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COVER STORY: RFK's children speak on Sirhan Sirhan Watch VideoAfter more than five decades, California's Parole Board has recommended that Sen. Robert F. Kennedy's assassin, Sirhan Sirhan, now 77, be granted parole from his life sentence. Correspondent Lee Cowan talks with Chris and Kerry Kennedy, who are adamantly opposed to giving their father's killer his freedom.
majja ni life album songs free 12
MUSIC: Pat Benatar and Neil Giraldo's rock & roll love story Watch VideoShe was a singer from Long Island, inspired by Liza Minnelli and coated in spandex; he was a guitarist from Cleveland. Together they are among rock's most enduring love stories, all while selling 36 million albums, recording 15 Top 40 hits, and winning four consecutive Grammys. Pat Benatar and Neil Giraldo talk with correspondent Jim Axelrod about their creative partnership, their 40-year-marriage, and their latest collaboration: the upcoming stage musical, "Invincible," a reimagining of "Romeo and Juliet" featuring their iconic rock songs.
MUSIC: Olivia Rodrigo on "Sour" and the artistry of heartbreak Watch VideoBeginning with her smash hit single, "Drivers License," 18-year-old Olivia Rodrigo is on a run that few singer-songwriters can even dream about, with her very first album, "Sour," debuting at #1 earlier this year. Correspondent Tracy Smith talks with Rodrigo about writing of heartbreak; the value of therapy; and what sudden fame hasn't changed about her life.\
Guru Paduka Stotram is a very powerful chant that glorifies the "sandals of the Guru," which are symbolically represented as "the boat to help cross the endless ocean of life." This chant enables one to become receptive to the Guru's Grace. The chant sung by Isha Brahmacharis is available as part of the Vairagya album and can be downloaded for free. It is also available as part of the Isha Chants app. The Sanskrit lyrics are also given below.
Kidney fibrosis is the main pathologic change in diabetic nephropathy (DN), which is the major cause of end-stage renal disease. Current therapeutic strategies slow down but cannot reverse the progression of renal dysfunction in DN. Plant-derived bioactive peptides in foodstuffs are widely used in many fields because of their potential pharmaceutical and nutraceutical benefits. However, this type of peptide has not yet been studied in renal fibrosis of DN. Previous studies have indicated that the peptide YWDHNNPQIR (named RAP), a natural peptide derived from rapeseed protein, has an antioxidative stress effect. The oxidative stress is believed to be associated with DN. The aim of this study was to evaluate the pharmacologic effects of RAP against renal fibrosis of DN and high glucose (HG)-induced mesangial dysfunction. Diabetes was induced by streptozotocin and high-fat diet in C57BL/6 mice and these mice were treated by subcutaneous injection of different doses of RAP (0.1 mg/kg and 0.5 mg/kg, every other day) or PBS for 12 weeks. Later, functional and histopathologic analyses were performed. Parallel experiments verifying the molecular mechanism by which RAP alleviates DN were carried out in HG-induced mesangial cells (MCs). RAP improved the renal function indices, including 24-h albuminuria, triglyceride, serum creatinine, and blood urea nitrogen levels, but did not lower blood glucose levels in DN mice. RAP also simultaneously attenuated extracellular matrix accumulation in DN mice and HG-induced MCs. Furthermore, RAP reduced HG-induced cell proliferation, but it showed no toxicity in MCs. Additionally, RAP inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. RAP can attenuate fibrosis in vivo and in vitro by antagonizing the MAPK and NF-κB pathways.
Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression. RAP poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) NPs were fabricated. NP accumulation and efficacy were examined in a rat monocrotaline model of PAH. Following intravenous (IV) administration, NP accumulation in diseased lungs was verified via LC/MS analysis and confocal imaging. Pulmonary arteriole thickness, right ventricular systolic pressures, and ventricular remodeling were determined to assess the therapeutic potential of RAP NPs. Monocrotaline-exposed rats showed increased NP accumulation within lungs compared to healthy controls, with NPs present to a high extent within pulmonary perivascular regions. RAP, in both free and NP form, attenuated PAH development, with histological analysis revealing minimal changes in pulmonary arteriole thickness and no ventricular remodeling. Importantly, NP-treated rats showed reduced systemic side effects compared to free RAP. This study demonstrates the potential for nanoparticles to significantly impact PAH through site-specific delivery of therapeutics. Copyright 2017 Elsevier B.V. All rights reserved.