Experimental Disease Models Research Articles

The effect of growth hormone on motor findings and dendrite morphology in an experimental Parkinson's disease model.

Approaches for the induction of neurogenesis and neuronal recovery through several modalities are gaining popularity in Parkinson's disease (PD). Growth hormone (GH) seems to have a role in the reversal of neural function following brain injury as well as in normal brain development and function; therefore, the use of GH may represent a feasible strategy in the management of PD. This experimental study aimed to evaluate the effect of growth hormone on motor function and dendrite morphology in rats with 6-hydroxydopamine (6-OHDA)-induced PD model. Thirty-six Sprague Dawley rats were included and randomly allocated into one of the six study groups: two controls and four treatment groups that received daily subcutaneous growth hormone injections for 21days, 1, 2, and 3months. PD model was induced through unilateral 6-OHDA injection to the nigrostriatal pathway. The following assessments were made: apomorphine rotation test, stepping test, and tissue examinations for tyrosine hydroxylase and dendrite morphology. The apomorphine rotation test and the stepping test confirmed the presence of PD. These tests as well as dendritic spine density/number and length assessments showed improvement in PD findings over time with GH administration. Findings of this study suggest that GH administration may improve dendrite morphology and motor function in the PD model, which may translate into symptom relief and quality of life improvement in patients with PD. Such potential benefits should be tested in robust clinical studies.

Neuroprotective properties of the Lilium brownii extracts in the experimental model of Parkinson's disease.

Lilium brownii (L. brownii) is a plant that can be used for both medicine and food. Its bulbs are commonly used to treat neurological disorders like depression, insomnia, and Parkinson's disease (PD). However, the mechanism by which it treats PD is not yet fully understood. This study aims to investigate the possible mechanism of L. brownii extract in treating PD and to compare the efficacy of ethanol and aqueous extracts of L. brownii. In this study, mice with PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) were given L. brownii extracts for 30 days, and the effects of both extracts were then evaluated. Our study demonstrated that both extracts of L. brownii effectively improved motor dysfunction in PD mice induced by MPTP. Additionally, they increased the number of neurons in the substantia nigra region of the mice. Moreover, both extracts reduced levels of malondialdehyde (MDA) and ferrous ion (Fe2+), while increasing levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum. They also influenced the expression of proteins associated with the p62-Keap1-Nrf2 pathway. Interestingly, while both extracts had similar behavioral effects, the ethanol extract appeared to have a more significant impact on individual proteins in the p62-Keap1-Nrf2 pathway compared to the aqueous extract, possibly due to its higher phenolic acid glyceride content. In conclusion, L. brownii shows promise as an effective and safe treatment for PD.

Exploring the Therapeutic Potential of Green-Synthesized Gold Nanoparticles and Ericaria selaginoides Extract for Inflammatory Bowel Disease.

Addressing disease remission and treatment adherence in inflammatory bowel diseases (IBDs), such as Crohn's disease, poses significant challenges due to underlying oxidative and inflammatory processes. Nanotechnology emerges as a promising avenue for enhancing therapeutic outcomes in IBD by optimizing drug bioactivity, reducing toxicity, and extending circulation time. Gold nanoparticles, known for their resistance to gastrointestinal pH and possessing antioxidant and anti-inflammatory properties, offer particular promise. They can be produced by green synthesis with seaweed Ericaria selaginoides (ES), itself associated with gastroprotective and anti-inflammatory activities. In a murine model of Crohn's disease induced with 8% acetic acid, pretreatment with dexamethasone (0.2 mL/30 g) or Au@ES (25 and 50 mg/kg) effectively mitigated inflammatory features. Notably, ES (50 mg/kg) and Au@ES (50 mg/kg) administration resulted in significant reductions in both macroscopic and microscopic inflammation scores compared to the disease control group. Furthermore, these treatments normalized inflammatory cytokine expression while safeguarding myenteric plexus glial cells. They also impeded neutrophil activation, leading to reduced myeloperoxidase activity and lipid peroxidation, coupled with increased glutathione levels. In conclusion, ES and Au@ES exhibit potent efficacy in counteracting inflammation and oxidation processes in an experimental Crohn's disease model, suggesting their potential as alternative therapeutic strategies for IBD.

Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action

Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features adhesions caused by estrogen-dependent periodic bleeding. It is characterised by a widely spread fibrotic interstitium that comprising of fibroblasts, myofibroblasts, collagen fibres, extracellular proteins, inflammatory cells, and active angiogenesis found outside the uterus. Thus, fibrosis is recognized as a critical component because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or non-cyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root cause, etiology, and complex pathogenesis of this debilitating condition, makes it challenging to diagnose early and to implement therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Research on understanding the pathogenesis of endometriosis is still ongoing to find biomarkers and develop non-hormonal therapeutic approaches. Current clinical research indicates a close relationship between endometriosis and fibrosis, which is thought to be tightly linked to pain, a major factor for the decline in the patient’s quality of life but little is known about the underlying pathophysiological cellular and molecular signaling pathways that lead to endometriosis-related fibrosis. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease to assess treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article’s goal is to examine recent developments in the field and pinpoint knowledge gaps that exist with a focus on the development of novel fibrotic mouse models for the early diagnosis and treatment of endometriosis and how this knowledge aids in the development of novel anti-fibrotic treatments which opens fresh avenues for a thorough investigation and extended research in the field of endometriosis.

Nonsteroidal Anti-Inflammatory Drugs and Experimental Chagas Disease: An Unsolved Question.

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T.cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti-inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding.

Sustained Alleviation of Autoimmunity by Activating α2B-adrenergic Receptors.

Catecholamines binding to α- and β-adrenergic receptors on immune cells have recently been shown to play an important role in regulating immune responses. Although α2-adrenergic receptors are known to modulate the immune response in different ways, the therapeutic exploration of their utility has been limited by the lack of agonists selective for the three α2-adrenergic subtypes. We report in this study the identification of the agonist AGN-762, which activates α2B- and α2C-adrenergic subtypes, but not the α2A subtype. We show that AGN-762 reduced clinical disease in an experimental autoimmune encephalitis model of autoimmune disease via direct or indirect effects on T regulatory cells. The activity of AGN-762 was abrogated by depletion of T regulatory cells, which express the α2B-adrenergic receptor. Furthermore, a drug-induced shift to an anti-inflammatory phenotype was demonstrated in immune cells in the spleen of drug-treated experimental autoimmune encephalitis mice. AGN-762 does not display sedative and cardiovascular side effects associated with α2A subtype agonists. Immune modulation by selective α2-adrenergic agonists represents a novel, to our knowledge, approach for treating autoimmune disease.

Neuroprotective Effect of Chlorogenic Acid in an Animal Model of Sporadic Alzheimer's Disease Induced by Streptozotocin.

Alzheimer's Disease is a degenerative neurological condition which leads to a decline in memory and cognitive function. Chlorogenic Acid (CGA) presents properties including neuroprotective, antioxidant and anti-inflammatory. The aim of this study was to examine the impact of CGA on cognitive impairments, neuroinflammation and neuronal damage in mice submitted to an experimental model of Sporadic Alzheimer Disease (SAD) induced by intracerebroventricular administration of streptozotocin (ICV-STZ). Male Swiss mice received bilateral ICV-STZ injections (3mg/Kg) on days 1 and 3. The treatment with CGA (5mg/Kg, orally) or vehicle (water, orally), was initiated and continued for 26days, starting 2h after the second induction procedure. At first, there was no change in serum glucose levels after SAD induction. ICV-STZ induces impairments in aversive, recognition, and spatial memory, while CGA treatment significantly alleviated these memory deficits. Furthermore, locomotor activity, working memory, and anxiety-related activities remained unaffected by the treatments. CGA treatment protects against ICV-STZ-induced increase in the nitrite/nitrate and TBARS levels. ICV-STZ induced a reduction in viable cells, depletion of BDNF, and triggered astrogliosis and microgliosis in the cortex and hippocampus. Treatment with CGA preserves viable cell count in the prefrontal cortex, CA1, and CA3 regions of the hippocampus. Additionally, it prevented BDNF depletion in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions), and mitigated astrogliosis and microgliosis in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions). These findings indicate the neuroprotective effects of CGA, underscoring their potential as therapeutic agents or adjuncts in the treatment of SAD.

