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1.
Brain Sci ; 13(9)2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37759910

ABSTRACT

OBJECTIVES: Cognitive impairment in cerebral small vessel disease (CSVD) is a common cause of vascular dementia and is often accompanied by mental disorders. The purpose of this study was to investigate the effect of continuous theta burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on the cognitive function and Hamilton depression (HAMD) scores in patients with CSVD. METHODS: A total of 30 CSVD patients who met the inclusion criteria were randomly assigned to either the sham or cTBS group. The patients in both groups received routine cognitive function training. All the patients were under treatment for 14 sessions, with one session per day (each cTBS conditioning session consisted of three-pulse bursts at 50 Hz repeated at 5 Hz, 80% MT, and 600 pulses). Before and after the treatment, the patients in both groups were evaluated using the Montreal Cognitive Assessment (MoCA), Stroop Color-Word Test (SCWT), Trail Marking Test (TMT), Digital Span Test (DST), and HAMD test. The time to complete the SCWT and TMT were recorded. The scores of the MoCA, DST and HAMD test were recorded. RESULTS: The HAMD scores in the cTBS group decreased significantly compared to the control (p < 0.05). There were no significant differences in the MoCA (including the MoCA subitems) or DST scores or in the SCWT or TMT completion times between the two groups (p > 0.05). For the HAMD scores and the MoCA subitem visuospatial/executive scores, the SCWT-B and SCWT-C completion times in the two groups both improved significantly before and after treatment (p < 0.05). For the MoCA scores, the DST-backward scores and the TMT-B completion times in the cTBS group improved significantly before and after treatment (p < 0.05). There was no significant difference in the SCWT-A, TMT-A completion times and MoCA subitems naming, attention, language, abstraction, delayed recall, and orientation scores either before or after treatment in the two groups or between the two groups (p > 0.05). CONCLUSIONS: In this study, cTBS over the right DLPFC decreased the HAMD scores significantly in patients with CSVD but had no significant improvement or impairment effects on cognitive function. cTBS over the right DLPFC could be used to treat CSVD patients with depression symptoms.

2.
Neural Regen Res ; 18(1): 176-182, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35799539

ABSTRACT

Based on the Wallerian degeneration in the spinal cord pathways, the changes in synaptic connections, and the spinal cord-related cellular responses that alter the cellular structure of the brain, we presumed that brain diffusion tensor imaging (DTI) parameters may change after spinal cord injury. However, the dynamic changes in DTI parameters remain unclear. We established a Beagle dog model of T10 spinal cord contusion and performed DTI of the injured spinal cord. We found dynamic changes in DTI parameters in the cerebral peduncle, posterior limb of the internal capsule, pre- and postcentral gyri of the brain within 12 weeks after spinal cord injury. We then performed immunohistochemistry to detect the expression of neurofilament heavy polypeptide (axonal marker), glial fibrillary acidic protein (glial cell marker), and NeuN (neuronal marker). We found that these pathological changes were consistent with DTI parameter changes. These findings suggest that DTI can display brain structure changes after spinal cord injury.

3.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: mdl-34893856

ABSTRACT

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.


Subject(s)
Genome , Sheep, Domestic , Animals , Asia , Europe , Genetic Variation , Iran , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Sheep/genetics , Sheep, Domestic/genetics
4.
Front Neurosci ; 16: 1107688, 2022.
Article in English | MEDLINE | ID: mdl-36726851

ABSTRACT

Objectives: To observe the efficacy of botulinum toxin type A (BoNT-A) for the spasticity of the lower-limb post-stroke on gait and posture control. Methods: A total of 46 patients with hemiplegia gait were randomly divided into the experimental group (23 patients) and the control group (23 patients). In patients in the experimental group received injections of BoNT-A by electrical stimulation-guided. At the same time, patients of the two groups received routine physical therapy. Gait analysis, plantar pressure analysis, lower-limb Fugl-Meyer assessment (L-FMA), 10 meter walking test (10MWT), timed "Up and Go" test (TUGT), and modified Ashworth Scale assess (MAS) of the lower limbs were performed at 0, 1, 4, and 12 weeks after treatment. Results: At 1, 4, and 12 weeks after treatment, the L-FMA, stride length, speed, and TUGT significantly improved than 0 week in both groups. The L-FMA and peak of forefoot pressure, and MAS results in the experimental group were better than those in the control group at 4 and 12 weeks. The TUGT, speed, and stride length in experimental group was significantly shortened than that in control group at 1, 4, and 12 weeks. Conclusion: Botulinum toxin type A injection can improve motor functions of the lower limb, gait, spasticity, forefoot pressure, and posture control of patients after stroke.

