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Topic Review
Methocinnamox in Opioid Use Disorder Treatment
Methocinnamox (MCAM) is a novel mu opioid receptor antagonist with an extended duration of action. MCAM has potential to reduce the burden of the opioid epidemic by being used as an overdose rescue treatment and a long-term treatment for opioid use disorder (OUD). The currently available treatments for OUD include naloxone, naltrexone, and methadone. These treatments have certain limitations, which include short duration of action, patient non-compliance, and diversion. MCAM could potentially be used as both a rescue and long-term treatment for opioid misuse. This is due to its pseudo-irreversible antagonism of the mu opioid receptor, abnormally long duration of action of nearly two weeks, and the possibility of using kappa or delta opioid receptor agonists for pain management during OUD treatment. MCAM’s novel pharmacokinetic and pharmacodynamic properties open a new avenue for treating opioid misuse.
  • 993
  • 29 Apr 2022
Topic Review
Protein Variants in Cancer-Related Genes
Large scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this entry we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and function was experimentally determined. We collected a set of 164 variants from 11 proteins to analyze the impact of missense mutations at structural and functional levels, and to assess the performance of state-of-the-art methods (FoldX and Meta-SNP) for predicting protein stability change and pathogenicity. 
  • 992
  • 22 Sep 2021
Topic Review
Applications of Adductomics in Chemically
Adductomics is a transformative biomedical research tool that uses an "omic" approach to characterize and quantify exogenous and endogenous reactive compounds to which an individual is exposed; the use of compound-specific adduct biomarkers. Exposure to chemicals is generally driven by a variety of factors such as environment, genetics and lifestyle, which are characterized by a high level of interpersonal variability and contain a life element that makes it unique to each individual.
  • 989
  • 27 Oct 2021
Topic Review
Metallo-Drugs in Cancer Therapy
Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities include inherent resistance, systemic toxicity and severe side effects. Out of 50% patients administrated to chemotherapy, only 5% survive. 
  • 986
  • 24 Oct 2022
Topic Review
Glycation-Associated Diabetic Nephropathy and Long Noncoding RNAs
The glycation of various biomolecules is the root cause of many pathological conditions associated with diabetic nephropathy and end-stage kidney disease. Glycation imbalances metabolism and increases renal cell injury. Numerous therapeutic measures have narrowed down the adverse effects of endogenous glycation, but efficient and potent measures are miles away. Recent advances in the identification and characterization of noncoding RNAs, especially the long noncoding RNAs (lncRNAs), have opened a mammon of new biology to explore the mitigations for glycation-associated diabetic nephropathy. Furthermore, tissue-specific distribution and condition-specific expression make lncRNA a promising key for second-generation therapeutic interventions.
  • 986
  • 03 Nov 2022
Topic Review
Immune Microenvironment in AML
Acute myeloid leukemia is a life-threatening malignant disorder arising in a complex and dysregulated microenvironment that, in part, promotes the leukemogenesis. Treatment of relapsed and refractory AML, despite the current overall success rates in management of pediatric AML, remains a challenge with limited options considering the heavy but unsuccessful pretreatments in these patients.
  • 985
  • 01 Apr 2021
Topic Review
Human Stem Cell Transplantation for Retinal Degenerative Diseases
Irreversible visual impairment is mainly caused by retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. Stem cell research has experienced rapid progress in recent years, and researchers and clinical ophthalmologists are trying to implement this promising technology to treat retinal degeneration. There is currently no surgical or pharmacological solution to regenerate an injured or degenerative retina, and the only approach ophthalmologists can take is to slow the progress of the loss of vision. In the last decade, many efforts have been made to take advantage of the promising properties of the stem cell technology and apply them to retinal degenerative diseases.
  • 982
  • 08 Feb 2022
Topic Review
Coating Polymers for Neurodegenerative Disorders
Many types of nanocarriers have been developed for treating brain disorders. Polymer-based therapeutic agents have been explored for the treatment of neurodegenerative diseases due to various fascinating advantages of polymers such as great biocompatibility, nontoxicity, controllable degradation rate, tunable architectures, the possibility of multiple interactions between amyloidogenic protein/peptide and polymer, and excellent in vivo stability. Some of the most commonly used coating polymers for neurodegenerative disorders are discussed.
