A STUDY ON DNA ADDUCTION WITH NICOTINE－DERIVED NITROSAMINE BY ACCELERATOR MASS SPECTROMETRY

DNA adduction with nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3- pyridy1)-1 -butanone (NNK) in mice at doses equivalent to human exposure has been studied using 14C-label by accelerator mass spectrometry(AMS). A detection limit of DNA adducts of 1 adduct Per 1010 nucleotides has been achieved. This sensitivity of AMS measurement is 3 or more orders of magnitude improved than that of radioimmunoassay.Formation of DNA adducts is linearly dependent on dose down to an exposure of 100 ng Per kg of body weight .The ultimate cheeical form of carcinogen NNK binding to DNA is speculated.

纳升电喷雾串联质谱(Q-TOF)测序中Na^+加合肽的分析

电喷雾串联质谱测序法是蛋白质组研究中蛋白质鉴定的最有力的手段之一.肽段离子在ESI-Q-TOF中往往以多电荷形式出现(2～4个电荷),其中m/z在500～1000之间带双电荷的离子最适合测序.……

Knee biomechanics of patients with total knee replacement during downhill walking on different slopes

Purpose:The purpose of this study was to compare knee biomechanics of the replaced limb to the non-replaced limb of total knee replacement(TKR)patients and healthy controls during walking on level ground and on decline surfaces of 5°,10°,and 15°.Methods:Twenty-five TKR patients and 10 healthy controls performed 5 walking trials on different decline slopes on a force platform and an instrumented ramp system.Two analyses of variance,2×2(limb×group)and 2×4(limb×decline slope),were used to examine selected biomechanics variables.Results:The replaced limb of TKR patients had lower peak loading-response and push-off knee extension moment than the non-replaced and the matched limb of healthy controls.No differences were found in loading-response and push-off knee internal abduction moments among replaced,non-replaced,and matched limb of healthy controls.The knee flexion range of motion,peak loading-response vertical ground reaction force,and peak knee extension moment increased across all slope comparisons between 0°and 15°in both the replaced and non-replaced limb of TKR patients.Conclusion:Downhill walking may not be appropriate to include in early stage rehabilitation exercise protocols for TKR patients.

Preparation of Conjugated Linoleic Acid of High Purity and Its Apparent Kinetic Characteristics During Formation

Conjugated linoleic acid (CLA) is a fatty acid with physiological activities and potential application prospect. This paper focuses on the method of synthesis of conjugated linoleic acid of high purity and the process line and conditions for its purification that can be used in large scale production. CLA of more than 95% purity was prepared by means of urea adduct purification and conjugation using safflower oil as material. The total recovery of the product adds up to more than 48%. The reactive kinetics about linoleic acid from sunflower oil converted into CLA was investigated, and its apparent kinetic model was also established, which can be used as a base for industrial designs.

Increased Q-Factor increases frontal-plane knee joint loading in stationary cycling

Background: Q-Factor(QF), or the inter-pedal width, in cycling is similar to step-width in gait. Although increased step-width has been shown to reduce peak knee abduction moment(KAbM), no studies have examined the biomechanical effects of increased QF in cycling at different workrates in healthy participants.Methods: A total of 16 healthy participants(8 males, 8 females, age: 22.4 ± 2.6 years, body mass index: 22.78 ± 1.43 kg/m^2, mean ± SD) participated.A motion capture system and customized instrumented pedals were used to collect 3-dimensional kinematic(240 Hz) and pedal reaction force(PRF)(1200 Hz) data in 12 testing conditions: 4 QF conditions—Q1(15.0 cm), Q2(19.2 cm), Q3(23.4 cm), and Q4(27.6 cm)—under 3 workrate conditions—80 watts(W), 120 W, and 160 W. A 3 × 4(QF × workrate) repeated measures of analysis of variance were performed to analyze differences among conditions(p < 0.05).Results: Increased QF increased peak KAbM by 47%, 56%, and 56% from Q1 to Q4 at each respective workrate. Mediolateral PRF increased from Q1 to Q4 at each respective workrate. Frontal-plane knee angle and range of motion decreased with increased QF. No changes were observed for peak vertical PRF, knee extension moment, sagittal plane peak knee joint angles, or range of motion.Conclusion: Increased QF increased peak KAbM, suggesting increased medial compartment loading of the knee. QF modulation may influence frontal-plane joint loading when using stationary cycling for exercise or rehabilitation purposes.

