Antioxidant and tyrosinase inhibitor from Leucaena leucocephala

The experimental design is divided into two parts: chemical analysis and bioactive assay. One antioxidant lupeol (4) and one inhibition of tyrosinase pheophorbide a methyl ester (7) were identified in Leucaena leucocephala. Both showed effective 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity compared with vitamin C, and mushroom tyrosinase compared with kojic acid. These results suggest that these constituents of L. leucocephala act as natural antioxidants and play a potential role in prevention of pigmentation.Keywords: Leucaenana leucocephala, lupeol, pheophorbide a methyl ester, antioxidant, mushroom tyrosinas

Thermal Effect on Structure of Silver in Ion-Exchanged Soda-Lime Glasses and Aluminum-Doped Zinc Oxide Films

Heat treatment is commonly used during device processing in order to achieve specific functionalities of the devices. How a series of heat treatment applies to accomplish this goal can be found in the literature. However, specific properties of the devices after the treatment are more emphasized than the details of the structural modifications in the industrial applications. In this paper, it is intended to illustrate the fundamental changes in the structure due to heat treatment which result in the desired physical properties of the devices. Two study cases, Ag ion-exchanged soda-lime glasses and aluminum doped ZnO (AZO) films, were illustrated. The changes in chemical states, the structural modification during and after heat treatment are explored. By understanding how the metallic Ag formed and accumulated during annealing, an optimum heat treatment to grow the proper size and density of silver quantum dots in the films are possible. Post annealing effect on the AZO films shows that the crystallinity, the peak positions shifts, and grain sizes were changed after annealing. Both illustrated cases indicate thermally induced changes in chemical state, the stress release, and rearrangement of atoms in materials during and after annealing

Comparison of clinical outcomes and toxicity in endometrial cancer patients treated with adjuvant intensity-modulated radiation therapy or conventional radiotherapy

PurposeTo evaluate the treatment outcomes and toxicity in endometrial cancer patients treated with hysterectomy and adjuvant intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).MethodsThere were 101 patients with stage IA-IIIC2 endometrial carcinoma treated with hysterectomy and adjuvant radiotherapy. In total, 36 patients received adjuvant CRT and 65 were treated with adjuvant IMRT. The endpoints were overall survival, local failure-free survival, and disease-free survival. Patients were assessed for acute toxicity weekly according to the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema.ResultsThe 5-year overall survival, local failure-free survival, and disease-free survival for the CRT group and the IMRT group were 82.9% versus 93.5% (p = 0.26), 93.7% versus 89.3% (p = 0.68), and 88.0% versus 82.8% (p = 0.83), respectively. Four (11.1%) patients had Grade 3 or greater acute gastrointestinal (GI) toxicity and three (8.3%) patients had Grade 3 or greater acute genitourinary (GU) toxicity in the CRT group, whereas four (6.2%) patients had Grade 3 or greater acute GI toxicity in the IMRT group and no patient had severe GU toxicity. There was one (2.8%) patient who had Grade 3 or greater late GI toxicity and one (2.8%) patient had Grade 3 or greater late GU toxicity in the CRT group, whereas no patient had severe GI or GU toxicity in the IMRT group.ConclusionAdjuvant IMRT for endometrial cancer patients had comparable clinical outcomes with CRT and had less acute and late toxicity

Safety assessment of poly-ε-caprolactone in the treatment of primary spontaneous pneumothorax

