Animal Models Of Injury Research Articles

Influence of Feeding Time on a Non-steroidal Anti-inflammatory Drug-induced Small Intestinal Injury Mouse Model.

Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely used pharmaceuticals, induce various adverse effects, including gastrointestinal injuries, such as ulcers and bleeding. Animal models of NSAID-induced small intestinal injury (NSI) have been extensively employed for the development of preventive and therapeutic agents. However, some experimental variations related to feeding times have been observed following NSI induction. This study aimed to investigate the impact of feeding time on an NSI mouse model. The mice were divided into eight groups: normal, sham, and model groups (with feeding times of 2 h, 6 h, 10 h, 14 h, 18 h, and 22 h; n=10 in each group). The mice were fasted for 18 h before the injection of indomethacin (15 mg/kg, subcutaneously), except for the normal group. Food supply was halted at specific time points (2 h, 6 h, 10 h, 14 h, 18 h, and 22 h); however, the normal and sham groups were continuously fed throughout the experiment. The length of the small intestine was measured, and histological analysis was performed 24 h after induction. Up to 14 h after induction, NSI, indicated by small intestine shortening, remained consistent, with a reduction in length of approximately 10-20%. However, feeding for more than 14 h significantly exacerbated NSI, both anatomically and histologically. The ulcerative changes observed in the small intestine 14 h after indomethacin injection may be closely associated with the influence of food on NSI.

Concussion Incidence and Recovery of Neurocognitive Dysfunction Among Youth Athletes Taking Antibiotics: A Preliminary, Multicenter Retrospective Cohort Study

Concussions are the leading cause of injury among youth athletes, and antibiotics are the most prescribed pediatric medication in the United States. Antibiotics have shown to exert neuroprotective effects in animal models of traumatic brain injury, but to date, no human studies exist. Between 2009 and 2019, 6,343 adolescent athletes with differential antibiotic use at baseline were administered Immediate Post-concussion Assessment and Cognitive Testing at baseline and twice postinjury. Chronic antibiotic use was associated with a reduced risk for concussion (odds ratio 0.54), increased postconcussive symptomology and neurocognitive burden, and improved recovery by follow-up, a median of 7 days after concussion. This preliminary retrospective analysis suggests antibiotic use may impart neuroprotection up to a certain severity threshold, leading to fewer, yet more severe concussions that tend to recover faster.

Redox nanodrugs alleviate chronic kidney disease by reducing inflammation and regulating ROS.

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn3O4 nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn3O4 NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn3O4 NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn3O4 protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.

Treatment with Rapamycin in Animal Models of Traumatic Brain Injuries; a Systematic Review and Meta-Analysis.

In light of the potential of enhanced functional and neurological recovery in traumatic brain injury (TBI) with the administration of rapamycin, this systematic review and meta-analysis aimed to investigate the efficacy of rapamycin treatment in animal models of TBI. An extensive search was conducted in the electronic databases of Medline, Embase, Scopus, and Web of Science by July 1st, 2023. Two independent researchers performed the screening process by reviewing the titles and abstracts and the full texts of the relevant articles, including those meeting the inclusion criteria. Apoptosis rate, inflammation, locomotion, and neurological status were assessed as outcomes. A standardized mean difference (SMD) with a 95% confidence interval (95%CI) was calculated for each experiment, and a pooled effect size was reported. Statistical analyses were performed using STATA 17.0 software. Twelve articles were deemed eligible for inclusion in this meta-analysis. Pooled data analysis indicated notable reductions in the number of apoptotic cells (SMD for Tunnel-positive cells = -1.60; 95%CI: -2.21, -0.99, p<0.001), p-mTOR (SMD=-1.41; 95%CI: -2.03, -0.80, p<0.001), and p-S6 (SMD=-2.27; 95%CI: -3.03, -1.50, p<0.001) in TBI post-treatment. Our analysis also indicated substantial IL-1β reductions after rapamycin administration (SMD= -1.91; 95%CI: -2.61, -1.21, p<0.001). Moreover, pooled data analysis found significant neurological severity score (NSS) improvements at 24 hours (SMD= -1.16; 95%CI: -1.69, -0.62, p<0.001; I²=0.00%), 72 hours (SMD= -1.44; 95%CI: -2.00, -0.88, p<0.001; I²=0.00%), and 168 hours post-TBI (SMD= -1.56; 95%CI: -2.44, -0.68, p<0.001; I²=63.37%). No such improvement was observed in the grip test. Low to moderate-level evidence demonstrated a significant decrease in apoptotic and inflammatory markers and improved neurological status in rodents with TBI. However, no such improvements were observed in locomotion recovery.

