Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we i...Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.展开更多
Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continu...Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their grasp.Within this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC.Excessive accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage polarization.Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic instability.Therefore,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases.In this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.展开更多
Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Ni...Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Nicotinamide mononucleotide (NMN), an antiaging supplement, is the precursor of coenzyme nicotinamide adenine dinucleotide (NAD) that plays an important role in intracellular redox reactions. Objective: The study compared the serum concentrations of NAD in normal healthy participants, supplemented with NMN 500 mg and NMN 500 mg + 5 mg BioPerine® (95% piperine). Methods: In a randomized, open-label, crossover study, NMN (500 mg) was compared to NMN + BioPerine® (500 mg + 5 mg) in 6 healthy adults, aged 18 - 45 years. The participants received a single oral dose of NMN or NMN + BioPerine® capsules with 240 mL water, and blood samples were collected over 8hr. After a 4-day washout period, the same procedures were repeated as per the crossover design. Total NAD (NADtotal), including oxidized NAD (the oxidized) and its reduced form NADH, was measured in human serum samples. Results: The maximum concentration (Cmax) of NAD in serum was higher with NMN + BioPerine® (282 pmol/mL) compared to NMN (246 pmol/mL) alone. In the presence of BioPerine®, the NAD concentrations reached 257 pmol/mL during the first 2 hr, whereas a comparable serum concentration (246 pmol/mL) was attained only after 6 hr in NMN alone. The AUC0-8hr was 1738 pmol/mL/hr in NMN compared to 2004 pmol/mL/hr in NMN+ BioPerine®. The time to reach peak concentration (t1/2) was similar (6hr) in both groups. No clinically relevant adverse events (AE) were observed, and safety parameters remained within normal ranges in all the participants with both formulations. Conclusion: These results reveal that BioPerine® can effectively increase the NAD concentrations in the serum following NMN supplementation in healthy volunteers. The present study was registered prospectively with the Clinical Trials Registry-India (CTRI/2023/11/059982).展开更多
Adenine phosphoribosyltransferase(APRT)deficiency is a rare autosomal recessive disease leading to generation of large amounts of 2,8-dihydroxyadenine(DHA).DHA is excreted in urine,where it precipitates into crystals ...Adenine phosphoribosyltransferase(APRT)deficiency is a rare autosomal recessive disease leading to generation of large amounts of 2,8-dihydroxyadenine(DHA).DHA is excreted in urine,where it precipitates into crystals due to its low solubility.DHA crystals can aggregate into stones or cause injury to the renal parenchyma(DHA nephropathy).Recurrent urolithiasis and DHA nephropathy are the two clinical manifestations of APRT deficiency.Diagnosis of APRT deficiency can be made during childhood as well as adulthood.Diagnosis mainly relies on the recognition of DHA in stones or urine crystals.Measurement of APRT activity and genetic testing are useful for confirmation of diagnosis,for family screening and should be considered in difficult cases of urolithiasis or crystalline nephropathy.Allopurinol therapy is the cornerstone of treatment and is highly effective in preventing recurrence of stones and kidney disease.High fluid intake and dietary modifications are also recommended.Early diagnosis and treatment are of paramount importance to prevent renal damage.Unfortunately,diagnosis of APRT deficiency is often overlooked and irreversible renal failure still occurs in a substantial proportion of patients.Clinicians must be alert to the possibility of APRT deficiency and consider the appropriate diagnostic tests in certain cases.This review discusses the genetic and biochemical mechanisms of APRT deficiency,and the issues of diagnosis and management.展开更多
Aim ,To study the mechanism relative to therapeutic effects of matrine on adenine-induced renal interstitial fibrosis in rats. Methods Sixty male Wistar rats were selected and randomly divided into 3 groups: normal c...Aim ,To study the mechanism relative to therapeutic effects of matrine on adenine-induced renal interstitial fibrosis in rats. Methods Sixty male Wistar rats were selected and randomly divided into 3 groups: normal control group (NCG) consisted of 8 rats, adenine treated group (ATG) 28 rats, and matrine treated group (MTG) 24 rats. Each rat in ATG and MTG was gavaged with adenine (250 mg·kg^-1·d^-1 ) for 21 d. After gavage with adenine for one week, each rat in MTG was administered intraperitoneally matrine(20 mg·kg^-1·d^-1 ) in vehicle ( 1 mL of 0.9% sodium chloride) daily. On days 14, 21, and 28, the serum levels of urea nitrogen, creatinine, and IL-6 were determined and the rat kidneys of ATG, MTG and NCGwere examined pathologically. Radioimmunoassay for serum IL- 6 immunohistochemical staining for TGF-β1 expression in the kidney and semiquantitative analysis were performed. HE staining for semiquantitative analysis of tubulointerstitial injury. Results The serum levels of urea nitrogen and creatinine in MTG were lower as compare to ATG ( P 〈 0.05 ) whereas serum IL- 6 and renal TGF-β1 expression levels were significantly lower than those in ATG (P 〈0.05 ), but all these indexes were higher than those in NCG (P 〈 0.01 ). In MTG, the index of tubulointerstitial lesion was lower than that in ATG (P 〈 0.05 ). Conclusion Matrine inhibits the renal tubulointerstial fibrosis in the adenine-induced rat model by suppressing serum level of IL-6 and expression of TGF-β1 in the tubulointerstitium.展开更多
Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under...Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however,excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research,coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.展开更多
Precise base editing is highly desired in plant functional genomic research and crop molecular breeding. In this study, we constructed a rice-codon optimized adenine base editor(ABE)-nC as9 tool that induced targeted ...Precise base editing is highly desired in plant functional genomic research and crop molecular breeding. In this study, we constructed a rice-codon optimized adenine base editor(ABE)-nC as9 tool that induced targeted A·T to G·C point mutation of a key single nucleotide polymorphism site in an important agricultural gene. Combined with the modified single-guide RNA variant, our plant ABE tool can efficiently achieve adenine base editing in the rice genome.展开更多
Oxaliplatin, an anticancer drug commonly used to treat colorectal cancer and other tumors, has a number of serious side effects, most notably neuropathy and ototoxicity. To gain insights into its ototoxic profile, oxa...Oxaliplatin, an anticancer drug commonly used to treat colorectal cancer and other tumors, has a number of serious side effects, most notably neuropathy and ototoxicity. To gain insights into its ototoxic profile, oxaliplatin was applied to rat cochlear organ cultures. Consistent with it neurotoxic propensity, oxaliplatin selectively damaged nerve fibers at a very low dose 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initial-ly increased with dose, but unexpectedly decreased at very high doses. This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms. Previous studies have demon-strated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide (NAD+). To determine if NAD+would protect spiral ganglion axons and the hair cells from oxaliplatin damage, cochlear cultures were treated with oxaliplatin alone at doses of 10 μM or 50 μM respectively as controls or combined with 20 mM NAD+. Treatment with 10 μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20 mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apop-totic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20 mM NAD+treatment great-ly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+provides signifi-cant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.展开更多
Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP cou...Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP could distinctly increase the activities of purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) when they were added into medium from 0 to 8 h. In the process of enzymatic synthesis of adenine arabinoside from adenine and uracil arabinoside with wet cells of Enterobacter aerogenes DGO-04 induced by cytidine or CMP, the reaction time could be shortened from 36 to 6 h. After enzymatic reaction the activity of NPase in the cells induced remained higher than that in the cells uninduced.展开更多
AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a hypobadc chamber simulating 5000 m high altitude for 23 h every day ...AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a hypobadc chamber simulating 5000 m high altitude for 23 h every day for 0 (H0), 1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS: Compared with H0 group, intra-mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group reached the lowest point (70.6%) (P〈 0.01) when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in H0 group, In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups. Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly lower than that in H0 group, whereas HI group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P〈0.01) when compared to H0 group. ANT activity in H30 group was higher than in H15 group, but still lower than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0 group decreased significantly, which in H5 group was the lowest, being 27.1% of that in H0 group (P〈0.01). ANT protein level in H30 group was higher than in H15 group, but still lower than in H0 group. CONCLUSION: Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure. The lower level of extra-mitochondrial ATP may be related to the decrease of ANT activity during hypoxia exposure.展开更多