Background/purposeBiomaterial-based implants are gaining traction as an option for pleurodesis treatment, yet the search for the best biomaterial or the most suitable shape to handle spontaneous pneumothorax continues. This forward-looking research assessed the use of a poly-ε-caprolactone membrane for its safety when applied as a sclerosant in pleurodesis procedures in human patients.MethodsFrom July 2017 to February 2018, we conducted a Phase I trial in which 10 patients with primary spontaneous pneumothorax were treated using video-assisted thoracoscopic surgery with a poly-ε-caprolactone membrane. These procedures encompassed bleb resection and mechanical pleurodesis through parietal pleura scrubbing. After resection, a 150 × 150 mm poly-ε-caprolactone membrane was applied to the apex. The primary outcome measures were the adverse events and laboratory outcomes.ResultsAfter surgery, we observed no cardiopulmonary-related adverse events or indications of systemic inflammation. Furthermore, no episodes of hypothermia or hyperthermia occurred. Chest radiographs showed no evident pneumonitis or effusion associated with tissue reactions. The average follow-up duration was 31.7 ± 17.7 months, during which two patients exhibited recurrence.ConclusionThis study is the first to show the biocompatibility of poly-ε-caprolactone in humans, suggesting its potential as a treatment option for patients with primary spontaneous pneumothorax. Despite the relatively small number of patients, we maintain confidence in the reliability and safety profile of the PCL membrane, bolstered by its previously established efficacy in applications involving other organs. Phase II and phase III clinical studies are needed to support these observations

RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype.

Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC

Broadband Loop Antenna on Soft Contact Lens for Wireless Ocular Physiological Monitoring

This paper presents a novel loop antenna with broadband for wireless ocular physiological monitoring (WOPM). The antenna is fabricated on a thin-film poly-para-xylylene C (parylene C) substrate with a small thickness of 11 μm and dimension of π×6.5×6.5 mm2. With the advantage of small size, the proposed antenna is suitable to apply to the soft contact lens and transmit the signal in microelectromechanical Systems (MEMS). Because the pig's eye and human's eye have similar parameters of conductivity and permittivity, the experimental results are obtained by applying the proposed antenna on the pig's eye and cover from 1.54 to 6 GHz for ISM band (2.4 and 5.8 GHz) applications. The measured antenna radiation patterns, antenna gains, and radiation efficiency will be demonstrated in this paper, which are suitable for application of wireless ocular physiological monitoring

Early iron production in the Levant: Smelting and smithing at early 1st millennium BC Tell Hammeh, Jordan, and Tel Beth-Shemesh, Israel

The use of iron in the Near East is first attested by the sporadic occurrence of iron artefacts during the Bronze Age. By the end of the Late Bronze Age, however, use of iron metal gradually increases to such a level that one can assume a reasonably regular production of iron metal from terrestrial ores by smelting. However, very few iron metallurgical workshops or installations have been discovered in the Near East thus far. Of these, most are apparently related to secondary smithing, and very few if any have clear evidence for iron smelting. Recent fieldwork at Tell Hammeh, Jordan, identified a major iron smelting operation dated to ca. 930 Cal BC. Excavations in 2001 and 2003 at Tel Beth- Shemesh, Israel, uncovered remains of a full-scale smithing operation, dating to ca. 900 Cal BC. Dedicated excavation techniques were developed and refined for both sites, aiming at optimal recovery of both technological and archaeological information. The excavated materials were comprehensively analysed using relevant scientific analytical techniques, which included the development and application of a calibration method for quantitative bulk chemical analysis of iron- rich materials by XRF. Combining laboratory data and fieldwork, this thesis explores the particular lime- rich and iron-oxide-poor nature of the Hammeh slags as a function of the composition of the local ore and the sacrificial contribution of technical ceramics (tuyeres and furnace wall). Furthermore, it compares the smelting operations at Tell Hammeh with the smithing at Tel Beth-Shemesh, both in terms of their respective archaeological contexts as well as of their technological residues. This aims at the identification and reconstruction of the chaine operatoire of the technologies at both sites. The reconstructed technological processes are discussed in terms of their place in the socio-economic and cultural context of the early first millennium BC of the Levant. Beyond providing new data about early iron metallurgy, the integrated archaeological and laboratory approach, the excavation methods applied, the analytical methodology, as well as the archaeometric data presented here may serve as a model for the excavation, interpretation, or comparison of future (and previous) discoveries of iron metallurgy in the Near East

Paradoxical roles of antioxidant enzymes:Basic mechanisms and health implications

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways

Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44+/CD24-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR+/ESA+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44+/CD24−/low, ESA+, CD133+, CXCR4+ and PROCR+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer