ABSTRACT
A fast, simple and reagent-free detection method for aflatoxin B1 (AFB1) is of great significance to food safety and human health. Visible and near-infrared (Vis-NIR) spectroscopy was applied to the discriminant analysis of AFB1 excessive standard of peanut meal as feedstuff materials. Two types of excessive standard discriminant models based on spectral quantitative analysis with partial least squares (PLS) and direct pattern recognition with partial least squares-discrimination analysis (PLS-DA) were established, respectively. Multi-parameter optimization of Norris derivative filtering (NDF) was used for spectral preprocessing; the two-stage wavelength screening method based on equidistant combination-wavelength step-by-step phase-out (EC-WSP) was used for wavelength optimization. A rigorous sample experimental design of calibration-prediction-validation was utilized. The calibration and prediction samples were used for modeling and parameter optimization, and the selected model was validated using the independent validation samples. For quantitative analysis-based, the positive, negative and total recognition-accuracy rates in validation (RARV+, RARV-, and RARV) were 84.8 %, 74.6 % and 79.8 %, respectively; but, the relative root mean square error of prediction was as high as 51.0 %. For pattern recognition-based, the RARV+, RARV-, and RARV were 93.3 %, 90.5 % and 91.9 %, respectively. Moreover, the number of wavelengths N was drastically reduced to 17, and the discrete wavelength combination was in NIR overtone frequency region. The results indicated that, the EC-WSP-PLS-DA model achieved significantly better discrimination effect. Thus demonstrated that Vis-NIR spectroscopy has feasibility for the excessive standard discrimination of aflatoxin B1 in feedstuff materials.
Subject(s)
Aflatoxin B1 , Arachis , Spectroscopy, Near-Infrared , Aflatoxin B1/analysis , Arachis/chemistry , Spectroscopy, Near-Infrared/methods , Discriminant Analysis , Least-Squares Analysis , Food Contamination/analysis , Calibration , Reproducibility of ResultsABSTRACT
Abundant evidence has shown the protective effect of aerobic exercise on central neuronal system, however, research about resistance exercise remains limited. To evaluate the effect and potential molecular mechanisms of resistance exercise in improving cognition and mental health, three-month-old male C57BL/6J mice underwent resistance training for five weeks. Body parameters, cognitive performance and synaptic plasticity were then assessed. In both groups, total RNA from the frontal cortex, hippocampus and gastrocnemius was isolated and sequenced, GO term and KEGG analysis were performed to identify molecular mechanisms. The results from RNA sequencing were then verified by RT-PCR. Our data found that mice in training group showed reduced anxiety-like behavior and better spatial memory. Accordingly, resistance exercise specifically increased the number of thin spines without affecting the number of other kind of spines. mRNA sequence analysis showed that resistance exercise induced differential expression of hundreds of genes in the above three tissues. KEGG analysis indicated the FoxO signaling pathway the most significant changed pathway throughout the brain and muscle. GO terms analysis showed that Sgk1 was enriched in the three key cognition related BP, including long-term memory, learning or memory and memory, and the expression level of Sgk1 was positive related with cognitive performance in the water maze. In conclusion, resistance exercise improved the mental health, cognition and synaptic plasticity of mice. Integrating analysis of mRNA expression profiles in frontal cortex, hippocampus and muscle reveals Sgk1 as the key mediator in brain-muscle crosstalk.
Subject(s)
Brain , Immediate-Early Proteins , Mice, Inbred C57BL , Muscle, Skeletal , Physical Conditioning, Animal , Protein Serine-Threonine Kinases , RNA, Messenger , Animals , Male , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Brain/metabolism , Mice , Muscle, Skeletal/metabolism , Resistance Training , Cognition/physiology , Transcriptome , Neuronal Plasticity/genetics , Hippocampus/metabolism , Anxiety/genetics , Anxiety/metabolismABSTRACT
Poststroke cognitive impairment (PSCI) is a common complication of stroke, but effective treatments are currently lacking. Repetitive transcranial magnetic stimulation (rTMS) is gradually being applied to treat PSCI, but there is limited evidence of its efficacy. To determine rTMS effects on PSCI, we constructed a transient middle cerebral artery occlusion (tMCAO) rat model. Rats were then grouped by random digital table method: the sham group (nâ¯=â¯10), tMCAO group (nâ¯=â¯10) and rTMS group (nâ¯=â¯10). The shuttle box and Morris water maze (MWM) tests were conducted to detect the cognitive functions of the rats. In addition, synaptic density and synaptic ultrastructural parameters, including the active zone length, synaptic cleft width, and postsynaptic density (PSD) thickness, were quantified and analyzed using an electron microscope. What's more, synaptic associated proteins, including PSD95, SYN, and BDNF were detected by western blot. According to the shuttle box and MWM tests, rTMS improved tMCAO rats' cognitive functions, including spatial learning and memory and decision-making abilities. Electron microscopy revealed that rTMS significantly increased the synaptic density, synaptic active zone length and PSD thickness and decreased the synaptic cleft width. The western blot results showed that the expression of PSD95, SYN, and BDNF was markedly increased after rTMS stimulation. Based on these results, we propose that 20â¯Hz rTMS can significantly alleviate cognitive impairment after stroke. The underlying mechanism might be modulating the synaptic plasticity and up-regulating the expression PSD95, SYN, and BDNF in the hippocampus.
