Characterizations of Centrifugal Electrospun Polyvinyl Alcohol/Sodium Alginate/Tamanu Oil/Silver Nanoparticles Wound Dressing.

Known for its water solubility, flexibility, strong adhesion, and eco-friendly nature, polyvinyl alcohol (PVA) is widely used in various industries. In the medical field, it is used for applications such as creating bandages and orthopaedic devices. Incorporating sodium alginate (SA) into PVA membranes enhances their structural integrity, breathability, and permeability, thereby minimising the risk of cellular damage in the wound zone. Moreover, the addition of tamanu oil (C alophyllum inophyllum L.) and silver nanoparticles, both of which are known for their antibacterial properties and benefits in traditional wound healing, further enhances the membranes' wound-healing effectiveness. Following production, the membranes undergo a series of tests designed to evaluate their physical properties as well as their antioxidant and antibacterial capabilities. Subsequently, in vitro testing is conducted using human skin cells; experiments on Wistar rats are then performed. Numerous experiments have consistently demonstrated that the performance of polyvinyl alcohol/sodium alginate/tamanu oil (PVA/SA/Oil) membrane is superior to that of polyvinyl alcohol/sodium alginate/tamanu oil/silver nanoparticles (PVA/SA/Oil/Ag NP) membrane. Specifically, the polyvinyl alcohol/sodium alginate (PVA/SA) combination exhibits an impressive wound-healing rate of 98.82% after 15 days, with cells maintaining a high viability of 92% in a nourishing environment. Moreover, these membranes exhibit exceptional resistance to the oxidation of free radicals, surpassing the 70% threshold, and they possess antibacterial activity against Staphylococcus aureus subsp. aureus in vitro. Based on the obtained results, the nanofiber membranes composed of polyvinyl alcohol/ alginate/ tamanu oil, with or without silver nanoparticles, have shown potential as wound dressings in the wound care discipline.

Extent and types of gender-based discrimination against female medical students and physicians at five university hospitals in Germany - results of an online survey.

Objective: There is a gap in research on gender-based discrimination (GBD) in medical education and practice in Germany. This study therefore examines the extent and forms of GBD among female medical students and physicians in Germany. Causes, consequences and possible interventions of GBD are discussed. Methods: Female medical students (n=235) and female physicians (n=157) from five university hospitals in northern Germany were asked about their personal experiences with GBD in an online survey on self-efficacy expectations and individual perceptions of the "glass ceiling effect" using an open-ended question regarding their own experiences with GBD. The answers were analyzed by content analysis using inductive category formation and relative category frequencies. Results: From both interviewed groups, approximately 75% each reported having experienced GBD. Their experiences fell into five main categories: sexual harassment with subcategories of verbal and physical, discrimination based on existing/possible motherhood with subcategories of structural and verbal, direct preference for men, direct neglect of women, and derogatory treatment based on gender. Conclusion: The study contributes to filling the aforementioned research gap. At the hospitals studied, GBD is a common phenomenon among both female medical students and physicians, manifesting itself in multiple forms. Transferability of the results beyond the hospitals studied to all of Germany seems plausible. Much is known about the causes, consequences and effective countermeasures against GBD. Those responsible for training and employers in hospitals should fulfill their responsibility by implementing measures from the set of empirically evaluated interventions.

Development of 2-deoxystreptamine-nucleobase conjugates for the inhibition of oncogenic miRNA production.

The discovery of new original scaffolds for selective RNA targeting is one of the main challenges of current medicinal chemistry since therapeutically relevant RNAs represent potential targets for a number of pathologies. Recent efforts have been devoted to the search for RNA ligands targeting the biogenesis of oncogenic miRNAs whose overexpression has been directly linked to the development of various cancers. In this work, we developed a new series of RNA ligands for the targeting of oncogenic miRNA biogenesis based on the 2-deoxystreptamine scaffold. The latter is part of the aminoglycoside neomycin and is known to play an essential role in the RNA interaction of this class of RNA binders. 2-deoxystreptamine was thus conjugated to natural and artificial nucleobases to obtain new binders of the oncogenic miR-372 precursor (pre-miR-372). We identified some conjugates exhibiting a similar biological activity to previously synthesized neomycin analogs and studied their mode of binding with the target pre-miR-372.

Bioactive compounds from Physalis angulata and their anti-inflammatory and cytotoxic activities.

A new compound, physalucoside A (1), together with seven withanolides (2-8) and three flavonoids (9-11), were isolated from Physalis angulata L. (Solanaceae), a medicinal plant native to Vietnam. The chemical structures of these compounds were elucidated by one- and two-dimensional NMR spectra, high-resolution electrospray ionization mass spectrometry analyses, and chemical reactivity. The anti-inflammatory and cytotoxic activities of isolated compounds were also evaluated. These data suggest that the anti-inflammatory activity of P. angulata is due primarily to its withanolide content. This study demonstrates the potential of withanolides as promising candidates for the development of new anti-inflammatory drugs.

