Sox9: A potential regulator of cancer stem cells in osteosarcoma.

Osteosarcoma is a highly aggressive bone tumor primarily affecting children and adolescents. Despite advancements in treatment modalities, the prognosis for osteosarcoma patients remains poor, emphasizing the need for a deeper understanding of its underlying mechanisms. In recent years, the concept of cancer stem cells (CSCs) has emerged as a crucial factor in tumor initiation, progression, and therapy resistance. These specialized subpopulations of cells possess self-renewal capacity, tumorigenic potential, and contribute to tumor heterogeneity. Sox9, a transcription factor known for its critical role in embryonic development and tissue homeostasis, has been implicated in various malignancies, including osteosarcoma. This review aims to summarize the current knowledge regarding the role of Sox9 in CSCs in osteosarcoma and its potential implications as a prognosis and therapeutic target.

Knowledge Mapping of Macrophage in Spinal Cord Injury: A Bibliometric Analysis.

BACKGROUND: Spinal cord injury (SCI) is a devastating condition, often leading to significant disability and impairment. As crucial immune cells, macrophages play a critical role in the pathophysiology of SCI. Understanding the current state of knowledge and research trends related to macrophages in SCI is crucial for developing effective therapeutic interventions. METHODS: Using search strategies, we retrieved relevant articles from the Web of Science Core Collection (WOSCC), resulting in a robust dataset for analysis. VOSviewer, Citespace, and PRISM were employed for analysis and visualization. Various bibliometric indicators, including publication trends, citation analysis, co-authorship networks, and keyword analysis, were utilized to assess the scholarly landscape of macrophage research in SCI. RESULTS: Our findings revealed a steady increase in publications over the past 33 years, indicating a growing interest in this field. We identified Popovich Phillip G was the most influential author, Ohio State University was the most influential institution, and identification of 2 distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord was the most influential paper in this field. CONCLUSIONS: This bibliometric analysis provides a comprehensive overview of the current knowledge landscape and research trends regarding macrophages in SCI. Neuroinflammation and macrophage polarization, transplation and molecular mechanism were emerging research areas and novel directions. Our study serves as a valuable resource for researchers in spinal cord injury research and therapeutic development.

Surgical outcomes of percutaneous endoscopic lumbar discectomy in obese adolescents with lumbar disc herniation.

In recent years, with improved living standards, adolescent obesity has been increasingly studied. The incidence of lumbar disc herniation (LDH) in obese adolescents is increasing yearly. No clinical studies have reported the use of percutaneous endoscopic lumbar discectomy (PELD) in obese adolescent lumbar disc herniation (ALDH) patients. This study evaluated the preliminary surgical outcomes of PELD in obese ALDH patients. Fifty-one ALDH patients underwent single-level PELD surgery between January 2014 and January 2020. Patients were divided into an obese group and a normal group. Patient characteristics and surgical variables were compared between the two groups. The VAS, ODI, and SF-36 scales were used preoperatively and postoperatively to evaluate the clinical efficacy. In this study, 19 patients were included in the obese group, and 28 were included in the normal group. There was no significant difference in age, sex, duration of low back pain, duration of leg pain, or operative level between the obese and normal groups preoperatively. The obese group had a longer operative time (OT) (101.9 ± 9.0 min vs. 84.3 ± 11.0 min, P < 0.001), more fluoroscopy exposures (41.0 ± 5.8 vs. 31.6 ± 7.0, P < 0.001) and a longer time to ambulation (29.9 ± 4.0 vs. 25.0 ± 2.9, p < 0.001) than the normal group. The groups did not significantly differ in complications. The VAS score for back and leg pain and the ODI and SF-36 score for functional status improved significantly postoperatively. The PELD procedure is a safe and feasible method for treating LDH in obese adolescents. Obese ALDH patients require a longer OT, more fluoroscopy exposures and a longer time to get out of bed than normal ALDH patients. However, PELD yields similar clinical outcomes in obese and normal ALDH patients.

