The structural basis of drugs targeting protein-protein interactions uncovered with the protein-ligand interaction profiler PLIP.

Background: Promiscuity of drugs and targets plays an important role in drug-target prediction, ranging from the explanation of side effects to their exploitation in drug repositioning. A specific form of promiscuity concerns drugs, which interfere with protein-protein interactions. With the rising importance of such drugs in drug discovery and with the large-scale availability of structural data, the question arises on the structural basis of this form of promiscuity and the commonalities of the underlying protein-ligand (PLI) and protein-protein interactions (PPI).

Corrigendum: Nickel oxide nanoparticles exposure as a risk factor for male infertility: "" effects on porcine pre-pubertal Sertoli cells.

[This corrects the article DOI: 10.3389/fendo.2023.

A new approach to lysozyme in cheese manufacture: boosting key enzyme activities in the ripening process.

The rational use of lactobacilli and lysozyme (LZ) could be a simple strategy for boosting key enzyme activities during cheese ripening. This study investigated the effect of the application of LZ on the cell envelopes and metabolic potential of two strains of mesophilic lactobacilli: 29 (L29) and 77 (L77). An in vitro study of LZ-sensitivity was carried out on the two strains.

Exploring Sertoli Cells' Innate Bulwark Role Against Infections: Performances on Biofilms.

This study aimed to evaluate the intrinsic performance of naïve porcine prepubertal Sertoli cells (SCs) and SCs loaded with blank poly(lactic acid) microparticles (MP) or amphotericin B poly(lactic acid) microparticles (AmB-MP) against , a prevalent pathogenic non- species. The objective was to assess their impact on biofilm formation and the cellular response mechanisms involved, building on previous findings that highlight SCs' potential as anti-infective agents and drug carriers. Our results demonstrated that SCs successfully internalized while maintaining viability and exhibited a strong anti-infective effect, inhibiting biofilm formation by 70%.

Comparative evaluation of SARS-CoV-2 serological tests shows significant variability in performance across different years of infection and between the tests.

Introduction: While the global COVID-19 pandemic is slowly coming under control, current efforts are focused on understanding the epidemiology of endemic SARS-CoV-2. The tool of choice for doing so remains serological tests that detect SARS-CoV-2 induced antibodies. However, the performance of these tests should be evaluated to ensure they comply with the specific performance criteria desired by each country that they are used in.

Identification and expression profile of the SMAX/SMXL family genes in chickpea and lentil provide important players of biotechnological interest involved in plant branching.

SMAX/SMXL family genes were successfully identified and characterized in the chickpea and lentil and gene expression data revealed several genes associated with the modulation of plant branching and powerful targets for use in transgenesis and genome editing. Strigolactones (SL) play essential roles in plant growth, rooting, development, and branching, and are associated with plant resilience to abiotic and biotic stress conditions. Likewise, karrikins (KAR) are "plant smoke-derived molecules" that act in a hormonal signaling pathway similar to SL playing an important role in seed germination and hairy root elongation.

Development of IFNβ-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis.

IFNβ (recombinant interferon Beta) has been widely used for the treatment of Multiple sclerosis for the last four decades. Despite the human origin of the IFNβ sequence, IFNβ is immunogenic, and unwanted immune responses in IFNβ-treated patients may compromise its efficacy and safety in the clinic. In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNβ-1a.

Expression profile of the NCED/CCD genes in chickpea and lentil during abiotic stress reveals a positive correlation with increased plant tolerance.

Carotenoid cleavage dioxygenase (CCD) gene family is organized in two subfamilies: (i) 9-cis epoxycarotenoid dioxygenase (NCED) genes and (ii) CCD genes. NCED genes are essential for catalyzing the first step of the abscisic-acid (ABA) biosynthesis, while CCD genes produce precursors of the strigolactones hormone. The functional characterization of these gene subfamilies has not been yet performed in chickpea and lentil.

Optimization and Validation of a Liquid Formulation for a New Recombinant Veterinary Product using QbD Approach.

