biochemical strategies that utilize the simultaneous delivery of angiogenic factors (e.g., vascular endothelial growth factor) and osteogenic factors (e.g., bone morphogenetic protein-2) effectively couple angiogenesis and osteogenesis. Additionally, co-culturing mesenchymal stem cells and endothelial progenitors accelerates the development of functional capillary networks. Preclinical studies consistently demonstrate superior outcomes for prevascularized grafts, as evidenced by enhanced vascular inosculation, increased bone formation, and improved mechanical stability compared to non-vascularized controls. These technological advancements collectively represent significant progress toward the clinical translation of engineered vascularized bone grafts capable of addressing complex and previously intractable bone defects. Full article

Background and Objectives: Methotrexate (MTX) is a widely utilised pharmaceutical agent in the treatment of various malignancies and inflammatory diseases. However, its clinical utility is often constrained by its potential for hepatotoxicity. Although pyridostigmine is a well-established reversible acetylcholinesterase inhibitor, its potential therapeutic role in preventing hepatic injury remains incompletely defined. The present study aimed to investigate whether pyridostigmine provides protective effects against MTX-triggered liver damage in a rat model. Methods: Thirty-six female Wistar albino rats randomly assigned to three groups: control (n = 12), MTX + saline (n = 12), and MTX + pyridostigmine (n = 12). Hepatotoxicity was induced by a single-dose MTX injection (20 mg/kg), followed by daily oral administration of either pyridostigmine (5 mg/kg) or saline for ten consecutive days. Hepatic function markers, oxidative stress parameters, fibrosis-associated mediators, and histopathological changes were assessed. Results: Pyridostigmine significantly attenuated MTX-induced elevations in plasma alanine aminotransferase (p < 0.05) and cytokeratin-18 levels (p < 0.001), and reduced liver and plasma malondialdehyde (MDA) levels (p < 0.05). Additionally, pyridostigmine treatment resulted in reduced levels of transforming growth factor-beta (p < 0.05), bone morphogenetic protein-9 (p < 0.001), and endoglin levels (p < 0.05), as well as increased sirtuin 1 level (p < 0.05). Histopathological examination revealed that pyridostigmine treatment significantly reduced MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. Conclusions: Pyridostigmine exerted hepatoprotective effects against MTX-induced liver injury by attenuating oxidative stress, restoring SIRT1 expression, and suppressing pro-fibrotic signaling. These findings indicate that pyridostigmine may hold therapeutic potential for the prevention of MTX-associated hepatotoxicity. Full article

Recently, there has been a gradual increase in the demand for chicken and eggs. The gut, as the vital place of nutrient digestion and absorption, is highly associated with the development of livestock and poultry and the quality of meat, eggs, and milk. Intestinal stem cells, as an important source of intestinal cell proliferation and renewal, exert a vital effect on repairing injured intestinal epithelial cells and keeping homeostasis. Intestinal stem cell-regulated intestinal epithelial balance is closely controlled and modulated by interlinked developmental loops that maintain cell proliferation and differentiation processes in balance. Some conservative signaling pathways, including the Wnt, Notch, hedgehog, and bone morphogenetic protein (BMP) loops, have been proved to modulate intestinal health in poultry. Meanwhile, studies have revealed the importance of the Hippo pathway in gastrointestinal tract physiology by regulating intestinal stem cells. Moreover, crosstalk between Hippo and other signaling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this review, we summarize studies on the role of the Hippo pathway in the intestine in these physiological processes and the underlying mechanisms responsible via interacting with these signaling pathways and discuss future research directions and potential therapeutic strategies targeting Hippo signaling in intestinal disease. A comprehensive understanding of how these signaling pathways regulate stem cell proliferation, differentiation, and self-renewal will help to understand the regulation of intestinal homeostasis. In addition, it has the capacity for creative ways to govern intestinal damage, enteritis, and associated disorders induced by different factors. Full article