BackgroundObesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO).ResultsZebrafish were assigned into two dietary groups. One group of zebrafish was overfed with Artemia (60 mg dry weight/day/fish), a living prey consisting of a relatively high amount of fat. The other group of zebrafish was fed with Artemia sufficient to meet their energy requirements (5 mg dry weight/day/fish). Zebrafish were fed under these dietary protocols for 8 weeks. The zebrafish overfed with Artemia exhibited increased body mass index, which was calculated by dividing the body weight by the square of the body length, hypertriglyceridemia and hepatosteatosis, unlike the control zebrafish. Calorie restriction for 2 weeks was applied to zebrafish after the 8-week overfeeding period. The increased body weight and plasma triglyceride level were improved by calorie restriction. We also performed comparative transcriptome analysis of visceral adipose tissue from DIO zebrafish, DIO rats, DIO mice and obese humans. This analysis revealed that obese zebrafish and mammals share common pathophysiological pathways related to the coagulation cascade and lipid metabolism. Furthermore, several regulators were identified in zebrafish and mammals, including APOH, IL-6 and IL-1β in the coagulation cascade, and SREBF1, PPARα/γ, NR1H3 and LEP in lipid metabolism.ConclusionWe established a zebrafish model of DIO that shared common pathophysiological pathways with mammalian obesity. The DIO zebrafish can be used to identify putative pharmacological targets and to test novel drugs for the treatment of human obesity.

Bioprinting holds great promise toward engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, a novel and mechanically robust biomaterial‐ink based on nonmulberry silk fibroin protein is developed. The silk‐based ink demonstrates suitable mechanical properties required in terms of elasticity and stiffness (≈40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allows the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which are able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin‐43, and maintain synchronously beating of cardiomyocytes. The printed constructs are found to be nonimmunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue‐on‐a‐chip, the silk‐based ink is used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC‐CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. The ability is confirmed of silk‐based supporting hydrogel toward maturation and viability of hiPSC‐CSs and endothelial cells, and for applications in evaluating drug toxicity.

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The increasing number of people suffering from metabolic syndrome and obesity is becoming a serious problem not only in developed countries, but also in developing countries. However, there are few agents currently approved for the treatment of obesity. Those that are available are mainly appetite suppressants and gastrointestinal fat blockers. We have developed a simple and rapid method for the measurement of the feeding volume of Danio rerio (zebrafish). This assay can be used to screen appetite suppressants and enhancers. In this study, zebrafish were fed viable paramecia that were fluorescently-labeled, and feeding volume was measured using a 96-well microplate reader. Gene expression analysis of brain-derived neurotrophic factor (bdnf), knockdown of appetite-regulating genes (neuropeptide Y, preproinsulin, melanocortin 4 receptor, agouti related protein, and cannabinoid receptor 1), and the administration of clinical appetite suppressants (fluoxetine, sibutramine, mazindol, phentermine, and rimonabant) revealed the similarity among mechanisms regulating appetite in zebrafish and mammals. In combination with behavioral analysis, we were able to evaluate adverse effects on locomotor activities from gene knockdown and chemical treatments. In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers.

Postoperative swallowing problems were investigated in 20 patients who had undergone various degrees of surgical resection for oral cancer. The swallowing problems were evaluated on the basis of type of food, degree of aspiration, and duration of postoperative nasogastric tube feeding. Two patients with tongue cancer who had had hemiglossectomy without reconstruction ate normal food without aspiration within a week after operation. Eight patients who had undergone two- to three-quarter glossectomy for tongue cancer ate gruel with no or occasional liquid aspiration. Among 4 patients who had had near-total or total glossectomy for tongue cancer, 3 ate thin gruel or liquid with occasional aspiration. The other could not eat orally because of consistent severe aspiration. One patient with mouth floor cancer underwent resection of the mouth floor in combination with hemiglossectomy and she ate gruel without aspiration. Among 5 patients with mouth floor cancer who had had surgical removal accompanied by near-total or total glossectomy, 3 ate gruel with no or occasional liquid aspiration, 1 ate thin gruel with no aspiration, and the other could not eat orally. A diagnosis of T4 lesions, extensive removal of the tongue base, removal of the geniohyoid and mylohyoid muscles, and removal of the lateral pharyngeal wall were significantly related to poor swallowing function.

Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No. PI 57-2 (ATCC53557) possessing potent and broad antifungal activity in vivo. They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations. Pradimicin Ashowed in vivo therapeutic activity against C. albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromizedmice. 5-Fluorocytosine-and azole-resistant C. albicans strains were susceptible to pradimicin A. This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment. The LD50values after a single iv or im administration were 120mg/kg and more than 400mg/kg, respectively. Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500 Mg/ml, and showed potent anti-influenza virus activity with an IC50 value of 6.8 jUg/ml.

Modern neuroscience increasingly relies on 3D models to study neural circuitry, nerve regeneration, and neural disease. Several different biofabrication approaches have been explored to create 3D neural tissue model structures. Among them, 3D bioprinting has shown to have great potential to emerge as a high-throughput/high precision biofabrication strategy that can address the growing need for 3D neural models. Here, we have reviewed the design principles for neural tissue engineering. The main challenge to adapt printing technologies for biofabrication of neural tissue models is the development of neural bioink, i.e., a biomaterial with printability and gelation properties and also suitable for neural tissue culture. This review shines light on a vast range of biomaterials as well as the fundamentals of 3D neural tissue printing. Also, advances in 3D bioprinting technologies are reviewed especially for bioprinted neural models. Finally, the techniques used to evaluate the fabricated 2D and 3D neural models are discussed and compared in terms of feasibility and functionality.

A crucial step in creating reliable in vitro platforms for neural development and disorder studies is the reproduction of the multicellular three-dimensional (3D) brain microenvironment and the capturing of cell-cell interactions within the model. The power of self-organization of diverse cell types into brain spheroids could be harnessed to study mechanisms underlying brain development trajectory and diseases. A challenge of current 3D organoid and spheroid models grown in petri-dishes is the lack of control over cellular localization and diversity. To overcome this limitation, neural spheroids can be patterned into customizable 3D structures using microfabrication. We developed a 3D brain-like co-culture construct using embedded 3D bioprinting as a flexible solution for composing heterogenous neural populations with neurospheroids and glia. Specifically, neurospheroid-laden free-standing 3D structures were fabricated in an engineered astrocyte-laden support bath resembling a neural stem cell niche environment. A photo-crosslinkable bioink and a thermal-healing supporting bath were engineered to mimic the mechanical modulus of soft tissue while supporting the formation of self-organizing neurospheroids within elaborate 3D networks. Moreover, bioprinted neurospheroid-laden structures exhibited the capability to differentiate into neuronal cells. These brain-like co-cultures could provide a reproducible platform for modeling neurological diseases, neural regeneration, and drug development and repurposing.