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Journal of Veterinary Internal Medicine 2024Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive...
BACKGROUND
Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive drug-resistant and self-sustaining character, and high morbidity and mortality. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking.
OBJECTIVES
To establish evidence-based guidelines and an agreement among board-certified specialists for the appropriate management of SE and CS in dogs and cats.
ANIMALS
None.
MATERIALS AND METHODS
A panel of 5 specialists was formed to assess and summarize evidence in the peer-reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recommendations, especially for the interventions where veterinary clinical evidence was lacking.
RESULTS
The majority of the evidence was on the first-line management (ie, benzodiazepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies.
CONCLUSIONS AND CLINICAL RELEVANCE
Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications.
Topics: Cats; Dogs; Animals; Humans; Emergencies; Cat Diseases; Dog Diseases; Status Epilepticus; Epilepsy; Anticonvulsants
PubMed: 37921621
DOI: 10.1111/jvim.16928 -
Cell Communication and Signaling : CCS Nov 2023Cardiovascular diseases pose a major threat worldwide. Common cardiovascular diseases include acute myocardial infarction (AMI), heart failure, atrial fibrillation (AF)... (Review)
Review
Cardiovascular diseases pose a major threat worldwide. Common cardiovascular diseases include acute myocardial infarction (AMI), heart failure, atrial fibrillation (AF) and atherosclerosis. Glycolysis process often has changed during these cardiovascular diseases. Lactate, the end-product of glycolysis, has been overlooked in the past but has gradually been identified to play major biological functions in recent years. Similarly, the role of lactate in cardiovascular disease is gradually being recognized. Targeting lactate production, regulating lactate transport, and modulating circulating lactate levels may serve as potential strategies for the treatment of cardiovascular diseases in the future. The purpose of this review is to integrate relevant clinical and basic research on the role of lactate in the pathophysiological process of cardiovascular disease in recent years to clarify the important role of lactate in cardiovascular disease and to guide further studies exploring the role of lactate in cardiovascular and other diseases. Video Abstract.
Topics: Humans; Cardiovascular Diseases; Lactic Acid; Myocardial Infarction; Atrial Fibrillation; Atherosclerosis
PubMed: 37924124
DOI: 10.1186/s12964-023-01350-7 -
Bioactive Materials Jul 2023The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between cell culture, animal models and the real human body has... (Review)
Review
The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between cell culture, animal models and the real human body has been pending for decades. The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis. The bone/cartilage organoid on-chip (BCoC) system is a novel platform of multi-tissue which faithfully emulate the essential elements, biologic functions and pathophysiological response under real circumstances. In this review, we propose the concept of BCoC platform, summarize the basic modules and current efforts to orchestrate them on a single microfluidic system. Current disease models, unsolved problems and future challenging are also discussed, the aim should be a deeper understanding of diseases, and ultimate realization of generic tools for further therapeutic strategies of pathological conditions.
PubMed: 37056252
DOI: 10.1016/j.bioactmat.2023.01.016 -
Emerging Topics in Life Sciences Dec 2023The young field of gastruloids brings promise to modeling and understanding early embryonic development. However, being a complex model, gastruloids are prone to...
The young field of gastruloids brings promise to modeling and understanding early embryonic development. However, being a complex model, gastruloids are prone to variability at different levels. In this perspective, we define the different levels of gastruloid variability, and parameters over which it can be measured. We discuss potential sources for variability, and then propose methods to better control and reduce it. We provide an example from definitive endoderm progression in gastruloids, where we harness gastruloid-to-gastruloid variation in early parameters to identify key driving factors for endoderm morphology. We then devise interventions that steer morphological outcome. A better control over the developmental progression of gastruloids will enhance their utility in both basic research and biomedical applications.
Topics: Female; Pregnancy; Humans; Gastrula; Endoderm; Embryonic Development
PubMed: 37815089
DOI: 10.1042/ETLS20230096 -
Brain : a Journal of Neurology Jan 2024Brain perivascular macrophages are specialized populations of macrophages that reside in the space around cerebral vessels, such as penetrating arteries and venules.... (Review)
Review
Brain perivascular macrophages are specialized populations of macrophages that reside in the space around cerebral vessels, such as penetrating arteries and venules. With the help of cutting-edge technologies, such as cell fate mapping and single-cell multi-omics, their multifaceted, pivotal roles in phagocytosis, antigen presentation, vascular integrity maintenance and metabolic regulation have more recently been further revealed under physiological conditions. Accumulating evidence also implies that perivascular macrophages are involved in the pathogenesis of neurodegenerative disease, cerebrovascular dysfunction, autoimmune disease, traumatic brain injury and epilepsy. They can act in either protective or detrimental ways depending on the disease course and stage. However, the underlying mechanisms of perivascular macrophages remain largely unknown. Therefore, we highlight potential future directions in research on perivascular macrophages, including the utilization of genetic mice and novel therapeutic strategies that target these unique immune cells for neuroprotective purposes. In conclusion, this review provides a comprehensive update on the current knowledge of brain perivascular macrophages, shedding light on their pivotal roles in central nervous system health and disease.
