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Cancer combination therapy with carnosic acid

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BIOCELL 2022年第10期46卷 2151-2157页

作者： NADIRE OZENVER thomas EFFERTH Hacettepe University Faculty of PharmacyDepartment of PharmacognosyAnkara06100Turkey Johannes Gutenberg University Institute of Pharmaceutical and Biomedical SciencesDepartment of Pharmaceutical BiologyMainz55128Germany

Carnosic acid(CA)is a natural phenolic diterpene mainly occurring in some species of the Lamiaceae family.Numerous studies described the cytotoxicity of CA towards different types of cancer both in vitro and in vivo.Particularly,the influence of CA in combination with other drugs,vitamins or natural products through affecting various targets has raised interest.Current experimental in vivo data suggested that CA may cooperate with clinically used anticancer drugs promoting their activity against cancer.From this point of view,CA gained importance,because it may alter pharmacodynamic profiles of various agents in the case of their co-administration,and thereby,act in a potentially synergistic manner,which can provide a basis for potential applications of CA in the management of cancer.In the present review,we give an overview of CA as well as CA co-treatment regimens with a special focus on cancer.In this context,the role of CA as an adjuvant treatment alternative is highlighted.

关键词： Carnosic acid Cancer Combination therapy Synergism

Paraneoplastic retinopathies: an update on pathogenesis, diagnosis and management

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Annals of Eye Science 2024年第1期9卷 34-42页

作者： Akshay S.thomas Tennessee Retina NashvilleTNUSA

The paraneoplastic retinopathies are a heterogeneous group of disorders with significant visual consequences occuring in the setting of a systemic malignancy.These conditions may be characterized by the presence of antiretinal antibodies and may predate or follow the diagnosis of an underlying malignancy.Herein I review the clinical findings,pathophysiology,laboratory testing and management of the paraneoplastic retinopathies:cancer-associated retinopathy(CAR),melanoma-associated retinopathy(MAR),bilateral diffuse uveal melanocytic proliferation(BDUMP)and paraneoplastic vitelliform maculopathy(PVM).The pathophysiology of the paraneoplastic retinopathies varies from molecular mimicry resulting in anti-retinal antibody production(CAR,MAR)to relases of soluble factors either by the primary tumor(BDUMP)and/or immune system in response to the primary tumor(PVM)which result in retinal and/or retinal pigment epithelium dysfunction.For each condition,structural and functional multimodal retinal testing can be helpful in establishing the diagnosis.Treatment for the paraneoplastic retinopathies involves a combination of treating the underlying malignancy plus additional local and/or systemic immunosuppressive agents though no systemic therapeutic protocols exist.Despite these interventions,the retinopathy may be progressive or the retinopathy may be a harbinger of poor survival.Nevertheless,prompt diagnosis may help identify an underlying malignancy earlier and may thus improve cancer-related survival.

关键词： Paraneoplastic retinopathy bilateral diffuse uveal melanocytic proliferation(BDUMP) cancer-associated retinopathy(CAR) vitelliform

A trade-off between space exploration and mobilization of organic phosphorus through associated microbiomes enables niche differentiation of arbuscular mycorrhizal fungi on the same root

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Science China(Life Sciences) 2023年第6期66卷 1426-1439页

作者： Jiachao Zhou thomas W Kuyper Gu Feng College of Resources and Environmental Sciences China Agricultural UniversityBeijing100193China Soil Biology Group Wageningen University&ResearchWageningen6700 AAThe Netherlands

