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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target. This review contains a very comprehensive critical description of the involvement of mitochondria and mitochondria-mediated mechanisms in ALS. The review covers several key areas related to mitochondria in ALS, including impaired mitochondrial function, mitochondrial bioenergetics, reactive oxygen species, metabolic processes and energy metabolism, mitochondrial dynamics, turnover, autophagy and mitophagy, impaired mitochondrial transport, and apoptosis. This review also highlights preclinical and clinical studies that have investigated various mitochondria-targeted therapies for ALS treatment. These include strategies to improve mitochondrial function, such as the use of dichloroacetate, ketogenic and high-fat diets, acetyl-carnitine, and mitochondria-targeted antioxidants. Additionally, antiapoptotic agents, like the mPTP-targeting agents minocycline and rasagiline, are discussed. The paper aims to contribute to the identification of effective mitochondria-targeted therapies for ALS treatment by synthesizing the current understanding of the role of mitochondria in ALS pathogenesis and reviewing potential convergent therapeutic interventions. The complex interplay between mitochondria and the pathogenic mechanisms of ALS holds promise for the development of novel treatment strategies to combat this devastating disease.

Anxiety disorders in dogs are ever-growing and represent an important concern in the veterinary behavior field. These disorders are often disregarded in veterinary clinical practice, negatively impacting the animal's and owner's quality of life. Moreover, these anxiety disorders can potentially result in the abandonment or euthanasia of dogs. Growing evidence shows that the gut microbiota is a central player in the gut-brain axis. A variety of microorganisms inhabit the intestines of dogs, which are essential in maintaining intestinal homeostasis. These microbes can impact mental health through several mechanisms, including metabolic, neural, endocrine, and immune-mediated pathways. The disruption of a balanced composition of resident commensal communities, or dysbiosis, is implicated in several pathological conditions, including mental disorders such as anxiety. Studies carried out in rodent models and humans demonstrate that the intestinal microbiota can influence mental health through these mechanisms, including anxiety disorders. Furthermore, novel therapeutic strategies using prebiotics and probiotics have been shown to ameliorate anxiety-related symptoms. However, regarding the canine veterinary behavior field, there is still a lack of insightful research on this topic. In this review, we explore the few but relevant studies performed on canine anxiety disorders. We agree that innovative bacterial therapeutical approaches for canine anxiety disorders will become a promising field of investigation and certainly pave the way for new approaches to these behavioral conditions., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Carina Sacoor et al.)

Sperm cells are particularly vulnerable to reactive oxygen species (ROS), impairing their fertilizing ability. Our objective was to study the effect of a novel mitochondrial-directed antioxidant, AntiOxBEN2, on bovine sperm function. This antioxidant was added to the semen capacitation medium (CAP), during the swim-up process, and to the fertilization medium (FERT) during the co-incubation of matured oocytes and capacitated spermatozoa, in concentrations of 0 (control), 1, and 10 µM. After the swim-up, sperm motility (CASA and visual analysis), vitality (eosin-nigrosin), mitochondrial membrane potential (JC1), intracellular ROS, adenosine triphosphate (ATP) levels, and basal metabolism (Seahorse Xfe96) were evaluated. Embryo development and quality were also assessed. Higher cleavage rates were obtained when 1 µM AntiOxBEN2 were added to CAP and FERT media (compared to control, p < 0.04). A positive effect of AntiOxBEN2 on intracellular ROS reduction (p = 0.01), on the increment of mitochondrial membrane potential (p ≤ 0.003) and, consequently, on the sperm quality was identified. However, the highest dose impaired progressive motility, ATP production, and the number of produced embryos. The results demonstrate a beneficial effect of AntiOxBEN2 (1 µM) on sperm capacitation and fertilization processes, thus improving embryonic development. This may constitute a putative novel therapeutic strategy to improve the outcomes of assisted reproductive techniques (ART).