Global research trends and hotspots on tendon-derived stem cell: a bibliometric visualization study.

Purpose: This study was aimed to examine the global research status and current research hotspots in the field of tendon stem cells. Methods: Bibliometric methods were employed to retrieve relevant data from the Web of Science Core Collection (WOSCC) database. Additionally, Citespace, Vosviewer, SCImago, and Graphad Prism were utilized to analyze the publication status in this field, identify the current research hotspots, and present a mini-review. Results: The most active countries in this field were China and the United States. Notable authors contributing significantly to this research included Lui Pauline Po Yee, Tang Kanglai, Zhang Jianying, Yin Zi, and Chen Xiao, predominantly affiliated with institutions such as the Hong Kong Hospital Authority, Third Military Medical University, University of Pittsburgh, and Zhejiang University. The most commonly published journals in this field were Stem Cells International, Journal of Orthopedic Research, and Stem Cell Research and Therapy. Moreover, the current research hotspots primarily revolved around scaffolds, molecular mechanisms, and inflammation regulation. Conclusion: Tendon stem cells hold significant potential as seed cells for tendon tissue engineering and offer promising avenues for further research Scaffolds, molecular mechanisms and inflammation regulation are currently research hotspots in this field.

Chemotherapy reinforces anti-tumor immune response and enhances clinical efficacy of immune checkpoint inhibitors.

New evidence suggests that the clinical success of chemotherapy is not merely due to tumor cell toxicity but also arises from the restoration of immunosurveillance, which has been immensely neglected in previous preclinical and clinical researches. There is an urgent need for novel insights into molecular mechanisms and regimens that uplift the efficacy of immunotherapy since only a minority of cancer patients are responsive to immune checkpoint inhibitors (ICIs). Recent findings on combination therapy of chemotherapy and ICIs have shown promising results. This strategy increases tumor recognition and elimination by the host immune system while reducing immunosuppression by the tumor microenvironment. Currently, several preclinical studies are investigating molecular mechanisms that give rise to the immunomodulation by chemotherapeutic agents and exploit them in combination therapy with ICIs in order to achieve a synergistic clinical activity. In this review, we summarize studies that exhibit the capacity of conventional chemotherapeutics to elicit anti-tumor immune responses, thereby facilitating anti-tumor activities of the ICIs. In conclusion, combining chemotherapeutics with ICIs appears to be a promising approach for improving cancer treatment outcomes.

Role of anti-angiogenic factors in the pathogenesis of breast cancer: A review of therapeutic potential.

Breast cancer is one of the most common cancers in women, which can metastasize to other organs and has a high mortality rate. Previous studies have shown that angiogenic factors can contribute to tumor growth, development, and metastasis by altering the tumor microenvironment (TME). These angiogenic factors include a wide range of molecules, and in contrast, anti-angiogenic factors also inhibit angiogenesis and inhibit tumor growth. Evidence suggests that an imbalance between angiogenic and anti-angiogenic factors leads to angiogenesis, facilitating the migration of tumor cells from the source tissue in the breast to other organs such as the lung, liver, bone, and brain. By supplying blood through these neomicrovascular vessels, the nutrients and oxygen needed to grow tumor cells are provided. Due to the significant anti-tumor role of anti-angiogenesis factors, cancer researchers have always considered these molecules, and it is believed that anti-angiogenesis factors can be employed in cancer treatment approaches. This review discusses the role of anti-angiogenesis agents in breast cancer pathogenesis and reviews therapeutic approaches based on anti-angiogenesis factors.

Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment.

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

State of the art of bone biomaterials and their interactions with stem cells: Current state and future directions.

