YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

Improved Muscle Mass and Function With Protein Supplementation in Older Adults With Sarcopenia: A Meta-Analysis

Objective To systematically review the effects of protein supplementation in older adults with sarcopenia. Methods A systematic literature search was conducted in PubMed, Cochrane Library, and Embase databases until May 2023. The inclusion criteria were as follows: (1) randomized controlled trials with a quantitative study design; (2) studies with a study group of older adults with sarcopenia; (3) studies comparing muscle mass, muscle strength, and performance of older adults with sarcopenia after protein supplementation; and (4) studies published up to May 2023. Results Six retrospective comparative studies, including 715 patients, met the inclusion criteria. The nutritional supplementation group exhibited significant improvement in appendicular skeletal muscle mass (standardized mean difference [SMD]=0.41; 95% confidence interval [CI], 0.24–0.58; p<0.001; I2=1%), while handgrip strength (SMD=0.37; 95% CI, -0.32–1.07; p=0.29; I2=94%) and Short Physical Performance Battery (SPPB) (SMD=0.35; 95% CI, -0.47–1.18; p=0.40; I2=94%) showed a tendency for improvement. Conclusion Nutritional supplementation with protein increased appendicular muscle mass in older adults with sarcopenia and improved handgrip strength and SPPB scores

Manumycin from a new Streptomyces strain shows antagonistic effect against methicillin-resistant Staphylococcus aureus (MRSA)/vancomycin-resistant enterococci (VRE) strains from Korean Hospitals

An antimicrobial compound, highly effective against multidrug-resistant (MDR) bacteria, purified from a Streptomyces strain was identified as manumycin. The minimal inhibitory concentrations (MICs) of manumycin against 8 different strains of methicillin-resistant Staphylococcus aureus (MRSA) were ranged 2 to 32 μg/ml. Similarly, MICs of manumycin against 4 vancomycin-resistant enterococci (VRE) strains were ranged 8 to 32 μg/ml while it remained ineffective against 4 other VRE strains. Compared to vancomycin, manumycin provided slightly weaker activity against MRSA strains but stronger activity against 4 VRE strains. This is the first report of antagonistic effect of manumycin against MDR pathogens.Keywords: Manumycin, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE)African Journal of Biotechnology Vol. 12(17), pp. 2249-225

Teatro e ensino da matemática: atividade desenvolvida num curso de formação docente

Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014Este trabalho relata uma aula desenvolvida pelas alunas do Curso de Formação de Docentes do Instituto Estadual de Educação de Londrina com a colaboração dos Bolsistas do Programa Institucional de Bolsas de Iniciação à Docência – PIBID – Subprojeto de Matemática, para alunos de primeiro ano do Ensino Fundamental utilizando o teatro como forma de apresentar conteúdos matemáticos como números, sequência de números, operações básicas como adição, subtração e conteúdos de língua portuguesa como leitura e escrita de número

Efekti korišćenja astaksantina u ishrani na rast, pigmentaciju mišića i antioksidantne aktivnosti mlađi kalifornijske pastrmke (oncorhynchus mykiss)

This study was designed to test the effects of dietary astaxanthin on growth, muscle pigmentation, antioxidant activity and biochemical composition of juvenile rainbow trout (Oncorhynchus mykiss). Experimental diets were formulated to contain 50, 75 and 100 ppm astaxanthin (designed as AS50, AS75 and AS100). The diet without supplementation of astaxanthin was considered as the control diet. Each experimental diet was fed to three replicate groups of fish (18.5 g/fish) to visual satiation two times a day for 10 weeks. Growth performance and proximate composition of muscle of fish were not affected by dietary AS levels (P> 0.05). Total carotenoid concentration in the muscle of fish fed the AS50 diet was higher than that of fish fed the control diet, but no different to that of fish fed the AS75 and AS100 diets. The astaxanthin concentration in the muscle of fish fed AS50, AS75 and AS100 diets were higher than that of control diet. The redness (a*) of the muscle of fish fed AS50, AS75 and AS100 diets were higher than that of fish fed the control diet (P 0.05) nije uticao na performansu rasta i hemijski sastav mišića ribe. Ukupna koncentracija karotenoida u mišiću ribe koja je hranjena AS50 hranom bila je viša nego kod riba hranjenih kontrolnom hranom, ali nije bila drugačija od riba hranjenih AS75 i AS100 hranom. Koncentracija astaksantina u mišiću riba hranjenih AS50, AS75 i AS100 hranom bila je viša nego kod riba hranjenih kontrolnom hranom. Crvena boja (a*) mišića ribe koja je hranjena AS50, AS75 i AS100 hranom bila je jača nego kod ribe hranjene kontrolnom hranom (P< 0.05). Antioksidantna aktivnost DPPH, radikala hidroksila i alkila u plazmi i jetri riba nisu zavisili od nivoa astaksantina osim kod plazme koja je imala antioksidantnu aktivnost alkilnih radikala. Rezultati ove studije nagoveštavaju da se hrana koja sadrži 50 ppm astaksantina može koristiti da bi se poboljšala crvena boja mišične pigmentacije kod mlađi kalifornijske pastrmke

