Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research.

The recent, controversial approval of antibody-based treatments for Alzheimer's disease (AD) is fueling a heated debate on the molecular determinants of this condition. The discussion should also incorporate a critical revision of the limitations of preclinical mouse models in advancing our understanding of AD. We critically discuss the limitations of animal models, stressing the need for careful consideration of how experiments are designed and results interpreted.

NAD Metabolism and Mitochondrial Activity in the Aged Oocyte: Focus on the Effects of NAMPT Stimulation.

The ovary experiences an age-dependent decline starting during the fourth decade of life. Ovarian aging is the predominant factor driving female reproductive aging. Modern trend to postpone childbearing age contributes to reduced fertility and natality worldwide.

Cold atmospheric plasma activated media selectively affects human head and neck cancer cell lines.

Objective: Cold atmospheric plasma (CAP) is a novel approach for cancer treatment. It can be used to treat liquids-plasma-activated media (PAM)-which are then transferred to the target as an exogenous source of reactive oxygen and nitrogen species (RONS). The present study aimed at chemically characterizing different PAM and assessing their in vitro selectivity against head and neck cancer cells (HNC).

Head and neck paragangliomas: Recent advances in translational and clinical research and guidelines for patient care.

Head and neck paragangliomas (HNPGLs), rare neuroendocrine tumors that mainly arise from parasympathetic ganglia along the cranial nerves, are challenging due to anatomic origin, tendency to aggressive neurovascular and skull base infiltration, unpredictable metastatic potential, radio-chemoresistance, and risk of multiplicity. Symptoms range from mild to life threatening depending on location/size, but rarely relate to catecholamine excess. Risk factors include female sex and pathogenic germline variants in genes affecting hypoxia signaling (foremost succinate dehydrogenase genes).

Functional Analysis of RE1 Silencing Transcription Factor as a Putative Tumor Suppressor in Human Endometrial Cancer.

Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC.

Autologous hGMSC-Derived iPS: A New Proposal for Tissue Regeneration.

The high mortality in the global population due to chronic diseases highlights the urgency to identify effective alternative therapies. Regenerative medicine provides promising new approaches for this purpose, particularly in the use of induced pluripotent stem cells (iPSCs). The aim of the work is to establish a new pluripotency cell line obtained for the first time by reprogramming human gingival mesenchymal stem cells (hGMSCs) by a non-integrating method.

Orally Ingested Micro- and Nano-Plastics: A Hidden Driver of Inflammatory Bowel Disease and Colorectal Cancer.

Micro- and nano-plastics (MNPLs) can move along the food chain to higher-level organisms including humans. Three significant routes for MNPLs have been reported: ingestion, inhalation, and dermal contact. Accumulating evidence supports the intestinal toxicity of ingested MNPLs and their role as drivers for increased incidence of colorectal cancer (CRC) in high-risk populations such as inflammatory bowel disease (IBD) patients.

Isolated hypoprolactinemia: The rarest of the rare?

Isolated hypoprolactinemia (IHP) can be defined as the presence of consistently low serum levels of prolactin in the absence of other anterior pituitary hormone abnormalities. It is an extremely rare condition, and consequently incompletely understood and unrecognized. A recent study has reported the first cases of IHP caused by mutation in the PRL gene.

The future of pharmacology and therapeutics of the arachidonic acid cascade in the next decade: Innovative advancements in drug repurposing.

Many drugs can act on multiple targets or disease pathways, regardless of their original purpose. Drug repurposing involves reevaluating existing compounds for new medical uses. This can include repositioning approved drugs, redeveloping unapproved drugs, or repurposing any chemical, nutraceutical, or biotherapeutic product for new applications.

Prevention of prostate cancer metastasis by a CRISPR-delivering nanoplatform for interleukin-30 genome editing.

Prostate cancer (PC) is a leading cause of cancer-related deaths in men worldwide. Interleukin-30 (IL-30) is a PC progression driver, and its suppression would be strategic for fighting metastatic disease. Biocompatible lipid nanoparticles (NPs) were loaded with CRISPR-Cas9gRNA to delete the human IL30 (hIL30) gene and functionalized with anti-PSCA-Abs (Cas9hIL30-PSCA NPs).

The multifaceted role of the stroma in the healthy prostate and prostate cancer.

Prostate cancer (PC) is an age-related disease and represents, after lung cancer, the second cause of cancer death in males worldwide. Mortality is due to the metastatic disease, which mainly involves the bones, lungs, and liver. In the last 20 years, the incidence of metastatic PC has increased in Western Countries, and a further increase is expected in the near future, due to the population ageing.

