Enhancing the biological characteristics of aminolysis surface-modified 3D printed nanocomposite polycaprolactone/nanohydroxyapatite scaffold via gelatin biomacromolecule immobilization: An in vitro and in vivo study.

The surface characteristics of scaffolds utilized in bone tissue engineering profoundly influence subsequent cellular response. This study investigated the efficacy of applying a gelatin coat to the surface of aminolysis surface-modified scaffolds fabricated through 3D printing with a polycaprolactone/hydroxyapatite nanocomposite, employing the hot-melt extrusion FDM technique. Initially, aminolysis surface modification using hexamethylenediamine enhanced surface hydrophilicity by introducing amine functional groups.

In vivo evolution of env in SHIV-AD8-infected rhesus macaques after AAV-vectored delivery of eCD4-Ig.

eCD4-immunoglobulin (Ig) is an HIV entry inhibitor that mimics the engagement of both CD4 and CCR5 with the HIV envelope (Env) protein, a property that imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in SHIV-AD8-infected rhesus macaques (RMs) treated with adeno-associated virus vectors encoding eCD4-Ig.

A biomimetic injectable chitosan/alginate hydrogel biocopmosites encapsulating selenium- folic acid nanoparticles for regeneration of spinal cord injury: An in vitro study.

Spinal cord injury (SCI) poses significant challenges to regenerative medicine due to its limited self-repair capabilities. In this study, we engineered a biomimetic injectable hydrogel using modified chitosan and alginate biopolymers encapsulating selenium-folic acid nanoparticles (Se-FA NPs) to facilitate SCI regeneration. The hydrogel exhibited a unique porous structure attributed to the incorporation of nanofiber fragments, enhancing its biocompatibility and bioactivity.

In vivo affinity maturation of the CD4 domains of an HIV-1-entry inhibitor.

Human proteins repurposed as biologics for clinical use have been engineered through in vitro techniques that improve the affinity of the biologics for their ligands. However, the techniques do not select against properties, such as protease sensitivity or self-reactivity, that impair the biologics' clinical efficacy. Here we show that the B-cell receptors of primary murine B cells can be engineered to affinity mature in vivo the human CD4 domains of the HIV-1-entry inhibitor CD4 immunoadhesin (CD4-Ig).

The emerging role of the microglia triggering receptor expressed on myeloid cells (TREM) 2 in multiple sclerosis.

Background: The chronic inflammatory condition known as multiple sclerosis (MS) causes inflammation and demyelination in the central nervous system (CNS). The activation of multiple cell types, including the CNS's resident immune cells called microglia, is a component of the immunological response in MS. Recently, the triggering receptor expressed on myeloid cells (TREM) family has emerged as a crucial player in modulating microglial function and subsequent neuroinflammation.

A hybrid 3D-printed and electrospun bilayer pharmaceutical membrane based on polycaprolactone/chitosan/polyvinyl alcohol for wound healing applications.

Skin injuries resulting from physical trauma pose significant health risks, necessitating advanced wound care solutions. This investigation introduces an innovative bilayer wound dressing composed of 3D-printed propolis-coated polycaprolactone (PCL/PP) and an electrospun composite of polyvinyl alcohol, chitosan, polycaprolactone, and diltiazem (PVA/CTS/PCL/DTZ). SEM analysis revealed a bilayer structure with 89.

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders.

Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metal-chelating capabilities, establishing itself as a promising candidate for the prevention and treatment of conditions affecting the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and other neurological disorders. These effects also include neuroprotection in epilepsy models, as evidenced by a reduction in seizure-like behavior, cell death in specific hippocampal regions, and lowered neuroinflammatory markers. In AD, SA treatment enhances memory, reverses cognitive deficits, and attenuates astrocyte activation.

Fabrication and Evaluation of a Soy Protein Isolate/Collagen/Sodium Alginate Multifunctional Bilayered Wound Dressing: Release of Cinnamaldehyde, Artemisia absinthium, and Oxygen.

Chronic wounds, such as diabetic ulcers and pressure sores, pose significant challenges in modern healthcare due to their prolonged healing times and susceptibility to infections. This study aims to engineer a bilayered wound dressing (BLWD) composed of soy protein isolate/collagen with the ability to release Cinnamaldehyde, (AA), and oxygen. Cinnamaldehyde, magnesium peroxide (MgO), and AA extract were encapsulated.

Neurological efficacy and safety of mesenchymal stem cells (MSCs) therapy in people with multiple sclerosis (pwMS): An updated systematic review and meta-analysis.

Background: Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS).

In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies.

Mice adoptively transferred with mouse B cells edited via CRISPR to express human antibody variable chains could help evaluate candidate vaccines and develop better antibody therapies. However, current editing strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that these key B-cell functions can be preserved by directly and simultaneously replacing recombined mouse heavy and kappa chains with those of human antibodies, using a single Cas12a-mediated cut at each locus and 5' homology arms complementary to distal V segments.