Topics: Mice; Animals; Neurodegenerative Diseases; Brain; Macrophages; Central Nervous System; Phagocytosis
PubMed: 37691438
DOI: 10.1093/brain/awad304 -
RNA (New York, N.Y.) Apr 2024Epitranscriptomics refers to chemical changes in RNAs and includes numerous chemical types with varying stoichiometry and functions. RNA modifications are highly diverse...
Epitranscriptomics refers to chemical changes in RNAs and includes numerous chemical types with varying stoichiometry and functions. RNA modifications are highly diverse in chemistry and respond in cell-type- and cell-state-dependent manners that enable and facilitate the execution of a wide array of biological functions. This includes roles in the regulation of transcription, translation, chromatin maintenance, immune response, and many other processes. This special issue presents the past, present, and future of epitranscriptomics research with a focus on mRNA. It includes perspectives from experts in the field, with the goal of encouraging discussions and debates that will further advance this area of research and enable it to realize its full potential in basic research and applications to human health and disease.
Topics: Humans; RNA, Messenger; RNA; RNA Processing, Post-Transcriptional
PubMed: 38531649
DOI: 10.1261/rna.079993.124 -
Journal of Fungi (Basel, Switzerland) Oct 2023Valley fever or coccidioidomycosis is a pulmonary infection caused by species of fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts... (Review)
Review
Valley fever or coccidioidomycosis is a pulmonary infection caused by species of fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues, causing significant pain and restricting mobility. Manifestations of such cases are usually nonspecific, making diagnosis very challenging, especially in non-endemic areas. The lack of basic knowledge and research data on the mechanisms defining susceptibility to extrapulmonary infection, especially when it involves bones and joints, prompted us to survey available clinical and animal data to establish specific research questions that remain to be investigated. In this review, we explore published literature reviews, case reports, and case series on the dissemination of coccidioidomycosis to bones and/or joints. We highlight key differential features with other conditions and opportunities for mechanistic and basic research studies that can help develop novel diagnostic, prognostic, and treatment strategies.
PubMed: 37888258
DOI: 10.3390/jof9101002 -
Audiology Research Sep 2023The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a...
The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a clinical product (a drug, therapeutic agent or means of monitoring a disease), as well as the inverse translation of clinical findings into basic research models [...].
PubMed: 37887844
DOI: 10.3390/audiolres13050063 -
Cell & Bioscience Jun 2023Acne is a chronic inflammatory skin disorder that profoundly impacts the quality of life of patients worldwide. While it is predominantly observed in adolescents, it can... (Review)
Review
Acne is a chronic inflammatory skin disorder that profoundly impacts the quality of life of patients worldwide. While it is predominantly observed in adolescents, it can affect individuals across all age groups. Acne pathogenesis is believed to be a result of various endogenous and exogenous factors, but the precise mechanisms remain elusive. Recent studies suggest that dysbiosis of the skin microbiota significantly contributes to acne development. Specifically, Cutibacterium acnes, the dominant resident bacterial species implicated in acne, plays a critical role in disease progression. Various treatments, including topical benzoyl peroxide, systemic antibiotics, and photodynamic therapy, have demonstrated beneficial effects on the skin microbiota composition in acne patients. Of particular interest is the therapeutic potential of probiotics in acne, given its direct influence on the skin microbiota. This review summarizes the alterations in skin microbiota associated with acne, provides insight into its pathogenic role in acne, and emphasizes the potential of therapeutic interventions aimed at restoring microbial homeostasis for acne management.
PubMed: 37344849
DOI: 10.1186/s13578-023-01072-w -
Advanced Science (Weinheim,... Sep 2023Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in...
Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin-dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin-resistant cells and tissues due to the loss of N6-methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient-derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl-CoA synthetase long-chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron-dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin-resistant CRC.
Topics: Humans; CDC2 Protein Kinase; Colorectal Neoplasms; Ferroptosis; Oxaliplatin; Proteolysis
PubMed: 37428466
DOI: 10.1002/advs.202301088