Expression of E-cadherin and N-cadherin in Epithelial-to-Mesenchymal Transition of Osteosarcoma: A Systematic Review.

Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However, many molecular mechanisms are still being uncovered and may offer greater avenues for screening and therapy. Cadherins, including E-cadherin and N-cadherin/vimentin, are involved in epithelial-to-mesenchymal transmission (EMT), which is key for tumor invasion. A study reviewing the relationship between OS and cadherins might elucidate a potential target for therapy and screening. A robust literature review was conducted by searching PubMed with the keywords "osteosarcoma", "cadherin", "e-cadherin" and "n-cadherin". Of a preliminary 266 papers, 25 were included in the final review. Review articles and those without primary data were excluded. Loss of E-cadherin is noted in metastatic cell lines of osteosarcoma. Overexpression of E-cadherin or knockout of N-cadherin/vimentin results in loss of metastatic potential. There are several methods of gene knockout, including CRISPR-Cas9 gene editing, viral vector insertion with micro RNA complementary to long noncoding RNA within gene segments, or proteomic editing. Screening for EMT and genetic treatment of EMT is a possible avenue for the treatment of refractory osteosarcoma. Several studies were conducted ex vivo. Further testing involving in vitro therapy is necessary to validate these methods. Limitations of this study involve a lack of in vivo trials to validate methods.

Utilizing Deep Learning for X-ray Imaging: Detecting and Classifying Degenerative Spinal Conditions.

Background Degenerative spinal conditions (DSCs) involve a diverse set of pathologies that significantly impact health and quality of life, affecting many individuals at least once during their lifetime. Treatment approaches are varied and complex, reflecting the intricacy of spinal anatomy and kinetics. Diagnosis and management pose challenges, with the accurate detection of lesions further complicated by age-related degeneration and surgical implants. Technological advancements, particularly in artificial intelligence (AI) and deep learning, have demonstrated the potential to enhance detection of spinal lesions. Despite challenges in dataset creation and integration into clinical settings, further research holds promise for improved patient outcomes. Methods This study aimed to develop a DSC detection and classification model using a Kaggle dataset of 967 spinal X-ray images at the Department of Neurosurgery of Arrowhead Regional Medical Center, Colton, California, USA. Our entire workflow, including data preprocessing, training, validation, and testing, was performed by utilizing an online-cloud based AI platform. The model's performance was evaluated based on its ability to accurately classify certain DSCs (osteophytes, spinal implants, and foraminal stenosis) and distinguish these from normal X-rays. Evaluation metrics, including accuracy, precision, recall, and confusion matrix, were calculated.  Results The model achieved an average precision of 0.88, with precision and recall values of 87% and 83.3%, respectively, indicating its high accuracy in classifying DSCs and distinguishing these from normal cases. Sensitivity and specificity values were calculated as 94.12% and 96.68%, respectively. The overall accuracy of the model was calculated to be 89%.  Conclusion These findings indicate the utility of deep learning algorithms in enhancing early DSC detection and screening. Our platform is a cost-effective tool that demonstrates robust performance given a heterogeneous dataset. However, additional validation studies are required to evaluate the model's generalizability across different populations and optimize its seamless integration into various types of clinical practice.

The Role of Sirtuin 1 (SIRT1) in Neurodegeneration.

Sirtuins (SIRT) are a class of histone deacetylases that regulate important metabolic pathways and play a role in several disease processes. Of the seven mammalian homologs currently identified, sirtuin 1 (SIRT1) is the best understood and most studied. It has been associated with several neurodegenerative diseases and cancers. As such, it has been further investigated as a therapeutic target in the treatment of disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). SIRT1 deacetylates histones such as H1 lysine 26, H3 lysine 9, H3 lysine 56, and H4 lysine 16 to regulate chromatin remodeling and gene transcription. The homolog has also been observed to express contradictory responses to tumor suppression and tumor promotion. Studies have shown that SIRT1 may have anti-inflammatory properties by inhibiting the effects of NF-κB, as well as stimulating upregulation of autophagy. The SIRT1 activators resveratrol and cilostazol have been shown to improve Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores in AD patients. In this review, we aim to explore the various roles of SIRT1 with regard to neuroprotection and neurodegeneration.

Evaluating the Utilization of Ethylenediaminetetraacetic Acid as a Treatment Supplement for Gliomas.

