Recent Advances in Peptide-Loaded PLGA Nanocarriers for Drug Delivery and Regenerative Medicine.

Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across therapeutic domains, including cancer therapy, neurodegenerative diseases, vaccine development, and regenerative medicine.

Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide.

Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (HO)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (HS) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. Isolated neural retinas from cows were exposed to oxidative damage using HO (100 µM) for 10 min.

Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making.

Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. Here we review 2D and 3D lung models in terms of their application for inhalation toxicity assessment.

Dysregulation of Mitochondrial Homeostasis in Cardiovascular Diseases.

Mitochondria dysfunction plays a central role in the development of vascular diseases as oxidative stress promotes alterations in mitochondrial morphology and function that contribute to disease progression. Redox imbalances can affect normal cellular processes including mitochondrial biogenesis, electrochemical equilibrium, and the regulation of mitochondrial DNA. In this review, we will discuss these imbalances and, in particular, the potential role of mitochondrial fusion, fission, biogenesis, and mitophagy in the context of vascular diseases and how the dysregulation of normal function might contribute to disease progression.

Ceftazidime-Avibactam Versus Colistin for the Treatment of Multidrug-Resistant Infections: A Multicenter Cohort Study.

To evaluate the real-world evidence of ceftazidime-avibactam (CAZ-AVI) compared to intravenous colistin for the treatment of multidrug-resistant (MDR) infections. This is a multicenter, retrospective cohort study conducted in the period between 2017 and 2023 at five institutions for patients who received either CAZ-AVI or colistin-based regimens for treating MDR infections. Outcomes were compared using multivariate logistic regression analysis.

The Role of Endogenous Beta-Endorphin and Enkephalins in the Crosstalk Between Ethanol and Morphine.

There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol, by causing the release of opioid peptides, may sensitize the system to the action of exogenous opioids such as morphine.

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies.

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development. Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited.

Non-Viral Delivery Systems to Transport Nucleic Acids for Inherited Retinal Disorders.

Inherited retinal disorders (IRDs) represent a group of challenging genetic conditions that often lead to severe visual impairment or blindness. The complexity of these disorders, arising from their diverse genetic causes and the unique structural and functional aspects of retinal cells, has made developing effective treatments particularly challenging. Recent advancements in gene therapy, especially non-viral nucleic acid delivery systems like liposomes, solid lipid nanoparticles, dendrimers, and polymersomes, offer promising solutions.

Real-Time Pharmacovigilance: Transforming Population-Based Monitoring of Post-Approval Vaccine Safety Through Rapid Cycle Analysis (RCA)-A Review of the Published Literature.

: Rapid cycle analysis (RCA) is an established and efficient methodology that has been traditionally utilized by United States health authorities to monitor post-approval vaccine safety. Initially developed in the Vaccine Safety Datalink (VSD) in early 2000s, RCA has evolved into a valuable approach for timely post-approval signal detection. Due to the availability of additional near real-time data sources and enhanced analytic approaches, the use of RCA has expanded.

Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study.

Kynurenine aminotransferase II (KAT-II) is a target for treating several diseases characterized by an excess of kynurenic acid (KYNA). Although KAT-II inactivators are available, they often lead to adverse side effects due to their irreversible inhibition mechanism. This study aimed to identify potent and safe inhibitors of KAT-II using computational and in vitro approaches.

Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance.

Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior.

Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.

Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing the non-cancerous and non-cellular composition of the tumor microenvironment (TME), plays a crucial role in oncogenesis and progression, through its interactions with biological, chemical, and mechanical signals. This review aims to analyze the challenges of stroma mimicry models, and highlight advanced personalized co-culture approaches for recapitulating tumor stroma using patient-derived tumor organoids (PDTOs).

Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women.

Background/objectives: This study aims to assess the effects of combined hormonal contraceptives (CHCs) on bone metabolism markers. It primarily measures osteocalcin and additionally examines other bone health markers, seeking to determine their responses to estrogen-progestogen treatments.

Methods: This study involved a comprehensive evaluation of the pertinent literature and a meta-analysis explicitly conducted on data describing women of reproductive age.

Harnessing the AI/ML in Drug and Biological Products Discovery and Development: The Regulatory Perspective.

Artificial Intelligence (AI) has the disruptive potential to transform patients' lives via innovations in pharmaceutical sciences, drug development, clinical trials, and manufacturing. However, it presents significant challenges, ethical concerns, and risks across sectors and societies. AI's rapid advancement has revealed regulatory gaps as existing public policies struggle to keep pace with the challenges posed by these emerging technologies.

Astrocytic HIV-1 Nef Expression Decreases Glutamate Transporter Expression in the Nucleus Accumbens and Increases Cocaine-Seeking Behavior in Rats.

Background/objectives: Cocaine use disorder is an intersecting issue in populations with HIV-1, further exacerbating the clinical course of the disease and contributing to neurotoxicity and neuroinflammation. Cocaine and HIV neurotoxins play roles in neuronal damage during neuroHIV progression by disrupting glutamate homeostasis in the brain. Even with combined antiretroviral therapy (cART), HIV-1 Nef, an early viral protein expressed in approximately 1% of infected astrocytes, remains a key neurotoxin.

GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy.

Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems.

Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3'-Processing Suppression.

: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3'-processing (3'P), thereby establishing its dual-targeting capability.

Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of .

A water extract of the Ayurvedic plant (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer's disease and affects dendritic arborization, mitochondrial activity, and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW, although little is known about how interactions between these compounds contribute to the plant's therapeutic benefit.

Natural Product Identification and Molecular Docking Studies of Leishmania Major Pteridine Reductase Inhibitors.

: Pteridine reductase 1 (PTR1) has been one of the prime targets for discovering novel antileishmanial therapeutics in the fight against Leishmaniasis. This enzyme catalyzes the NADPH-dependent reduction of pterins to their tetrahydro forms. While chemotherapy remains the primary treatment, its effectiveness is constrained by drug resistance, unfavorable side effects, and substantial associated costs.

Glucose-Lowering Agents Developed in the Last Two Decades and Their Perioperative Implications.

The last two decades have provided far more options f both patients and their physicians in the treatment of diabetes mellitus. While dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been approved for nearly two decades, sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are relatively new. Of interest to perioperative physicians, these drugs present specific perioperative concerns, prompting many societies to issue guidelines.

Molecular Epidemiology, Drug-Resistant Variants, and Therapeutic Implications of Hepatitis B Virus and Hepatitis D Virus Prevalence in Nigeria: A National Study.

Information on circulating HBV (sub-)genotype, variants, and hepatitis D virus (HDV) coinfection, which vary by geographical area, is crucial for the efficient control and management of HBV. We investigated the genomic characteristics of HBV (with a prevalence of 8.1%) and the prevalence of HDV in Nigeria.

Serovars from the C-Complex and the B- and C-Related Complexes Are Significantly More Pathogenic than Those from the B-Complex in C3H/HeN but Not in BALB/c Mice.

Studies in humans indicate that certain serovars are more pathogenic than others. Specifically, several studies concluded that serovars from the C-complex are more pathogenic than those from the B-complex, although there are reports that do not support this finding. To investigate these results in an animal model, the eight genitourinary serovars were tested in two strains of mice: C3H/HeN and BALB/c.

The Role of Pathogens in Bumblebee Decline: A Review.

Bumblebees, the most important wild pollinators in both agricultural and natural ecosystems, are declining worldwide. The global decline of bumblebees may threaten biodiversity, pollination services, and, ultimately, agricultural productivity. Several factors, including pesticide usage, climate change, habitat loss, and species invasion, have been documented in the decline of bumblebee species, but recent studies have revealed the dominating role of pathogens and parasites over any of these causes.

Pradofloxacin Minimum Inhibitory Concentration Profiling of Isolates: Insights into Antimicrobial Susceptibility in Swine.

This study evaluated the minimum inhibitory concentration (MIC) of pradofloxacin against various swine respiratory pathogens, including , , , , and (), associated with disease in swine. This research was conducted in two phases: the initial phase examined isolates from the lungs that could be either commensal or pathogenic, while the second phase focused on systemic strains that spread from the respiratory tract to the brain. The pradofloxacin MIC values of the second phase were within the MIC range of the initial phase, with MIC and MIC values highlighting its potential as an effective antimicrobial agent.

A Conserved Di-Lysine Motif in the E2 Transactivation Domain Regulates MmuPV1 Replication and Disease Progression.

The papillomavirus E2 protein regulates the transcription, replication, and segregation of viral episomes within the host cell. A multitude of post-translational modifications have been identified which control E2 functions. A highly conserved di-lysine motif within the transactivation domain (TAD) has been shown to regulate the normal functions of the E2 proteins of BPV-1, SfPV1, HPV-16, and HPV-31.