  • 982
  • 19 Jan 2023
Topic Review
Melatonin and Its Effects on the Human Body
Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective, immunomodulatory, and anti-apoptotic effects. Melatonin is also one of the most powerful natural antioxidants, directly acting on free radicals and the intracellular antioxidant enzyme system. Furthermore, it participates in antitumor activity, hypopigmentation processes in hyperpigmentary disorders, anti-inflammatory, and immunomodulating activity in inflammatory dermatoses, maintaining the integrity of the epidermal barrier and thermoregulation of the body. 
  • 979
  • 10 Mar 2023
Topic Review
Murine Animal Models in Osteogenesis Imperfecta
Osteogenesis imperfecta (OI), also known as “brittle bone disease”, is a rare genetic disorder that encompasses a group of conditions affecting the connective tissue. It is characterized by a decreased bone-mineral-density (BMD) alongside increased susceptibility to bone fractures, due to an abnormality in the synthesis and/or processing of the main protein of the bone extracellular matrix (ECM), the type I collagen molecule. In approximately 85% of cases, it is caused by mutations in the COL1A1 or COL1A2 genes, encoding the α1 (I) and α2 (I) chains of type I collagen, respectively. In the remainder of the cases, mutations in up to 19 different genes related to type I collagen synthesis or processing have been identified. All these mutations contribute to two types of collagen I defects; quantitative (based on the reduction of type I collagen expression) and qualitative (structural alterations of the collagen I molecule). In addition to the genetic heterogeneity, OI exhibits clinical heterogeneity, mainly governed by the mutated gene, the type of mutation, the position of the mutation along the gene and the genetic background of the patient. Hence, genetic heterogeneity is translated into clinical phenotypes that range from mild (barely affected) associated with quantitative defects, to severe forms (qualitative ones), that in some cases (in the most severe phenotypes) result in perinatal mortality.
  • 974
  • 29 Dec 2022
Topic Review
Kynurenines in Neurodegenerative Diseases
Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to the abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes, which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. 
  • 972
  • 25 Oct 2022
Topic Review
Breast Cancer-Associated Fibroblasts
Breast cancer-associated fibroblasts (BCAFs) are the CAFs present in breast cancers with genetic and phenotypic characteristics similar to CAFs. CAFs originate from a diverse range of cells, including endothelial cells, adipocytes, pericytes, and MSCs. Although CAFs were derived from endothelial cells and pericytes, the derivation was not tested in breast cancer models similar to other cancers. BCAFs have also been derived from adipocytes that lead to a desmoplastic microenvironment. BCAFs can originate from MSCs, which contribute to angiogenesis through up-regulation of clusterin leading to tumorigenesis. BCAFs possess the fibrillar collagen receptor, DDR2, which rearranges collagen fibers to develop an invasive and metastatic TME. Additionally, integrin α11 in BCAFs interacts with platelet-derived growth factor receptor beta (PDGFRβ) and promotes invasiveness by activating c-Jun N-terminal kinase (JNK) and producing a matricellular protein, tenascin C.
  • 970
  • 14 Jan 2022
Topic Review
Internal Ribosome Entry Site-Dependent Translation Dysregulation-Related Diseases
Internal ribosome entry site (IRES)-mediated translation is an alternative mechanism of translation initiation, known for maintaining protein synthesis when canonical translation is impaired. During a stress response, it contributes to cell reprogramming and adaptation to the new environment. 
  • 968
  • 23 Aug 2022
Topic Review
Clinical and Experimental Studies of TTFields on Glioblastomas
Glioblastoma (GBM) is the most common malignant primary brain tumor. Although the standard of care, including maximal resection, concurrent radiotherapy with temozolomide (TMZ), and adjuvant TMZ, has largely improved the prognosis of these patients, the 5-year survival rate is still < 10%. Tumor-treating fields (TTFields), a noninvasive and innovative therapeutic approach, has emerged as the fourth most effective treatment option for the management of this most deadly brain cancer.