Subject(s)
Brain Ischemia , Cognitive Dysfunction , Disease Models, Animal , Hippocampus , Neuronal Plasticity , Rats, Sprague-Dawley , Transcranial Magnetic Stimulation , Animals , Neuronal Plasticity/physiology , Cognitive Dysfunction/therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Male , Rats , Hippocampus/metabolism , Brain Ischemia/therapy , Brain Ischemia/physiopathology , Infarction, Middle Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/physiopathology , Infarction, Middle Cerebral Artery/complications , Disks Large Homolog 4 Protein/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Maze Learning/physiologyABSTRACT
Background: The mechanism by which high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) improves swallowing function by regulating intestinal flora remains unexplored. We aimed to evaluate this using fecal metabolomics and 16S rRNA sequencing. Methods: A Post-stroke dysphagia (PSD) rat model was established by middle cerebral artery occlusion. The magnetic stimulation group received HF-rTMS from the 7th day post-operation up to 14th day post-surgery. Swallowing function was assessed using a videofluoroscopic swallowing study (VFSS). Hematoxylin-eosin (H&E) staining was used to assess histopathological changes in the intestinal tissue. Intestinal flora levels were evaluated by sequencing the 16S rRNA V3-V4 region. Metabolite changes within the intestinal flora were evaluated by fecal metabolomics using liquid chromatography-tandem mass spectrometry. Results: VFSS showed that the bolus area and pharyngeal bolus speed were significantly decreased in PSD rats, while the bolus area increased and pharyngeal transit time decreased after HF-rTMS administration (p < 0.05). In the PSD groups, H&E staining revealed damaged surface epithelial cells and disrupted cryptal glands, whereas HF-rTMS reinforced the integrity of the intestinal epithelial cells. 16S rRNA sequencing indicated that PSD can disturb the intestinal flora and its associated metabolites, whereas HF-rTMS can significantly regulate the composition of the intestinal microflora. Firmicutes and Lactobacillus abundances were lower in the PSD group than in the baseline group at the phylum and genus levels, respectively; however, both increased after HF-rTMS administration. Levels of ceramides (Cer), free fatty acids (FA), phosphatidylethanolamine (PE), triacylglycerol (TAG), and sulfoquinovosyl diacylglycerol were increased in the PSD group. The Cer, FA, and DG levels decreased after HF-rTMS treatment, whereas the TAG levels increased. Peptococcaceae was negatively correlated with Cer, Streptococcus was negatively correlated with DG, and Acutalibacter was positively correlated with FA and Cer. However, these changes were effectively restored by HF-rTMS, resulting in recovery from dysphagia. Conclusion: These findings suggest a synergistic role for the gut microbiota and fecal metabolites in the development of PSD and the therapeutic mechanisms underlying HF-rTMS.
