Optimizing TDP-43 silencing with siRNA-loaded polymeric nanovectors in neuronal cells for therapeutic applications: balancing knockdown and function.

TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed DNA/RNA binding protein critical for regulating gene expression, including transcription, splicing, mRNA stability, and protein translation. Aggregation of pathological TDP-43 proteins in the cytoplasm of neurons and glial cells appears to be a common feature of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as frontotemporal dementia (FTD), contributing to motor neuron degeneration and clinical symptoms. Downregulation of TDP-43 expression to prevent or reduce the formation of pathological aggregates is a potential therapeutic approach for treating TDP-43-related diseases.

Assessing yellow fever outbreak potential and implications for vaccine strategy.

Yellow fever (YF), a vector-borne viral hemorrhagic fever, is endemic in tropical regions of Africa and South America, with large vaccination programmes being used for control. However, significant outbreaks have occurred in recent years. Data on infection rates and seroprevalence is often sparse, requiring robust mathematical models to estimate the burden of yellow fever.

Outcomes and Follow-Up Trends in Adrenal Leiomyosarcoma: A Comprehensive Literature Review and Case Report.

: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than 50 documented cases in English medical literature, the diagnosis and management of adrenal LMS remain challenging. The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers and report our specific case.

Extracellular Vesicles from NSC-34 MN-like Cells Transfected with Mutant SOD1 Modulate Inflammatory Status of Raw 264.7 Macrophages.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs-macrophage communication is pivotal.

Advancing amyotrophic lateral sclerosis disease diagnosis: A lab-on-chip electrochemical immunosensor for ultra-sensitive TDP-43 protein detection and monitoring in serum patients'.

The global increase in population aging has led to a rise in neurodegenerative diseases (NDs), posing significant challenges to public health. Developing selective and specific biomarkers for early diagnosis and drug development is crucial addressing the growing burden of NDs. In this context, the RNA-binding protein TDP-43 has emerged as a promising biomarker for amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and TDP-43-associated proteinopathies.

The Evolution of Technology-Driven In Vitro Models for Neurodegenerative Diseases.

The alteration in the neural circuits of both central and peripheral nervous systems is closely related to the onset of neurodegenerative disorders (NDDs). Despite significant research efforts, the knowledge regarding NDD pathological processes, and the development of efficacious drugs are still limited due to the inability to access and reproduce the components of the nervous system and its intricate microenvironment. 2D culture systems are too simplistic to accurately represent the more complex and dynamic situation of cells in vivo and have therefore been surpassed by 3D systems.

The New Frontiers of Gene Therapy and Gene Editing in Inflammatory Diseases.

Inflammatory diseases are conditions characterized by abnormal and often excessive immune responses, leading to tissue and organ inflammation. The complexity of these disorders arises from the intricate interplay of genetic factors and immune responses, which challenges conventional therapeutic approaches. However, the field of genetic manipulation has sparked unprecedented optimism in addressing these complex disorders.

Compost application boosts soil restoration in highly disturbed hillslope vineyard.

A field trial was carried out to investigate the effects of compost application on a young Cabernet sauvignon vineyard located in a hilly area in the North-East of Italy and subjected to land terracing before plantation. The use of a compost based on manure, pruning residues and pomace at a rate of 65 t ha was compared to the mineral fertilization regime recommended for the vineyards in the area (NPK: 80, 50, 200 kg ha). A multi-factorial approach that considered soil chemical properties, microbial community structure and function, vine nutritional and vegetative indexes, yield and quality parameters was applied in the attempt of depict interrelated effects of compost on all these factors.

Novel Mutations Associated with Mitochondrial Disorder: Functional Characterization in Patient Fibroblasts and .

Genetic defects in the nuclear encoded subunits and assembly factors of cytochrome c oxidase (mitochondrial complex IV) are very rare and are associated with a wide variety of phenotypes. Biallelic pathogenic variants in the COX11 protein were previously identified in two unrelated children with infantile-onset mitochondrial encephalopathies. Through comprehensive clinical, genetic and functional analyses, here we report on a new patient harboring novel heterozygous variants in , presenting with Leigh-like features, and provide additional experimental evidence for a direct correlation between COX11 protein expression and sensitivity to oxidative stress.

Case report: Urbanized non-human primates as sentinels for human zoonotic diseases: a case of acute fatal toxoplasmosis in a free-ranging marmoset in coinfection with yellow fever virus.

Free-ranging non-human primates (NHP) can live in anthropized areas or urban environments in close contact with human populations. This condition can enable the emergence and transmission of high-impact zoonotic pathogens. For the first time, we detected a coinfection of the yellow fever (YF) virus with in a free-ranging NHP in a highly urbanized area of a metropolis in Brazil.

Inflammasomes: Mechanisms of Action and Involvement in Human Diseases.

Inflammasome complexes and their integral receptor proteins have essential roles in regulating the innate immune response and inflammation at the post-translational level. Yet despite their protective role, aberrant activation of inflammasome proteins and gain of function mutations in inflammasome component genes seem to contribute to the development and progression of human autoimmune and autoinflammatory diseases. In the past decade, our understanding of inflammasome biology and activation mechanisms has greatly progressed.

Yellow Fever Virus Maintained by Mosquitoes during the Dry Season in Cerrado, a Semiarid Region of Brazil, in 2021.