BACKGROUND: There has been a rapid increase in bone tissue regeneration since the concept of "tissue engineering." Stem cell-based biomaterials have revolutionized the field of tissue regeneration. Biomaterials play an essential part in bone regeneration through their crucial substratum for cell differentiation, cohesion, and proliferation by manipulating cells. Numerous studies have been carried out in order to create a biomaterial with diverse biological and physical characteristics. Furthermore, they developed a cell microenvironment with the desired pore magnitude to stimulate stem cells to transform them from artificial to biological microenvironments. PURPOSE AND SCOPE: The current review aims to give a comprehensive overview of stem cells and biomaterials in bone tissue regeneration. SUMMARY: Initially, bone biology and its interaction with stem cells and biomaterials are briefly explained. Following that, the behavior and mechanism of biomaterials influencing the stem cells during bone tissue regeneration are emphasized. Lastly, the future outlook for tackling the current challenges for designing biomaterials/stem cell materials for bone tissue engineering (TE) is discussed. CONCLUSION: Compatible biomaterial for bone regeneration requires evaluating the structure, matrix, composition, flexibility, and nature of native bone tissue defects. The concept of TE offers a platform for designing biologically, physically, and chemically biocompatible biomaterials for stem cells to proliferate and differentiate. Currently, stem cells are increasingly used for TE with a promising outcome due to their self-renewal and differentiation potential. Furthermore, they can secrete biological-active compounds and modulate the fate and behavior of other cells in native tissues. Bone TE may flourish more rapidly and efficiently using stem cells.

Application of nanoparticles in drug delivery for the treatment of osteosarcoma: focussing on the liposomes.

Osteosarcoma (OS) is one of the most common primary bone malignancies in children and adolescents. The toxicity to healthy tissues from conventional therapeutic strategies, including chemotherapy and radiotherapy, and drug resistance, severely affects OS patients' quality of life and cancer-specific outcomes. Many efforts have been made to develop various nanomaterial-based drug delivery systems with specific properties to overcome these limitations. Among the developed nanocarriers, liposomes are the most successful and promising candidates for providing targeted tumour therapy and enhancing the safety and therapeutic effect of encapsulated agents. Liposomes have low immunogenicity, high biocompatibility, prolonged half-life, active group protection, cell-like membrane structure, safety and effectiveness. This review will discuss various nanomaterial-based carriers in cancer therapy and then the characteristics and design of liposomes with a particular focus on the targeting feature. We will also summarise the recent advances in the liposomal drug delivery system for OS treatment in preclinical and clinical studies.

Carvacrol Suppresses Human Osteosarcoma Cells via the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: Carvacrol is a monoterpenic phenol extracted from traditional Chinese herbs, including oregano and thyme. Currently, carvacrol has been widely studied for its therapeutic role in central nervous system diseases, liver diseases and digestive system cancer. OBJECTIVE: However, the role of carvacrol in osteosarcoma and its underlying molecular mechanism remain elusive. Here, we aimed to examine the anticancer effects of carvacrol on osteosarcoma. METHODS: The effects of carvacrol on the osteosarcoma proliferation capacity were revealed by CCK-8 and colony formation assays. Flow cytometry and Hoechst assays were used to determine the effects of carvacrol on osteosarcoma cell apoptosis. The effect of carvacrol on migration and invasion of osteosarcoma cells was determined by wound healing and transwell tests. Protein expression was evaluated by WB assays. The suppressive effects of carvacrol on osteosarcoma in vivo were examined by a xenograft animal model, immunohistochemistry and HE staining. RESULTS: We demonstrated that carvacrol treatment reduced viability and inhibited the colony formation of U2OS and 143B cells in a concentration-dependent manner. Apoptotic cell number increased after exposure to carvacrol. Meanwhile, the expression of Bax increased, and that of Bcl-2 decreased by carvacrol treatment. In addition, the MMP-9 expression and migration and invasion of 143B and U2OS cells were inhibited by carvacrol. We also found that these carvacrol-induced effects on osteosarcoma are associated with the regulation of the Wnt/ß-catenin signaling pathway. CONCLUSION: Our findings suggest that carvacrol suppresses proliferation, migration, invasion and promotes apoptosis in osteosarcoma cells, in part by regulating the Wnt/ß-catenin signaling pathway.