Studies on Ion-molecule Reaction of Disubstituted Benzene with Ion System of Acetyl Chloride in Gas Phase

The ion-molecule reactions of disubstituted benzenes with the ion system of acetyl chloride under the chemical ionization condition were examined and the fragmentation reactions of the adduct ions formed by the ion-molecule reactions were studied by using collision-induced dissociation technique. It was found that the electron-releasing groups favored the adduct reactions and the electron-withdrawing groups did not. The position and properties of substituting groups had an effect on the relative abundance of the adduct ions. The fragmentation reaction of the adduct ions formed by ortho-benzene diamine with the acetyl ion was similar to the reductive alkylation reaction of amine in condensed phase.

Rare pattern of Maisonneuve fracture:A case report

BACKGROUND Maisonneuve fracture is a special type of ankle fracture that consists of proximal fibular fracture,a lesion of the inferior tibiofibular syndesmotic complex(interosseous ligament,anterior inferior tibiofibular ligament and posterior inferior tibiofibular ligament),and injury of the medial structure of the ankle(deltoid ligament tear or medial malleolar fracture).The accepted mechanism of Maisonneuve fracture is pronation external rotation according to the Lauge-Hansen classification.In this paper,we report a rare pattern of Maisonneuve fracture,which has the characteristics of both pronation external rotation ankle fracture and supination adduction ankle fracture.CASE SUMMARY A 31-year-old female patient accidentally sprained her right ankle while walking 5 d before hospitalization in our hospital.The patient was initially missed in other hospitals and later rediagnosed in our outpatient department.Full-length radiographs of the lower leg revealed proximal fibula fracture,inferior tibiofibular joint separation,and medial malleolar fracture involving the posterior malleolus,which was also revealed on computed tomography scans.Magnetic resonance imaging revealed rupture of the anterior inferior tibiofibular ligament and anterior talofibular ligament.We diagnosed a rare pattern of Maisonneuve fracture with proximal fibular fracture,inferior tibiofibular joint separation,medial malleolar fracture and ruptures of the anterior inferior tibiofibular ligament and anterior talofibular ligament.The patient underwent open reduction and internal fixation in our hospital.A 6-mo postoperative follow-up confirmed a good clinical outcome.CONCLUSION To our knowledge,this rare pattern of Maisonneuve fracture has not been previously described.The possible mechanism of injury is supination adduction combined with pronation external rotation.Careful analysis of the injury mechanism of Maisonneuve fracture is of great clinical significance and can better guide clinical treatment.

Congenital Club Foot in Children Younger than 24 Months: Decancelous Cuboid Combined with Selective Soft Tissue Release

Purpose: To evaluate 2 surgical prosedures in treatment of congenital clubfeet in children younger than 24 months. Materials and methods: Data were analyzed on 319 patients (448 feet) from July 1990 to December 2005. Clinical and classification for all patients according to Diméglio. Operated patients were devided into two group: Group1, selective soft tissue release;and Group 2, selective soft tissue release combined with cuboid decancelation. Surgical result were classified according to McKay’s system. Results: There were 103 females (32.3%) and 216 males (67.7%) in this study. There were 192 patients (268 feet) in group 1, 127 patients (180 feet) in group 2. Bilateral involvement was found in 129 patients (40.4%), only the left foot affected in 65 patients (20.4%), and only the right in 125 patients (39.2%). According to the classification of Diméglio Grade II was seen in 32.4%, Grade III in 53,1%, and Grade IV in 14.5%. Postoperatively, in group 1, we got excellent result in 29.1%, good result in 49.2%, fair result in 18.3%, and poor result in 3.4%. In group 2, we attained excellent result in 50.6%, good result in 42.2%, fair result in 6.1% and poor result in 1.1%. The good to excellent result in group 2 was significantly higher in group 1 with p = 0.000042. There was no failure in both groups. Residual adduction of forefoot in frontal plane was seen in 78.0% of group 1, and 10.6% of group 2, which was also statistically significant with p ~ 0. Conclusion: Generally speaking, the procedure of selective soft tissue releases combined with cuboid decancelation showed an outstanding result with good to excellent result of 92.8%. Surgical procedure is simple, safe, and applicable for all patients with clubfeet’s deformyties.