Among all the DNA components, extremely redox-active guanine (G) and adenine (A) bases are subject to facile loss of an electron and form cation radicals (G+" and A+') when exposed to irradiation or radical ...Among all the DNA components, extremely redox-active guanine (G) and adenine (A) bases are subject to facile loss of an electron and form cation radicals (G+" and A+') when exposed to irradiation or radical oxidants. The subsequent deprotonation of G+' and A+' can invoke DNA damage or interrupt hole transfer in DNA. However, compared with intensive reports for G+, studies on the deprotonation of A+ are still limited at present. Herein, we investigate the deprotonation behavior of A+. by time-resolved laser flash photolysis. The deprotonation product of A(N6-H)' is observed and the deprotonation rate constant, (2.0±0.1)×10 7 s-1, is obtained at room temperature. Further, the deprotonation rate con- stants of A+. are measured at temperatures varying from 280 K to 300 K, from which the activation energy for the N6-H deprotonation is determined to be (17.1±1.0) kJ/mol by Arrhenius equation. In addition, by incorporating the aqueous solvent effect, we perform density functional theory calculations for A+ deprotonation in free base and in duplex DNA. Together with experimental results, the deprotonation mechanisms of A+ in free base and in duplex DNA are revealed, which are of fundamental importance for understanding the oxidative DNA damage and designing DNA-based electrochemical devices.展开更多
Two new CdⅡ-based coordination polymers(CPs) with mixed adenine(Hade) nucleobase and 5-nitroisophathalate(nip) ligands, {[Cd(Hade)_(0.5)(H_2O)_2(nip)]·H_2O}n 1 and {[Cd(Hade)(H_2O)_(1.25)(CH_3OH)0.75(nip)]·...Two new CdⅡ-based coordination polymers(CPs) with mixed adenine(Hade) nucleobase and 5-nitroisophathalate(nip) ligands, {[Cd(Hade)_(0.5)(H_2O)_2(nip)]·H_2O}n 1 and {[Cd(Hade)(H_2O)_(1.25)(CH_3OH)0.75(nip)]·0.75 CH_3OH·0.5H_2 O}_n 2, were successfully obtained by varying the preparation methods and structurally characterized. Crystal data for 1: monoclinic, C2/c space group with a = 10.5546(6), b = 17.3496(6), c = 16.1198(9) ?, β = 104.2800(10)o, V = 2860.6(2) ?3, Dc = 2.058 g/cm^3, Mr = 443.13, Z = 8, F(000) = 1752, μ = 1.585 mm^(–1), the final R = 0.0394 and wR = 0.1109 for 2285 observed reflections with I > 2σ(I). For 2: triclinic, P1 space group with a = 10.2032(7), b = 10.5098(8), c = 11.0223(8) ?, a = 65.7050(10)o, β = 74.5750(10)o, g = 61.5280(10)o, V = 943.38(12) ?~3, Dc = 1.888 g/cm3, Mr = 536.24, Z = 2, F(000) = 537, μ = 1.225 mm^(–1), the final R = 0.0225 and wR = 0.0702 for 3143 observed reflections with I > 2σ(I). 1 presents a crisscrossed layer with mutually orthogonal {Cd(nip)} chains aggregated by neutral m-N(7),N(9)-Hade connector. By contrast, 2 displays a linear chain with CdⅡ ions extended by bis-bidentate chelating-nip2–connectors, which are further assembled into a broad ribbon by N-H···N hydrogen-bonding interactions. Additionally, the two solid-state samples with comparable thermal stability exhibit favorable luminescent emissions at room temperature, suggesting their potential applications as fluorescence materials.展开更多
The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37℃ for ...The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37℃ for 24h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growtfi. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The re- suits after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100mgkg-1 d-1.展开更多
Eukaryotic DNA methylation has been receiving increasing attention for its crucial epigenetic regulatory function.The recently developed single-molecule real-time(SMRT)sequencing technology provides an efficient way t...Eukaryotic DNA methylation has been receiving increasing attention for its crucial epigenetic regulatory function.The recently developed single-molecule real-time(SMRT)sequencing technology provides an efficient way to detect DNA N6-methyladenine(6mA)and N4-methylcytosine(4mC)modifications at a single-nucleotide resolution.The family Rosaceae contains horticultural plants with a wide range of economic importance.However,little is currently known regarding the genome-wide distribution patterns and functions of 6mA and 4mC modifications in the Rosaceae.In this study,we present an integrated DNA 6mA and 4mC modification database for the Rosaceae(MDR,http://mdr.xieslab.org).MDR,the first repository for displaying and storing DNA 6mA and 4mC methylomes from SMRT sequencing data sets for Rosaceae,includes meta and statistical information,methylation densities,Gene Ontology enrichment analyses,and genome search and browse for methylated sites in NCBI.MDR provides important information regarding DNA 6mA and 4mC methylation and may help users better understand epigenetic modifications in the family Rosaceae.展开更多
Electron transfer (ET) reactions between 1,8-dihydroxyanthraquinone (DHAQ) and two DNA bases, adenine (A) and cytosine (C), have been investigated in CH3CN/H20 solution with nanosecond time-resolved laser flas...Electron transfer (ET) reactions between 1,8-dihydroxyanthraquinone (DHAQ) and two DNA bases, adenine (A) and cytosine (C), have been investigated in CH3CN/H20 solution with nanosecond time-resolved laser flash photolysis. After irradiation at 355 nm, the triplet DHAQ is produced via intersystem crossing and reacts with two nucleobases. ET processes for both reactions have been definitely identified, in which two bases play a significant role of electron donor. Based on the measured decay dynamics of various intermediates and the corresponding quenching rates, an initial ET process followed by a secondary proton-transfer reaction is suggested for both the overall reactions. By plotting the observed quenching rate against the concentration of two DNA bases, the bimolecular quenching rate constants are determined as 9.0-10s L/(mol.s) for the 3DHAQ*+C reaction and 3.3x10^8 L/(mol.s) for the 3DHAQ*+A reaction, respectively.展开更多
