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Topic Review
Mechanisms and Biomarkers of Metal Allergy
Metal allergy is mainly an environmental disorder which can cause allergic contact dermatitis. Environmental metal exposures include jewelry, everyday metal items, mobile phones, leather, metal-rich food and implants, including stents or anchors. While consumer exposure is liable for the majority of metal hypersensitivity cases, the significance of occupational exposure to metals remains relevant. The most common metal allergens are nickel, chromium, and cobalt.
  • 841
  • 08 Jan 2023
Topic Review
Diffuse Large B-Cell Lymphoma
The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy. Antibody-drug conjugates (ADC’s) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide (LEN) in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.
  • 841
  • 24 Nov 2020
Topic Review
Gene Therapy in PolyQ SCAs
Polyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death.
  • 841
  • 27 Apr 2021
Topic Review Peer Reviewed
Simple Formulae, Deep Learning and Elaborate Modeling for the Covid-19 Pandemic
Predictive modelling of infectious diseases is very important in planning public health policies, particularly during outbreaks. This work reviews the forecasting and mechanistic models published earlier. It is emphasized that researchers’ forecasting models exhibit, for large t, algebraic behavior, as opposed to the exponential behavior of the classical logistic-type models used usually in epidemics. Remarkably, a newly introduced mechanistic model also exhibits, for large t, algebraic behavior in contrast to the usual Susceptible-Exposed-Infectious-Removed (SEIR) models, which exhibit exponential behavior. The unexpected success of researchers’ simple forecasting models provides a strong support for the validity of this novel mechanistic model. It is also shown that the mathematical tools used for the analysis of the first wave may also be useful for the analysis of subsequent waves of the COVID-19 pandemic.
  • 841
  • 28 Sep 2022
Topic Review
Belantamab Mafodotin and Multiple Myeloma
Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed
  • 841
  • 24 Feb 2021
Topic Review
Tripartite Motif Family
The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers.
  • 841
  • 22 Sep 2021
Topic Review
OPV AIDS Hypothesis
The oral polio vaccine (OPV) AIDS hypothesis posits that the AIDS pandemic originated from live polio vaccines prepared in chimpanzee tissue cultures and then administered to up to one million Africans between 1957 and 1960 in experimental mass vaccination campaigns. Data analyses in molecular biology and phylogenetic studies contradict the OPV AIDS hypothesis; consequently, scientific consensus regards the hypothesis as disproven. The journal Nature has described the hypothesis as "refuted".
  • 841
  • 09 Oct 2022
Topic Review
Effects of Statins on Cancer via Autophagy
Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy.
  • 841
  • 09 Jun 2022
Topic Review
Nociceptive TRP Channel
Transient receptor potential (TRP) channels have emerged as key molecular identities in the sensory transduction of pain-producing stimuli. The ability of nociceptors to behave as noxious stimuli detectors relies on the presence of specialized transducing molecules at their peripheral nerve terminals capable of transforming the harmful physical (thermal and mechanical) and chemical stimuli into generator potentials. Upon nerve terminal stimulation, the output signal conveying to the central nervous system depends on the properties of transducer channels which produce generator potentials. Voltage-gated channels subsequently translate it into action potential firing. Nociceptive TRP channels are among the most studied transducer channels expressed in nociceptors and play a pivotal role in the study of pain.
  • 841
  • 09 Feb 2021
Topic Review
Natural Products for Alleviating Non-alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of fat deposits (>5%) in the liver with subsequent inflammation and fibrosis. Studies in the literature show that insulin resistance (IR) may be considered as the key mechanism in the onset and progression of NAFLD. Using natural products, for example, spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, and bromelain, as an alternative approach in the treatment of NAFLD has drawn growing attention among physicians.
  • 840
  • 06 Jan 2022
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