Methodology for rapid development of a continuous loss-in-weight feeding process.

The pharmaceutical industry has been shifting towards continuous manufacturing, specifically for tablet production. Compared to batch processing, continuous tableting exhibits higher process efficiency, better process control, reduced footprint, and consistent product quality. Understanding mass flow variability and feed factor profile of raw materials in the loss-in-weight feeding process is essential for controlling continuous processes.

LigExtract: Large-scale Automated Identification of Ligands from Protein Structures in the Protein Data Bank.

The Protein Data Bank is an ever-growing database of 3D macromolecular structures that has become a crucial resource for the drug discovery process. Exploring complexed proteins and accessing the ligands in these proteins is paramount to help researchers understand biological processes and design new compounds of pharmaceutical interest. However, currently available tools to perform large-scale ligand identification do not address many of the more complex ways in which ligands are stored and represented in PDB structures.

Enzyme-responsive vitamin D-based micelles for paclitaxel-controlled delivery and synergistic pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most feared diseases worldwide owing to its poor prognosis, negligible therapeutic advances, and high mortality. Herein, multifunctional enzyme-responsive micelles for the controlled delivery of paclitaxel (PTX) were prepared to circumvent its current clinical challenges. Accordingly, two enzyme-responsive structural units composed of Vitamin D (VD) conjugated with polyethylene glycol of different molecular weights (600 Da and 2000 Da) were synthesized and characterized using different analytical methods.

Harnessing sulfur-doped carbon nanodots conjugated with IDO inhibitors act as a dual-mode breast cancer immunotherapy.

Fluorescent ultrasmall nanoparticles (d < 10 nm), such as carbon nanodots (CDs), are promising nanosystems for precision cancer therapy. Their optimal size allows them to diffuse within complex microenvironments, enabling drug delivery, imaging, and monitoring. Additionally, CDs can be engineered to hold inherent nanotoxicity toward cancer cells, overcoming multidrug resistance associated with conventional drugs.

Flavonoids as Potential Modulators of Pancreatic Lipase Catalytic Activity.

: Obesity has reached pandemic proportions, with predictions suggesting that, by 2030, over 1.5 billion people will be affected. Pancreatic lipase (PL), the enzyme primarily responsible for the absorption of dietary lipids, presents a potential target for obesity management.

Exploring the Link Between Periodontitis and Alzheimer's Disease-Could a Nanoparticulate Vaccine Break It?

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, as approximately 55 million people worldwide are affected, with a significant tendency to increase. It reveals three main pathological features: amyloid plaques, neurofibrillary tangles, and neuroinflammation, responsible for the neurodegenerative changes that slowly lead to deterioration of personality and cognitive control. Over a century after the first case report, effective treatments remain elusive, likely due to an incomplete understanding of the precise mechanisms driving its pathogenesis.

Correction: Oliveira et al. Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice. 2021, , 5289.

In the original publication [...

Optimization of Supercritical Fluid Extraction for the Recovery of γ-Oryzanol-Rich Extracts with Improved Bioactivity from Rice Bran.

Rice bran (RB) is a rice processing by-product recognized to be a source of bioactive compounds, including γ-oryzanol and fatty acids, which have interesting bioactivities such as antioxidant and anti-inflammatory effects. This study aims to optimize the supercritical fluid extraction process for recovering these high-value compounds from rice bran with improved bioactivity. A Central Composite Face-Centered Design was employed to optimize the extraction process by varying the temperature (40-80 °C) and pressure (200-500 bar).

Sustaining Brain Youth by Neural Stem Cells: Physiological and Therapeutic Perspectives.

In the last two decades, stem cells (SCs) have attracted considerable interest for their research value and therapeutic potential in many fields, namely in neuroscience. On the other hand, the discovery of adult neurogenesis, the process by which new neurons are generated in the adult brain, challenged the traditional view that the brain is a static structure after development. The recent findings showing that adult neurogenesis has a significant role in brain plasticity, learning and memory, and emotional behavior, together with the fact that it is strongly dependent on several external and internal factors, have sparked more interest in this area.

Prophage dynamics in gastric and enterohepatic environments: unraveling ecological barriers and adaptive transitions.

Phage predation plays a critical role in shaping bacterial genetic diversity, with prophages playing a comparable role. However, the prevalence and genetic variability of prophages within the genus remain inadequately studied. species are clinically significant and occupy distinct digestive system regions, with gastric species (e.

Reshaping the Treatment Landscape of a Galactose Metabolism Disorder.

The Leloir pathway was elucidated decades ago, unraveling how galactose is metabolized in the body. Different inborn errors of metabolism in this pathway are known, the most frequent and well-studied being Classic Galactosemia (CG) (OMIM 230400) due to pathogenic variants in the GALT gene. Substrate reduction using dietary restriction of galactose is currently the only available treatment option.

Curcumin in Ophthalmology: Mechanisms, Challenges, and Emerging Opportunities.

Ocular diseases affecting the anterior and posterior segments of the eye are major causes of global vision impairment. Curcumin, a natural polyphenol, exhibits anti-inflammatory, antioxidant, antibacterial, and neuroprotective properties, making it a promising candidate for ocular therapy. However, its clinical use is hindered by low aqueous solubility, poor bioavailability, and rapid systemic elimination.

The Expanding Role of Aquaporin-1, Aquaporin-3 and Aquaporin-5 as Transceptors: Involvement in Cancer Development and Potential Druggability.

Aquaporins (AQPs) are transmembrane proteins that facilitate the transport of water and small solutes, including glycerol, hydrogen peroxide and ions, across cell membranes. Beyond their established physiological roles in water regulation and metabolic processes, AQPs also exhibit receptor-like signaling activities in cancer-associated signaling pathways, integrating the dual roles of transporters and receptors, hence functioning as transceptors. This dual functionality underpins their critical involvement in cancer biology, where AQPs play key roles in promoting cell proliferation, migration, and invasion, contributing significantly to carcinogenesis.

Designing Functional and Responsive Molecules with Boronic Acids.

ConspectusBoronic acids (BAs) are one of the most important classes of reagents in modern synthesis, enabling a wide range of powerful transformations that facilitate the formation of key carbon-carbon and carbon-heteroatom bonds. While their success as reagents is well-known, their remarkable potential as building blocks for creating functional molecules is often overlooked.At the core of BAs' uniqueness is their ability to form reversible covalent bonds, thanks to the interconversion of the boron atom between its uncharged trigonal planar structure and an anionic sp-hybridized form.

Off-The-Shelf Multivalent Nanoconjugate Cancer Vaccine Rescues Host Immune Response against Melanoma.

Tumor-associated antigen-based cancer vaccines suffer from limited clinical success compared to alternative immunotherapies in melanoma, an aggressive skin cancer with an immunosuppressive tumor microenvironment. The anti-tumor potential of a multivalent nanoconjugate cancer vaccine platform - a cross-linked star-shaped polyglutamate carrier (StCl) with marked lymphotropic character conjugated with melanoma-associated peptide antigens is evaluated through redox-responsive linkers. The co-delivery of melanoma-associated peptide antigens by the nanoconjugate platform induced significant effector immune responses in a mouse melanoma model.

Helicobacter pylori Infection in Colombia: Phylogeny, Resistome, and Virulome.

Helicobacter pylori is a successful etiologic gastric agent that reaches a prevalence around 80% in Colombia. This bacterium is extremely diverse and has shown a phylogeographic pattern. The objective of this study was to perform an analysis of genomic epidemiology of H.

Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models.

Skin acts as a dynamic interface with the environment. Pathological alterations in the skin barrier are associated with skin diseases. These conditions are characterized by specific impairments in epidermal barrier functions.

A step forwarded on the in vitro and in vivo validation of rifabutin-loaded liposomes for the management of highly virulent MRSA infections.

Staphylococcus aureus (S. aureus) infections, especially methicillin resistant (MRSA), constitute an alarming public health issue due to its association with high mortality, morbidity, and hospitalization costs. The increasing antibiotic resistance and biofilm-associated infections of MRSA prompted the discovery of novel and more effective therapeutic strategies.

Assessing the impact of TiO nanomaterials on intestinal cells: New evidence for epithelial translocation and potential pro-inflammatory effects.

Understanding the potential impact of nanomaterials (NMs) on human health requires further investigation into the organ-specific nano-bio interplay at the cellular and molecular levels. We showed increased chromosomal damage in intestinal cells exposed to some of in vitro digested Titanium dioxide (TiO) NMs. The present study aimed to explore possible mechanisms linked to the uptake, epithelial barrier integrity, cellular trafficking, as well as activation of pro-inflammatory pathways, after exposure to three TiO-NMs (NM-102, NM-103, and NM-105).

Novel Strategy of Antibody Affinity Maturation and Enhancement of Nucleolin-Mediated Antibody-Dependent Cellular Cytotoxicity Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer that remains an unmet medical need. Because TNBC cells do not express the most common markers of breast cancers, there is an active search for novel molecular targets in triple-negative tumors. Additionally, this subtype of breast cancer presents strong immunogenic characteristics which have been encouraging the development of immunotherapeutic approaches against the disease.

Chitosan Nanoparticles for Enhanced Immune Response and Delivery of Multi-Epitope Vaccines in a BALB/c Mouse Model.

: is the leading cause of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosal-associated lymphoma. Due to the emerging problems with antibiotic treatment against in clinical practice, vaccination has gained more interest. Oral immunization is considered a promising approach for preventing initial colonization of this bacterium in the gastrointestinal tract, establishing a first line of defense at gastric mucosal surfaces.

Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis.

Nitroaromatic-based triazene prodrugs to target the hypoxic microenvironment in glioblastoma.

Hypoxia is a hallmark of the glioblastoma multiforme microenvironment and represents a promising therapeutic target for cancer treatment. Herein, we report nitroaromatic-based triazene prodrugs designed for selective activation by tumoral endogenous reductases and release of the cytotoxic methyldiazonium ion a self-immolative mechanism. While compounds bearing a 2-nitrofuran bioreductive group were more efficiently activated by nitroreductases, 4-nitrobenzyl prodrugs 1b, 1d and 1e elicited a more pronounced cytotoxic effect against LN-229 and U-87 MG glioblastoma cell lines under hypoxic conditions when compared to temozolomide (TMZ), the golden standard for glioblastoma treatment.