Article type: Review

Concise Review on Modulation Mechanism of Matrix Metalloproteinase via Oncoviruses in Aggressiveness of Malignancies

Matrix metalloproteinases (MMPs) are a member of the protein family intimately associated with zinc-containing endopeptidases, which are the main proteases implicated in extracellular matrix (ECM) degradation. The high ability of MMPs in the degradation of extracellular proteins is an important event in many normal biological as well as pathologic processes, including tumor progression, tissue repair, wound healing, developmental morphogenesis, and inflammatory diseases. This review is focused on the description of the modulation mechanism of MMPs via oncoviruses. Up to now, a large number of oncogenic viruses have been detected and recognized as etiologic factors of multiple human cancers. Actually, by expression of several viral oncoproteins of tumorigenic viruses with the simple genetic system, we are able to deregulate or modulate the pathways of cell transformation procedure in malignancy. In brief, upregulated expression of MMPs genes by direct (through DNA binding) , as well as indirect interactions (by activating PI-3K/AKT, ERK/MAPK, IFN/JAK/STAT, JNK, NF-κB signaling pathways and/or immune response) with tumorigenic viruses, have a noticeable role in the proliferation of cells, as well as angiogenesis, mobility, EMT, invasiveness, and metastatic features. In fact, the growth of tumor-related researchers offers a future perspective for the efficiency of targeted, molecular-based therapies and its anticancer effects via diverse mechanisms such as the suppression of viral oncoproteins.

Biotribology of the Total Hip Replacement – Review of the Current Bearing Surfaces

Total hip replacement surgery (THR) is one of the most common surgeries performed in modern orthopedics, and in most cases offers a significant improvement in the quality of the patient's life. However, after some time, wear and osteolysis do appear, which leads to the need for revision surgery. With the indication being widened to a more young and active population, the need for extending the lifespan of the prosthesis is mandatory. Although several bearing surfaces have been studied over the years, and a lot of couplings are in use, the choice of the right combination of materials is still controversial. Biotribology tries to answer some of the current questions regarding the best bearing surface to use, being the branch of science and technology that studies friction, wear, and lubrication of different materials in the human body. In the present day, a large number of materials are in use for total hip replacement, but choosing the right combination of materials is still controversial, and is being done on one hand by the surgeon’s experience and on the other hand by the age and activity of the patient. The objective of this review is to try to present the main advantages and disadvantages of different materials and try to answer the most difficult question of them all: What is the right material to use for THR-bearing surfaces?

The Role of Vitamin D in the Development and Progression of Osteoarthritis

Low levels of vitamin D in patients with osteoarthritis (ΟΑ) rather adversely affect the structure and function of articular cartilage. Low levels of vitamin D are also associated with joint pain, limited physical activity, quality of life, as well as decreased muscle strength, primarily in the lower extremities with adverse OA progression. A high percentage of low vitamin D levels was found in patients with OA and joint arthroplasty as well as a less satisfactory postoperative follow-up in patients with low vitamin D levels. The administration of vitamin D supplementation in patients with knee osteoarthritis has been associated with improved articular cartilage architecture, and reduced joint pain, combined with improved functionality and quality of life in patients with OA.

Melanoma: A Historical Walk-through from Palliative Treatment to Modern-day Practice

Melanoma is one of the most common types of malignancy in the world, and one known to carry a very poor prognosis until recent years. This review aims to outline the events in the history of the disease and the impact made by the discoveries along the way, as well as the modern-day consensus by referencing the updated literature regarding the present approach and future directions. In the last two decades, several studies and research have brought significant improvement in the diagnosis and clinical management of melanomas. The development of sentinel lymph node biopsy has brought major changes to the surgical approach to the disease, and modern therapies based on recently developed knowledge changed the death sentence this diagnosis once meant to a manageable condition despite its aggressiveness, keeping in mind that early diagnosis and safe margin excision remain the best and most optimistic course of treatment.

The Role of Inflammation in the Pathogenesis of Psoriasis

Psoriasis is a chronic inflammatory skin condition with genetic determinism characterized by the presence of well- defined, erythematous plaques, covered by white, pearly, stratified scales, located on the extension areas, the skin of the scalp, intertriginous regions. The origin of psoriasis is multifactorial, involving hereditary and environmental pathogenic mechanisms. It is triggered by various risk factors involving a variety of processes, such as inflammation, antigen presentation, cell signaling, and transcriptional regulation.

