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Skeletal muscle atrophy remains a complication occurring both as a natural response to muscle disuse and as a pathophysiological response to illness such as diabetes mellitus and nerve injury, such as traumatic muscle denervation. The ubiquitin-proteasome system (UPS) is the predominant proteolytic machinery responsible for atrophy of skeletal muscle, and Nedd4-1 (neural precursor cell-expressed developmentally down-regulated 4-1) is one of a series of E3 ubiquitin ligases identified to mediate inactivity-induced muscle wasting. Targets of Nedd4-1 mediated ubiquitination in skeletal muscle remain poorly understood. In the present study, we identified PDLIM7 (PDZ and LIM domain 7, Enigma), a member of the PDZ-LIM family of proteins, as a novel target of Nedd4-1 in skeletal muscle. The PDZ-LIM family of proteins is known to regulate muscle development and function. We show that Nedd4-1 expression in muscle atrophied by denervation is co-incident with a decrease in PDLIM7 and that PDLIM7 protein levels are stabilized in denervated muscle of Nedd4-1 skeletal muscle-specific knockout mice (SMS-KO). Exogenous PDLIM7 and Nedd4-1 transfected into human embryonic kidney (HEK)293 cells co-immunoprecipitate through binding between the PY motif of PDLIM7 and the second and third WW domains of Nedd4-1 and endogenous PDLIM7 and Nedd4-1 interact in the cytoplasm of differentiated C2C12 myotubes, leading to PDLIM7 ubiquitination. These results identify PDLIM7 as a bona fide skeletal muscle substrate of Nedd4-1 and suggest that this interaction may underlie the progression of skeletal muscle atrophy. This offers a novel therapeutic target that could be potentially used to attenuate muscle atrophy.

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HS may help to accelerate the recovery of renal function post-obstruction and attenuates renal injury associated with UUO. It is possible that HS mitigates fibrosis by regulating the TGF-β1-mediated EMT pathway. Taken together, our data suggest that HS may be a potential novel therapy for improving renal function and limiting renal injury associated with obstructive uropathy.

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FT-IR to determine the biochemical structure and the matrix material content. The matrix material component was calculated as percentage to total biochemical components. The stone microanalysis for heavy metals and trace elements contents (22 elements/stone) was carried out by using ICP-OES. The correlation between matrix material content, biochemical structure and heavy metals was evaluated.RESULTS: FT-IR analyses revealed; 268 (48.6%) Ca oxalate, 166 (30.15) uric acid, 68 (12.3%) mixed and 19 (3.4) Ca phosphate, 13 (2.4%) struvite and 12 (2.2%) cystine stones. ICP-OES showed significant increase in the concentration of 15 elements (Al,

Introduction: We sought to design a partial nephrectomy (PN) with contralateral total nephrectomy porcine model and assess the underlying mechanisms of ischemia reperfusion injury (IRI) after PN using a novel, clinically approved resection device. Methods: Domestic male pigs (n=9) underwent left lower pole PN, allocated to either standard (Group 1) or no ischemia PN (Group 2), followed by contralateral nephrectomy. Biochemical studies were performed at baseline, Day 2, and Day 7; after sacrifice, kidneys were processed for histological analysis. Apoptotic markers were measured by Western blot analyses. Urinary biomarkers were measured to assess acute kidney injury. Results: At Day 2 following PN, there was a significant rise in serum creatinine in Group 1 compared to Group 2 (355 vs. 136 mmol/L; p=0.008). Intra-renal tissue oxygen saturation after PN was inversely correlated with postoperative creatinine (r s -0.75; p=0.012) and the grade of acute tubular necrosis (r s -0.70; p=0.036). We observed a rise in expression of pro-apoptotic markers and pro-inflammatory markers in Group 1 following PN compared to Group 2. Histological analysis revealed higher grade of apoptosis in Group 1. Conclusions: IRI associated with standard PN has a deleterious impact on acute renal function, markers of tissue injury, and histological parameters, compared to off-clamp PN using the ALTRUS device. We identified several intraoperative and postoperative markers that may be used as predictors for functional and histological injury following PN.

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