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Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.

Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascul

Googling the Guggul (Commiphora and Boswellia) for Prevention of Chronic Diseases.

Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug disc

Multimodal Treatment of Bone Metastasis-A Surgical Perspective.

Over the past decades there has been an increase in the incidence of cancer worldwide. With the advancement in treatment, patient survival has improved in tandem with the increasing incidence. This, together with the availability of advanced modern diagnostic modalities, has resulted in more cases of metastatic bone disease being identified. Bone metastasis is an ongoing problem and has significant morbidity implications for patients affected. Multimodal treatment strategies are required in dealing with metastatic bone disease, which include both surgical and non-surgical treatment options. In

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… The five main classes of antiresorptives used clinically include: Bisphosphonates, estrogens, calcitonin, selective estrogen receptor modulators (SERMs), and monoclonal antibodies such as Denosumab. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption ( 74 , 75 ). …

Ferroptosis: Frenemy of Radiotherapy.

Recently, it was established that ferroptosis, a type of iron-dependent regulated cell death, plays a prominent role in radiotherapy-triggered cell death. Accordingly, ferroptosis inducers attracted a lot of interest as potential radio-synergizing drugs, ultimately enhancing radioresponses and patient outcomes. Nevertheless, the tumor microenvironment seems to have a major impact on ferroptosis induction. The influence of hypoxic conditions is an area of interest, as it remains the principal hurdle in the field of radiotherapy. In this review, we focus on the implications of hypoxic conditions

Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.

New anticancer therapeutic strategies, including targeting of iron dysregulation in affected cancer types and stages, are urgently needed to decrease the associated annual cancer death rate of about 10 million worldwide. Many tumours evade treatment and support metastatic potential by effluxing iron and upregulating antioxidant systems, leading to suppression of lipid peroxidation and ferroptotic cell death. Similarly, many tumours manipulate the tumour microenvironment (TME) by ensuring the continuous supply of iron. This involves phenotypic modulation of immune cells, including macrophages,

Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

Role of Actinomyces spp. and related organisms in the development of medication-related osteonecrosis of the jaw (MRONJ): Clinical evidence based on a case series.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common consequence of antiresorptive treatment, which often leads to the development of necrotic exposed bone surfaces with inflammatory processes affecting the jawbone. Although the development of MRONJ is often associated with the inflammatory response or infections caused by the colonizing members of the oral microbiota, the exact pathogenesis of MRONJ is still not fully understood. In the present paper, we aimed to provide additional, microbiological culture-supported evidence, supporting the "infection hypothesis" that

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… Advanced age, the presence of other underlying conditions (e.g., Type II diabetes) affecting tissue healing and circulation, comorbidities affecting the patient's immune status, simultaneous use of other treatments (e.g., steroids, immune suppressants, estrogen receptor modulators, radiation therapy) …

Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw.

Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event of bisphosphonate or denosumab administration; it is associated with severe pain and a deteriorated quality of life. Since its first report in 2003, there have been many studies on its definition, epidemiology, pathophysiology, diagnosis, and treatment. Nevertheless, the epidemiology and mechanisms underlying this condition have not yet been fully delineated and several risk factors are known. Moreover, as there is no effective treatment currently available for osteonecrosis of the jaw, prevention is es

Triple‑negative breast cancer cell‑derived piR‑31115 promotes the proliferation and migration of endothelial cells via METTL3‑mediated m6A modification of YAP1.

Triple‑negative breast cancer (TNBC), a highly malignant breast cancer subtype with a pronounced metastatic propensity, forms the focus of the present investigation. MDA‑MB‑231, a prevalently utilized TNBC cell line in cancer research, was employed. In accordance with the tumour angiogenesis theory, cancer cells are capable of instigating angiogenesis and the formation of a novel vascular system within the tumour microenvironment, which subsequently sustains malignant proliferation and metastasis. Consequently, impeding the growth of tumour blood vessels holds substantial significance in suppr

IgG N-glycan Signatures as Potential Diagnostic and Prognostic Biomarkers.

IgG N-glycans are an emerging source of disease-specific biomarkers. Over the last decade, the continued development of glycomic databases and the evolution of glyco-analytic methods have resulted in increased throughput, resolution, and sensitivity. IgG N-glycans promote adaptive immune responses through antibody-dependent cellular cytotoxicity (ADCC) and complement activation to combat infection or cancer and promote autoimmunity. In addition to the functional assays, researchers are examining the ability of protein-specific glycosylation to serve as biomarkers of disease. This literature re

Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells.

