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Nicotinamide overload may play a role in the development of type 2 diabetes

World Journal of Gastroenterology 2009年第45期15卷 5674-5684页

作者： Shi-Sheng Zhou Da Li Wu-Ping Sun Ming Guo Yong-Zhi Lun Yi-Ming Zhou fu-Cheng Xiao Li-Xin Jing Shen-Xia Sun Li-Bin Zhang ning Luo fu-ning bian Wei Zou Lai-Bin Dong Zhi-Gang Zhao Sheng-Fan Li Xiao-Jie Gong Zeng-Guo Yu Chang-Bin Sun Cong-Long Zheng Dong-Ju Jiang Zheng-ning Li Institute of Basic Medical Sciences Medical College Dalian University Dalian 116622 Liaoning Province China College of Environmental and Chemical Engineering -Dalian University Dalian 116622 Liaoning Province China Okazaki Institute for Integrative Bioscience National Institutes of Natural Sciences Okazaki 444-8787 Japan Department of Physiology Xinxiang Medical College Xinxiang 453003 Henan Province China Department of Life Sciences Liaoning Normal University Dalian 116029 Liaoning Province China - Department of Neurology PLA No. 91 HospitalJiaozuo 454003 Henan Province China Department of Medicine PLA No. 210 Hospital Dalian 116021 Liaoning Province China

AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels and tissue nicotinamide adenine dinucleotide （NAD） contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS： Diabetic subjects had significantly higher plasma N^1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects （0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P 〈 0.001）. Cumulative doses of nicotinamide （2 g/kg） significantly increased rat plasma Nl-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by Nl-methy-Inicotinamide. Moreover, cumulative exposure to N^1- methylnicotinamide （2 g/kg） markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N^1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide （5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load）. Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N^1- methylnicotinamide clearance. CONCLUSION： These findings suggest that nicotinamide overload, which induced an increase in plasma N^1- methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

关键词： Type 2 diabetes Nicotinamide N^1-methyl-nicotinamide Insulin resistance Oxidative stress Liver Sweat glands

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ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China Life Sciences 2025年第1期68卷 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan bian Yong Zhang State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

关键词： spatial transcriptome histological images spatial resolution enhancement

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

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Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine

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World Journal of Clinical Oncology 2025年第1期16卷 25-33页

作者： Jiang-Yu bian Yu-Fang Feng Wen-Ting He Tong Zhang Department of Oncology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China Department of Oncology The Fourth Clinical Medical College of Xinjiang Medical UniversityUrumqi 830001China Department of Oncology Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830001China

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor *** the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal ***,we further explored the survival benefits in the population with BRAF V600E mutant *** To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal *** A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December *** patients were divided into two *** A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,*** analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

关键词： Metastatic colorectal cancer BRAF V600E mutation Integrated Chinese and Western medicine Cohort study

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Polymeric nanoparticles of poly(2-oxazoline),tannic acid and doxorubicin for controlled release and cancer treatment

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Chinese Chemical Letters 2020年第2期31卷 501-504页

作者： Lin Liu Liying Yin Hang bian ning Zhang Department of Chemistry Northeast Normal UniversityChangchun 130024China School of Material Science and Engineering Jilin Jianzhu UniversityChangchun 130118China

A straightforward coassembly strategy was developed for the preparation of polymeric nanoparticles driving by the intermolecular hydrogen bond between neutral poly(2-methyl-2-oxaozline)(PMeOx),tannic acid(TA) and doxorubicin hydrochloride(Dox).The occurrence of the hydrogen-bonding amongst the different functionalities within the formed nanoparticles was verified by infrared(IR) *** electron microscopy(SEM),dynamic light scattering(DLS),UV-vis absorption and photoluminescent measurements indicated the rapid formation of uniform and water dispersible/stable *** relative poor stability of PMeOx-TA-Dox in fetal bovine serum(FBS) solution enabled the rapid separation of Dox and PMeOx-TA,facilitating the release of Dox and its entrance into cellular nuclei as revealed by confocal laser scanning microscopy(CLSM).The presented strategy may provide an efficient alternative for the construction of multifunctional nanomedicines.