Subject(s)
Deglutition Disorders , Disease Models, Animal , Feces , Gastrointestinal Microbiome , Metabolomics , RNA, Ribosomal, 16S , Stroke , Animals , RNA, Ribosomal, 16S/genetics , Feces/microbiology , Feces/chemistry , Rats , Metabolomics/methods , Stroke/complications , Stroke/therapy , Deglutition Disorders/therapy , Male , Transcranial Magnetic Stimulation/methods , Rats, Sprague-Dawley , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Bacteria/metabolismABSTRACT
BACKGROUND: Post-stroke dysphagia (PSD) is a common symptom of stroke. Clinical complications of PSD include malnutrition and pneumonia. Clinical studies have shown that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) can improve the swallowing function in stroke patients. However, few studies have elucidated the underlying molecular mechanisms. METHODS: A PSD rat model was established using transient middle cerebral artery occlusion (tMCAO). Rats were randomly divided into sham-operated groups, PSD groups, PSD + sham-rTMS groups, PSD + 5 Hz-rTMS groups, PSD + 10 Hz-rTMS groups and PSD + 20 Hz-rTMS groups. Rats were weighed and videofluoroscopic swallowing studies were conducted. Pulmonary inflammation, levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in the serum, lung, and nucleus tractus solitarius (NTS), brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5HT) in NTS were evaluated. RESULTS: Rats in the PSD group experienced weight loss, reduced bolus area and pharyngeal bolus speed, and increased pharyngeal transit time (PTT) and inter-swallow interval (ISI) on day 7 and day 14 after operation. Moreover, PSD rats showed pulmonary inflammation, reduced levels of SP in the lung and serum, increased levels of CGRP in the lung and NTS, reduced levels of BDNF and 5HT in the NTS. There was no significant difference between the PSD group and the PSD + sham-rTMS group in the results of weight and VFSS. Comparing with the PSD group, there significant increases in the bolus area, decreases in PTT of rats following 5 Hz rTMS intervention. HF-rTMS at 10 Hz significantly increased the weight, bolus area, pharyngeal bolus speed and decreased the PTT and ISI of rats. There were also significant increases in the bolus area (p < 0.01) and pharyngeal bolus speed, decreases in PTT and ISI of rats following 20 Hz rTMS intervention. Furthermore, compared with the PSD + 5 Hz-rTMS group, there were significant increases in the bolus area and pharyngeal bolus speed, decreases in ISI in the swallowing function of rats in the PSD + 10 Hz-rTMS group. Besides, compared with the PSD + 5 Hz-rTMS group, there were significant decreases in ISI in the swallowing function of rats in the PSD + 20 Hz-rTMS group. HF-rTMS at 10 Hz alleviated pulmonary inflammation, increased the levels of SP in the lung, serum, and NTS, CGRP in the serum and NTS, 5HT in the NTS of PSD rats. CONCLUSION: Compared with 5 Hz and 20 Hz rTMS, 10 Hz rTMS more effectively improved the swallowing function of rats with PSD. HF-rTMS at 10 Hz improved the swallowing function and alleviated pneumonia in PSD rats. The mechanism may be related to increased levels of SP in the lung, serum and NTS, levels of CGRP in the serum and NTS, 5HT in the NTS after HF-rTMS treatment.
Subject(s)
Deglutition Disorders , Pneumonia , Stroke , Humans , Animals , Rats , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Deglutition/physiology , Transcranial Magnetic Stimulation/methods , Brain-Derived Neurotrophic Factor , Calcitonin Gene-Related Peptide , Pneumonia/therapy , Pneumonia/complicationsABSTRACT
Heart failure (HF) is an advanced stage of most heart diseases. Some studies reported that Dengzhanshengmai (DZSM) capsule may improve HF, but its mechanisms are unclear. This study attempts to determine the function of DZSM in treating HF and investigates its potential mechanism. We demonstrated that DZSM can considerably reduce systemic inflammation, improve intestinal barrier functions and enhance cardiac functions in HF rats. Further investigations displayed that the beneficial effects of DZSM were related to the reduction of gut microbiota metabolite phenylacetylglutamine (PAGln) levels in serum and heart tissue. In addition, we demonstrated that PAGln can exacerbate the severity of HF in rats, and the serum PAGln levels in HF patients were higher than in healthy subjects. Moreover, by using microbial sequencing, we found that DZSM could alter the composition and function of the intestinal microbiota in HF rats, including decreased relative abundance of Turicibacter and Turicibacter_sp.TS3, and regulated the gene expression of PAGln synthesis-related enzymes. Therefore, our findings have contributed novel perspectives on the involvement of DZSM in treating HF, specifically in its regulation of intestinal flora and associated detrimental metabolites. Furthermore, our results have offered empirical evidence supporting the utilization of DZSM as a therapeutic approach for HF.
