Employing Animal Models Research Articles

Evaluating anticancer potentials of potentized preparations in an in-vivo xenograft model

BackgroundXenografts in immunodeficient mice play a pivotal role in testing novel anti-cancer treatments. Xenograft models expedite the drug discovery process, offering a cost-effective alternative to conventional animal models and providing essential data for clinical trials. We have followed the approach described by the Developmental Therapeutics Program of the National Cancer Institute (NCI), USA to investigate the therapeutic responses. ObjectivesIn this research, potentized preparations derived from biomaterial, referred to as nosodes, have exhibited promising effectiveness against cancer in laboratory experiments. This study seeks to further substantiate these findings by employing animal models. MethodPotentized preparations from category nosodes sourced from biomaterials of HIV, Cancer tissue, Hepatitis C and a combination underwent testing within the NCI's preclinical evaluation protocols using Xenograft models (HOP62). All the experimental mice were randomly assigned to one of six groups (n = 6), including vehicle and positive controls. These preparations were administered orally at a dosage of 0.1 ml, five days a week, over a four-week period. The mice were closely monitored at regular intervals for 32 days, with observations regarding changes in body weight, tumor volume, morbidity, and mortality. Relative tumor volume (RTV) was calculated as the tumor volume on the day of measurement divided by the tumor volume on day 1. ResultsThe groups treated with Hepatitis C 30c and HIV 100c nosodes have not shown effect with respect to Relative Tumor Volume (RTV). Evidence of significant tumor regression was observed for RTV on day 30 in groups treated with HIV nosode 30c (P = 0.002), and Cancer nosode 30c (P = 0.005). Percentage Survival was noted better in HIV nosode 30c treated group from day 25, however, in other groups survival percentage remained constant. Varied animal body weight in all groups was noted. Significant differences in tumor volume with respect to time in all treated groups were observed. ConclusionResults are suggestive of tumor regression which is encouraging to undertake further clinical trials to explore the anticancer potential of HIV nosode and Cancer nosode.

Genetic parameters for direct and maternal genetic components of calving ease in Korean Holstein Cattle using animal models.

We investigated genetic parameters of calving ease (CE) using several animal models in Korean Holstein and searched for suitable models for routine evaluation of CE. Two phenotypic datasets of CE (DS5 and DS10) on first-parity Korean Holstein calves were prepared. DS5 and DS10 included at least 5 and 10 CE records per herd-year level and comprised 117,921 and 80,389 observations, respectively. The CE phenotypes ranged from 1 to 4, from a normal to extreme difficulty calving scale. The CE was defined as a trait of the calf. The BLUPF90+ software was used for (co)variances estimation through four animal models with a maternal effect (M1 to M4), where all models included effects of a fixed calf-sex, a fixed dam calving age (covariate), and one or more fixed contemporary group (CG) terms. The CG effects were different across models-a herd-year-season (M1, HYS), a herd-year and year-season (M2, HY+YS), a herd-year and season (M3, HY+S), and a herd and year-season (M4, H+YS). Direct heritability (h2) estimates of CE ranged from 0.005 to 0.234 across models and datasets. Maternal h2 values were low (0.001 to 0.090). Genetic correlations between direct and maternal effects were strongly negative to lowly positive (-0.814 to 0.078), further emphasizing its importance in CE evaluation models. These genetic parameter estimates also indicate slower future selection progress of CE in Korean Holsteins. The M1 fitted many levels with fewer observations per level deriving unreliable parameters, and the M4 did not account for confounded herd and animal structures. The M2 and M3 were deemed more realistic for implementation, and they were better able to account for data structure issues (incompleteness and confounding) than other models. As the pioneering study to employ animal models in Korean Holstein CE evaluation, our findings hold significant potential for this breed's future and routine evaluation development.

Advances in the Differentiation of hiPSCs into Cerebellar Neuronal Cells.

