CLEC12B Regulates Melanocyte Immunity and Homeostasis in the Skin through the Signal Transducer and Activator of Transcription 1/IRF1 Axis.

CLEC12B is a C-type lectin receptor involved in the inhibition of NKs-mediated cytotoxicity. We have previously shown that CLEC12B is predominantly expressed on melanocytes and inhibits melanin production and pigmentation as well as proliferation of melanoma. To date, the role of CLEC12B in skin immunity is unknown.

UVB radiation suppresses Dicer expression through β-catenin.

Ultraviolet (UV) rays prompt a natural response in epidermal cells, particularly within melanocytes. The changes in gene expression and related signaling pathways in melanocytes following exposure to UV radiation are still not entirely understood. Our findings reveal that UVB irradiation suppresses the expression of Dicer (also known as Dicer1).

Novel mechanisms of MITF regulation identified in a mouse suppressor screen.

MITF, a basic Helix-Loop-Helix Zipper (bHLHZip) transcription factor, plays vital roles in melanocyte development and functions as an oncogene. We perform a genetic screen for suppressors of the Mitf-associated pigmentation phenotype in mice and identify an intragenic Mitf mutation that terminates MITF at the K316 SUMOylation site, leading to loss of the C-end intrinsically disordered region (IDR). The resulting protein is more nuclear but less stable than wild-type MITF and retains DNA-binding ability.

Design of Collagen and Gelatin-based Electrospun Fibers for Biomedical Purposes: An Overview.

Collagen and gelatin are essential natural biopolymers commonly utilized in biomaterials and tissue engineering because of their excellent physicochemical and biocompatibility properties. They can be used either in combination with other biomacromolecules or particles or even exclusively for the enhancement of bone regeneration or for the development of biomimetic scaffolds. Collagen or gelatin derivatives can be transformed into nanofibrous materials with porous micro- or nanostructures and superior mechanical properties and biocompatibility using electrospinning technology.

The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017.

Human H3N2 influenza viruses are subject to rapid antigenic evolution which translates into frequent updates of the composition of seasonal influenza vaccines. Despite these updates, the effectiveness of influenza vaccines against H3N2-associated disease is suboptimal. Seasonal influenza vaccines primarily induce hemagglutinin-specific antibody responses.

Novel mechanisms of MITF regulation and melanoma predisposition identified in a mouse suppressor screen.

MITF, a basic-Helix-Loop-Helix Zipper (bHLHZip) transcription factor, plays vital roles in melanocyte development and functions as an oncogene. To explore MITF regulation and its role in melanoma, we conducted a genetic screen for suppressors of the Mitf-associated pigmentation phenotype. An intragenic Mitf mutation was identified, leading to termination of MITF at the K316 SUMOylation site and loss of the C-end intrinsically disordered region (IDR).

Loss of Dicer in Newborn Melanocytes Leads to Premature Hair Graying and Changes in Integrin Expression.

Premature hair graying occurs owing to the depletion of melanocyte stem cells in the hair follicle, which can be accelerated by stress caused by genetic or environmental factors. However, the connection between stress and melanocyte stem cell loss is not fully understood. MicroRNAs are molecules that control gene expression by regulating mRNA stability and translation and are produced by the enzyme Dicer, which is repressed under stress.

Design of Tailor-Made Biopolymer-Based Capsules for Biological Application by Combining Porous Particles and Polysaccharide Assembly.

Various approaches have been described in the literature to demonstrate the possibility of designing biopolymer particles with well-defined characteristics, such as size, chemical composition or mechanical properties. From a biological point of view, the properties of particle have been related to their biodistribution and bioavailability. Among the reported core-shell nanoparticles, biopolymer-based capsules can be used as a versatile platform for drug delivery purposes.

Derivation and Use of Cell Lines from Mouse Models of Melanoma.

The establishment of consistent genetically modified mouse melanoma models and cell lines is of paramount importance for prevention and treatment. In this study, we review the different mouse melanoma cell lines that have been established. After careful molecular characterization of the established mouse melanoma cell lines, modification of the genome, microenvironment, or even the environment using appropriate in cellulo and in vivo assays may reveal novel genetic and nongenetic changes.

tLyp-1: A peptide suitable to target NRP-1 receptor.

Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity.

Definitive urine drug test findings in patients prescribed opioids for pain from a large national database.

Objective: Clinicians and policymakers have been wrestling with the appropriateness and safety of opioid therapy during the opioid crisis. Policy and clinical decisions have often been made without much current data on trends in drug use in patients with pain. Thus, we evaluated definitive urine drug test (UDT) results in patients being treated for pain to see if those taking their prescribed opioids were less likely to be positive for the primary illicit drugs currently driving overdose deaths: cocaine, heroin, fentanyl, and methamphetamine.

