Clinical features and outcomes of elderly patients with antineutrophil cytoplasmic antibody-positive vasculitis: a single-center retrospective study

Background We aimed to investigate the clinical characteristics and outcomes of patients aged ≥65 years with antineutrophil cytoplasmic autoantibody (ANCA)-positive ANCA-associated vasculitis (AAV) in Korea. Methods Seventy patients diagnosed with ANCA-positive AAV from 2006 to 2019 at a single center were analyzed and categorized into younger (aged <65 years) or elderly (aged ≥65 years) groups. Initial induction treatments were investigated according to age group. All-cause mortality and kidney outcomes were evaluated. Results After categorization by age, 34 (48.6%) and 36 patients (51.4%) were in the younger and elderly groups, respectively. In the elderly group, more patients were treated with oral cyclophosphamide (CYC) (30.6%) than with intravenous CYC (19.4%). During a median follow-up of 14.6 months (range, 3.0–53.1 months), 13 patients died (elderly group: 11 patients, 84.6%). In the elderly group, older age (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09–1.90; p = 0.01), lower hemoglobin (HR, 0.21; 95% CI, 0.08–0.60; p = 0.003), and higher serum creatinine level (HR 14.17; 95% CI, 1.29–155.84; p = 0.03) were significant risk factors for all-cause mortality after adjustment. Oral CYC + steroid treatment was associated with decreased all-cause mortality compared to untreated induction immunosuppressants (HR, 0.01; 95% CI, 0.001–0.47; p = 0.02). Kidney failure or kidney recovery outcomes were not significantly different between the younger and elderly groups. Conclusion Patients aged ≥65 years had higher mortality rates than younger patients, and mortality was associated with older age, lower hemoglobin, higher serum creatinine level, and nontreatment compared to oral CYC + steroids

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

Heterogeneous nuclear ribonucleoprotein (hnRNP) L promotes DNA damage-induced cell apoptosis by enhancing the translation of p53

The tumor suppressor p53 is an essential gene in the induction of cell cycle arrest, DNA repair, and apoptosis. p53 protein is induced under cellular stress, blocking cell cycle progression and inducing DNA repair. Under DNA damage conditions, it has been reported that post-transcriptional regulation of p53 mRNA contributes to the increase in p53 protein level. Here we demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) L enhances p53 mRNA translation. We found that hnRNP L is increased and binds to the 5&apos; UTR of p53 mRNA in response to DNA damage. Increased hnRNP L caused enhancement of p53 mRNA translation. Conversely, p53 protein levels were decreased following hnRNP L knock-down, rendering them resistant to apoptosis and arrest in the G2/M phase after DNA damage. Thus, our findings suggest that hnRNP L functions as a positive regulator of p53 translation and promotes cell cycle arrest and apoptosis.11Ysciescopu

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

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

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