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Molecular Imaging and Radionuclide... Jun 2024Meckel scintigraphy is used to diagnose Meckel's diverticulum. Previously, premedication with ranitidine was the most frequently used method to increase the accuracy of...
OBJECTIVES
Meckel scintigraphy is used to diagnose Meckel's diverticulum. Previously, premedication with ranitidine was the most frequently used method to increase the accuracy of scintigraphy. However, ranitidine can no longer be used because it is banned by the Food and Drug Administration. The aim of this study was to investigate the usability of pantoprazole as a premedication instead of ranitidine in Meckel scintigraphy.
METHODS
Twelve New Zealand rabbits were used in this experimental study. Rabbits were divided into two groups: pantoprazole and control. Six rabbits were premedicated with pantoprazole for three days. Meckel scintigraphy was performed on all rabbits. Counts were made and compared by drawing regions of interest from the stomach walls.
RESULTS
According to the findings of this experimental study, pantoprazole significantly increased Tc-99m-pertechnetate uptake in the stomach of rabbits on both visual and quantitative evaluation.
CONCLUSION
Pantoprazole increases the gastric wall uptake of Tc-99m-pertechnetate in rabbits and is a potential drug for premedication in Meckel scintigraphy.
PubMed: 38949418
DOI: 10.4274/mirt.galenos.2024.48254 -
Preclinical determination of wound-healing activity of halibut oil cream in rat model of burn wound.Journal of Asian Natural Products... Jul 2024This study investigated the effects of halibut oil cream, containing omega-3 fatty acids, vitamins A and D, and hydroxyproline, on burn wound healing in rats. Acute...
This study investigated the effects of halibut oil cream, containing omega-3 fatty acids, vitamins A and D, and hydroxyproline, on burn wound healing in rats. Acute dermal toxicity tests confirmed its nontoxicity. Wistar rats were divided into five groups: a control, a positive control treated with silver sulfadiazine 1% (SSD), and three groups treated with 3%, 9%, and 27% halibut oil cream Formulation (HBOF). The SSD and HBOF groups showed significant healing improvements compared to the control. Histopathological analysis indicated increased collagen production in the HBOF groups, suggesting halibut oil cream's potential as a topical treatment for burn wounds.
PubMed: 38949206
DOI: 10.1080/10286020.2024.2368835 -
Clinical and Translational Science Jul 2024Activation of receptor-interacting protein kinase 1 (RIPK1), a broadly expressed serine/threonine protein kinase, by pro-inflammatory cytokines and pathogens can result... (Randomized Controlled Trial)
Randomized Controlled Trial
Activation of receptor-interacting protein kinase 1 (RIPK1), a broadly expressed serine/threonine protein kinase, by pro-inflammatory cytokines and pathogens can result in apoptosis, necroptosis, or inflammation. RIPK1 inhibition has been shown to reduce inflammation and cell damage in preclinical studies and may have therapeutic potential for degenerative and inflammatory diseases. SIR2446 is a potent and selective novel small molecule RIPK1 kinase inhibitor. This phase I, randomized, double-blind, placebo-controlled study in Australia (ACTRN12621001621808) evaluated the safety (primary objective), pharmacokinetics, and pharmacodynamics of single (3-600 mg) and multiple (5-400 mg for 10 days) ascending oral doses of SIR2446M (SIR2446 magnesium salt form) in healthy adults from Nov 24, 2021, until May 01, 2023. All treatment-emergent adverse events (TEAEs) were mild/moderate. The most reported TEAEs were vascular access site pain, headache, and rash morbilliform. SIR2446M plasma half-lives ranged from 11 to 19 h and there were no major deviations from dose proportionality for maximum concentration and area under the curve across doses. Renal excretion of unchanged SIR2446 was minimal. No marked accumulation was observed (mean accumulation ratio, 1.2-1.6) after multiple daily doses. A high-fat meal mildly reduced the exposure but was not considered clinically significant. SIR2446M had a rapid and sustained inhibitory effect on the activity of RIPK1, with an overall 90% target engagement at repeated doses ranging from 30 to 400 mg in peripheral blood mononuclear cells ex vivo stimulated to undergo necroptosis. The favorable safety, pharmacokinetic, and pharmacodynamic profile of SIR2446M in healthy participants supports its further clinical development in patients with degenerative and inflammatory diseases.
Topics: Humans; Adult; Male; Double-Blind Method; Female; Healthy Volunteers; Receptor-Interacting Protein Serine-Threonine Kinases; Middle Aged; Young Adult; Dose-Response Relationship, Drug; Protein Kinase Inhibitors; Administration, Oral; Adolescent; Drug Administration Schedule
PubMed: 38949195
DOI: 10.1111/cts.13857 -
EFORT Open Reviews Jul 2024The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new...
PURPOSE
The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced.
METHODS
A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics.
RESULTS
Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected.
CONCLUSION
There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.
PubMed: 38949173
DOI: 10.1530/EOR-23-0133 -
Small Methods Jul 2024The construction of reliable preclinical models is crucial for understanding the molecular mechanisms involved in gastric cancer and for advancing precision medicine....
The construction of reliable preclinical models is crucial for understanding the molecular mechanisms involved in gastric cancer and for advancing precision medicine. Currently, existing in vitro tumor models often do not accurately replicate the human gastric cancer environment and are unsuitable for high-throughput therapeutic drug screening. In this study, droplet microfluidic technology is employed to create novel gastric cancer assembloids by encapsulating patient-derived xenograft gastric cancer cells and patient stromal cells in Gelatin methacryloyl (GelMA)-Gelatin-Matrigel microgels. The usage of GelMA-Gelatin-Matrigel composite hydrogel effectively alleviated cell aggregation and sedimentation during the assembly process, allowing for the handling of large volumes of cell-laden hydrogel and the uniform generation of assembloids in a high-throughput manner. Notably, the patient-derived xenograft assembloids exhibited high consistency with primary tumors at both transcriptomic and histological levels, and can be efficiently scaled up for preclinical drug screening efforts. Furthermore, the drug screening results clearly demonstrated that the in vitro assembloid model closely mirrored in vivo drug responses. Thus, these findings suggest that gastric cancer assembloids, which effectively replicate the in vivo tumor microenvironment, show promise for enabling more precise high-throughput drug screening and predicting the clinical outcomes of various drugs.
