Convergence of Neuroinflammation, Microbiota, and Parkinson's Disease: Therapeutic Insights and Prospects.

Parkinson's disease (PD) is a complex neurodegenerative disorder. Recent evidence reveals connections between neuroinflammatory processes and intestinal microbiota alterations in the progression of this pathology. This comprehensive review explores the intricate relationships between them, highlighting their combined impact on PD.

Prediction of future microplastic accumulation in agricultural soils.

This study shows the general exponential rise in microplastic accumulation in agricultural soils, with fertilizer application speeding up this increase, and future predictions of microplastic concentrations. Utilizing data from the Broadbalk winter wheat experiment at Rothamsted Research, UK, from 1846 to 2022, Poisson regression models were applied to microplastic counts under different soil treatments, including farmyard manure, inorganic fertilizers, and control conditions. A mass conversion factor was applied to obtain the w/w relationship.

Role of TFEB in Huntington's Disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of the CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. This expansion leads to a polyglutamine (polyQ) tract at the N-terminal end of HTT, which reduces the solubility of the protein and promotes its accumulation. Inefficient clearance of mutant HTT (mHTT) by the proteasome or autophagy-lysosomal system leads to accumulation of oligomers and toxic protein aggregates in neurons, resulting in impaired proteolytic systems, transcriptional dysregulation, impaired axonal transport, mitochondrial dysfunction and cellular energy imbalance.

Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer.

Purpose: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC.

Experimental Design: We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial.

The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases.

Cardiolipin (CL) is a mitochondria-exclusive phospholipid synthesized in the inner mitochondrial membrane. CL plays a key role in mitochondrial membranes, impacting a plethora of functions this organelle performs. Consequently, it is conceivable that abnormalities in the CL content, composition, and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of diseases.

Immunological aspects of central neurodegeneration.

The etiology of various neurodegenerative disorders that mainly affect the central nervous system including (but not limited to) Alzheimer's disease, Parkinson's disease and Huntington's disease has classically been attributed to neuronal defects that culminate with the loss of specific neuronal populations. However, accumulating evidence suggests that numerous immune effector cells and the products thereof (including cytokines and other soluble mediators) have a major impact on the pathogenesis and/or severity of these and other neurodegenerative syndromes. These observations not only add to our understanding of neurodegenerative conditions but also imply that (at least in some cases) therapeutic strategies targeting immune cells or their products may mediate clinically relevant neuroprotective effects.

Heat shock and thermotolerance in Caenorhabditis elegans: An overview of laboratory techniques.

The soil nematode worm Caenorhabditis elegans is a simple and well-established model for the study of many biological processes. Heat shock and thermotolerance assays have been developed for this nematode, and have been used to decipher the molecular relationships between thermal stress and aging, among others. Nevertheless, a systematic and methodological comparison of the different approaches and tools utilized is lacking in the literature.

Vitamin D Receptor Polymorphisms in a Spanish Cohort of Parkinson's Disease Patients.

Vitamin D receptor (VDR) is a nuclear hormone receptor widely expressed in the substantia nigra. Its association with an increased risk of Parkinson's disease (PD) is based on vitamin D deficiency and/or different polymorphisms in its gene receptor. This fact has been demonstrated by several case-control studies.

Ligand Hydrogenation during Hydroformylation Catalysis Detected by In Situ High-Pressure Infra-Red Spectroscopic Analysis of a Rhodium/Phospholene-Phosphite Catalyst.

Phospholane-phosphites are known to show highly unusual selectivity towards branched aldehydes in the hydroformylation of terminal alkenes. This paper describes the synthesis of hitherto unknown unsaturated phospholene borane precursors and their conversion to the corresponding phospholene-phosphites. The relative stereochemistry of one of these ligands and its Pd complex was assigned with the aid of X-ray crystal structure determinations.

Lysosomal Dysfunction: Connecting the Dots in the Landscape of Human Diseases.

Lysosomes are the main organelles responsible for the degradation of macromolecules in eukaryotic cells. Beyond their fundamental role in degradation, lysosomes are involved in different physiological processes such as autophagy, nutrient sensing, and intracellular signaling. In some circumstances, lysosomal abnormalities underlie several human pathologies with different etiologies known as known as lysosomal storage disorders (LSDs).