5.
Neural Plast ; 2021: 6636999, 2021.
Article in English | MEDLINE | ID: mdl-33574837

ABSTRACT

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed "Up and Go" test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life.


Subject(s)
Cognition/physiology , Gait Disorders, Neurologic/physiopathology , Gait/physiology , Postural Balance/physiology , Stroke/physiopathology , Adult , Case-Control Studies , Female , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/psychology , Humans , Male , Middle Aged , Retrospective Studies , Stroke/complications , Stroke/psychology , Stroke Rehabilitation
6.
Mol Biol Evol ; 38(3): 838-855, 2021 03 09.
Article in English | MEDLINE | ID: mdl-32941615

ABSTRACT

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.


Subject(s)
Adaptation, Biological/genetics , Disease Resistance/genetics , Genetic Introgression , Sheep/genetics , Animals , Biological Evolution , Climate Change , Genetic Variation , Phylogeography , Pneumonia/immunology , Sheep/immunology
7.
Neural Regen Res ; 16(2): 375-381, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32859801

ABSTRACT

Singing, as a method of combining respiratory function exercise and vocal intonation therapy, provides a new direction for respiratory function exercise in patients with spinal cord injury. This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury. Among 31 included patients with spinal cord injury, 18 completed the treatment. These 18 patients were randomly assigned to undergo music therapy (intervention group, 30 min/d, 5 times a week, for a total of 12 weeks; n = 9, 7 males and 2 females; 30.33 ± 11.74 years old) or normal respiratory training (control group, n = 9; 8 males and 1 female; 34.78 ± 11.13 years old). Both patient groups received routine treatment concurrently. Before and at 6 and 12 weeks after intervention, a standard respiratory function test, a voice test, the St. George's Respiratory Questionnaire, and a quality of life questionnaire were administered. The results showed that the inspiratory capacity, forced expiratory volume in 1 second, forced vital capacity, maximal mid-expiratory flow rate, sing-loud pressure level, and sustained note length were significantly increased in the intervention group compared with the control group. The St. George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group. These findings suggest that oral motor respiratory exercise and vocal intonation therapy, as respiratory training methods in music therapy, are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2019-78-1) on May 27, 2019 and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1900026922) on October 26, 2019.

8.
Nat Commun ; 11(1): 2815, 2020 06 04.
Article in English | MEDLINE | ID: mdl-32499537

ABSTRACT

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.


Subject(s)
Animal Husbandry/methods , Animals, Wild/genetics , Platelet-Derived Growth Factor/metabolism , Sheep, Domestic/genetics , Alleles , Animals , Breeding , Female , Gene Frequency , Genetic Variation , Genetics , Genomics , Genotype , High-Throughput Nucleotide Sequencing , Linkage Disequilibrium , Mutation , Phenotype , Polymorphism, Single Nucleotide , Selection, Genetic , Sequence Analysis, DNA , Sheep , Species Specificity , Whole Genome Sequencing
9.
Neural Regen Res ; 15(2): 212-221, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31552886

ABSTRACT

Non-coding RNAs (ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs (tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18-40 nucleotides, known as tRNA-derived small RNAs (tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points: (1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes. (2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. (3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma. (4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 74-79, 2019 Feb.
Article in Chinese | MEDLINE | ID: mdl-30738450