Resistance to the Insulin and Elevated Level of Androgen: A Major Cause of Polycystic Ovary Syndrome.

PCOS has a wide range of negative impacts on women's health and is one of the most frequent reproductive systemic endocrine disorders. PCOS has complex characteristics and symptom heterogeneity due to the several pathways that are involved in the infection and the absence of a comm14on cause. A recent study has shown that the main etiology and endocrine aspects of PCOS are the increased level of androgen, which is also known as "hyperandrogenemia (HA)" and secondly the "insulin resistance (IR)". The major underlying cause of the polycystic ovary is these two IR and HA, by initiating the disease and its severity or duration. As a consequence, study on Pathogenesis is crucial to understand the effect of "HA" and "IR" on the pathophysiology of numerous symptoms linked to PCOS. A deep understanding of the pattern of the growth in PCOS for HA and IR can help ameliorate the condition, along with adjustments in nutrition and life, as well as the discovery of new medicinal products. However, further research is required to clarify the mutual role of IR and HA on PCOS development.

Towards exertion of immunotherapeutics in the treatment of colorectal cancer; adverse sides, challenges, and future directions.

Immunotherapy has growingly been prosperous as a promising therapeutic option for several kinds of solid tumors, such as colorectal cancer (CRC), subsequent to initial successful outcomes in the treatment of melanoma. The use of immunotherapy, like nivolumab and pembrolizumab (which are monoclonal antibodies against programmed cell death 1) has shown prosperous outcomes in a group of CRC patients who represent mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). However, a successful outcome of treatment by immune checkpoint inhibitors (ICIs) has not been observed in all of the metastatic CRC patients with dMMR-MSI-H tumors. ICIs are able to block the co-inhibitory signaling transduced in T cells, resulting in increased cytotoxic activity of T cells and efficient killing of tumor cells. In spite of availability of diverse immunotherapeutics in treatment of advanced CRC, a poor survival rate of such approaches has been reported along with challenges in the clinical practice. It is necessary to identify novel biomarkers and molecular signatures to approximate the outcome of ICI therapy in the metastatic CRC patients with dMMR-MSI-H tumors. Here we tried to clarify the current line of evidence regarding immunotherapeutics in the treatment of CRC, and discuss the challenges and hurdles in the management of these patients.

Cranial capacity measurement for modern Chinese adults based on 3D reconstruction.

OBJECTIVES: To determine the average modern adult cranial capacity in China, and assess the gender differences and trends in order to establish normal reference values and provide theoretical basis for individualized treatment in clinical practice. METHODS: We conducted a cross-sectional study between January 2019 to June 2020. Thin-slice (0.9 mm) CT scans of 309 males and 238 females from China were obtained, and classified into the 18-32, 33-47, 48-62, 63-77 and 78-92 years age groups. Three-dimensional reconstruction was performed using mimics software to obtain the cranial capacity for statistical analysis. RESULTS: The average cranial capacity of men was 1497.12±120.70 cm3 and that of women was 1326.24±95.72 cm3. The average cranial capacity of men was larger than that of women in all age groups. In addition, cranial capacity across the different age groups showed significant differences among both men and women. CONCLUSION: The average cranial capacity of modern Chinese male is larger that of females, and both sexes show a tendency to an increase in the intracranial volume over the past few decades. Our findings provide important data for establishing normal reference values for cranial capacity of modern Chinese adults and theoretical basis for individualized treatment of certain cranial diseases with increased intracranial pressure.

Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines.

Mesenchymal stem cells (MSCs) show homing capacity towards tumor sites. Numerous reports indicate that they are involved in multiple tumor-promoting processes through several mechanisms, including immunosuppression; stimulation of angiogenesis; transition to cancer-associated fibroblasts; inhibition of cancer cell apoptosis; induction of epithelial-mesenchymal transition (EMT); and increase metastasis and chemoresistance. However, other studies have shown that MSCs suppress tumor growth by suppressing angiogenesis, incrementing inflammatory infiltration, apoptosis and cell cycle arrest, and inhibiting the AKT and Wnt signaling pathways. In this review, we discuss the supportive and suppressive impacts of MSCs on tumor progression and metastasis. We also discuss MSC-based therapeutic strategies for cancer based on their potential for homing to tumor sites.