Subject(s)
Gastrointestinal Microbiome , Heart Failure , Rats , Humans , Animals , Heart Failure/drug therapy , Glutamine/pharmacology , InflammationABSTRACT
Objective: To evaluate the effectiveness of ultrasound-guided injection of botulinum toxin type A (BTX-A) in treating sialorrhea. Methods: We recruited 32 sialorrhea subjects and they received an ultrasound-guided injection of BTX-A. The extent of salivation was evaluated according to the Visual Analog Scale (VAS), Drooling Severity and Frequency Scale (DSFS), and Saliva Flow Rate (SFR). Laryngeal secretions were evaluated based on Fiberoptic Endoscopic Evaluation of Swallowing (FEES) rated according to the Murray Secretion Scale (MSS). We assessed the extent of salivation and laryngeal secretions before injection and at 1, 2, and 4 weeks after injection. Results: The scores for the VAS, DSFS-S, DSFS-F, and DSFS-T decreased significantly at 1, 2, and 4 weeks after injection compared with before injection (p < .05). Based on VAS, the efficacy was substantially higher at 2 and 4 weeks after injection than at 1 week after injection (p < .05). According to DSFS-S and DSFS-T, the efficacy was significantly higher at 4 weeks than at 1 week after injection (p < .05). The SFR and MSS scores at 1 and 2 weeks after injection were superior to those before injection (p < .05). Meanwhile, the SFR score 2 weeks after injection was superior to that 1 week after injection (p < .05). Conclusion: The ultrasound-guided injection of BTX-A can effectively reduce saliva secretion in patients with neurogenic dysphagia. Furthermore, it has the advantages of early onset time and lasting curative effects, which indicates that clinical promotion and application of this technique are justified. Level of Evidence: Level 3.
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Adulteration detection of adding ordinary milk powder to high-end dedicated milk powder is challenging due to the high similarity. Using visible and near-infrared (Vis-NIR) spectroscopy combined with k-nearest neighbor (kNN), the discriminant analysis models of pure brand milk powder and its adulterated milk powder (including unary and binary adulteration) were established. Standard normal variate transformation and Norris derivative filter (D = 2, S = 11, G = 5) were jointly used for spectral preprocessing. The separation degree and separation degree spectrum between two spectral populations were proposed and used to describe the differences between the two spectral populations, based on which, a novel wavelength selection method, named separation degree priority combination-kNN (SDPC-kNN), was proposed for wavelength optimization. SDPC-wavelength step-by-step phase-out-kNN (SDPC-WSP-kNN) models were established to further eliminate interference wavelengths and improve the model effect. The nineteen wavelengths in long-NIR region (1100-2498 nm) with a separation degree greater than 0 were used to establish single-wavelength kNN models, the total recognition-accuracy rates in prediction (RARP) all reached 100%, and the total recognition-accuracy rate in validation (RARV) of the optimal model (1174 nm) reached 97.4%. In the visible (400-780 nm) and short-NIR (780-1100 nm) regions with the separation degree all less than 0, the SDPC-WSP-kNN models were established. The two optimal models (N = 7, 22) were determined, the RARP values reached 100% and 97.4% respectively, and the RARV values reached 96.1% and 94.3% respectively. The results indicated that Vis-NIR spectroscopy combined with few-wavelength kNN has feasibility of high-precision milk powder adulteration discriminant. The few-wavelength schemes provided a valuable reference for designing dedicated miniaturized spectrometer of different spectral regions. The separation degree spectrum and SDPC can be used to improve the performance of spectral discriminant analysis. The SDPC method based on the separation degree priority proposed is a novel and effective wavelength selection method. It only needs to calculate the distance between two types of spectral sets at each wavelength with low computational complexity and good performance. In addition to combining with kNN, SDPC can also be combined with other classifier algorithms (e.g. PLS-DA, PCA-LDA) to expand the application scope of the method.
Subject(s)
Milk , Spectroscopy, Near-Infrared , Animals , Spectroscopy, Near-Infrared/methods , Discriminant Analysis , Milk/chemistry , Powders/analysis , Cluster Analysis , Least-Squares Analysis , Food Contamination/analysisABSTRACT
Poststroke cognitive impairment (PSCI) often occurs during the stroke recovery period and greatly increases the difficulty of rehabilitation. Activation of neuroinflammation and long-term changes in gene expression patterns in the hippocampus could be essential in the development of PSCI. Therefore, this study aimed to identify neuroinflammation and changes in gene expression patterns in the hippocampus in rats with PSCI. Rats underwent transient middle cerebral artery occlusion (tMCAO) or sham surgery. The infarct volume was measured on day 3 after surgery. The Morris water maze (MWM) test was used to assess cognitive function. Microglial activation and white matter (WM) lesions in the hippocampus were evaluated on day 28 after surgery. In addition, we compared differentially expressed genes (DEGs) in the hippocampus between tMCAO group rats and sham group rats by RNA sequencing. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses were conducted to investigate these DEGs. The results showed that the tMCAO group rats showed extensive infarction and cognitive dysfunction compared with the sham group rats. Microglial activation and WM damage were obvious in the hippocampus of tMCAO group rats. We found 43 DEGs by RNA sequencing: 29 genes with upregulated expression and 14 genes with downregulated expression. The GO analysis indicated that DEGs were mainly involved in cell proliferation and differentiation, cholesterol synthesis, and metabolism. The KEGG pathway analysis suggested that the DEGs were significantly enriched in intestinal immune network for IgA production and steroid biosynthesis. Acta2, Calb2, and Cxcl12 were notable in the PPI analysis. Our results suggest that microglial activation and WM damage are maintained in rats with PSCI. The mechanism may be related to the regulation of steroid biosynthesis, intestinal immunity, and potential key genes such as Acta2, Calb2, and Cxcl12 in the hippocampus.
