Design of Experiments to Tailor the Potential of BSA-Coated Peptide Nanocomplexes for Temozolomide/p53 Gene Co-Delivery.

Gene therapy can be viewed as a promising/valuable therapeutic approach directed to cancer treatment, including glioblastoma. Concretely, the combination of gene therapy with chemotherapy could increase its therapeutic index due to a synergistic effect. In this context, bovine serum albumin (BSA)-coated temozolomide (TMZ)-peptide (WRAP5)/p53 gene-based plasmid DNA complexes were developed to promote payload co-delivery.

High-Risk HPV Detection in Paraffin-Embedded Tissue from Cervical Lesions.

Background: Human papillomavirus (HPV), a leading cause of cervical cancer, is present in most cases of the disease and ranks as the fourth most common cancer in women globally. Among the HPV types, fourteen (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68) are recognized as high-risk (hrHPV), each with varying levels of oncogenic potential. Detecting and genotyping these hrHPV types in cervical lesions is crucial, requiring the development of new diagnostic methods.

Estimated number of lives directly saved by COVID-19 vaccination programmes in the WHO European Region from December, 2020, to March, 2023: a retrospective surveillance study.

Background: By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023.

Methods: In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature.

Upgrading Mitochondria-Targeting Peptide-Based Nanocomplexes for Zebrafish In Vivo Compatibility Assays.

The lack of effective delivery systems has slowed the development of mitochondrial gene therapy. Delivery systems based on cell-penetrating peptides (CPPs) like the WRAP (tryptophan and arginine-rich peptide) family conjugated with a mitochondrial targeting sequence (MTS) have emerged as adequate carriers to mediate gene expression into the mitochondria. In this work, we performed the PEGylation of WRAP/pDNA nanocomplexes and compared them with previously analyzed nanocomplexes such as (KH)/pDNA and CpMTP/pDNA.

Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells.

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy.

Mannosylated polyethylenimine-cholesterol-based nanoparticles for targeted delivery of minicircle DNA vaccine against COVID-19 to antigen-presenting cells.

DNA vaccines can be a potential solution to protect global health, triggering both humoral and cellular immune responses. DNA vaccines are valuable in preventing intracellular pathogen infections, and therefore can be explored against coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). This work explored different systems based on polyethylenimine (PEI), functionalized for the first time with both cholesterol (CHOL) and mannose (MAN) to deliver parental plasmid (PP) and minicircle DNA (mcDNA) vectors encoding the receptor-binding domain (RBD) of SARS-CoV-2 to antigen-presenting cells (APCs).

The impact of biological clock and sex hormones on the risk of disease.

Molecular clocks are responsible for defining 24-h cycles of behaviour and physiology that are called circadian rhythms. Several structures and tissues are responsible for generating these circadian rhythms and are named circadian clocks. The suprachiasmatic nucleus of the hypothalamus is believed to be the master circadian clock receiving light input via the optic nerve and aligning internal rhythms with environmental cues.

The Role of Biological Rhythms in New Drug Formulations to Cross the Brain Barriers.

For brain protection, the blood-brain barrier and blood-cerebrospinal fluid barrier limit the traffic of molecules between blood and brain tissue and between blood and cerebrospinal fluid, respectively. Besides their protective function, brain barriers also limit the passage of therapeutic drugs to the brain, which constitutes a great challenge for the development of therapeutic strategies for brain disorders. This problem has led to the emergence of novel strategies to treat neurological disorders, like the development of nanoformulations to deliver therapeutic agents to the brain.

A Potential Effect of Circadian Rhythm in the Delivery/Therapeutic Performance of Paclitaxel-Dendrimer Nanosystems.

The circadian clock controls behavior and physiology. Presently, there is clear evidence of a connection between this timing system and cancer development/progression. Moreover, circadian rhythm consideration in the therapeutic action of anticancer drugs can enhance the effectiveness of cancer therapy.

Facile Gram-Scale Synthesis of NiO Nanoflowers for Highly Selective and Sensitive Electrocatalytic Detection of Hydrazine.

The design and development of efficient and electrocatalytic sensitive nickel oxide nanomaterials have attracted attention as they are considered cost-effective, stable, and abundant electrocatalytic sensors. However, although innumerable electrocatalysts have been reported, their large-scale production with the same activity and sensitivity remains challenging. In this study, we report a simple protocol for the gram-scale synthesis of uniform NiO nanoflowers (approximately 1.

Development and Characterization of Quercetin-Loaded Delivery Systems for Increasing Its Bioavailability in Cervical Cancer Cells.

Quercetin is a natural flavonoid with high anticancer activity, especially for related-HPV cancers such as cervical cancer. However, quercetin exhibits a reduced aqueous solubility and stability, resulting in a low bioavailability that limits its therapeutic use. In this study, chitosan/sulfonyl-ether-β-cyclodextrin (SBE-β-CD)-conjugated delivery systems have been explored in order to increase quercetin loading capacity, carriage, solubility and consequently bioavailability in cervical cancer cells.

Delivery Systems for Mitochondrial Gene Therapy: A Review.

Mitochondria are membrane-bound cellular organelles of high relevance responsible for the chemical energy production used in most of the biochemical reactions of cells. Mitochondria have their own genome, the mitochondrial DNA (mtDNA). Inherited solely from the mother, this genome is quite susceptible to mutations, mainly due to the absence of an effective repair system.

Development of WRAP5 Peptide Complexes for Targeted Drug/Gene Co-Delivery toward Glioblastoma Therapy.