The cerebellum has historically been primarily associated with the regulation of precise motor functions. However, recent findings suggest that it also plays a pivotal role in the development of advanced cognitive functions, including learning, memory, and emotion regulation. Pathological changes in the cerebellum, whether congenital hereditary or acquired degenerative, can result in a diverse spectrum of disorders, ranging from genetic spinocerebellar ataxias to psychiatric conditions such as autism, and schizophrenia. While studies in animal models have significantly contributed to our understanding of the genetic networks governing cerebellar development, it is important to note that the human cerebellum follows a protracted developmental timeline compared to the neocortex. Consequently, employing animal models to uncover human-specific molecular events in cerebellar development presents significant challenges. The emergence of human induced pluripotent stem cells (hiPSCs) has provided an invaluable tool for creating human-based culture systems, enabling the modeling and analysis of cerebellar physiology and pathology. hiPSCs and their differentiated progenies can be derived from patients with specific disorders or carrying distinct genetic variants. Importantly, they preserve the unique genetic signatures of the individuals from whom they originate, allowing for the elucidation of human-specific molecular and cellular processes involved in cerebellar development and related disorders. This review focuses on the technical advancements in the utilization of hiPSCs for the generation of both 2D cerebellar neuronal cells and 3D cerebellar organoids.

Cancer and its Prevalent Treatment Strategies - A Review

One of the main forms of cancer treatment is chemotherapy. Chemotherapy failure is a common occurrence, primarily because of dose-limiting toxicity linked to medication resistance. Effective treatment resistance management is essential for chemotherapy to be successful. Numerous reports in Chinese literature suggest that organic materials can overcome medication resistance in cancer cells, and these findings should be shared with scientific and industrial groups. The reports were condensed into four categories by us: 1. research on cell line models in-vitro; 2. serum pharmacokinetics; 3. in-vivo research employing animal models; and 4. clinical research. For the first time, antidrug resistance activity was found in 14 single compounds. Drugs have been proven to overcome drug resistance in-vitro in a dose-dependent manner by blocking drug transporters, cell detoxification ability, or cell apoptosis sensitivity, even at nontoxic and subtoxic concentrations. Research conducted in-vivo revealed that herbal extracts, single components, and formulations all exhibited strong antidrug resistance properties. A significant number of individual chemicals, herbal extracts, and combinations have been applied in clinical settings to treat a range of illnesses, including cancer. Comprehensive information on the utilization of natural compounds in China to combat drug resistance in cancer cells is provided by this review, which could help in the creation of organic substances for the therapeutic treatment of drug resistance in cancer patients.

Variability in rat weight gain during development.

The rat is one of the most employed animal models in biomedicine. Traditionally, weight gain has been utilized to gauge development and compare across species. Numerous studies have conducted longitudinal analyses of rat development, with emphasis on weight gain analysis. Given the high variability in these patterns, experimental data from a single laboratory may not be reliable for generalized estimation. This study aimed to analyze the effect of different factors on the pattern of weight gain during rat development. A literature survey was conducted to compile a database comprising nearly 300 data points of age and weight from 15 longitudinal studies. The database comprised both pre- and postnatal data. Utilizing the Gompertz equation, the data was analyzed to formulate a comprehensive model describing rat development. Differences in growth patterns became increasingly evident at later developmental stages, when significant differences in the maximum asymptote between sexes and strains were reached.

Treatment options applied to the preclinical studies using animal models for Chagas Disease: a systematic review and meta-analysis

Background Chagas disease (CD) is a neglected tropical disease endemic to Latin America, has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, by difficulty to obtain appropriate diagnoses and poor treatment, the search for novel therapeutic options remains. Methods In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines. Results Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies Conclusions This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD. Inplasy registration INPLASY202430101 (25/03/2024)

Lung surfactant inhibition and cytotoxicity at the air-liquid interface of dry particle aerosols

Industrial processes generate chemicals that have the potential to be aerosolized and inhaled by workers, thereby posing health risks. Traditional toxicology methods employing animal models cannot keep up with the pace of emerging hazards. Nascent in vitro practices face challenges regarding translatability to the real world. To address this critical gap, this study demonstrated a workflow utilizing aerosol characterization in a more realistic exposure scenario: dry powder aerosolization onto the air-liquid interface of lung cells. This study delves into biophysical aspects of lung function by examining lung surfactant inhibition. A set of particulates, including aluminum, aluminum oxide, carbon nanotubes, diesel particulate matter, and colloidal silica, was selected for investigation. Particles were in the respirable regime, with mean aerodynamic diameters ranging from 111 to 162 nm by number and 369–2884 nm by mass. Carbon nanotubes and colloidal silica were identified as surfactant inhibitors. Aerosol doses reduced cell viability, up to 38%, with the most pronounced effects observed in response to exposure to aluminum and diesel particulate matter. Dry particle exposure at the air-liquid interface shows promise even at low doses, compared with nebulization or inoculation to submerged cultures. Our findings underscore the potential of this innovative approach for assessing the hazards of aerosolized particulates and emerging contaminants, offering a more accurate representation of real-world exposure scenarios.