Subject(s)
Cognitive Dysfunction , Neuroinflammatory Diseases , Rats , Animals , Hippocampus/metabolism , Gene Expression , Steroids/metabolismABSTRACT
Current treatments for severe chronic neurogenic dysphagia (SCND) are limited. Modified pharyngeal electrical stimulation (mPES) was modified from pharyngeal electrical stimulation (PES). This prospective study aimed to explore the efficacy and safety of mPES on SCND. 30 patients with severe chronic neurogenic dysphagia were recruited. mPES was administered to patients once daily until the functional oral intake scale score (FOIS) reach 3. Videofluoroscopic swallow study (VFSS), flexible endoscopic evaluation of swallowing (FEES), and high-resolution manometry (HRM) were utilized for evaluating the swallowing function. After mPES, 24 of 30 patients (80%) reached the endpoint (FOIS = 3) (P < 0.001). 3 of 6 tracheotomized patients (50%) removed the tracheal tube. The median number of mPES sessions for the 24 patients who met the criteria was 28 (17, 38) and the median period was 43 (29, 63) days. Moreover, a significant increase was observed in hypopharyngeal peak pressure (P = 0.015), hypopharyngeal contraction duration (P = 0.023), velopharyngeal peak pressure (P = 0.044), and velopharyngeal contraction duration (P = 0.031). A reduction was observed in PAS (P < 0.001), secretion (P = 0.001), vallecular residue (P < 0.001), left (P = 0.001), and right (P < 0.001) pyriform sinus residue. The median FOIS of 30 patients at 3-month follow-up was 5 (3, 6). No serious side effects were reported. mPES is a promising effective and safe therapeutic approach that is simple to use in patients with SCND.
Subject(s)
Deglutition Disorders , Humans , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Prospective Studies , Pharynx , Deglutition/physiology , Electric StimulationABSTRACT
Poststroke cognitive impairment (PSCI) occurs frequently after stroke, but effective treatments are lacking. Previous studies have revealed that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has a beneficial effect on PSCI, but the mechanism is unclear. This study aimed to evaluate the effect of 10 and 20 Hz HF-rTMS on PSCI and the possible mechanisms. An ischemic stroke rat model was established by transient middle cerebral artery occlusion (tMCAO). The modified neurological deficit score (mNSS) and Morris water maze tests were conducted to assess neurological function and cognitive function. Luxol Fast Blue (LFB) staining was performed to evaluate white matter damage. Proinflammatory and anti-inflammatory cytokines were measured using enzyme-linked immunosorbent assays (ELISA). Immunofluorescence was used to assess microglial activation and polarization. Western blotting was performed to measure JAK2-STAT3 pathway-related protein expression. We found that HF-rTMS decreased the neurological deficit score. Compared with 10 Hz HF-rTMS, 20 Hz HF-rTMS more markedly improved the cognitive function of tMCAO rats at day 28 after operation. Furthermore, 20 Hz HF-rTMS attenuates white matter lesion, decreased proinflammatory cytokine levels, and increased anti-inflammatory cytokine levels. It also decreased the number of CD68- and CD16/32-positive microglia and increased the number of CD206-positive microglia. In addition, p-JAK2, JAK2, p-STAT3 and STAT3 expression was increased. These findings suggest that HF-rTMS improves cognitive function and attenuates white matter lesion in tMCAO rats by shifting microglia toward the M2 phenotype. Mechanisms may be related to regulation JAK2-STAT3 pathways.