Despite the great progress over the past few decades in both the diagnosis and treatment of a great variety of human cancers, glioblastoma remains the most lethal brain tumor. In recent years, cancer gene therapy focused on non-viral vectors which emerged as a promising approach to glioblastoma treatment. Transferrin (Tf) easily penetrates brain cells of the blood-brain barrier, and its receptor is highly expressed in this barrier and glioblastoma cells.

Circadian rhythm and disease: Relationship, new insights, and future perspectives.

The circadian system is responsible for internal functions and regulation of the organism according to environmental cues (zeitgebers). Circadian rhythm dysregulation or chronodisruption has been associated with several diseases, from mental to autoimmune diseases, and with life quality change. Following this, some therapies have been developed to correct circadian misalignments, such as light therapy and chronobiotics.

An Action-Independent Role for Midfrontal Theta Activity Prior to Error Commission.

Error-related electroencephalographic (EEG) signals have been widely studied concerning the human cognitive capability of differentiating between erroneous and correct actions. Midfrontal error-related negativity (ERN) and theta band oscillations are believed to underlie post-action error monitoring. However, it remains elusive how early monitoring activity is trackable and what are the pre-response brain mechanisms related to performance monitoring.

Maximization of the Minicircle DNA Vaccine Production Expressing SARS-CoV-2 RBD.

Nucleic acid vaccines have been proven to be a revolutionary technology to induce an efficient, safe and rapid response against pandemics, like the coronavirus disease (COVID-19). Minicircle DNA (mcDNA) is an innovative vector more stable than messenger RNA and more efficient in cell transfection and transgene expression than conventional plasmid DNA. This work describes the construction of a parental plasmid (PP) vector encoding the receptor-binding domain (RBD) of the S protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the use of the Design of Experiments (DoE) to optimize PP recombination into mcDNA vector in an orbital shaker.

Flavonoids-Based Delivery Systems towards Cancer Therapies.

Cancer is the second leading cause of death worldwide. Cervical cancer, for instance, is considered a major scourge in low-income countries. Its development is mostly associated with the human papillomavirus persistent infection and despite the availability of preventive vaccines, they are only widely administered in more developed countries, thus leaving a large percentage of unvaccinated women highly susceptible to this type of cancer.

Peptides vs. Polymers: Searching for the Most Efficient Delivery System for Mitochondrial Gene Therapy.

Together with the nucleus, the mitochondrion has its own genome. Mutations in mitochondrial DNA are responsible for a variety of disorders, including neurodegenerative diseases and cancer. Current therapeutic approaches are not effective.

The Influence of Circadian Rhythm on Cancer Cells Targeting and Transfection Efficiency of a Polycation-Drug/Gene Delivery Vector.

The conception of novel anticancer delivery systems and the combination of chronobiology with nanotechnology may provide a powerful tool to optimize cancer therapy. In this work, polyethylenimine (PEI) has been used to complex p53 encoded plasmid DNA (pDNA), and the anticancer drug methotrexate (MTX) has also been loaded into the vectors. To investigate the influence of circadian clock on drug/gene delivery efficiency, HeLa, C33A and fibroblast cells have been transfected with developed PEI/pDNA/MTX delivery vectors at six different time points.

A neuronal theta band signature of error monitoring during integration of facial expression cues.

Error monitoring is the metacognitive process by which we are able to detect and signal our errors once a response has been made. Monitoring when the outcome of our actions deviates from the intended goal is crucial for behavior, learning, and the development of higher-order social skills. Here, we explored the neuronal substrates of error monitoring during the integration of facial expression cues using electroencephalography (EEG).

Burnout in the Pharmaceutical Activity: The Impact of COVID-19.

Importance: Pharmacists are among the healthcare professionals involved in the response to the COVID-19 pandemic, maintaining essential services. In the context of restrictions and reorganization of human resources, as a result of policies recently applied to the health sector, following international guidelines, and given the scarcity of data on burnout in pharmaceutical activity, it was considered highly relevant to promote a nationwide survey aiming to collect more complete evidence on the burnout syndrome and to understand how pharmacists have viewed their work and the people they worked closely with.

Objectives: The study aimed to assess the occurrence of pharmacist burnout and determine outcomes for each of its dimensions; identify potentially associated characteristics; and determine profiles and critical limits.

An update of advanced nanoplatforms for Glioblastoma Multiforme Management.

Glioblastoma multiforme (GBM) is a very aggressive and heterogeneous glioma. Currently, GBM is treated with a combination of surgery, radiotherapy, chemotherapy (e.g.

Classification of erroneous actions using EEG frequency features: implications for BCI performance.

Several studies have demonstrated that error-related neuronal signatures can be successfully detected and used to improve the performance of brain-computer interfaces. However, this has been tested mainly in well-controlled environments and based on temporal features, such as the amplitude of event-related potentials. In this study, we propose a classification algorithm combining frequency features and a weighted SVM to detect the neuronal signatures of errors committed in a complex saccadic go/no-go task.

Design of Experiments to Achieve an Efficient Chitosan-Based DNA Vaccine Delivery System.

In current times, DNA vaccines are seen as a promising approach to treat and prevent diseases, such as virus infections and cancer. Aiming at the production of a functional and effective plasmid DNA (pDNA) delivery system, four chitosan polymers, differing in the molecular weight, were studied using the design of experiments (DoE) tool. These gene delivery systems were formulated by ionotropic gelation and exploring the chitosan and TPP concentrations as DoE inputs to maximize the nanoparticle positive charge and minimize their size and polydispersity index (PDI) as DoE outputs.