Xenogenic Application of Human Placenta-Derived Mesenchymal Stromal Cells in a Porcine Large Animal Model.

In animal models, cell therapies for different diseases or injuries have been very successful. Preclinical studies with cells aiming at a stroke, heart attack, and other emergency situations were promising but sometimes failed translation in clinical situations. We, therefore, investigated if human placenta-derived mesenchymal stromal cells can be injected in pigs without provoking rejection to serve as a xenogenic transplantation model to bridge preclinical animal studies to more promising future preclinical studies. Male human placenta-derived mesenchymal stromal cells were isolated, expanded, and characterized by flow cytometry, in vitro differentiation, and quantitative reverse-transcription polymerase chain reaction to prove their nature. Such cells were injected into the sphincter muscle of the urethrae of female pigs under visual control by cystoscopy employing a Williams needle. The animals were observed over 7 days of follow-up. Reactions of the host to the xenogeneic cells were explored by monitoring body temperature, and inflammatory markers including IL-1ß, CRP, and haptoglobin in blood. After sacrifice on day 7, infiltration of inflammatory cells in the tissue targeted was investigated by histology and immunofluorescence. DNA of injected human cells was detected by PCR. Upon injection in vascularized porcine tissue, human placenta-derived mesenchymal stromal cells were tolerated, and systemic inflammatory parameters were not elevated. DNA of injected cells was detected in situ 7 days after injection, and moderate local infiltration of inflammatory cells was observed. The therapeutic potential of human placenta-derived mesenchymal stromal cells can be explored in porcine large animal models of injury or disease. This seems a promising strategy to explore technologies for cell injections in infarcted hearts or small organs and tissues in therapeutically relevant amounts requiring large animal models to yield meaningful outcomes.

Creating a Reproducible Model of Spinal Cord Injury in Rats: A Contusion Approach.

Spinal cord injury (SCI) is a devastating clinical condition that affects millions of people worldwide. SCI primarily affects males in younger age groups. It is characterized by a complex of neurological dysfunctions that can lead to permanent disability. We describe an adapted technique for SCI, i.e., a contusion model of SCI, in this chapter. This model is widely used to study the pathology of SCI and test potential therapies. The experimental contusion is performed by using a compression device, which allows the creation of a reproducible injury animal model through the definition of specific injury parameters. A detailed methodology has been developed and described here that utilizes a stereotactic frame and impactor to produce reproducible injuries.

Polypathologies and Animal Models of Traumatic Brain Injury.

Traumatic brain injury (TBI) is an important health issue for the worldwide population, as it causes long-term pathological consequences for a diverse group of individuals. We are yet to fully elucidate the significance of TBI polypathologies, such as neuroinflammation and tau hyperphosphorylation, and their contribution to the development of chronic traumatic encephalopathy (CTE) and other neurological conditions. To advance our understanding of TBI, it is necessary to replicate TBI in preclinical models. Commonly used animal models include the weight drop model; these methods model human TBI in various ways and in different animal species. However, animal models have not demonstrated their clinical utility for identifying therapeutic interventions. Many interventions that were successful in improving outcomes for animal models did not translate into clinical benefit for patients. It is important to review current animal models and discuss their strengths and limitations within a TBI context. Modelling human TBI in animals encounters numerous challenges, yet despite these barriers, the TBI research community is working to overcome these difficulties. Developments include advances in biomarkers, standardising, and refining existing models. This progress will improve our ability to model TBI in animals and, therefore, enhance our understanding of TBI and, potentially, how to treat it.

