NLRP3-dependent pyroptosis exacerbates coxsackievirus A16 and coxsackievirus A10-induced inflammatory response and viral replication in SH-SY5Y cells.

Coxsackievirus A16 (CV-A16) and coxsackievirus A10 (CV-A10), more commonly etiological agents of hand, foot and mouth disease (HFMD), are capable of causing severe neurological syndromes with high fatalities, but their neuropathogenesis has rarely been studied. Mounting evidence indicated that pyroptosis is an inflammatory form of cell death that might be widely involved in the pathogenic mechanisms of neurotropic viruses. Our study was designed to examine the effects of NLRP3-mediated pyroptosis in CV-A16- and CV-A10-induced inflammatory neuropathologic formation. In this work, it was showed that SH-SY5Y cells were susceptible to CV-A16 and CV-A10, and meanwhile their infections could result in a decreasing cell viability and an increasing LDH release as well as Caspase1 activation. Moreover, CV-A16 and CV-A10 infections triggered NLRP3-mediated pyroptosis and promoted the release of inflammatory cytokines. Additionally, activated NLRP3 accelerated the pyroptosis formation and aggravated the inflammatory response, but inhibited NLRP3 had a dampening effect on the above situation. Finally, it was further revealed that NLRP3 agonist enhanced the viral replication, but NLRP3 inhibitor suppressed the viral replication, suggesting that NLRP3-driven pyroptosis might support CV-A16 and CV-A10 production in SH-SY5Y cells. Together, our findings demonstrated a mechanism by which CV-A16 and CV-A10 induce inflammatory responses by evoking NLRP3 inflammasome-regulated pyroptosis, which in turn further stimulated the viral replication, providing novel insights into the pathogenesis of CV-A16 and CV-A10 infections.

Elucidating salt-reduction mechanisms of aroma-active compounds from yeast extracts through sensomics approaches and electroencephalography.

This study investigated the savory intensity of aroma-active compounds derived from yeast extract Maillard reaction models. Sensory evaluation results revealed that beef flavoring model (28.00 g) exhibited the highest savory perception intensity when the yeast extract FA34 (0.50 g) the added. Eleven aroma-active compounds associated with saltiness perception were identified via solid-phase microextraction and extraction combined with gas chromatography-mass spectrometry/olfactory. The odorant-NaCl mixture model and saltiness intensity evaluation results revealed that thiazole and 4-methylpentanoic acid could significantly (p < 0.05) enhance the saltiness perception of salt solution (5.00 g/L), 2-methylpyrazine, 2-methyl-3-furanthiol, 2,6-dimethylpyrazine, furfuryl mercaptan, and methyl 2-methyl-3-furyl disulfide could significantly (p < 0.01) enhance the saltiness perception of a salt solution (5.00 g/L). Electroencephalography revealed that the main mechanisms underlying aroma-induced saltiness perception enhancement included the strengthening of the saltiness perception signal and prolonging signal stimulation time in the frontal regions of the cerebral cortex.

Decoding the Effect of Running on Flavor Perception Changes during Consumption of Sports Drinks.

An online survey was conducted to show that most respondents preferred sports drinks with sweet and fruity characteristics. Eleven sports drinks with higher consumers' preferences were further selected for aroma and taste evaluation. Temporal dominance of sensations analysis showed that fruity and fresh attributes were dominant, while sour and fruity sweet were dominant tastes during consumption. ß-Damascenone, ß-ionone, and linalool contributing to floral perception, γ-decalactone, ethyl cinnamate, and isoamyl acetate contributing to fruity perception, and menthol contributing to fresh perception were confirmed by odor activity value analysis. Running affected the nasal air flow and the saliva secretion, resulting in the flavor perception changing from fruity sweet, sweet, and fruity to sour because the recognition threshold decreased for sweet, fruity, floral, and fresh flavors and increased for saltiness, astringency, and sour tastes.

Electronic tongue, proton-transfer-reaction mass spectrometry, spectral analysis, and molecular docking characterization for determining the effect of α-amylase on flavor perception.

