A novel multitargeted self-assembling peptide-siRNA complex for simultaneous inhibition of SARS-CoV-2-host cell interaction and replication.

Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and restrict SARS-CoV-2 replication. Cell-penetrating peptides is a robust method for siRNA delivery, enhancing siRNA stability and targeting specific receptors.

Macrophage CD5L is a target for cancer immunotherapy.

Background: Reprogramming of immunosuppressive tumor-associated macrophages (TAMs) presents an attractive therapeutic strategy in cancer. The aim of this study was to explore the role of macrophage CD5L protein in TAM activity and assess its potential as a therapeutic target.

Methods: Monoclonal antibodies (mAbs) against recombinant CD5L were raised by subcutaneous immunization of BALB/c mice.

Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.

Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer.

Recent Advances in Synthetic and Natural Biomaterials-Based Therapy for Bone Defects.

Synthetic and natural biomaterials are a promising alternative for the treatment of critical-sized bone defects. Several parameters such as their porosity, surface, and mechanical properties are extensively pointed out as key points to recapitulate the bone microenvironment. Many biomaterials with this pursuit are employed to provide a matrix, which can supply the specific environment and architecture for an adequate bone growth.

Oxidative metabolism in the cardiorespiratory system after an acute exposure to nickel-doped nanoparticles in mice.

There is an increasing concern over the harmful effects that metallic nanoparticles (NP) may produce on human health. Due to their redox properties, nickel (Ni) and Ni-containing NP are particularly relevant. Hence, the aim of this study was to establish the toxicological mechanisms in the cardiorespiratory oxidative metabolism initiated by an acute exposure to Ni-doped-NP.

Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer.

CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have shown impressive efficacy in estrogen receptor-positive advanced breast cancer. However, most patients will eventually experience disease progression on this combination, underscoring the need for effective subsequent treatments or better initial therapies. Here, we show that triple inhibition with fulvestrant, CDK4/6i and AKT inhibitor (AKTi) durably impairs growth of breast cancer cells, prevents progression and reduces metastasis of tumor xenografts resistant to CDK4/6i-fulvestrant combination or fulvestrant alone.

Non-covalent Encapsulation of siRNA with Cell-Penetrating Peptides.

SiRNAs may act as selective and potent therapeutics, but poor deliverability in vivo is a limitation. Among the recently proposed vectors, cell-penetrating peptides (CPPs), also referred as protein transduction domains (PTDs), allow siRNA stabilization and increased cellular uptake. This chapter aims to guide scientists in the preparation and characterization of CPP-siRNA complexes, particularly the evaluation of novel CPPs variants for siRNA encapsulation and delivery.

Evaluation of siRNA Stability and Interaction with Serum Components Using an Agarose Gel-Based Single-Molecule FRET Labeling Method.

Small interfering RNAs (siRNAs) are RNA molecules with promising therapeutic potential as a result of their selective mRNA cleavage. However, despite recent progress, low stability in the bloodstream is an impediment to successful administration in vivo. Thus, the availability of flexible and rapid methods for studying siRNA stability and vehicles is crucial for future novel siRNA-based therapeutics.

Stimuli-Responsive Materials for Tissue Engineering and Drug Delivery.

Smart or stimuli-responsive materials are an emerging class of materials used for tissue engineering and drug delivery. A variety of stimuli (including temperature, pH, redox-state, light, and magnet fields) are being investigated for their potential to change a material's properties, interactions, structure, and/or dimensions. The specificity of stimuli response, and ability to respond to endogenous cues inherently present in living systems provide possibilities to develop novel tissue engineering and drug delivery strategies (for example materials composed of stimuli responsive polymers that self-assemble or undergo phase transitions or morphology transformations).

Simple FRET Electrophoresis Method for Precise and Dynamic Evaluation of Serum siRNA Stability.

Small interfering RNAs (siRNAs) are potent therapeutic molecules, but despite recent progress, their administration in vivo remains challenging due to their low stability in the bloodstream. Thus, techniques for investigating the stability of siRNA are fundamental for the development of efficient siRNA delivery systems. We designed a simple FRET electrophoresis method to dynamically evaluate serum siRNA stability in parallel with its interaction with the serum components.

Development of Silver Nanoparticles/Gelatin Thermoresponsive Nanocomposites: Characterization and Antimicrobial Activity.

Background: Skin and soft tissue infections involve microbial invasion of the skin and underlying soft tissues. To overcome this problem, nanocomposites were obtained using gelatin as a biopolymer scaffold and silver nanoparticles as a wide spectrum antimicrobial agent. Water and glycerol have been used as solvents for the gelatin hydrogel synthesis.

Nanoformulation for potential topical delivery of Vismodegib in skin cancer treatment.

Vismodegib (Erivedge®, Genentech) is a first-in-class inhibitor of the hedgehog signaling pathway for the treatment of basal cell carcinoma (BCC). The treatment currently consists of the oral administration of Erivedge® capsules. Although it has shown therapeutic efficacy in clinical trials, there are many side effects related to its systemic distribution.

