Histone H3 mutations and their impact on genome stability maintenance.

Histones are essential for maintaining chromatin structure and function. Histone mutations lead to changes in chromatin compaction, gene expression, and the recruitment of DNA repair proteins to the DNA lesion. These disruptions can impair critical DNA repair pathways, such as homologous recombination and non-homologous end joining, resulting in increased genomic instability, which promotes an environment favorable to tumor development and progression.

Mouse sarcopenia model reveals sex- and age-specific differences in phenotypic and molecular characteristics.

Our study was to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition to investigate the underlying molecular mechanisms. Aged male (23-32 months old) and female (27-28 months old) C57BL/6J mice were classified as non-, probable-, or sarcopenic based on assessments of grip strength, muscle mass, and treadmill running time, using 2 SDs below the mean of their young counterparts as cutoff points. A 9%-22% prevalence of sarcopenia was identified in 23-26 month-old male mice, with more severe age-related declines in muscle function than mass.

Clinical Relevance of Physical Function Outcomes in Cancer Cachexia.

Managing clinical manifestations of cancer/treatment burden on functional status and quality of life remains paramount across the cancer trajectory, particularly for patients with cachexia who display reduced functional capacity. However, clinically relevant criteria for classifying functional impairment at a single point in time or for classifying meaningful functional changes subsequent to disease and/or treatment progression are lacking. This unmet clinical need remains a major obstacle to the development of therapies for cancer cachexia.

Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic infection.

Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite, Currently, approximately 8 million people are infected worldwide, most of whom are in the chronic phase of the disease, which involves cardiac, digestive, or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective in the initial phase of infection, which is generally underdiagnosed. The selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that has a complex life cycle with both intracellular and bloodstream circulating parasite stages in vertebrate hosts.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3.

A Review of Nutraceuticals in Cancer Cachexia.

Cancer cachexia is largely characterized by muscle wasting and inflammation, leading to weight loss, functional impairment, poor quality of life (QOL), and reduced survival. The main barrier to therapeutic development is a lack of efficacy for improving clinically relevant outcomes, such as physical function or QOL, yet most nutraceutical studies focus on body weight. This review describes clinical and pre-clinical nutraceutical studies outside the context of complex nutritional and/or multimodal interventions, in the setting of cancer cachexia, in view of considerations for future clinical trial design.

The Trypanosoma cruzi TcTASV-C protein subfamily administrated with U-Omp19 promotes a protective response against a lethal challenge in mice.

The development of a Chagaś disease vaccine has yet the need for the identification of novel combinations of antigens and adjuvants. Here, the performance of TcTASV-C proteins that are virulence factors of trypomastigotes and belong to a novel surface protein family specific for T. cruzi, have been evaluated as antigens for a prophylactic vaccine.

Transmigration of Trypanosoma cruzi trypomastigotes through 3D cultures resembling a physiological environment.

To disseminate and colonise tissues in the mammalian host, Trypanosoma cruzi trypomastogotes should cross several biological barriers. How this process occurs or its impact in the outcome of the disease is largely speculative. We examined the in vitro transmigration of trypomastigotes through three-dimensional cultures (spheroids) to understand the tissular dissemination of different T.

Transmigration of Trypanosoma cruzi Trypomastigotes through 3D Spheroids Mimicking Host Tissues.

While cellular invasion by T. cruzi trypomastigotes and intracellular amastigote replication are well-characterized events that have been described by using 2D monolayer cultures, other relevant parasite-host interactions, like the dynamics of tissue invasiveness, cannot be captured using monolayer cultures. Spheroids constitute a valuable three-dimensional (3D) culture system because they mimic the microarchitecture of tissues and provide an environment similar to the encountered in natural infections, which includes the presence of extracellular matrix as well as 3D cell-cell interactions.

TcTASV-C, a protein family in Trypanosoma cruzi that is predominantly trypomastigote-stage specific and secreted to the medium.

Among the several multigene families codified by the genome of T. cruzi, the TcTASV family was the latest discovered. The TcTASV (Trypomastigote, Alanine, Serine, Valine) family is composed of ∼40 members, with conserved carboxi- and amino-termini but with a variable central core.