Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli

BACKGROUND: Common inbred mouse strains are genotypically diverse, but it is still poorly understood how this diversity relates to specific differences in behavior. To identify quantitative trait genes that influence taste behavior differences, it is critical to utilize assays that exclusively measure the contribution of orosensory cues. With a few exceptions, previous characterizations of behavioral taste sensitivity in inbred mouse strains have generally measured consumption, which can be confounded by post-ingestive effects. Here, we used a taste-salient brief-access procedure to measure taste sensitivity to eight stimuli characterized as bitter or aversive in C57BL/6J (B6) and DBA/2J (D2) mice. RESULTS: B6 mice were more sensitive than D2 mice to a subset of bitter stimuli, including quinine hydrochloride (QHCl), 6-n-propylthiouracil (PROP), and MgCl(2). D2 mice were more sensitive than B6 mice to the bitter stimulus raffinose undecaacetate (RUA). These strains did not differ in sensitivity to cycloheximide (CYX), denatonium benzoate (DB), KCl or HCl. CONCLUSION: B6-D2 taste sensitivity differences indicate that differences in consumption of QHCl, PROP, MgCl(2 )and RUA are based on immediate orosensory cues, not post-ingestive effects. The absence of a strain difference for CYX suggests that polymorphisms in a T2R-type taste receptor shown to be differentially sensitive to CYX in vitro are unlikely to differentially contribute to the CYX behavioral response in vivo. The results of these studies point to the utility of these common mouse strains and their associated resources for investigation into the genetic mechanisms of taste

Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats

Abstract Background Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis. Methods We compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats. Results We show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36. Conclusion Based on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.https://deepblue.lib.umich.edu/bitstream/2027.42/145618/1/13293_2018_Article_202.pd

NF-κB Mediates FGF Signal Regulation of msx-1 Expression

AbstractThe nuclear factor-κB (NF-κB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-κB activity is necessary for both chicken and mouse limb development. We report here that the NF-κB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-κB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential κB-binding sites similar to the interferon-γ (IFN-γ) κB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-κB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-κB mediates the FGF-2/-4 signal regulation of msx-1 gene expression

Effects of Infrared Radiation on Skin Photo-Aging and Pigmentation

Infrared radiation is increasingly and uncritically used for cosmetic and wellness purposes, despite the poorly understood biologic effects of such treatments on humans. In the present study, we investigated the effects of infrared radiation on collagen and elastin production in dermal fibroblasts, as well as the clinical and histopathologic effects of infrared radiation on photo-aged facial skin lesions. In order to determine the effects of infrared radiation on collagen and elastin production, dermal fibroblasts were exposed to infrared radiation for varying lengths of time and collagen and elastin contents were subsequently determined. Additionally, 20 patients with mild to moderate facial wrinkles and hyperpigmented lesions received daily treatments of far infrared radiation (900 to 1000 µm) for six-months. During the treatment, patients and a medical observer conducted independent photographic and clinical evaluations every 4 weeks, and skin biopsies were obtained for histological analysis at baseline and one month post-treatment. We found that the content of collagen and elastin produced by the fibroblasts increased after infrared radiation, and that this increase was proportional to the duration of irradiation exposure. Following 6 months of treatment, all patients reported good (51-75%) improvements in skin texture and roughness. Additionally, patients noted fair (25-50%) improvement in color tone of the skin; however, improvements in hyperpigmented lesions were not observed. Objective medical evaluation of the patients indicated that roughness and laxity were fairly improved, but there was no significant improvement in hyperpigmented lesions. Histological examination failed to reveal any differences as well. These results suggest that infrared radiation may have beneficial effects on skin texture and wrinkles by increasing collagen and elastin contents from the stimulated fibroblasts. Therefore, skin treatment with infrared radiation may be an effective and safe non-ablative remodeling method, and may also be useful in the treatment of photo-aged skin

Molecular Mechanisms and In Vivo Mouse Models of Skin Aging Associated with Dermal Matrix Alterations

Skin is the most superficial body organ and plays an important role in protecting the body from environmental damage and in forming social relations. With the increase of the aging population in our society, dermatological and cosmetic concerns of skin aging are rapidly increasing. Skin aging is a complex process combined with intrinsic and extrinsic factors. Intrinsic or chronological skin aging results from the passage of time and is influenced by genetic factors. Extrinsic skin aging is mainly determined by UV irradiation, also called photoaging. These two types of aging processes are superimposed on sun-exposed skin, and have a common feature of causing dermal matrix alterations that mostly contribute to the formation of wrinkles, laxity, and fragility of aged skin. The dermal matrix contains extracellular matrix proteins such as collagen, elastin, and proteoglycans that confer the strength and resiliency of skin. Skin aging associated with dermal matrix alterations and atrophy can be caused by cellular senescence of dermal cells like fibroblasts, and decreased synthesis and accelerated degradation of dermal matrix components, especially collagen fibers. Both intrinsic aging and photoaging exert influence during each step of dermal matrix alteration via different mechanisms. Mouse models of skin aging have been extensively developed to elucidate intrinsic aging and photoaging processes, to validate in vitro biochemical data, and to test the effects of pharmacological tools for retarding skin aging because they have the advantages of being genetically similar to humans and are easily available

5-α reductase inhibitors and prostate cancer prevention: where do we turn now?

With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research