Experimental models for peri-implant diseases: a narrative review.

Peri-implant diseases, being the most common implant-related complications, significantly impact the normal functioning and longevity of implants. Experimental models play a crucial role in discovering potential therapeutic approaches and elucidating the mechanisms of disease progression in peri-implant diseases. This narrative review comprehensively examines animal models and common modeling methods employed in peri-implant disease research and innovatively summarizes the in vitro models of peri-implant diseases. Articles published between 2015 and 2023 were retrieved from PubMed/Medline, Web of Science, and Embase. All studies focusing on experimental models of peri-implant diseases were included and carefully evaluated. Various experimental models of peri-implantitis have different applications and advantages. The dog model is currently the most widely utilized animal model in peri-implant disease research, while rodent models have unique advantages in gene knockout and systemic disease induction. In vitro models of peri-implant diseases are also continuously evolving to meet different experimental purposes. The utilization of experimental models helps simplify experiments, save time and resources, and promote advances in peri-implant disease research. Animal models have been proven valuable in the early stages of drug development, while technological advancements have brought about more predictive and relevant in vitro models. This review provides clear and comprehensive model selection strategies for researchers in the field of peri-implant diseases, thereby enhancing understanding of disease pathogenesis and providing possibilities for developing new treatment strategies.

Immunogenic effects of enamel matrix derivative on human alveolar ridge mucosa-derived vascular endothelial cells under lipopolysaccharide stimulation.

Early peri-implant disease detection remains difficult. Enamel matrix derivative (EMD), which is used for periodontal tissue regeneration, promotes leukocyte chemotactic factor and adhesion molecule expression in vascular endothelial cells. We hypothesized that stimulating vascular endothelial cells with EMD would induce an inflammatory response in the peri-implant mucosa, enabling early peri-implant infection detection. To verify this hypothesis, we assessed the intercellular adhesion between human alveolar ridge mucosa-derived vascular endothelial cells (ARMEC) stimulated with lipopolysaccharide (LPS) and EMD and human periodontal ligament-derived vascular endothelial cells (PDLEC). Leukocyte chemotactic factors and cell adhesion molecules were investigated and we established an experimental model of peri-implant disease by stimulating ARMEC (representing the peri-implant mucosa) with Porphyromonas gingivalis-derived LPS. ARMEC and PDLEC were obtained from patients (n = 6) who visited the Nippon Dental University Niigata Hospital. The cells were divided into four subcategories, each cultured with: LPS (1µg/mL), EMD (100µg/mL), LPS + EMD, and pure medium. Cell viability, leukocyte chemotactic factor (interleukin-8: IL-8), adhesion molecules (intercellular adhesion molecule-1: ICAM-1), tight junction protein gene expression (zonula occludens-1: ZO-1 and Occludin), and transendothelial electrical resistance (TEER) was then determined. LPS reduced ARMEC viability, whereas simultaneous stimulation with EMD improved it. LPS and EMD stimulation enhanced IL-8 and ICAM-1 gene expression, suppressed TEER, and decreased ZO-1 and Occludin expression levels compared to that with stimulation with LPS alone. EMD stimulates leukocyte migration, increase vascular permeability, and trigger an immune response in the peri-implant mucosa, thus facilitating the early detection and treatment of peri-implant disease.

Effect of Trehalose Disaccharide on Activation of Microglia and Indices of Systemic Inflammation in an Experimental Model of Alzheimer's Disease.

In an experimental model of Alzheimer's disease in mice, oral administration of trehalose disaccharide reduces neuroinflammation assessed by the expression level of microglia activation marker Iba1 and affects the neutrophil degranulation activity. A potential anti-inflammatory effect of 4% trehalose solution associated with a decrease in the activity of leukocyte elastase in plasma was revealed.