Immunoliposome-based targeted delivery of the CRISPR/Cas9gRNA-IL30 complex inhibits prostate cancer and prolongs survival.

The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity.

Serum hepcidin evaluation as a promising biomarker in juvenile idiopathic arthritis.

Objectives: An important area of research in juvenile idiopathic arthritis (JIA) aims to identify sensitive and reliable biomarkers of disease activity. The key iron-regulatory hormone hepcidin-25 (HEP) has been advocated as a potential biomarker to assess anaemia of chronic disease and iron deficiency in adults with rheumatoid arthritis.

Methods: We performed a cross-sectional study evaluating the utility of serum HEP in 79 non-systemic onset JIA patients (14 males, 65 females), with/without anaemia, determining its correlations with disease activity, assessed by the JIA Disease Activity Score (JADAS)-27, anaemia parameters, and iron status indices.

Data-driven analysis of whole-brain intrinsic connectivity in patients with chronic low back pain undergoing osteopathic manipulative treatment.

Background: Chronic Low Back Pain (cLBP) poses a significant health challenge, leading to functional disability and reduced quality of life. Osteopathic Manipulative Treatment (OMT) is emerging as a therapeutic option for cLBP, but the brain mechanisms underlying its analgesic effect remain unclear.

Materials And Methods: Thirty cLBP patients were randomly exposed to either four weekly sessions of OMT (N=16) or Sham treatment (N=14).

Application of Metagenomics Sequencing in a Patient with Dementia: A New Case Report.

(1) Background: The study of the microbiome is crucial for its role in major systemic diseases, in particular the oral and gut microbiota. In recent years, the study of microorganisms correlated, for example, with neurodegenerative disease has increased the prospect of a possible link between gut microbiota and the brain. Here, we report a new case concerning a patient who was initially evaluated genetically for dementia and late-onset dyskinesia, and later tested with 16S metagenomics sequencing.

Pain from Internal Organs and Headache: The Challenge of Comorbidity.

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature.

Differential Regulation of Wingless-Wnt/c-Jun N-Terminal Kinase Crosstalk via Oxidative Eustress in Primary and Metastatic Colorectal Cancer Cells.

In the tumor microenvironment (TME), ROS production affects survival, progression, and therapy resistance in colorectal cancer (CRC). HO-mediated oxidative stress can modulate Wnt/β-catenin signaling and metabolic reprogramming of the TME. Currently, it is unclear how mild/moderate oxidative stress (eustress) modulates Wnt/β-catenin/APC and JNK signaling relationships in primary and metastatic CRC cells.

A Very Early Diagnosis of Complete Androgen Insensitivity Syndrome Due to a Novel Variant in the AR Gene: A Neonatal Case Study.

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene.

Banking of post-SMILE stromal lenticules for additive keratoplasty: A new challenge for eye banks?

Purpose: ReLEx (Refractive Lenticule Extraction) Small Incision Lenticule Extraction (SMILE), the second generation of ReLEx Femtosecond Lenticule Extraction (FLEx), is a minimally invasive, flapless procedure designed to treat refractive errors such as myopia, hyperopia, presbyopia, and astigmatism. This review aims to provide a comprehensive overview of the methods for preserving SMILE-derived lenticules and discusses their potential future applications.

Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases, focusing on articles published up to January 2024 and available in English.

Chemical characteristics and sources apportionment of volatile organic compounds in the primary urban area of Shijiazhuang, North China Plain.

VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources.

Sil1-deficient fibroblasts generate an aberrant extracellular matrix leading to tendon disorganisation in Marinesco-Sjögren syndrome.

Background: Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins.

Comparative renal outcomes of matched cohorts of patients with type 2 diabetes receiving SGLT2 inhibitors or GLP-1 receptor agonists under routine care.

Aims/hypothesis: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria.

Methods: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching.

Primary stability evaluation of different morse cone implants in low-density artificial bone blocks: A comparison between high-and low-speed drilling.

This study aimed to evaluate various biomechanical parameters associated with the primary stability of Maestro and Due Cone implants placed in low-density artificial bones, prepared using high-speed drilling with irrigation and low-speed drilling without irrigation. The insertion torque (IT), removal torque (RT), and implant stability quotient (ISQ) values were recorded for Maestro and Due Cone implants placed in low-density polyurethane blocks (10 and 20 pounds per cubic foot (PCF) with and without a cortical layer) prepared using high-speed and low-speed with or without irrigation using a saline solution, respectively. A three-way ANOVA model and Tukey's post-hoc test were conducted, presenting data as means and standard deviations.