The effects of α-amylase on of flavor perception were investigated via spectrum analysis, electronic tongue, on-line mass spectrometry, and molecular docking. Aroma release results showed that α-amylase exhibited variable release patterns of different aroma compounds. Electronic tongue analysis showed that the perception of bitterness, sweetness, sour, and saltiness was subtly increased and that of umami was significantly increased (p < 0.01) along with the increasing enzyme activity of α-amylase. Ultraviolet absorption and fluorescence spectroscopy analyses showed that static quenching occurred between α-amylase and eight flavor compounds and their interaction effects were spontaneous. One binding pocket was confirmed between the α-amylase and flavor compounds, and molecular docking simulation results showed that the hydrogen, electrostatic, and hydrophobic bonds were the main force interactions. The TYP82, TRP83, LEU173, HIS80, HIS122, ASP297, ASP206, and ARG344 were the key α-amylase amino acid residues that interacted with the eight flavor compounds.

Decoding the Different Aroma-Active Compounds in Soy Sauce for Cold Dishes via a Multiple Sensory Evaluation and Instrumental Analysis.

Screening the suitability of soy sauce for specific cooking methods from various products is beneficial for the fine development of the soy sauce industry. Multiple sensory evaluation and gas chromatography-mass spectrometry/olfactometry (GC-MS/O) analysis were combined to decode the suitability of soy sauces for cold dishes and characterize their differential aroma-active compounds. Thirty-two kinds of soy sauce with 42 sensory descriptors were determined via a check-all-that-apply analysis, and werefurther classified into six categories via a cluster analysis. The sensory evaluation results showed that seven soy sauce samples had the highest acceptance in each category. Solid-phase microextraction and solid phase extraction results combined with the GC-MS/O analysis results showed that a total of 38 aroma-active compounds were identified in seven soy sauce samples, among which 2-methoxy-phenol (6-93), ethyl acetate (2-48), 3-methyl-1-butanol (4-30), 3-methyl-butanal (5-24), methional (0-22), dimethyl trisulfide (5-19) and dimethyl disulfide (0-8) showed a higher relative odor activity value (ROAV). A partial least squares regression prediction combined with additional tests further confirmed that 2,5-dimethyl-pyrazine; 2,6-dimethyl-pyrazine; and 2-ethyl-6-methyl-pyrazine significantly contributed to the roasted attributes, methional significantly contributed to the sauce-like notes, ethanol significantly contributed to the alcoholic notes and 2-methoxy-phenol significantly contributed to the smoky notes. 2,5-Dimethyl-pyrazine; methional; 2,6-dimethyl-pyrazine and 2-ethyl-6-methyl-pyrazine significantly contributed to the caramel-like attributes.

The neuropathological mechanism of EV-A71 infection attributes to inflammatory pryoptosis and viral replication via activating the hsa_circ_0045431/ hsa_miR_584/NLRP3 regulatory axis.

Neuropathological damage has been considered to be the main cause of death from EV-A71 infection, but the underlying mechanism has not been elucidated. Pyroptosis, a new form of inflammatory programmed cell death, has been verified to be involved in the pathogenesis of various viruses. circRNAs are a novel type of endogenous noncoding RNA gaining research interest in recent years, especially their special roles in the process of virus infection. Thus, in this study, we combined EV-A71, pyroptosis and circRNA to find a breakthrough in the pathogenesis of EV-A71 infection. Firstly, whether EV-A71 infection leaded to pyroptosis formation was examined by a series detection of cell death, cell viability, LDH release, caspase 1 activity, the expression levels of pyroptosis-related molecules and the concentrations of IL-1ß and IL-18. Secondly, high-throughput sequencing of circRNAs was carried out to excavate the circRNA-miRNA-mRNA regulatory axis which might be associated with pyroptosis formation. Finally, the gain- and loss-of-functional experiments were further conducted to identify their functions. Our results showed that EV-A71 infection caused pyroptosis formation in SH-SY5Y cells. The circRNA sequencing analyzed the differentially expressed circRNAs and their possible functions. It was found that the hsa_circ_0045431/hsa_miR_584/NLRP3 regulatory axis might be involved in pyroptosis formation during EV-A71 infection. Then, hsa_circ_0045431 sponged hsa_miR_584 and hsa_miR_584 directly targeted NLRP3 were validated by IF, dual-luciferase, qRT-PCR and WB assays. Functional experiments were performed to further uncover that the up-regulation of hsa_circ_0045431 and NLRP3 promoted the inflammatory pyroptosis and viral replication, while the up-regulation of hsa_miR_584 suppressed the inflammatory pyroptosis and viral replication, and vice versa. Collectively, our study demystified that EV-A71 infection induced pyroptosis formation by activating hsa_circ_0045431/hsa_miR_584/NLRP3 regulatory axis, which could further effect viral replication. These findings provided novel insights into the pathogenesis of EV-A71 infection, and meanwhile revealed that the hsa_circ_0045431/ hsa_miR_584/NLRP3 regulatory axis can serve as a potential biological therapeutic target for EV-A71 infection.

