Comparison of the Effects of Prebiotics and Synbiotics Supplementation on the Immune Function of Male University Football Players.

This study was conducted to compare the effects of long-term prebiotic and synbiotic supplementations on the immunosuppression of male football players after daily high-intensity training and a one-time strenuous exercise. A total of 30 male university student-athletes were recruited and randomly assigned to the prebiotic (PG, n = 15) or synbiotic group (SG, n = 15), receiving a prebiotic or synbiotic once per day for six weeks. Physiological assessments were conducted by a maximal oxygen uptake (VO2max) test and an exhaustive constant load exercise (75% VO2max test). Inflammatory cytokine and secretory immunoglobulin A (SIgA) were measured. VO2max, maximal heart rate (HRmax), and lactic acid elimination rate (ER) were used to evaluate aerobic capacity. Upper respiratory tract infection (URTI) complaints were evaluated using a questionnaire. URTI incidence and duration were significantly lower in the SG group than that in the PG group (p < 0.05). At baseline, SIgA and interleukin-1ß (IL-1ß) levels in the SG group (p < 0.01) as well as IL-1ß and IL-6 in the PG group (p < 0.05) were significantly increased, and IL-4 concentration was markedly reduced in the PG group (p < 0.01). The concentrations of IL-4, IL-10 and transforming growth factor-ß1 (TGF-ß1) were significantly reduced in the PG and SG group immediately after the constant load exercise. Significantly decreased HRmax and enhanced ER (increased by 193.78%) were detected in the SG group, not in the PG group, during the constant load experiment (p < 0.05) and the recovery period (p < 0.01), respectively. However, VO2max value was not changed. These data suggest that synbiotic supplementation for six weeks has a more positive effect than prebiotics on the immune function and athletic performance of male university football players.

Ultrasound-mediated piezoelectric nanoparticle modulation of intrinsic cardiac autonomic nervous system for rate control in atrial fibrillation.

Rate control is a cornerstone of atrial fibrillation treatment. Barium titanate nanoparticles (BTNPs) are piezoelectric nanomaterials that can generate local electromagnetic fields under ultrasound activation, stimulating nearby neuronal tissue. This study aimed to modulate the inferior right ganglionated plexus (IRGP) of the heart and reduce the ventricular rate during rapid atrial pacing (RAP)-induced atrial fibrillation using ultrasound-mediated BTNPs. Adult male beagles were randomly divided into a phosphate-buffered saline (PBS) group (n = 6) and a BTNP group (n = 6). PBS or nanoparticles were injected into the IRGP of both groups before RAP. The biological safety of the material was evaluated according to electrophysiology recordings, thermal effects and level of inflammation. Compared to the PBS group, the BaTiO3 piezoelectric nanoparticle group had reduced ventricular rates in the sinus rhythm and atrial fibrillation models after stimulating the IRGP by applying ultrasound. In addition, transient stimulation by BTNPs did not lead to sustained neuronal excitation in the IRGP. The activation of the BTNPs did not induce inflammation or thermal damage effects in the IRGP. Ultrasound-mediated BTNP neuromodulation can significantly reduce the ventricular rate by stimulating the IRGP. Thus, ultrasound-mediated BTNP neuromodulation is a potential therapy for atrial fibrillation rate control.

Modeling the effects of vaccination, nucleic acid testing, and face mask wearing interventions against COVID-19 in large sports events.

The transmission of SARS-CoV-2 leads to devastating COVID-19 infections around the world, which has affected both human health and the development of industries dependent on social gatherings. Sports events are one of the subgroups facing great challenges. The uncertainty of COVID-19 transmission in large-scale sports events is a great barrier to decision-making with regard to reopening auditoriums. Policymakers and health experts are trying to figure out better policies to balance audience experiences and COVID-19 infection control. In this study, we employed the generalized SEIR model in conjunction with the Wells-Riley model to estimate the effects of vaccination, nucleic acid testing, and face mask wearing on audience infection control during the 2021 Chinese Football Association Super League from 20 April to 5 August. The generalized SEIR modeling showed that if the general population were vaccinated by inactive vaccines at an efficiency of 0.78, the total number of infectious people during this time period would decrease from 43,455 to 6,417. We assumed that the general population had the same odds ratio of entering the sports stadiums and becoming the audience. Their infection probabilities in the stadium were further estimated by the Wells-Riley model. The results showed that if all of the 30,000 seats in the stadium were filled by the audience, 371 audience members would have become infected during the 116 football games in the 2021 season. The independent use of vaccination and nucleic acid testing would have decreased this number to 79 and 118, respectively. The combined use of nucleic acid testing and vaccination or face mask wearing would have decreased this number to 14 and 34, respectively. The combined use of all three strategies could have further decreased this number to 0. According to the modeling results, policymakers can consider the combined use of vaccination, nucleic acid testing, and face mask wearing to protect audiences from infection when holding sports events, which could create a balance between audience experiences and COVID-19 infection control.

