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Metformin and metabolic diseases： a focus on hepatic aspects

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Frontiers of Medicine 2015年第2期9卷 173-186页

作者： Juan Zheng Shih-Lung Woo Xiang Hu rachel Botchlett Lulu Chen Yuqing Huo Chaodong Wu Department of Nutrition and Food Science Texas A &M University College Station TX 77843 USA Department of Endocrinology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China Drug Discovery Center Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School Shenzhen 518055 China

Metformin has been widely used as a diabetes （T2D）. As a drug that primarily targets first-line anti-diabetic medicine for the treatment ot type Z the liver, metformin suppresses hepatic glucose production （HGP）, serving as the main mechanism by which metformin improves hyperglycemia of T2D. BiochemicaUy, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase （AMPK）-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.

关键词： metformin diabetes hepatic steatosis inflammatory response insulin resistance

The benefits of being dominant:health correlates of male social rank and age in a marmot

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Current Zoology 2022年第1期68卷 19-26页

作者： Kenta UCHIDA rachel NG Samuel A.VYDRO Jennifer E.SMITH Daniel T.BLUMSTEIN Department of Ecology&Evolutionary Biology University of CaliforniaLos AngelesCA 90095-1606USA Department of Biology Mills CollegeOaklandCA 94613USA The Rocky Mountain Biological Laboratory Crested ButteCO 81224USA

The benefits of dominance may not come without costs,particularly for *** example,the“immunocompetence handicap hypothesis”states that males with enhanced mating success allocate resources to enhance reproductive output at a cost to their current health,whereas the“resource quality hypothesis”predicts that high-ranking males may benefit from increased reproduction and good *** the predictions from each have been well tested in captive animals and in a variety of highly social primates,fewer studies have been carried out in free-living,facultatively social *** adult male yellow-bellied marmots(Marmota flaviventer),we evaluated predictions of these hypotheses by examining the relationship between social rank and 2 health indicators—fecal glucocorticoid metabolite(FCM)levels,and neutrophil/lymphocyte(N/L)ratios—after accounting for variation explained by age,body mass,and *** found that higher-ranking males tended to have a lower N/L ratio(reflecting good health)than lower-ranking individuals,whereas FCM levels were not significantly related to *** addition,heavier male marmots had lower N/L ratios,whereas body mass was not associated with FCM *** also found that older adult males had lower FCM levels(reflecting less physiological stress)but higher N/L ratios than younger ***,we found that FCM levels decreased as the active season progressed and FCM levels were associated with the time of the ***,our results suggest that socially-dominant male marmots enjoyed better,not worse health in terms of lower N/L ratios.

关键词： immunocompetence handicap hypothesis life history trade-offs N/L ratio physiological stress resource quality hypothesis

Crohn’s disease: Why the ileum?

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World Journal of Gastroenterology 2023年第21期29卷 3222-3240页

作者： Nicolas Richard Guillaume Savoye Mathilde Leboutte Asma Amamou Subrata Ghosh rachel Marion-Letellier University of Rouen Normandie INSERMADEN UMR 1073NutritionInflammation and Microbiota-Gut-Brain AxisRouen F-76000France CHU Rouen Department of GastroenterologyRouen University Hospital-Charles NicolleRouen F-76000France Institute for Research and Innovation in Biomedicine University of Rouen NormandieRouen F-76000France APC Microbiome Ireland Biosciences BuildingUniversity College CorkCork T12 YT20Ireland

Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission *** CD,the ileum is frequently affected and about one third of patients presents with a pure ileal ***,the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility *** of these genes are associated with Paneth cell dysfunction,a cell type found in the intestinal crypts of the ***,a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota,which in turn modulates the susceptibility of the ileum to ***,the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ***,both immune response and cellular healing processes harbour differences between ileal and non-ileal *** together,these findings advocate for a dedicated therapeutic approach to managing ileal ***,interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease ***,the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.