Characterization of the Key Aroma Compounds in Different Yeast Proteins by GC-MS/O, Sensory Evaluation, and E-Nose.

The unique odors of yeast proteins (YPs) are decisive for their application in meat substitutes. Sensory evaluation, electronic nose, and gas chromatography-mass spectrometry/olfactory (GC-MS/O) were combined to characterize the aroma profiles and aroma-active compounds of YPs. The sensory evaluation results indicate that the sweaty aroma had the strongest intensity in YP #10, followed by rice bran, sour, and plastic. The electronic nose could effectively distinguish the aroma differences among five YPs. A total of 27 aroma-active compounds in the five YPs were identified by GC-MS/O. The concentration of 2-methyl-propanoic acid (6.37 µg/kg), butanoic acid (47.46 µg/kg), 3-methyl-butanoic acid (22.50 µg/kg), and indole (943.40 µg/kg) in YP #10's aroma was higher than that of the other YPs. The partial least squares regression method results show that o-cresol, (3S)-3,7-dimethyloct-7-en-1-ol, benzyl alcohol, octanal, 2-methyl-propanoic acid, butanoic acid, 3-methyl-butanoic acid, hexanal, heptanal, and indole were predicted as the potential aroma-active compounds significantly contributing to the aroma profiles of the five YPs. Addition experiments confirmed that the overall aroma profile intensities of the five YP samples were extended with the addition of these ten compounds, verifying their significant contributions.

Molecular mechanisms of caramel-like odorant-olfactory receptor interactions based on a computational chemistry approach.

Molecular mechanisms of caramel-like odorant-olfactory receptor interactions were investigated based on molecular docking and molecular dynamics simulations. The transmembrane regions TM-3, TM-5 and TM-6 of receptors were main contributors of amino acid residues in the docking. Molecular docking results showed that hydrogen bonding and pi-pi stacking were the key forces for the stabilization of caramel-like odorants. The binding energies were positively correlated with the molecular weight of caramel-like odorants. Residues Asn155 (84%, OR2W1), Asn206 (86%, OR8D1), Ser155 (77%, OR8D1), Asp179 (87%, OR5M3), Val182 (84%, OR2J2) and Tyr260 (94%, OR2J2) with high frequencies played an important role in the complexes formation. Odorants 4-hydroxy-5-methylfuran-3(2H)-one (16#) and methylglyoxal (128#) were screened by molecular field-based similarity analysis, which tended to bind to the receptors OR1G1 and OR52H1 respectively, resulting a caramel-like aroma perception. The obtained results are useful for better understanding the perception of caramel-like odorants and their high-throughput screening.

Identification of Novel Umami Peptides in Chicken Breast Soup through a Sensory-Guided Approach and Molecular Docking to the T1R1/T1R3 Taste Receptor.

Ultrafiltration combined with nanoliquid chromatography quadrupole time-of-flight mass spectrometry (nano-LC-QTOF-MS) and sensory evaluation was used to separate and identify umami peptides in chicken breast soup. Fifteen peptides with umami propensity scores of >588 were identified from the fraction (molecular weight ≤1 kDa) using nano-LC-QTOF-MS, and their concentrations ranged from 0.02 ± 0.01 to 6.94 ± 0.41 µg/L in chicken breast soup. AEEHVEAVN, PKESEKPN, VGNEFVTKG, GIQKELQF, FTERVQ, and AEINKILGN were considered as umami peptides according to sensory analysis results (detection threshold: 0.18-0.91 mmol/L). The measurement of point of subjective equality showed that these six umami peptides (2.00 g/L) were equivalent to 0.53-0.66 g/L of monosodium glutamate (MSG) in terms of umami intensity. Notably, the sensory evaluation results showed that the peptide of AEEHVEAVN significantly enhanced the umami intensity of the MSG solution and chicken soup models. The molecular docking results showed that the serine residues were the most frequently observed binding sites in T1R1/T1R3. The binding site Ser276 particularly contributed to the formation of the umami peptide-T1R1 complexes. The acidic glutamate residues observed in the umami peptides were also involved in their binding to the T1R1 and T1R3 subunits.