ABSTRACT

OBJECTIVE: To investigate the prognostic evaluation value of fluorodeoxyglucose (FDG) interim positron emission tomography/computed tomography (PET/CT) for diffuse large B cell lymphoma (DLBCL). METHODS: Two hundred and twenty-seven patients with pathologically diagnosed DLBCL underwent 18F-FDG scans at baseline and before 3 cycles of a rituximab-containing chemotherapy regimen. The Visual Deauville score (DS) and changes in maximum standard uptake values (ΔSUVmax) were calculated for tracer for the predominant lesion of each patient, for prediction of progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier method and COX regression. RESULTS: The median follow-up period was 71 months. Receiver operating characteristic analysis indicated that the best ΔSUV cut-off values for FDG (ΔSUVFDG) was 71%. The sensitivity, specificity and accuracy of DS and ΔSUVmax were 86.9%, 74.3%, 82.8% and 77.8%, 63.5%, 73.1%, respectively in response assessment. Kaplan-Meier analysis showed DS, ΔSUVmax and IPI had significance for prediction of PFS and OS (P = 0.001). The DS 4-5 and IPI 3-5 were independent risk factors of poor prognosis by COX regression analysis. CONCLUSION: Interim PET/CT is important predictor for evaluation therapeutic response and prognosis in DLBCL patients.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Disease-Free Survival , Fluorodeoxyglucose F18 , Humans , Prognosis
11.
Neural Regen Res ; 14(5): 886-895, 2019 May.
Article in English | MEDLINE | ID: mdl-30688275

ABSTRACT

Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I (steep rise) 1-7 hours, stage II (steady rise) 8-38 hours, and stage III (descending) 39-72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages II and III of spinal cord injury.

12.
CNS Neurosci Ther ; 25(2): 261-272, 2019 02.
Article in English | MEDLINE | ID: mdl-30076687

ABSTRACT

AIM: Exploration of the mechanism of spinal cord degeneration may be the key to treatment of spinal cord injury (SCI). This study aimed to investigate the degeneration of white matter and gray matter and pathological mechanism in canine after SCI. METHODS: Diffusion tensor imaging (DTI) was performed on canine models with normal (n = 5) and injured (n = 7) spinal cords using a 3.0T MRI scanner at precontusion and 3 hours, 24 hours, 6 weeks, and 12 weeks postcontusion. The tissue sections were stained using H&E and immunohistochemistry. RESULTS: For white matter, fractional anisotropy (FA) values significantly decreased in lesion epicenter, caudal segment 1 cm away from epicenter, and caudal segment 2 cm away from epicenter (P = 0.003, P = 0.004, and P = 0.013, respectively) after SCI. Apparent diffusion coefficient (ADC) values were initially decreased and then increased in lesion epicenter and caudal segment 1 cm away from epicenter (P < 0.001 and P = 0.010, respectively). There are no significant changes in FA and ADC values in rostral segments (P > 0.05). For gray matter, ADC values decreased initially and then increased in lesion epicenter (P < 0.001), and overall trend decreased in caudal segment 1 cm away from epicenter (P = 0.039). FA values did not change significantly (P > 0.05). Pathological examination confirmed the dynamic changes of DTI parameters. CONCLUSION: Diffusion tensor imaging is more sensitive to degeneration of white matter than gray matter, and the white matter degeneration may be not symmetrical which meant the caudal degradation appeared to be more severe than the rostral one.


Subject(s)
Gray Matter/diagnostic imaging , Gray Matter/pathology , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/pathology , White Matter/diagnostic imaging , White Matter/pathology , Animals , Anisotropy , Diffusion Tensor Imaging , Dogs , Female , Immunohistochemistry , Nerve Degeneration/diagnostic imaging , Nerve Degeneration/pathology , Spinal Cord/diagnostic imaging , Spinal Cord/pathology
13.
Neural Regen Res ; 13(5): 877-886, 2018 May.
Article in English | MEDLINE | ID: mdl-29863019

ABSTRACT

Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T10 spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord (R = 0.919, P = 0.027), white matter (R = 0.932, P = 0.021), and gray matter (R = 0.882, P = 0.048). Additionally, the other parameters had almost no correlation with the score (P > 0.05). In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.