Building of neomycin-nucleobase-amino acid conjugates for the inhibition of oncogenic miRNAs biogenesis.

MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs are aberrantly expressed in a variety of human cancers, thus being oncogenic. The inhibition of oncogenic miRNAs (defined as the blocking of miRNAs' production or function) would find application in the therapy of different types of cancer in which these miRNAs are implicated. In this work, we describe the design and synthesis of new small-molecule RNA ligands with the aim of inhibiting Dicer-mediated processing of oncogenic miRNAs. One of the synthesized compound (4b) composed of the aminoglycoside neomycin conjugated to an artificial nucleobase and to amino acid histidine is able to selectively decrease miR-372 levels in gastric adenocarcinoma (AGS) cells and to restore the expression of the target LATS2 protein. This activity led to the inhibition of proliferation of these cells. The study of the interactions of 4b with pre-miR-372 allowed for the elucidation of the molecular mechanism of the conjugate, thus leading to new perspectives for the design of future inhibitors.

Modulation of oncogenic miRNA biogenesis using functionalized polyamines.

MicroRNAs are key factors in the regulation of gene expression and their deregulation has been directly linked to various pathologies such as cancer. The use of small molecules to tackle the overexpression of oncogenic miRNAs has proved its efficacy and holds the promise for therapeutic applications. Here we describe the screening of a 640-compound library and the identification of polyamine derivatives interfering with in vitro Dicer-mediated processing of the oncogenic miR-372 precursor (pre-miR-372). The most active inhibitor is a spermine-amidine conjugate that binds to the pre-miR-372 with a KD of 0.15 µM, and inhibits its in vitro processing with a IC50 of 1.06 µM. The inhibition of miR-372 biogenesis was confirmed in gastric cancer cells overexpressing miR-372 and a specific inhibition of proliferation through de-repression of the tumor suppressor LATS2 protein, a miR-372 target, was observed. This compound modifies the expression of a small set of miRNAs and its selective biological activity has been confirmed in patient-derived ex vivo cultures of gastric carcinoma. Polyamine derivatives are promising starting materials for future studies about the inhibition of oncogenic miRNAs and, to the best of our knowledge, this is the first report about the application of functionalized polyamines as miRNAs interfering agents.

Small-molecule approaches toward the targeting of oncogenic miRNAs: roadmap for the discovery of RNA modulators.

miRNAs are a recently discovered class of small noncoding RNAs implicated in the regulation of gene expression. The deregulation of miRNAs levels has been linked to the development of various cancers where oncogenic miRNAs are overexpressed and tumor suppressor miRNAs are underexpressed. Here we report the three main strategies developed in order to discover small-molecule drugs able to selectively interfere with oncogenic miRNAs: the high throughput screening of large libraries of compounds, the focused screening of small libraries of molecules that are known to be able to interact with RNA thus being supposed modulators of miRNAs pathway and the design of small molecules based on the secondary structure of targeted RNA and/or three-dimensional structure of enzymes involved in miRNAs pathway.

Oncogenic MicroRNAs Biogenesis as a Drug Target: Structure-Activity Relationship Studies on New Aminoglycoside Conjugates.

MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs are aberrantly expressed in a variety of human cancers and that the inhibition of these oncogenic miRNAs could find application in the therapy of different types of cancer. Herein, we describe the synthesis and biological evaluation of new small-molecule drugs that target oncogenic miRNAs production. In particular, we chose to target two miRNAs (i.e., miRNA-372 and -373) implicated in various types of cancer, such as gastric cancer. Their precursors (pre-miRNAs) are overexpressed in cancer cells and lead to mature miRNAs after cleavage of their stem-loop structure by the enzyme Dicer in the cytoplasm. Some of the newly synthesized conjugates can inhibit Dicer processing of the targeted pre-miRNAs in vitro with increased efficacy relative to our previous results (D.D. Vo et al., ACS Chem. Biol. 2014, 9, 711-721) and, more importantly, to inhibit proliferations of adenocarcinoma gastric cancer (AGS) cells overexpressing these miRNAs, thus representing promising leads for future drug development.

Ribosome-targeting antibiotics as inhibitors of oncogenic microRNAs biogenesis: Old scaffolds for new perspectives in RNA targeting.

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at the post-transcriptional level. It is now well established that the overexpression of some miRNAs (oncogenic miRNAs) is responsible for initiation and progression of human cancers and the discovery of new molecules able to interfere with their production and/or function represents one of the most important challenges of current medicinal chemistry of RNA ligands. In this work, we studied the ability of 18 different antibiotics, known as prokaryotic ribosomal RNA, to bind to oncogenic miRNA precursors (stem-loop structured pre-miRNAs) in order to inhibit miRNAs production. In vitro inhibition, binding constants, thermodynamic parameters and binding sites were investigated and highlighted that aminoglycosides and tetracyclines represent interesting pre-miRNA ligands with the ability to inhibit Dicer processing.