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Advancing cancer cachexia diagnosis with -omics technology and exercise as molecular medicine

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Sports Medicine and Health Science 2024年第1期6卷 1-15页

作者： stuart j.Hesketh University of Central Lancashire School of MedicinePrestonUK

Muscle atrophy exacerbates disease outcomes and increases mortality,whereas the preservation of skeletal muscle mass and function play pivotal roles in ensuring long-term health and overall *** atrophy represents a significant clinical challenge,involving the continued loss of muscle mass and strength,which frequently accompany the development of numerous types of *** cachexia is a highly prevalent multifactorial syndrome,and although cachexia is one of the main causes of cancer-related deaths,there are still no approved management strategies for the *** etiology of this condition is based on the upregulation of systemic inflammation factors and catabolic stimuli,resulting in the inhibition of protein synthesis and enhancement of protein *** necessary cellular processes are disrupted by cachectic pathology,which mediate intracellular signalling pathways resulting in the net loss of muscle and ***,the exact underpinning molecular mechanisms of how these changes are orchestrated are incompletely *** work is still required,but structured exercise has the capacity to counteract numerous detrimental effects linked to cancer *** through the stimulation of muscle protein synthesis,enhancement of mitochondrial function,and the release of *** a result,muscle mass and strength increase,leading to improved mobility,and *** review summarises existing knowledge of the complex molecular networks that regulate cancer cachexia and exercise,highlighting the molecular interplay between the two for potential therapeutic ***,the utility of mass spectrometry-based proteomics is considered as a way of establishing early diagnostic biomarkers of cachectic patients.

关键词： Cancer cachexia Exercise Muscle atrophy Molecular medicine Omics

Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.mcdonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer Barry j.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

Preliminary Insights into the Habitat Preferences of the Centralian Bandy Bandy (Vermicella vermiformis)(Squamata: Elapidae) in Central Australia

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Asian Herpetological Research 2014年第1期5卷 49-53页

作者： Peter j.mcdonald Gary W.LUCK Flora and Fauna Division Department of Land Resource Management Northern Territory Government School of Environmental Sciences Charles Sturt University Institude for Land Water and Society Charles Sturt University

Bandy Bandy’s（Vermicella spp.）are a striking,black-and-white ringed genus of small elapid snakes endemic to *** taxa are burrowers and little is known of their biology and *** investigated the habitat preferences of the only arid-dwelling species,the centralian bandy bandy（Vermicella vermiformis）,in the MacDonnell Ranges west of Alice Springs in the Northern *** systematic road-cruising,we encountered *** over a 12 months period between 2009 and *** used logistic regression to model the occurrence of the species against a range of different habitat variables collected at multiple *** the small sample size,*** exhibited a clear preference for acacia shrubland habitats,with acacia variables present in all AICc ranked models in the 95%confidence *** factors driving this association,together with the preference for habitat not burnt in the most recent wildfires,may be related to the abundance of their only known prey,blind snakes（Ramphotyphlops spp.）.

关键词： Snake Arid Acacia Fire Ramphotyphlops

Decreased bioavailability of aminomethylphosphonic acid(AMPA)in genetically modified corn with activated carbon or calcium montmorillonite clay inclusion in soil

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journal of Environmental Sciences 2021年第2期33卷 131-143页

作者： Sara E.Hearon Meichen Wang Thomas j.mcdonald Timothy D.Phillips Veterinary Integrative Biosciences Department College of Veterinary Medicine and Biomedical Sciences Texas A&M Uniuersity College StationTx 77845USA Department of Environmental and Occupational Health School of Public Health Texas A&M UniversityCollege Station400 Bizzell St College StationTX 77843USA