Subject(s)
Cognitive Dysfunction , White Matter , Rats , Animals , Microglia , Transcranial Magnetic Stimulation , White Matter/pathology , Infarction, Middle Cerebral Artery/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/therapy , Cognitive Dysfunction/metabolism , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolismABSTRACT
Introduction: Modified pharyngeal electrical stimulation (mPES) is a novel therapeutic modality for patients with neurogenic dysphagia. However, the underlying neural mechanism remains poorly understood. This study aimed to use functional near-infrared spectroscopy (fNIRS) to explore the influence of mPES on swallowing-related frequency-specific neural networks and ethology. Methods: Twenty-two healthy right-handed volunteers participated in the study. Each participant was randomly assigned to either the sham or the mPES group and provided a 10-min intervention program every day for 5 days. Oxyhemoglobin and deoxyhemoglobin concentration changes verified by fNIRS were recorded on days 1, 3, and 5. Five characteristic frequency signals (0.0095-2 Hz) were identified using the wavelet transform method. To calculate frequency-specific functional connectivity, wavelet phase coherence (WPCO) was adopted. Furthermore, behavioral performance was assessed pre- and post-mPES using a 150 ml-water swallowing stress test. Results: Compared with sham stimulation on day 1, the significantly decreased WPCO values were mainly associated with the dorsolateral prefrontal lobe, Broca's area, and middle temporal lobe. Compared with the sham mPES on day 1, the mPES showed a noticeable effect on the total swallow duration. Compared with the baseline, the WPCO values on days 3 and 5 showed a stepwise decrease in connectivity with the application of mPES. Furthermore, the decreased WPCO was associated with a shortened time per swallow after mPES. Conclusions: The mPES could modulate swallowing-related frequency-specific neural networks and evoke swallowing cortical processing more efficiently. This was associated with improved performance in a water swallowing stress test in healthy participants.
ABSTRACT
Background: Acquired lymphedema is a common and often severe complication of breast cancer surgery and radiology that seriously affects patients' quality of life. Nevertheless, the pathogenesis for acquired lymphedema is complex and remains unclear. The aim of this study is to find out possible genetic markers and potential drugs for acquired lymphedema. Methods: First, the GSE4333 datasets, which include expression data for six female humanized hairless immunocompetent SKH-1 mice (the condition of whom mimics acquired lymphedema), were reanalyzed. According to the criteria of a fold change (FC) ≥1.4 and an adjusted P value <0.05, we identified the differentially expressed genes (DEGs) between a normal group and the lymphedema group. Next, we analyzed the Gene Ontology (GO) terms and enriched signaling pathways associated with these DEGs with an online tool DAVID. We also constructed protein-protein interaction (PPI) networks and selected meaningful gene modules for additional gene-drug interaction research. Finally, the extant drugs targeting these module genes were identified for further study of their therapeutic effects against acquired lymphedema. Results: A total of 481 DEGs were identified that were closely associated with the immune system, inflammatory response, and extracellular matrix (ECM) structural constituent terms, among others. Moreover, we identified the top 10 significant genes in the PPI networks and identified one extant drug, fiboflapon, that targets the ALOX5AP gene. Conclusions: We ultimately identified 10 hub genes, molecular mechanisms, and one extant drug related to acquired lymphedema. The findings identified targets and a potential drug for further research on acquired lymphedema.
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The identification of high-quality wine brands can avoid adulteration and fraud and protect the rights and interests of producers and consumers. Since the main components of wine are roughly the same, the characteristic components that can distinguish wine brands are usually trace amounts and not unique. The conventional quantitative detection method for brand identification is complicated and difficult. The naive Bayes (NB) classifier is an algorithm based on probability distribution, which is simple and particularly suitable for multiclass discriminant analysis. However, the absorbance probability between spectral wavelengths is not necessarily strongly independent, which limits the application of Bayes method in spectral pattern recognition. This research proposed a Bayes classifier algorithm based on wavelength optimization. First, a large-scale wavelength screening for equidistant combination (EC) was performed, and then wavelength step-by-step phase-out (WSP) was carried out to reduce the correlation between wavelengths and improve the accuracy of Bayes discrimination. The proposed EC-WSP-Bayes method was applied to the 5-category discriminant analysis of wine brand identification based on visible and near-infrared (Vis-NIR) spectroscopy. Among them, four types of wine brands were collected from regular sales channels as identification brands. The fifth type of samples was composed of 21 other commercial brand wines and home-brewed wines from various sources, as the interference brand. The optimal EC-WSP-Bayes model was selected, the corresponding wavelength combination was 404, 600, 992, 2,070, 2,266, and 2,462 nm located in the visible light, shortwave NIR, and combination frequency regions. In modeling and independent validation, the total recognition accuracy rate (RAR Total ) reached 98.1 and 97.6%, respectively. The technology is quick and easy, which is of great significance to regulate the alcohol market. The proposed model of less-wavelength and high-efficiency (N = 6) can provide a valuable reference for small special instruments. The proposed integrated chemometric method can reduce the correlation between wavelengths, improve the recognition accuracy, and improve the applicability of the Bayesian method.
