-
Frontiers in Immunology 2024C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin... (Review)
Review
C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions . The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases .
Topics: Humans; C-Reactive Protein; Animals; Inflammation; Immunity, Innate; Protein Conformation; Structure-Activity Relationship; Complement Activation
PubMed: 38947332
DOI: 10.3389/fimmu.2024.1425168 -
World Journal of Orthopedics Jun 2024Osteoarthritis (OA) presents a growing health concern, with substantial societal and healthcare burdens. Current management focuses on symptom relief, lacking...
Osteoarthritis (OA) presents a growing health concern, with substantial societal and healthcare burdens. Current management focuses on symptom relief, lacking disease-modifying options. Emerging research suggests the sodium channel Nav1.7 as a pivotal target in OA treatment. Preclinical studies demonstrate carbamazepine's efficacy in Nav1.7 blockade, offering significant joint protection in animal models. However, human trials are needed to validate these findings. Carbamazepine's repurposing holds promise for OA management, potentially revolutionizing treatment paradigms. Further research is essential to bridge the gap between preclinical evidence and clinical application, offering hope for improved OA management and enhanced patient quality of life.
PubMed: 38947258
DOI: 10.5312/wjo.v15.i6.602 -
MedRxiv : the Preprint Server For... Jun 2024Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among...
Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In this head-to-head comparison study including 9 cohorts and 1534 individuals, we found that plasma p-tau217 and medial temporal lobe Tau-PET signal showed similar associations with cognitive decline on a global cognitive composite test (R =0.32 vs R =0.32, p =0.812) and with progression to mild cognitive impairment (Hazard ratio[HR] =1.56[1.43-1.70] vs HR =1.63[1.50-1.77], p =0.627). Combined plasma and PET models were superior to the single biomarker models (R =0.36, p<0.01). Furthermore, sequential selection using plasma p-tau217 and then Tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 75% reduction when using plasma p-tau217 alone. We conclude that plasma p-tau217 and Tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use (i.e., plasma p-tau217 followed by Tau-PET in a subset with high plasma p-tau217) is useful for screening in clinical trials in preclinical AD.
PubMed: 38947004
DOI: 10.1101/2024.06.12.24308824 -
World Journal of Gastroenterology Jun 2024In this editorial we comment on the article published in a recent issue of the . Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular... (Review)
Review
In this editorial we comment on the article published in a recent issue of the . Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
Topics: Humans; Liver Failure, Acute; Ferroptosis; Pyroptosis; Hepatocytes; Animals; Sirtuin 1; Signal Transduction; Liver; Lipid Peroxidation; Liver Transplantation; Iron
PubMed: 38946877
DOI: 10.3748/wjg.v30.i23.2931 -
Pharmaceutical Biology Dec 2024Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management... (Review)
Review
CONTEXT
Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety.
OBJECTIVE
To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed.
METHODS
Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023.
RESULTS
This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function.
CONCLUSIONS
TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.
Topics: Humans; Diabetic Neuropathies; Medicine, Chinese Traditional; Drugs, Chinese Herbal; Animals; Quality of Life; Oxidative Stress; Drug Evaluation, Preclinical
PubMed: 38946248
DOI: 10.1080/13880209.2024.2369301 -
Radiation Oncology Journal Jun 2024This scoping review presents the preclinical and clinical data on the effects of high-dose radiation therapy (RT) on bone structure and function.
PURPOSE
This scoping review presents the preclinical and clinical data on the effects of high-dose radiation therapy (RT) on bone structure and function.
MATERIALS AND METHODS
An extensive PubMed search was performed for the relevant questions. The data were then synthesized into a comprehensive summary of the available relevant in-vitro, preclinical and clinical literature.
