Project description:The treatment of many dermatological disorders, such as autoimmune and immune-mediated diseases, consists of the use of systemic corticosteroids alone or in combination with other steroid-sparing immunosuppressants. Often, these treatment regimens are sufficient to control disease activity with relatively few side effects if monitored by a diligent physician. Some patients, however, may be refractory to treatment or develop intolerable side effects from therapy. For these patients, alternative treatment modalities with less toxicity and greater efficacy are required. Rituximab is a genetically engineered, chimeric monoclonal antibody directed against the B-cell lineage specific CD20 antigen. Originally developed for the treatment of B-cell non-Hodgkin"s lymphoma, rituximab has increasingly been used to treat a variety of autoimmune and immune-mediated disorders, such as rheumatoid arthritis, pemphigus diseases, systemic lupus erythematosus, dermatomyositis, and idiopathic thrombocytopenic purpura to name a few. Since very few randomized, controlled, clinical trials exist regarding the use of rituximab in the treatment of dermatological disorders, guidelines for the off-label use of this medication come from anecdotal case reports and cohort studies. Further clinical studies are needed to validate the safety and efficacy of rituximab therapy in dermatological disorders. Until then, we present a literature review of the emerging use of this B-cell depletion therapy. (J Clin Aesthetic Dermatol. 2009;2(5):29-37.).
Project description:The expanding genome editing toolbox has revolutionized life science research ranging from the bench to the bedside. These "molecular scissors" have offered us unprecedented abilities to manipulate nucleic acid sequences precisely in living cells from diverse species. Continued advances in genome editing exponentially broaden our knowledge of human genetics, epigenetics, molecular biology, and pathology. Currently, gene editing-mediated therapies have led to impressive responses in patients with hematological diseases, including sickle cell disease and thalassemia. With the discovery of more efficient, precise and sophisticated gene-editing tools, more therapeutic gene-editing approaches will enter the clinic to treat various diseases, such as acquired immunodeficiency sydrome (AIDS), hematologic malignancies, and even severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These initial successes have spurred the further innovation and development of gene-editing technology. In this review, we will introduce the architecture and mechanism of the current gene-editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease-based tools and other protein-based DNA targeting systems, and we summarize the meaningful applications of diverse technologies in preclinical studies, focusing on the establishment of disease models and diagnostic techniques. Finally, we provide a comprehensive overview of clinical information using gene-editing therapeutics for treating various human diseases and emphasize the opportunities and challenges.
Project description:Additively manufactured nano-MEH systems are widely used to harvest energy from renewable and sustainable energy sources such as wind, ocean, sunlight, raindrops, and ambient vibrations. A comprehensive study focusing on in-depth technology evolution, applications, problems, and future trends of specifically 3D printed nano-MEH systems with an energy point of view is rarely conducted. Therefore, this paper looks into the state-of-the-art technologies, energy harvesting sources/methods, performance, implementations, emerging applications, potential challenges, and future perspectives of additively manufactured nano-mechanical energy harvesting (3DP-NMEH) systems. The prevailing challenges concerning renewable energy harvesting capacities, optimal energy scavenging, power management, material functionalization, sustainable prototyping strategies, new materials, commercialization, and hybridization are discussed. A novel solution is proposed for renewable energy generation and medicinal purposes based on the sustainable utilization of recyclable municipal and medical waste generated during the COVID-19 pandemic. Finally, recommendations for future research are presented concerning the cutting-edge issues hurdling the optimal exploitation of renewable energy resources through NMEHs. China and the USA are the most significant leading forces in enhancing 3DP-NMEH technology, with more than 75% contributions collectively. The reported output energy capacities of additively manufactured nano-MEH systems were 0.5-32 mW, 0.0002-45.6 mW, and 0.3-4.67 mW for electromagnetic, piezoelectric, and triboelectric nanogenerators, respectively. The optimal strategies and techniques to enhance these energy capacities are compiled in this paper.
Project description:Achillea spp. is well known for its broad range of applications and long history of use in traditional medicine around the world. Health benefits of Achillea extracts result from the multitude of secondary metabolites identified in the plants from this genus that include flavonoids, phenolic acids, terpenes, guaianolides, phytosterols, fatty acids, and organic acids. The properties of several Achillea extracts meet also the expectations of a vividly developing cosmetic market. An increasing number of studies on the dermatological properties of Achillea spp. are observed in the recent years, with Achillea millefolium L. being the most studied and used representative of the genus. There is strong scientific evidence showing that also other yarrow species might be rich sources of effective cosmetic ingredients, with skin calming and rejuvenating properties, wound healing activity, and anti-inflammatory potential. Several Achillea extracts and isolated compounds were also shown to display significant tyrosinase inhibitory, antioxidant, and antimicrobial properties and thus are interesting candidates for active ingredients of medications and cosmetic products protecting the skin from the harmful impact of environmental stressors. The aim of this review is to collect the current information on the composition and cosmeceutical significance of different Achillea species.