Transcriptional regulation of hexokinase 2 by BRD4 drives perivascular adipose tissue meta-inflammation in cardiometabolic disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Holcim Stiftung SwissLife Stiftung Background/Introduction BRD4 is an epigenetic reader that modulates inflammatory transcriptional programmes implicated in cancer. The therapeutic potential of BRD4 modulation in cardiometabolic disorders remains elusive. Purpose We investigate BRD4-related transcriptional programmes and therapeutic modulation in mouse and human models of cardiometabolic disease. Methods Small arteries (100-300 μM) from healthy subjects (n=16) and patients with obesity and hypertension (n=16) were dissected from visceral fat biopsies and mounted on a pressurised myograph to assess ex-vivo vascular function. Vasorelaxation to acetylcholine and acetylcholine+L-NAME was evaluated at baseline and after incubation with the BRD4 inhibitor RVX-208 and with selective anti-inflammatory and anti-metabolic drugs. Vasorelaxation was assessed in the presence or in the absence of perivascular adipose tissue (PVAT). An experimental mouse model of cardiometabolic disease (high-fat diet+L-NAME supplementation) was orally administered RVX-208 (150 mg/kg) or vehicle for 10 days (n=6 each group) to test in vivo effect of chronic BRD4 inhibition on endothelial and PVAT functions. Vascular and PVAT levels of cytosolic and mitochondrial ROS and nitric oxide were assessed by confocal microscopy; protein and gene expression were measured by Western blot and qPCR. Transcriptional changes upon BRD4 inhibition were investigated by a custom PCR array and confirmed by ChIP, qPCR and Western blot and further characterised by metabolomics, lipidomics and mitochondrial swelling assays. Results Endothelial-dependent vasorelaxation and tissue levels of TNF-α, IL-1β and IL-6 were altered in the vessel wall and PVAT from cardiometabolic patients and mice. RVX-208 substantially attenuated ex-vivo vascular dysfunction. Distinct ex-vivo modulation of well-established inflammatory pathways showed that the effect observed with BRD4 inhibition was stronger than with anti-IL-1β, anti-IL-6 receptor and anti-TNF-α. The effect was more pronounced in vessels with intact PVAT, suggesting a restoration of the PVAT anti-contractile phenotype. (Figure 1). Gene expression profiling in PVAT from cardiometabolic mice unveiled hexokinase-2 (HK2) - a glycolytic enzyme implicated in mitochondrial dysfunction and inflammation - as the top downregulated gene by RVX-208 treatment. Increased binding of BRD4 to HK2 promoter in PVAT samples from cardiometabolic mice was confirmed by ChIP assays. Metabolomics assays further validated the findings, showing a PVAT glycolytic shift in condition of disease. Finally, ex-vivo selective inhibition of HK2 restored vascular dysfunction (Figure 2). Conclusions Targeting the deleterious BRD4-HK2 interplay restores cardiometabolic-related vascular dysfunction reversing the PVAT meta-inflammatory shift. Epigenetic modulators of meta-inflammatory pathways might represent a promising strategy to prevent and vascular dysfunction, key signature of cardiometabolic disease.Figure 1Figure 2

#1290 Adverse proinflammatory responses in the kidney after FGF23 administration in three murine kidney disease models