关键词： Ileum Crohn’s disease Bile acids Paneth cells Diet Genetics Strictures

P. fluorescens and B. megaterium Effect on the Lifespan of Mutant-Type dpy-11 and Wild-Type of C. elegans

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CellBio 2022年第1期11卷 1-9页

作者： rachel Ross Biotechnoloy High School Freehold NJ USA

The research question being studied in this paper is how do different types of bacteria as food (Pseudomonas fluorescens and Bacillus megaterium) affect the lifespan of Caenorhabditis elegans in dpy-11 mutant-type and wild-type? P. fluorescens and B. megaterium will be the two pathogens that will be tested on two different types of C. elegans: mutant-type dpy-11 and wild-type. From the analysis of primary articles studying these pathogens, it can be concluded that P. fluorescens and B. megaterium are decent contenders for allowing C. elegans to grow and possibly extend the lifespan of it. P. fluorescens will allow the lifespan of the two types of nematodes to be longer. Additionally, the mu-tant-type dpy-11 of C. elegans will have a much longer lifespan, even double, compared to that of the wild-type. The results showed P. fluorescens had a longer lifespan than B. megaterium but not as long as C. elegans’ main food source, E. coli. C. elegans mutant dpy-11 had a longer lifespan than the wild-type. Furthermore, there were no C. elegans present in the B. megaterium wild-type plates.

关键词： C. elegans P. fluorescens B. megaterium E. coli

Soil fungal and prokaryotic community structure exhibits differential short-term responses to timber harvest in the Pacific Northwest

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Pedosphere 2020年第1期30卷 109-125页

作者： rachel E.DANIELSON Megan L.MCGINNIS Scott M.HOLUB David D.MYROLD Department of Crop and Soil Science Oregon State UniversityCorvallis OR 97331-7306(USA) United State Forest Service Helena-Lewis and Clark National Forest2880 Skyway DriveHelena MT 59602(USA) Weyerhaeuser Company PO Box 275Springfield OR 97477(USA) Department of Land Airand Water ResourcesUniversity of CaliforniaDavis CA 95616USA

Conventional clear-cut timber harvest is a widespread industrial practice across the Pacific Northwest;however,information regarding how these practices impact soil microbial community structure at the regional scale is *** evidence of consistent and substantial impact of harvest on soil microbial functional profiles across the region(despite a range of environmental conditions),the objective of this study was to determine the extent to which harvest also influences the structure of prokaryotic and fungal soil microbial communities,and how generalized these trends are throughout the geographic *** soil samples were collected one year before and after harvest across nine second-growth Douglas-fir forests in the Pacific *** community DNA was extracted from the soils,and high-throughput targeted gene sequencing of the 16 S r RNA gene for prokaryotes and the internal transcribed spacer(ITS)gene for fungi was *** diversity was consistently and significantly higher after harvest;it was moderately so for fungal communities(+14.6%),but only marginally so for prokaryotic communities(+2.0%).Similarly,on average,a greater proportion of the variation in the community structure of fungi(20.1%)at each site was associated with forest harvest compared to that of prokaryotes(13.2%).Overall,the greatest influence of timber harvest on soil microbial communities appeared to be a relative depletion of ectomycorrhizal fungi,with a concomitant enrichment of saprotrophic *** the short-term responses of soil microbial communities across the region,particularly those of tree root-associated symbionts,may aid our understanding of the role soil microbial communities play in ecological succession.

关键词： clear-cut Douglas-fir forest ectomycorrhizal fungi forest soil microbial community microbial diversity root-associated symbiont saprotrophic fungi

Vegetation and Environment History for the Past 14 000 yr BP from Dingnan, Jiangxi Province, South China

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Journal of Integrative Plant Biology 2006年第9期48卷 1018-1027页

作者： John Richard Dodson Shirene Hickson rachel Khoo Xiao-Qiang Li Jemina Toia Wei-Jian Zhou Institute for the Environment Brunel University Uxbridge UB8 3PH England School of Earth and Geographical Sciences University of Western Australia Perth WA 6009 Australia State Key Laboratory of Loess and Quaternary Institute for Earth Environment the Chinese Academy of Sciences Xi＇an 710075 China

