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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Sporophytic control of anther development and male fertility by glucose-6-phosphate/phosphate translocator 1(OsGPT1) in rice

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Journal of Genetics and Genomics 2021年第8期48卷 695-705页

作者： Aili Qu Yan Xu Xinxing Yu Qi Si Xuwen Xu Changhao Liu Liuyi Yang Yueping Zheng Mengmeng Zhang Shuqun Zhang Juan Xu State Key Laboratory of Plant Physiology and biochemistry College of Life SciencesZhejiang UniversityHangzhouZhejiang 310058China Department of Plant Pathology College of Plant ProtectionNanjing Agricultural UniversityNanjingJiangsu 210095China division of biochemistry University of MissouriColumbiaMO 65211USA

Coordination between the sporophytic tissue and the gametic pollen within anthers is tightly controlled to achieve the optimal pollen fitness. Glucose-6-phosphate/phosphate translocator(GPT) transports glucose-6-phosphate, a key precursor of starch and/or fatty acid biosynthesis, into plastids. Here, we report the functional characterization of Os GPT1 in the rice anther development and pollen fertility. Pollen grains from homozygous osgpt1 mutant plants fail to accumulate starch granules, resulting in pollen sterility. Genetic analyses reveal a sporophytic effect for this mutation. Os GPT1 is highly expressed in the tapetal layer of rice anther. Degeneration of the tapetum, an important process to provide cellular contents to support pollen development, is impeded in osgpt1 plants. In addition, defective intine and exine are observed in the pollen from osgpt1 plants. Expression levels of multiple genes that are important to tapetum degeneration or pollen wall formation are significantly decreased in osgpt1 anthers. Previously, we reported that At GPT1 plays a gametic function in the accumulation of lipid bodies in Arabidopsis pollen. This report highlights a sporophytic role of Os GPT1 in the tapetum degeneration and pollen development. The divergent functions of Os GPT1 and At GPT1 in pollen development might be a result of their independent evolution after monocots and dicots diverged.

关键词： Glucose-6-phosphate/phosphate translocator Male fertility Starch accumulation Sporophytic control Pollen development Tapetum degeneration Intine and exine formation Rice

Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years

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World Journal of Gastroenterology 2014年第29期20卷 9775-9827页

作者： Mariusz Panczyk Laboratory of Molecular Diagnostics and Pharmacogenomics Department of Pharmaceutical BiochemistryMedical University of Lodz division of Teaching and Outcomes of Education Faculty of Health ScienceMedical University of Warsaw

During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation,as a result of large international research projects(Human Genome Project,the 1000 Genomes Project International HapMap Project,and Programs for Genomic Applications NHLBI-PGA).This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of *** clinical use in the treatment of patients with colorectal cancer(CRC),in addition to fluoropyrimidines,another two new cytostatic drugs were allowed:irinotecan and *** research into new treatment regimens and a new generation of drugs used in targeted therapy has also been *** last 20years was a time of numerous in vitro and in vivo studies on the molecular basis of drug *** of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer *** the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized *** hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/*** the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application *** review is a synthetic presentation of drug resistance in the context of CRC patient *** multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review.

关键词： Pharmacogenetics Pharmacogenomics Drug resistance Colorectal cancer Chemoresistance Individualized medicine

Preventive Regulation of Jelly Seed Disorder in ‘Amrapali' Mango (Mangifera indica) by Preharvest Spray

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Horticultural Plant Journal 2019年第2期5卷 70-78页

作者： Shivashankar Seshadri Sumathi Manoharan Hari Shankar Singh division of Plant Physiology and biochemistry ICAR-Indian Institute of Horticultural ResearchHesaraghatta Lake PO ICAR-National Centre for Integrated Pest Management Pusa Campus