Effect of Protein Nutrition Level on Protein Metabolism during Volleyball Exercise Based on Edge Computing in the Medical System.

With the rapid development of the Internet of Things, 5G, and communication technologies, the growth of various types of data has shown an exponential trend. Edge computing technology provides users with almost unlimited computing power through a large number of high-performance servers in the data center. It is one of the important solutions for big data analysis and processing. Volleyball has caused a great wave in China as early as the 1960s, but people pay little attention to the physical quality of volleyball players. At the same time, in the medical field, it is difficult to give a clear value to the athlete's protein requirement. Therefore, this article aims to observe the specific values of protein metabolism in volleyball at different levels of protein nutrition. By designing controlled experiments, then these rats under three nutrient levels of protein were observed and protein metabolism was analyzed after volleyball. The results of the study show that volleyball exercise can reduce the nitrogen balance and gastrocnemius nitrogen content. The nitrogen balance of the 17% group decreased from 388 mg/day before exercise to 336 mg/day, and the gastrocnemius nitrogen content decreased by up to 5.2%; serum urea nitrogen concentration and liver nitrogen content are increased, indicating the enhancement of protein catabolism. Different protein nutrition levels have different effects on protein metabolism during volleyball. The protein intake level of 17% is more conducive to resist the protein decomposition caused by volleyball. It can be seen that, based on edge computing technology, the influence factors of protein nutrition level on protein metabolism during volleyball sports can be well explored, and the research results are also very valuable.

Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson's Disease Rats.

The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating α7 nicotinic receptor (α7nAChR) on macrophages. Parkinson's disease (PD) patients and PD rats with substantia nigra (SN) lesions exhibit gastroparesis and a decayed vagal pathway. To investigate whether activating α7nAChR could ameliorate inflammation and gastric dysmotility in PD rats, ELISA, western blot analysis, and real-time PCR were used to detect gastric inflammation. In vitro and in vivo gastric motility was investigated. Proinflammatory mediator levels and macrophage numbers were increased in the gastric muscularis of PD rats. α7nAChR was located on the gastric muscular macrophages of PD rats. The α7nAChR agonists PNU-282987 and GTS-21 decreased nuclear factor κB (NF-κB) activation and monocyte chemotactic protein-1 mRNA expression in the ex vivo gastric muscularis of PD rats, and these effects were abolished by an α7nAChR antagonist. After treatment with PNU-282987 in vivo, the PD rats showed decreased NF-κB activation, inflammatory mediator production, and contractile protein expression and improved gastric motility. The present study reveals that α7nAChR is involved in the development of gastroparesis in PD rats and provides novel insight for the treatment of gastric dysmotility in PD patients.

Nabe: an energetic database of amino acid mutations in protein-nucleic acid binding interfaces.

Protein-nucleic acid complexes play essential roles in regulating transcription, translation, DNA replication, repair and recombination, RNA processing and translocation. Site-directed mutagenesis has been extremely useful in understanding the principles of protein-DNA and protein-RNA interactions, and experimentally determined mutagenesis data are prerequisites for designing effective algorithms for predicting the binding affinity change upon mutation. However, a vital challenge in this area is the lack of sufficient public experimentally recognized mutation data, which leads to difficulties in developing computational prediction methods. In this article, we present Nabe, an integrated database of amino acid mutations and their effects on the binding free energy in protein-DNA and protein-RNA interactions for which binding affinities have been experimentally determined. Compared with existing databases and data sets, Nabe is the largest protein-nucleic acid mutation database, containing 2506 mutations in 473 protein-DNA and protein-RNA complexes, and of that 1751 are alanine mutations in 405 protein-nucleic acid complexes. For researchers to conveniently utilize the data, Nabe assembles protein-DNA and protein-RNA benchmark databases by adopting the data-processing procedures in the majority of models. To further facilitate users to query data, Nabe provides a searchable and graphical web page. Database URL: http://nabe.denglab.org.

PMDFI: Predicting miRNA-Disease Associations Based on High-Order Feature Interaction.

