ABSTRACT
Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.
Subject(s)
Alkaloids , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Quality of Life , IntestinesABSTRACT
The brain receives sensory information about food, evaluates its desirability and value, and responds with approach or withdrawal. The evaluation process of food in the brain with obesity may involve a variety of neurocircuit abnormalities in the integration of internal and external information processing. There is a lack of consistency of the results extant reported for aberrant changes in the brain with obesity that prohibits key brain alterations to be identified. Moreover, most studies focus on the observation of neural plasticity of function or structure, and the evidence for functional and structural correlations in the neuronal plasticity process of obesity is still insufficient. The aims of this article are to explore the key neural structural regions and the hierarchical activity pattern of key structural nodes and evaluate the correlation between changes in functional modulation and eating behavior. Forty-two participants with obesity and 33 normal-weight volunteers were recruited. Gray matter volume (GMV) and Granger causality analysis (GCA) were performed using the DPARSF, CAT12, and DynamicBC toolbox. Compared with the normal weight group, the obesity group exhibited significantly increased GMV in the left parahippocampal gyrus (PG). The obesity group showed decreased causal inflow to the left PG from the left orbitofrontal cortex (OFC), right calcarine, and bilateral supplementary motor area (SMA). Decreased causal outflow to the left OFC, right precuneus, and right SMA from the left PG, as well as increased causal outflow to the left middle occipital gyrus (MOG) were observed in the obesity group. Negative correlations were found between DEBQ-External scores and causal outflow from the left PG to the left OFC, and DEBQ-Restraint scores and causal inflow from the left OFC to the left PG in the obesity group. Positive correlation was found between DEBQ-External scores and causal outflow from the left PG to the left MOG. These results show that the increased GMV in the PG may play an important role in obesity, which may be related to devalued reward system, altered behavioral inhibition, and the disengagement of attentional and visual function for external signals. These findings have important implications for understanding neural mechanisms in obesity and developing individual-tailored strategies for obesity prevention.
ABSTRACT
The rapid development of intelligent manufacturing provides strong support for the intelligent medical service ecosystem. Researchers are committed to building Wise Information Technology of 120 (WIT 120) for residents and medical personnel with the concept of simple smart medical care and through core technologies such as Internet of Things, Big Data Analytics, Artificial Intelligence, and microservice framework, to improve patient safety, medical quality, clinical efficiency, and operational benefits. Among them, how to use computers and deep learning technology to assist in the diagnosis of tongue images and realize intelligent tongue diagnosis has become a major trend. Tongue crack is an important feature of tongue states. Not only does change of tongue crack states reflect objectively and accurately changed circumstances of some typical diseases and TCM syndrome but also semantic segmentation of fissured tongue can combine the other features of tongue states to further improve tongue diagnosis systems' identification accuracy. Although computer tongue diagnosis technology has made great progress, there are few studies on the fissured tongue, and most of them focus on the analysis of tongue coating and body. In this paper, we do systematic and in-depth researches and propose an improved U-Net network for image semantic segmentation of fissured tongue. By introducing the Global Convolution Network module into the encoder part of U-Net, it solves the problem that the encoder part is relatively simple and cannot extract relatively abstract high-level semantic features. Finally, the method is verified by experiments. The improved U-Net network has a better segmentation effect and higher segmentation accuracy for fissured tongue image dataset. It can be used to design a computer-aided tongue diagnosis system.
Subject(s)
Artificial Intelligence , Ecosystem , Humans , Image Processing, Computer-Assisted , Neural Networks, Computer , Tongue/diagnostic imagingABSTRACT
The development of endoscopic treatment technology has further promoted the minimally invasive treatment of early gastric cancer (EGC). Endoscopic treatment has achieved better therapeutic effects in terms of safety and prognosis and is the preferred treatment method for patients who meet the indications for endoscopic treatment. However, the consequent problem is that some patients receiving endoscopic treatment may undergo non-curative resection, and the principle of follow-up management for non-curative resection patients deserves further attention. In addition, there are still debates on how to improve the accuracy of clinical staging, select a reasonable treatment method for patients who meet the expanded indications for endoscopic treatment, manage patients with positive endoscopic surgical margins, conduct research on function-preserving surgery, and manage the treatment of EGC under the current situation in China. Consequently, we aim to review current indications for endoscopic submucosal dissection of EGC in order to better inform treatment options.