Intravenous administration of human chorionic membrane mesenchymal stem cells promotes functional recovery in a rat traumatic brain injury model.

Human chorionic membrane mesenchymal stem cells (hCM-MSCs) have increasingly emerged as an excellent source of transplanted cells for regenerative therapy as they can be isolated via a non-invasive and simple method with high proliferative capabilities. However, the roles and mechanisms of hCM-MSCs on traumatic brain injury (TBI) animal models have not been investigated yet. The aim of this study was to investigate the therapeutic potential and mechanism of hCM-MSCs transplantation in a rat model of TBI. Adult male Sprague-Dawley rats were subjected to moderate lateral fluid percussion-induced TBI. At 2 h after TBI, hCM-MSCs, or PBS were administered intravenously via the tail vein. Neurological function, brain water content, Evans blue dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were evaluated. The results showed that transplanted hCM-MSCs were observed in the injured brain. Compared with the PBS group, hCM-MSCs treatment significantly decreased the numbers of M1 macrophages/microglia, MPO + neutrophils and caspase-3 + cells ( P < 0.01). Meanwhile, hCM-MSCs treatment significantly reduced the expression levels of the pro-inflammatory cytokines (TNF-α, interleukin-(IL)6 and IL-1β) while increasing the numbers of M2 macrophages/microglia and the expression of the anti-inflammatory cytokines IL-10 ( P < 0.01). In addition, hCM-MSCs treatment significantly reduced brain water content and Evans blue extravasation. Lastly, hCM-MSCs treatment significantly promoted neurogenesis and angiogenesis, and attenuated neurological deficits. Collectively, these findings indicate that hCM-MSCs exhibited effective therapeutic efficacy in a rat TBI model, and its mechanism may be by reducing inflammation, apoptosis and the blood-brain barrier disruption, promoting angiogenesis and neurogenesis.

Screening of potent RIPK3 inhibitors to attenuate necroptosis and inflammation in mouse traumatic brain injury models

Necroptosis is a type of cell death that occurs when cells are exposed to external stressors such as inflammation, infections, or injury. In necroptosis, cells use a different set of proteins including: receptor-interacting kinase 1 (RIPK1 or RIP1), receptor-interacting kinase 3 (RIPK3 or RIP3) and the phosphorylation of its substrate mixed lineage kinase domain-like protein (MLKL) and pathways to trigger their own death. Mutations in the gene encoding RIPK3 have been associated with many diseases, including neurodegenerative diseases, neuroinflammatory diseases, inflammatory diseases，tumors, and it is being studied as a potential target for inflammatory injury therapy. RIPK3 has also been implicated in the pathology of neuroinflammation following Traumatic brain injury and is currently being explored as a potential therapy. We screened through necroptosis blocking compounds, a library of FDA-approved compounds. We found four compounds:1D6-Foretinib GSK1363089; 15F6-Poziotinib (HM781-36B); 15F9-Dasatinib monohydrate; 15A10-Pexmetinib (ARRY-614); acts as potent inhibitors of necroptosis (Necroptosis Blocking Compounds, NBCs) by blocking the RIPK3 kinase activity. These four compounds effectively block necroptosis induced by death receptor ligands Toll-like receptors as well as viral infections in human, rat and mouse cells. The cellular activation of RIPK3 and MLKL stimulated by necroptosis was strongly inhibited by NBCs. The compounds are promising for targeting RIPK3 kinase activity, thereby preventing necroptosis and inflammatory responses. In our study, we explored the role of NBCs in neuroprotection after traumatic brain injury. It's effectiveness in traumatic brain injury animal models and favorable safety profiles make it a potential candidate for the advances of new therapies for necroptosis-associated neuroinflammatory disorders.

Grapevine Shoot Extract Rich in Trans-Resveratrol and Trans-ε-Viniferin: Evaluation of Their Potential Use for Cardiac Health.

