Studies In Animal Models Research Articles

Non-Host Factors Influencing Onset and Severity of Celiac Disease

Celiac Disease (CeD) is a chronic autoimmune condition driven by gluten ingestion in genetically predisposed individuals, resulting in inflammatory lesions in the proximal small intestine. While the presence of specific human leukocyte antigen (HLA) linked haplotypes and gluten consumption are necessary for disease development, they alone do not account for the variable onset of CeD in susceptible individuals. This review explores the multifaceted role of non-host factors in CeD development, including dietary and microbial influences. We discuss clinical associations and observations highlighting the impact of these factors on disease onset and severity. Furthermore, we discuss studies in CeD-relevant animal models that offer mechanistic insights into how diet, the microbiome, and enteric infections modulate CeD pathogenesis. Finally, we address the clinical implications and therapeutic potential of understanding these cofactors, offering a promising avenue for preventive and therapeutic interventions in CeD management.

Research advances of Zanthoxylum bungeanum Maxim. polyphenols in inflammatory diseases.

Zanthoxylum bungeanum Maxim., commonly known as Chinese prickly ash, is a well-known spice and traditional Chinese medicine ingredient with a rich history of use in treating inflammatory conditions. This review provides a comprehensive overview of the botanical classification, traditional applications, and anti-inflammatory effects of Z. bungeanum, with a specific focus on its polyphenolic components. These polyphenols have exhibited considerable promise, as evidenced by preclinical studies in animal models, suggesting their therapeutic potential in human inflammatory diseases such as ulcerative colitis, arthritis, asthma, chronic obstructive pulmonary disease, cardiovascular disease, and neurodegenerative conditions. This positions them as a promising class of natural compounds with the potential to enhance human well-being. However, further research is necessary to fully elucidate their mechanisms of action and develop safe and effective therapeutic applications.

Comparative efficacy of Salix aegyptiaca's active compound versus phenytoin in healing full-thickness rat skin wounds: An animal model study

BackgroundWound healing poses a challenging therapeutic scenario, requiring diverse clinical approaches. ObjectivesThis study aims to assess the wound-healing potential of Salix aegyptiaca's flower ointment compared to phenytoin, considering the active constituents of S. aegyptiaca and its traditional usage. MethodsInitially, the active components of S. aegyptiaca were isolated and identified through the GC-MS technique. Subsequently, for the experimental intervention, thirty-five rats were divided into five distinct groups: control (C), phenytoin (F), and three S. aegyptiaca ointment groups at different concentrations (5 % - S5, 25 % - S25, and 50 % - S50). Anesthesia was administered, and wounds were induced on the animals' necks following a standard procedure. These wounds were then treated for a duration of 21 days. Wound healing progress was quantified, and histopathological assessments were conducted using hematoxylin and eosin staining and Mason's trichrome staining. ResultsThe main active compounds of S. aegyptiaca, namely n-hexadecanoic acid and oleic acid, were identified via GC-MS analysis. Although the initial group weights did not show a significant difference (P = 0.271), a significant variation was observed in the final weights (P = 0.003). The S50 group exhibited a lower wound healing rate than the S25 group on the 7th and 14th days but surpassed it on the 21st day (C < F < S5≈S25<S50). Pathological analysis of the S50 group revealed advanced re-epithelialization, heightened skin regeneration, increased angiogenesis, folliculogenesis, more orderly collagen fibers, and a marked reduction in cellular infiltration compared to the F group. ConclusionThe findings highlight the superior wound-healing efficacy of 50 % S. aegyptiaca ointment over phenytoin ointment.

Mild cognitive impairment in Huntington's disease: challenges and outlooks.

Although Huntington's disease (HD) has classically been viewed as an autosomal-dominant inherited neurodegenerative motor disorder, cognitive and/or behavioral changes are predominant and often an early manifestation of disease. About 40% of individuals in the presymptomatic period of HD meet the criteria for mild cognitive impairment, later progressing to dementia. The heterogenous spectrum of cognitive decline is characterized by deficits across multiple domains, particularly executive dysfunctions, but the underlying pathogenic mechanisms are still poorly understood. Investigating the pathophysiology of cognitive changes may give insight into important and early neurodegenerative events. Multimodal imaging revealed circuit-wide gray and white matter degenerative processes in several key brain regions, affecting prefronto-striatal/cortico-basal ganglia circuits and many other functional brain networks. Studies in transgenic animal models indicated early synaptic dysfunction, deficient neurotrophic transport and other molecular changes contributing to neuronal death. Synaptopathy within the cerebral cortex, striatum and hippocampus may be particularly important in mediating cognitive and neuropsychiatric manifestations of HD, although many other neuronal systems are involved. The interaction of mutant huntingtin protein (mHTT) with tau and its implication for cognitive impairment in HD is a matter of discussion. Further neuroimaging and neuropathological studies are warranted to better elucidate early pathophysiological mechanisms and to develop validated biomarkers to detect patients' cognitive status during the early stages of the condition significantly to implement effective preventing or management strategies.

Action of Curcumin on Glioblastoma Growth: A Systematic Review with Meta-Analysis of Animal Model Studies.

Gliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several preclinical studies evaluating the anticancer effect of curcumin in animal models of glioma are reported, but a systematic review with meta-analysis of these studies, considering the different experimental conditions used, has not been made up to this date. A search in different databases (Pubmed, Web of Science, Scopus, and SciELO) following the PRISMA statement was conducted during November 2023 to systematically identify articles assessing the effect of curcumin in murine xenograft models of glioma and identified 15 articles, which were subdivided into 24 studies. Tumor volume before and after treatment with curcumin or vehicle was extracted and the efficacy of curcumin was evaluated by performing a random effects meta-analysis of the data. Publication bias and the impact of different experimental conditions on curcumin efficacy were assessed. Treatment with curcumin decreased tumor volume. Comparing curcumin with control groups, the overall weighted standardized difference in means was -2.079 (95% CI: -2.816 to -1.341; p-value < 0.001). The curcumin effect was observed for different animal models, types of glioma cells, administration routes, and curcumin formulations. Publication bias was identified but does not invalidate curcumin's effectiveness. The findings suggest the potential therapeutic efficacy of curcumin against glioma.

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective.

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem-cell niches in the marrow. Stem-cell niches, in particular, can be altered by the effects of previous treatments, aging, and the paracrine effects of leukemic cells, which create inhospitable bone-marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem-cell niches can be restored to favor normal hematopoiesis may be key to reducing leukemic relapses following transplant.

Keratinocyte Exosomes for Topical Delivery of Tofacitinib in Treatment of Psoriasis: an In Vitro/ In Vivo Study in Animal Model of Psoriasis

IntroductionExosomes are extracellular vesicles in the range of 40-150 nm released from the cell membrane. Exosomes secreted by keratinocytes can communicate with other keratinocytes and immune cells with specific biomarkers at their surface, which may be effective on inflammation of psoriasis and its pathogenesis.ObjectiveThe present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC).MethodsTFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms.ResultsExosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC.ConclusionsThis method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration.Graphical abstract

Trametinib ameliorates aging-associated gut pathology in Drosophila females by reducing Pol III activity in intestinal stem cells