ABSTRACT
Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Asteraceae/chemistry , Lactones/isolation & purification , Lactones/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Apoptosis/genetics , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Humans , Immunohistochemistry , Lactones/chemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Melanoma/pathology , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Molecular Structure , Oxidative Stress/drug effects , Plant Extracts/chemistry , Proto-Oncogene Proteins B-raf/genetics , Reactive Oxygen Species/metabolism , Sesquiterpenes/chemistry , Tumor Microenvironment/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing.
Subject(s)
Brain Mapping , Reward , Brain/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , ObesityABSTRACT
AIMS: It has been reported that allopregnanolone (APα) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6-hydroxydopamine (6-OHDA)-treated mice by binding to γ-aminobutyric acid A receptor (GABAAR) and then opening voltage-gated L-type Ca2+ channel, but the underlying mechanisms remain elusive. The aim of this study was to explore the possible involvement of GABAAR and calcium/calmodulin-dependent protein kinase II delta 3 (CaMKIIδ3) in this process. METHODS: 6-OHDA-treated mice and primary cultured midbrain cells were administrated with APα and GABAAR antagonist bicuculline (Bic), and the proliferation and differentiation of NPCs, the tyrosine hydroxylase (TH)-positive neurons and their fibers, the expression levels of CaMKIIδ3 and brain-derived neurotrophic factor (BDNF), and motor functions were measured using ELISA, immunohistochemical staining, real-time RT-PCR, Western blot, and behavioral test. RESULTS: Allopregnanolone significantly promoted the phosphorylation of cytoplasmic CaMKIIδ3 and its nuclear translocation by binding to GABAAR, which, in turn, increased the expression levels of BDNF. This may account for the findings that the exogenous APα enhanced the proliferation and differentiation of NPCs, and ameliorated the nigrostriatal system and behavioral performance in 6-OHDA-treated mice. CONCLUSIONS: Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCs via upregulating the expression levels of CaMKIIδ3, and finally contribute to the restoration of dopaminergic neurons in 6-OHDA-treated mice.
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OBJECTIVE: This study aimed to investigate regional neural activity and regulation of patterns in the reorganized neural network of obesity and explore the correlation between brain activities and eating behavior. METHODS: A total of 23 individuals with obesity and 23 controls with normal weight were enrolled. Functional magnetic resonance imaging (fMRI) data were acquired using 3.0-T MRI. Amplitude of low-frequency fluctuation and functional connectivity (FC) analyses were conducted using Data Processing Assistant for resting-state fMRI and Resting-State fMRI Data Analysis Toolkit (REST). RESULTS: The group with obesity showed increased amplitude of low-frequency values in left fusiform gyrus/amygdala, inferior temporal gyrus (ITG), hippocampus/parahippocampal gyrus, and bilateral caudate but decreased values in right superior temporal gyrus. The group with obesity showed increased FC between left caudate and right superior temporal gyrus, left fusiform gyrus/amygdala and left ITG, right caudate and left fusiform gyrus/amygdala, and right caudate and left hippocampus/parahippocampal gyrus. Dutch Eating Behavior Questionnaire-Emotional scores were positively correlated with FC between left hippocampus/parahippocampal gyrus and right caudate but negatively correlated with FC between left fusiform gyrus/amygdala and left ITG. CONCLUSIONS: The study indicated the reorganized neural network presented as a bilateral cross-regulation pattern across hemispheres between reward and various appetite-related functional processing, thus affecting emotional and external eating behavior. These results could provide further evidence for neuropsychological underpinnings of food intake and their neuromodulatory therapeutic potential in obesity.