The authors made rat model of chronic renal failure by feeding the animals with foodcontaining 0.5 % adenine and treated with Niaoduqing(NDQ),a Chinese patent medicine,whichcomposed of Rhizoma Rhei,Radix Glycyrrhizae,...The authors made rat model of chronic renal failure by feeding the animals with foodcontaining 0.5 % adenine and treated with Niaoduqing(NDQ),a Chinese patent medicine,whichcomposed of Rhizoma Rhei,Radix Glycyrrhizae,Radix Paeoniae Alba,etc.The rats were divid-ed into four groups:model control,normal control;and two NDQ-treated groups with high andlow doses separately.The blood tests including urea nitrogen(BUN),serum creatinine(Scr),red blood cell(RBC),hemoglobin (Hb) hematocrit (HCT),sodium (Na),potassium (K),cal-cium(Ca)and phosphate(P)levels were performed atthe fourth week and the eighth week,thetime of sacrifice.The results showed that in the NDQ-treated groups the mean levels of BUN andScr were lower and the mean values of RBC,Hb and HCT,higher than those in the untreatedcontrol group.In the NDQ-treated groups,hyperphosphatemia and hypocalcemia of rats im-proved,the deposited crystals of adenine metabolite and the proliferation of fibroid tissue in kid-ney decreased.These findings indicate that NDQ can ameliorate the symptoms of chronic renalfailure and delay the progress of this disease.展开更多
A novel adenine(Ade) salt of 12-phosphotungstic acid was synthesized and characterized by elemental analyses,IR, 1H NMR,CV and single crystal X-ray diffraction. The compound crystallized in a triclinic system with...A novel adenine(Ade) salt of 12-phosphotungstic acid was synthesized and characterized by elemental analyses,IR, 1H NMR,CV and single crystal X-ray diffraction. The compound crystallized in a triclinic system with a space group P 1 and a =1.3108(3) nm, b =1.3515(3) nm,c =1.3870(3) nm, V =2.0217(7) nm 3,Z =1,R _1=0.0391,wR _2=0.0959. The structure unit of the complex was constructed from [HPW_ 12 ·O_ 40 ] -,(C_5H_6N_5) + and C_3H_7NO,which further extends to form a novel three-dimensional host-guest network via hydrogen-bonding interactions. The anti-tumor activity of the compound was examined in two human tumor cell lines in vitro .展开更多
The radiation damage of adenine base was studied by B3LYP and MP2 methods in the presence of hydroxyl radicals to probe the reactivities of five possible sites of an isolated adenine molecule. Both methods predict tha...The radiation damage of adenine base was studied by B3LYP and MP2 methods in the presence of hydroxyl radicals to probe the reactivities of five possible sites of an isolated adenine molecule. Both methods predict that the C8 site is the more vulnerable than the other sites. For its bonding covalently with the hydroxyl radicals, B3LYP predicts a barrierless pathway, while MP2 finds a transition state with an energy of 106.1 kJ/mol. For the hydroxylation at the C2 site, the barrier was calculated to be 165.3 kJ/mol using MP2 method. For the dehydrogenation reactions at five sites of adenine, B3LYP method predicts that the free energy barrier decreases in the order of H8 〉 H2 〉 HN62 〉 HN61 〉 HN9.展开更多
BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferati...BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferating potential in kidney injury in mice.METHODS Human umbilical cord blood(UCB)-derived CD34+cells were incubated for one week in vasculogenic conditioning medium.Vasculogenic culture significantly increased the number of CD34+cells and their ability to form endothelial progenitor cell colony-forming units.Adenineinduced tubulointerstitial injury of the kidney was induced in immunodeficient non-obese diabetic/severe combined immunodeficiency mice,and cultured human UCB-CD34+cells were administered at a dose of 1×106/mouse on days 7,14,and 21 after the start of adenine diet.RESULTS Repetitive administration of cultured UCB-CD34+cells significantly improved the time-course of kidney dysfunction in the cell therapy group compared with that in the control group.Both interstitial fibrosis and tubular damage were significantly reduced in the cell therapy group compared with those in the control group(P<0.01).Microvasculature integrity was significantly preserved(P<0.01)and macrophage infiltration into kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group(P<0.001).CONCLUSION Early intervention using human cultured CD34+cells significantly improved the progression of tubulointerstitial kidney injury.Repetitive administration of cultured human UCB-CD34+cells significantly improved tubulointerstitial damage in adenine-induced kidney injury in mice via vasculoprotective and anti-inflammatory effects.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81871024 (to HN),82301957 (to XW),82001382 (to LL),62127810 (to HN)the Natural Science Foundation of Jiangsu Province of China,No.SBK2020040785 (to LL)。
文摘Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.
基金Supported by Youth Independent Innovation Science Fund Project from Chinese PLA General Hospital,No.22QNFC075.
文摘Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their grasp.Within this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC.Excessive accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage polarization.Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic instability.Therefore,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases.In this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.
文摘Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Nicotinamide mononucleotide (NMN), an antiaging supplement, is the precursor of coenzyme nicotinamide adenine dinucleotide (NAD) that plays an important role in intracellular redox reactions. Objective: The study compared the serum concentrations of NAD in normal healthy participants, supplemented with NMN 500 mg and NMN 500 mg + 5 mg BioPerine® (95% piperine). Methods: In a randomized, open-label, crossover study, NMN (500 mg) was compared to NMN + BioPerine® (500 mg + 5 mg) in 6 healthy adults, aged 18 - 45 years. The participants received a single oral dose of NMN or NMN + BioPerine® capsules with 240 mL water, and blood samples were collected over 8hr. After a 4-day washout period, the same procedures were repeated as per the crossover design. Total NAD (NADtotal), including oxidized NAD (the oxidized) and its reduced form NADH, was measured in human serum samples. Results: The maximum concentration (Cmax) of NAD in serum was higher with NMN + BioPerine® (282 pmol/mL) compared to NMN (246 pmol/mL) alone. In the presence of BioPerine®, the NAD concentrations reached 257 pmol/mL during the first 2 hr, whereas a comparable serum concentration (246 pmol/mL) was attained only after 6 hr in NMN alone. The AUC0-8hr was 1738 pmol/mL/hr in NMN compared to 2004 pmol/mL/hr in NMN+ BioPerine®. The time to reach peak concentration (t1/2) was similar (6hr) in both groups. No clinically relevant adverse events (AE) were observed, and safety parameters remained within normal ranges in all the participants with both formulations. Conclusion: These results reveal that BioPerine® can effectively increase the NAD concentrations in the serum following NMN supplementation in healthy volunteers. The present study was registered prospectively with the Clinical Trials Registry-India (CTRI/2023/11/059982).
文摘Adenine phosphoribosyltransferase(APRT)deficiency is a rare autosomal recessive disease leading to generation of large amounts of 2,8-dihydroxyadenine(DHA).DHA is excreted in urine,where it precipitates into crystals due to its low solubility.DHA crystals can aggregate into stones or cause injury to the renal parenchyma(DHA nephropathy).Recurrent urolithiasis and DHA nephropathy are the two clinical manifestations of APRT deficiency.Diagnosis of APRT deficiency can be made during childhood as well as adulthood.Diagnosis mainly relies on the recognition of DHA in stones or urine crystals.Measurement of APRT activity and genetic testing are useful for confirmation of diagnosis,for family screening and should be considered in difficult cases of urolithiasis or crystalline nephropathy.Allopurinol therapy is the cornerstone of treatment and is highly effective in preventing recurrence of stones and kidney disease.High fluid intake and dietary modifications are also recommended.Early diagnosis and treatment are of paramount importance to prevent renal damage.Unfortunately,diagnosis of APRT deficiency is often overlooked and irreversible renal failure still occurs in a substantial proportion of patients.Clinicians must be alert to the possibility of APRT deficiency and consider the appropriate diagnostic tests in certain cases.This review discusses the genetic and biochemical mechanisms of APRT deficiency,and the issues of diagnosis and management.
