Publication

HETEROGENEITY IN DIABETES AND BETA CELLS

As well as being a key risk factor for the development of nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) also appears to accelerate NAFLD progression. Liver biopsy is the reference standard for the diagnosis of the severe form of NAFLD, nonalcoholic steatohepatitis (NASH), and there are two key, non-interchangeable, standardized histologic scoring systems used to evaluate disease features.

Potential antipruritic neuronal targets of nalfurafine in the murine spinal dorsal horn

We examined whether an exogenous KOR agonist, nalfurafine, inhibit scratching bouts evoked by i.t. injection of GRP (FIG. 1). GRP-evoked scratching bouts were reduced by ~56.7% (FIG. 1 A) with no sedation (FIG. 1 B). We next examined the itch-dedicated pathway in the spinal dorsal horn by using in vivo electrophysiology (FIG. 2). In this experiment, CQ was selected as a pruritogen causing nonhistaminergic itch, because nalfurafine also targets nonhistaminergic itch. A few of the CQ-responsive neurons showed reduced firings in a duration of nalfurafine (a blue box in FIG. 2 A).

Selective Janus kinase 1 inhibition resolves inflammation and restores hair growth offering a viable treatment option for alopecia areata

Background Janus Kinase (JAK) inhibition has recently demonstrated therapeutic efficacy in both restoring hair growth and resolving inflammation in Alopecia Areata (AA). These effects are dose dependent and mainly efficacious at ranges close to a questionable risk profile. Objectives We explored the possibility to separate the beneficial and adverse effects of JAK inhibition by selectively inhibiting JAK1 and thereby avoiding side effects associated with JAK2 blockade.

Whole-Mount Multicolor Fluorescent Labeling by In Situ Hybridization in Astyanax mexicanus Embryos and Larvae

Gene expression analyses by molecular histology are a crucial step in understanding gene function in any model organism. In the teleost _Astyanax mexicanus_, here we describe in detail the method we have developed to perform double fluorescent in situ hybridization on whole-mount samples. As an illustration, in the result section, we present an analysis of the expression patterns of four mRNAs expressed in the hypothalamus of the surface and cave morphs of _A. mexicanus_ at 3.5 days postfertilization, three neuropeptides (_npy_, _pomca_, _agrp_) and one transcription factor (_isl1_).

Reversing the NK inhibitory tumor microenvironment by targeting suppressive immune effectors

The efficacy of natural killer (NK) cell-based therapies against solid tumors has been poor. Solid tumors generate a hostile tumor microenvironment (TME) comprising multiple cell types including inhibitory immune cells that play a key role in depressing the antitumor functions of therapeutic NK cells. Understanding how inhibitory immune effectors operate within the confines of the TME is critical to developing therapies to reverse this inhibition.

Leveraging circuits to understand addiction

Advancements in neuroscientific methods often drive new waves of insight into our understanding of addiction. While addiction research questions persist, technical improvements can augment our observational sensitivity, allowing us to update and extend existing addiction models through method development, creative application, and scientific discovery.

Clinicopathologic diagnosis of dVIN related vulvar squamous cell carcinoma: An extended appraisal from a tertiary women's hospital

Background Differentiated vulvar intraepithelial neoplasia (dVIN) is a non-human papilloma virus (HPV)-related high-grade precursor lesion to vulvar squamous cell carcinoma (vSCCa). Although TP53 gene mutations have been identified in 80% of dVIN, its role in dVIN pathogenesis as well as malignant transformation is still being poorly understood. Poor reproducible diagnostic criteria and ambiguous p53 immunostaining patterns, along with morphologic discordance still pose a diagnostic challenge. Methods A series of 60 cases of dVIN-related vSCCa along with adjacent dVIN were evaluated.

Strain-specific responsiveness of hepatitis D virus to interferon-alpha treatment

Background & Aims Pegylated interferon alpha (pegIFNα) is commonly used for the treatment of hepatitis D virus (HDV)-infected patients. However, its mode of action (MoA) in HDV-infected cells remains elusive and only a minority of patients responds to pegIFNα therapy. Herein, we aimed to assess the responsiveness of three different cloned HDV strains to pegIFNα. We used a previously cloned HDV genotype 1 strain (dubbed HDV-1a) that appeared insensitive to IFNα in vitro (Zhang, J.Hepatol.

Analysis of mitochondrial double-stranded RNAs in human cells

Human mitochondrial genome is transcribed bidirectionally, generating long complementary RNAs that can form double-stranded RNAs (mt-dsRNAs). When released to the cytosol, these mt-dsRNAs can activate antiviral signaling. Here, we present a detailed protocol for the analysis of mt-dsRNA expression. The protocol provides three approaches that can complement one another in examining mt-dsRNAs. While the described protocol is optimized for human cells, this approach can be adapted for use in other animal cell lines and tissue samples.

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