Analysis of Urine Drug Test Results From Substance Use Disorder Treatment Practices and Overdose Mortality Rates, 2013-2020.

Importance: Drug overdose deaths in the US are currently the highest ever recorded; data collected from public health surveillance sources can help to identify emerging drug use patterns associated with overdose mortality rates, but the time lag in results often limits utility. Urine drug testing (UDT) is one potentially underused source that could augment surveillance efforts through timely data collection.

Objective: To evaluate the correlation between real-time UDT results from a proprietary national database and overdose mortality data from the National Vital Statistics System.

ZEB1 transcription factor promotes immune escape in melanoma.

Background: The efficacy of immunotherapies in metastatic melanoma depends on a robust T cell infiltration. Oncogenic alterations of tumor cells have been associated to T cell exclusion. Identifying novel cancer cell-intrinsic non-genetic mechanisms of immune escape, the targeting of which would reinstate T cell recruitment, would allow to restore the response to anti-programmed cell death protein 1 (PD-1) antibody therapy.

Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma.

G-protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established.

Adipocyte Extracellular Vesicles Decrease p16 in Melanoma: An Additional Link between Obesity and Cancer.

Obesity is a recognized factor for increased risk and poor prognosis of many cancers, including melanoma. In this study, using genetically engineered mouse models of melanoma (Nras transgenic expression, associated or not with Cdkn2a heterozygous deletion), we show that obesity increases melanoma initiation and progression by supporting tumor growth and metastasis, thereby reducing survival. This effect is associated with a decrease in p16 expression in tumors.

Pre-existing antibodies directed against a tetramerizing domain enhance the immune response against artificially stabilized soluble tetrameric influenza neuraminidase.

The neuraminidase (NA) is an abundant antigen at the surface of influenza virions. Recent studies have highlighted the immune-protective potential of NA against influenza and defined anti-NA antibodies as an independent correlate of protection. Even though NA head domain changes at a slightly slower pace than hemagglutinin (HA), NA is still subject to antigenic drift, and therefore an NA-based influenza vaccine antigen may have to be updated regularly and thus repeatedly administered.

Design of a Targeting and Oxygen-Independent Platform to Improve Photodynamic Therapy: A Proof of Concept.

Photodynamic therapy (PDT) is a promising technique to treat different kinds of disease especially cancer. PDT requires three elements: molecular oxygen, a photoactivatable molecule called the photosensitizer (PS), and appropriate light. Under illumination, the PSs generate, in the presence of oxygen, the formation of reactive oxygen species including singlet oxygen, toxic, which then destroys the surrounding tissues.

Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage.

The canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulates transcription of Mitf-M, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, whereas the second wave of melanocytes is derived from Schwann cell precursors (SCPs).

TBX2 controls a proproliferative gene expression program in melanoma.

Senescence shapes embryonic development, plays a key role in aging, and is a critical barrier to cancer initiation, yet how senescence is regulated remains incompletely understood. TBX2 is an antisenescence T-box family transcription repressor implicated in embryonic development and cancer. However, the repertoire of TBX2 target genes, its cooperating partners, and how TBX2 promotes proliferation and senescence bypass are poorly understood.

Molecular Profiling of Spermatozoa Reveals Correlations between Morphology and Gene Expression: A Novel Biomarker Panel for Male Infertility.

Choosing spermatozoa with an optimum fertilizing potential is one of the major challenges in assisted reproductive technologies (ART). This selection is mainly based on semen parameters, but the addition of molecular approaches could allow a more functional evaluation. To this aim, we used sixteen fresh sperm samples from patients undergoing ART for male infertility and classified them in the high- and poor-quality groups, on the basis of their morphology at high magnification.

Polysubstance Use Among Patients Treated With Buprenorphine From a National Urine Drug Test Database.

Importance: Polysubstance use is a concern for patients treated for opioid use disorder (OUD). While buprenorphine can curtail harmful opioid use, co-occurring use of nonprescribed substances, such as cocaine, methamphetamine, and other opioids, may negatively affect treatment outcomes.

Objective: To characterize factors associated with urine drug positivity for nonprescribed substances among patients prescribed buprenorphine.

Impact of genetic variation in CYP2C19, CYP2D6, and CYP3A4 on oxycodone and its metabolites in a large database of clinical urine drug tests.

Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens collected from 14,684 genotyped patients prescribed oxycodone.