In recent decades, waves of yellow fever virus (YFV) from the Amazon Rainforest have spread and caused outbreaks in other regions of Brazil, including the Cerrado, a savannah-like biome through which YFV usually moves before arriving at the Atlantic Forest. To identify the vectors involved in the maintenance of the virus in semiarid environments, an entomological survey was conducted after confirmation of yellow fever (YF) epizootics at the peak of the dry season in the Cerrado areas of the state of Minas Gerais. In total, 917 mosquitoes from 13 taxa were collected and tested for the presence of YFV.

Recurrent Sensory-Motor Neuropathy Mimicking CIDP as Predominant Presentation of PDH Deficiency.

Introduction: Pyruvate dehydrogenase complex (PDH) deficiency (Online Mendelian Inheritance in Man # 312170) is a relatively common mitochondrial disorder, caused by mutations in the X-linked gene and presenting with a variable phenotypic spectrum, ranging from severe infantile encephalopathy to milder chronic neurological disorders.Isolated peripheral neuropathy as predominant clinical presentation is uncommon.

Results: We report on a patient, now 21 years old, presenting at the age of 2 years with recurrent symmetric weakness as first symptom of a PDH deficiency.

Wave-induced cross-shore distribution of different densities, shapes, and sizes of plastic debris in coastal environments: A laboratory experiment.

Plastic debris is a significant threat to marine and coastal ecosystems. Previous research found that waves, wind, as well as density, size, and shape of microplastics, drive their transport and dispersion. In this paper, a set of laboratory experiments on the effect of waves and wave-induced currents on the input rate and cross-shore transport and dispersion of different types of plastic debris, including the macro and mesosizes, in addition to microplastics is presented.

Identification of Gene Products Upregulation Marking the Intestinal Epithelial Monolayer of Ulcerative Colitis Patients.

SLC15A4/PHT1 is an endolysosome-resident carrier of oligopeptides and histidine recently come into view as a key path marker of immune/autoimmune/inflammatory pathways in immune cells. Yet, its emerging role in inflammatory processes directly targeting the gastrointestinal epithelial layer, as in the multifactorial pathophysiology of inflammatory bowel disease (IBD), is poorly investigated. Here, the first identification of gene products in human colonic epithelium of ulcerative colitis (UC) patients is reported, showing protein primarily localized in intracellular vesicle-like compartments.

Retrospective Investigation in Horses with Encephalitis Reveals Unnoticed Circulation of West Nile Virus in Brazil.

During these past years, several studies have provided serological evidence regarding the circulation of West Nile virus (WNV) in Brazil. Despite some reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the country. Recently, genomic monitoring activities in horses revealed the circulation of WNV in several Brazilian regions.

Hepato-pathological hallmarks for the surveillance of Yellow Fever in South American non-human primates.

The early detection and diagnosis of deaths in free-ranging non-human primates (NHPs) are key points for the surveillance of Yellow Fever (YF) in Brazil. The histopathological identification of infectious diseases remains very useful and reliable in the screening and detection of emerging zoonotic diseases such as YF. We surveyed data records and liver slides stained with hematoxylin and eosin from the Epizootics Surveillance Network to control YF, Ministry of Health of Brazil, to evaluate histopathological hallmarks for the diagnosis of the YF virus infection.

Fatal Human Alphaherpesvirus 1 Infection in Free-Ranging Black-Tufted Marmosets in Anthropized Environments, Brazil, 2012-2019.

Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features.

Evaluation of an Innovative and Sustainable Pre-Commercial Compound as Replacement of Fish Meal in Diets for Rainbow Trout during Pre-Fattening Phase: Effects on Growth Performances, Haematological Parameters and Fillet Quality Traits.

The aim of the study was to determine the potential and sustainable use of pre-commercial product ITTINSECT™ APS V1 as a major protein source in rainbow trout () diets. A 60-day feeding experiment was conducted to potentially use ITTINSECT as fish meal replacement in the diets of rainbow trout. Five isonitrogenous in dry matter (38% crude protein) and isolipidic (15% crude lipid) diets were produced: a control diet (fishmeal-based) (ITT) and four experimental diets replacing fishmeal by 25 (ITT), 50 (ITT), 75 (ITT) and 100 (ITT) %, with ITTINSECT™ APS V1.

First evidence for N7-Platinated Guanosine derivatives cell uptake mediated by plasma membrane transport processes.

Nucleos(t)ide analogues (NA) belong to a family of compounds widely used in anticancer/antiviral treatments. They generally exhibit a cell toxicity limited by cellular uptake levels and the resulting nucleos(t)ides metabolism modifications, interfering with the cell machinery for nucleic acids synthesis. We previously synthesized purine nucleos(t)ide analogues N7-coordinated to a platinum centre with unaltered sugar moieties of the type: [Pt(dien)(N7-dGuo)] (1; dien = diethylenetriamine; dGuo = 2'-deoxy-guanosine), [Pt(dien)(N7-dGMP)] (2; dGMP = 5'-(2'-deoxy)-guanosine monophosphate), and [Pt(dien)(N7-dGTP)] (3; dGTP = 5'-(2'-deoxy)-guanosine triphosphate), where the indicated electric charge is calculated at physiological pH (7.