MicroRNAs (miRNAs) are non-coding RNA molecules that make a significant contribution to diverse biological processes, and their mutations and dysregulations are closely related to the occurrence, development, and treatment of human diseases. Therefore, identification of potential miRNA-disease associations contributes to elucidating the pathogenesis of tumorigenesis and seeking the effective treatment method for diseases. Due to the expensive cost of traditional biological experiments of determining associations between miRNAs and diseases, increasing numbers of effective computational models are being used to compensate for this limitation. In this study, we propose a novel computational method, named PMDFI, which is an ensemble learning method to predict potential miRNA-disease associations based on high-order feature interactions. We initially use a stacked autoencoder to extract meaningful high-order features from the original similarity matrix, and then perform feature interactive learning, and finally utilize an integrated model composed of multiple random forests and logistic regression to make comprehensive predictions. The experimental results illustrate that PMDFI achieves excellent performance in predicting potential miRNA-disease associations, with the average area under the ROC curve scores of 0.9404 and 0.9415 in 5-fold and 10-fold cross-validation, respectively.

Enhanced Contractive Tension and Upregulated Muscarinic Receptor 2/3 in Colorectum Contribute to Constipation in 6-Hydroxydopamine-Induced Parkinson's Disease Rats.

Constipation and defecatory dysfunctions are frequent symptoms in patients with Parkinson's disease (PD). The pathology of Lewy bodies in colonic and rectal cholinergic neurons suggests that cholinergic pathways are involved in colorectal dysmotility in PD. However, the underlying mechanism is unclear. The aim of the present study is to examine the effect of central dopaminergic denervation in rats, induced by injection 6-hydroxydopamine into the bilateral substania nigra (6-OHDA rats), on colorectal contractive activity, content of acetylcholine (ACh), vasoactive intestinal peptide (VIP) and expression of neural nitric oxide synthase (nNOS) and muscarinic receptor (MR). Strain gauge force transducers combined with electrical field stimulation (EFS), gut transit time, immunohistochemistry, ELISA, western blot and ultraperformance liquid chromatography tandem mass spectrometry were used in this study. The 6-OHDA rats exhibited outlet obstruction constipation characterized by prolonged transit time, enhanced contractive tension and fecal retention in colorectum. Pretreatment with tetrodotoxin significantly increased the colorectal motility. EFS-induced cholinergic contractions were diminished in the colorectum. Bethanechol chloride promoted colorectal motility in a dose-dependent manner, and much stronger reactivity of bethanechol chloride was observed in 6-OHDA rats. The ACh, VIP and protein expression of nNOS was decreased, but M2R and M3R were notably upregulated in colorectal muscularis externa. Moreover, the number of cholinergic neurons was reduced in sacral parasympathetic nucleus (SPN) of 6-OHDA rats. In conclusion, central nigrostriatal dopaminergic denervation is associated with decreased cholinergic neurons in SPN, decreased ACh, VIP content, and nNOS expression and upregulated M2R and M3R in colorectum, resulting in colorectal dysmotility, which contributes to outlet obstruction constipation. The study provides new insights into the mechanism of constipation and potential therapeutic targets for constipation in PD patients.

[Source, metabolism and function of dopamine in digestive tract].

Dopamine (DA), as a catecholamine neurotransmitter widely distributed in the central nervous system and the peripheral tissues, has attracted a lot of attention. Especially in recent years, DA has been found to regulate the function of the immune system, and the involvement of DA in the intestinal mucosal inflammation-related diseases has become a hot research topic. The digestive tract is an important source of peripheral DA, and DA is not only produced in the enteric nervous system and gastrointestinal epithelium, but also produced by intestinal microorganisms. In addition to the synthetases of DA, the DA contents in body tissues are also affected by the two kinds of metabolic enzymes, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). This article reviewed the sources, metabolism, and functions of DA in digestive tract, especially focusing on the distribution and function of MAO and COMT, the enzymes degrading DA.

Eccentric exercise and dietary restriction inhibits M1 macrophage polarization activated by high-fat diet-induced obesity.

AIMS: Obesity induce low-grade inflammation and elicit insulin resistance (IR), exercise training accompanied by a low-fat diet has been prescribed as part of the treatment for managing obesity and IR. The purpose of this study is to evaluate the effect of eccentric exercise accompanied by a low-fat diet on glycolipid metabolism, exercise capacity, and macrophage polarization in obesity-induced IR mice. MATERIALS AND METHODS: Mice were fed with 60% high fat diet (HFD) for 12 weeks and subsequently treated with eccentric exercise or/and dietary restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the ability of glycolipid metabolism. Exercise capacity was measured to verify the results of biochemical index. At 12 weeks and 12 + 8 weeks, infiltration was observed by H&E staining in adipose tissue, and macrophage polarization was detected by Immunofluorescence staining and ELISA. KEY FINDING: 1) obesity-induced IR model was established by HFD fed for 12 weeks accompanied by impaired exercise ability and increased M1 macrophage, 2) eccentric exercise accompanied by a low-fat diet markedly rescued obesity-induced IR and improved exercise capacity, 3) eccentric exercise accompanied by a low-fat diet markedly inhibited M1 macrophage polarization and activated M2 macrophage. SIGNIFICANCE: Eccentric exercise accompanied by a low-fat diet rescued obesity-induced IR and improved exercise capacity, which were associated with the inhibition of M1 macrophage polarization and the activation of M2 macrophage. These indicate that macrophage polarization provides the potential target of intervention for inflammation and IR in obesity.