文摘Aim ,To study the mechanism relative to therapeutic effects of matrine on adenine-induced renal interstitial fibrosis in rats. Methods Sixty male Wistar rats were selected and randomly divided into 3 groups: normal control group (NCG) consisted of 8 rats, adenine treated group (ATG) 28 rats, and matrine treated group (MTG) 24 rats. Each rat in ATG and MTG was gavaged with adenine (250 mg·kg^-1·d^-1 ) for 21 d. After gavage with adenine for one week, each rat in MTG was administered intraperitoneally matrine(20 mg·kg^-1·d^-1 ) in vehicle ( 1 mL of 0.9% sodium chloride) daily. On days 14, 21, and 28, the serum levels of urea nitrogen, creatinine, and IL-6 were determined and the rat kidneys of ATG, MTG and NCGwere examined pathologically. Radioimmunoassay for serum IL- 6 immunohistochemical staining for TGF-β1 expression in the kidney and semiquantitative analysis were performed. HE staining for semiquantitative analysis of tubulointerstitial injury. Results The serum levels of urea nitrogen and creatinine in MTG were lower as compare to ATG ( P 〈 0.05 ) whereas serum IL- 6 and renal TGF-β1 expression levels were significantly lower than those in ATG (P 〈0.05 ), but all these indexes were higher than those in NCG (P 〈 0.01 ). In MTG, the index of tubulointerstitial lesion was lower than that in ATG (P 〈 0.05 ). Conclusion Matrine inhibits the renal tubulointerstial fibrosis in the adenine-induced rat model by suppressing serum level of IL-6 and expression of TGF-β1 in the tubulointerstitium.
基金partially supported by Merit Review Award(I01RX-001964-01)from the US Department of Veterans Affairs Rehabilitation Research and Development Service(to YD)the National Natural Science Foundation of China(81501141)+1 种基金Beijing New Star of Science and Technology Program of China(xx2016061)Beijing Tongzhou District Financial Fund,and Scientific Research Common Program of Beijing Municipal Commission of Education,China(KM201610025028)(to XG)
文摘Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however,excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research,coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.
基金supported by the National Natural Science Foundation of China (Grant No. 31501239)the Genetically Modified Breeding Major Projects (Grant No. 2016ZX08010-002-008)
文摘Precise base editing is highly desired in plant functional genomic research and crop molecular breeding. In this study, we constructed a rice-codon optimized adenine base editor(ABE)-nC as9 tool that induced targeted A·T to G·C point mutation of a key single nucleotide polymorphism site in an important agricultural gene. Combined with the modified single-guide RNA variant, our plant ABE tool can efficiently achieve adenine base editing in the rice genome.
文摘Oxaliplatin, an anticancer drug commonly used to treat colorectal cancer and other tumors, has a number of serious side effects, most notably neuropathy and ototoxicity. To gain insights into its ototoxic profile, oxaliplatin was applied to rat cochlear organ cultures. Consistent with it neurotoxic propensity, oxaliplatin selectively damaged nerve fibers at a very low dose 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initial-ly increased with dose, but unexpectedly decreased at very high doses. This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms. Previous studies have demon-strated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide (NAD+). To determine if NAD+would protect spiral ganglion axons and the hair cells from oxaliplatin damage, cochlear cultures were treated with oxaliplatin alone at doses of 10 μM or 50 μM respectively as controls or combined with 20 mM NAD+. Treatment with 10 μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20 mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apop-totic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20 mM NAD+treatment great-ly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+provides signifi-cant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.
基金Project (No. 07C26213101283) supported by the Innovation Fundfor Technology Based Firms from the Ministry of Science andTechnology of China
文摘Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP could distinctly increase the activities of purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) when they were added into medium from 0 to 8 h. In the process of enzymatic synthesis of adenine arabinoside from adenine and uracil arabinoside with wet cells of Enterobacter aerogenes DGO-04 induced by cytidine or CMP, the reaction time could be shortened from 36 to 6 h. After enzymatic reaction the activity of NPase in the cells induced remained higher than that in the cells uninduced.
基金Supported by the Natural Science Foundation of China, No.30270509
文摘AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a hypobadc chamber simulating 5000 m high altitude for 23 h every day for 0 (H0), 1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS: Compared with H0 group, intra-mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group reached the lowest point (70.6%) (P〈 0.01) when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in H0 group, In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups. Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly lower than that in H0 group, whereas HI group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P〈0.01) when compared to H0 group. ANT activity in H30 group was higher than in H15 group, but still lower than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0 group decreased significantly, which in H5 group was the lowest, being 27.1% of that in H0 group (P〈0.01). ANT protein level in H30 group was higher than in H15 group, but still lower than in H0 group. CONCLUSION: Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure. The lower level of extra-mitochondrial ATP may be related to the decrease of ANT activity during hypoxia exposure.