Protein formulation and drug characterization are one of the most difficult and time-consuming tasks because of the complexity of biotherapeutic proteins. Hence, maintaining a protein drug in its active state typically requires preventing changes in its physical and chemical properties. Quality by Design (QbD) is a systematic approach emphasizing product and process understanding.

Design and characterization of chimeric Rabies-SARS-CoV-2 virus-like particles for vaccine purposes.

Due to the high number of doses required to achieve adequate coverage in the context of COVID-19 pandemics, there is a great need for novel vaccine developments. In this field, there have been research approaches that focused on the production of SARS-CoV-2 virus-like particles. These are promising vaccine candidates as their structure is similar to that of native virions but they lack the genome, constituting a biosafe alternative.

Nickel oxide nanoparticles exposure as a risk factor for male infertility: "" effects on porcine pre-pubertal Sertoli cells.

Lately, nickel oxide nanoparticles (NiO NPs) have been employed in different industrial and biomedical fields. Several studies have reported that NiO NPs may affect the development of reproductive organs inducing oxidative stress and, resulting in male infertility. We investigated the effects of NiO NPs on porcine pre-pubertal Sertoli cells (SCs) which undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposure at two subtoxic doses of NiO NPs of 1 μg/ml and 5 μg/ml.

Zinc restores functionality in porcine prepubertal Sertoli cells exposed to subtoxic cadmium concentration regulating the Nrf2 signaling pathway.

Introduction: Among substances released into the environment by anthropogenic activities, the heavy metal cadmium (Cd) is known to induce severe testicular injury causing male subfertility/infertility. Zinc (Zn) is another heavy metal that, unlike Cd, is physiologically present in the testis, being essential for spermatogenesis. We aimed to examine the possibility that 50 µM ZnCl could counteract the toxic effects induced by Cd in an model of porcine prepubertal Sertoli cells (SCs) exposed to both subtoxic (5 μM) and toxic (10 μM) concentrations of CdCl for 48 h.

Biological skin regeneration using epigenetic targets.

Epigenetics targets are the newest branches for building a novel platform of drugs for preventive and regenerative skin health care. Epigenetic regions [vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor beta (TGFβ), DNA methyltransferases (DNMTs), histone deacetylase 1/2 (HDAC1/2), and miRNA) are innovative druggable targets. As we discuss here, a series of epigenetic-based small molecules are undergoing both clinical and preclinical trials for skin regeneration.

Physicochemical Characterization of a Recombinant eCG and Comparative Studies with PMSG Commercial Preparations.

Equine chorionic gonadotropin (eCG) is a glycoprotein hormone widely used in timed artificial ovulation (TAI) and superovulation protocols to improve the reproductive performance in livestock. Until recently, the only eCG products available in the market for veterinary use consisted in partially purified preparations of pregnant mare serum gonadotropin (PMSG). Here, a bioactive recombinant eCG (reCG) produced in suspension CHO-K1 cells was purified employing different chromatographic methods (hydrophobic interaction chromatography and reverse-phase (RP)-HPLC) and compared with a RP-HPLC-purified PMSG.

Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor.

Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy.

Design and optimization of an IgG human ELISA assay reactive to recombinant RBD SARS-CoV-2 protein.

Serology assays are essential tools to mitigate the effect of COVID-19, help to identify previous SARS-CoV-2 infections or vaccination, and provide data for surveillance and epidemiologic studies. In this study, we report the production and purification process of the receptor-binding domain (RBD) of SARS-CoV-2 in HEK293 cells, which allowed the design, optimization, and validation of an indirect ELISA (iELISA) for the detection of human anti-RBD antibodies. To find the optimal conditions of this iELISA, a multivariate strategy was performed throughout design of experiments (DoE) and response surface methodology (RSM), one of the main tools of quality by design (QbD) approach.

Fertility Preservation and Restoration Options for Pre-Pubertal Male Cancer Patients: Current Approaches.