14.
Front Mol Neurosci ; 11: 497, 2018.
Article in English | MEDLINE | ID: mdl-30692912

ABSTRACT

Spinal cord injury (SCI) is mostly caused by trauma. As primary mechanical injury is unavoidable in SCI, a focus on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising treatments for SCI patients. Circular RNAs (circRNAs) are associated with various diseases. Nevertheless, studies to date have not yet determined the functional roles of circRNAs in traumatic SCI. We examined circRNA expression profiles in the contused spinal cords of rats using microarray and quantitative reverse transcription-PCR (qRT-PCR) then predict their potential roles in post-SCI pathophysiology with bioinformatics. We found a total of 1676 differentially expressed circRNAs (fold change ≥ 2.0; P < 0.05) in spinal cord 3 days after contusion using circRNA microarray; 1261 circRNAs were significantly downregulated, whereas the remaining 415 were significantly upregulated. Then, five selected circRNAs, namely, rno_circRNA_005342, rno_circRNA_015513, rno_circRNA_002948, rno_circRNA_006096, and rno_circRNA_013017 were all significantly downregulated in the SCI group after verification by qRT-PCR, demonstrating a similar expression pattern in both microarray and PCR data. The next section of the study was concerned with the prediction of circRNA/miRNA/mRNA interactions using bioinformatics analysis. In the final part of the study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated carbohydrate metabolic process was one of the most significant enrichments and meaningful terms after GO analysis, and the top two signaling pathways affected by the circRNAs-miRNAs axes were the AMP-activated protein kinase signaling pathway and the peroxisome related pathway. In summary, this study showed an altered circRNA expression pattern that may be involved in physiological and pathological processes in rats after traumatic SCI, providing deep insights into numerous possibilities for SCI treatment targets by regulating circRNAs.

16.
Fish Shellfish Immunol ; 63: 304-313, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28212834

ABSTRACT

Death-associated protein 1 (DAP1) is a small proline-rich cytoplasmic protein that functions both in the apoptosis and autophage process of mammalian and in the clinical cancer of human. However, little knowledge is known about the homologue gene of DAP1 and its roles in the physiological process of invertebrates. In this paper, we report a novel function of DAP1 in the antivirus immunity of shrimp. A homologue gene of DAP1 was cloned from Marsupenaeus japonicus and named as Mjdap-1. The full-length of Mjdap-1 was 1761 bp with a 309 bp open reading frame that encoded 102 amino acids. Reverse transcription-PCR results showed that Mjdap-1 was expressed in all tested tissues, including hemocytes, gills, intestines, stomach, heart, hepatopancreas, testes, and ovaries. In shrimp, Mjdap-1 transcripts were up-regulated by white spot syndrome virus (WSSV) infection; Mjdap-1 knockdown decreased the virus copy in vivo and the mortality of M. japonicus to WSSV challenge. Conversely, injecting the purified recombinant MjDAP1 protein promoted the amplification of virus in shrimp. Flow cytometric assay showed, the virus infection-induced apoptosis of hemocytes was enhanced by MjDAP1 protein injection and inhibited in MjDAP1 knockdown shrimp. Furthermore, the expression of apoptosis-inducing factor (AIF) was regulated by Mjdap-1, but the caspase transcripts were not affected. Our results suggested that MjDAP1 facilitated the amplification of virus in shrimp, which may be attributed to the promotion of hemocyte apoptosis in an AIF-dependent manner. These results provided a new insight into the function of this protein that may be used for virus disease control.


Subject(s)
Apoptosis Regulatory Proteins/genetics , Apoptosis/genetics , Penaeidae/genetics , Penaeidae/virology , Virus Replication/genetics , White spot syndrome virus 1/physiology , Amino Acid Sequence , Animals , Apoptosis Inducing Factor/genetics , Apoptosis Inducing Factor/metabolism , Apoptosis Regulatory Proteins/chemistry , Apoptosis Regulatory Proteins/metabolism , Arthropod Proteins/chemistry , Arthropod Proteins/genetics , Arthropod Proteins/metabolism , Base Sequence , Cloning, Molecular , DNA, Complementary/genetics , DNA, Complementary/metabolism , Gene Expression , Hemocytes/immunology , Hemocytes/virology , Penaeidae/classification , Penaeidae/immunology , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment
17.
Mol Imaging Biol ; 17(5): 625-32, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25666290

