Topic Review
Inflammatory Bowel Disease Treatments
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time.
  • 859
  • 05 Jul 2022
Topic Review
NLRP3 and Preeclampsia
Preeclampsia (PE) is a specific syndrome of human pregnancy, being one of the main causes of maternal death. Persistent inflammation in the endothelium stimulates the secretion of several inflammatory mediators, activating different signaling patterns. One of these mechanisms is related to NLRP3 activation, initiated by high levels of danger signals such as cholesterol, urate, and glucose, producing IL-1, IL-18, and cell death by pyroptosis. Furthermore, reactive oxygen species (ROS), act as an intermediate to activate NLRP3, contributing to subsequent inflammatory cascades and cell damage. Moreover, increased production of ROS may elevate nitric oxide (NO) catabolism and consequently decrease NO bioavailability. NO has many roles in immune responses, including the regulation of signaling cascades. At the site of inflammation, vascular endothelium is crucial in the regulation of systemic inflammation with important implications for homeostasis.
  • 859
  • 19 Nov 2021
Topic Review
PET for Microenvironment-Targeted Therapy
 Quantitative parameters of FDG-PET, such as SUV and TLG have been used to evaluate therapeutic response. Recent advancement in anti-cancer therapeutics showed that tumor response to molecular-targeted drugs and immune-checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration and morphological change after the course of effective therapy. Metabolic changes and temporal enlargement due to immune cell infiltration seen after immune-checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies facilitated the modification of conventional Response Evaluation Criteria in Solid Tumor and FDG-PET response evaluation criteria. Tumor microenvironment including cancer stem cells (CSCs) that is thought to be a root cause of tumor heterogeneity; is considered a target of novel and effective therapy.   Accumulation of FDG reflects glucose metabolism of both cancer cells and immunologically competent cells in the tumor microenvironment. Immunological reaction to the therapy differs among patients according to the individual immune function. Considering the heterogeneity of tumor tissue and individual variation in tumor response to immunotherapy, radiomics approach combines quantitative image features with deep learning algorithm have the potentials to improve response assessment in more personalized treatment.   Stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-targeted α-particle therapy has been introduced, because SDF-1/CXCR4 axis is known to increase epithelial-mesenchymal transition to facilitate invasion and metastasis, and regulate immune response by accelerating T cell proliferation as well as PD-1 and PD-L1 expression in cancer cells and cytotoxic T lymphocytes, respectively. Prominent energy profile and biological effect of α-particles are promising as an alternative in targeted radionuclide therapy (TRT). Radiation dosimetry according to the theranostics approach will permit accurate TRT and artificial intelligence-based treatment decision making and precise response evaluation would be a precision nuclear medicine in the future.
  • 859
  • 08 Feb 2021
Topic Review
DNA Polymerases
Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. 
  • 859
  • 14 Dec 2020
Topic Review
Contact Dermatitis of the Vulva
The vulvar area is a common site of contact dermatitis due to the thin skin, easily traversable by irritant and allergic substances. The nonkeratinized vulvar vestibule is likely to be more permeable than the keratinized portions of the vulva and thus more susceptible to exogenous topical agents. The vulva is an area of occlusion due to both its intrinsic anatomical structure and the frequent use of occlusive napkins or underwear, which increase penetration or absorption of both irritants and allergens. Furthermore, women at different ages, due to urine and feces as children and to vaginal mucosal atrophy and the increase in the vulvar pH in menopause, may have an altered barrier function and, in incontinent elderly subjects, the use of diapers may contribute to increased susceptibility to irritants and allergens.
  • 859
  • 16 Nov 2021
Topic Review
Idiopathic Osteoporosis
Osteoporosis is defined as a decrease in bone density that results in micro-architecture deterioration, predisposing the affected patients to fractures. Operationally, osteoporosis has been defined on the basis of a bone mineral density assessment using dual energy X-ray absorptiometry.
  • 858
  • 28 Sep 2021
Topic Review
Interventions for Hemodialysis Patients
The hemodialytic clinic must today be directed towards a greater biocompatibility tecnology , the evaluation of the most valid tools to evaluate the nutritional status of patients on every kind of extracorporeal substitutive treatments. Good nutrition is a cultural background that must represent the daily routine of nephrologists. In our opinion, the loss of amino acids up to 1 kg / year is a good starting point. Many parameters used for nutritional outcomes are uncertain and by now the figure of the nutritionist must support tthe nephrologist from pre-dialysis, to dialysis and also in the course of the transplant.
  • 858
  • 05 Nov 2020
Topic Review
ALA against COVID-19-Induced Cardiovascular Diseases
Cardiovascular complications are rapidly emerging as a major peril in COVID-19 in addition to respiratory disease. The mechanisms underlying the excessive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities remain only partly understood. SARS-CoV-2 infection is caused by binding of the viral surface spike (S) protein to the human angiotensin-converting enzyme 2 (ACE2), followed by the activation of the S protein by transmembrane protease serine 2 (TMPRSS2). ACE2 is expressed in the lung (mainly in type II alveolar cells), heart, blood vessels, small intestine, etc., and appears to be the predominant portal to the cellular entry of the virus. Based on current information, most people infected with SARS-CoV-2 virus have a good prognosis, while a few patients reach critical condition, especially the elderly and those with chronic underlying diseases. The “cytokine storm” observed in patients with severe COVID-19 contributes to the destruction of the endothelium, leading to “acute respiratory distress syndrome” (ARDS), multiorgan failure, and death. At the origin of the general proinflammatory state may be the SARS-CoV-2-mediated redox status in endothelial cells via the upregulation of ACE/Ang II/AT1 receptors pathway or the increased mitochondrial reactive oxygen species (mtROS) production. Furthermore, this vicious circle between oxidative stress (OS) and inflammation induces endothelial dysfunction, endothelial senescence, high risk of thrombosis and coagulopathy. The microvascular dysfunction and the formation of microthrombi in a way differentiate the SARS-CoV-2 infection from the other respiratory diseases and bring it closer to cardiovascular diseases like myocardial infarction and stroke. Due the role played by OS in the evolution of viral infection and in the development of COVID-19 complications, the use of antioxidants as adjuvant therapy seems appropriate in this new pathology. Alpha-lipoic acid (ALA) could be a promising candidate that, through its wide tissue distribution and versatile antioxidant properties, interferes with several signaling pathways.
  • 858
  • 12 Aug 2021
Topic Review
Targeting Chemosensitive Channels for Dysphagia
Swallowing is a physiological process that transports ingested foods, liquids, and saliva from the oral cavity into the stomach. Difficulty in the oropharyngeal swallowing process or oropharyngeal dysphagia is a major health problem. There is no established pharmacological therapy for the management of oropharyngeal dysphagia. Studies have suggested that the current clinical management of oropharyngeal dysphagia has limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia.
  • 857
  • 27 Oct 2020
Topic Review
Targeting CDK9 for Glioblastoma Treatment
Glioblastoma is the most common and aggressive primary malignant brain tumor, and more than two-thirds of patients with glioblastoma die within two years of diagnosis. The challenges of treating this disease mainly include genetic and microenvironmental features that often render the tumor resistant to treatments. Despite extensive research efforts, only a small number of drugs tested in clinical trials have become therapies for patients. Targeting cyclin-dependent kinase 9 (CDK9) is an emerging therapeutic approach that has the potential to overcome the challenges in glioblastoma management.
  • 857
  • 02 Jul 2021
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