文摘Among all the DNA components, extremely redox-active guanine (G) and adenine (A) bases are subject to facile loss of an electron and form cation radicals (G+" and A+') when exposed to irradiation or radical oxidants. The subsequent deprotonation of G+' and A+' can invoke DNA damage or interrupt hole transfer in DNA. However, compared with intensive reports for G+, studies on the deprotonation of A+ are still limited at present. Herein, we investigate the deprotonation behavior of A+. by time-resolved laser flash photolysis. The deprotonation product of A(N6-H)' is observed and the deprotonation rate constant, (2.0±0.1)×10 7 s-1, is obtained at room temperature. Further, the deprotonation rate con- stants of A+. are measured at temperatures varying from 280 K to 300 K, from which the activation energy for the N6-H deprotonation is determined to be (17.1±1.0) kJ/mol by Arrhenius equation. In addition, by incorporating the aqueous solvent effect, we perform density functional theory calculations for A+ deprotonation in free base and in duplex DNA. Together with experimental results, the deprotonation mechanisms of A+ in free base and in duplex DNA are revealed, which are of fundamental importance for understanding the oxidative DNA damage and designing DNA-based electrochemical devices.
基金supported by the National Natural Science Foundation of China(Nos.21571140 and 21671149)the Program for Innovative Research Team in University of Tianjin(TD13-5074)
文摘Two new CdⅡ-based coordination polymers(CPs) with mixed adenine(Hade) nucleobase and 5-nitroisophathalate(nip) ligands, {[Cd(Hade)_(0.5)(H_2O)_2(nip)]·H_2O}n 1 and {[Cd(Hade)(H_2O)_(1.25)(CH_3OH)0.75(nip)]·0.75 CH_3OH·0.5H_2 O}_n 2, were successfully obtained by varying the preparation methods and structurally characterized. Crystal data for 1: monoclinic, C2/c space group with a = 10.5546(6), b = 17.3496(6), c = 16.1198(9) ?, β = 104.2800(10)o, V = 2860.6(2) ?3, Dc = 2.058 g/cm^3, Mr = 443.13, Z = 8, F(000) = 1752, μ = 1.585 mm^(–1), the final R = 0.0394 and wR = 0.1109 for 2285 observed reflections with I > 2σ(I). For 2: triclinic, P1 space group with a = 10.2032(7), b = 10.5098(8), c = 11.0223(8) ?, a = 65.7050(10)o, β = 74.5750(10)o, g = 61.5280(10)o, V = 943.38(12) ?~3, Dc = 1.888 g/cm3, Mr = 536.24, Z = 2, F(000) = 537, μ = 1.225 mm^(–1), the final R = 0.0225 and wR = 0.0702 for 3143 observed reflections with I > 2σ(I). 1 presents a crisscrossed layer with mutually orthogonal {Cd(nip)} chains aggregated by neutral m-N(7),N(9)-Hade connector. By contrast, 2 displays a linear chain with CdⅡ ions extended by bis-bidentate chelating-nip2–connectors, which are further assembled into a broad ribbon by N-H···N hydrogen-bonding interactions. Additionally, the two solid-state samples with comparable thermal stability exhibit favorable luminescent emissions at room temperature, suggesting their potential applications as fluorescence materials.
文摘The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37℃ for 24h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growtfi. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The re- suits after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100mgkg-1 d-1.
基金supported by grants from the National Natural Science Foundation of China(grant numbers 31760316,31600667,and 31871326)Priming Scientific Research Foundation of Hainan University(grant number KYQD(ZR)1721)Science Foundation for The Youth Teachers of Hainan University in 2017(grant number hdkyxj201702).
文摘Eukaryotic DNA methylation has been receiving increasing attention for its crucial epigenetic regulatory function.The recently developed single-molecule real-time(SMRT)sequencing technology provides an efficient way to detect DNA N6-methyladenine(6mA)and N4-methylcytosine(4mC)modifications at a single-nucleotide resolution.The family Rosaceae contains horticultural plants with a wide range of economic importance.However,little is currently known regarding the genome-wide distribution patterns and functions of 6mA and 4mC modifications in the Rosaceae.In this study,we present an integrated DNA 6mA and 4mC modification database for the Rosaceae(MDR,http://mdr.xieslab.org).MDR,the first repository for displaying and storing DNA 6mA and 4mC methylomes from SMRT sequencing data sets for Rosaceae,includes meta and statistical information,methylation densities,Gene Ontology enrichment analyses,and genome search and browse for methylated sites in NCBI.MDR provides important information regarding DNA 6mA and 4mC methylation and may help users better understand epigenetic modifications in the family Rosaceae.