Decoding the Effect of Age on the Taste Perception of Chicken Breast Soup Based on LC-QTOF-MS/MS Combined with a Chemometric Approach.

A nontargeted fingerprinting approach combined with the chemometrics method and sensory analysis was used to assess the differences in taste-chemical compositions of chicken breast soup with different ages and their sensory qualities. The sensory evaluation results showed that the overall taste as well as the sourness, saltiness, and umami scores of the soup were increased with the age of chicken. Fifty-nine compounds were identified from four soup samples by liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS), and their total content was the highest in the 90 wk soup samples. Six upregulated compounds (carnosine, hypoxanthine, inosine, inosine 5'-monophosphate (5'-IMP), adenosine 5'-monophosphate (5'-AMP), and lactic acid) were identified as potential contributors to the taste characteristics of the 90 wk soup samples by orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Additional experiments showed that 5'-AMP particularly contributed to the sourness of the soup, while carnosine contributed to the saltiness and umami of the soup.

Development of an Effective Protocol for Evaluating the Saltiness Intensity Enhancement of Umami Compounds.

Reducing sodium intake without decreasing saltiness perception remains an important target in the food industry. This study developed an effective protocol for evaluating the saltiness perception enhanced by umami compounds. Two sodium chloride solutions (2.00 and 6.00 g/L) were the preferred concentrations for consumers. Two-alternative forced-choice evaluation results confirmed that at a concentration of 2.00 g/L (sodium concentration), the highest replacement ratios of monosodium glutamate and l-alanine (Ala) were 10 and 20% in sodium chloride solution without saltiness intensity decrease, respectively. The highest replacement ratios of l-glycine (Gly) and Ala were 10 and 20% compared to 6.00 g/L, respectively. Temporal dominance of sensations analysis figured out that gum Arabic (GA) could compensate for the decrease of the retention time and increase the overall saltiness perception in the sodium-reduced sample. Quartz crystal microbalance with dissipation results showed that Ala and Gly could inhibit the binding of Na+ to mucin, thereby increasing the saltiness perception. GA exhibited the best saltiness enhancement effect in sodium-reduced solution by producing the nanoparticles from GA, decreasing the stability of the solution system, enhancing the loading effect of mucin on Na+, and prolonging the saltiness perception.

Decoding of the Saltiness Enhancement Taste Peptides from the Yeast Extract and Molecular Docking to the Taste Receptor T1R1/T1R3.

The development of saltiness or saltiness enhancement peptides is important to decrease the dietary risk factor of high sodium. Taste peptides in the yeast extract were separated by ultrafiltration and subsequently identified by UPLC-Q-TOF-MS/MS. The 377 identified peptides were placed into the umami receptor T1R1/T1R3. The results showed that eight taste peptides with higher binding energies were screened by molecular virtual docking, and the results revealed that Asp218, Ser276, and Asn150 of T1R1 play key roles in umami docking of peptides. The taste characteristic description and saltiness enhancement effect results suggested that PKLLLLPKP (sourness and umami, 0.18 mM), GGISTGNLN (sourness, 0.59 mM), LVKGGLIP (umami, 0.28 mM), and SSAVK (umami, 0.35 mM) had higher saltiness enhancement effects. The sigmoid curve analysis further confirmed that the taste detection threshold of the GGISTGNLN in the peptide and salt model (157.47 mg/L) was lower than 320.99 mg/L and exhibited a synergistic effect on saltiness perception, whereas SSAVK, PKLLLLPKP, and LVKGGLIP exhibited additive effects on the saltiness perception. This work also corroborated previous research, which indicated that the sourness and umami taste attributes could enhance the saltiness perception.

Recent Progress in the Study of Taste Characteristics and the Nutrition and Health Properties of Organic Acids in Foods.

Organic acids could improve the food flavor, maintain the nutritional value, and extend the shelf life of food. This review summarizes the detection methods and concentrations of organic acids in different foods, as well as their taste characteristics and nutritional properties. The composition of organic acids varies in different food. Fruits and vegetables often contain citric acid, creatine is a unique organic acid found in meat, fermented foods have a high content of acetic acid, and seasonings have a wide range of organic acids. Determination of the organic acid contents among different food matrices allows us to monitor the sensory properties, origin identification, and quality control of foods, and further provides a basis for food formulation design. The taste characteristics and the acid taste perception mechanisms of organic acids have made some progress, and binary taste interaction is the key method to decode multiple taste perception. Real food and solution models elucidated that the organic acid has an asymmetric interaction effect on the other four basic taste attributes. In addition, in terms of nutrition and health, organic acids can provide energy and metabolism regulation to protect the human immune and myocardial systems. Moreover, it also exhibited bacterial inhibition by disrupting the internal balance of bacteria and inhibiting enzyme activity. It is of great significance to clarify the synergistic dose-effect relationship between organic acids and other taste sensations and further promote the application of organic acids in food salt reduction.