PubMed: 38948952
DOI: 10.1002/smtd.202400204 -
Chemistry & Biodiversity Jul 2024Current industrial herbicides have a negative impact on the environment and have widespread resistance, so computational studies on their properties, elimination, and...
Current industrial herbicides have a negative impact on the environment and have widespread resistance, so computational studies on their properties, elimination, and overcoming resistance can be helpful. On the other hand, developing new herbicides, especially bioherbicides, is slow and costly. Therefore, computational studies that guide the design and search for new herbicides that exist in various plant sources, can alleviate the pain associated with the many obstacles. This review summarizes for the first time the most recent studies on both aspects of herbicides over 10 years.
PubMed: 38948948
DOI: 10.1002/cbdv.202400531 -
BioRxiv : the Preprint Server For... Jun 2024Ionizable lipid nanoparticles (LNPs) have been pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic...
Ionizable lipid nanoparticles (LNPs) have been pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA by 14%, and increase the transfection efficiency of mRNA up to 1.67 times in the current study. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to other membranous organelles. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, our work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes.
PubMed: 38948864
DOI: 10.1101/2024.06.19.599708 -
BioRxiv : the Preprint Server For... Jun 2024Pain is a prominent and debilitating symptom in myotonic disorders, yet its physiological mechanisms remain poorly understood. This study assessed preclinical pain-like...
Pain is a prominent and debilitating symptom in myotonic disorders, yet its physiological mechanisms remain poorly understood. This study assessed preclinical pain-like behavior in murine models of pharmacologically induced myotonia and myotonic dystrophy type 1 (DM1). In both myotonia congenita and DM1, impairment of the gene, which encodes skeletal muscle voltage-gated CLC-1 chloride channels, reduces chloride ion conductance in skeletal muscle cells, leading to prolonged muscle excitability and delayed relaxation after contraction. We used the CLC-1 antagonist anthracene-9- carboxylic acid (9-AC) at intraperitoneal doses of 30 or 60 mg/kg and HSA LR20b DM1 mice to model CLC-1-induced myotonia. Our experimental approach included pain behavioral testing, calcium imaging, and whole-cell current-clamp electrophysiology in mouse dorsal root ganglion (DRG) neurons. A single injection of 9-AC induced myotonia in mice, which persisted for several hours and resulted in long-lasting allodynic pain-like behavior. Similarly, HSA LR20b mice exhibited both allodynia and hyperalgesia. Despite these pain-like behaviors, DRG neurons did not show signs of hyperexcitability in either myotonic model. These findings suggest that myotonia induces nociplastic pain-like behavior in preclinical rodents, likely through central sensitization mechanisms rather than peripheral sensitization. This study provides insights into the pathophysiology of pain in myotonic disorders and highlights the potential of using myotonic mouse models to explore pain mechanisms and assess novel analgesics. Future research should focus on the central mechanisms involved in myotonia-induced pain and develop targeted therapies to alleviate this significant clinical burden.
PubMed: 38948724
DOI: 10.1101/2024.06.19.599732 -
BioRxiv : the Preprint Server For... Jun 2024Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune...
Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers are the mainstay. The design and interpretation of human biomarker studies require additional insights in the trajectories and drivers of peripheral immune markers. The current study mapped maternal inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17A, IL-23, interferon- ) during pregnancy and investigated the impact of demographic, environmental and genetic drivers on maternal inflammatory marker levels in four multi-ethnic and socio-economically diverse population-based cohorts with more than 12,000 pregnant participants. Additionally, pregnancy inflammatory markers were compared to pre-pregnancy levels. Cytokines showed a high correlation with each other, but not with CRP. Inflammatory marker levels showed high variability between individuals, yet high concordance within an individual over time during and pre-pregnancy. Pre-pregnancy body mass index (BMI) explained more than 9.6% of the variance in CRP, but less than 1% of the variance in cytokines. The polygenic score of CRP was the best predictor of variance in CRP (>14.1%). Gestational age and previously identified inflammation drivers, including tobacco use and parity, explained less than 1% of variance in both cytokines and CRP. Our findings corroborate differential underlying regulatory mechanisms of CRP and cytokines and are suggestive of an individual inflammatory marker baseline which is, in part, genetically driven. While prior research has mainly focused on immune marker changes throughout pregnancy, our study suggests that this field could benefit from a focus on intra-individual factors, including metabolic and genetic components.
PubMed: 38948713
DOI: 10.1101/2024.06.19.599718 -
Cancer Innovation Feb 2024In recent years, the three-dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue... (Review)
Review
In recent years, the three-dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo. This system offers several advantages, including high throughput, efficiency, and retention of tumor heterogeneity. Traditional Matrigel-submerged organoid cultures primarily support the long-term proliferation of epithelial cells. One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types, either in dual, triple or even multiple combinations. Another solution is a holistic approach including patient-derived tumor fragments, air-liquid interface, suspension 3D culture, and microfluidic tumor-on-chip models. Organoid co-culture models have also gained popularity for studying the tumor microenvironment, evaluating tumor immunotherapy, identifying predictive biomarkers, screening for effective drugs, and modeling infections. By leveraging these 3D culture systems, it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.
PubMed: 38948532
DOI: 10.1002/cai2.101