Deep Myofascial Kinetic Lines in Horses, Comparative Dissection Studies Derived from Humans

Seven superficial myofascial kinetic lines have been described earlier in horses in a comparative dissection study to the human lines. The lines act as an anatomical basis for understanding locomotion, stabilization, and posture. Further dissections verified three profound equine lines comparable to those described in humans and a fourth line not described previously. Forty-four horses of different breed and gender were dissected, imaged and video recorded. The horses were euthanized due to reasons not related to this study. A Deep Ventral Line (DVL) very similar to that in the human was verified in these studies. The line spans from the insertion of the profound flexor tendon in the hindlimb to the base of the cranium and oral part of the cavities of the head. It includes the profound, hypaxial myofascial structures, the ventral coccygeal muscles, the psoas muscles, the diaphragm, the longus colli/capitis muscles and the ventral capital muscles. The inner lining of the pelvic, abdominal and thoracic cavities with all the organs, vessels and nerves are also included. The line is closely connected to the autonomic nervous system by the vagus nerve, the pelvic nerves, the sympathetic trunk and several of the prevertebral nerves and ganglia. The new line identified in this study, is a Deep Dorsal Line (DDL), which starts in the dorsal tail muscles. It comprises myofascial structures of the spinocostotransversal system from the tail to the head including the nuchal ligament. It connects to the dura mater and has a major role in controlling the motion and stabilization of the Columna vertebralis. Both the DDL and the DVL include the coccygeal myofascia and periosteum of the skull. Due to differences in biped and quadruped anatomy the Front Limb Adduction Line (FADL) and the Front Limb Abduction Line (FABL) differ from the human lines. The lines are identified as slings in the brachial and antebrachial regions. The FABL includes structures for abduction and internal rotation connecting to the Front Limb Retraction Line (FLRL), and the FADL structures of adduction and external rotation in close proximity to the Front Limb Protraction Line (FLPL). The front limb lines support the movement of the front limb around the “thoraco-scapula pivot joint” medially at the level of the upper third of the scapula. The DVL identified in this study is similar to the human DFL whereas the front limb lines differ somewhat from the deep human arm lines due to differences in bi- and quadruped anatomy and biomechanics. We have identified and described this new equine DDL. The lines altogether explain a profound body balance and confirm the three-dimensional equine fascial network, which is of great clinical and biomechanical importance.

Spectral Differences of the Molecule-ion Adducts of β-Cyclodextrin and Lithium Carbonate

A small shielding effect on the hydrogen atoms of chiral carbons of β-cyclodextrin （β-CD） was detected by 1H nuclear magnetic resonance, but a large environmental change of the chiral carbon atoms at high concentration ratios of lithium carbonate （Li2CO3） to β-CD was observed by polarimetry in aqueous solution. These findings urged us to investigate whether different formation conditions of the molecule-ion system between Li2CO3 and β-CD in solid state were involved in different spectral performances. To answer the question, we prepared three adducts of Li2CO3 to β-CD, i.e., samples 1, 2, and 3, by magnetic stirring, solvothermal and grinding conditions, respectively. Powder X-ray diffraction and Fourier transformation infrared spectroscopy provided the information of formation of the three molecule-ion adducts. Besides, scanning electron microscope images provided different surface information of the three adducts. Further, significant spectral differences in thermal behavior of these adducts were found by thermogravimetry and derivative thermogravimetry.

Pathogenesis of alcoholic liver disease:Role of oxidative metabolism

Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-&#x003b2;-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility.

Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis,treatment, and outcomes

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.

Immunological response in alcoholic liver disease

The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies, infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD.