Recent trends in aroma release and perception during food oral processing: A review.

The dynamic and complex peculiarities of the oral environment present several challenges for controlling the aroma release during food consumption. They also pose higher requirements for designing food with better sensory quality. This requires a comprehensive understanding of the basic rules of aroma transmission and aroma perception during food oral processing and its behind mechanism. This review summarized the latest developments in aroma release from food to retronasal cavity, aroma release and delivery influencing factors, aroma perception mechanisms. The individual variance is the most important factor affecting aroma release and perception. Therefore, the intelligent chewing simulator is the key to establish a standard analytical method. The key odorants perceived from the retronasal cavity should be given more attention during food oral processing. Identification of the olfactory receptor activated by specific odorants and its binding mechanisms are still the bottleneck. Electrophysiology and image technology are the new noninvasive technologies in elucidating the brain signals among multisensory, which can fill the gap between aroma perception and other senses. Moreover, it is necessary to develop a new approach to integrate the relationship among aroma binding parameters, aroma concentration, aroma attributes and cross-modal reactions to make the aroma prediction model more accurate.

Identification and Inhibition of the Key Off-Odorants in Duck Broth by Means of the Sensomics Approach and Binary Odor Mixture.

To improve the sensory quality and promote the diversified development of duck meat, the identification and inhibition of key off-odorants in duck broth were comparatively characterized by using the sensomics approach and binary odor mixture analysis. Sensory evaluation results showed that Litsea pungens Hemsl (LPH) could strongly inhibit the duck broth off-odorants. Fifty-four aroma-active compounds with flavor dilution factors ranging from 1 to 2048 were identified in duck broth and duck broth stewed by LPH. Recombination and omission tests confirmed that trans-4,5-epoxy-(E)-2-decenal, (E)-2-octenal, p-cresol, 1-octen-3-ol, and 4-methyloctanoic acid were the key off-odorants in duck broth. Additionally, trans-4,5-epoxy-(E)-2-decenal (9.26 µg/L) and p-cresol (718.91 µg/L) were identified as the key off-odorants in duck meat for the first time. The results of binary odor mixture and off-odorants inhibition curves demonstrated that linalool with the lowest theoretical inhibitory concentration (109.65 µg/L) had the best aroma masking ability among the five off-odorants, followed by geraniol (123.03 µg/L), (Z)-3,7-dimethyl-2,6-octadien-1-ol (301.99 µg/L), (E)-3,7-dimethyl-2,6-octadienal (2187.76 µg/L), and (Z)-3,7-dimethyl-2,6-octadienal (2691.53 µg/L). The spiking test verified that these compounds with the lowest theoretical inhibitory concentrations effectively inhibited the off-odorants of duck broth.

Analysis of Sodium Content in 4082 Kinds of Commercial Foods in China.

High-sodium intake is associated with the increased risk of hypertension and cardiovascular disease. Monitoring and analyzing the sodium content in commercial food is instructive for reducing sodium intake in the general population. The sodium content of 4082 commercial foods across 12 food groups and 41 food categories was collected and analyzed, including 4030 pre-packaged foods and 52 artisanal foods. The food group with the highest average sodium content (6888.6 mg/100 g) contained sauces, dressings, springs and dips, followed by bean products (1326.1 mg/100 g) and fish, meat and egg products (1302.1 mg/100 g). The average sodium content of all the collected commercial foods was 1018.6 mg/100 g. Meanwhile, the sodium content of non-alcoholic beverages (49.7 mg/100 g), confectionery (111.8 mg/100 g) and dairy products (164.1 mg/100 g) was much lower than the average sodium content of the 12 food groups. The sodium contents of different food groups and categories were significantly different. The proportion of high-sodium food (600 mg/100 g) was more than one-third of all the products. There are a few products marked with salt reduction on the package. Sixteen salt-reduced products were collected, which belong to the food category of soy sauce and account for 16% of all the soy sauce products. The average sodium content in salt-reduced soy sauce is 2022.8 mg/100 g lower than that of non-salt-reduced soy sauce products. These data provide a primary assessment with sodium content in commercial foods and potential improvements for the food industry to achievement the goal of sodium reduction.