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The identification of soy sauce brands can avoid adulteration and fraud, which is meaningful for food safety screening. Using visible and near-infrared (Vis-NIR) spectroscopy combined with k-nearest neighbor (kNN), the four-category discriminant models of soy sauce brands were established. The soy sauce of three brands (identification) and the other ten brands (interference) were collected, and a total of four categories of samples were obtained. The spectral datasets of two measurement modals (1 mm, 10 mm) were obtained. Based on moving-window (MW) waveband screening and wavelength step-by-step phase-out (WSP), the MW-WSP-kNN algorithm was proposed and applied to the wavelength optimization for the four-category discriminant analysis. Using calibration-prediction-validation experiment design, various high accuracy models with a small number of wavelengths located in NIR region were determined. In the independent validation, for the 1 mm measurement modal, the selected thirty-five dual-wavelength models and one three-wavelength model were located in NIR combined and overtone frequency regions respectively, all achieved 100% total recognition accuracy rate (RARTotal); for the 10 mm measurement modal, the selected seven three-wavelength models located in NIR overtone frequency region all reached more than 96.8% RARTotal, and the optimal RARTotal was 97.8%. The results showed the feasibility of small number of wavelengths' NIR spectroscopy applied to multi-category discriminant of soy sauce brands, with the advantages of rapid, simple and miniaturized. The proposed various small number of wavelengths' models provided a valuable reference for the design of small dedicated spectrometer with different measurement modals. The integrated optimization method and wavelength selection strategy here are also expected to be applied to other fields.
Subject(s)
Soy Foods , Spectroscopy, Near-Infrared , Calibration , Cluster Analysis , Discriminant Analysis , Least-Squares Analysis , Soy Foods/analysis , Spectroscopy, Near-Infrared/methodsABSTRACT
Metabolic inflammation is a crucial factor in the pathogenesis of obesity and promotes related complications. Accumulating evidence has indicated that regulating intestinal integrity and the gut microbiota may be new treatment strategies for metabolic inflammation and obesity. Cordycepin has been reported to improve obesity, but the mechanism is not yet clear. Here, we showed that cordycepin considerably alleviated systemic inflammation while reducing body weight gain and metabolic disorders in Western diet (WD)-fed mice. Further investigations showed that cordycepin significantly ameliorated WD-induced damage to the intestinal barrier and decreased the leakage of lipopolysaccharide (LPS) into the blood in mice by suppressing intestinal inflammation, oxidative stress damage, and decreasing intestinal epithelial cell apoptosis and pyroptosis. In addition, by using metagenomic sequencing, we found that cordycepin could also regulate the homeostasis of intestinal flora, including selectively increasing the abundance of Akkermansia muciniphila and reducing the production of fecal LPS. Besides, we demonstrated that the intestinal flora partially mediated the beneficial effects of cordycepin on improving intestinal barrier function, and obesity-related symptoms in WD-fed mice by a fecal microbiota transplantation experiment. Hence, our findings provided new insights into the role of cordycepin in improving metabolic inflammation and obesity from the perspective of regulating the intestinal barrier function and intestinal flora, and further provided data support for the utility of cordycepin in the treatment of obesity and its complications.
Subject(s)
Gastrointestinal Microbiome , Animals , Deoxyadenosines , Diet, High-Fat/adverse effects , Diet, Western/adverse effects , Inflammation/complications , Inflammation/drug therapy , Lipopolysaccharides/pharmacology , Mice , Mice, Inbred C57BL , Obesity/metabolismABSTRACT
Running wheel exercise training (RWE) and skilled reaching training (SRT) are physical training approaches with positive effects on cognitive function. However, few studies have compared the different effects of these exercises on long-term memory, and their mechanism remains unknown. This study investigated the effects of SRT and RWE, at the recovery stage, on the cognitive function of transient middle cerebral artery occlusion (tMCAO) rats and explored their association with NgR1/Rho-A/ROCK/LOTUS/LGI1 signaling. Adult Sprague-Dawley rats (n = 55) were divided into four groups after pretraining: SRT, RWE, tMCAO, and Sham. Rats were subjected to modified neurological severity score (mNSS) measurements and forelimb grip strength and the Morris water maze tests. Using immunofluorescence and western blotting, we evaluated axonal growth inhibitor expression in the peri-infarct cortex on days 28 and 56 after tMCAO. Results showed the mNSS reduced, whereas the grip strengths improved in RWE and SRT groups. The escape latency in the Morris water maze test was shorter, whereas the number of times of crossing the platform was higher in both the SRT and RWE groups than in the tMCAO group on day 56; furthermore, the parameters in the SRT group improved compared to those in the RWE group. Physical exercise training could improve cognitive functions by reducing the expression of the NgR1/RhoA/ROCK axon growth inhibitors and increasing the expression of the endogenous antagonists LOTUS/LGI1. Exercise training beginning at the recovery stage could improve the cognitive function in tMCAO rats through a mechanism probably associated with the axonal growth inhibitor pathway.