Comparative Genetic Analysis of the Promoters of the ATG16L1 and ATG5 Genes Associated with Sporadic Parkinson's Disease.

Sporadic Parkinson's disease, characterised by a decline in dopamine, usually manifests in people over 65 years of age. Although 10% of cases have a genetic (familial) basis, most PD is sporadic. Genome sequencing studies have associated several genetic variants with sporadic PD.

Mitochondrial Dysfunction in Repeat Expansion Diseases.

Repeat expansion diseases are a group of neuromuscular and neurodegenerative disorders characterized by expansions of several successive repeated DNA sequences. Currently, more than 50 repeat expansion diseases have been described. These disorders involve diverse pathogenic mechanisms, including loss-of-function mechanisms, toxicity associated with repeat RNA, or repeat-associated non-ATG (RAN) products, resulting in impairments of cellular processes and damaged organelles.

Urethral Slings for Irradiated Patients With Male Stress Urinary Incontinence: A Meta-analysis.

Objective: To systematically compare success, cure and complication rates of urethral sling surgeries in stress urinary incontinence patients with and without a history of pelvic radiotherapy (RT).

Materials And Methods: We searched PUBMED, EMBASE, and Web of Science to identify relevant articles. The primary outcomes were the success and cure rates.

Detection of rare genetic variations in the promoter regions of the ATG16L gene in Parkinson's patients.

Mutations in the ATG genes have been related to impair autophagic function, contributing to the sporadic onset of Parkinsońs Disease (PD). However, scarce studies have been performed about ins/del within the regulatory domains of the autophagy genes in sporadic PD patients. This study was aimed to found ins/del within part of the crucial core autophagy promotor gene region of the ATG16L1 in a groups of sporadic PD patients.

Changes in Liver Lipidomic Profile in G2019S- Mouse Model of Parkinson's Disease.

The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis.

Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.

Background: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives.

Methods: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain.

Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1).

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. Autophagy has been widely studied in DM1, although the endocytic pathway has not.

Estimating spatio-temporal fields through reinforcement learning.

Prediction and estimation of phenomena of interest in aquatic environments are challenging since they present complex spatio-temporal dynamics. Over the past few decades, advances in machine learning and data processing contributed to ocean exploration and sampling using autonomous robots. In this work, we formulate a reinforcement learning framework to estimate spatio-temporal fields modeled by partial differential equations.

Loss of KEAP1 Causes an Accumulation of Nondegradative Organelles.

KEAP1 is a cytoplasmic protein that functions as an adaptor for the Cullin-3-based ubiquitin E3 ligase system, which regulates the degradation of many proteins, including NFE2L2/NRF2 and p62/SQSTM1. Loss of KEAP1 leads to an accumulation of protein ubiquitin aggregates and defective autophagy. To better understand the role of KEAP1 in the degradation machinery, we investigated whether Keap1 deficiency affects the endosome-lysosomal pathway.

haploinsufficiency in CD1 mice results in metabolic alterations and exacerbates age-associated retinal degeneration.

Macroautophagy/autophagy is a key process in the maintenance of cellular homeostasis. The age-dependent decline in retinal autophagy has been associated with photoreceptor degeneration. Retinal dysfunction can also result from damage to the retinal pigment epithelium (RPE), as the RPE-retina constitutes an important metabolic ecosystem that must be finely tuned to preserve visual function.

Assessing the Variability of Cell-Associated HIV DNA Quantification through a Multicenter Collaborative Study.

Reliable and accurate quantification of cell-associated HIV DNA (CA HIV DNA) is critical for early infant diagnosis, clinical management of patients under therapy, and to inform new therapeutics efficacy. The present study assessed the variability of CA HIV DNA quantification obtained from various assays and the value of using reference materials to help harmonize the measurements. Using a common set of reagents, our multicenter collaborative study highlights significant variability of CA HIV DNA quantification and lower limit of quantification across assays.

Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study.

Objective: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence.

Methods: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population.