3D hydrogel/ bioactive glass scaffolds in bone tissue engineering: Status and future opportunities

From Elsevier via Jisc Publications RouterHistory: accepted 2023-06-06, issued 2023-07-05Article version: AMPublication status: AcceptedRepairing significant bone defects remains a critical challenge, raising the clinical demand to design novel bone biomaterials that incorporate osteogenic and angiogenic properties to support the regeneration of vascularized bone. Bioactive glass scaffolds can stimulate angiogenesis and osteogenesis. In addition, natural or synthetic polymers exhibit structural similarity with extracellular matrix (ECM) components and have superior biocompatibility and biodegradability. Thus, there is a need to prepare composite scaffolds of hydrogels for vascularized bone, which incorporates bioactive glass to improve the mechanical properties and bioactivity of natural polymers. In addition, those composites' 3-dimensional (3D) form offers regenerative benefits such as direct doping of the scaffold with ions. This review presents a comprehensive discussion of composite scaffolds incorporated with BaG, focusing on their effects on osteo-inductivity and angiogenic properties. Moreover, the adaptation of the ion-doped hydrogel composite scaffold into a 3D scaffold for the generation of vascularized bone tissue is exposed. Finally, we highlight the future challenges of manufacturing such biomaterials

Biomaterials in Traumatic Brain Injury: Perspectives and Challenges

Traumatic brain injury (TBI) is a leading cause of mortality and long-term impairment globally. TBI has a dynamic pathology, encompassing a variety of metabolic and molecular events that occur in two phases: primary and secondary. A forceful external blow to the brain initiates the primary phase, followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, a rise in oxidative stress, activation of glial cells, and damage to the blood–brain barrier (BBB), resulting in paracellular leakage. Currently, there are no FDA-approved drugs for TBI, but existing approaches rely on delivering micro- and macromolecular treatments, which are constrained by the BBB, poor retention, off-target toxicity, and the complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for the diagnosis and treatment of TBI. Tissue engineering, which includes the use of biomaterials, is one such alternative approach. Biomaterials, such as hydrogels, including self-assembling peptides and electrospun nanofibers, can be used alone or in combination with neuronal stem cells to induce neurite outgrowth, the differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines the inclusion of biomaterials as potential treatments for TBI, including their types, synthesis, and mechanisms of action. This review also discusses the challenges faced by the use of biomaterials in TBI, including the development of biodegradable, biocompatible, and mechanically flexible biomaterials and, if combined with stem cells, the survival rate of the transplanted stem cells. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help to guide the design of future TBI therapies

Medicago orbicularis Has Antioxidant, Antihemolytic, and Anti-cancerous Activities and Augments Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells

Cancer is the second leading cause of death, worldwide. Lung cancer is the leading cause of cancer-related mortality. Plant-based therapeutics and herbal medicine have played a vital role in the development of several anti-cancerous agents, and has been used to reduce the severe side effects of chemotherapy as well. Since the anti-lung cancer properties of the plant Medicago. orbicularis are not explored yet, we identified its phytochemical composition and investigated the anti-oxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. Results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable anti-oxidant and hemolytic activities. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells; with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts activated Caspase-3 and PARPP-1, and reduced the ratio of anti-apoptotic BCL-2/ pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. M. orbicularis may be a potential source of anti-cancerous agents to manage progression of lung cancer and its resistance to therapy.This work was supported by the a grant from the Lebanese University to SN and student grants number QUST-1-BRC-2022-315; QUST-1-BRC-2022-316, QUST-1-BRC-2023-836; and QUST-1-BRC-2023-846 to AS. Publication fees APC were covered by Qatar National Library (QNL)

Association between lifestyle factors and COVID-19: findings from Qatar Biobank

Coronavirus Disease 2019 (COVID-19) exhibits a significant variation in presentation of symptoms ranging from mild to severe life-threatening symptoms, including death. COVID-19 infection susceptibility has been linked with various covariates, but studies in Qatar are limited. Data from Qatar Biobank (QBB) (n = 10,000; 18- to 79-year-old adults) were analyzed for associations between sociodemographic and lifestyle factors and susceptibility to COVID-19. Logistic regression was used to assess the associations between COVID-19 and age, gender, body mass index (BMI), smoking status, education level, dietary patterns, supplement use, physical activity, history of bariatric surgery, diabetes, and hypertension. In total, 10.5% (n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR]= 0.55; 95% CI: 0.44-0.68 and OR= 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction of the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥30 kg/m2), history of bariatric surgery and higher adherence to the modern dietary pattern– characterized by consumption of foods high in saturated fat and refined carbohydrates– were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.Qatar National Research Fund (QNRF) grant number RRC02-0807-210,022 to A.A.S. The funding source (QNRF) had no role in study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the article for publication. Institutional Review Board Statement: This study was approved by Qatar University IRB (QU-IRB 1779-E/22) and QBB IRB (EX-2021-QF-QBB-RES-ACC-00065-0181

Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms

Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy

Acute exposure to cigarette smoking followed by myocardial infarction aggravates renal damage in an in vivo mouse model

Cigarette smoking (S) is a risk factor for progressive chronic kidney disease, renal dysfunction, and renal failure. In this study, the effect of smoking on kidney function was investigated in a mouse model of myocardial infarction (MI) using 4 groups: control (C), smoking (S), MI, and S+MI. Histological analysis of S+MI group showed alterations in kidney structure including swelling of the proximal convoluted tubules (PCTs), thinning of the epithelial lining, focal loss of the brush border of PCTs, and patchy glomerular retraction. Molecular analysis revealed that nephrin expression was significantly reduced in the S+MI group, whereas sodium-hydrogen exchanger-1 (NHE-1) was significantly increased, suggesting altered glomerular filtration and kidney functions. Moreover, S+MI group, but not S alone, showed a significant increase in the expression of connective tissue growth factor (CTGF) and fibrotic proteins fibronectin (FN) and α-smooth muscle actin (SMA), in comparison to controls, in addition to a significant increase in mRNA levels of IL-6 and TNF-α inflammatory markers. Finally, reactive oxygen species (ROS) production was significantly accentuated in S+MI group concomitant with a significant increase in NOX-4 protein levels. In conclusion, smoking aggravates murine acute renal damage caused by MI at the structural and molecular levels by exacerbating renal dysfunction.This work was supported by grants from the Medical Practice Plan (MPP) at AUB (grant title "Effect of Second Hand Smoking (SHS) on Cardiac and Vascular Smooth Muscle Remodeling: A Targeted and Global Approach." Lead PI: Firas Kobeissy, co-PIs: Asad Zeidan and Ahmad Husari), from Lebanese National Council for Scientific Research (Kazem Zibara), from AUB URB (Firas Kobeissy), and from Lebanese University grant (Kazem Zibara).Scopu

Unveiling a Biomarker Signature of Meningioma: the Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation in grades classified from I to III. Meningiomas tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningioma, with a focus on Neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in preoperative and postoperative decision-making. Discovery of novel biomarkers will allow more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.This research is funded by a grant from Morehouse School of Medicine to Firas Kobeissy and a grant from Qatar University to Abdullah A. Shaito

Origanum syriacum L. Attenuates the Malignant Phenotype of MDA-MB231 Breast Cancer Cells

Breast cancer is the leading cause of cancer-related deaths among women. Among breast cancer types, triple negative breast cancer (TNBC) is the most aggressive, and is resistant to hormonal and chemotherapeutic treatments. As such, alternative approaches that may provide some benefit in fighting this debilitating pathology are critically needed; hence the utilization of herbal medicine. Origanum syriacum L., one of the most regularly consumed plants in the Mediterranean region, exhibits antiproliferative effect on several cancer cell lines. However, whether this herb modulates the malignant phenotype of TNBC remains poorly investigated. Here, we show that in MDA-MB-231, a TNBC cell line, Origanum syriacum L. aqueous extract (OSE) inhibited cellular viability, induced autophagy determined by the accumulation of lipidized LC3 II, and triggered apoptosis. We also show that OSE significantly promoted homotypic cell-cell adhesion while it decreased cellular migration, adhesion to fibronectin, and invasion of MDA-MB-231 cells. This was supported by decreased activity of focal adhesion kinase (FAK), reduced α2 integrin expression, and downregulation of secreted PgE2, MMP2 and MMP-9, in OSE-treated cells. Finally, we also show that OSE significantly inhibited angiogenesis and downregulated the level of nitric oxide (NO) production. Our findings demonstrate the ability of OSE to attenuate the malignant phenotype of the MDA-MB-231 cells, thus presenting Origanum syriacum L. as a promising potential source for therapeutic compounds for TNBC

Overview of Composite Materials and their Automotive Applications

This chapter presents an overview of recent automotive applications of advanced composites. A summary of available composites that could be used in automotive industries is presented. The chapter work mainly deals with new research and studies done in order to investigate the present and potential use of composites for automotive structural components. In general, composite materials are composed from at least two materials, where one is the reinforcing phase and the other is the matrix. In the automotive industry, some applications of metal matrix composites (MMC) can be found, such as brake rotors, pistons, connecting rods and integrally cast MMC engine blocks. Two main methods are used to determine the mechanical behavior of composites: analytical models and numerical models