Subject(s)
Appetite Regulation/physiology , Brain/diagnostic imaging , Feeding and Eating Disorders/diagnosis , Nerve Net/diagnostic imaging , Nerve Net/pathology , Obesity/psychology , Adolescent , Adult , Brain/pathology , Brain/physiopathology , Brain Mapping/methods , Case-Control Studies , Feeding Behavior/physiology , Feeding Behavior/psychology , Feeding and Eating Disorders/complications , Feeding and Eating Disorders/physiopathology , Feeding and Eating Disorders/psychology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Obesity/complications , Obesity/diagnosis , Obesity/physiopathology , Rest/physiology , Rest/psychology , Young AdultABSTRACT
Small heat shock proteins (shsps) are conserved across invertebrate species. They are implicated in the modulation of various biological processes, such as immune responses, abiotic stress tolerance metamorphosis, and embryonic development. Herein, we identified a heat shock protein 20 from the red swamp crayfish, Procambarus clarkii (named as Pc-Hsp20), and performed in vivo studies to elucidate its physiological functions in the innate immunity. The open reading frame of Pc-Hsp20 was 609 base pair, encoding a protein of 202 amino acid residues with a hsp20/alpha crystallin family domain. Pc-Hsp20 was ubiquitously expressed in various tissues; however, it was highest in the hepatopancreas. The challenge with immune elicitors remarkably enhanced the transcript level of Pc-Hsp20 in the hepatopancreas when compared with the control. Administration of double-stranded RNA could significantly reduce expression of the Pc-Hsp20 mRNAs, and most of the immune-related genes expression enhanced with a variable concentration in the hepatopancreas. Altogether, these results suggest that Pc-Hsp20 may participate in innate immunity against microbial pathogens.
Subject(s)
Arthropod Proteins/genetics , Astacoidea/immunology , HSP20 Heat-Shock Proteins/genetics , Hepatopancreas/physiology , Infections/immunology , Animals , Arthropod Proteins/metabolism , Cloning, Molecular , HSP20 Heat-Shock Proteins/metabolism , Immunity, Innate , Phylogeny , Protein Domains/genetics , RNA, Double-Stranded/immunology , Sequence Alignment , Stress, Physiological , Transcriptome , alpha-Crystallins/geneticsABSTRACT
BACKGROUND: Abdominal drainage allows for timely detection of hemorrhage, but it cannot prevent hemorrhage. Whether routine abdominal drainage is needed during bariatric procedures remains controversial. Few reports describe the role of abdominal drainage in the diagnosis and treatment of abdominal hemorrhage in bariatric surgery. CASE SUMMARY: Six cases of hemorrhage after bariatric surgery were described, including three cases with and three without abdominal drainage during the first surgery. The hemorrhage in five of the six cases was controlled by conservative treatment. Abdominal hemorrhage was found through the drainage tube on the day of the operation in the three patients with abdominal drainage during the first surgery. Emergency treatment was initiated, and their conditions gradually stabilized within 48 h. No patients required a reoperation. Abdominal hemorrhage was found later in the patients without abdominal drainage. Although the hemorrhage was controlled by conservative treatment in two cases (1 and 2), reoperation and percutaneous drainage were performed for abdominal infection and pelvic hemorrhage. An obsolete encapsulated effusion that may require treatment in the future was left in the abdominal cavity of a patient (Case 1). CONCLUSION: The possibility of controlling abdominal hemorrhage after bariatric/metabolic surgery by conservative treatment is high. When hemorrhage occurs, abdominal drainage can reduce the probability of reoperation by reducing the formation of blood clots behind the stomach.
