UCHL1/PGP 9.5 Dynamic in neuro-immune-cutaneous milieu : focusing on axonal nerve terminals and epidermal keratinocytes in psoriatic itch

Psoriasis is an immunogenetic skin disease manifesting as plaque lesions on the skin. Patients with psoriasis frequently suffer from itch, an unpleasant sensation causing a desire to scratch. Psoriatic itch is mainly transmitted by unmyelinated C-fibers; however, the exact molecular mechanism of psoriatic itch is still unexplained. Protein gene product 9.5 (PGP 9.5) is a panneurological marker commonly used for analysis of peripheral peptidergic and nonpeptidergic nerves and identification of cutaneous neuro-immune-endocrine cells. However, some studies suggested that nonneuronal cells, like keratinocytes, may also express PGP 9.5. This phenomenon might be linked with impaired axonal transport, keratinocyte injury, or dysfunctions of neuro-immune-cutaneous connections. The aim of this study was to analyze the expression of PGP 9.5 in psoriatic skin. We observed significantly altered density of PGP 9.5-positive axonal nerve terminals in pruritic lesional (p=0.04) and nonlesional psoriatic skin (p>0.001) compared with controls. In contrast, no significant differences were observed between psoriatic skin without itch and controls. Furthermore, PGP 9.5 expression by suprabasal keratinocytes (SBKs) was significantly increased in itchy skin lesions (p=0.007) compared to skin without itch, and a positive correlation was observed between PGP 9.5 expression and itch intensity (r=0.64; p=0.02). Our findings indicate changes in peripheral innervations and psoriatic keratinocytes, which may influence neuro-immune-cutaneous homeostasis and modulate itch transmission

Bioactive Compounds as Potential Agents for Sexually Transmitted Diseases Management: A Review to Explore Molecular Mechanisms of Action

Sexually transmitted diseases (STDs) are produced by pathogens like bacteria, fungi, parasites, and viruses, and may generate severe health problems such as cancer, ulcers, and even problems in the newborn. This narrative review aims to present updated information about the use of natural bioactive compounds for the prevention and treatment of sexually transmitted infections. A search of the literature was performed using databases and search engines such as PubMed, Scopus, Google Scholar and Science Direct. From the pharmacotherapeutic management point of view, any strategies for prevention should contain medical approaches. The bioactive compounds obtained from natural products have shown biological effects against different microorganisms for the treatment of these diseases. The main results showed antimicrobial, antiprotozoal, antifungal and antiviral effects such as HIV. Also, the molecular mechanisms, signalling pathways and action targets of natural compounds were highlighted, thus justifying bacterial and antifungal inhibition, apoptosis or reduction of viral replication. From the data of our study, we can conclude that natural compounds may be a significant source for adjuvant drugs / complementary therapies in the treatment of STDs. With all these benefits, the future must conduct extensive clinical trials and the development of pharmaceutical nanotechnologies for a greater therapeutic effect.This work was supported by CONICYT PIA/APOYO CCTE AFB170007. The project is supported under the program of the Minister of Science and Higher Education under the name “Regional Initiative of Excellence” in 2019–2022 project number: 024/RID/2018/19 and by Medical University of Lublin, Poland, University Grant number: DS 07/2021. This study partially supported by Canakkale Onsekiz Mart University (Scientific Research Projects, ID: FYL-2017–1339 and FBA-2017–1268)

Hot Nano-particles in Polar or Paramagnetic Liquids Interact as Monopoles.

When neutral nano-particles are heated or cooled in a polar liquid, they will interact with each other as if they carry an electrostatic charge that is proportional to the temperature difference between the particle and the surrounding fluid. The same should hold for suspensions liquids of asymmetric ferromagnetic particles, in which case the heated nano-particles should behave as magnetic monopoles. However, the analogy with electrostatics/magnetostatics is not complete: heated/cooled nano-particles do not move under the influence of an applied homogeneous field. They should, however, interact as monopoles with each other and should move in inhomogeneous fields.This is the author accepted manuscript. The final version is available from the American Chemical Society via https://doi.org/10.1021/acs.jpcb.6b0184

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11–q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11–q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m−/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m−/p+), but not paternal (m+/p−), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone

Toxicity of parasites and their unconventional use in medicine

Introduction. Over 300 species of parasites can possibly be passed on humans. Most of the parasitic infections are defined based on their pathogenicity; however, some positive effects of a parasite existence within the human body have recently been suggested. Beneficial outcomes of parasite infections might result from the production and release of metabolites, modification of host immune response or products uptake of the host. Objective. The aim of the study was a comprehensive analysis of a wide range of effects of parasites on the human body, including an overview of the toxic and positive effects. State of knowledge. In the light of the latest research presenting the unconventional use of parasites in medicine, the widely understood of their impact on the human body can also be considered in a positive context. Clinical cases from diseases caused by the toxic effects of parasites, as described in recent years, indicate that the problem of parasitic infections still persists. Despite a great deal of knowledge about the toxic effects of parasites on the human organism and, above all, despite the improvement in sanitary conditions, there is a resurgence of parasitic infections, as evidenced, e.g. by the examples presented in this review. Conclusions. The examples of positive effects of parasites presented so far give hope for the future in terms of fighting many diseases for which pharmacological treatment has not yet brought a positive effect. A better understanding of those processes might lead to the development of new methods of unconventional medical treatment

Indications of post-zygotic copy number variation in a region between <i>IL10Rβ</i> and <i>IFNAR1</i>.

<p>Results from eight Illumina genotyping experiments are shown using blood DNA from two pairs of monozygotic twins (panel A for twin 012_01 versus co-twin 012_02, and in panel B for twin 159201 versus co-twin 159202) and two unrelated individuals, where two different tissues were analyzed from each subject (Panels C and D; subjects ML36 and SK58, respectively). Abbreviations BL, PT and UM indicate peripheral blood DNA, primary breast tumor and healthy morphologically normal breast tissue from a patient affected with breast cancer, respectively. Illumina 610 or 660W SNP arrays were used, which also contain so called “intensity only probes” (often with cvni-prefix), only useful for copy number analyses. Therefore, only Log R Ratio (LRR) windows of Illumina experiments are shown here, since the B Allele Frequency (BAF) values are not informative for this type of probes. LRR values below and above zero suggest a deletion or a gain, respectively. The four array probes showing variation between the studied samples are labeled as red dots in yellow fields.</p