Ecology seeks to explain species coexistence,but experimental tests of mechanisms for coexistence are difficult to conduct.We synthesized an arbuscular mycorrhizal(AM)fungal community with three fungal species that differed in their capacity of foraging for orthophosphate(P)due to differences in soil exploration.We tested whether AM fungal species-specific hyphosphere bacterial assemblages recruited by hyphal exudates enabled differentiation among the fungi in the capacity of mobilizing soil organic P(P_(o)).We found that the less efficient space explorer,Gigaspora margarita,obtained less ^(13)C from the plant,whereas it had higher efficiencies in P_(o)mobilization and alkaline phosphatase(Al Pase)production per unit C than the two efficient space explorers,Rhizophagusintraradices and Funneliformis mosseae.Each AM fungus was associated with a distinct alp gene harboring bacterial assemblage,and the alp gene abundance and P_(o)preference of the microbiome associated with the less efficient space explorer were higher than those of the two other species.We conclude that the traits of AM fungal associated bacterial consortia cause niche differentiation.The trade-off between foraging ability and the ability to recruit effective P_(o)mobilizing microbiomes is a mechanism that allows co-existence of AM fungal species in a single plant root and surrounding soil habitat.

关键词： arbuscular mycorrhizal fungi carbon space exploration hyphosphere bacterial assemblages organic phosphorus mobilization

EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana thomas Karagiannis Julia J.Liang Lina Mariana thomas Loudovaris thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release insulin.In type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-cells.Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.Consequently,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell function.We and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation capacity.Default transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 methyltransferase.In the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell identity.The transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin modification.Targeting EZH2 is fundamental toβ-cell regenerative potential.Reprogrammed pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex vivo.These pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

ICRU 95号报告:外照射实用量及其对剂量学的影响

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辐射防护 2023年第1期43卷 11-16页

作者： Hans Menzel thomas Otto Heidelberg Germany and ICRU CERN 1211 Geneva 23Switzerland and ICRU

国际放射防护委员会(ICRP)提出了“防护量”这一概念。最常用的防护量,即有效剂量E,用于设定照射限值,并在实用辐射防护中使用,以实现最优化原则。然而,有效剂量不是一个可测量的量,基于此国际辐射单位与测量委员会(ICRU)为外照射的剂... 详细信息

国际放射防护委员会(ICRP)提出了“防护量”这一概念。最常用的防护量,即有效剂量E,用于设定照射限值,并在实用辐射防护中使用,以实现最优化原则。然而,有效剂量不是一个可测量的量,基于此国际辐射单位与测量委员会(ICRU)为外照射的剂量测定提出了一个可测量的量,即实用量,用于估计有效剂量。目前使用的实用量定义于20世纪80年代,当时核工业是职业辐射防护的主要关注点。当前,在其他辐射领域,特别是高能辐射,实用量的不足之处变得很明显:可能高估或低估有效剂量。因此,ICRU和ICRP在全面研究的基础上,为外照射的剂量测定提出了新的实用量,以克服上述缺点。实用量的新定义与防护量(包括有效剂量)的定义更具相关性,特别是使用了相同的仿真体模。当前提出的实用量通过缩小防护量与实用量之间的定义差异简化了辐射防护量体系,并从整体上改进了对有效剂量的估计。本文讨论了提出的新实用量对实际剂量测定的影响。

关键词：剂量学实用量防护量有效剂量

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固定导线的不同位点对漂浮传感器振动的影响

固定导线的不同位点对漂浮传感器振动的影响

The embryology of persistent cloaca and urogenital sinus malformations

中华医学会第十次全国耳鼻咽喉-头颈外科学术会议

作者：佘万东 D Jiang A Fitzgerald O connor 南京大学医学院附属鼓楼医院耳鼻咽喉科 Department of Otolaryngology-Head and Neck Surgery Guy’s and St.Thomas’ HospitalsLondonUK

目的固定漂浮传感器(floating mass transducer,FMT)导线的不同位点,探讨对 FMT 振动的影响。方法固定距 FMT 分别为10mm、5mm 和0mm 导线位点,应用激光多普勒(laser doppler vibra- tion,LDV),观测在声刺激强度为100dB SPL 和80dB SPL...