Pharmacological therapies are promising interventions to slow down aging and reduce multimorbidity in the elderly. Studies in animal models are the first step toward translation of candidate molecules into human therapies, as they aim to elucidate the molecular pathways, cellular mechanisms, and tissue pathologies involved in the anti-aging effects. Trametinib, an allosteric inhibitor of MEK within the Ras/MAPK (Ras/Mitogen-Activated Protein Kinase) pathway and currently used as an anti-cancer treatment, emerged as a geroprotector candidate because it extended lifespan in the fruit fly Drosophila melanogaster. Here, we confirm that trametinib consistently and robustly extends female lifespan, and reduces intestinal stem cell (ISC) proliferation, tumor formation, tissue dysplasia, and barrier disruption in guts in aged flies. In contrast, pro-longevity effects of trametinib are weak and inconsistent in males, and it does not influence gut homeostasis. Inhibition of the Ras/MAPK pathway specifically in ISCs is sufficient to partially recapitulate the effects of trametinib. Moreover, in ISCs, trametinib decreases the activity of the RNA polymerase III (Pol III), a conserved enzyme synthesizing transfer RNAs and other short, non-coding RNAs, and whose inhibition also extends lifespan and reduces gut pathology. Finally, we show that the pro-longevity effect of trametinib in ISCs is partially mediated by Maf1, a repressor of Pol III, suggesting a life-limiting Ras/MAPK-Maf1-Pol III axis in these cells. The mechanism of action described in this work paves the way for further studies on the anti-aging effects of trametinib in mammals and shows its potential for clinical application in humans.

Sudapyridine (WX-081) antibacterial activity against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo.

Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000-2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

Investigation, scaffold hopping of novel donepezil-based compounds as anti-Alzhiemer's agents: synthesis, in-silico and pharmacological evaluations.

Alzheimer's disease (AD) is a multifaceted neurodegenerative condition. The pathogenesis of AD is highly intricate and the disease is apparent in the aged population ~ 50-70years old. Even after > 100years of research, the root origin of AD and its pathogenesis is unclear, complex and multifaceted. Herein, we have designed and synthesized 9 novel molecules with three different heterocyclic scaffolds namely pyrrolidone-2-one, quinoline & indoline-2-one to imitate and explore the novel chemical space around donepezil. The synthesized molecules were evaluated for their potential as anti-Alzheimer's agents through in-vitro and in-vivo studies in appropriate animal models. To further understand their interaction with acetylcholinesterase enzyme (AChE), extra-precision docking, and molecular dynamics simulation studies were carried out. As the number of compounds was limited to thoroughly explore the structure-activity relationship, atom-based 3D-quantitative structure-activity relationships (QSAR) studies were carried out to get more insights. All the designed compounds were found to inhibit AChE with IC50 in the micromolar range. From pyrrolidone-2-one series, 6-chloro-N-(1-(1-(3,4-dimethoxybenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)pyridine-3-sulfonamide (9), 2-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-4-(4-methoxyphenyl)quinoline (18) from quinoline series and N-(1-benzylpiperidin-4-yl)-2-(2-oxoindolin-3-yl)acetamide (23) from indolin-2-one series inhibited AChE with an IC50 value of 0.01µM. Based on other biochemical studies like lipid peroxidation, reduced glutathione, superoxide dismutase, catalase, nitrite, and behavioural studies (Morris water maze), compound 9 was found to be a potent AChE inhibitor which can be further explored as a lead molecule to design more potent and effective anti-Alzheimer's agents.

Chronic and acute exposure to rotenone reveals distinct Parkinson's disease-related phenotypes in human iPSC-derived peripheral neurons

Peripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority of PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological and animal model studies suggest an association with pesticides and other environmental toxins. However, the cellular mechanisms underlying toxin induced P-ANS dysfunctions remain unclear. Here, we mapped the global transcriptome changes in human induced pluripotent stem cell (iPSC) derived P-ANS sympathetic neurons during inhibition of the mitochondrial respiratory chain by the PD-related pesticide, rotenone. We revealed distinct transcriptome profiles between acute and chronic exposure to rotenone. In the acute stage, there was a down regulation of specific cation channel genes, known to mediate electrophysiological activity, while in the chronic stage, the human P-ANS neurons exhibited dysregulation of anti-apoptotic and Golgi apparatus-related pathways. Moreover, we identified the sodium voltage-gated channel subunit SCN3A/Nav1.3 as a potential biomarker in human P-ANS neurons associated with PD. Our analysis of the rotenone-altered coding and non-coding transcriptome of human P-ANS neurons may thus provide insight into the pathological signaling events in the sympathetic neurons during PD progression.