A grapevine shoot extract (GSE) was obtained using ultrasound-assisted extraction and characterized. The main phenolic constituents were identified as stilbenoids. Among them, trans-resveratrol and trans-ε-viniferin stood out. The GSE was administered to an isoproterenol-induced myocardial injury animal model. The extract alleviated the associated symptoms of the administration of the drug, i.e., the plasma lipid profile was improved, while the disturbed plasma ion concentration, the cardiac dysfunction markers, the DNA laddering, and the necrosis of myocardial tissue were diminished. This effect could be related to the anti-oxidative potential of GSE associated with its antioxidant properties, the increased levels of endogenous antioxidants (glutathione and enzymatic antioxidants), and the diminished lipid peroxidative markers in the heart. The results also revealed angiotensin-converting enzyme (ACE)-inhibitory activity, which indicated the potential of GSE to deal with cardiovascular disease events. This work suggests that not only trans-resveratrol has a protective role in heart function but also GSE containing this biomolecule and derivatives. Therefore, GSE has the potential to be utilized in the creation of innovative functional ingredients.

Mechanisms of Wharton’s Jelly-derived MSCs in enhancing peripheral nerve regeneration

Warton’s jelly-derived Mesenchymal stem cells (WJ-MSCs) play key roles in improving nerve regeneration in acellular nerve grafts (ANGs); however, the mechanism of WJ-MSCs-related nerve regeneration remains unclear. This study investigated how WJ-MSCs contribute to peripheral nerve regeneration by examining immunomodulatory and paracrine effects, and differentiation potential. To this end, WJ-MSCs were isolated from umbilical cords, and ANGs (control) or WJ-MSCs-loaded ANGs (WJ-MSCs group) were transplanted in injury animal model. Functional recovery was evaluated by ankle angle and tetanic force measurements up to 16 weeks post-surgery. Tissue biopsies at 3, 7, and 14 days post-transplantation were used to analyze macrophage markers and interleukin (IL) levels, paracrine effects, and MSC differentiation potential by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The WJ-MSCs group showed significantly higher ankle angle at 4 weeks and higher isometric tetanic force at 16 weeks, and increased expression of CD206 and IL10 at 7 or 14 days than the control group. Increased levels of neurotrophic and vascular growth factors were observed at 14 days. The WJ-MSCs group showed higher expression levels of S100β; however, the co-staining of human nuclei was faint. This study demonstrates that WJ-MSCs' immunomodulation and paracrine actions contribute to peripheral nerve regeneration more than their differentiation potential.

First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung.

Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats.

Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of β-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/β-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/β-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/β-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/β-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.

Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries

Over 3 million people in the United States live with long-term disability because of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50–75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. A unilateral (left directed) blast and repeat blast model injury with coup-contra-coup injury patterns were compared to a midline blunt injury. Injuries were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to the right optic chiasm and tract whereas bilateral injury follows a single blunt TBI. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by amyloid precursor protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm ahead of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggests that there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.

Enhancing biofilm penetration and antibiofilm efficacy with protein nanocarriers against pathogenic biofilms

Nanocarriers play an important role in enhancing the efficacy of antibiotics against biofilms by improving their penetration and prolonging retention in pathogenic biofilms. Herein, the multifunctional nanocarriers including nanospheres (NS) and nanotubes (NT) with a high biocompatibility and biodegradability were prepared through self-assembly of partially hydrolyzed α-lactalbumin. The effects of these two different shaped nanocarriers on the delivery of antibiotics for biofilm treatment were examined by conducting in vitro antibiofilm experiment and in vivo infected wound model. The strong affinity of NS and NT for the bacterial surface allows antibiotics to be concentrated in the bacteria. Notably, the high permeability of NT into biofilms facilitates deeper penetration and the easier diffusion of loaded antibiotics within the biofilm. Furthermore, the acidic biofilm environment triggers the release of antibiotics from the NT, resulting in the accumulation of high local antibiotic concentrations. Therefore, NT could efficiently clean and inhibit the biofilm formation while also destroying the mature biofilms. In a S. aureus infected wound animal model, treatment with antibiotic-loaded NT demonstrated accelerated healing of S. aureus infected wounds when compared to free antibiotic treatment. These findings indicate that NT nanocarrier strategy is promising for treating bacterial biofilm infections, offering the potential for lower antibiotics dosages and preventing the overuse of antibiotics.