ABSTRACT
BACKGROUND: The reward-related regions have been considered a crucial component in the regulation of eating behavior. Furthermore, appetite-related regions associated with reward can influence eating behaviors through altered functional activity related to food in brain areas associated with emotion, memory, sensory processing, motor function, and cognitive control. PURPOSE: To investigate the key nodes in obese females of reward-related regions and, based on key nodes, to evaluate the directionality of functional connectivity between key nodes and appetite-related regions. STUDY TYPE: Prospective. POPULATION: Twenty-eight obese and 28 normal-weight female controls of similar age. FIELD STRENGTH/SEQUENCE: 3.0 T MRI and echo planar imaging (EPI) sequence, 3D BRAVO sequence. ASSESSMENT: The fMRI data preprocessing was based on the Data Processing & Analysis of Brain Imaging and Statistical Parametric Mapping 12. Degree centrality calculation was based on the GRETNA toolkit and granger causality analysis were based on the DynamicBC toolbox. Statistical Tests: Independent two-sample t-tests were used to assess the differences in demographic and clinical data between two groups. Two-sample t-tests were conducted to test the difference in degree centrality and effective connectivity of key nodes between two groups. RESULTS: Compared with normal-weight controls, obese females showed an increased degree centrality in the left ventral striatum/caudate (t = 2.96808, P < 0.05) and decreased degree centrality in right orbitofrontal cortex (OFC) (t = -3.3558, P < 0.05). The obese females showed directional effective connectivity between left ventral striatum/caudate and several regions (left inferior temporal gyrus, fusiform gyrus, postcentral gyrus, and right precentral gyrus) (P < 0.05). Directional effective connectivity was also observed between the right OFC and several regions (left middle temporal gyrus, cuneus, OFC, superior temporal gyrus, middle frontal gyrus, and right inferior parietal lobule) (P < 0.05). DATA CONCLUSION: The left ventral striatum/caudate and right OFC are key nodes in reward-related regions. The key nodes with reward processing mainly enhance visual processing of information and further participate in cognitive, attention, and sensorimotor processing. LEVEL OF EVIDENCE: 1. Technical Efficacy: Stage 4. J. Magn. Reson. Imaging 2019;50:541-551.
Subject(s)
Appetite/physiology , Brain/physiopathology , Magnetic Resonance Imaging/methods , Obesity/physiopathology , Obesity/psychology , Reward , Adolescent , Adult , Brain Mapping/methods , Echo-Planar Imaging , Female , Humans , Imaging, Three-Dimensional , Middle Aged , Prospective Studies , Signal Transduction/physiology , Young AdultABSTRACT
Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC0-t), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P<0.05) compared with PN. The AUC0-t values of GRg1 and GRb1 were 1.7- and 3.4-fold greater, respectively, in FXT than in PN. The compatible herbs of FXT could prolong the retention time and increase the systemic exposure of NR1, GRg1, and GRb1 compared with PN in vivo, providing some scientific basis for the compatibility and clinical use of FXT.
Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Panax notoginseng/chemistry , Administration, Oral , Animals , Blood Chemical Analysis , Cardiovascular Agents/administration & dosage , Cardiovascular Agents/pharmacokinetics , Chromatography, High Pressure Liquid , Diabetic Retinopathy/drug therapy , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Ginsenosides/administration & dosage , Ginsenosides/pharmacokinetics , Humans , Male , Rats , Rats, Sprague-Dawley , Spectrometry, Mass, Electrospray Ionization , Tandem Mass SpectrometryABSTRACT
AIM: Bitter taste is sensed by the bitter taste receptor (TAS2R), which is mainly expressed in the tongue as well as in extra-oral organs, such as the gastrointestinal tract, respiratory tract, brain, heart and testis. This study aimed to investigate whether TAS2R is expressed in the mesenteric, cerebral and omental arteries. MAIN METHODS: The expression levels of TAS2R mRNA and protein were determined by reverse-transcription polymerase chain reaction and Western blotting, respectively. The location of TAS2R was determined by immunofluorescence imaging. TAS2R agonists were used in a sensitive myograph to study the function of TAS2R in arteries. KEY FINDINGS: The mRNA of rat TAS2Rs, including rTAS2R39, rTAS2R40, rTAS2R108, rTAS2R114, rTAS2R130, rTAS2R137, and rTAS2R140, was expressed in rat mesenteric and cerebral arteries, but rTAS2R114 was not expressed in the cerebral arteries. The mRNA of human TAS2Rs, including hTAS2R3, hTAS2R4, hTAS2R7, hTAS2R10, hTAS2R14, hTAS2R39 and hTAS2R40, was expressed in human omental arteries. The TAS2R7 protein was expressed in rat mesenteric and cerebral arteries, as well as in human omental arteries. Immunofluorescence imaging confirmed that TAS2R7 was located in vascular smooth muscle cells and endothelial cells. The TAS2R agonists, chloroquine and quinine relaxed rat mesenteric arteries and cerebral arteries and human omental arteries in a concentration-dependent manner. SIGNIFICANCE: TAS2R is expressed in the arteries of systemic circulation, including rat mesenteric and cerebral arteries and human omental arteries. This study provides evidence that TAS2R do exist in the arteries and may be involved in the mediation of vessel functions.