Modeling of inflicted head injury by shaking trauma in children: what can we learn? : Update to parts I&II: A systematic review of animal, mathematical and physical models.

Inflicted shaking trauma can cause injury in infants, but exact injury mechanisms remain unclear. Controversy exists, particularly in courts, whether additional causes such as impact are required to produce injuries found in cases of (suspected) shaking. Publication rates of studies on animal and biomechanical models of inflicted head injury by shaking trauma (IHI-ST) in infants continue rising. Dissention on the topic, combined with its legal relevance, makes maintaining an up-to-date, clear and accessible overview of the current knowledge-base on IHI-ST essential. The current work reviews recent (2017-2023) studies using models of IHI-ST, serving as an update to two previously published reviews. A systematic review was conducted in Scopus and PubMed for articles using animal, physical and mathematical models for IHI-ST. Using the PRISMA methodology, two researchers independently screened the publications. Two, five, and ten publications were included on animal, physical, and mathematical models of IHI-ST, respectively. Both animal model studies used rodents. It is unknown to what degree these can accurately represent IHI-ST. Physical models were used mostly to investigate gross head-kinematics during shaking. Most mathematical models were used to study local effects on the eye and the head's internal structures. All injury thresholds and material properties used were based on scaled adult or animal data. Shaking motions used as inputs for animal, physical and mathematical models were mostly greatly simplified. Future research should focus on using more accurate shaking inputs for models, and on developing or and validating accurate injury thresholds applicable for shaking.

SARS-CoV-2 immunity in animal models.

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals. These complications encompass symptoms such as coughing, respiratory distress, fever, infectious shock, acute respiratory distress syndrome (ARDS), and even multiple-organ failure. Animal models serve as crucial tools for investigating pathogenic mechanisms, immune responses, immune escape mechanisms, antiviral drug development, and vaccines against SARS-CoV-2. Currently, various animal models for SARS-CoV-2 infection, such as nonhuman primates (NHPs), ferrets, hamsters, and many different mouse models, have been developed. Each model possesses distinctive features and applications. In this review, we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection, as well as the corresponding immune responses and applications of these models. A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients. Finally, we highlighted the current gaps in related research between animal model studies and clinical investigations, underscoring lingering scientific questions that demand further clarification.

Mechanisms of 5-HT receptor antagonists in the regulation of fibrosis in a 3D human liver spheroid model

Non-alcoholic steatohepatitis (NASH) is a major health problem leading to liver fibrosis and hepatocellular carcinoma, among other diseases, and for which there is still no approved drug treatment. Previous studies in animal models and in LX-2 cells have indicated a role for serotonin (5-HT) and 5-HT receptors in stellate cell activation and the development of NASH. In the current study, we investigated the extent to which these findings are applicable to a human NASH in vitro model consisting of human liver spheroids containing hepatocytes and non-parenchymal cells. Treatment of the spheroids with 5-HT or free fatty acids (FFA) induced fibrosis, whereas treatment of the spheroids with the 5-HT receptor antagonists ketanserin, pimavanserin, sarpogrelate, and SB269970 inhibited FFA-induced fibrosis via a reduction in stellate cell activation as determined by the expression of vimentin, TGF-β1 and COL1A1 production. siRNA-based silencing of 5-HT2A receptor expression reduced the anti-fibrotic properties of ketanserin, suggesting a role for 5-HT receptors in general and 5-HT2A receptors in particular in the FFA-mediated increase in fibrosis in the human liver spheroid model. The results suggest a contribution of the 5-HT receptors in the development of FFA-induced human liver fibrosis with implications for further efforts in drug development.

Tryptophan intake and pancreatic cancer: findings from a case-control study.

Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors. Limited data are available assessing the association between tryptophan intake and risk of pancreatic cancer. We aimed to evaluate this association in a case-control study in Vietnam. We analyzed data from a case-control study, including 3759 cancer cases and 2995 control subjects of whom 37 with pancreatic cancer cases. Tryptophan intake was derived from food frequency questionnaire. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for different levels of tryptophan intake with pancreatic cancer risk. Overall, tryptophan intake was inversely associated with pancreatic cancer risk in a dose-dependent manner. The ORs and 95% CIs of pancreatic cancer were 0.51 (0.29-0.92) for continuous scale, 0.27 (0.10-0.73) for tertile 2 and 0.34 (0.11-1.06) for tertile 3, compared with tertile 1 (the lowest intake) ( Ptrend = 0.02). In stratified analysis, this inverse association pattern was present among those with BMI < 23 kg/m 2 and ever drinkers. A diet with a higher intake of tryptophan was significantly associated with a lower incidence of pancreatic cancer among Vietnamese population. These suggest that dietary modification may be an effective strategy for primary prevention of pancreatic cancer development.

Optimization of a Photobiomodulation Protocol to Improve the Cell Viability, Proliferation and Protein Expression in Osteoblasts and Periodontal Ligament Fibroblasts for Accelerated Orthodontic Treatment.

Numerous pieces of evidence have supported the therapeutic potential of photobiomodulation (PBM) to modulate bone remodeling on mechanically stimulated teeth, proving PBM's ability to be used as a coadjuvant treatment to accelerate orthodontic tooth movement (OTM). However, there are still uncertainty and discourse around the optimal PBM protocols, which hampers its optimal and consolidated clinical applicability. Given the differential expression and metabolic patterns exhibited in the tension and compression sides of orthodontically stressed teeth, it is plausible that different types of irradiation may be applied to each side of the teeth. In this sense, this study aimed to design and implement an optimization protocol to find the most appropriate PBM parameters to stimulate specific bone turnover processes. To this end, three levels of wavelength (655, 810 and 940 nm), two power densities (5 and 10 mW/cm2) and two regimens of single and multiple sessions within three consecutive days were tested. The biological response of osteoblasts and periodontal ligament (PDL) fibroblasts was addressed by monitoring the PBM's impact on the cellular metabolic activity, as well as on key bone remodeling mediators, including alkaline phosphatase (ALP), osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANK-L), each day. The results suggest that daily irradiation of 655 nm delivered at 10 mW/cm2, as well as 810 and 940 nm light at 5 mW/cm2, lead to an increase in ALP and OPG, potentiating bone formation. In addition, irradiation of 810 nm at 5 mW/cm2 delivered for two consecutive days and suspended by the third day promotes a downregulation of OPG expression and a slight non-significant increase in RANK-L expression, being suitable to stimulate bone resorption. Future studies in animal models may clarify the impact of PBM on bone formation and resorption mediators for longer periods and address the possibility of testing different stimulation periodicities. The present in vitro study offers valuable insights into the effectiveness of specific PBM protocols to promote osteogenic and osteoclastogenesis responses and therefore its potential to stimulate bone formation on the tension side and bone resorption on the compression side of orthodontically stressed teeth.

Enhancing Spermatogenesis in Non-obstructive Azoospermia Through Mesenchymal Stem Cell Therapy22.

Stem cells hold great promise as novel and encouraging therapeutic tools in the treatment of degenerative disorders due to their differentiation potential while maintaining the capability to self-renewal and their unlimited ability to divide and regenerate tissue. A variety of different types of stem cells can be used in cell therapy. Among these, mesenchymal stem cell (MSC) therapy has gradually established itself as a novel method for treating damaged tissues that need restoration and renewal. Male infertility is an important health challenge affecting approximately 8-12% of people around the world. This abnormality can be caused by primary, congenital, acquired, or idiopathic reasons. Men with no sperm in their semen have a condition called azoospermia, caused by non-obstructive (NOA) causes and post-testicular obstructive causes. Accumulating evidence has shown that various types of MSCs can differentiate into germ cells and improve spermatogenesis in the seminiferous tubules of animal models. In addition, recent studies in animal models have exhibited that extracellular vesicles derived from MSCs can stimulate the progression of spermatogenesis and germ cell regeneration in the recipient testes. In spite of the fact that various improvements have been made in the treatment of azoospermia disorder in animal models by MSC or their extracellular vesicles, no clinical trials have been carried out to test their therapeutic effect on the NOA. In this review, we summarize the potential of MSC transplantation for treating infertility caused by NOA.

Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis.

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived-cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy's promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

A Comparative Review of Two Major Topical Hemostasis Agents in Spine Surgery

Achieving adequate hemostasis in spine surgery is critical for both the patient and surgeon. Currently, there are two major topical hemostatic matrix agents used in spine surgery—Floseal (Baxter Healthcare, Deerfield, Illinois, USA) and Surgiflo (Ethicon Inc., Raritan, New Jersey, USA). While both products have been shown to be effective at achieving hemostasis, there is no consensus supporting the use of one agent over another in spine surgery. There are studies comparing outcomes and cost between Floseal and Surgiflo, but a significant portion of the studies have industry affiliations. Generally, existing literature reports low to moderate cost savings in favor of one agent or the other, with no clinically significant differences in other patient-based outcomes such as postoperative hematomas. Animal model studies also suggest unique complications, including epidural fibrosis and associated nerve root compression with use of a flowable topical hemostatic agent. Further non-industry-affiliated studies are warranted to compare efficacy, patient outcomes, cost analyses, and possible unique complications associated with the two hemostatic agents.

Is bladder outlet obstruction rat model to induce overactive bladder (OAB) has similarity to human OAB? Research on the events in smooth muscle, collagen, interstitial cell and telocyte distribution

BackgroundCellular and cytoskeletal events of overactive bladder (OAB) have not been sufficiently explored in human bladder due to different limitations. Bladder outlet obstruction (BOO) had been induced in different animal models with different methods to induce (OAB). Similarity of the animal models of BOO to the human OAB is postulated but has not been confirmed. The interstitial cells of Cajal (ICCs), and telocytes (TCs) are an important players in smooth muscles conductivity, they had not been well investigated in the previous BOO models. Objectives are to investigate the morphological pattern of cellular, cytoskeleton and telocytes distribution in BOO rat model and to match the events in two time periods and compare it to the findings in real-world human OAB.MethodsFemale Sprague-Dawley rats (Rattus norvegicus) were randomly divided into: sham (n = 10), BOO 6 W (n = 10), BOO 8 W (n = 10). Operative procedure to Induce BOO was done under anesthesia with intraperitoneal Ketamine administration. The Effect of induction of BOO was evaluated after 6 and 8 weeks. The rats were anesthetized, and the urinary bladder was removed, while the rat was unconscious under anaesthesia it was transferred to the inhalation anaesthesia cage for euthanasia, rats were sacrificed under light anesthesia using isoflurane. Care of animals, surgical procedure, and euthanasia adhered to Guide for the Care and Use of Laboratory Animals, and AVMA Guidelines for the Euthanasia of Animals. The retrieved bladder was processed for examination with histopathology, immunohistochemistry (IHC), and transmission electron microscopy (EM).ResultsHistological examination of the bladder shows thinner urothelium, condensation of collagen between muscle bundles. IHC with c-kit shows the excess distribution of ICCs between smooth muscle bundles. EM shows frequent distribution of TCs that were situated between collagen fibers. Finings in BOO 6 W group and BOO 8 W group were comparable.ConclusionThe animal model study demonstrated increased collagen/ smooth muscle ratio, high intensity of ICCs and presence of TCs. Findings show that a minimally invasive procedure to induce BOO in rats had resulted in an OAB that has morphological changes that were stable in 6 & 8 weeks. We demonstrated the distribution of TCs and ICCs in the rat animal model and defined them. The population of TCs in the BOO rat model is described for the first time, suggests that the TCs and ICCs may contribute to the pathophysiology of OAB. Similarity of animal model to human events OAB was demonstrated. These findings warrant further study to define the role of TCs in OAB.Clinical trial registryThe study does not require a clinical trial registration; it is an experimental animal study in basic science and does not include human subjects.