ABSTRACT

PURPOSE: We aimed to explore the feasibility of transfection methods for antisense imaging. PROCEDURES: Antisense oligonucleotides (ASON) targeted to the mRNA of hTERT gene were synthesized and labeled with Technetium-99m and fluorescein isothiocyanate (FITC), respectively. Then, ASON was combined with transfection reagent Lipofectamine 2000 and Xfect(TM), named Lipo-ASON and Xfect-ASON, respectively. After transfection, the labeled ASON was characterized in hNPCs-G3 and hRPE cells. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were performed to assay the hTERT mRNA and protein levels after hNPCs-G3 cells were incubated with Lipo-ASON, Xfect-ASON, and naked ASON. In addition, Lipo-ASON, Xfect-ASON, and naked ASON were injected into tumor-bearing mice, and the biodistribution in vivo was performed. RESULTS: The presence of two transfection reagents significantly increased intracellular uptake of radiolabeled ASON in both cell lines compared with naked ASON (p < 0.05). However, there was no significant difference in cellular uptake rates of Lipo-ASON and Xfect-ASON between hNPCs-G3 and hRPE cells. In comparison with naked ASON, the fluorescence intensity was strongly enhanced after binding to transfection reagents. Furthermore, the levels of hTERT mRNA and protein were significantly reduced in cells treated with Lipo-ASON and Xfect-ASON (p < 0.05), but naked ASON had no significant effect on hTERT expression level. The biodistribution study indicated that tumor radioactivity uptake of radiolabeled ASON for naked ASON, Lipo-ASON, and Xfect-ASON group was low and shown no significant difference in vivo. CONCLUSIONS: Lipofectamine transfection and Xfect(TM) transfection were not effective delivery methods of ASON for antisense imaging.


Subject(s)
Drug Delivery Systems/methods , Molecular Imaging/methods , Oligonucleotides, Antisense/chemistry , Animals , Cell Line , Fluorescein-5-isothiocyanate/chemistry , Humans , Mice , Mice, Nude , Oligonucleotides, Antisense/pharmacokinetics , Radioisotopes/chemistry , Radioisotopes/pharmacokinetics , Technetium/chemistry , Technetium/pharmacokinetics , Tissue Distribution , Transfection
18.
PLoS One ; 8(4): e60104, 2013.
Article in English | MEDLINE | ID: mdl-23565188

ABSTRACT

OBJECTIVE: Based on the results of a recently accomplished multicenter clinical trial for the incremental value of a dual-tracer (18F-FDG and 18F-FLT), dual-modality (PET and CT) imaging in the differential diagnosis of pulmonary lesions, we investigate some issues that might affect the image interpretation and result reporting. METHODS: The images were read in two separate sessions. Firstly the images were read and reported by physician(s) of the imaging center on completion of each PET/CT scanning. By the end of MCCT, all images collected during the trial were re-read by a collective of readers in an isolated, blinded, and independent way. RESULTS: One hundred sixty two patients successfully passed the data verification and entered into the final analysis. The primary reporting result showed adding 18F-FDG image information did not change the clinical performance much in sensitivity, specifity and accuracy, but the ratio between SUVFLT and SUVFDG did help the differentiation efficacy among the three subgroups of patients. The collective reviewing result showed the diagnostic achievement varied with reading strategies. ANOVA indicated significant differences among (18)F-FDG, (18)F-FLT in SUV (F = 14.239, p = 0.004). CT had almost the same diagnostic performance as 18F-FLT. When the 18F-FDG, 18F-FLT and CT images read in pair, both diagnostic sensitivity and specificity improved. The best diagnostic figures were obtained in full-modality strategy, when dual-tracer PET worked in combination with CT. CONCLUSIONS: With certain experience and training both radiologists and nuclear physicians are qualified to read and to achieve the similar diagnostic accuracy in PET/CT study. Making full use of modality combination and selecting right criteria seems more practical than professional back ground and personal experience in the new hybrid imaging technology, at least when novel tracer or application is concerned.


