Frequency: Quarterly E- ISSN: 2250-0332 P- ISSN: 2249-362X IBI Factor 3.8 Abstracted/ Indexed in: Ulrich's International Periodical Directory, Google Scholar, SCIRUS, Genamics Journal Seek, PSOAR, getCITED, Infobase Index, EBSCO Information Services
Quarterly published in print and online "Inventi Impact: Animal Models & Cell Assays" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals. It focuses on multidimensional aspects of animal models and cell assays particularly leading to bio-profiling and drug development. The journal accepts articles based on in-vivo studies, as well as in-vitro.
Pathogenesis of AKI is complex and involves both local events in the kidney as well as systemic effects in the body that are\ninterconnected and interdependent. Despite intensive investigations there is still no pharmacological agent that could provide\ncomplete protection against cisplatin nephrotoxicity. In the last decade mesenchymal stem cells (MSCs) have been proposed as a\npotentially useful therapeutic strategy in various diseases, including acute kidney injury. Although MSCs have potent\nimmunosuppressive properties, animal studies also suggest that transplanted MSCs may elicit immune response. Interestingly,\ntumorigenicity of transplanted MSCs in animal studies has been rarely studied. Since the risk of tumorigenicity of particular\ntherapy as well as the immune response to solid or cell grafts is a major issue in clinical trials, the aim of the present paper is to\ncritically summarize the results of MSC transplantation on animal models of AKI, particularly cisplatin-induced animal models,\nand to expose results and main concerns about immunogenicity and tumorigenicity of transplanted MSCs, two important issues\nthat need to be addressed in future studies....
This study investigated the effects of ?-alanine\n(BA) ingestion on the behavioral and neuroendocrine\nresponse of post-traumatic stress disorder (PTSD) in a\nmurine model. Animals were fed a normal diet with or without\n(PL) BA supplementation (100 mg kg?1) for 30 days.\nAnimals were then exposed to a predator-scent stress (PSS)\nor a sham (UNEX). Behaviors were evaluated using an elevated\nplus maze (EPM) and acoustic startle response (ASR)\n7 days following exposure to the PSS. Corticosterone concentrations\n(CS), expression of brain-derived neurotrophic\nfactor (BDNF), and brain carnosine concentrations were\nanalyzed a day later. Animals in PSS+PL spent significantly\nless time in the open arms and in the number of entries in\nthe EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals\nin PSS+BA had comparable scores to UNEX+BA.\nAnxiety index was higher (p < 0.05) in PSS+PL compared\nto PSS+BA or animals that were unexposed. ASR\nand freezing were greater (p < 0.05) in animals exposed to\nPSS compared to animals unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared to\nunexposed animals. Brain carnosine concentrations in the\nhippocampus and other brain sections were significantly\ngreater in animals supplemented with BA compared to PL.\nBDNF expression in the CA1 and DG subregions of the\nhippocampus was lower (p < 0.05) in animals exposed and\nfed a normal diet compared to animals exposed and supplemented\nwith BA, or animals unexposed. In conclusion,\nBA supplementation in rats increased brain carnosine concentrations\nand resulted in a reduction in PTSD-like behavior,\nwhich may be mediated in part by maintaining BDNF\nexpression in the hippocampus....
The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUVmax), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUVmax was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R2 = 71.48%) between SUVmax values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area....
Abstract: The failure of drug efficacy in clinical trials remains a big issue in cancer research. This is\nlargely due to the limitations of two-dimensional (2D) cell cultures, the most used tool in drug\nscreening. Nowadays, three-dimensional (3D) cultures, including spheroids, are acknowledged\nto be a better model of the in vivo environment, but detailed cell death assays for 3D cultures\n(including those for ferroptosis) are scarce. In this work, we show that a new cell death analysis\nmethod, named 3D Cell Death Assay (3DELTA), can efficiently determine different cell death types\nincluding ferroptosis and quantitatively assess cell death in tumour spheroids. Our method uses\nSytox dyes as a cell death marker and Triton X-100, which efficiently permeabilizes all cells in\nspheroids, was used to establish 100% cell death. After optimization of Sytox concentration, Triton\nX-100 concentration and timing, we showed that the 3DELTA method was able to detect signals from\nall cells without the need to disaggregate spheroids. Moreover, in this work we demonstrated that\n2D experiments cannot be extrapolated to 3D cultures as 3D cultures are less sensitive to cell death\ninduction. In conclusion, 3DELTA is a more cost-effective way to identify and measure cell death\ntype in 3D cultures, including spheroids....
