LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress.

Parkinson's disease (PD) is a complex multifactorial progressive neurodegenerative disease characterized by locomotor alteration due to the specific deterioration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). Mounting evidence shows that human LRRK2 (hLRRK2) kinase activity is involved in oxidative stress (OS)-induced neurodegeneration, suggesting LRRK2 inhibition as a potential therapeutic target. We report that the hLRRK2 inhibitor PF-06447475 (PF-475) prolonged lifespan, increased locomotor activity, maintained DAergic neuronal integrity, and reduced lipid peroxidation (LPO) in female Drosophila melanogaster flies chronically exposed to paraquat (PQ), a redox cycling compound, compared to flies treated with vehicle only.

Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials.

The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights.

Potential Advantages of a Well-balanced Nutrition Regimen for People Living with Human Immunodeficiency Virus Type -1.

This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary interventions, including, the importance of omega-3 fatty acids, vitamins D and B-12, and the Mediterranean diet, we delineate how these beneficial nutritional strategies can improve the effectiveness of combined antiretroviral therapy (cART), mitigate its side effects, and ameliorate metabolic disorders in people living with HIV-1 (PLWH). Our review advocates for the integration and implementation of personalized nutritional assessments into the care plan for PLWH, proposing actionable strategies for healthcare providers in HIV-1 field.

Rotenone Induces a Neuropathological Phenotype in Cholinergic-like Neurons Resembling Parkinson's Disease Dementia (PDD).

Parkinson's disease with dementia (PDD) is a neurological disorder that clinically and neuropathologically overlaps with Parkinson's disease (PD) and Alzheimer's disease (AD). Although it is assumed that alpha-synuclein ( -Syn), amyloid beta (A ), and the protein Tau might synergistically induce cholinergic neuronal degeneration, presently the pathological mechanism of PDD remains unclear. Therefore, it is essential to delve into the cellular and molecular aspects of this neurological entity to identify potential targets for prevention and treatment strategies.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience.

Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.

Somatic and autonomic nerve density and distribution within the clitoris: an immunohistochemical study in adult female cadavers.

Introduction And Hypothesis: Knowledge of clitoral neuroanatomy is critical to vulvar surgery. We sought to characterize the density and distribution of autonomic and somatic nerves supplying the clitoris.

Methods: Pelvic tissue harvested from female cadavers was sectioned axially at three anatomic levels: the proximal aspect of the clitoral body (CB), the distal CB, and the glans.

Antibody-drug conjugates in advanced lung cancer: Is this a new frontier?

Over the past decade, the lung cancer landscape has been dominated by targeted and immunotherapeutic approaches that have drastically shifted treatment paradigms for patients with advanced non-small cell lung cancer (NSCLC). Despite these scientific and clinical advances, there are still many unmet needs underscoring the importance of novel strategies. Antibody-drug conjugates (ADCs) represent one such strategy that is beginning to alter the therapeutic strategies for patients with advanced NSCLC.

Cholinergic Mechanisms in Gastrointestinal Neoplasia.

Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia.

Targeting ferroptosis in ovarian cancer: Novel strategies to overcome chemotherapy resistance.

Aims: This review investigates the role of ferroptosis in combating chemotherapy resistance in ovarian cancer, with a focus on its underlying mechanisms and therapeutic implications.

Main Methods: A database search was conducted up to December 2023 using PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library. The keywords "ovarian cancer," "ferroptosis," "cisplatin," and "cisplatin resistance" were employed.

Deep PIM kinase substrate profiling reveals new rational cotherapeutic strategies for acute myeloid leukemia.

Provirus integration site for Moloney murine leukemia virus (PIM) family serine/threonine kinases perform protumorigenic functions in hematologic malignancies and solid tumors by phosphorylating substrates involved in tumor metabolism, cell survival, metastasis, inflammation, and immune cell invasion. However, a comprehensive understanding of PIM kinase functions is currently lacking. Multiple small-molecule PIM kinase inhibitors are currently being evaluated as cotherapeutics in patients with cancer.

Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

Importance: In newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), disease progression due to acquired resistance to first- or second-generation BCR::ABL1 tyrosine kinase inhibitors is common. Ponatinib inhibits BCR::ABL1 and all single-mutation variants, including T315I.

Objective: To compare frontline ponatinib vs imatinib in adults with newly diagnosed Ph+ ALL.

Radiomic biomarkers of locoregional recurrence: prognostic insights from oral cavity squamous cell carcinoma preoperative CT scans.

Introduction: This study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients.

Methods: Computed tomography scans were collected from 78 patients with OSCC who underwent surgical treatment at a single medical center. We extracted 1,092 radiomic features from gross tumor volume in each patient's pre-treatment CT.

Dual targeting of glutamine and serine metabolism in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by disrupted blood cell production and function. Recent investigations have highlighted the potential of targeting glutamine metabolism as a promising therapeutic approach for AML. Asparaginases, enzymes that deplete circulating glutamine and asparagine, are approved for the treatment of acute lymphoblastic leukemia, but are also under investigation in AML, with promising results.

Novel Nonthermal Atmospheric Plasma Irradiation of Titanium Implants Promotes Osteogenic Effect in Osteoporotic Conditions.

Osteoporosis is a metabolic disease characterized by bone density and trabecular bone loss. Bone loss may affect dental implant osseointegration in patients with osteoporosis. To promote implant osseointegration in osteoporotic patients, we further used a nonthermal atmospheric plasma (NTAP) treatment device previously developed by our research group.

Advancing immunotherapy using biomaterials to control tissue, cellular, and molecular level immune signaling in skin.

Immunotherapies have been transformative in many areas, including cancer treatments, allergies, and autoimmune diseases. However, significant challenges persist in extending the reach of these technologies to new indications and patients. Some of the major hurdles include narrow applicability to patient groups, transient efficacy, high cost burdens, poor immunogenicity, and side effects or off-target toxicity that results from lack of disease-specificity and inefficient delivery.

Clinical prediction of carrier status in Parkinson's disease.

Introduction: Given the unique natural history of -related Parkinson's disease (-PD) and the potential for novel treatments in this population, genetic testing prioritization for the identification of -PD patients is crucial for prognostication, individualizing treatment, and stratification for clinical trials. Assessing the predictive value of certain clinical traits for the -variant carrier status will help target genetic testing in clinical settings where cost and access limit its availability.

Methods: In-depth clinical characterization through standardized rating scales for motor and non-motor symptoms and self-reported binomial information of a cohort of subjects with PD (n = 100) from our center and from the larger cohort of the Parkinson's Progression Marker Initiative (PPMI) was utilized to evaluate the predictive values of clinical traits for variant carrier status.

Top-down suppression of negative features applies flexibly contingent on visual search goals.

Visually searching for a frequently changing target is assumed to be guided by flexible working memory representations of specific features necessary to discriminate targets from distractors. Here, we tested if these representations allow selective suppression or always facilitate perception based on search goals. Participants searched for a target (i.

Reprogramming Chromosome Ends by Functional Histone Acetylation.

Cancers harness embryonic programs to evade aging and promote survival. Normally, sequences at chromosome ends called telomeres shorten with cell division, serving as a countdown clock to limit cell replication. Therefore, a crucial aspect of cancerous transformation is avoiding replicative aging by activation of telomere repair programs.

Intravenous iron-induced hypophosphatemia and kidney stone disease.

Patients with Crohn's disease are at increased risk for symptomatic nephrolithiasis. Stones in these patients are most commonly composed of calcium oxalate monohydrate or mixed calcium-oxalate and calcium-phosphate. Precipitation of both minerals depends on urinary pH, calcium, phosphate and oxalate excretion.