The widespread use of pesticides has resulted in detectable residues throughout the environment,sometimes at concentrations well above regulatory ***,the development of safe,effective,field-practical,and economically feasible strategies to mitigate the effects of pesticides is *** is an organophosphorus herbicide that is degraded to aminomethylphosphonic acid(AMPA),a toxic and persistent metabolite that can accumulate in soil and sediment and translocate to *** this study,we investigated the binding efficacy of activated carbon(AC)and calcium montmorillonite(CM)clay to decrease AMPA bioavailability from soil and AMPA translocation to *** isotherms and thermodynamic studies on AC and CM were conducted and showed tight binding(enthalpy values>-20 k j/mol)for AMPA with high capacities(0.25 mol/kg and 0.38 mol/kg,respectively),based on derivations from the Langmuir model.A hydra assay was utilized to indicate toxicity of AMPA and the inclusion of 1%AC and CM both resulted in 90%protection of the hydra(**p≤0.01).Further studies in glyphosate-contaminated soil showed that AC and CM significantly reduced AMPA bioavailability by 53%and 44%,*** in genetically modified(GM)corn showed a conversion of glyphosate to AMPA in roots and sprouts over a 10-day exposure *** of AC and CM reduced AMPA residues in roots and sprouts by 47%-61%.These studies collectively indicate that AC and CM are effective sorbents for AMPA and could be used to reduce AMPA bioavailability from soil and AMPA residues in GM corn plants.

关键词： Glyphosate AMPA Activated carbon Calcium montmorillonite Sorbent

Elimination of antibiotic resistance genes and control of horizontal transfer risk by UV-based treatment of drinking water: A mini review

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Frontiers of Environmental Science & Engineering 2019年第3期13卷 3-11页

作者： Virender K.Sharma Xin Yu Thomas j.mcdonald Chetan jinadatha Dionysios D.Dionysiou Mingbao Feng Department of Environmental and Occupational Health School of Public Health Texas A&M University College Station TX 77843 USA Institute of Urban Environment Chinese Academy of Sciences Xiamen 361021 China Central Texas Veterans Health Care System Temple TX 76504 USA College of Medicine Texas A&M Health Science Center Bryan TX 77807 USA Environmental Engineering and Science Program Department of Chemical and Environmental Engineering (DChEE) 705 Engineering Research Center University of Cincinnati Cincinnati OH 45221 USA

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have been recognized as one of the biggest public health issues of the 21 st century. Both ARB and ARGs have been determined in water after treatment with conventional disinfectants. Ultraviolet (UV) technology has been seen growth in application to disinfect the water. However, UV method alone is not adequate to degrade ARGs in water. Researchers are investigating the combination of UV with other oxidants (chlorine, hydrogen peroxide (H2O2), peroxymonosulfate (PMS), and photocatalysts) to harness the high reactivity of produced reactive species (C1-, C1O -, Cl2-,-OH, and SO4-_) in such processes with constituents of cell (e.g., deoxyribonucleic acid (DNA) and its components) in order to increase the degradation efficiency of ARGs. This paper briefly reviews the current status of different UV-based treatments (UV/chlorination, UV/H2O2, UV/PMS, and UV-photocatalysis) to degrade ARGs and to control horizontal gene transfer (HGT) in water. The review also provides discussion on the mechanism of degradation of ARGs and application of q-PCR and gel electrophoresis to obtain insights of the fate of ARGs during UV-based treatment processes.

关键词： Antibiotic resistance bacteria Advanced oxidation processes Disinfection Reactive chlorine species Sulfate radicals Reactive oxygen species

The complexity of sediment recycling as revealed by common Pb isotopes in K-feldspar

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Geoscience Frontiers 2018年第5期9卷 1515-1527页

作者： Simon P.johnson Christopher L.Kirkland Noreen j.Evans Brad j.mcdonald Huntly N.Cutten Geological Survey of Western Australia Mineral House100 Plain StreetEast PerthWestern Australia6004Australia Centre for Exploration Targeting-Curtin Node The Institute for Geoscience ResearchDepartment of Applied GeologyWestern Australian School of MinesCurtin UniversityPerthWestern Australia6102Australia john de Laeter Centre The Institute for Geoscience ResearchDepartment of Applied Geology and Applied PhysicsCurtin UniversityPerthWestern Australia6102Australia