Clinical outcomes of chemoradiotherapy for locally recurrent rectal cancer

<p>Abstract</p> <p>Background</p> <p>To assess the clinical outcome of chemoradiotherapy with or without surgery for locally recurrent rectal cancer (LRRC) and to find useful and significant prognostic factors for a clinical situation.</p> <p>Methods</p> <p>Between January 2001 and February 2009, 67 LRRC patients, who entered into concurrent chemoradiotherapy with or without surgery, were reviewed retrospectively. Of the 67 patients, 45 were treated with chemoradiotherapy plus surgery, and the remaining 22 were treated with chemoradiotherapy alone. The mean radiation doses (biologically equivalent dose in 2-Gy fractions) were 54.6 Gy and 66.5 Gy for the chemoradiotherapy with and without surgery groups, respectively.</p> <p>Results</p> <p>The median survival duration of all patients was 59 months. Five-year overall (OS), relapse-free (RFS), locoregional relapse-free (LRFS), and distant metastasis-free survival (DMFS) were 48.9%, 31.6%, 66.4%, and 40.6%, respectively. A multivariate analysis demonstrated that the presence of symptoms was an independent prognostic factor influencing OS, RFS, LRFS, and DMFS. No statistically significant difference was found in OS (p = 0.181), RFS (p = 0.113), LRFS (p = 0.379), or DMFS (p = 0.335) when comparing clinical outcomes between the chemoradiotherapy with and without surgery groups.</p> <p>Conclusions</p> <p>Chemoradiotherapy with or without surgery could be a potential option for an LRRC cure, and the symptoms related to LRRC were a significant prognostic factor predicting poor clinical outcome. The chemoradiotherapy scheme for LRRC patients should be adjusted to the possibility of resectability and risk of local failure to focus on local control.</p

Suppression of STAT3 and HIF-1 Alpha Mediates Anti-Angiogenic Activity of Betulinic Acid in Hypoxic PC-3 Prostate Cancer Cells

Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various cellular processes such as cell survival, angiogenesis and proliferation. In the present study, we examined that betulinic acid (BA), a triterpene from the bark of white birch, had the inhibitory effects on hypoxia-mediated activation of STAT3 in androgen independent human prostate cancer PC-3 cells. Methodology/Principal Findings: BA inhibited the protein expression and the transcriptional activities of hypoxia-inducible factor-1a (HIF-1a) under hypoxic condition. Consistently, BA blocked hypoxia-induced phosphorylation, DNA binding activity and nuclear accumulation of STAT3. In addition, BA significantly reduced cellular and secreted levels of vascular endothelial growth factor (VEGF), a critical angiogenic factor and a target gene of STAT3 induced under hypoxia. Furthermore, BA prevented in vitro capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxic PC-3 cells, implying anti-angiogenic activity of BA under hypoxic condition. Of note, chromatin immunoprecipitation (ChiP) assay revealed that BA inhibited binding of HIF-1a and STAT3 to VEGF promoter. Furthermore, silencing STAT3 using siRNA transfection effectively enhanced the reduced VEGF production induced by BA treatment under hypoxia. Conclusions/Significance: Taken together, our results suggest that BA has anti-angiogenic activity by disturbing th

Treatment of two Asiatic black bears (Ursus thibetanus) with severe injuries and their subsequent release into the wild: a case report

Background The rehabilitation of injured wildlife and their subsequent release into the wild is a humane act as well as important in wildlife conservation. However, little is known about the animals fate after release. Therefore, to address these uncertainties, it is essential to adequately describe how the injured animals were treated and managed before releasing into the wild; moreover, post-release monitoring should also be performed. Herein, we document for the first time the process of rescue, surgery, and rehabilitation of severely injured Asiatic black bears (Ursus thibetanus; endangered species in South Korea) and their fate after returning to the wild. Case presentation A six-year-old female (bear-01) and a three-year-old male (bear-02) bears were injured by an illegal snare and collision with a bus, respectively. Bear-01 had broad muscle necrosis and ruptures from the snared ankle on the right thoracic limb, with myiasis, and elbow disarticulation was performed. In bear-02, a non-reducible comminuted fracture of the left humerus was confirmed radiologically, and the operation was performed by using dual plate fixation with hydroxyapatite and recombinant human bone morphogenetic protein-2. The bear-01 and -02 were completely healed approximately 30 and 60 days after surgery, respectively. After that, they underwent rehabilitation for 8 and 25 days, respectively, in an outdoor enclosure similar to their natural habitat. Bear-01 and -02 were released into the wild after 45 and 99 days after surgery, respectively, and their mean daily movement distance during the first 30 days after releasing was 2.9 ± 2.1 and 1.3 ± 1.6 km, respectively. The annual mean 95% Kernel home-range size of bear-01 and bear-02 was 265.8 and 486.9 km2, respectively. They hibernated every winter, gained weight, gave birth to cubs (bear-01), were not found to have any abnormalities in the veterinary tests, and were not involved in any conflicts with humans after returning to the wild. Conclusions Bears without one leg or those with dual plates could adapt well in their natural habitat, which shows that our surgical and post-operative treatments were effective. Additionally, minimizing human contact and observing/evaluating behavior during the rehabilitation is essential in reducing human-bear conflicts after release.This work conducted as part of a restoration project of endangered Asiatic black bears by the Ministry of Environment. In addition, this work was financially supported by a grant of the Korea Health Technology Development R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0642), Rural Development Administration, Republic of Korea and Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through Useful Agricultural Life Resources Industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFR A)(120054021HD020). These three funders had no role in the study design, data collection and analysis, interpretation of the results, manuscript preparation, or decision to disseminate and publish the study findings

Preclinical evaluation of injectable sirolimus formulated with polymeric nanoparticle for cancer therapy

Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)–sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP–sirolimus has prolonged circulation in the blood. In addition, PNP–sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP–sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP–sirolimus is a promising strategy for human cancer treatment