Subject(s)
Axons/metabolism , Cerebral Cortex/metabolism , Cognitive Dysfunction/rehabilitation , Growth Inhibitors/metabolism , Ischemic Stroke/rehabilitation , Physical Conditioning, Animal/physiology , Stroke Rehabilitation , Animals , Behavior, Animal/physiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Disease Models, Animal , Exercise Therapy , Ischemic Stroke/complications , Ischemic Stroke/metabolism , Male , Rats , Rats, Sprague-Dawley , Signal Transduction/physiologyABSTRACT
[This corrects the article DOI: 10.3389/fneur.2022.1006013.].
ABSTRACT
OBJECTIVES: This study aimed to determine the effect of ischemic occlusion duration and recovery time course on motor and cognitive function, identify optimal conditions for assessing cognitive function with minimal interference from motor deficits, and elucidate the underlying mechanism of axonal inhibitors. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly allocated to the transient middle cerebral artery occlusion (tMCAO) 60-min (tMCAO60min), tMCAO90min, tMCAO120min, and sham groups. We conducted forelimb grip strength, two-way shuttle avoidance task, and novel object recognition task (NORT)tests at three time points (14, 21, and 28 days). Expression of Nogo receptor-1 (NgR1), the endogenous antagonist lateral olfactory tract usher substance, ras homolog family member A (Rho-A), and RhoA-activated Rho kinase (ROCK) was examined in the ipsilateral thalamus. RESULTS: There was no difference in grip strength between sham and tMCAO90min rats at 28 days. tMCAO90min and tMCAO120min rats showed lower discrimination indices in the NORT than sham rats on day 28. Compared with that in sham rats, the active avoidance response rate was lower in tMCAO90min rats on days 14, 21, and 28 and in tMCAO120min rats on days 14 and 21. Furthermore, 50-54% of rats in the tMCAO90min group developed significant cognitive impairment on day 28, and thalamic NgR1, RhoA, and ROCK expression were greater in tMCAO90min rats than in sham rats. CONCLUSION: Employing 90-min tMCAO in SD rats and assessing cognitive function 28 days post-stroke could minimize motor dysfunction effects in cognitive function assessments. Axonal inhibitor deregulation could be involved in poststroke cognitive impairment.
ABSTRACT
Poststroke cognitive impairment (PSCI) occurs frequently after stroke, but lacks effective treatments. Previous studies have revealed that high-frequency repetitive transcranial magnetic stimulation (rTMS) has a beneficial effect on PSCI and is often used with other cognitive training methods to improve its effect. This study aimed to evaluate the effect of different combinations of rTMS and cognitive training (rTMS-COG) on PSCI and identify the optimal combination protocol. A cerebral infarction rat model was established by transient middle cerebral artery occlusion (tMCAO). The Morris water maze test was conducted to assess the cognitive function of rats. RNA sequencing and bioinformatics analysis were employed to study the underlying mechanisms. rTMS, COG and rTMS-COG all had beneficial effects on PSCI, while cognitive training immediately after rTMS (rTMS-COG0h) achieved a better effect than cognitive training 1 h and 4 h after rTMS, rTMS and COG. We identified 179 differentially expressed genes (DEGs), including 24 upregulated and 155 downregulated genes, between the rTMS-COG0h and rTMS groups. GO analysis revealed that the major categories associated with the DEGs were antigen procession and presentation, regulation of protein phosphorylation and axoneme assembly. KEGG analysis showed that the DEGs were enriched in processes related to phagosome, circadian entrainment, dopaminergic synapse, apelin signaling pathway, long-term depression, neuroactive ligand-receptor interaction, axon guidance and glucagon signaling pathway. PPI analysis identified Calb2, Rsph1, Ccdc114, Acta2, Ttll9, Dnah1, Dlx2, Dlx1, Ccdc40 and Ccdc113 as related genes. These findings prompt exploration of the potential mechanisms and key genes involved in the effect of rTMS-COG0h on PSCI.