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Cells Aug 2022The golden Syrian hamster () has long been a valuable rodent model of human diseases, especially infectious and metabolic diseases. Hamsters have also been valuable... (Review)
Review
The golden Syrian hamster () has long been a valuable rodent model of human diseases, especially infectious and metabolic diseases. Hamsters have also been valuable models of several chemically induced cancers such as the DMBA-induced oral cheek pouch cancer model. Recently, with the application of CRISPR/Cas9 genetic engineering technology, hamsters can now be gene targeted as readily as mouse models. This review describes the phenotypes of three gene-targeted knockout (KO) hamster cancer models, , , and . Notably, these hamster models demonstrate cancer phenotypes not observed in mouse KOs. In some cases, the cancers that arise in the KO hamster are similar to cancers that arise in humans, in contrast with KO mice that do not develop the cancers. An example is the development of aggressive acute myelogenous leukemia (AML) in KO hamsters. The review also presents a discussion of the relative strengths and weaknesses of mouse cancer models and hamster cancer models and argues that there are no perfect rodent models of cancer and that the genetically engineered hamster cancer models can complement mouse models and expand the suite of animal cancer models available for the development of new cancer therapies.
Topics: Animals; Cloning, Molecular; Cricetinae; Genetic Engineering; Humans; Mesocricetus; Mice; Mouth Neoplasms
PubMed: 35954238
DOI: 10.3390/cells11152395 -
Journal of Biomedical Optics Aug 2022The creation of subepithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable biomaterials toward a clinically...
SIGNIFICANCE
The creation of subepithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable biomaterials toward a clinically viable therapy for vocal fold scarring.
AIM
We aim to prove that subepithelial voids can be created in a live animal model and that the ablation process does not engender additional scar formation. We demonstrate localization and long-term retention of an injectable biomaterial within subepithelial voids.
APPROACH
A benchtop nonlinear microscope was used to create subepithelial voids within healthy and scarred cheek pouches of four Syrian hamsters. A model biomaterial, polyethylene glycol tagged with rhodamine dye, was then injected into these voids using a custom injection setup. Follow-up imaging studies at 1- and 2-week time points were performed using the same benchtop nonlinear microscope. Subsequent histology assessed void morphology and biomaterial retention.
RESULTS
Focused ultrashort pulses can be used to create large subepithelial voids in vivo. Our analysis suggests that the ablation process does not introduce any scar formation. Moreover, these studies indicate localization, and, more importantly, long-term retention of the model biomaterial injected into these voids. Both nonlinear microscopy and histological examination indicate the presence of biomaterial-filled voids in healthy and scarred cheek pouches 2 weeks postoperation.
CONCLUSIONS
We successfully demonstrated subepithelial void formation, biomaterial injection, and biomaterial retention in a live animal model. This pilot study is an important step toward clinical acceptance of a new type of therapy for vocal fold scarring. Future long-term studies on large animals will utilize a miniaturized surgical probe to further assess the clinical viability of such a therapy.
Topics: Animals; Biocompatible Materials; Cheek; Cicatrix; Cricetinae; Mesocricetus; Pilot Projects; Vocal Cords
PubMed: 36008882
DOI: 10.1117/1.JBO.27.8.080501 -
Journal of Anatomy May 2022The platysma of the rhesus monkey consists of two parts: a platysma myoides located similar to the human platysma, and a platysma cervicale passing the dorsal cervical...
The platysma of the rhesus monkey consists of two parts: a platysma myoides located similar to the human platysma, and a platysma cervicale passing the dorsal cervical region and being in contact with the cheek pouch. Our investigation showed that the muscle fiber morphology was comparable in both parts. Muscle spindles were only present in regions connected to the cheek pouch and contained only nuclear chain fibers. It is tempting to speculate that they sense the filling of the cheek pouch rather than mimic activities.
Topics: Animals; Cheek; Macaca mulatta; Muscle Fibers, Skeletal; Muscle Spindles; Superficial Musculoaponeurotic System
PubMed: 34893983
DOI: 10.1111/joa.13604 -
Frontiers in Immunology 2023Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for...
INTRODUCTION
Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments.
METHODS
Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later.
RESULTS AND DISCUSSION
Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-β, and TGF-β. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-β-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-β-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.
Topics: Humans; Pulmonary Fibrosis; Aspirin; Docosahexaenoic Acids; Lung; Bleomycin; Transforming Growth Factor beta
PubMed: 36960058
DOI: 10.3389/fimmu.2023.886601 -
Life (Basel, Switzerland) Jul 2022BNCT (Boron Neutron Capture Therapy) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Although...
Boron Neutron Capture Therapy (BNCT) Mediated by Maleimide-Functionalized -Dodecaborate Albumin Conjugates (MID:BSA) for Oral Cancer: Biodistribution Studies and BNCT in the Hamster Cheek Pouch Oral Cancer Model.