Jelly seed, a physiological disorder in ‘Amrapali' mango fruit, is characterized by the excessive softening of pulp around the stone in ripe fruits. The disorder is caused by the onset of germination associated events in the seed of developing fruit due to decreased level of very-longchain fatty acids(VLCFAs) in seed. Field trials involving preharvest application of spray formulations on developing fruits, between 50% and 60%maturity, showed that formulation V(10 g·L^(-1) NaCl, 25 g·L^(-1) CaCl_2, 0.5 g·L^(-1) KCl, 0.01 g·L^(-1) H_3 BO_3, 0.01 g·L^(-1) Cu SO_4, 0.01 g·L^(-1) Zn SO_4,0.01 g·L^(-1) FeSO_4, 0.01 g·L^(-1) MnSO_4, and 0.002 g·L^(-1) EDTA) was the most effective in preventing the jelly seed disorder. Further studies to understand the mode of action of the formulation in controlling jelly seed development, revealed increased synthesis of VLCFAs in seed followed by the rapid production of ABA and germination-inhibiting phenolic acids, besides increased accumulation of calcium in seed. These factors acting in unison delayed seed germination and decreased the activities of pectinolytic enzymes in pulp to produce healthy fruits, free from jelly seed *** was an increase of mineral nutrient content in pulp of treated healthy fruits. Thus, the study helped to develop a remedy to prevent jelly seed besides revealing the biochemical mechanism by which formulation V acted to produce ‘Amrapali' mango fruits free of jelly seed with improved nutritional quality.

关键词： Amrapali mango jelly seed physiological disorder prevention preharvest treatment

Insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration Research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An M.Voets Tim Vanmierlo Rudy Schreiber BIOMED Biomedical Research Institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium Department of Psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands University MS Center(UMSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

关键词： academic approval consequences

Influences of Catch Crop and Its Incorporation Time on Soil Carbon and Carbon-Related Enzymes

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Pedosphere 2015年第4期25卷 569-579页

作者： Anna PIOTROWSKA-DLUGOSZ Edward WILCZEWSKI Department of Soil Science and Soil Protection Division of Biochemistry Faculty of Agriculture and Biotechnology UTP University of Science and Technology Department of Agrotechnology Faculty of Agriculture and Biotechnology UTP University of Science and Technology

Catch crops that are cultivated for green manure play an important role in improving soil properties. A 3-year field experi- ment was conducted to investigate the effect of catch crop （pea, Pisum sativum L.） management, i.e., incorporation of catch crop in October/November （autumn） and March （spring）, and without catch crop （control）, on soil organic carbon （SOC）, microbial biomass carbon （MBC） and the activities of carbon （C）-cycle enzymes, including cellulase （Cel）, β-glucosidase （Glu） and invertase （Inv）. Additionally, soil total nitrogen （TN） and pHKcl were investigated. The catch crop was cultivated from August to October each year during 2008-2010. Soil samples were collected from the field of spring barley （Hordeum vulgate L.） that had been grown after the catch crop. Soil samples for microbial activity determination were taken in March, May, June and August in 2009, 2010 and 2011, while SOC and TN contents as well as pHKc1 were determined in March and August. The chemical properties studied did not show significant changes as influenced by the experimental factors. The use of catch crop significantly increased the MBC content and the activities of C-cycle enzymes compared to the control. When the catch crop was incorporated in spring, a significantly higher MBC content was noted in March and May compared to autumn incorporation. Moreover, the spring incorporation of the catch crop significantly increased the Glu activity （except March）, while the activities of Cel and Inv as well as the rate of soil basal respiration were usually unaffected by the time of catch crop incorporation. Greater microbial biomass and higher enzyme activities in the catch crop-treated soil, compared to the control, indicated that the application of the catch crop as a green manure could be recommended as a promising technique to increase the biological activity of the soil. Since there was no significant effect or no consistent results were obtained related to the time of catch crop

关键词： cellulase β-glucosidase invertase microbial biomass carbon soil basal respiration

Phosphorus Starvation Tolerance in Rice Through Combined Physiological,Biochemical,and Proteome Analyses

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Rice science 2023年第6期30卷 613-631页

作者： Prathap V Suresh KUMAR Nand Lal MEENA Chirag MAHESHWARI Monika DALAL Aruna TYAGI division of biochemistry Indian Council of Agricultural Research-Indian Agricultural Research InstituteNew Delhi 110012India division of Germplasm Evaluation National Bureau of Plant Genetic ResourcesNew Delhi 110012India National Institute for Plant Biotechnology New Delhi 110012India