Focusing on the recent progress of tea polyphenol chemistry and perspectives

Myriad evidence attests to the health-promoting benefits of tea drinking.While there are multiple factors of tea influencing the effective biological properties,tea polyphenols are the most significant and valuable components.The chemical characterization and physical characteristics of tea polyphenols have been comprehensively studied over the previous years.Still the emergence of new chemistry in tea,particularly the property of scavenging reactive carbonyl species(RCS)and the newly discovered flavoalkaloid compounds,has drawn increasing attention.In this review,we summarize recent findings of a new class of compounds in tea-flavonoid alkaloids(flavoalkaloids),which exist in fresh tea leaves and can be generated during the process of post-harvesting,and also postulate the formation mechanism of flavoalkaloids between catechins and theanine-derived Strecker aldehyde.Additionally,we detail the up-to-date research results of tea polyphenols regarding their ability to trap RCS and their in vivo aminated metabolites to suppress advanced glycation ends products(AGEs).We further raise questions to be addressed in the near future,including the synthetic pathways for the generation of flavoalkaloids and AGEs in fresh tea leaves before processing and the concentrations of tea polyphenols that affect their RCS scavenging capability due to their pro-oxidant nature.More intensive research is warranted to elucidate the mechanisms of action underlying the biological activity of flavoalkaloids and the pharmacological application of tea polyphenols in scavenging RCS and impeding detrimental AGEs.

Significant Positive Correlation of Plasma BPDE-Albumin Adducts to Urinary 1-Hydroxypyrene in Coke Oven Workers

Objective To investigate the application of BPDE-albumin adducts as monitoring biomarkers for coke oven workers exposed to polycyclic aromatic hydrocarbons （PAHs） and to explore possible relationship between BPDE-albumin adducts and urinary 1-hydroxypyrene （1-OHP） levels in them. Methods Thirty-seven coke oven workers from a coke plant and 47 controls without the occupational exposure to PAHs were recruited in this study. The levels of plasma BPDE-albumin adducts and urinary 1-OHP were analyzed using high performance liquid chromatography. Results The median levels of BPDE-albumin adducts （42.10 fmol/mg albumin） and urinary 1-OHP （5.46 μmol/mol creatinine） were significantly higher in coke oven workers than in controls （14.16 fmol/mg albumin, 2.96μmol/mol creatinine, respectively; P〈0.01）. Multiple logistic regression analysis showed that coke oven workers were at higher risk of having BPDE-albumin adduct levels above 25.30 μmol/mg albumin （OR=1.79, P〈0.01） and urinary 1-OHP levels above 4.13 μmol/mol creatinine （OR=2.45, P〈0.05）. There was a positive correlation between the levels of BPDE-albumin adducts and urinary 1-OHP in all subjects （rs=0.349, P〈0.01）. Conclusion BPDE-albumin adduct is a useful biomarker for monitoring long-term exposure to PAHs, and plasma BPDE-albumin adducts level is significantly correlated to urinary 1-OHP levels in coke oven workers.

Chem oprevention of 2-amino-1-methyl-6-phenyli-midazo[4,5-b]pyridine-induced carcinogen-DNA adducts by Chinese cabbage in rats

AIM The food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces colon and mammary gland tumors in rats and has been implicated in the etiology of human colorectal cancer. This study was conducted to examine the potentially preventive effect of Chinese cabbage (Brassica chinensis), a brassica vegetable most commonly consumed in China, against this carcinogen-induced DNA adduct formation in rats and its possible mechanisms.METHODS Sprague-Dawley rats were maintained for 10 days on basal diet or diet containing 20% (w/ w) freeze-dried cabbage powder prior to administration of a single dose of PhIP (10 mg/ kg) by oral gavage. Rats were sacrificed at 20 h after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung and liver were analyzed using 32P-postlabeling technique. Levels of hepatic cytochrome P450 (CYP) 1A1 and 1A2, as indicated by 7-ethoxyresorufin O-deethylase and 7-methlxyresorufin O-demethylase activity, and cytosolic glutathione S-transferases (GSTs) towards 1-chloro-2, 4-dinitrobenzene (CDNB) in the liver, lung and colon were measured.RESULTS Rats pre-treated with Chinese cabbage and given a single dose of PhIP had reduced levels of PhIP-DNA adducts in the colon, heart, lung and liver, with inhibition rates of 82.3%, 60.6%, 48.4% and 48.9%, respectively (P＜0.01). The enzyme assays revealed that Chinese cabbage induced both CYP1A1 and 1A2 activity, but the induction was preferential for CYP1A1 over 1A2 (81% vs 51%). GST activity towards CDNB in the liver and lung, but not colon, was also significantly increased by cabbage treatment.CONCLUSION The results indicate that Chinese cabbage has a preventive effect on PhIP-initiated carcinogenesis in rats and the mechanism is likely to involve the induction of detoxification enzymes.