  • 967
  • 17 Aug 2022
Topic Review
CFTR Lifecycle Map
Cystic Fibrosis (CF) is one of the most common genetic diseases prevalent among the Caucasian population and is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, several hundred disease-causing mutations are known, resulting in a vast range of geno- and phenotypes, which makes the development of therapeutics especially challenging. To support the development of novel therapeutics, systems biological disease maps can be used. Disease maps represent existing knowledge on disease mechanisms in a computationally readable and comprehensive manner so they can then be used by clinicians and experimental scientists as well as computational scientists for different purposes, such as structuring high-throughput data, identifying disease biomarkers, developing better diagnostics and also identifying potential drug targets and drug repositioning. The CFTR Lifecycle Map in particular details the biogenesis of CFTR in cells to support ongoing drug discovery endeavours in CF research.
  • 966
  • 22 Nov 2021
Topic Review
Immunomodulatory Role of Cell-Free DNA
The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders. Immunocompetent cells express pattern-recognition receptors on their cell membrane and cytoplasm. The majority of endogenous DNA is located intracellularly within nuclei and mitochondria. Extracellular, cell-free DNA (cfDNA) can also be detected in a variety of diseases, which has sparked interest in using cfDNA as a possible biomarker. The widespread use of liquid biopsies and the increasing demand for screening, as well as monitoring disease activity and therapy response, have enabled the revival of cfDNA research.
  • 964
  • 21 Nov 2022
Topic Review
Diabetic Foot with Exercise Therapy
Diabetic foot (DF) is a long-term diabetes complication that can increase morbidity and mortality in addition to affecting mobility and the overall well-being of patients. In particular, the DF has a complex multifactorial pathogenesis that makes it difficult to prevent and treat. In this sense, it is well known that the prevention and treatment of DF disease requires a multidisciplinary approach. Physical activity has always been considered a potential pillar in the prevention of DFD. More recently, it has been reported, that physical activity can contribute in the wound healing phase. Unfortunately, to date, there is no clear and definitive evidence on the role that protocols of physical activity can play in the treatment of patients at risk or with DFD. In order to pursue this objective, it is important to standardize exercise training protocols for the prevention or treatment of these patients. Moreover, it is now possible to organize innovative methods of conducting, monitoring and analysing physical activity performed by patients, even remotely.
  • 962
  • 29 Mar 2022
Topic Review
Caspase-1 Inhibition
The inflammatory protease caspase-1 is associated with the release of cytokines. An excessive number of cytokines (a “cytokine storm”) is a dangerous consequence of COVID-19 infection and has been indicated as being among the causes of death by COVID-19. The anti-inflammatory drug colchicine (which is reported in the literature to be a caspase-1 inhibitor) and the corticosteroid drugs, dexamethasone and methylprednisolone, are among the most effective active compounds for COVID-19 treatment.
  • 962
  • 18 Feb 2022
Topic Review
PARK7/DJ-1 in Gut-Brain Axis Diseases
Parkinson’s disease 7 (PARK7/DJ-1) is a multifunctional protein whose protective role has been widely demonstrated in neurodegenerative diseases, including PD, AD, or ischemic stroke. Recent studies also revealed the importance of PARK7/DJ-1 in the maintenance of the gut microbiome and also in the regulation of intestinal inflammation. All these findings suggest that PARK7/DJ-1 may be a link and also a potential therapeutic target in gut and brain diseases.
  • 962
  • 26 Apr 2023
Topic Review
Live Attenuated Influenza Vaccines
To induce broadly protective immune responses by vaccination, various strategies using live attenuated influenza vaccines (LAIVs) and novel vaccine platforms are under investigation. Despite superior cross-protection ability, very little attention has been paid to LAIVs for the development of UIV.
  • 960
  • 18 Apr 2021
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