Detrital zircon U-Pb geochronology has become the gold standard in evaluating source to sink relationships in sedimentary basins. However, the physical and chemical robustness of zircon, which make it such a useful mineral for provenance studies, is also a hindrance as zircon can be recycled through numerous sedimentary basins, thus obscuring the first cycle source to sink relationship. An elegant approach to addressing this potential issue is to compare the Pb isotope composition of detrital K-feldspar, a mineral which is unlikely to survive more than one erosion-transport-deposition cycle, with that of magmatic K-feldspar from potential basement source terranes. Here we present new in situ Pb isotope data on detrital K-feldspar from two Proterozoic arkosic sandstones from Western Australia, and magmatic K-feldspar grains from potential igneous source rocks, as inferred by the age and Hf isotope composition of detrital zircon grains. The data indicate that the detrital zircon and K-feldspar grains could not have been liberated from the same source rocks, and that the zircon has most likely been recycled through older sedimentary basins. These results provide a more complete understanding of apparently simple source to sink relationships in this part of Proterozoic Western Australia.

关键词： Detrital zircon K-feldspar Pb isotopes Sediment provenance Sediment recycling

Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy

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Bone Research 2018年第2期6卷 167-176页

作者： Babita Madan Mitchell j.mcdonald Gabrielle E.Foxa Cassandra R.Diegel Bart O.Williams David M.Virshup Program in Cancer and Stem Cell Biology Duke-NUS Medical School Center for Cancer and Cell Biology and Program for Skeletal Disease and Tumor Microenvironment Van Andel Research Institute Department of Pediatrics Duke University

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine（PORCN） that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159（ETC-159） had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN *** of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.

关键词： Wnt ETC Bone loss Wnt inhibition mitigated concurrent alendronate therapy

Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5

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骨研究:英文版 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer Charles Moes Gabrielle E.Foxa Mitchell j.mcdonald Zachary B.Madaj Sabine Guth jun Liu jennifer L.Harris Michaela Kneissel Bart O.Williams Department of Cell Biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland Bioinformatics and Biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in Lrp5(equivalent to human G171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

Investigation on the Solidification and Phase Transformation in Pb-Free Solders Using In Situ Synchrotron Radiography and Diffraction:A Review

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Acta Metallurgica Sinica(English Letters) 2022年第1期35卷 49-66页

作者： Guang Zeng Shiqian Liu Qinfen Gu Zebang Zheng Hideyuki Yasuda stuart D.mcdonald Kazuhiro Nogita School of Materials Science and Engineering Central South UniversityChangsha 410083China Nihon Superior Centre for the Manufacture of Electronic Materials(NS CMEM) School of Mechanical and Mining EngineeringThe University of QueenslandBrisbaneQLD 4072Australia Graduate School Shenzhen Technology UniversityShenzhen 515118China Australian Synchrotron ANSTO.800 Blackburn RdClaytonVIC 3168Australia State Key Laboratory of Solidification Processing School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Department of Materials Science and Engineering Kyoto UniversitySakyo‑kuKyoto 606‑8501Japan

It is widely accepted that further development of Pb-free solder alloys for improved processing and in-service properties of next-generation electronics,can be accelerated through a fundamental understanding of phase transformation and microstructure control in Pb-free solder *** characterization techniques including synchrotron radiation provide a comprehensive toolset to measure the composition,crystallography,morphology,and properties of the major components of solder *** research using such techniques is reviewed in detail including the characterization of the eff ects of microalloy additions on the microstructure and properties of Pb-free solder joints,especially those on the intermetallic *** discoveries outlined are of scientific and industrial relevance and have implications for new solder alloy composition design and the reliability of lead-free solder joints.

关键词： Cu_(6)Sn_(5)intermetallic Synchrotron radiation Solidification Phase transformation