文摘Electron transfer (ET) reactions between 1,8-dihydroxyanthraquinone (DHAQ) and two DNA bases, adenine (A) and cytosine (C), have been investigated in CH3CN/H20 solution with nanosecond time-resolved laser flash photolysis. After irradiation at 355 nm, the triplet DHAQ is produced via intersystem crossing and reacts with two nucleobases. ET processes for both reactions have been definitely identified, in which two bases play a significant role of electron donor. Based on the measured decay dynamics of various intermediates and the corresponding quenching rates, an initial ET process followed by a secondary proton-transfer reaction is suggested for both the overall reactions. By plotting the observed quenching rate against the concentration of two DNA bases, the bimolecular quenching rate constants are determined as 9.0-10s L/(mol.s) for the 3DHAQ*+C reaction and 3.3x10^8 L/(mol.s) for the 3DHAQ*+A reaction, respectively.
文摘The authors made rat model of chronic renal failure by feeding the animals with foodcontaining 0.5 % adenine and treated with Niaoduqing(NDQ),a Chinese patent medicine,whichcomposed of Rhizoma Rhei,Radix Glycyrrhizae,Radix Paeoniae Alba,etc.The rats were divid-ed into four groups:model control,normal control;and two NDQ-treated groups with high andlow doses separately.The blood tests including urea nitrogen(BUN),serum creatinine(Scr),red blood cell(RBC),hemoglobin (Hb) hematocrit (HCT),sodium (Na),potassium (K),cal-cium(Ca)and phosphate(P)levels were performed atthe fourth week and the eighth week,thetime of sacrifice.The results showed that in the NDQ-treated groups the mean levels of BUN andScr were lower and the mean values of RBC,Hb and HCT,higher than those in the untreatedcontrol group.In the NDQ-treated groups,hyperphosphatemia and hypocalcemia of rats im-proved,the deposited crystals of adenine metabolite and the proliferation of fibroid tissue in kid-ney decreased.These findings indicate that NDQ can ameliorate the symptoms of chronic renalfailure and delay the progress of this disease.
文摘A novel adenine(Ade) salt of 12-phosphotungstic acid was synthesized and characterized by elemental analyses,IR, 1H NMR,CV and single crystal X-ray diffraction. The compound crystallized in a triclinic system with a space group P 1 and a =1.3108(3) nm, b =1.3515(3) nm,c =1.3870(3) nm, V =2.0217(7) nm 3,Z =1,R _1=0.0391,wR _2=0.0959. The structure unit of the complex was constructed from [HPW_ 12 ·O_ 40 ] -,(C_5H_6N_5) + and C_3H_7NO,which further extends to form a novel three-dimensional host-guest network via hydrogen-bonding interactions. The anti-tumor activity of the compound was examined in two human tumor cell lines in vitro .
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11564015 and 61404062)the Research Fund for the Doctoral Program of China(Grant No.3000990110)the Fund for Distinguished Young Scholars of Jiangxi Science&Technology Normal University(Grant Nos.2015QNBJRC002 and 2016QNBJRC006)
文摘The radiation damage of adenine base was studied by B3LYP and MP2 methods in the presence of hydroxyl radicals to probe the reactivities of five possible sites of an isolated adenine molecule. Both methods predict that the C8 site is the more vulnerable than the other sites. For its bonding covalently with the hydroxyl radicals, B3LYP predicts a barrierless pathway, while MP2 finds a transition state with an energy of 106.1 kJ/mol. For the hydroxylation at the C2 site, the barrier was calculated to be 165.3 kJ/mol using MP2 method. For the dehydrogenation reactions at five sites of adenine, B3LYP method predicts that the free energy barrier decreases in the order of H8 〉 H2 〉 HN62 〉 HN61 〉 HN9.
文摘BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferating potential in kidney injury in mice.METHODS Human umbilical cord blood(UCB)-derived CD34+cells were incubated for one week in vasculogenic conditioning medium.Vasculogenic culture significantly increased the number of CD34+cells and their ability to form endothelial progenitor cell colony-forming units.Adenineinduced tubulointerstitial injury of the kidney was induced in immunodeficient non-obese diabetic/severe combined immunodeficiency mice,and cultured human UCB-CD34+cells were administered at a dose of 1×106/mouse on days 7,14,and 21 after the start of adenine diet.RESULTS Repetitive administration of cultured UCB-CD34+cells significantly improved the time-course of kidney dysfunction in the cell therapy group compared with that in the control group.Both interstitial fibrosis and tubular damage were significantly reduced in the cell therapy group compared with those in the control group(P<0.01).Microvasculature integrity was significantly preserved(P<0.01)and macrophage infiltration into kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group(P<0.001).CONCLUSION Early intervention using human cultured CD34+cells significantly improved the progression of tubulointerstitial kidney injury.Repetitive administration of cultured human UCB-CD34+cells significantly improved tubulointerstitial damage in adenine-induced kidney injury in mice via vasculoprotective and anti-inflammatory effects.