Project description:Background: Since disulfiram's discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods: For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases. The key search terms were "disulfiram" and "Antabuse". Animal studies and in vitro studies highlighting important mechanisms and safety issues were also included. Results: In total, 196 sources addressing our research focus spanning 1948-2022 were selected for inclusion. In addition to alcohol use disorder, emerging data support a potential role for disulfiram in the treatment of other addictions (e.g., cocaine), infections (e.g., bacteria such as Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, and cancers. The side effects range from minor to life-threatening, with lower doses conveying less risk. Caution in human use is needed due to the considerable inter-subject variability in disulfiram pharmacokinetics. Conclusions: While disulfiram has promise as a "repurposed" agent in human disease, its risk profile is of concern. Animal studies and well-controlled clinical trials are needed to assess its safety and efficacy for non-alcohol-related indications.
Project description:Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.
Project description:Insulin-degrading enzyme (IDE) is an atypical zinc-metalloendopeptidase that hydrolyzes insulin and other intermediate-sized peptide hormones, many of which are implicated in skin health and wound healing. Pharmacological inhibitors of IDE administered internally have been shown to slow the breakdown of insulin and thereby potentiate insulin action. Given the importance of insulin and other IDE substrates for a variety of dermatological processes, pharmacological inhibitors of IDE suitable for topical applications would be expected to hold significant therapeutic and cosmetic potential. Existing IDE inhibitors, however, are prohibitively expensive, difficult to synthesize and of undetermined toxicity. Here we used phage display to discover novel peptidic inhibitors of IDE, which were subsequently characterized in vitro and in cell culture assays. Among several peptide sequences tested, a cyclic dodecapeptide dubbed P12-3A was found to potently inhibit the degradation of insulin (Ki = 2.5 ± 0.31 μM) and other substrates by IDE, while also being resistant to degradation, stable in biological milieu, and highly selective for IDE. In cell culture, P12-3A was shown to potentiate several insulin-induced processes, including the transcription, translation and secretion of alpha-1 type I collagen in primary murine skin fibroblasts, and the migration of keratinocytes in a scratch wound migration assay. By virtue of its potency, stability, specificity for IDE, low cost of synthesis, and demonstrated ability to potentiate insulin-induced processes involved in wound healing and skin health, P12-3A holds significant therapeutic and cosmetic potential for topical applications.
Project description:Zika virus is an arbovirus that has rapidly spread within the Americas since 2014, presenting a variety of clinical manifestations and neurological complications resulting in congenital malformation, microcephaly, and possibly, in male infertility. These significant clinical manifestations have led investigators to develop several candidate vaccines specific to Zika virus. In this review we describe relevant targets for the development of vaccines specific for Zika virus, the development status of various vaccine candidates and their different platforms, as well as their clinical progression.
Project description:Molecularly defined subgroups of tumors characterized by specific driver mutations have been identified in the majority of cancers. The availability of novel drugs capable of targeting signaling pathways activated by genetic derangements has led to hypothesize the possibility to treat patients based on their genomic profile. A clear example is represented by lung adenocarcinoma for which it has been possible to identify driver genetic alterations in approximately 75% of the cases. Among these, RET fusion transcripts are detectable in about 1-2% of lung adenocarcinomas and might represent targets for therapeutic intervention with RET kinase inhibitors. However, a number of issues need to be addressed to make genomics-driven oncology routinely accessible for cancer patients, including: 1) the availability of novel methods in molecular diagnostics that allow a comprehensive molecular characterization of lung tumors starting from a low input DNA/RNA; 2) identification of reliable and reproducible biomarkers of response/resistance to targeted agents; 3) the assessment of the role of tumor heterogeneity in the response to drugs targeting molecular pathways.
Project description:Ionizing radiation has historically been used to treat cancer by killing tumour cells, in particular by inducing DNA damage. This view of radiotherapy (RT) as a simple cytotoxic agent has dramatically changed in recent years, and it is now widely accepted that RT can deeply reshape the tumour environment by modulating the immune response. Such evidence gives a strong rationale for the use of immunomodulators to boost the therapeutic value of RT, introducing the era of 'immunoradiotherapy'. The increasing amount of preclinical and clinical data concerning the combination of RT with immunomodulators, in particular with immune checkpoint inhibitors such as anti-PD-1/PD-L1 and anti-CTLA4, reflects the interest of the scientific and medical community concerning immunoradiotherapy. The expectations are enormous since the rationale for performing such combinations is strong, with the possibility to use a local treatment such as RT to amplify a systemic antitumour response, as illustrated by the case of the abscopal effect. Nevertheless, several points remain to be addressed such as the need to find biomarkers to identify patients who will benefit from immunoradiotherapy, the identification of the best sequences/schedules for combination with immunomodulators and mechanisms to overcome resistance. Additionally, the effects of immunoradiotherapy on healthy tissues and related toxicity remain largely unexplored. To answer these critical questions and make immunoradiotherapy keep its promising qualities, large efforts are needed from both the pharmaceutical industry and academic/governmental research. Moreover, because of the work of both these entities, the arsenal of available immunomodulators is quickly expanding, thus opening the field to increasing combinations with RT. We thus forecast that the field of immunoradiotherapy will further expand in the coming years, and it needs to be supported by appropriate investment plans.