Antioxidant peptides, the guardian of life from oxidative stress.

Reactive oxygen species (ROS) are produced during oxidative metabolism in aerobic organisms. Under normal conditions, ROS production and elimination are in a relatively balanced state. However, under internal or external environmental stress, such as high glucose levels or UV radiation, ROS production can increase significantly, leading to oxidative stress. Excess ROS production not only damages biomolecules but is also closely associated with the pathogenesis of many diseases, such as skin photoaging, diabetes, and cancer. Antioxidant peptides (AOPs) are naturally occurring or artificially designed peptides that can reduce the levels of ROS and other pro-oxidants, thus showing great potential in the treatment of oxidative stress-related diseases. In this review, we discussed ROS production and its role in inducing oxidative stress-related diseases in humans. Additionally, we discussed the sources, mechanism of action, and evaluation methods of AOPs and provided directions for future studies on AOPs.

Early life stress induces irritable bowel syndrome from childhood to adulthood in mice.

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder. Traditionally, early life stress (ELS) is predisposed to IBS in adult. However, whether ELS induces IBS in early life remains unclear. Methods: Separated cohort studies were conducted in neonatal male pups of C57BL/6 mice by maternal separation (MS) model. MS and non-separation mice were scheduled to be evaluated for prime IBS-phenotypes, including visceral hypersensitivity, intestinal motility, intestinal permeability, and anxiety-like behavior. Ileal contents and fecal samples were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Subcellular structures of intestinal epithelial, such as epithelial tight junctions and mitochondria, were observed under transmission electron microscopy. Results: MS induced visceral hypersensitivity and decreased total intestinal transit time from childhood to adulthood. In addition, MS induced intestinal hyperpermeability and anxiety-like behavior from adolescence to adulthood. Besides, MS affected intestinal microbial composition from childhood to adulthood. Moreover, MS disrupted intestinal mitochondrial structure from childhood to adulthood. Conclusion: The study showed for the first time that MS induced IBS from early life to adulthood in mice. The disrupted intestinal mitochondrial structure and the significant dysbiosis of intestinal microbiota in early life may contribute to the initiation and progress of IBS from early life to adulthood.

Knockout of SlbZIP68 reduces late blight resistance in tomato.

Tomato (Solanum lycopersicum) is one of the most widely cultivated vegetable crop species in the world. Tomato late blight caused by Phytophthora infestans is a severe disease, which can cause serious losses in tomato production. In this study, tomato SlbZIP68 was identified as a transcription factor that can be induced by P. infestans, salicylic acid (SA) and jasmonic acid (JA). Knockout of SlbZIP68 via clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) technology revealed a significant decrease in tomato resistance to P. infestans. Furthermore, knockout of SlbZIP68 reduced the activity of defense enzymes and increased the accumulation of reactive oxygen species (ROS). Our findings also indicated that SlbZIP68 can activate the expression of the PR genes and enhance resistance to P. infestans. In addition, SlbZIP68 can bind to the PR3 and PR5 promoters and induce gene expression, as revealed by yeast one-hybrid (Y1H) and dual-luciferase (LUC) assays. These findings not only elucidate the mechanisms of response to P. infestans but also enable targeted breeding strategies for tomato resistance to P. infestans.

Genome-Wide Identification of PEBP Gene Family in Solanum lycopersicum.

The PEBP gene family is crucial for the growth and development of plants, the transition between vegetative and reproductive growth, the response to light, the production of florigen, and the reaction to several abiotic stressors. The PEBP gene family has been found in numerous species, but the SLPEBP gene family has not yet received a thorough bioinformatics investigation, and the members of this gene family are currently unknown. In this study, bioinformatics was used to identify 12 members of the SLPEBP gene family in tomato and localize them on the chromosomes. The physicochemical characteristics of the proteins encoded by members of the SLPEBP gene family were also examined, along with their intraspecific collinearity, gene structure, conserved motifs, and cis-acting elements. In parallel, a phylogenetic tree was built and the collinear relationships of the PEBP gene family among tomato, potato, pepper, and Arabidopsis were examined. The expression of 12 genes in different tissues and organs of tomato was analyzed using transcriptomic data. It was also hypothesized that SLPEBP3, SLPEBP5, SLPEBP6, SLPEBP8, SLPEBP9, and SLPEBP10 might be related to tomato flowering and that SLPEBP2, SLPEBP3, SLPEBP7, and SLPEBP11 might be related to ovary development based on the tissue-specific expression analysis of SLPEBP gene family members at five different stages during flower bud formation to fruit set. This article's goal is to offer suggestions and research directions for further study of tomato PEBP gene family members.

Vitamin D improves irritable bowel syndrome symptoms: A meta-analysis.

Background & aims: Approximately 5%-10% of the population in most geographical regions suffer from irritable bowel syndrome (IBS), which creates a significant burden on individual patients, their families, and society. Recent advances in IBS therapies have indicated that vitamin D supplementation is potential to relieve its symptoms, but evidence of this is lacking. This meta-analysis aimed to estimate the effect of vitamin D on gastrointestinal (GI) symptoms in IBS patients. Methods: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched from their inception to March 2022. Statistical analyses were performed with Stata 12.0 and Review Manager 5.4, and statistical significance was defined as P < 0.05. The pooled results are presented as weighted mean differences (WMD) and 95% confidence intervals (CI). Results: The meta-analysis including 6 randomized controlled trials (RCT) with 572 patients found a significant difference in IBS symptom severity score (WMD, -34.88; 95% CI, -62.48 to -7.27; P = 0.013; random-effects model) but no significant difference in IBS quality of life score (WMD, 3.33; 95% CI, -5.12 to -11.77; P = 0.440; random-effects model). Conclusions: Overall, IBS patients may benefit from vitamin D supplementation to reduce the GI symptoms.