Biomedical materials for bone therapy are usually assessed for their biocompatibility and safety employing animal models or in vitro\nmonolayer cell culture assays.However, alternative in vitro models may offer controlled conditions closer to physiological responses\nand reduce animal testing. In this work, we developed a 3D spheroidal cell culture with potential to evaluate simultaneously\nmaterial-cell and cell-cell interactions. Different cell densities of murine MC3T3-E1 preosteoblasts or human primary osteoblasts\n(HOb) were used to determine the ideal procedure of spheroidal cultures and their adequacy to material testing. Cells were seeded\non 96-well plates coated with agar and incubated in agitation from 1 to 7 days. Aggregate morphology was qualitatively evaluated\nconsidering the shape, size, repeatability, handling, and stability of spheroids. Higher cell densities induced more stable spheroids,\nand handling was considered appropriate starting from 2 Ã?â?? 104 cells. Confocal microscopy and Scanning Electron Microscopy\nindicate that most cells within the aggregate core are viable. Exposure to positive controls has shown a dose dependent cell\ndeath as measured by XTT assay. Aggregates were stable and presented good viability when employed on standardized testing\nof metallic and polymer-based biomaterials. Therefore, osteoblast spheroids may provide a promising tool for material screening\nand biocompatibility testing....
Moscatilin can protect rat pheochromocytoma cells against methylglyoxal-induced damage.\nElimination of the effect of advanced glycation end-products (AGEs) but activation of AMP-activated\nprotein kinase (AMPK) are the potential therapeutic targets for the neurodegenerative diseases.\nOur study aimed to clarify AMPK signalingâ??s role in the beneficial effects of moscatilin on the\ndiabetic/hyperglycemia-associated neurodegenerative disorders. AGEs-induced injury in SH-SY5Y\ncells was used as an in vitro neurodegenerative model. AGEs stimulation resulted in cellular\nviability loss and reactive oxygen species production, and mitochondrial membrane potential collapse.\nIt was observed that the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase\nincreased in SH-SY5Y cells following AGEs exposure. AGEs decreased Bcl-2 but increased Bax\nand p53 expression and nuclear factor kappa-B activation in SH-SY5Y cells. AGEs also attenuated\nthe phosphorylation level of AMPK. These AGEs-induced detrimental effects were ameliorated by\nmoscatilin, which was similar to the actions of metformin. Compound C, an inhibitor of AMPK,\nabolished the beneficial effects of moscatilin on the regulation of SH-SY5Y cellsâ?? function, indicating\nthe involvement of AMPK. In conclusion, moscatilin offers a promising therapeutic strategy to\nreduce the neurotoxicity or AMPK dysfunction of AGEs. It provides a potential beneficial effect with\nAGEs-related neurodegenerative diseases....
RNA synthesis by the genotype 1b hepatitis C virus (HCV) polymerase (NS5B) transiently expressed in Human embryonic kidney 293T cells or liver hepatocytes was found to robustly stimulate RIG-I-dependent luciferase production from the interferon �Ÿ promoter in the absence of exogenously provided ligand. This cell-based assay, henceforth named the 5BR assay, could be used to examine HCV polymerase activity in the absence of other HCV proteins. Mutations that decreased de novo initiated RNA synthesis in biochemical assays decreased activation of RIG-I signaling. In addition, NS5B that lacks the C-terminal transmembrane helix but remains competent for RNA synthesis could activate RIG-I signaling. The addition of cyclosporine A to the cells reduced luciferase levels without affecting agonist-induced RIG-I signaling. Furthermore, non-nucleoside inhibitor benzothiadiazines (BTDs) that bind within the template channel of the 1b NS5B were found to inhibit the readout from the 5BR assay. Mutation M414T in NS5B that rendered the HCV replicon resistant to BTD was also resistant to BTDs in the 5BR assay. Co-expression of the HCV NS5A protein along with NS5B and RIG-I was found to inhibit the readout from the 5BR assay. The inhibition by NS5A was decreased with the removal of the transmembrane helix in NS5B. Lastly, NS5B from all six major HCV genotypes showed robust activation of RIG-I in the 5BR assay. In summary, the 5BR assay could be used to validate inhibitors of the HCV polymerase as well as to elucidate requirements for HCV-dependent RNA synthesis....