BACKGROUND
BNCT (Boron Neutron Capture Therapy) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Although -boronophenylalanine (BPA) has been clinically used, new boron compounds are needed for the advancement of BNCT. Based on previous studies in colon tumor-bearing mice, in this study, we evaluated MID:BSA (maleimide-functionalized -dodecaborate conjugated to bovine serum albumin) biodistribution and MID:BSA/BNCT therapeutic effect on tumors and associated radiotoxicity in the hamster cheek pouch oral cancer model.
METHODS
Biodistribution studies were performed at 30 mg B/kg and 15 mg B/kg (12 h and 19 h post-administration). MID:BSA/BNCT (15 mg B/kg, 19 h) was performed at three different absorbed doses to precancerous tissue.
RESULTS
MID:BSA 30 mg B/kg protocol induced high BSA toxicity. MID:BSA 15 mg B/kg injected at a slow rate was well-tolerated and reached therapeutically useful boron concentration values in the tumor and tumor/normal tissue ratios. The 19 h protocol exhibited significantly lower boron concentration values in blood. MID:BSA/BNCT exhibited a significant tumor response vs. the control group with no significant radiotoxicity.
CONCLUSIONS
MID:BSA/BNCT would be therapeutically useful to treat oral cancer. BSA toxicity is a consideration when injecting a compound conjugated to BSA and depends on the animal model studied.
PubMed: 35888170
DOI: 10.3390/life12071082 -
Scientific Reports Feb 2022Platypuses (Ornithorhynchus anatinus) forage for macroinvertebrate prey exclusively in freshwater habitats. Because food material in their faeces is well digested and...
Platypuses (Ornithorhynchus anatinus) forage for macroinvertebrate prey exclusively in freshwater habitats. Because food material in their faeces is well digested and mostly unidentifiable, previous dietary studies have relied on cheek pouch assessments and stable isotope analysis. Given DNA metabarcoding can identify species composition from only fragments of genetic material, we investigated its effectiveness in analysing the diet of platypuses, and to assess variation across seasons and sexes. Of the 18 orders and 60 families identified, Ephemeroptera and Diptera were the most prevalent orders, detected in 100% of samples, followed by Trichoptera, Pulmonata, and Odonata (86.21% of samples). Caenidae and Chironomidae were the most common families. Diptera had a high average DNA read, suggesting it is an important dietary component that may have been underestimated in previous studies. We found no variation in diet between sexes and only minimal changes between seasons. DNA metabarcoding proved to be a highly useful tool for assessing platypus diet, improving prey identification compared to cheek pouch analysis, which can underestimate soft-bodied organisms, and stable isotope analysis which cannot distinguish all taxa isotopically. This will be a useful tool for investigating how platypus prey diversity is impacted by habitat degradation as a result of anthropogenic stressors.
Topics: Animals; DNA Barcoding, Taxonomic; Diet; Female; Male; Platypus
PubMed: 35145160
DOI: 10.1038/s41598-022-06023-y -
American Journal of Physiology. Heart... Sep 2017Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used... (Comparative Study)
Comparative Study
Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5-trisphosphate receptors (IPRs; 100 μM 2-aminoethoxydiphenylborane), protein kinase C (10 μM bisindolylmaleimide I), angiotensin II type 1 receptors (1 μM losartan), Rho kinase (10 nM-30 μM Y27632 or 300 nM H1152), stretch-activated ion channels (10 nM-1 μM Gd or 5 μM spider venom toxin GsMTx-4) and L-type voltage-gated Ca channels (0.3-100 μM diltiazem) in myogenic tone of cannulated, pressurized (80 cmHO), second-order hamster cremaster or cheek pouch arterioles. Effective inhibition of either PLC or IPRs dilated cremaster arterioles, inhibited Ca waves, and reduced global Ca levels. In contrast, cheek pouch arterioles did not display Ca waves and inhibition of PLC or IPRs had no effect on myogenic tone or intracellular Ca levels. Inhibition of Rho kinase dilated both cheek pouch and cremaster arterioles with equal efficacy and potency but also reduced intracellular Ca signals in both arterioles. Similarly, inhibition of mechanosensitive ion channels with Gd or GsMTx-4 produced comparable dilation in both arterioles. Inhibition of L-type Ca channels with diltiazem was more effective in dilating cremaster (86 ± 5% dilation, = 4) than cheek pouch arterioles (54 ± 4% dilation, = 6, < 0.05). Thus, there are substantial differences in the mechanisms underlying myogenic tone in hamster cremaster and cheek pouch arterioles. Regional heterogeneity in myogenic mechanisms could provide new targets for drug development to improve regional blood flow in a tissue-specific manner. Regional heterogeneity in the mechanisms of pressure-induced myogenic tone implies that resistance vessels may be able to alter myogenic signaling pathways to adapt to their environment. A better understanding of the spectrum of myogenic mechanisms could provide new targets to treat diseases that affect resistance artery and arteriolar function.