Research progress on animal models of corneal epithelial-stromal injury.

A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring. Given the rising prevalence of blindness caused by corneal scarring, increasing attention has been focused on corneal epithelial-stromal defects. Currently, the etiology and pathogenesis of these defects remain inadequately understood, necessitating further investigation through experimental research. Various modeling methods exist both domestically and internationally, each with distinct adaptive conditions, advantages, and disadvantages. This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury, including mechanical modeling, chemical alkali burns, post-refractive surgery infections, and genetic engineering. The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.

Efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models: a systematic review protocol

BackgroundWounds inflict pain and affect human health causing high expenditure on treatment and management. Herbal crude extracts are used in traditional medicine as a treatment for wounds and other illnesses. However, the progress in the use of plants has been deterred due to their poor solubility and poor bioavailability requiring administration at high doses. It has been established that nanoencapsulation of herbal products in nanocarriers (size 1 nm to 100 nm) such as nanofibers, nanoparticles, nanospheres, and nanoliposomes greatly improves their efficacy. Due to their small and large surface area, nanocarriers are more biologically active, improve bioavailability, protect the drug from deterioration, and release it to the targeted site in a sustainable manner.AimThe review aims to collate and appraise evidence on the efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models.MethodsThe review will be protocol-driven and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) and protocol guidelines for systematic review and meta-analysis for animal intervention studies. The final review will be conducted and reported with reference to PRISMA 2020 statement. Studies will be searched in Pub Med, ProQuest, Web of Science, Medline Ovid, EMBASE, and Google Scholar. The PRISMA flow criteria will be followed in screening the articles for inclusion. Data extraction form will be designed in Excel spreadsheet 2013 and data extracted based on the primary and secondary outcomes. Risk of bias assessment will be done using SYRCLE’s risk of bias tool for animal studies. Data analysis will be done using narrative and quantitative synthesis.Expected resultsWe hope to make meaningful comparisons between the effectiveness of the herb-loaded nanomaterials and other interventions (controls) in the selected studies, based on the primary and secondary outcome measures. We expect that these findings to inform clinical practice on whether preclinical studies show enough quality evidence on the efficacy and safety of herbal-loaded nanomaterials that can be translated into clinical trials and further research.Systemic review registrationPROSPERO 330330. The protocol was submitted on the 11th of May 2022.

Protective effect of Tibetan medicine Qiwei Tiexie pills on liver injury induced by acetaminophen overdose: an integrated strategy of network pharmacology, metabolomics and transcriptomics

BackgroundDrug-induced liver injury, particularly from acetaminophen (APAP), has emerged as a significant public health concern. Unfortunately, there is currently no effective treatment strategy available. Qiwei Tiexie pills (QWTX), a traditional Tibetan medicine, have demonstrated considerable clinical efficacy in treating various liver diseases. Nevertheless, the protective effect of QWTX against drug-induced liver injury and its underlying mechanism remains poorly understood. PurposeThis study aimed to assess the therapeutic potential of QWTX, a Tibetan medicine, in an animal model of APAP-induced liver injury. Additionally, we sought to investigate the molecular mechanism through which QWTX exerts its effects. MethodsWe employed LC-MS and network pharmacology to predict the potential targets of QWTX in drug-induced liver injury. Subsequently, we employed HE staining, transcriptomics, metabolomics, and qRT-PCR to analyze the mechanism underlying QWTX treatment in drug-induced liver injury. ResultsNetwork pharmacology analysis revealed that the active components of QWTX are involved in inflammatory and drug metabolism-related pathways. In mouse models, pretreatment with QWTX effectively mitigated the elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory factors (IL-1β, IL-6, and TNF-α) induced by APAP overdose. Moreover, APAP inhibited 1459 differentially expressed genes (DEGs) and 874 differential accumulation metabolites (DAMs), while QWTX promoted their expression. Conversely, APAP promoted 874 genes and 119 metabolites, which were inhibited by QWTX. Further analysis demonstrated that QWTX ameliorated the metabolic disorders induced by APAP overdose and potentially exerted a protective effect by inhibiting the expression of critical genes in crucial inflammatory pathways. QWTX also up-regulated antioxidant enzymes, thereby mitigating the oxidative stress resulting from APAP overdose. ConclusionQWTX treatment effectively protects against APAP-induced liver damage in mice. Transcriptomic and metabolomic analyses further revealed that QWTX ameliorated hepatic metabolic disorders induced by APAP overdose while significantly suppressing the inflammatory response and oxidative stress associated with drug-induced liver injury. This study provides a new insight into the treatment of drug-induced liver injury by the TCM system and provides a basis for the development of new therapies for drug-induced liver injury by QWTX and its active ingredients.