关键词： Polymeric nanoparticle Poly(2-oxazoline) Drug delivery Self-assembly Doxorubicin

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Chronic niacin overload may be involved in the increased prevalence of obesity in US children

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World Journal of Gastroenterology 2010年第19期16卷 2378-2387页

作者： Li, Da Sun, Wu-Ping Zhou, Yi-Ming Liu, Qi-Gui Zhou, Shi-Sheng Luo, ning bian, fu-ning Zhao, Zhi-Gang Guo, Ming Dalian Univ Coll Med Inst Basic Med Sci Dalian 116622 Liaoning Peoples R China Natl Inst Nat Sci Okazaki Inst Integrat Biosci Okazaki Aichi 8787 Japan Dalian Med Univ Dept Hlth Stat Dalian 116044 Liaoning Peoples R China PLA 210 Hosp Dept Nucl Med Dalian 116021 Liaoning Peoples R China Dalian Univ Coll Environm & Chem Engn Dalian 116622 Liaoning Peoples R China

AIM: To investigate nicotinamide’s action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS: Dynamic nicotinamide’s effect on plasma hydrogen peroxide and glucose metabolism was in- vestigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy ***-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic Research Service of the US Department of Agriculture and from US Centers for Disease Control and Prevention, respectively. RESULTS: Compared with the control oral glucose tolerance test, the 1-h plasma hydrogen peroxide (1.4 ± 0.1 μmol/L vs 1.6 ± 0.1 μmol/L, P = 0.016) and insulin levels (247.1 ± 129.0 pmol/L vs 452.6 ± 181.8 pmol/L, P = 0.028) were signif icantly higher, and the 3-h blood glucose was signif icantly lower (5.8 ± 1.2 mmol/L vs 4.5 ± 1.1 mmol/L, P = 0.002) after coadministration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption (R2 = 0.814, 0.961 and 0.94 for 2-5 years, 6-11 years and 12-19 years age groups, respectively). CONCLUSION: The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.

关键词： Obesity Diabetes Niacin Nicotinamide

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Synthesis and characterization of ceria nanoparticles by complex-precipitation route

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International Journal of Minerals,Metallurgy and Materials 2022年第2期29卷 292-297页

作者： Yanping Li Xue bian Yang Liu Wenyuan Wu Gaofeng fu School of Metallurgy Northeastern UniversityShenyang 110819China

Ceria(CeO_(2))nanoparticles were successfully synthesized via a simple complex-precipitation route that employs cerium chloride as cerium source and citric acid as *** elemental analysis results of carbon,hydrogen,oxygen,and cerium in the precursors were calculated,and the results revealed that the precursors were composed of Ce(OH)_(3),Ce(H_(2)Cit)_(3),or CeCit.X-ray diffraction analysis showed that all ceria nanoparticles had a face-centered cubic *** the molar ratio of citric acid to Ce^(3)+(n)of 0.25 and pH of 5.5,the specific surface area of the sample reached the maximum value of 83.17 m^(2)/*** nanoparticles were observed by scanning electron *** area electron diffraction patterns of several samples were obtained by transmission electron microscopy,and the crystal plane spacing of each low-exponent crystal plane was *** ultraviolet(UV)–visible transmittance curve showed that ceria can absorb UV light and pass through visible *** all samples,the minimum average transmittance of ultraviolet radiation a(UVA)was 4.42%,and that of ultraviolet radiation b(UVB)was 1.56%.

