Deletion of IRS-1 leads to growth failure and insulin resistance with downregulation of liver and muscle insulin signaling in rats.

Insulin receptor substrate (IRS)-1 and IRS-2 are major molecules that transduce signals from insulin and insulin-like growth factor-I receptors. The physiological functions of these proteins have been intensively investigated in mice, while little is known in other animals. Our previous study showed that the disruption of IRS-2 impairs body growth but not glucose tolerance or insulin sensitivity in rats, which led us to hypothesize that IRS-1 plays more pivotal roles in insulin functions than IRS-2.

Regulation of RHOV signaling by interaction with SH3 domain-containing adaptor proteins and phosphorylation by PKA.

RHOV and RHOU are considered atypical Rho-family small GTPases because of the existence of N- and C-terminal extension regions, abnormal GDP/GTP cycling, and post-translational modification. Particularly, RHOV and RHOU both have a proline-rich (PR) motif in the N-terminal region. It has been reported that the PR motif of RHOU interacts with GRB2, a SH3 domain-containing adaptor protein, and regulates its activity through EGF receptor signaling.

Risk factor analysis for cisplatin-induced nephrotoxicity with the short hydration method in diabetic patients.

The occurrence of cisplatin (CDDP)-induced nephrotoxicity (CIN) has decreased with advancements in supportive care. In contrast, we reported that baseline diabetes mellitus (DM) complications significantly worsen CIN. This study aimed to determine further risk factors associated with CIN development in DM patients.

In Vivo Modeling of Skeletal Muscle Diseases Using the CRISPR/Cas9 System in Rats.

The CRISPR/Cas9 system is a powerful gene editing tool that can be used to modify a target gene in almost all species. It unlocks the possibility of generating knockout or knock-in genes in laboratory animals other than mice. The Dystrophin gene is implicated in human Duchenne muscular dystrophy; however, Dystrophin gene mutant mice do not show severe muscle degenerating phenotypes when compared to humans.

Suppression of MyoD induces spontaneous adipogenesis in skeletal muscle progenitor cell culture.

The degree of intramuscular adipose tissue accumulation is one of the factors affecting meat quality. Accumulation of adipocytes is also observed under the pathological condition of skeletal muscle such as muscular dystrophy and sarcopenia. The origin of adipocytes seen in skeletal muscle is mesenchymal progenitor cells that can give rise to both adipocytes and fibroblasts.

Cellular senescence-mediated exacerbation of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive disease characterised by chronic muscle degeneration and inflammation. Our previously established DMD model rats (DMD rats) have a more severe disease phenotype than the broadly used mouse model. We aimed to investigate the role of senescence in DMD using DMD rats and patients.

Evaluation of Proteinuria Using Urine Protein : Creatine Ratio in Treatment with Molecular Targeted Agents for Advanced Renal Cell Carcinoma.

The usefulness of the urine protein : creatine ratio (UPCR) in management of molecular targeted therapy and immunotherapy has not been studied, although urine protein dipstick testing (uPr) is widely used in the clinical setting. The aim of this study was to investigate the usefulness of UPCR as compared to uPr in patients undergoing molecular targeted therapy for advanced renal cell carcinoma (RCC). A total of 25 patients (median age 68 years) with advanced RCC were included.

Pathological evaluation of rats carrying in-frame mutations in the dystrophin gene: a new model of Becker muscular dystrophy.

Dystrophin, encoded by the gene on the X chromosome, stabilizes the sarcolemma by linking the actin cytoskeleton with the dystrophin-glycoprotein complex (DGC). In-frame mutations in cause a milder form of X-linked muscular dystrophy, called Becker muscular dystrophy (BMD), characterized by the reduced expression of truncated dystrophin. So far, no animal model with in-frame mutations in has been established.

Disruption of insulin receptor substrate-2 impairs growth but not insulin function in rats.

Insulin receptor substrate (IRS)-2, along with IRS-1, is a key signaling molecule that mediates the action of insulin and insulin-like growth factor (IGF)-I. The activated insulin and IGF-I receptors phosphorylate IRSs on tyrosine residues, leading to the activation of downstream signaling pathways and the induction of various physiological functions of insulin and IGF-I. Studies using IRS-2 knockout (KO) mice showed that the deletion of IRS-2 causes type 2 diabetes due to peripheral insulin resistance and impaired β-cell function.

Reduced fibrillar collagen accumulation in skeletal muscle of secreted protein acidic and rich in cysteine (SPARC)-null mice.

We have previously shown that secreted protein acidic and rich in cysteine (SPARC) promotes myogenic differentiation of rat skeletal muscle progenitor cells in vitro, and in vivo small interfering RNA (siRNA)-mediated transient suppression of SPARC expression in skeletal muscle of mice causes atrophic changes of myofibers, suggesting that SPARC plays a role in the maintenance of skeletal muscle function. In order to know the effect of long-term deficiency of SPARC on skeletal muscle, we performed phenotypic analyses of skeletal muscle of SPARC-null mice. Age-associated changes of myofiber diameters were comparable between wild type (WT) and SPARC-null mice at all ages examined, indicating that the growth of myofibers is unaffected by the absence of SPARC.

Pneumothorax as an Adverse Event in Patients with Lung Metastasis of Soft Tissue Sarcoma under Eribulin Treatment.

Pneumothorax has been reported as a pazopanib-associated adverse event in patients with lung metastases of soft tissue sarcoma (STS). However, pneumothorax triggered by eribulin treatment has never been reported. We herein report two cases of spontaneous pneumothorax in patients with STS treated with eribulin.

Attributes' Importance for Zero-Shot Pose-Classification Based on Wearable Sensors.

This paper presents a simple yet effective method for improving the performance of zero-shot learning (ZSL). ZSL classifies instances of unseen classes, from which no training data is available, by utilizing the attributes of the classes. Conventional ZSL methods have equally dealt with all the available attributes, but this sometimes causes misclassification.

Roles of chondroitin sulfate proteoglycan 4 in fibrogenic/adipogenic differentiation in skeletal muscle tissues.

Intramuscular adipose tissue and fibrous tissue are observed in some skeletal muscle pathologies such as Duchenne muscular dystrophy and sarcopenia, and affect muscle strength and myogenesis. They originate from common fibrogenic/adipogenic cells in the skeletal muscle. Thus, elucidating the regulatory mechanisms underlying fibrogenic/adipogenic cell differentiation is an important step toward the mediation of these disorders.

Possible involvement of the cerebellum in motor-function impairment in progranulin-deficient mice.

Progranulin (PGRN) is a multifunctional growth factor involved in many physiological and pathological processes in the brain such as sexual differentiation, neurogenesis, neuroinflammation, and neurodegeneration. Previously, we showed that PGRN was expressed broadly in the brain and the Purkinje cells in the cerebellum were one of the regions with the highest expression level of PGRN. Thus, in the present study, we investigated the possible roles of PGRN in the cerebellum by comparing wild-type (WT) and PGRN-deficient (KO) mice with immunohistochemical staining for calbindin, a marker of Purkinje cells.

Basic fibroblast growth factor is pro-adipogenic in rat skeletal muscle progenitor clone, 2G11 cells.

Intramuscular adipose tissue (IMAT) formation is a hallmark of marbling in cattle. IMAT is considered to originate from skeletal muscle progenitor cells with adipogenic potential. However, the mechanism involved in IMAT formation from these progenitor cells in vivo remains unclear.

[Transdisciplinary Approach for Sarcopenia. Molecular mechanism of sarcopenia : The role of skeletal muscle niche component SPARC in the regulation of myogenesis and adipogenesis and its alteration with age].

Sarcopenia, an age-related decline in skeletal muscle mass and strength, causes the decline of the quality of life in the elderly. The age-related alteration in the differentiation potency of satellite cells, myogenic tissue specific stem cells in skeletal muscle, and preadipocytes in skeletal muscle is possibly involved in the disruption of homeostasis in skeletal muscle. The differentiation of the cells is affected by the microenvironment surrounding the cells, called niche.

Generation of muscular dystrophy model rats with a CRISPR/Cas system.

Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin. DMD model animals, such as mdx mice and canine X-linked muscular dystrophy dogs, have been widely utilized in the development of a treatment for DMD. Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats.

Myotube formation is affected by adipogenic lineage cells in a cell-to-cell contact-independent manner.

Intramuscular adipose tissue (IMAT) formation is observed in some pathological conditions such as Duchenne muscular dystrophy (DMD) and sarcopenia. Several studies have suggested that IMAT formation is not only negatively correlated with skeletal muscle mass but also causes decreased muscle contraction in sarcopenia. In the present study, we examined w hether adipocytes affect myogenesis.

Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells.

Aging causes phenotypic changes in skeletal muscle progenitor cells (Skm-PCs), such as reduced myogenesis and increased adipogenesis due to alterations in their environment or niche. Secreted protein acidic and rich in cysteine (SPARC), which is secreted into the niche of Skm-PCs, inhibits adipogenesis and promotes myogenesis. We have previously reported that Skm-PC responsiveness to SPARC declines with age, although the mechanism underlying this decline is unknown.

Ex vivo bupivacaine treatment results in increased adipogenesis of skeletal muscle cells in the rat.

Intramuscular adipose tissue (IMAT) is observed in some skeletal muscle pathologies. IMAT is implicated not only in the disorders of muscle contraction, but also of metabolism and insulin sensitivity due to its nature as a secretary organ. Several studies indicate the presence of cells with adipogenic potential in skeletal muscle.

Loss of SPARC in mouse skeletal muscle causes myofiber atrophy.

Introduction: The expression of secreted protein acidic and rich in cysteine (SPARC) in skeletal muscle decreases with age. Here, we examined the role of SPARC in skeletal muscle by reducing its expression.

Methods: SPARC expression was suppressed by introducing short interfering RNA (siRNA) into mouse tibialis anterior muscle.

In vivo electroporation induces cell cycle reentry of myonuclei in rat skeletal muscle.

Adult urodele amphibians such as newts are capable of regenerating lost structures including their limbs. In these species, dedifferentiation of myofiber is essential for the regenerative process. Upon terminal differentiation, nuclei of myofiber (myonuclei) are withdrawn from cell cycle, but prior to dedifferentiation, myonuclei reenter the cell cycle.

Age-related resistance of skeletal muscle-derived progenitor cells to SPARC may explain a shift from myogenesis to adipogenesis.

Aging causes phenotypic changes in skeletal muscle progenitor cells (SMPCs) that lead to the loss of myogenicity and adipogenesis. Secreted protein acidic and rich in cysteine (SPARC), which is secreted from SMPCs, stimulates myogenesis and inhibits adipogenesis. The present study aimed to examine whether changes in SPARC expression, its signaling pathway, or both are involved in age-related phenotypic changes in SMPCs.