Protective Effect of Silymarin on Attenuating of Rhabdomyolysis -induced Acute Kidney Injury in Animal Models

Acute kidney injury is one of the most serious complications of rhabdomyolysis characterized by an acute loss of renal function. The study aims to investigate the renoprotective effect of silymarin against rhabdomyolysis-induced acute kidney injury in rats. Twenty-four healthy rats were equally divided into three groups: control, induction, and treatment groups. Rats in the control and induction groups received distilled water, while rats in the treatment group received silymarin (50 mg /kg/day p.o) for three consecutive days. On the first day, all rats (except rats of control group) received a single intramuscular injection of glycerol (10 mL/kg, 50% v/v in sterile saline) divided equally into each hind leg for induction of acute kidney injury. On the fourth day of experiment, blood and kidney,s were collected from all rats for biochemical and histopathological assay. Silymarin efficiently attenuated acute kidney injury caused by rhabdomyolysis evidenced by a significant decrease in serum creatinine and blood urea nitrogen(BUN), along with a significant reduction in renal homogenate levels of TNF-α, IL-6, NF-κB, caspase-3, and MDA with a significant increase in GSH level, which was further confirmed by improving renal histological changes when compared to that of induction group. This study found that silymarin has a potential attenuating effect on acute kidney injury due to its antioxidant, anti-inflammatory and antiapoptotic actions.

Role of macrophage-to-myofibroblast transition in chronic liver injury and liver fibrosis

BackgroundChronic liver injury contributes to liver fibrosis, which is characterized by the excessive deposition of extracellular matrix (ECM) components. ECM is mainly composed of myofibroblasts. Recently, macrophage-to-myofibroblasts transition (MMT), has been identified as a novel origin for myofibroblasts. However, the potential functions of MMT in chronic liver injury and liver fibrosis remain unknown.MethodsTo clarify the transformation of fibrotic cells in hepatic fibrosis, liver specimens were collected from people at different stages in the progression of hepatic fibrosis and stained with immunofluorescence. Models of hepatic fibrosis such as the CCL4 model, HFD-induced NAFLD model, MCD-induced NAFLD model and ethanol-induced AFLD model were demonstrated and were stained with immunofluorescence.ResultsHere, we uncovered macrophages underwent MMT in clinical liver fibrosis tissue samples and multiple animal models of chronic liver injury. MMT cells were found in specimens from patients with liver fibrosis on the basis of co-expression of macrophage (CD68) and myofibroblast (a-SMA) markers. Moreover, macrophages could transform into myofibroblasts in CCL4-induced liver fibrosis model, high-fat diet (HFD) and methionine-choline-deficient diet (MCD)-induced nonalcoholic fatty liver diseases (NAFLD) model, and ethanol-induced alcoholic fatty liver diseases (AFLD) model. In addition, we highlighted that MMT cells mainly had a predominant M2 phenotype in both human and experimental chronic liver injury.ConclusionsTaken together, MMT acts a crucial role in chronic liver injury and liver fibrosis.