Impact of coexisting type 2 diabetes mellitus on the urinary microbiota of kidney stone patients.

Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies. During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3-V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform. The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05). The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine.

Deciphering the molecular pathways associated with N-methyl-D-aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain-derived models that are amenable to studying the neurobiology of schizophrenia may contribute to filling the gaps left by the widely employed animal models. Here, we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK-801 on human brain slice cultures obtained from adult donors submitted to respective neurosurgery. Initially, we demonstrated that MK-801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass-spectrometry-based proteomics and systems biology in silico analyses, we found that MK-801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology, including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid, and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK-801-induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset, we identified potential modulators of the MK-801-induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia. This dataset is publicly available and may be helpful in further studies aimed at evaluating the effects of MK-801 and antipsychotics in the human brain.

Advances in Nanotechnology for Enhanced Leukemia Therapy: A Systematic Review of In Vivo Studies

Abstract Background/Objective: Leukemia, a heterogeneous group of blood cancers, can present a significant clinical challenge due to its varying subtypes and complexity. The application of nanotechnology has the potential to revolutionize the treatment of leukemia. Based on in vivo studies, this systematic review provides an accurate and current assessment of nanotechnology therapeutic advances in leukemia treatment. Methods: The present systematic review focused on in vivo studies investigating nanotechnology's therapeutic potential for leukemia treatment. Comprehensive searches were conducted across leading databases, including PubMed, Scopus, and Google Scholar, to identify relevant publications. Selection criteria encompassed studies that employed animal models to assess nanotechnology effects on leukemia progression. Data extracted from selected articles were rigorously analyzed. This review included studies published between 2010 and 2022. Results: Based on the inclusion criteria, 24 relevant studies were identified. According to the findings of this review, nanotechnology has made substantial progress in the treatment of leukemia, as demonstrated by in vivo studies. Advanced nanoparticle-based drug delivery systems, precision gene therapies, and targeted therapeutic approaches have consistently exhibited superior outcomes in treating various leukemia subtypes in animal models. These compelling results emphasize the transformative potential of nanotechnology for leukemia therapy. Conclusion: In conclusion, the meticulous analyses of the in vivo studies underscore the role that nanotechnology plays in the advancement of the treatment of leukemia. Nanotechnology has demonstrated efficacy in preclinical models, indicating that it can be translated into clinical applications, offering new avenues for treating leukemia and reinforcing its position as an innovative therapeutic approach.

Inbreeding Depression and Purging for Meat Performance Traits in German Sheep Breeds.

This study provides estimates on genetic parameters, inbreeding depression and purging for meat performance measures from 25 German sheep breeds. All German meat, merino sheep breeds and breeds of other breeding directions with a sufficient number of pedigree and performance data were included in this study. Phenotypic traits retrieved from the national database OviCap were evaluated: daily weight gain, meatiness score and ultrasound measurements for muscle and fat thickness. We employed animal models to estimate heritability, variance and covariance components for these meat performance traits as well as inbreeding depression and purging. The heritabilities, on average, reached estimates of 0.55, 0.34, 0.53 and 0.61 for daily weight gain, meatiness score and ultrasound measurements for muscle and fat thickness, respectively. We estimated the linear regression slopes for the individual rate of inbreeding, new and ancestral inbreeding, as well as the inbreeding coefficient and its interaction with the inbreeding coefficient of Ballou, employing animal models with non-genetic effects and the additive genetic effect of the animal. Across all breeds, inbreeding was only significant for daily weight gain, whereas for all other traits, estimates were not significant. Within sheep breeds, we found significant inbreeding depression for daily weight gain in German Mutton Merino and German Blackheaded Mutton as well as for the meatiness score in German Whiteheaded Mutton. Significant effects for purging, based on ancestral inbreeding and the interaction effect of the classical inbreeding coefficient with the inbreeding coefficient of Ballou, were not obvious either across or within any sheep breed. A 1% increase in inbreeding significantly decreased the phenotypic trait median of daily weight gain across all sheep breeds by 0.50% and 0.70% of phenotypic and genetic standard deviation, respectively. Purging effects due to ancestral inbreeding were not significant in any breed or across breeds. The results of this study may indicate that inbreeding depression may be more harmful in traits under stronger selection than in traits that exert low selection pressure. The results of this study demonstrate the different effects that result in meat performance traits due to inbreeding. With increasing rates of inbreeding and critical effective population sizes, selection intensity for breeding objectives has to be critically reviewed for each sheep breed. Inbreeding depression and purging should be evaluated in order to prevent a decrease in trait means due to inbreeding and to determine whether detrimental alleles are eliminated.