A Late Pleistocene-Holocene pollen, phosphorus, and charcoal record was reconstructed from a peatland in southern Jiangxi Province in southern China. The area today has a mountainous and rolling landscape with villages, small towns, and agriculture dominated by rice paddies, vegetable, and fruit gardens, as well as areas of secondary forest and pine re-afforestation. The record opens before 14 300 yr BP, with Alnus woodland dominating the wetland areas and with an open Quercus woodland on the surrounding slopes. The forest area becomes more complex from approximately 12 800 yr BP and further from 9 000 yr BP. At approximately 6 000 yr BP, there is evidence of clearing and, by 4 500-4 000 yr BP, a complete collapse in the wetland Alnus and terrestrial forest as the low-lying areas are converted to rice production. For much of the record, the occurrence of fire around the site was low, although there is evidence of regional fires. Fire was used as a tool in clearing and then used in the annual cycles of stubble burning after rice harvest. Nutrient levels, as reflected by total phosphorus in the sediment, seem to be closely related to forest changes and high values in the surface layers probably result from land-management techniques associated with agriculture. Therefore, human impact greatly altered forest cover, fire frequency, and nutrient dynamics; this has been evident for approximately 6 000 yr BP and then intensities towards the present day.

关键词： development of rice agriculture nutrient and fire history South China vegetation history

Eat more natural dietary fiber and whole grains to minimize liver disease risk

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Hepatobiliary Surgery and Nutrition 2022年第4期11卷 601-604页

作者： rachel M.Golonka Beng San Yeoh Matam Vijay-Kumar Department of Physiology and Pharmacology University of Toledo College of Medicine and Life SciencesToledoOHUSA

Nutritional habits in the United States have dramatically changed since the Industrial Revolution in the 18th ***,not every‘advancement’from then to now has improved human dietary habits and *** is evident from the rising epidemic of nutritional insufficiencies associated with the increasing prevalence of age-related diseases(1).Work from Dennis Burkett in the late 1960s was one of the first to hypothesize that refinement of grains and removal of dietary fiber could explain the regional dichotomy in disease incidence(2).

关键词： fiber refinement grains

Advances in targeted nanotherapeutics： From bioconjugation to biomimicry

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Nano Research 2018年第10期11卷 4999-5016页

作者： Danielle M. Valcourt Jenna Harris rachel S. Riley Megan Dang Jianxin Wang Emily S. Day 161 Colburn L ab Department of Biomedical Engineering University of Delaware Newark DE 19716 USA 201 DuPont Hall Department of Materials Science & Engineering University o f Delaware Newark DE 79716 USA 4701 Ogletown Stanton Road Helen F. Graham Cancer Center & Research Institute Newark DE 19713 USA

Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.

关键词： targeting nanoparticles cancer biomimicry bioconjugation delivery

Immune checkpoint inhibitors in breast cancer: development, mechanisms of resistance and potential management strategies

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Cancer Drug Resistance 2023年第4期6卷 768-787页

作者： rachel SJ Wong Rebecca JM Ong Joline SJ Lim Department of Haematology-Oncology National University Cancer InstituteNational University HospitalSingapore 119228Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore

The use of immune checkpoint inhibitors(iCls)has increased exponentially in the past decade,although its progress specifically for breast cancer has been *** first *** and Drug Administration approval for ICl in breast cancer came in 2019,eight years after the first-ever approval of an *** present,current indications for ICls are relevant only to a subset of patients with triple-negative breast cancer,or those displaying high microsatellite instability or deficiency in the mismatch repair protein *** an increasing understanding of the limitations of using ICls,which stem from breast cancer being innately poorly immunogenic,as well as the presence of various intrinsic and acquired resistance pathways,ongoing trials are evaluating different combination therapies to overcome these *** this review,we aim to describe the development timeline of ICls and resistance mechanisms limiting their utility,and summarise the available approaches and ongoing trials relevant to overcoming each resistance mechanism.

关键词： Immunotherapy immune checkpoint inhibitors resistance mechanisms breast cancer