Topics: Abdominal Muscles; Animals; Arterioles; Blood Pressure; Calcium Channels, L-Type; Calcium Signaling; Cheek; Dose-Response Relationship, Drug; In Vitro Techniques; Inositol 1,4,5-Trisphosphate Receptors; Male; Mechanotransduction, Cellular; Mesocricetus; Microcirculation; Organ Specificity; Protein Kinase C; Time Factors; Type C Phospholipases; Vascular Resistance; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents
PubMed: 28667050
DOI: 10.1152/ajpheart.00183.2017 -
Scanning Nov 2016The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen...
The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p < 0.05) than control tissue (0.73 ± 0.04), indicating increased fiber alignment within the scar. Depth-resolved average voxel density measurements indicated scarred tissues contained greater (p < 0.005) fiber density (0.72 ± 0.09) compared to controls (0.18 ± 0.03). In the present study, image analysis of both fiber alignment and density from depth-resolved second-harmonic generation images in epi-detection mode enabled the quantification of the increased collagen fiber deposition and alignment typically observed in fibrosis. The epi-detection geometry is the only viable method for in vivo imaging as well as imaging thick turbid tissues. These quantitative endpoints, clearly differentiating between control and scarred hamster cheek pouches, provide an objective means to characterize the extent of vocal fold scarring in vivo in preclinical and clinical research. In particular, this non-invasive method offers advantages for monitoring scar treatments in live animals and following the effects of scarring-related treatments such as application of steroids or drugs targeting pathways involved in fibrosis. SCANNING 38:684-693, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cheek; Cicatrix; Collagen; Cricetinae; Male; Mesocricetus; Microscopy
PubMed: 27111090
DOI: 10.1002/sca.21316 -
Brazilian Dental Journal Jun 2020Oral mucositis is a common inflammatory complication among patients with cancer. This study evaluated the histopathological, stereological, and antioxidant markers of 2%...
Oral mucositis is a common inflammatory complication among patients with cancer. This study evaluated the histopathological, stereological, and antioxidant markers of 2% eucalyptus extract in induced oral mucositis in male golden hamsters. In this animal study, oral mucositis was induced in 30 male golden hamsters by 5-FU (60 mg/kg) on days 0, 5, and 10 of the study. The cheek pouch was scratched with a sterile needle once daily on days 3 and 4. On days 14-17, 2% eucalyptus hydroalcoholic extract gel and Calendula officinalis extract gel groups were treated and then compared with a non-treated control group. The histopathological and stereological scores and the pouch content of malondialdehyde, as well as the activities of glutathione and myeloperoxidase in the pouch tissue, were evaluated. Histopathologic scores of oral mucositis were lower in the eucalyptus gel group than those of the calendula and control groups (p<0.05). Also, a lower malondialdehyde level and higher myeloperoxidase and glutathione activities were detected in the eucalyptus group in comparison to the calendula and control groups (p<0.001). The thickness of the mucosa and submucosa increased in the eucalyptus group. The numerical density of the fibroblast and the volume density of the collagen significantly increased in the eucalyptus group. In conclusion, the use of eucalyptus hydroalcoholic extract may be associated with reduced intensity of oral mucositis, diminished concentration of malondialdehyde, increased activity of myeloperoxidase and glutathione, increased volume of mucosa and submucosa, increased fibroblast and collagen in the induced oral mucositis in golden hamsters undergoing 5-FU consumption.
Topics: Animals; Cricetinae; Eucalyptus; Fluorouracil; Male; Mesocricetus; Mouth Mucosa; Mucositis; Plant Extracts; Stomatitis
PubMed: 32667525
DOI: 10.1590/0103-6440202003140 -
Pharmaceutics Mar 2023Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various...
Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various non-invasive traditional oral dosage forms such as tablets, capsules, and liquid preparations of iron, they are hard to consume for special populations such as pregnant women, pediatric, and geriatric patients with dysphagia and vomiting tendency. The objective of the present study was to develop and characterize pullulan-based iron-loaded orodispersible films (i-ODFs). Microparticles of iron were formulated by a microencapsulation technique, to mask the bitter taste of iron, and ODFs were fabricated by a modified solvent casting method. Morphological characteristics of the microparticles were identified by optical microscopy and the percentage of iron loading was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The fabricated i-ODFs were evaluated for their morphology by scanning electron microscopy. Other parameters including thickness, folding endurance, tensile strength, weight variation, disintegration time, percentage moisture loss, surface pH, and in vivo animal safety were evaluated. Lastly, stability studies were carried out at a temperature of 25 °C/60% RH. The results of the study confirmed that pullulan-based i-ODFs had good physicochemical properties, excellent disintegration time, and optimal stability at specified storage conditions. Most importantly, the i-ODFs were free from irritation when administered to the tongue as confirmed by the hamster cheek pouch model and surface pH determination. Collectively, the present study suggests that the film-forming agent, pullulan, could be successfully employed on a lab scale to formulate orodispersible films of iron. In addition, i-ODFs can be processed easily on a large scale for commercial use.
PubMed: 36986887
DOI: 10.3390/pharmaceutics15031027