Multilayer PVA/gelatin nanofibrous scaffolds incorporated with Tanacetum polycephalum essential oil and amoxicillin for skin tissue engineering application.

Wound infection is still an important challenge in healing of different types of skin injuries. This highlights the need for new and improved antibacterial agents with novel and different mechanisms of action. In this study, by electrospinning process Tanacetum polycephalum essential oil (EO), as a natural antibacterial and anti-inflammatory agent, along with Amoxicillin (AMX) as an antibiotic are incorporated into PVA/gelatin-based nanofiber mats individually and in combination to fabricate a novel wound dressing.

Predicting potential SARS-CoV-2 mutations of concern via full quantum mechanical modelling.

quantum mechanical models can characterize and predict intermolecular binding, but only recently have models including more than a few hundred atoms gained traction. Here, we simulate the electronic structure for approximately 13 000 atoms to predict and characterize binding of SARS-CoV-2 spike variants to the human ACE2 (hACE2) receptor using the quantum mechanics complexity reduction (QM-CR) approach. We compare four spike variants in our analysis: Wuhan, Omicron, and two Omicron-based variants.

affinity maturation of murine B cells reprogrammed to express human antibodies.

CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3'-most J segments and 5' homology arms complementary to distal V segments.

Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability.

During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components are distinct. Here, we compared the effect of ionizable lipids, untranslated regions (UTRs), and nucleotide composition of the two vaccines, focusing on mRNA delivery, antibody generation, and long-term stability.

An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern.

Immunoinformatics-based multi-epitope vaccine design for the re-emerging monkeypox virus.

Background: On May 7, 2022, WHO reported a new monkeypox case. By May 2023 over 80,000 cases had been reported worldwide outside previously endemic nations. (This primarily affected the men who have sex with men (MSM) community in rich nations).

Heavy-chain CDR3-engineered B cells facilitate in vivo evaluation of HIV-1 vaccine candidates.

V2-glycan/apex broadly neutralizing antibodies (bnAbs) recognize a closed quaternary epitope of the HIV-1 envelope glycoprotein (Env). This closed structure is necessary to elicit apex antibodies and useful to guide the maturation of other bnAb classes. To compare antigens designed to maintain this conformation, we evaluated apex-specific responses in mice engrafted with a diverse repertoire of B cells expressing the HCDR3 of the apex bnAb VRC26.

Multiple sclerosis and the incidence of venous thromboembolism: a systematic review and meta-analysis.

A number of studies have suggested that multiple sclerosis (MS) can be associated with serious vascular complications, for which pulmonary thromboembolism (PTE) is a potentially lethal complication. The purpose of this study is to establish a current literature-based estimate of the incidence of venous thromboembolism (VTE), deep vein thrombosis (DVT), and PTE in patients with MS (pwMS) due to the lack of systematic reviews and meta-analyses on this topic. In this systematic review and meta-analysis, studies were assessed regarding the association between MS and the incidence of VTE.

The processes behind drug loading and release in porous drug delivery systems.

Porous materials are ubiquitous and exhibit properties suitable for depositing therapeutic compounds. Drug loading in porous materials can protect the drug, control its release rate, and improve its solubility. However, to achieve such outcomes from porous delivery systems, effective incorporation of the drug in the internal porosity of the carrier must be guaranteed.

A strategy for high antibody expression with low anti-drug antibodies using AAV9 vectors.

Introduction: Use of adeno-associated virus (AAV) vectors is complicated by host immune responses that can limit transgene expression. Recent clinical trials using AAV vectors to deliver HIV broadly neutralizing antibodies (bNAbs) by intramuscular administration resulted in poor expression with anti-drug antibodies (ADA) responses against the bNAb.

Methods: Here we compared the expression of, and ADA responses against, an anti-SIV antibody ITS01 when delivered by five different AAV capsids.

The effect of infusion time on Echium amoenum extract -induced hepatotoxicity in vitro.

Echium amoenum is an annual herb native to the northern mountains of Iran which has medicinal application. Petals of Echium amoenum (Gole-Gavzaban) is one of the most valuable medicinal plants in Iranian folk medicine. The dry petals of E.

Protective effects of vanillic acid on autistic-like behaviors in a rat model of maternal separation stress: Behavioral, electrophysiological, molecular and histopathological alterations.

Compounds derived from herbs exhibit a range of biological properties, including anti-inflammatory, antioxidant, and neuroprotective properties. However, the exact mechanism of action of these compounds in various neurological disorders is not fully discovered yet. Herein, the present work detected the effect of Vanillic acid (VA), a widely-used flavoring agent derived from vanillin, on autistic-like behaviors to assess the probable underlying mechanisms that mediate behavioral, electrophysiological, molecular, and histopathological alterations in the rat model of maternal separation (MS) stress.