MADOKA: an ultra-fast approach for large-scale protein structure similarity searching.

BACKGROUND: Protein comparative analysis and similarity searches play essential roles in structural bioinformatics. A couple of algorithms for protein structure alignments have been developed in recent years. However, facing the rapid growth of protein structure data, improving overall comparison performance and running efficiency with massive sequences is still challenging. RESULTS: Here, we propose MADOKA, an ultra-fast approach for massive structural neighbor searching using a novel two-phase algorithm. Initially, we apply a fast alignment between pairwise structures. Then, we employ a score to select pairs with more similarity to carry out a more accurate fragment-based residue-level alignment. MADOKA performs about 6-100 times faster than existing methods, including TM-align and SAL, in massive alignments. Moreover, the quality of structural alignment of MADOKA is better than the existing algorithms in terms of TM-score and number of aligned residues. We also develop a web server to search structural neighbors in PDB database (About 360,000 protein chains in total), as well as additional features such as 3D structure alignment visualization. The MADOKA web server is freely available at: http://madoka.denglab.org/ CONCLUSIONS: MADOKA is an efficient approach to search for protein structure similarity. In addition, we provide a parallel implementation of MADOKA which exploits massive power of multi-core CPUs.

Dopamine promotes colonic mucus secretion through dopamine D5 receptor in rats.

Dopamine regulates gastrointestinal mucosal barrier. Mucus plays important roles in the protection of intestinal mucosa. Here, the regulatory effect of dopamine on rat colonic mucus secretion was investigated. RT-PCR, immunofluorescence, Periodic Acid-Schiff reagent assay, Alcian blue-Periodic Acid-Schiff staining, and enzyme-linked immunosorbent assay were used to observe the expression of dopamine receptor and the direct effect of dopamine on the colonic mucus. Mice injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) destroying enteric dopamine (DA) neurons, rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra damaging central dopaminergic neurons, and dopamine D5 receptor-downregulated transgenic mice were used to detect the effect of endogenous enteric dopamine or dopamine receptors on distal colonic mucus. Our results indicated that D5 immunoreactivity was widely distributed on the colonic goblet cells. Dopamine dose-dependently increased rat distal colonic mucus secretion in vitro. D1-like receptor antagonist SCH23390 inhibited dopamine (1 µΜ)-induced distal colonic mucus secretion. D1-like receptor agonist SKF38393 promoted mucin 2 (MUC2) secretion and increased the intracellular cAMP level of colonic mucosa. D5 receptor-downregulated transgenic mice showed a decreased colonic MUC2 content. MPTP-treated mice exhibited lower colonic dopamine content and decreased colonic mucus content. 6-OHDA rats had an increase in the dopamine content in colonic mucosa but decreases in the protein levels of D1 and D5 receptors and MUC2 content in the colonic mucosa. These findings reveal that dopamine is able to promote distal colonic mucus secretion through the D5 receptor, which provides important evidence to better understand the possible role of dopamine in the colonic mucosal barrier.

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease.

AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The ß2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The ß2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.

Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine-induced Parkinson's disease rats.

Constipation is common in Parkinson's disease (PD), in which monoamines (dopamine [DA], norepinephrine [NE], and 5-hydroxytryptamine [5-HT]) play an important role. Rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra (SN) exhibit constipation, but the role of monoamines and their receptors is not clear. In the present study, colonic motility, monoamine content, and the expression of monoamine receptors were examined using strain gauge force transducers, ultraperformance liquid chromatography tandem mass spectrometry, immunofluorescence, and Western blot. The 6-OHDA rats displayed a significant reduction in dopaminergic neurons in the SN and a decreased time on rota-rod test and a marked decrease in daily fecal production and fecal water content. The amplitude of colonic spontaneous contraction was obviously decreased in 6-OHDA rats. Blocking D1-like receptor and ß3-adrenoceptor (ß3-AR) significantly reduced the inhibition of DA and NE on the colonic motility, respectively, whereas the 5-HT and 5-HT4 receptor agonists promoted the colonic motility. Moreover, DA content was increased in the colonic muscularis externa of 6-OHDA rats. The protein expression of ß3-ARs was notably upregulated, but 5-HT4 receptors were significantly decreased in the colonic muscularis externa of 6-OHDA rats. We conclude that enhanced DA and ß3-ARs and decreased 5-HT4 receptors may be contributed to the colonic dysmotility and constipation observed in 6-OHDA rats.