Nanotechnology Assisted Targeted Drug Delivery for Bone Disorders: Potentials and Clinical Perspectives.

Nanotechnology and its allied modalities have brought revolution in tissue engineering and bone healing. The research on translating the findings of the basic and preclinical research into clinical practice is ongoing. Advances in the synthesis and design of nanomaterials along with advances in genomics and proteomics, and tissue engineering have opened a bright future for bone healing and orthopedic technology. Studies have shown promising outcomes in the design and fabrication of porous implant substrates that can be exploited as bone defect augmentation and drug-carrier devices. However, there are dozens of applications in orthopedic traumatology and bone healing for nanometer-sized entities, structures, surfaces, and devices with characteristic lengths ranging from tens 10s of nanometers to a few micrometers. Nanotechnology has made promising advances in the synthesis of scaffolds, delivery mechanisms, controlled modification of surface topography and composition, and biomicroelectromechanical systems. This study reviews the basic and translational sciences and clinical implications of the nanotechnology in tissue engineering and bone diseases. Recent advances in NPs assisted osteogenic agents, nanocomposites, and scaffolds for bone disorders are discussed.

Recent developments in strontium-based biocomposites for bone regeneration.

Recent advances in biomaterial designing techniques offer immense support to tailor biomimetic scaffolds and to engineer the microstructure of biomaterials for triggering bone regeneration in challenging bone defects. The current review presents the different categories of recently explored strontium-integrated biomaterials, including calcium silicate, calcium phosphate, bioglasses and polymer-based synthetic implants along with their in vivo bone formation efficacies and/or in vitro cell responses. The role and significance of controlled drug release scaffold/carrier design in strontium-triggered osteogenesis was also comprehensively described. Furthermore, the effects of stem cells and growth factors on bone remodeling are also elucidated.

Resveratrol can inhibit Notch signaling pathway to improve spinal cord injury.

Spinal cord injury (SCI) is one of the severe central nervous system (CNS) diseases. Although various therapeutic approaches have been researched, there are still no effective therapeutic measures for SCI. Development of novel, safe and effective therapeutics for SCI have currently gained a lot of interest. Medicinal and chemical agents have the tendency of regulating signaling pathways. Notch signaling pathway plays an important role in neuronal cell differentiation, neuroinflammation and axonal regeneration in the wake of SCI. Resveratrol has been reported to exert neuroprotective effects in CNS conditions. Resveratrol can inhibit Notch signaling pathway to curtail SCI. Herein, we systematically review potential mechanisms of resveratrol-inhibiting Notch signaling pathway in SCI treatment.

Inhibition of NF-κB Signaling Pathway by Resveratrol Improves Spinal Cord Injury.

Spinal cord injury (SCI) can have a significant impact on an individual's life. Herein, we discuss how resveratrol improves SCI by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Evidences show resveratrol suppresses NF-κB signaling pathway to exert its beneficial effects on various diseases. NF-κB signaling pathway plays a significant role in the pathophysiological mechanisms of SCI including increase in inflammation, augmentation of damage caused by free radicals and lipid peroxidation as well as facilitation of apoptosis and axonal demyelination. We also discuss mechanisms between resveratrol and NF-κB signaling pathway in the wake of SCI, which can be potential targets for resveratrol to treat SCI.

Beneficial Effects of Resveratrol-Mediated Inhibition of the mTOR Pathway in Spinal Cord Injury.

Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway. Herein, we explicate the role of resveratrol in the repair of SCI through the inhibition of the mTOR signaling pathway. The inhibition of the mTOR pathway by resveratrol has the potential of serving as a neuronal restorative mechanism following SCI.