Protein misfolding: an additional player in the stroke-heart syndrome

Abstract Background Patients suffering from acute ischemic stroke experience an increased risk of major adverse cardiovascular events, introducing the term of stroke-heart syndrome (SHS). Beside common risk factors, the so-called brain-heart axis represents a relevant yet not fully understood biological matrix driving this multi-organ condition. Together with inflammatory and neurohormonal signals, protein misfolding appears as an additional component of this matrix. In fact, previous studies employing animal models of cerebral ischemia identified wrongly arranged toxic proteins (oligomers). In light of the spreading capabilities of such proteins, we questioned whether protein misfolding plays a role in the SHS. Purpose The purpose of this study is to investigate the occurrence of protein misfolding in the post-stroke cardiac dysfunction by assessing presence, origin, localization and routes of oligomers in the heart following an acute ischemic stroke. Its biological and physiological relevance are evaluated by in vivo and in vitro assessments of the myocardium. Methods Acute cerebral ischemic injury was induced in the mouse by left transient middle cerebral artery occlusion for 45 minutes followed by 48 hours of reperfusion in 3-4 month-old C57BL/6J wild type males. Sham operated littermate mice were used as controls. Forty-eight hours after acute cerebral ischemia, cardiac function was evaluated by electrocardiography and compared to pre-operative assessment. Organs were harvested after the abovementioned assessment for the localization and semi-quantification of oligomers in heart and lymph nodes. Furthermore, biological responses related to protein homeostasis in the myocardium were assessed on mRNA and protein levels. Results Our preliminary results show that acute ischemic stroke is associated with an increased presence of oligomers in the heart. In addition, higher levels of oligomers were detected in axillary lymph nodes isolated from stroke mice, suggesting a possible route of oligomers spreading (Fig 1A). Correlating with oligomers occurrence, molecular analyses showed significant upregulation of the inositol-requiring enzyme 1 (IRE1), and catalase at mRNA level (Fig 1B). On the other hand, the expression of the 78-kDa glucose-regulated protein (GRP78), and catalase significantly decreased at protein level, indicating impaired myocardial protein quality control and oxidative stress after acute ischemic stroke (Fig 1C). Stroke-induced cardiac dysfunction was presented by decreased heart weight to tibia length ratio as well as slower and irregular heart rhythm suggesting signs of arrhythmia (Fig 2). Conclusions Acute ischemic stroke is associated with an increased oligomers occurrence in the myocardium and ultimately correlates with altered cardiac resistance against proteotoxicity. Further experiments will be conducted in order to elucidate the role of oligomers as active players or bystanders in the stroke-heart syndrome.

Review On Synthetic Vs Herbal Drugs, Its Various Extraction Methods And Animal Models Related To Depression

Depression is a neuropsychiatric disorder The focus of the current review article is on the most recent antidepressants drugs , their mechanisms of action, their pathophysiology, their side effects, and the methods for preventing drug-induced toxicity. There is also a description of phytochemicals that have been found to have antidepressant effects. Widely used synthetic drugs are, i. tricyclic antidepression ii. Selective serotonin reuptake inhibitors iii. monoamine oxidase inhibitors, iv. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) It has been reported that most antidepressants have negative health effects. An account of phytochemicals found to be acting as antidepressant is also included. Their beneficial effects to the human body have been attributed to the presence of active phytochemical ingredients with some efficiency for disease treatment as well as for beauty and health enhancement. Public awareness on the adverse effects of synthetic chemical products also increased the demand for herbal products. Highly efficient herbal processing and extraction technologies have been developed to obtain the optimal amounts of active ingredients from herbs Soxhlet extraction, supercritical fluid extraction cold Maceration Extraction, steam distillation, Hot Water Extraction, microwave assisted extraction. This review focuses on recent findings regarding some of the most widely employed animal models used currently to predict antidepressant potential. Here we, studies the assessment behavioral test by using various animal models force swimming test, tail suspension Test, rotarod test. In that for study of synthetic and herbal drugs in treatment of depression. Their advantageous effects on the human body have been related to the existence of active phytochemical components that are effective in treating certain diseases as well as enhancing attractiveness and health. The demand for herbal items increased as a result of growing public knowledge of the negative consequences of synthetic chemical products.