Fertility preservation for prepubertal male patients undergoing gonadotoxic therapies, potentially depleting spermatogonial cells, is an expanding necessity, yet most of the feasible options are still in the experimental phase. We present our experience and a summary of current and novel possibilities regarding the different strategies to protect or restore fertility in young male patients, before proceeding with chemotherapy or radiotherapy for malignances or other diseases. Adult oncological patients should always be counselled to cryopreserve the semen before starting treatment, however this approach is not suitable for prepubertal boys, who aren't capable to produce sperm yet.

Gelatin and Tannic Acid Based Iongels for Muscle Activity Recording and Stimulation Electrodes.

Iongels are soft ionic conducting materials, usually composed of polymer networks swollen with ionic liquids (ILs), which are being investigated for applications ranging from energy to bioelectronics. The employment of iongels in bioelectronic devices such as bioelectrodes or body sensors has been limited by the lack of biocompatibility of the ILs and/or polymer matrices. In this work, we present iongels prepared from solely biocompatible materials: (i) a biobased polymer network containing tannic acid as a cross-linker in a gelatin matrix and (ii) three different biocompatible cholinium carboxylate ionic liquids.

Melatonin modulates Nrf2 activity to protect porcine pre-pubertal Sertoli cells from the abnormal H O generation and reductive stress effects of cadmium.

Melatonin (MLT) is a cytoprotective agent holding potential to prevent cadmium (Cd) toxicity and its impact in testicular function and fertility. In this study, we explored such potential in porcine pre-pubertal Sertoli cells (SCs). Cd toxicity resulted in impaired SC viability and function, abnormal cellular H O generation and efflux, and induction of reductive stress by the upregulation of Nrf2 expression and activity, cystine uptake and glutathione biosynthesis, glutathione-S-transferase P (GSTP) expression, and protein glutathionylation inhibition.

In Vivo Analysis of Pathways Regulating Epithelial Polarity and Secretion Using Drosophila Salivary Glands.

The experimental versatility of the fruit fly has helped to uncover the molecular basis of epithelial cell polarity. In this chapter, we provide protocols to dissect Drosophila larval salivary glands (SGs) for ex vivo culture and live imaging, and for fixing and immunostaining for analysis by fluorescence microscopy. We describe how to combine these approaches with genetic and pharmacological assays.

Screening of CHO-K1 endogenous promoters for expressing recombinant proteins in mammalian cell cultures.

For the production of recombinant protein therapeutics in mammalian cells, a high rate of gene expression is desired and hence strong viral-derived promoters are commonly used. However, they usually induce cellular stress and can be susceptible to epigenetic silencing. Endogenous promoters, which coordinates their activity with cellular and bioprocess dynamics while at the same time they maintain high expression levels, may help to avoid such drawbacks.

Effects of Titanium Dioxide Nanoparticles on Porcine Prepubertal Sertoli Cells: An "" Study.

The increasing use of nanomaterials in a variety of industrial, commercial, medical products, and their environmental spreading has raised concerns regarding their potential toxicity on human health. Titanium dioxide nanoparticles (TiO NPs) represent one of the most commonly used nanoparticles. Emerging evidence suggested that exposure to TiO NPs induced reproductive toxicity in male animals.

Rational design of novel fusion rabies glycoproteins displaying a major antigenic site of foot-and-mouth disease virus for vaccine applications.

Chimeric virus-like particles are self-assembling structures composed of viral proteins that had been modified to incorporate sequences from different organisms, being able to trigger immune responses against the heterologous sequence. However, the identification of suitable sites for that purpose in the carrier protein is not an easy task. In this work, we describe the generation of rabies chimeric VLPs that expose a major antigenic site of foot-and-mouth disease virus (FMDV) by identifying suitable regions in rabies glycoprotein (RVG), as a proof of concept of a novel heterologous display platform for vaccine applications.

Development, Production, and Characterization of Hepatitis B Subviral Envelope Particles as a Third-Generation Vaccine.

Vaccination still represents the most efficient and inexpensive strategy in the control of hepatitis B virus (HBV) infection. However, about 10% of the population vaccinated with the current S yeast-derived vaccine fail to induce an adequate immune response. Our group has developed a new-generation hepatitis B vaccine candidate composed by the three surface proteins of the HBV.