RESULTS
In-vitro studies of high-dose RT on cell cultures show considerable damage in the viability and functional capacity of the primary cells of the bones; the osteoclasts, the osteoblasts, and the osteocytes. In-vivo animal models show that high-dose RT induces significant morphological changes to the bone, inhibits the ability of bone to repair damage, and increases the fragility of the bone. Clinical data show that there is an increasing risk over time of damage to the bone, such as fractures, after high-dose RT.
CONCLUSION
These findings suggest that there may be a limit to the safe dose for single-fraction RT, and the long-term consequences of high-dose RT for the patients must be considered.
PubMed: 38946071
DOI: 10.3857/roj.2023.00969 -
Nihon Yakurigaku Zasshi. Folia... 2024Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as... (Review)
Review
Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants. In 2016, Carhart-Harris and colleagues reported that psilocybin, the hallucinogenic compound derived from magic mushrooms, exhibits rapid and enduring antidepressant effects in patients with treatment-resistant depression. Subsequent clinical studies have found the therapeutic potential of psilocybin in MDD, depressive episode in bipolar disorder, anorexia, and drug addiction. In 2018 and 2019, the U.S. Food and Drug Administration designated psilocybin as a "breakthrough medicine" for treatment-resistant depression and MDD, respectively. Notably, the side effects of psilocybin are limited to transient and mild issues, such as headache and fatigue, suggesting its safety. In 2023, we published a review on the role of serotonin 5-HT receptors in the antidepressant effects of serotonergic psychedelics (Nihon Yakurigaku Zasshi, Volume 158, Issue 3, Page 229-232). Here, we present our study alongside the latest clinical and preclinical research on the antidepressant effects of psilocybin and provide an overview of the potential and issues related to psilocybin therapy.
Topics: Psilocybin; Humans; Animals; Antidepressive Agents; Hallucinogens; Depressive Disorder, Major; Receptor, Serotonin, 5-HT2A
PubMed: 38945903
DOI: 10.1254/fpj.24007 -
The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321 -
Brain and Behavior Jul 2024Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances...
Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.
INTRODUCTION
Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.
METHODS
Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods.
RESULTS
The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor.
CONCLUSION
Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.
Topics: Animals; Isoflurane; Female; Cognitive Dysfunction; Pregnancy; Sleep Deprivation; Mice; Hippocampus; Prenatal Exposure Delayed Effects; Neuroinflammatory Diseases; Anesthetics, Inhalation; Synapses; Male; Mice, Inbred C57BL; Maternal Deprivation; Brain-Derived Neurotrophic Factor
PubMed: 38945806
DOI: 10.1002/brb3.3610 -
Journal of Pharmaceutical Sciences Jun 2024Interspecies scaling of the pharmacokinetics (PK) of CB 4332, a 150 kDa recombinant complement factor I protein, was performed using traditional and model-based...
Interspecies scaling of the pharmacokinetics (PK) of CB 4332, a 150 kDa recombinant complement factor I protein, was performed using traditional and model-based approaches to inform first-in-human dose selection. Plasma concentration versus time data from four preclinical PK studies of single intravenous and subcutaneous (SC) CB 4332 dosing in mice, rats and nonhuman primates (NHPs) were modeled simultaneously using naive pooling including allometric scaling. The human-equivalent dose was calculated using the preclinical no observed adverse effect level (NOAEL) as part of the dose-by-factor approach. Pharmacokinetic modeling of CB 4332 revealed species-specific differences in the elimination, which was accounted for by including an additional rat-specific clearance. Signs of anti-drug antibodies (ADA) formation in all rats and some NHPs were observed. Consequently, an additional ADA-induced clearance parameter was estimated including the time of onset. The traditional dose-by-factor approach calculated a maximum recommended starting SC dose of 0.9 mg/kg once weekly, which was predicted it to result in a trough steady-state concentration lower than the determined efficacy target range for CB 4332 in humans. Model simulations predicted the efficacy target range to be reached using 5 mg/kg once weekly SC dosing.
PubMed: 38945365
DOI: 10.1016/j.xphs.2024.06.022