Copper-induced cell death and the protective role of glutathione: the implication of impaired protein folding rather than oxidative stress.

Copper (Cu) is a bioelement essential for a myriad of enzymatic reactions, which when present in high concentration leads to cytotoxicity. Whereas Cu toxicity is usually assumed to originate from the metal's ability to enhance lipid peroxidation, the role of oxidative stress has remained uncertain since no antioxidant therapy has ever been effective. Here we show that Cu overload induces cell death independently of the metal's ability to oxidize the intracellular milieu.

Kinetics and growth mechanism of the photoinduced synthesis of silver nanoparticles stabilized with lysozyme.

A fast and single-step procedure is reported for the preparation of stable solutions of spherical-shaped silver nanoparticles (AgNPs) coated with lysozyme (LZ). The preparation of the AgNP@LZ nanocomposites was based on the reduction of Ag with ketyl radicals photo-generated by the UVA-photolysis of the benzoin I-2959. Both reaction precursors bind to LZ, modifying its superficial charge and conformational structure.

Reorganization of Hydration Water of DPPC Multilamellar Vesicles Induced by l-Cysteine Interaction.

The aim of this study is to analyze the consequences of water redistribution on the structure and stability of phospholipid bilayers induced by cysteine (Cys). This interaction is studied with 1,2-dipalmitoyl- sn-glycero-3-phosphatidylcholine (DPPC) multilamellar vesicles in gel (30 °C) and liquid crystalline (50 °C) state; experimental studies were performed by means of Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and differential scanning calorimetry (DSC). The polar head sites of the lipid molecules to which water can bind are identified by competition with compounds that form hydrogen bonds, such as Cys.

One-step FPLC-size-exclusion chromatography procedure for purification of rDMBT1 6 kb with increased biological activity.

Deleted in Malignant Brain Tumor 1 (DMBT1, alias SAG or gp340) is a pattern recognition receptor involved in immune defense, cell polarization, differentiation and regeneration. To investigate the role of the protein in physiological and pathological processes, the protein has often been isolated from saliva or produced in vitro and purified by a multistep affinity purification procedure using bacteria, followed by FPLC. Here, we compared a simple, one-step FPLC-SEC protocol for purification of recombinant DMBT1 6 kb, with that of the standard bacteria affinity purification-based protocol.

Human DMBT1-Derived Cell-Penetrating Peptides for Intracellular siRNA Delivery.

Small interfering RNA (siRNA) is a promising molecule for gene therapy, but its therapeutic administration remains problematic. Among the recently proposed vectors, cell-penetrating peptides show great promise in in vivo trials for siRNA delivery. Human protein DMBT1 (deleted in malignant brain tumor 1) is a pattern recognition molecule that interacts with polyanions and recognizes and aggregates bacteria.

Advances in collagen, chitosan and silica biomaterials for oral tissue regeneration: from basics to clinical trials.

Different materials have distinct surface and bulk characteristics; each of them potentially useful for the treatment of a particular wound or disease. By reviewing those materials that have reached a clinical stage the reader will have a broad panorama of the possibilities a particular material can offer, regarding its ability to support fast tissue regeneration. This review covers the most recent advances made towards the development of biomaterials aimed to support regenerative processes.

Nanoparticles and capillary electrophoresis: A marriage with environmental impact.

The impact of nanomaterials in the environment and human health is a cause of big concern and even though intensive studies are currently being carried out, there is still a lot to elucidate. The development of validated methods for the characterization and quantification of nanomaterials and their impact on the environment should be encouraged to achieve a proper, safe, and sustainable use of nanoparticles (NPs). Recently, CE emerged as a well-adapted technique for the analysis of environmental samples.

Innovative Immobilization Matrices.

We present a brief survey of some of the recent work of Professor Luis E. Díaz, performed together with his students and collaborators at the University of Buenos Aires. Dr Luis E.

Gas-phase structure of 2,2,2-trichloroethyl chloroformate studied by electron diffraction and quantum-chemical calculations.

The molecular structure and conformational properties of 2,2,2-trichloroethyl chloroformate, ClC(O)OCH2CCl3 were determined experimentally using gas-phase electron diffraction (GED) and theoretically based on quantum-chemical calculations at the MP2 and DFT levels of theory. Further experimental measurements such as UV-visible, IR and Raman spectroscopy were complemented with the corresponding theoretical studies. All experimental results and calculations confirm the presence of two conformers namely anti-gauche (C1 symmetry) and anti-anti (Cs symmetry).

Molecular view of the interaction of S-methyl methanethiosulfonate with DPPC bilayer.

We present molecular dynamics (MD) simulation studies of the interaction of a chemo preventive and protective agent, S-methyl methanethiosulfonate (MMTS), with a model bilayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We analyzed and compared its diffusion mechanisms with the related molecule dimethyl sulfoxide (DMSO). We obtained spatially resolved free energy profiles of MMTS partition into a DPPC bilayer in the liquid-crystalline phase through potential of mean force (PMF) calculations using an umbrella sampling technique.