Subject(s)
Cerebrovascular Circulation , Mesentery/blood supply , Omentum/blood supply , Receptors, G-Protein-Coupled/metabolism , Taste , Animals , Cerebral Arteries/metabolism , Chloroquine/chemistry , Female , Gene Expression Regulation , Humans , Liver/metabolism , Male , Microscopy, Fluorescence , Middle Aged , Omentum/metabolism , Quinine/chemistry , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Tongue/metabolism , VasodilationABSTRACT
Three new aconitine-type C19-diterpenoid alkaloids, taipeinines A-C (1-3), were isolated from the roots of Aconitum taipaicum. The chemical structures of these three compounds were established as (1α,6α,8α,14α,16α)-20-ethyl-8,14-dihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-aconitane (1), (1α,6α,8α,14α,16ß)-20-ethyl-8,14-dihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-aconitane (2) and (1α,6α,8α,14α,16α)-20-ethyl-1,8,14-trihydroxy-6,16-dimethoxy-4-(methoxymethyl)-aconitane (3), respectively, on the basis of spectroscopic analyses, mainly MS, 1D and 2D NMR. The cytotoxic activities of these compounds were also assayed, and the results were quite impressive.
Subject(s)
Aconitine/analogs & derivatives , Aconitine/isolation & purification , Aconitum/chemistry , Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Aconitine/chemistry , Aconitine/pharmacology , Algorithms , Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Doxorubicin , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , K562 Cells , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistry , StereoisomerismABSTRACT
OBJECTIVE: To explore genotype distributions at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci in healthy Chinese living in northern area, and to assess the association of single or combined gene mutations with folic acid, Vit.B(12), Hcy levels and CHD. METHODS: 192 patients having CHD and their biological parents in Liaoning province registered as birth defects were included in this study as case group, and 124 healthy subjects (age and gender matched) and their biological parents were simultaneously selected from the same geographic area as control. To all subjects, the gene polymorphism at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci was examined with PCR-RFLP. The serum folic acid and homocysteine (Hcy) level were analyzed with Radioimmunoassay or fluorescence polarization immunoassay (FPIA). RESULTS: In healthy Chinese living in northern China, the mutant allele frequencies of these four loci were MTHFR 51.18%, MS 7.58%, MTHFD 24.32%, and CBS insertion 2.36%, respectively. The heterozygosity of CBS 844 ins68bp was more prevalent in case than in control (12.57% vs 2.97% in children, 10.88% vs 3.09% in father and 11.54% vs 1.02% in mother, respectively), and yielded an odds ratio (OR) of 4.70 (95% CI 1.34-25.15) in children, 3.83 (95% CI 1.05-20.98) in fathers and 12.65 (95% CI 1.92-532.47) in mothers. There is no existed significant difference at the other three loci. The percents of mothers with MTHFR, CBS and MTHFD gene polymorphisms, of mothers with MTHFR and CBS being polymorphisms (OR=8.44, 95aCI 1.23-362.26), of mothers with MTHFD and CBS being polymorphisms in case were higher than those in control. Serum folic acid levels of mothers and fathers in case were significantly higher than those of counterparts in control. Serum Hcy level of mothers in case was higher than that of counterparts in control without significant difference. Homozygous mutation at MTHFR and MTHFD loci made serum folic acid and Vit.B(12) levels slightly decreased and serum Hcy level increased. CONCLUSION: The study showed presence of ethnic and district difference of gene polymorphisms at these four loci. 68 bp insertion at exon 8 of CBS gene base 844 could be a risk factor for CHD, and the insertion in parents (especially in mothers) could increase CHD risk in offspring.