Subject(s)
Clinical Competence , Fluorodeoxyglucose F18 , Lung Diseases/diagnosis , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(3): 603-7, 2012 Jun.
Article in Chinese | MEDLINE | ID: mdl-22739164

ABSTRACT

The aim of this study was to evaluate the role of (18)F-FLT positron emission tomography/computed tomography (PET/CT) in diagnosis and staging of diffuse large B-cell lymphoma (DLBCL) patients and compare with CT. Thirty-six patients with DLBCL in our hospital from September 2008 to December 2009 were prospectively evaluated. All 36 patients underwent whole body and head (18)F-FLT PET/CT and CT (chest, abdomen cavity and pelvis) were studied before therapy. The maximal standardized uptake value (SUV(max)) of every single focus and the SUV(max) of aortic arch blood pool were measured and used to calculate the median T/MB value (tumor SUV(max)/mediastinal SUV(max)) of every patient. The results showed that the consistency of (18)F-FLT PET/CT and CT examinations in focus of DLBCL was 79.10%, the sensitivity, specificity, positive predictive value, negative predictive value and accurate rate of (18)F-FLT PET/CT were 96.65%, 100%, 100%, 61.11% and 96.82%, respectively, which were much higher than that of CT (85.44%, 57.14%, 96.70%, 21.05% and 83.64%). It is concluded that the (18)F-FLT PET/CT is a good means for DLBCL diagnosis and staging, which is more sensitive and specific than CT.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/pathology , Multimodal Imaging , Positron-Emission Tomography , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm Staging , Sensitivity and Specificity , Tomography, X-Ray Computed , Young Adult
20.
World J Gastroenterol ; 16(43): 5416-23, 2010 Nov 21.
Article in English | MEDLINE | ID: mdl-21086558

ABSTRACT

AIM: To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with (18)F-fluorothymidine ((18)F-FLT) and (18)F-fluorodeoxyglucose ((18)F-FDG) small-animal position emission tomography (micro-PET). METHODS: The primary and metastatic CRC cell lines, SW480 and SW620, were irradiated with 5, 10 and 20 Gy. After 24 h, the cell cycle phases were analyzed. A dual-tumor-bearing mouse model of primary and metastatic cancer was established by injecting SW480 and SW620 cells into mice. micro-PET with (18)F-FLT and (18)F-FDG was performed before and 24 h after irradiation with 5, 10 and 20 Gy. The region of interest (ROI) was drawn over the tumor and background to calculate the ratio of tumor to non-tumor (T/NT) in tissues. Immunohistochemical assay and Western blotting were used to examine the levels of integrin ß(3,) Ki-67, vascular endothelial growth factor receptor 2 (VEGFR2) and heat shock protein 27 (HSP27). RESULTS: The proportion of SW480 and SW620 cells in the G(2)-M phase was decreased with an increasing radiation dose. The proportion of SW480 cells in the G(0)-G(1) phase was increased from 48.33% ± 4.55% to 87.09% ± 7.43% (P < 0.001) and that of SW620 cells in the S-phase was elevated from 43.57% ± 2.65% to 66.59% ± 7.37% (P = 0.021). In micro-PET study, with increasing dose of radiation, (18)F-FLT uptake was significantly reduced from 3.65 ± 0.51 to 2.87 ± 0.47 (P = 0.008) in SW480 tumors and from 2.22 ± 0.42 to 1.76 ± 0.45 (P = 0.026) in SW620 tumors. (18)F-FDG uptake in SW480 and SW620 tumors was reduced but not significantly (F = 0.582, P = 0.633 vs F = 0.273, P = 0.845). Dose of radiation was negatively correlated with (18)F-FLT uptake in both SW480 and SW620 tumors (r = -0.727, P = 0.004; and r = -0.664, P = 0.009). No significant correlation was found between (18)F-FDG uptake and radiation dose in SW480 or SW620 tumors. HSP27 and integrin ß(3) expression was higher in SW480 than in SW620 tumors. The T/NT ratio for (18)F-FLT uptake was positively correlated with HSP27 and integrin ß(3) expression (r = 0.924, P = 0.004; and r = 0.813, P = 0.025). CONCLUSION: (18)F-FLT is more suitable than (18)F-FDG in monitoring early responses to irradiation in both primary and metastatic lesions of colorectal cancer.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/radiotherapy , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/radiotherapy , Adenocarcinoma/physiopathology , Animals , Cell Cycle/radiation effects , Cell Line, Tumor , Colorectal Neoplasms/physiopathology , Disease Models, Animal , Dose-Response Relationship, Radiation , Fluorodeoxyglucose F18 , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Monitoring, Physiologic , Positron-Emission Tomography , Radiotherapy , Transplantation, Heterologous
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