Insights into platinum-induced peripheral neuropathy–current perspective

Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of platinum-based chemotherapy agents. This cluster of complications is often so debilitating that patients occasionally have to discontinue the therapy. Sensory neurons of dorsal root ganglia are at the core of chemotherapy-induced peripheral neuropathy symptoms. In these postmitotic cells, DNA damage caused by platinum chemotherapy interferes with normal functioning. Accumulation of DNA-platinum adducts correlates with neurotoxic severity and development of sensation of pain. While biochemistry of DNA-platinum adducts is the same in all cell types, molecular mechanisms affected by DNA-platinum adducts are different in cancer cells and non-dividing cells. This review aims to raise awareness about platinum associated chemotherapy-induced peripheral neuropathy as a medical problem that has remained unexplained for decades. We emphasize the complexity of this condition both from clinical and mechanistical point of view and focus on recent findings about chemotherapy-induced peripheral neuropathy in in vitro and in vivo model systems. Finally, we summarize current perspectives about clinical approaches for chemotherapy-induced peripheral neuropathy treatment.

Synthesis and Crystal Structure of New Supramolecular Adducts of[PtCl_6]^(2-) with Cucurbit [7] uril:[(H_3O)_2 [PtCl_6]_3 [C_(42)H_(42)N_(28)O_ (14)_2·H_2O

A novel supramolecular adduct 3(C 42H 42N 28O 14) 2·H 2O (1) was synthesized by mixing 2- and cucurbit uril in solution of hydrochloric acid. The crystal structure was determined by single crystal X-ray diffraction analysis. The crystal belongs to orthorhombic system and space group F dd2 with cell dimensions: a=4.705 33 (5) nm, b=7.153 80 (6) nm, c= 1.894 61 (2) nm, Z=16, V=63.7744 (11) nm3, D c= 1.534 g/cm3, μ=3.007 mm -1, F(000)=29 120, R 1= 0.070 7, wR 2=0.169 2. In crystal, the cucurb uril molecules form two zig-zag chains.

GSTM1 and XRCC3 Polymorphisms:Effects on Levels of Aflatoxin B1-DNA Adducts

Objective： Aflatoxin B1 （AFB1）, which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 （GSTM1） and DNA repair gene x-ray repair cross-complementing group 3 （XRCC3）, can affect the levels of AFB1-DNA adducts in Guangxi Population （n= 966） from an AFB1-exposure area. Methods： AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP. Results： The GSTM1-null genotype [adjusted odds ratio （OR） = 2.09; 95% confidence interval （CI） = 1.61-2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs （95% CI） were 1.43 （1.08-1.89） and 2.42 （1.13-5.22）, respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference （OR = 1）, individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels （adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM）. Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts. Conclusion： These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.

Critical role of mitochondrial aldehyde dehydrogenase 2 in acrolein sequestering in rat spinal cord injury

Lipid peroxidation-derived aldehydes,such as acrolein,the most reactive aldehyde,have emerged as key culprits in sustaining post-spinal cord injury(SCI)secondary pathologies leading to functional loss.Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2(ALDH2),a key oxidoreductase and powerful endogenous anti-aldehyde machinery,is likely important for protecting neurons from aldehydesmediated degeneration.Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator(Alda-1),we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2.Over an acute 2 day period post injury,we found that ALDH2 expression was significantly lowered post-SCI,but not so in rats given Alda-1.This lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction,which was revealed in co-immunoprecipitation experiments.We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord,and reduced cyst pathology.In addition,Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI.Finally,ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure.It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims.All animal work was approved by Purdue Animal Care and Use Committee(approval No.1111000095)on January 1,2021.