Characterization of Taste Compounds and Sensory Evaluation of Soup Cooked with Sheep Tail Fat and Prickly Ash.

Sheep tail fat and prickly ash play an important role in improving the umami taste of mutton soup. In this work, the effects of prickly ash on key taste compounds in stewed sheep tail fat soup were investigated. Results showed that the taste intensity of sheep tail fat soup cooked with 0.2% prickly ash increased significantly. The concentration of organic acids and free amino acids in sheep tail fat soup significantly increased with the addition of prickly ash. The concentration of succinic acid (2.637 to 4.580 mg/g) and Thr (2.558 to 12.466 mg/g) increased the most among organic acids and amino acids, respectively. Spearman's correlation analysis elucidated that seven taste compounds were positively correlated (correlation coefficient > 0.7) with the overall taste intensity of the soup sample including Thr, Asp, oxalic acid, lactic acid, citric acid, succinic acid, and ascorbic acid. Additional experiments and quantitative descriptive analysis further confirmed that Asp, lactic acid and citric acid were the key taste compounds to improve saltiness and umami taste in sheep tail fat soup with prickly ash.

The Effect of Prickly Ash (Zanthoxylum bungeanum Maxim) on the Taste Perception of Stewed Sheep Tail Fat by LC-QTOF-MS/MS and a Chemometrics Analysis.

This work aims to explore the contribution of prickly ash (Zanthoxylum bungeanum Maxim) on the taste perception of stewed sheep tail fat. Liquid chromatography-tandem quadrupole time of flight mass spectrometry (LC-QTOF-MS) was applied to analyze the taste-related compounds. A total of 99 compounds in different sheep tail fat samples were identified. The semi-quantitative results showed that there were differences between the samples. The partial least squares discriminant analysis (PLS-DA) model without overfitting was used to investigate the effect of prickly ash. Eleven marker compounds were predicted with a variable importance for projection > 1, fold change > 2 and p < 0.05. An additional experiment showed that guanosine 5'-monophosphate, malic acid, inosine and adenosine 5'-monophosphate could improve the umami and saltiness taste of stewed sheep tail fat.

circRNA expression patterns and circRNA-miRNA-mRNA networks during CV-A16 infection of SH-SY5Y cells.

Coxsackievirus A16 (CV-A16) has caused worldwide epidemics of hand, foot, and mouth disease (HFMD) in infants and preschool children. Circular RNAs (circRNAs), a class of noncoding RNA molecules, participate in the progression of viral infectious diseases. Although the function of circRNAs has been a heavily researched topic, their role in CV-A16 infection is still unclear. In this study, the viral effects of CV-A16 on the cellular circRNA transcriptome were investigated using next-generation sequencing technology. The results showed that a total of 8726, 8611, and 6826 circRNAs were identified at 0, 12, and 24 h postinfection, respectively. Moreover, it was found that 1769 and 1192 circRNAs were differentially expressed in at 12 and 24 h postinfection, respectively. The common differentially expressed circRNAs were used for functional annotation analysis, and it was found that the parent genes of differentially expressed circRNAs might be associated with the viral infection process, especially the "Immune system process" in GO analysis and the "Inflammation mediated by chemokine and cytokine signaling pathway" in KEGG analysis. Subsequently, circRNA-miRNA-mRNA regulatory networks were constructed, and the hsa_circ_0004447/hsa-miR-942-5p/MMP2, hsa_circ_0078617/hsa-miR-6780b-5p/MMP2 and hsa_circ_0078617/hsa-miR-5196-5p/MMP2 regulatory axes were identified by enrichment analysis as important networks during the progression of CV-A16 infection. Finally, six dysregulated circRNAs were selected for validation and were verified to be consistent with the sequencing results. Considering all of these results, to the best of our knowledge, this study is the first to present a comprehensive overview of circRNAs induced by CV-A16 infection, and this research demonstrated that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of CV-A16 infection, thereby helping to elucidate the mechanisms underlying CV-A16-host interactions.

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies.

BACKGROUND: Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF. METHODS: We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software. RESULTS: A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI -2.58 to -1.51, P < 0.001, I2 = 90%). CONCLUSIONS: MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.