关键词： ceria nanoparticle complex-precipitation crystal plane spacing ultraviolet light

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Selective modification of two-dimensional MoS_2 nanosheets by polymer grafting

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Chinese Chemical Letters 2019年第2期30卷 311-313页

作者： Hang bian Xuejian Zhang Dexin Huang ning Zhang School of Material Science and Engineering Jilin Jianzhu University Key Laboratory of Synthetic Rubber Changchun Institute of Applied ChemistryChinese Academy of Sciences

As an emerging two-dimensional (2D) nanomaterial, single layer ora few layers of molybdenum disulfide (MoS_2) has drawn significant attention in the past decade. In the present work, we report a strategy in direct creating polymer brushes on MoS_2 surfaces via S—C bond in the presence of UV light. The modification of MoS_2 nanosheets can be achieved bilaterally or homolaterally by performing the UVgrafting polymerization on exfoliated MoS_2 nanosheets or a single layer of MoS_2 deposited on a silicon substrate. A series of vinyl monomers including methyl methacrylate (MMA), styrene (St) and 2-isopropenyl-2-oxazoline (IPOx) could be applied to this approach, leading to the formation of poly (methyl methacrylate) (PMMA), polystyrene (PS) and poly (2-isopropenyl-2-oxazoline) (PIPOx) ***, IR, and XPS characterizations indicate the successful formation of homogeneous brush layers on MoS_2 surfaces. The polymer brushes modified MoS_2 may found potential applications in photo dynamic therapy and sensing technologies.

关键词： Molybdenum disulfide Polymer brushes SIPGP Surface modification S-C bond

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Controlled synthesis of silver nanoparticles from polyoxometalates-immobilized poly(4-vinylpyridine) brushes

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Chinese Chemical Letters 2019年第5期30卷 1097-1099页

作者： Hang bian Xuejian Zhang Hongkai Zhao ning Zhang School of Material Science and Engineering Jilin Jianzhu UniversityChangchun 130118China Department of Chemistry Northeast Normal UniversityChangchun 130024China

This contribution reports the immobilization of polyoxometalate(POM)into poly(4-vinyl pyridine)(P4 VP)brushes and the controlled reduction of silver ions,in-situ generating metal nanoparticles in the brushes.P4 VP brushes were straightforwardly created by UV-assisted photopolymerization of 4-vinyl pyridine(4VP)on silicon or glass *** acid(H3 PW12 O40),one of the most widely used Keggin-type POM was anchored onto these pyridine moieties through electrostatic interaction,leading to the P4 VP/POM hybrid *** immobilized POM was further reduced to heteropolyblue,which could be used to generate silver nanoparticles in a controlled ***,UV-vis and IR characterization indicate that P4 VP brushes not only provide an efficient platform in the controlled preparation of Ag nanoparticles,but also efficiently disperse and stabilize POM,thus preventing the aggregation of the generated Ag nanoparticles.

关键词： Polymer brushes Polyoxometalate Ag nanoparticles Grafting polymerization

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Effect of tadalafil in chronic renal failure rabbits:relevance to erectile dysfunction

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第6期12卷 455-459页

作者： Meng-yuan ZHANG Qiang fu Wei bian Department of Urology Provincial Hospital Affiliated to Shandong University Jinan 250021 China

It is of great importance to investigate an effective and reliable medication against chronic renal failure (CRF)-related erectile dysfunction (ED),which aims to improve patients' life *** concentrations of cyclic guanosine monophosphate (cGMP) in the corpus cavernosal smooth muscle of both CRF and control rabbits were *** effects of various concentrations of tadalafil,papaverine,and sodium nitroprusside on the relaxation responses of corpus cavernosal smooth muscle pre-contracted with phenylephrine in CRF rabbits were *** was significant difference in the concentration of cGMP between CRF and control rabbits (P<0.01).Tadalafil had the greatest impacts on CRF rabbits when given the same concentration of papaverine or sodium nitroprusside and particularly significant differences were identified under the concentration levels of 10-5 and 10-4 mol/L (P<0.01).The results suggest that the cGMP concentrations of the corpus cavernosum had been greatly reduced in CRF rabbits compared with control rabbits and that tadalafil may be an ideal medication for use in the treatment of CRF-related ED.

关键词： Chronic renal failure Erectile dysfunction Phosphodiesterase inhibitor Tadalafil

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