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic

Medication-Related Osteonecrosis of the Jaw: A Cross-Sectional Survey among Urologists in Switzerland, Germany, and Austria.

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially preventable adverse side effect of mainly antiresorptive drugs. MRONJ is expected to become a growing clinical problem due to the aging population and the increasing number of patients requiring antiresorptive agents. Knowledge and awareness about MRONJ and elimination of the oral and dental risk factors before starting antiresorptive therapy (AR) are fundamental to reducing the incidence of MRONJ. In urology, ARs are used primarily in patients suffering from bone metastases due to prostate cancer and to prevent cancer-treatm

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… Recently, other agents such as mechanistic target of rapamycin (mTOR) inhibitors (e.g., everolimus), selective estrogen receptor modulators (SERMs) (e.g., raloxifene), fusion proteins (e.g., aflibercept), and antitumor necrosis factor (TNF) antibodies have been reported to induce MRONJ possibly. …

Imaging of vertebral fractures.

Vertebral fracture is a common clinical problem. Osteoporosis is the leading cause of non-traumatic vertebral fracture. Often, vertebral fractures are not clinically suspected due to nonspecific presentation and are overlooked during routine interpretation of radiologic investigations. Moreover, once detected, many a times the radiologist fails to convey to the clinician in a meaningful way. Hence, vertebral fractures are a constant cause of morbidity and mortality. Presence of vertebral fracture increases the chance of fracture in another vertebra and also increases the risk of subsequent hip

Levothyroxine dose and risk of fractures in older adults: nested case-control study.

OBJECTIVE: To quantify the effect of levothyroxine dose on risk of fractures in older adults. DESIGN: Nested case-control study. SETTING: Population based health databases, Ontario, Canada. PARTICIPANTS: Adults aged 70 or more prescribed levothyroxine between 1 April 2002 and 31 March 2007 and followed for fractures until 31 March 2008. Cases were cohort members admitted to hospital for any fracture, matched with up to five controls from within the cohort who had not yet had a fracture. MAIN OUTCOME MEASURE: Primary outcome was fracture (wrist or forearm, shoulder or upper arm, thoracic sp

Non-Interventional Prospective Observational Study of Platelet Rich Fibrin as a Therapy Adjunctive in Patients with Medication-Related Osteonecrosis of the Jaw.

BACKGROUND: Medication-related osteonecrosis (MRONJ) of the jaw is a severe and feared side effect of antiresorptive therapy in the oncological setting. With growing evidence that impaired angiogenesis may represent a key factor in pathogenesis, the aim of this study was to evaluate an autologous platelet concentrate as a possible additive in surgical therapy to optimize vascularization and, subsequently, resolution rates. MATERIAL AND METHODS: A non-interventional, prospective, multicenter study was conducted, and all patients with stage I-III MRONJ, undergoing antiresorptive therapy for an

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… Furthermore, there is rising evidence of MRONJ unrelated to bisphosphonates or denosumab—such as immune modulatory medications, tyrosine kinase inhibitors, monoclonal antibodies, mammalian target of rapamycin inhibitors, radiopharmaceuticals, selective estrogen receptor modulators [ 9 ] and, as a possible …

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

CD11c + микроглиа: от базовых исследований к клиническому применению.

CD11c + микроглиа - функционально специализированная подгруппа микроглий, играющая ключевую роль в патофизиологических процессах различных заболеваний центральной нервной системы. Этот обзор обобщает убедительные доказательства того, что CD11c + микроглиа демонстрируют уникальные транскриптомные и фигоцитические характеристики. Эти характеристики отличают их от гомеостатической микроглии и поддерживают их специализированные функции. Во время разработки CD11c + микроглиа имеют решающее значение для созревания олигодендроцитов и целостности белой материи, особенно в таких регионах, как corpus ca

Symptomatic spinal metastasis: A systematic literature review of the preoperative prognostic factors for survival, neurological, functional and quality of life in surgically treated patients and methodological recommendations for prognostic studies.

PurposeWhile several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs.MethodsSeven electronic databases were searched (1990-2015), without language restriction, to identify studie

The Role of IL-33/ST2 Pathway in Tumorigenesis.

Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane o

Small molecule inhibitors targeting the cancers.

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatme