Intranasal Multiepitope PD-L1-siRNA-Based Nanovaccine: The Next-Gen COVID-19 Immunotherapy.

The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are nanotechnology-based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection.

Using Combination therapy to overcome diverse challenges of Immune Checkpoint Inhibitors treatment.

Immune checkpoint inhibitors (ICIs) have heralded a new era in immunotherapy, representing a pivotal breakthrough in cancer treatment. Their impact is profound, with ICIs standing as some of the most prescribed anticancer therapies today. Notably, their ability to induce long-term remission even after treatment cessation provides genuine hope for achieving durable cures.

Unique features of KGN granulosa-like tumour cells in the regulation of steroidogenic and antioxidant genes.

The ovarian KGN granulosa-like tumour cell line is commonly used as a model for human granulosa cells, especially since it produces steroid hormones. To explore this further, we identified genes that were differentially expressed by KGN cells compared to primary human granulosa cells using three public RNA sequence datasets. Of significance, we identified that the expression of the antioxidant gene TXNRD1 (thioredoxin reductase 1) was extremely high in KGN cells.

Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.

Paediatric patients with relapsed B cell acute lymphoblastic leukaemia (B-ALL) have poor prognosis, as relapse-causing clones are often refractory to common chemotherapeutics. While the molecular mechanisms leading to chemoresistance are varied, significant evidence suggests interactions between B-ALL blasts and cells within the bone marrow microenvironment modulate chemotherapy sensitivity. Importantly, bone marrow mesenchymal stem cells (BM-MSCs) and BM adipocytes are known to support B-ALL cells through multiple distinct molecular mechanisms.

A broad-spectrum antibacterial hydrogel based on the synergistic action of Fmoc-phenylalanine and Fmoc-lysine in a co-assembled state.

Multicomponent biomolecular self-assembly is fundamental for accomplishing complex functionalities of biosystems. Self-assembling peptides, amino acids, and their conjugates serve as a versatile platform for developing biomaterials. However, the co-assembly of multiple building blocks showing synergistic interplay between individual components and producing biomaterials with emergent functional attributes is much less explored.

Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes.

Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through -1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features.

Perceived challenges in treatment decision-making for endometriosis: healthcare professional perspectives.

Background: Endometriosis, a systemic chronic inflammatory condition which has no cure, has a high symptom burden that can negatively impact every facet of life. Given the absence of a gold-standard treatment, the best symptom management regimen in endometriosis is heavily reliant on a patient's values and preferences, making shared decision-making (SDM) vital. However, a comprehensive patient decision aid (PtDA) intervention that could facilitate patient decision-making and promote SDM is lacking in endometriosis, and there is little research on the decisional support needs of individuals with this condition.

REPRODUCTIVE AGEING: BGP-15 mitigates adverse impacts of aging on sperm quality, fertility, and offspring health in male mice.

In Brief: Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies. This study in mice identifies a therapeutic compound that, when administered to aged males, improves sperm quality, subsequent embryo development and post-natal offspring health.

Abstract: Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies.

Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.

Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques.

Characterization of human aquaporin ion channels in a yeast expression system as a tool for novel ion channel discovery.

Aquaporin (AQP) channels found in all domains of life are transmembrane proteins which mediate passive transport of water, glycerol, signaling molecules, metabolites, and charged solutes. Discovery of new classes of ion-conducting AQP channels has been slow, likely reflecting time- and labor-intensive methods required for traditional electrophysiology. Work here defines a sensitive mass-throughput system for detecting AQP ion channels, identified by rescue of cell growth in the K+-transport-defective yeast strain CY162 following genetic complementation with heterologously expressed cation-permeable channels, using the well characterized human AQP1 channel for proof of concept.

Increasing age and lethal opiate use.

Opioid abuse is a leading cause of drug-related morbidity and mortality worldwide. It has been suggested that the age of opiate users in Australia is rising. To evaluate this further in a local population, toxicology and pathology case files from Forensic Science SA, Adelaide, South Australia, were examined for all cases with lethal opioid levels from 2000 to 2019 ( = 499; M:F 2.

Tree failure - A natural phenomenon with forensic implications.

Tree failure, or summer branch drop, refers to situations where large branches or whole trees may unexpectedly drop on unsuspecting victims. On occasion, this involves vehicles impacted by falling overhanging trees or branches. To study this phenomenon further review of the Forensic Science SA, Adelaide, Australia, database and an internet news search were undertaken over a 20 year period from March 2004 to February 2024 for all cases where unexpected accidental deaths in South Australia had been caused by falling branches or trees.

Dietary interventions and tumor response to chemotherapy in breast cancer: A comprehensive review of preclinical and clinical data.

Background & Aims: Optimizing treatment efficacy is still a critical part in advancing the treatment of breast cancer. Dietary interventions have drawn significant attention for their potential to increase tumor sensitivity, with a plethora of strategies evaluated both preclinically and clinically. The aim of this paper is to explore these strategies, ranging from entire dietary programs to specific supplements, for their potential to directly enhance tumor sensitivity and chemotherapy adherence.

Deferiprone and Gallium-Protoporphyrin Chitogel as an antimicrobial treatment: Preclinical studies demonstrating antimicrobial activity for S. aureus infected cutaneous wounds.

Staphylococcus aureus (S. aureus) is one of the most common wound pathogens with increased resistance towards currently available antimicrobials. S.

Granulosa cell metabolism at ovulation correlates with oocyte competence and is disrupted by obesity and aging.

Study Question: Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism?

Summary Answer: GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development.

What Is Known Already: The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood.

Ferroptosis - a potential feature underlying neratinib-induced colonic epithelial injury.

Purpose: Neratinib, a small-molecule tyrosine kinase inhibitor (TKI) that irreversibly binds to human epidermal growth factor receptors 1, 2 and 4 (HER1/2/4), is an approved extended adjuvant therapy for patients with HER2-amplified or -overexpressed (HER2-positive) breast cancers. Patients receiving neratinib may experience mild-to-severe symptoms of gut toxicity including abdominal pain and diarrhoea. Despite being a highly prevalent complication in gut health, the biological processes underlying neratinib-induced gut injury, especially in the colon, remains unclear.

-Associated Parkinson's Disease Is a Distinct Entity.

-associated Parkinson's disease (-PD) is increasingly recognized as a distinct entity within the spectrum of parkinsonian disorders. This review explores the unique pathophysiological features, clinical progression, and genetic underpinnings that differentiate -PD from idiopathic Parkinson's disease (iPD). -PD typically presents with earlier onset and more rapid progression, with a poor response to standard PD medications.

Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference.

In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2.

Osteoblast-specific down-regulation of NLRP3 inflammasome by aptamer-functionalized liposome nanoparticles improves bone quality in postmenopausal osteoporosis rats.

NLRP3 inflammasome is critical in the development and progression of many metabolic diseases driven by chronic inflammation, but its effect on the pathology of postmenopausal osteoporosis (PMOP) remains poorly understood. We here firstly examined the levels of NLRP3 inflammasome in PMOP patients by ELISA. Then we investigated the possible mechanisms underlying the effect of NLRP3 inflammasome on PMOP by RNA sequencing of osteoblasts treated with NLRP3 siRNA and qPCR.

Expression levels of the selenium-uptake receptor LRP8, the antioxidant selenoprotein GPX1 and steroidogenic enzymes correlate in granulosa cells.

Abstract: Reactive oxygen species (ROS) are a by-product of the activity of cytochrome P450 steroidogenic enzymes. Antioxidant enzymes protect against ROS damage. To identify if any particular antioxidant enzyme is used to protect against ROS produced by granulosa cells as follicles enlarge and produce oestradiol, we measured in the bovine granulosa cells the expression of two steroidogenic enzymes (CYP11A1, CYP19A1), important for progesterone and oestradiol production.