Pulmonary Hypertension in Autoimmune Diseases – A Review of New Concepts in Screening, Diagnosis and Therapeutic Management

Pulmonary hypertension (PH) has gained more and more attention in the last years given the increased mortality and morbidity rate and in particular pulmonary arterial hypertension associated with autoimmune diseases (a specific subgroup of PH), entities with an increasing incidence and prevalence globally. Among these, systemic sclerosis is of particular interest, being the most common among connective tissue diseases (CTDs) with PH as a major complication. Other CTDs such as mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), primary Sjogren's syndrome, and dermatomyositis may also develop PH as a complication of these severe and complex conditions, which can have a major impact on prognosis and quality of life. PH has also been reported in rheumatoid arthritis and ankylosing spondylitis but further studies are necessary. Several studies have shown that the 3-year survival rate for patients with systemic sclerosis-associated with pulmonary hypertension (SSc-PH) is between 31% and 52%, while the 5-year survival rate is below <50%. Therefore, an early and accurate diagnosis as well as subsequent management of PH in these conditions is mandatory, since survival remains suboptimal despite treatment advances. The aim of this article is to provide an overview of different autoimmune diseases associated with PH and to provide an easy reference source on current best practices.

Lynch Syndrome – An Overview of the Worldwide Management of This Silent Killer Within Our Genes

Lynch syndrome, also known as hereditary non-polyposis cancer syndrome, represents the most common autosomal dominant genetic predisposition for the early onset development of several malignancies. Nearly three decades ago, the discovery of microsatellite instability, a distinctive feature of pathogenic variants within genes encoding mismatch repair proteins, marked a significant leap forward in understanding cancer biology and the underlying spectrum of cancers triggered by these mutations – typical of Lynch syndrome. In recent years, a new treatment paradigm, using immune checkpoint inhibitors, as well as preventive measures has drastically improved the survival rates. Identifying individuals with an inherent predisposition to cancer, through diagnostic protocols followed by personalized screening and treatment algorithms, holds the potential to mitigate premature cancer-related fatalities as well as preventable mortality. It is estimated that only a limited number of patients have been diagnosed, underscoring the importance of implementing specific screening programs for early detection of malignancies to which these patients are susceptible. This article aims to underline the importance of a national protocol tailored to guide a Western-inspired practice for Lynch syndrome patient management, the main aim of the Romanian Society for Lynch Syndrome, by providing an overview of similar initiatives throughout the world.

Lynch Syndrome: Approach from the Gastroenterologist’s Point of View

Colorectal cancer is one of the main causes of death by cancer in the European Union and in Romania. Lynch Syndrome is an autosomal dominant inherited disease that affects around 3% of all colorectal cancer patients, defined by mutations in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Aside from the high risk for colorectal cancer (CRC), they exhibit a high risk for endometrial cancer, ovarian cancer, gastric cancer, pancreatic cancer, brain cancer, small bowel cancer, and sebaceous gland cancer. Diagnosis is often made by the gastroenterologist, usually when he meets a young patient with symptoms suggesting the presence of a colonic tumor and a family history of CRC. The role of the gastroenterologist is to investigate the best practices in order to have an early diagnosis and to prevent interval cancers according to the newest guidelines or other gastrointestinal tract tumors associated with Lynch Syndrome. Registries play an important role in the optimal surveillance of these particular categories of patients and should be put into place in every country. They will allow clinicians to have a better understanding of the disease and a more standardized quality of care for them.

Emotional Regulation Strategies in Lynch Syndrome Diagnosis Psychological Adjustment – A Review

The purpose of this article is to investigate the role of emotional regulation (ER) as a process underlying a variety of symptoms associated with Lynch syndrome (depression, anxiety, fear of cancer recurrence (FCR), insomnia, fatigue, pain, and subjective cognitive difficulties in patients with Lynch syndrome. Firstly, we provided an overview of the main psychopathological symptoms found in cancer patients and their impact, and then an overview of emotional regulation strategies and discussed the main impact ER strategies have on cancer patients, especially emotional suppression and experiential avoidance, as found in evidence-based studies. Recent research has shown that two ER strategies generally considered maladaptive, emotional suppression and experiential avoidance were significantly associated with higher levels of anxiety, depression, FCR, fatigue, and cognitive difficulties. We propose that experiential avoidance and emotional suppression may be common transdiagnostic mechanisms for a common set of psychological symptoms in Lynch syndrome patients, a hypothesis to be tested in a future study.

Cardiotoxicity of Chemotherapy in Lynch Syndrome – A Literature Review

Chemotherapy is an important treatment in oncological disease, with a vast number of side effects. The cardiotoxicity of several chemotherapeutic agents and appropriate risk stratification and patient follow-up must be ensured by a multidisciplinary team which must include an oncologist and a cardiologist. Lynch syndrome is associated with younger-onset malignant tumors of various localizations, requiring aggressive chemotherapy. FOLFOX chemotherapy which is frequently used in Lynch syndrome-associated colorectal cancer has several cardiotoxic effects with mechanisms ranging from increased reactive oxidative species to Krebs cycle blockade or coronary vasospasm. These complex effects on the cardiovascular system have varied clinical effects, such as heart failure, arrhythmias, or acute ischemic events.