Osteopontin is linked with AKT, FoxO1, and myostatin in skeletal muscle cells

Introduction: Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN). Methods: Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in-vitro studies were employed in myogenic cells and the mdx mouse treated with recombinant mouse (rm) or human (Hu) OPN protein. Results: OPN was increased and MSTN was decreased and levels correlated inversely in GRMD hypertrophied muscle. RM-OPN treatment led to induced AKT1 and FoxO1 phosphorylation, microRNA-486 modulation, and decreased MSTN. An AKT1 inhibitor blocked these effects, whereas an RGD-mutant OPN protein and an RGDS blocking peptide showed similar effects to the AKT inhibitor. RMOPN induced myotube hypertrophy and minimal Feret diameter in mdx muscle. Discussion: OPN may interact with AKT1/MSTN/FoxO1 to modify normal and dystrophic muscle

A Critical Role for Muscle Ring Finger-1 in Acute Lung Injury–associated Skeletal Muscle Wasting

Rationale: Acute lung injury (ALI) is a debilitating condition associated with severe skeletal muscle weakness that persists in humans long after lung injury has resolved. The molecular mechanisms underlying this condition are unknown

SCROLLING AND RESIZING-AWARE ANNOTATION FEATURE FOR COMMUNICATION AND COLLABORATION PLATFORMS

In communication and collaboration platforms (which may support, among other things, video conferencing, online meetings, screen sharing, webinars, etc.), annotation is a critical feature. That feature is playing a very important role during the Coronavirus Disease 2019 (COVID-19) period where, for example, universities and companies are relying heavily upon online meeting experiences to seamlessly deliver classes, sessions, presentations, etc. However, current annotation capabilities are not able to adapt to the dynamic nature of a screen share. To address such a challenge, techniques are presented herein that enhance scrolling within or the resizing of an underlying application. Aspects of the presented techniques encompass the binding of a scroll position to drawn annotations, the establishment of a relationship between annotations and application size, the automatic adjustment of pixel density following the resizing of an application, and the normalizing of a pixel\u27s density

Apoptosis in epithelial ovarian tumors

It is now recognized that apoptosis plays an important role in the pathogenesis of tumors. This study evaluated the extent of apoptosis in different grades of ovarian tumors and correlated it with the expression of apoptosis regulatory genes, p53 and bcl-2 and with the total proliferative compartment of the tumor defined by the expression of the proliferating cell nuclear antigen (PCNA). Apoptosis was evaluated by the TUNEL(Tdt-mediated dUTPbiotin nick end labelling) assay. Expressions of p53, bcl-2 and PCNA were analyzed by immunohistochemistry. A negative correlation was observed between the expression of bcl-2 and the extent of apoptosis (r=–0.3336, p=0.019). P53 accumulation directly correlated with the extent of apoptosis (r=0.485, p=0.00041). The labelling index of PCNA also showed correlation with expression of p53 (r=0.49, p=0.00000). Apoptosis was significantly higher in poorly differentiated tumors when compared to the well- and moderately-differentiated tumors (r=0.49152, p=0.00034). Such poorly-differentiated tumors also showed high p53 overexpression and loss of bcl-2 expression. The present study thus provides evidence that dysregulation of apoptosis and its regulatory genes is associated with increasing malignant potential and may thus contribute to the pathogenesis of ovarian tumors

Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry Estimation of Quercetin-Loaded Nanoemulsion in Rabbit Plasma : In Vivo-In Silico Pharmacokinetic Analysis Using GastroPlus

In the present study, we developed and validated a rapid, specific, sensitive, and reproducible liquid chromatography-electrospray ionization tandem mass spectrometry method for quantifying quercetin (QT) in rabbit plasma using hydrochlorothiazide as the internal standard. Animals were orally administered with optimized QT-loaded nanoemulsion (QTNE) and QT suspension (QTS), equivalent to 30 mg/kg, to the test and control group, respectively. The blood samples were collected at pre-determined time points up to 48 h. The linearity range was from 5 to 5000 ng mL-1 with R2 = 0.995. Further, we analyzed the various pharmacokinetic parameters and established the in vitro-in vivo correlation (IVIVC) of QTNE using GastroPlus software. The method was successfully developed and validated, and when applied for the determination of QT in rabbit plasma, it exhibited an increase in C-max from 122.56 ng mL(-1) (QTS) to 286.51 ng mL(-1) (QTNE) (2.34-fold) and AUC(0-48) from 976 ng h mL(-1) (QTS) to 4249 ng h mL(-1) (QTNE) (4.35-fold), indicating improved oral bioavailability QT when administered as QTNE. Statistical analysis revealed that the Loo-Riegelman method (two-compartmental method) best fitted the deconvolution approach (R-2 = 0.998, SEP = 4.537, MAE = 2.759, and AIC = 42.38) for establishing the IVIVC. In conclusion, the established bioanalytical method and IVIVC studies revealed that QTNE is a potential carrier for the effective delivery of QT with enhanced oral bioavailability.Peer reviewe