Chronic inflammatory enteropathies in dogs are characterized by persistent or recurrent gastrointestinal signs that last for more than 3 weeks. Despite unclear etiopathogenesis, it is considered that a genetic predisposition associated with environmental factors, such as dietary antigens and intestinal microbiota, might induce an abnormal immune response in the host. The diagnosis of this condition requires full investigation in order to exclude all other possible causes. Currently, the observation of clinical signs associated with histopathologic evaluation and systematic therapeutic trials is the gold standard for the diagnosis of chronic enteropathies. Furthermore, diagnosis, monitoring the disease progression, and treatment response evaluation can be exhausting, since this whole process is time-consuming, costly, and partially invasive. Therefore, biomarkers appear as non-invasive tools, which can be useful in evaluating gastrointestinal function, identifying the presence of the disease and assessing its natural progression, monitoring gastrointestinal inflammation, predicting response to treatment, and clinical outcomes. Over the past decade, several studies were conducted in order to explore the clinical utility of biomarkers. Thus, the aim of this dissertation is to provide an overview of the biomarkers considered relevant in the diagnosis and management of dogs with chronic inflammatory enteropathies. The biomarkers addressed in this study may be serological, present in urine and feces, or even tissue-derived. This study argues that biomarkers, in particular calprotectin and calgranulin C, have great potential to be used in clinical practice in the diagnosis and management of affected dogs. However, a single biomarker cannot assuredly predict disease severity, progression, response to treatment, and clinical outcomes. Therefore, in order to achieve greater accuracy, it would be beneficial if these tools are used in conjunction with contemporary ones. Future research is needed with the aim to better determine the usefulness of these tools in chronic inflammatory enteropathies in dogs., Competing Interests: The authors declare that there is no conflict of interest.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease or Charcot disease, is a fatal neurodegenerative disease that affects motor neurons (MNs) and leads to death within 2-5 years of diagnosis, without any effective therapy available. Although the pathological mechanisms leading to ALS are still unknown, a wealth of evidence indicates that an excessive reactive oxygen species (ROS) production associated with an inefficient antioxidant defense represents an important pathological feature in ALS. Substantial evidence indicates that oxidative stress (OS) is implicated in the loss of MNs and in mitochondrial dysfunction, contributing decisively to neurodegeneration in ALS. Although the modulation of OS represents a promising approach to protect MNs from degeneration, the fact that several antioxidants with beneficial effects in animal models failed to show any therapeutic benefit in patients raises several questions that should be analyzed. Using specific queries for literature search on PubMed, we review here the role of OS-related mechanisms in ALS, including the involvement of altered mitochondrial function with repercussions in neurodegeneration. We also describe antioxidant compounds that have been mostly tested in preclinical and clinical trials of ALS, also describing their respective mechanisms of action. While the description of OS mechanism in the different mutations identified in ALS has as principal objective to clarify the contribution of OS in ALS, the description of positive and negative outcomes for each antioxidant is aimed at paving the way for novel opportunities for intervention. In conclusion, although antioxidant strategies represent a very promising approach to slow the progression of the disease, it is of utmost need to invest on the characterization of OS profiles representative of each subtype of patient, in order to develop personalized therapies, allowing to understand the characteristics of antioxidants that have beneficial effects on different subtypes of patients., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 Teresa Cunha-Oliveira et al.)

Li(+) transport, intracellular immobilisation and Li(+)/Mg(2+) competition were studied in Li(+)-loaded bovine chromaffin cells. Li(+) influx rate constants, k(i), obtained by atomic absorption (AA) spectrophotometry, in control (without and with ouabain) and depolarising (without and with nitrendipine) conditions, showed that L-type voltage-sensitive Ca(2+) channels have an important role in Li(+) uptake under depolarising conditions. The Li(+) influx apparent rate constant, k(iapp), determined under control conditions by (7)Li NMR spectroscopy with the cells immobilised and perfused, was much lower than the AA-determined value for the cells in suspension. Loading of cell suspensions with 15 mmol l(-1) LiCl led, within 90 min, to a AA-measured total intracellular Li(+) concentration, [Li(+)](iT)=11.39+/-0.56 mmol (l cells)(-1), very close to the steady state value. The intracellular Li(+) T(1)/T(2) ratio of (7)Li NMR relaxation times of the Li(+)-loaded cells reflected a high degree of Li(+) immobilisation in bovine chromaffin cells, similar to neuroblastoma, but larger than for lymphoblastoma and erythrocyte cells. A 52% increase in the intracellular free Mg(2+) concentration, Delta[Mg(2+)](f)=0.27+/-0.05 mmol (l cells)(-1) was measured for chromaffin cells loaded with the Mg(2+)-specific fluorescent probe furaptra, after 90-min loading with 15 mmol l(-1) LiCl, using fluorescence spectroscopy, indicating significant displacement of Mg(2+) by Li(+) from its intracellular binding sites. Comparison with other cell types showed that the extent of intracellular Li(+)/Mg(2+) competition at the same Li(+) loading level depends on intracellular Li(+) transport and immobilisation in a cell-specific manner, being maximal for neuroblastoma cells.

Li(+) influx by bovine chromaffin cells, obtained from bovine adrenal medulla, was studied in intact cell suspensions using (7)Li NMR spectroscopy with the shift reagent [Tm(HDOTP)](4-). The influx rate constants, k(i), were determined in the absence and in the presence of two Na(+) membrane transport inhibitors. The values obtained indicate that both voltage sensitive Na(+) channels and (Na(+)/K(+))-ATPase play an important role in Li(+) uptake by these cells. (7)Li NMR T(1) and T(2) relaxation times for intracellular Li(+) in bovine chromaffin cells provided a T(1)/T(2) ratio of 305, showing that Li(+) is highly, immobilized due to strong binding to intracellular structures. Using fluorescence spectroscopy and the Mg(2+) fluorescent probe, furaptra, the free intracellular Mg(2+) concentration in the bovine chromaffin cells incubated with 15 mM LiCl was found to increase by about mM after the intracellular Li(+) concentration reached a steady state. Therefore, once inside the cell, Li(+) is able to displace Mg(2+) from its binding sites.