目的固定漂浮传感器(floating mass transducer,FMT)导线的不同位点,探讨对 FMT 振动的影响。方法固定距 FMT 分别为10mm、5mm 和0mm 导线位点,应用激光多普勒(laser doppler vibra- tion,LDV),观测在声刺激强度为100dB SPL 和80dB SPL 时的 FMT 振动强度。结果 FMT 在1k、1．5k 处振动强度较小,向两侧振动强度渐增大,0．25k 和8k 处最大。有利

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Asian Journal of Andrology 2020年第2期22卷 124-128页

作者： David F M thomas University of Leeds LeedsWest Yorkshire LS29JTUK

Cloacal malformations are characterized by the confluence of the lower urinary tract,the female reproductive tract,and the rectum to create a common channel with a single opening on the perineum.The presence of a cloaca is a normal phase of early human embryological development.Between the 4^th and 7^th weeks of gestation,the cloaca undergoes subdivision to form the hindgut and urogenital sinus.Failure of this process results in the congenital anomaly termed persistent cloaca(PC).The term urorectal septum malformation sequence(URSMS)is also used to describe this anomaly.The classic description of this process which is still cited in many standard textbooks dates from the 19th century.However,this has been increasingly called into question by the findings of studies using modern scientific methodology.Urogenital sinus anomalies are defined by the confluence of the urethra and vagina to form a common channel of varying length with a single perineal opening.In this condition,the anorectal canal opens separately on the perineum.The presence of a urogenital sinus represents a transient phase of the normal development of the lower genital tract in the female fetus.However,the form of urogenital sinus most commonly encountered in the developed world is a feature of disordered sexual differentiation and does not arise simply from the persistence of the anatomical structure which is a feature of normal fetal development.

关键词： cloaca embryology urogenital sinus

Evaluation of a model for providing cost effective,accessible continuing education to the forensic science community

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Forensic Sciences Research 2021年第4期6卷 224-230页

作者： thomas J.Gluodenis Department of chemistry&Physics Lincoln UniversityLincoln UniversityPAUSA

This study presents a detailed model and its subsequent assessment for the development and optimized delivery of continuing education for the forensic science community.Online continuing education is on the rise as this modality of content dissemination allows for accessibility,convenience,and affordability.The model,which includes an educational needs assessment,gap analysis,online content delivery and archival,was evaluated through the launch of a global training event/symposium series.The four-year study of over 6000 participants representing>75 countries provides empirical support for the model based upon registration/attendance data and participant self-assessment surveys.Best practices are identified relative to content and format,operational excellence,technology,and financing of the event.Future directions along with opportunities to further enhance the model are also discussed.

关键词： Forensic sciences continuing education educational requirements online web-based certification

Continuous flow synthesis of plasmonic gold patches and nearly-complete nanoshells on polystyrene core particles

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Particuology 2023年第4期75卷 137-150页

作者： thomas Meincke Robin N.Klupp Taylor Institute of Particle Technology Friedrich-Alexander University Erlangen-NürnbergCauerstrasse 491058ErlangenGermany Collaborative Research Center 1411-Design of Particulate Products Friedrich-Alexander University Erlangen-Nürnberg Cauerstrasse 391058 Erlangen Germany

We describe the development of a T-mixer based continuous flow process for the coating of 86-500 nm diameter spherical polystyrene particles with thin gold patches by heterogeneous nucleation and growth.After establishing a suitable flow rate for good mixing and sufficiently uniform product morphology we systematically investigate the main reaction parameters.This reveals a considerable tunability of the patch morphology and,by virtue of the localized surface plasmon resonance of gold,the optical properties of the product dispersions.In order to further widen the range of nanostructures accessible by our process,a second T-mixer was added.This introduced new gold precursor,leading to further growth of the patches that were formed after the first mixer.By this approach,nearly-complete gold nanoshells could be produced in high yield on both small and large core particles,without the unwanted production of free-standing gold nanoparticles.Due to the pronounced optical properties of nearly-complete gold nanoshells on small core particles,we could estimate from electrodynamic sim-ulations the equivalent shell thickness to be as low as 8.6 nm.This is significantly thinner than can be routinely achieved using the standard seeded growth approach to synthesise gold nanoshells.Our results are therefore highly promising for the gram-scale synthesis of plasmon resonant nanostructures with designed optical properties.

关键词： Continuous flow Core-shell particles Patchy particles Nucleation Diffusion limited growth