Abstract Background and Aims The hormone FGF23 is a biomarker associated with morbidity and mortality in individuals with and without kidney disease, but the role of FGF23 excess as a pathogenic factor is incompletely understood. Here, we investigated renal FGF23 signaling in kidney disease models. Method This study used three independent disease models: i) Male C57BL/6 mice (n = 16) were treated with Freud's adjuvant and nephrotoxic serum (NTS) to induce anti-glomerular basement membrane (anti-GBM) disease. ii) Female BALB/c mice (n = 8) were treated with adriamycin (doxorubicin) 10.5 mg/kg to induce focal and segmental glomerulosclerosis (FSGS). iii) Male DBA/2J mice (n = 20) were fed a diet containing adenine 0.2%. Control mice of the respective same strain and sex received vehicle injections. Mice of the anti-GBM and FSGS models and controls received intravenous injections of recombinant FGF23 1 µg or vehicle for six consecutive days (anti-GBM) or once (FSGS), with dissection 24 h after the last injection. Mice of the adenine model were dissected after 15 weeks. Following dissection, ex vivo precision-cut kidney slices (PCKS) were obtained from n = 4 mice and maintained for 24 at 37°C, 95% O2 and 5% CO2, followed by a 1 h treatment with recombinant FGF23 200 ng/ml or vehicle. Glomerular filtration rate (GFR) or renal retention parameters in serum and albuminuria were assessed. Kidneys underwent histological assessment using hematoxylin & eosin or Masson's trichrome. Renal RNA was isolated for bulk RNAseq. Differential gene expression was assessed to determine the effect of FGF23 treatment in disease-free controls, in each disease model, and the interaction between FGF23 X disease effect for the anti-GBM and FSGS groups. Gene set enrichment analysis was performed with a focus on the immune system. Results Anti-GBM mice showed a 45 ± 27% GFR decline (mean ± SD) compared to baseline, whereas controls showed an GFR increase of 11 ± 36% (p < 0.01). Kidney histology revealed an interstitial infiltrate. The FSGS model showed elevated serum creatinine and albuminuria, and hypercellularity in some glomeruli. Mice of the adenine model showed progressively increased blood urea nitrogen concentrations starting after 2 weeks, up to a 3-fold increase at week 14. Histology revealed interstitial fibrosis and tubular atrophy. Bulk RNAseq revealed proinflammatory transcriptional signatures after FGF23 treatment in all disease models, regardless of which timepoint or model: In the anti-GBM model, Hallmark gene sets of inflammatory response, interferon-α response, interferon-β response and allograft rejection were significantly increased after 6 days of FGF23 treatment, whereas disease-free controls showed no significantly changed immune gene sets after 6 days of FGF23. In FSGS mice, none of the Hallmark gene sets were changed after 1 FGF23 injection, but top individual gene expression affected by 1 FGF23 injection were an increased proinflammatory transcription factor Cebpb and an increased DNA damage transcript Dclre1b. Finally, the PCKS of adenine model revealed no significant Hallmark gene sets, but the two genes with differential expression were a proinflammatory macrophage/fibroblast chemokine Ccl4 (increased) and an immunoglobulin heavy variable Ighv2-2 (decreased). Conclusion FGF23-driven patterns of proinflammatory gene expression were observed in three experimental models of kidney disease, both in vivo and ex vivo assessment of FGF23 signaling, thus excluding effects of FGF23 on other organs. As these findings were limited to transcriptional analyses, the present data warrant further confirmation and exploration of FGF23 as a pathogenic agent in kidney disease.

The translational value of calcium pyrophosphate deposition disease experimental mouse models

The deposition of calcium pyrophosphate (CPP) crystals in joint tissues causes acute and chronic arthritis that commonly affect the adult and elderly population. Experimental calcium pyrophosphate deposition disease (CPPD) models are divided into genetically modified models and crystal-induced inflammation models. The former do not reproduce phenotypes overlapping with the human disease, while in the latter, the direct injection of crystals into the ankles, dorsal air pouch or peritoneum constitutes a useful and reliable methodology that resembles the CPP induced-inflammatory condition in humans. The translational importance of the induced model is also strengthened by the fact that the key molecular and cellular mediators involved in inflammation are shared between humans and laboratory rodents. Although, in vivo models are indispensable tools for studying the pathogenesis of the CPPD and testing new therapies, their development is still at an early stage and major efforts are needed to address this issue. Here, we analyze the strenghts and limitations of each currently available CPPD in vivo model, and critically discuss their translational value.

The atypical chemokine receptor 2 reduces T cell expansion and tertiary lymphoid tissue but does not limit autoimmune organ injury in lupus-prone B6lpr mice.