This study was aimed at extracting, characterizing, and exploring the detoxification activity of the peptide-containing polysaccharide from Agaricus balchaschensis. An anion adsorption fraction was acquired through hot water extraction. Its structure was analyzed, and the potential protective effect against cadmium-intoxicated mice was explored. Structural analysis revealed that the principal component of the peptide-containing polysaccharide of A. balchaschensis (ABPCP) is polysaccharide, which consists of glucose, mannose, galactose, and xylose, containing (1 → 4)-linked α-D-glucan, (1 → 3)-linked β-D-Glcp, (1 → 4)-linked β-D-Glcp, (1 → 6)-linked β-D-Glcp, (1 → 6)-linked β-D-Manp, (1 → 3)-linked β-D-Galp, (1 → 6)-linked β-D-Galp, and (1 → 4)-linked β-D-xylan. The amino acid content of ABPCP is 11.747 mg/g. Threonine, serine, glutamate, glycine, alanine, cysteine, valine, methionine, lysine, and arginine were detected in ABPCP, among which the content of glutamate was the highest. The alleviating effect of ABPCP on cadmium poisoning in mice was investigated. ABPCP significantly reduced the cadmium content in serum and the heart, kidneys, and liver, which indicates that ABPCP could promote cadmium discharge. ABPCP also significantly decreased serum nitric oxide, endothelin-1, urea, uric acid, and serum creatinine, alleviating kidney and liver damage caused by cadmium. All these results manifest that ABPCP can lower the cadmium content in organs and alleviate the damage to kidneys and livers damaged by Cd....
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic\neczematous lesions that are commonly treated with topical corticosteroids and calcineurin inhibitors. Side-effects\nand safety concerns associated with these agents restrict their use, and new, safe treatment options are therefore\nneeded. Recent reports suggest that serotonin, i.e. 5-hydroxytryptamine (5-HT) and the 5-HT2 receptor family may\ncontribute to inflammation and pruritus in the skin. The objective of this particular study was to investigate the\n5HT2B receptor antagonist AM1030 with respect to its anti-inflammatory profile and potential.\nMethods: AM1030 was tested in a set of distinct human and rodent in vitro and in vivo models, differing with\nrespect to e.g. T cell involvement, triggering stimulus, main read-outs and route of drug administration. The in vitro\nsystems used were staphylococcal enterotoxin A (SEA)-stimulated human peripheral blood mononuclear cells,\nlipopolysaccharide (LPS)-stimulated human primary monocytes, LPS-stimulated human THP-1 monocytes and\nLPS-stimulated mouse primary macrophages. The in vivo systems used were LPS- and SEA-induced cytokine\nproduction in the mouse, antigen-induced arthritis in the rat, glucose-6-phosphate isomerase-induced arthritis in\nthe mouse and delayed-type hypersensitivity reaction in the mouse. In addition, different cell populations were\nanalyzed with respect to their expression of the 5-HT2B receptor at the mRNA level.\nResults: AM1030 significantly reduced both T cell-dependent and T cell-independent inflammatory responses, in\nvivo and in vitro. Due to the low or absent expression of the 5-HT2B receptor on T cell populations, the influence of\nAM1030 in T cell-dependent systems is suggested to be mediated via an indirect effect involving\nantigen-presenting cell types, such as monocytes and macrophages.\nConclusion: Based on the wide range of model systems used in this study, differing e.g. with respect to species,\nT cell involvement, triggering stimuli, route of drug administration and read-outs, our results suggest a broad\nanti-inflammatory effect of AM1030 and identify the 5-HT2B receptor as a promising future target for\nanti-inflammatory intervention, e.g. in AD....
Background: Atopic dermatitis (AD) is characterized by chronic inflammation of the skin. AD develops\nmainly in infants and young children. It induces skin disorders and signals the initiation of the allergic march\nincluding allergic asthma and rhinitis. Probiotics modify intestinal microbial populations in a beneficial way\nfor human and animal hosts by reducing inflammatory cytokines.\nObjective: As a result of their immunomodulatory properties, probiotics have been considered a promising\ntherapeutic option for the prevention and treatment of AD.\nDesign: In this study, we examined the effects of GI7, a potential probiotic mixture consisting of seven strains\nof bifidobacteria and lactic acid bacteria, on AD in a mouse model.\nResults: Administration of GI7 for 8 weeks reduced AD-like skin lesions and induced changes in the levels of\nserum markers such as immunoglobulin E and cytokines related to T helper (Th)1 and Th2 cells, and in skin\nbarrier genes. Alleviation of AD seems to be associated with GI7-induced generation of CD4Foxp3\nregulatory T cells.\nConclusions: The probiotic mixture may have potential to improve symptoms of AD....
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