The microtubule signature in cardiac disease: etiology, disease stage, and age dependency

Employing animal models to study heart failure (HF) has become indispensable to discover and test novel therapies, but their translatability remains challenging. Although cytoskeletal alterations are linked to HF, the tubulin signature of common experimental models has been incompletely defined. Here, we assessed the tubulin signature in a large set of human cardiac samples and myocardium of animal models with cardiac remodeling caused by pressure overload, myocardial infarction or a gene defect. We studied levels of total, acetylated, and detyrosinated α-tubulin and desmin in cardiac tissue from hypertrophic (HCM) and dilated cardiomyopathy (DCM) patients with an idiopathic (n = 7), ischemic (n = 7) or genetic origin (n = 59), and in a pressure-overload concentric hypertrophic pig model (n = 32), pigs with a myocardial infarction (n = 28), mature pigs (n = 6), and mice (n = 15) carrying the HCM-associated MYBPC32373insG mutation. In the human samples, detyrosinated α-tubulin was increased 4-fold in end-stage HCM and 14-fold in pediatric DCM patients. Acetylated α-tubulin was increased twofold in ischemic patients. Across different animal models, the tubulin signature remained mostly unaltered. Only mature pigs were characterized by a 0.5-fold decrease in levels of total, acetylated, and detyrosinated α-tubulin. Moreover, we showed increased desmin levels in biopsies from NYHA class II HCM patients (2.5-fold) and the pressure-overload pig model (0.2–0.3-fold). Together, our data suggest that desmin levels increase early on in concentric hypertrophy and that animal models only partially recapitulate the proliferated and modified tubulin signature observed clinically. Our data warrant careful consideration when studying maladaptive responses to changes in the tubulin content in animal models.Graphical

New Perspectives on Micronised Purified Flavonoid Fraction in Chronic Venous Disease: From Microvalves to Clinical Effectiveness.

The importance of chronic venous disease (CVD), as a cause of reduced quality of life and increased costs to healthcare systems, is expected to rise in parallel with population aging and the increasing prevalence of obesity. Venoactive drugs (VADs) are frequently used to treat the symptoms and signs of CVD. The most commonly used and widely studied VAD, micronised purified flavonoid fraction (MPFF), is effective at all stages of CVD, and has been shown to significantly reduce leg pain, leg heaviness and swelling, as well as ankle oedema and functional discomfort, in clinical trials. Recently, experiments employing animal models of CVD have demonstrated that MPFF has anti-inflammatory and venotonic effects at the microvalve level, and a pilot clinical study in patients with CVD has provided support for these findings. Collectively, these results suggest that early initiation of MPFF treatment may have the potential to favourably alter the clinical course of the disease, although further clinical data are required to confirm these findings. International guidelines on CVD management strongly recommend MPFF to reduce symptoms and improve quality of life. Studies are now needed to investigate the impact of long-term treatment on disease progression.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02218-x.

Antinociceptive effect of ethanolic extract of Bauhinia brachycarpa Benth on neuropathic pain model induced by partial sciatic nerve ligation