Phosphorus(P) deficiency limits the growth,development,and productivity of *** better understand the underlying mechanisms in P-deficiency tolerance and the role of Pup1 QTL in enhancing P use efficiency(PUE) for the development of P-efficient rice cultivars,a pair of contrasting rice genotypes(Pusa-44 and NIL-23) was applied to investigate the morpho-physio-biochemical and proteomic variation under P-starvation *** rice genotypes were grown hydroponically in a PusaRich medium with adequate P(16 mg/kg,+P) or without P(0 mg/kg,-P) for 30 d.P-starvation manifested a significant reductions in root and shoot biomass,shoot length,leaf area,total chlorophyll,and P,nitrogen and starch contents,as well as protein kinase *** stress increased root-to-shoot biomass ratio,root length,sucrose content,and acid phosphatase activity,particularly in the P-tolerant genotype(NIL-23).Comparative proteome analysis revealed several P metabolism-associated proteins(including OsCDPKs,OsMAPKs,OsCPKs,OsLecRK2,and OsSAPks) to be expressed in the shoot of NIL-23,indicating that multiple protein kinases were involved in P-starvation/deficiency ***,the up-regulated expression of OsrbcL,OsABCG32,OsSUS5,OsPoll-like B,and ClpC2 proteins in the shoot,and OsACA9,OsACA8,OsSPS2F,OsPP2C15,and OsBiP3 in the root of NIL-23,indicated their role in P-starvation stress control through the Pup1 QTL. Thus,our findings indicated that-P stress-responsive proteins,in conjunction with morpho-physio-biochemical modulations,improved PUE and made NIL-23 a P-deficiency tolerant genotype due to the introgression of the Pup1 QTL in the Pusa-44 background.

关键词： phosphorus deficiency Pup1 QTL protein kinase acid phosphatase proteome analysis rice

Identification of Iron Oxides Qualitatively/Quantitatively Formed during the High Temperature Oxidation of Superalloys in Air and Steam Environments

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Journal of Materials Science & Technology 2009年第4期25卷 479-482页

作者： M. Siddique N. Hussain M. Shafi Physics division PINSTECH Materials division PINSTECH

Mossbauer spectroscopy has been used to study the morphology of iron oxides formed during the oxidation of superalloys, such as SS-304L （1.4306S）, Incoloy-800H, Incoloy-825, UBHA-25L, Sanicro-28 and Inconel-690, at 1200℃ exposed in air and steam environments for 400 h. The basic aim was to identify and compare the iron oxides qualitatively and quantitatively, formed during the oxidation of these alloys in two environments. The behaviour of alloy UBHA-25L in high temperature oxidation in both environments indicates that it has good oxidation resistance especially in steam, whereas Sanicro-28 has excellent corrosion resistance in steam environment. In air oxidation of Inconel-690 no iron oxide, with established Mossbauer parameters, was detected.

关键词： Superalloys Mossbauer spectroscopy Oxidation Corrosion products

Molecular Cloning, Expression and Characterization of Ribokinase of Leishmania major

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Acta Biochimica et Biophysica Sinica 2007年第6期39卷 462-466页

作者： Patrick. O. J. OGBUNUDE Nadia LAMOUR Michael P. BARRETT Department of Medical biochemistry University of Nigeria Enugu 1000004 Nigeria Department of biochemistry and Massey Cancer Center Virginia Commonwealth University Richmond 23298-0614 USA Institute of Biomedical and Life Sciences Division of Infection and Immunity Joseph Black Building University of Glasgow Glasgow G12 8QQ UK

Ribokinase （EC 2.***.7.15） from Leishmania major was cloned, sequenced and overexpressed in Escherichia coli. The gene expressed an active enzyme that had comparable activity to the same enzyme studied in E. coli. It specifically phosphorylated D-ribose. Under defined conditions, the Km for the substrates D-ribose and ATP were 0.3±0.04 mM and 0.2±0.02mM, respectively. The turnover numbers of the enzyme for the substrates were 10.8s-1and 10.2 s-1, respectively. The enzyme product ribose 5-phosphate inhibited the phosphorylation of D-ribose with an apparent Kiof 0.4 mM, which is close to the Km（0.3mM） of Dribose, suggesting that it might play a role in regulating flux through the enzyme.

关键词： Leishmania major D-ribose ribokinase molecular cloning