The atypical chemokine receptor 2 (ACKR2) is a chemokine scavenger receptor, which limits inflammation and organ damage in several experimental disease models including kidney diseases. However, potential roles of ACKR2 in reducing inflammation and tissue injury in autoimmune disorders like systemic lupus erythematosus (SLE) and lupus nephritis are unknown, as well as its effects on systemic autoimmunity. To characterize functional roles of ACKR2 in SLE, genetic Ackr2 deficiency was introduced into lupus-prone C57BL/6lpr (Ackr2-/- B6lpr) mice. Upon inflammatory stimulation in vitro, secreted chemokine levels increased in Ackr2 deficient tubulointerstitial tissue but not glomeruli. Moreover, Ackr2 expression was induced in kidneys and lungs of female C57BL/6lpr mice developing SLE. However, female Ackr2-/- B6lpr mice at 28 weeks of age showed similar renal functional parameters as wildtype (WT)-B6lpr mice. Consistently, assessment of activity and chronicity indices for lupus nephritis revealed comparable renal injury. Interestingly, Ackr2-/- B6lpr mice showed significantly increased renal infiltrates of CD3+ T and B cells, but not neutrophils, macrophages or dendritic cells, with T cells predominantly accumulating in the tubulointerstitial compartment of Ackr2-/- B6lpr mice. In addition, histology demonstrated significantly increased peribronchial lung infiltrates of CD3+ T cells in Ackr2-/- B6lpr mice. Despite this, protein levels of pro-inflammatory chemokines and mRNA expression of inflammatory mediators were not different in kidneys and lungs of WT- and Ackr2-/- B6lpr mice. This data suggests compensatory mechanisms for sufficient chemokine clearance in Ackr2-deficient B6lpr mice in vivo. Analysis of systemic autoimmune responses revealed comparable levels of circulating lupus-associated autoantibodies and glomerular immunoglobulin deposition in the two genotypes. Interestingly, similar to kidney and lung CD4+ T cell numbers and activation were significantly increased in spleens of Ackr2-deficient B6lpr mice. In lymph nodes of Ackr2-/- B6lpr mice abundance of activated dendritic cells decreased, but CD4+ T cell numbers were comparable to WT. Moreover, increased plasma levels of CCL2 were present in Ackr2-/- B6lpr mice, which may facilitate T cell mobilization into spleens and peripheral organs. In summary, we show that ACKR2 prevents expansion of T cells and formation of tertiary lymphoid tissue, but is not essential to limit autoimmune tissue injury in lupus-prone B6lpr mice.

Molecular approaches to deploy singlet oxygen in a Leishmania model as an unassailable biocide for disease mitigation and vector control

Singlet oxygen (1O2) is a potent biocide potentially deployable for integrated control of tropical diseases and their insect vectors. This very short-lived free radical is highly destructive of cellular molecules when generated intracellularly. Most organisms, including parasites and vectors, are defenseless against 1O2 except for plants, which produce it abundantly during photosynthesis, hence, the acquisition of specific mechanisms for its detoxification. In the presence of O2 under physiological conditions, certain dyes or photosensitizers (PS), e.g., porphyrins and phthalocyanines (PC), are excitable by light to produce biocidal 1O2. Its half-life is in the order of microseconds, necessitating its intracellular generation in order to harness its biocidal activity most effectively. This is achievable by loading cells with PS for excitation with light to produce 1O2in situ. One example to achieve this is the genetic engineering of Leishmania to complement its inherent defects in porphyrin biosynthesis, resulting in cytosolic accumulation of abundant PS in the form of uroporphyrin 1 (URO). Another example is the chemical engineering of PC for hydrophilicity, thereby facilitating the endocytosis of such PS by cells. Leishmania loaded with cytosolic URO and endosomal PC are inactivated by the 1O2 produced via light-activation of these PS in the two different cell compartments. The inactivated Leishmania are nonviable, but have their natural vaccines and adjuvants well-preserved for prophylactic vaccination against experimental leishmaniasis. 1O2-inactivated Leishmania is potentially useful to serve as a platform for the safe and effective delivery of transgenically add-on vaccines against malignant and viral diseases in experimental models. Hydrophilic and cationic PC were also shown experimentally to act as a new type of dim light-activable insecticides, i.e., their mosquito larvicidal activities with <µM LD50 values. Similar results are expected by studying PC in additional laboratory insect models. A significant advantage has long been attributed to this type of insecticide, i.e., their aversion to a selection of genetic variants for resistance. An additional advantage of PC is their excitability to produce insecticidal 1O2 with deep-penetrating red or infrared light invisible to most insects, thereby potentially increasing the range and scope of targetable insect vectors.

Effects of Pterostilbene on Heart and Lung Oxidative Stress Parameters in 2 Experimental Models of Cardiovascular Disease: Myocardial Infarction and Pulmonary Arterial Hypertension.

Myocardial infarction (MI) and pulmonary arterial hypertension (PAH) are 2 prevalent cardiovascular diseases. In both conditions, oxidative stress is associated with a worse prognosis. Pterostilbene (PTE), an antioxidant compound, has been studied as a possible therapy for cardiovascular diseases. This study aims to evaluate the effect of PTE on oxidative stress in the hearts of animals with MI and in the lungs of animals with PAH. Male Wistar rats were used in both models. In the MI model, the experimental groups were sham, MI, and MI + PTE. In the PAH model, the experimental groups were control, PAH, and PAH + PTE. Animals were exposed to MI through surgical ligation of the left coronary artery, or to PAH, by the administration of monocrotaline (60 mg/kg). Seven days after undergoing cardiac injury, the MI + PTE animals were treated with PTE (100 mg/kg day) for 8 days. After this, the heart was collected for molecular analysis. The PAH + PTE animals were treated with PTE (100 mg/kg day) for 14 days, beginning 7 days after PAH induction. After this, the lungs were collected for biochemical evaluation. We found that PTE administration attenuated the decrease in ejection fraction and improved left ventricle end-systolic volume in infarcted animals. In the PAH model, PTE improved pulmonary artery flow and decreased reactive oxygen species levels in the lung. PTE administration promoted protective effects in terms of oxidative stress in 2 experimental models of cardiac diseases: MI and PAH. PTE also improved cardiac function in infarcted rats and pulmonary artery flow in animals with PAH.

Brazil nut–enriched diet modulates bone mineral density and body composition in an experimental model of chronic kidney disease

ObjectiveThis study investigates the effects of a Brazil nut-enriched diet on body composition and bone parameters in CKD animal model. MethodsMale Wistar rats were assigned to the following groups: Sham (n=8), Nx (n=6), nephrectomized rats, and NxBN (n=6), nephrectomized rats and an enricheddiet with 5% Brazil nut. Body composition parameters were obtained by dual-energy X- ray absorptiometry (DXA). Bioclin kits determined plasmatic calcium. The femurs werecollected to determine absolute mass and length, bone mineral density, and biomechanical tests. ResultsThe NxBN group exhibited a higher total body bone mineral density (BMD) value than the Nx group (0.177±0.004g/cm2vs 0,169±0.003g/cm2; p=0.0397). No significant differences were observed regarding absolute mass, length, BMD, and biomechanical parameters in the femurs of the groups. Moreover, no significant differences were found in plasmatic calcium levels among the groups. ConclusionsBrazil-nut enriched diet modulated BMD in CKD experimental model, and further studies are demanded to understand the pathways involved in this finding.

Investigating pulmonary neuroendocrine cells in human respiratory diseases with airway models.

Despite accounting for only ∼0.5% of the lung epithelium, pulmonary neuroendocrine cells (PNECs) appear to play an outsized role in respiratory health and disease. Increased PNEC numbers have been reported in a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma. Moreover, PNECs are the primary cell of origin for lung neuroendocrine cancers, which account for 25% of aggressive lung cancers. Recent research has highlighted the crucial roles of PNECs in lung physiology, including in chemosensing, regeneration and immune regulation. Yet, little is known about the direct impact of PNECs on respiratory diseases. In this Review, we summarise the current associations of PNECs with lung pathologies, focusing on how new experimental disease models, such as organoids derived from human pluripotent stem cells or tissue stem cells, can help us to better understand the contribution of PNECs to respiratory diseases.

In vivo and in vitro effects of resveratrol in experimental models of Parkinson's disease

In vivo and in vitro effects of resveratrol in experimental models of Parkinson's disease

Experimental Animal Models of Periodontal Diseases

Abstract Periodontal diseases involve several conditions that are defined by pathologic loss of the periodontal ligament and alveolar bone. Periodontitis is an inflammatory disease of periodontal tissue caused by a host immune response to dysbiotic microbial biofilm whose progression associated with destruction of tooth supporting tissue is promoted by host proteinases. Periradicular periodontitis is the most commonly diagnosed disease that affects the pathology of periodontal tissue in the area of the tooth root. This disease has also been described as apical periodontitis. Several experimental models of periodontal diseases have been developed in recent years. This paper provides an overview of experimentally induced animal models of periodontal disease (periodontitis and periradicular periodontitis) and the possibility of using different experimental animals to study aspects of periodontal disease, each with advantages and disadvantage.