Ethnopharmacological relevanceThe plant Bauhinia brachycarpa Benth (BBB) has been traditionally used for treating muscle aches such as bone pain, and neuralgia for a long time, on account of its sedative and antinociceptive activities in Yunnan province of China. However, there was no experimental evidence to confirm its traditional medicinal use. Aim of the studyThe antinociceptive effect and possible mechanism of ethanolic extract of BBB on neuropathic pain was evaluated through a model of partial sciatic nerve ligation in mice. Materials and methodsA commonly employed animal model induced by partial sciatic nerve ligation (PSNL) in mice was established in the aim of studying neuropathic pain. Ethanolic extract of BBB (1000, 500, 250 mg/kg) and pregabalin (60 mg/kg) were intragastric administrated daily for 7 days post-PSNL. Mechanical and thermal hyperalgesia were assessed throughout the experimental period.After the experiment, the levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in serum were determined by ELISA. The mRNA expressions of ionized calcium binding adaptor molecule 1 (Iba-1), CD16, CD206, arginine-1 (Arg-1), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) in the spinal cord were detected by qPCR. The protein levels of Iba-1, CD16, CD206, and p38 phosphorylation in the spinal cord were detected by immunohistochemistry and western blotting. The phytochemical analysis of BBB was performed through the colorimetric test. ResultsNeuropathic pain induced by PSNL was significantly alleviated by BBB treatment, which decreased pro-inflammatory cytokines such as TNF-α, IL-1β and iNOS, increased anti-inflammatory cytokine such as IL-10 and Arg-1, and attenuated p38 phosphorylation. BBB also reduced the number of Iba-1 and CD16 positive cells, but it enhanced the number of CD206 positive cells. n-Butanol portion that was partitioned from the ethanolic extract had the highest content of total flavonoids among all the portions, and the antinociceptive effect of n-butanol portion is better than that of other portions. ConclusionsOur findings indicate that the antinociceptive effect of BBB is mediated by inhibiting the inflammatory response and regulating the differentiation of microglia. The antinociceptive effect of BBB was related to the content of total flavonoids.

Functional genomics and the future of iPSCs in disease modeling.

SummaryInduced pluripotent stem cells (iPSCs) are valuable in disease modeling because of their potential to expand and differentiate into virtually any cell type and recapitulate key aspects of human biology. Functional genomics are genome-wide studies that aim to discover genotype-phenotype relationships, thereby revealing the impact of human genetic diversity on normal and pathophysiology. In this review, we make the case that human iPSCs (hiPSCs) are a powerful tool for functional genomics, since they provide an in vitro platform for the study of population genetics. We describe cutting-edge tools and strategies now available to researchers, including multi-omics technologies, advances in hiPSC culture techniques, and innovations in drug development. Functional genomics approaches based on hiPSCs hold great promise for advancing drug discovery, disease etiology, and the impact of genetic variation on human biology.

Thinking Outside the Box: Utilizing Nontraditional Animal Models for COVID-19 Research

The ongoing COVID-19 pandemic continues to affect the lives, wellbeing, and stability of communities worldwide. The race to save human lives is critical, and the development of useful translational animal models to elucidate disease pathogenesis and prevention, and to test therapeutic interventions, is essential to this response. However, significant limitations exist with the currently employed animal models that slow our ability to respond to the pandemic. Non-human primates serve as an excellent animal model for SARS-CoV-2 disease and interventions, but the availability of these animals is scarce, and few facilities are able to house and utilize this model. Adapted murine models are accessible and improving but lack natural hACE-2 receptors and are only moderate representatives of human COVID-19 disease, transmission, and immune responses. On the other hand, there are several animal species that are both naturally and experimentally infected, such as domestic cats, hamsters, ferrets, and mink. Several of these have proven animal-to-animal transmission and evidence of significant clinical and histopathologic disease that mimics acute COVID-19 in humans. Mobilizing these nontraditional animal models could have a crucial role in SARS-CoV-2 research efficiency and impact. This review focuses on what is known about these nontraditional animal models, including their immune responses to SARS-CoV-2 infection, evidence of clinical and histopathologic disease, transmission potential, and the practicality of each model in a research setting. Comparative insight into these animal models for COVID-19 can strengthen the efforts to mitigate this pandemic.

Characterization of a spontaneous cell line from primary mouse fibroblasts as a model to study Sanfilippo syndrome.

To evaluate a new approach to Mucopolysaccharidosis type IIIA (MPS-IIIA), work was initiated on primary fibroblasts from a well-known mouse model in which sulfamidase deficiency correlates with the accumulation of heparan sulfate - the hallmark of this disease. Once the culture of fibroblasts was established, we observed continuous proliferation with a rapid growth rate, loss of contact inhibition and late passage stability, corresponding to a spontaneously immortalized cell line. The presence of the single point D31N mutation was verified and both rapid and abundant intracellular accumulation of low molecular weight HS was observed, confirming both genotype and phenotype. This cell line is a potential in vitro model system for future studies of MPS-IIIA prior to employing animal models.

Impact on Discrimination Performance of Repeatability of Virtual Monoenergetic Images-Derived Radiomics Features: A Multi-Scanner Comparison Employing Animal Models

Impact on Discrimination Performance of Repeatability of Virtual Monoenergetic Images-Derived Radiomics Features: A Multi-Scanner Comparison Employing Animal Models