Gliomas are the most common primary tumors of the nervous system, accounting for approximately 81% of brain tumors. The primary treatment for these primary brain tumors, especially those of high grade, is surgical resection with subsequent therapy such as targeted radiotherapy, chemotherapy, or supportive care. In an effort to devise nuanced ways to treat gliomas, studies have examined various chemical agents to expand therapeutic avenues for gliomas. In this study, we investigate the applications of ethylenediaminetetraacetic acid (EDTA) in the investigation and treatment of gliomas. Searches were conducted on PubMed to find studies about the use of EDTA in the treatment of glioma. We identified 36 studies that had the information needed for analysis. We collected information on the dosage of EDTA, the agent that EDTA was complexed with, the route of administration, the outcome of the EDTA usage, and the type of glioma cells that were involved. In addition, a one-way analysis of variance was performed to identify any relationships between the effect of cell type, study purpose, and year published on dosage. We identified 36 articles that met our inclusion criteria. In-vitro studies utilized EDTA in various complexes to evaluate cellular viability, including proliferation and toxicity, intracellular enzyme kinetics, and intercellular interactions such as chelation and cellular aggregation. In-vivo studies predominantly utilized the versatile nature of EDTA as a tracer for imaging studies involved in diagnostics and identifying recurrent tumor growth and localization in human patients. Our statistical analysis failed to identify any significant relationships between cell type, study purpose, and publication year on EDTA dosage. We identified a variety of uses for EDTA in the investigation hopefully providing physicians with information regarding the context and applications of EDTA to assist in exploring new treatment options for glioma patients.

Assessing the Efficacy of Alkylating Agent Regimens in the Treatment of Infantile Malignant Osteopetrosis: Cyclophosphamide, Busulfan, or Thiotepa.

Infantile malignant osteopetrosis is a debilitating disease that requires total bone marrow irradiation and transplant procedures for patients to survive. The major complication of this procedure is graft vs host disease (GVHD), followed by infections and end organ toxicity. Therefore, current research efforts into treatment mainly aim to reduce GVHD while limiting infections and organ toxicity. Different regimens of alkylating agents have been used to try to reduce GVHD. The most common regimen is cyclophosphamide (Cy) with busulfan (Bu), followed by Cy with Bu and thiotepa (Thio). This meta-analysis aimed to evaluate the efficacy of different treatments by comparing mortality and morbidity causes and rates across groups. The mean one-year survival rate for the Cy, Bu, Thio regimen studies in the human leukocyte antigen (HLA) unmatched group (45.01%) was statistically lower than the one-year survival rate for the studies using just a Cy, Bu regimen (70.8%) in the HLA unmatched studies (p<0.00142). The one-year survival in the studies which had HLA-matched donors was 80.56%, which is statistically higher (p<0.001) than the one-year survival in the HLA-unmatched studies (53.96%), indicating a benefit of finding HLA-matched donors. It seems that price and availability could be a factor in the widespread use of Cy.

A narrative review on the effects of a ketogenic diet on patients with Alzheimer's disease.

Alzheimer's disease (AD) has been very difficult to prevent and cure using the medicine available today. However, there has been some hope with using a ketogenic diet (KD) to reduce the cognitive and quality of life decline experienced by patients with AD. In this review, the authors discuss the research done on the effect of a KD on AD to provide some potential avenues for future research and to determine a KD that can be best adopted by patients. The authors also go over the effects of KD's and low-carbohydrate diets (LCDs) on the cognitive function of healthy patients and on patients without AD to determine the similar and dissimilar effects of the diets. The authors found that the KD was able to improve the cognitive abilities and quality of life of patients ranging from mild to severe AD. Several types of memory were improved as a result of the diets. Further research needs to be conducted to determine the cause behind these improvements. However, the several studies that were done were mostly in agreement that once ketosis was reached, cognitive improvements were observed in patients ranging from mild to severe AD or mild to moderate cognitive impairment. Through the use of a KD, potential mechanisms can be found to reduce the cognitive decline of patients with AD, and potentially even prevent the damaging effects of cognitive decline from AD altogether.

The Relationship Between Arterial Stiffness and Resistance Training.

Exercise is a critical factor that impacts arterial stiffness. In this narrative review, we noted multiple findings that could not be reconciled with one another. Some studies indicated that arterial stiffness increases after a regimen of resistance training. However, such studies were limited by a lack of specification of the resistance training protocols, as well as varying results reported from different areas of the body, undermining the internal validity of the studies. Another factor explored in this review was how the order of performing exercises can affect arterial stiffness. Low-intensity resistance training before high-intensity resistance training resulted in increased arterial stiffness, whereas vice versa showed no change in arterial stiffness. Other studies indicated that resistance exercise results in reduced arterial stiffness. Intensity is a variable in studies that produces inconsistent results of arterial stiffness, with some studies suggesting high-intensity resistance training increases arterial stiffness and low-intensity resistance training decreases arterial stiffness, while other studies pointing to a significant decrease in arterial stiffness, regardless of the intensity of resistance training. Demographic factors such as gender, age, and diet play an important role in explaining these differences. In terms of future implications, there is potential clinical significance as increased arterial stiffness serves as a prognostic marker in diagnosing coronary heart disease.