Genome-Wide Identification and Expression Analysis of Cysteine-Rich Polycomb-like Protein (CPP) Gene Family in Tomato.

The cysteine-rich polycomb-like protein (CPP) gene family is a class of transcription factors containing conserved cysteine-rich CRC structural domains that is involved in the regulation of plant growth and stress tolerance to adversity. Relative to other gene families, the CPP gene family has not received sufficient attention. In this study, six SlCPPs were identified for the first time using the most recent genome-wide identification data of tomato. Subsequently, a phylogenetic analysis classified SlCPPs into four subfamilies. The analysis of cis-acting elements in the promoter indicates that SlCPPs are involved in plant growth and development and also stress response. We present for the first time the prediction of the tertiary structure of these SlCPPs proteins using the AlphaFold2 artificial intelligence system developed by the DeepMind team. Transcriptome data analysis showed that SlCPPs were differentially expressed in different tissues. Gene expression profiling showed that all SlCPPs except SlCPP5 were up-regulated under drought stress; SlCPP2, SlCPP3 and SlCPP4 were up-regulated under cold stress; SlCPP2 and SlCPP5 were up-regulated under salt stress; all SlCPPs were up-regulated under inoculation with Cladosporium fulvum; and SlCPP1, SlCPP3, and SlCPP4 were up-regulated under inoculation with Stemphylium lycopersici. We performed a virus-induced gene silencing experiment on SlCPP3, and the results indicated that SlCPP3 was involved in the response to drought stress. Finally, we predicted the interaction network of the key gene SlCPP3, and there was an interaction relationship between SlCPP3 and 10 genes, such as RBR1 and MSI1. The positive outcome showed that SlCPPs responded to environmental stress. This study provides a theoretical and empirical basis for the response mechanisms of tomato in abiotic stresses.

Transcriptome Analysis and Screening of Genes Associated with Flower Size in Tomato (Solanum lycopersicum).

Flower development is not only an important way for tomato reproduction but also an important guarantee for tomato fruit production. Although more and more attention has been paid to the study of flower development, there are few studies on the molecular mechanism and gene expression level of tomato flower development. In this study, RNA-seq analysis was performed on two stages of tomato flower development using the Illumina sequencing platform. A total of 8536 DEGs were obtained by sequencing, including 3873 upregulated DEGs and 4663 down-regulated DEGs. These differentially expressed genes are related to plant hormone signaling, starch and sucrose metabolism. The pathways such as pentose, glucuronate interconversion, and Phenylpropanoid biosynthesis are closely related and mainly involved in plant cellular and metabolic processes. According to the enrichment analysis results of DEGs, active energy metabolism can be inferred during flower development, indicating that flower development requires a large amount of energy and material supply. In addition, some plant hormones, such as GA, may also have effects on flower development. Combined with previous studies, the expression levels of Solyc02g087860 and three of bZIPs were significantly increased in the full flowering stage compared with the flower bud stage, indicating that these genes may be closely related to flower development. These genes were previously reported in Arabidopsis but not in tomatoes. Our next work will conduct a detailed functional analysis of the identified bZIP family genes to characterize their association with tomato flower size. This study will provide new genetic resources for flower formation and provide a basis for tomato yield breeding.

Serum Syndecan-1 levels in patients with immunoglobulin A vasculitis in children

Abstract Objective The aim of this study was to evaluate the serum Syndecan-1 (SDC-1) levels in patients with immunoglobulin-A vasculitis (IgAV) in children and its relation with gastrointestinal involvements. Methods Sixty-eight children with IgAV and 48 healthy children were enrolled in this cross-sectional study. Clinical and related laboratory data were collected from a computerized hospital database. Serum SDC-1 was collected on admission prior to treatment. Results Forty-eight patients fully met the IgAV diagnostic criteria at admission (IgAV group), 20 patients with rash only and diagnosed IgAV during hospitalization (Purpura group). In IgAV group, 30 patients with gastrointestinal involvements (IgAV-GI group) and 18 patients without gastrointestinal involvements (IgAV-NGI group). SDC-1 serum levels were significantly higher in the IgAV group (86.37 ng/mL (IQR 59.16-117.14 ng/mL)) than in the controls (20.37 ng/mL (IQR 15.52-26.45 ng/mL)) and the Purpura group (32.66 ng/mL (IQR 14.87-49.89 ng/mL)). Additionally, SDC-1 (OR = 1.08) was independently associated with IgAV with a cut-off value (sensitivity and specificity) of 66.55 ng/mL (68.8%, 95.0%), and the area under the curve was 0.908. The serum SDC-1 levels of the IgAV-GI group (106.92 ± 50.12 ng/mL) were significantly higher than those in the IgAV-NGI group (67.52 ± 17.59 ng/mL). Logistic regression analysis showed that SDC-1 (OR = 1.03) was independently associated with IgAV-GI with a cut-off value of 89.39 ng/mL. Conclusions SDC-1 serum levels may mirror vascular endothelium injury and mucosal damage in IgAV. Its applicability as a surrogate biomarker in IgAV remains to be determined.

Relevance of Intestinal Microbiota in Immunoglobulin A Vasculitis With Abdominal Involvement.

Background: We explored the intestinal microbiota changes in IgAV with abdominal involvement (IgAV-GI) at the acute and convalescent stages and evaluated the role of intestinal microbiota in the clinical course of patients with IgAV. Methods: A total of 37 patients with IgAV were included, and the control group comprised 37 age- and sex-matched healthy children. Stool samples were collected from 28 children with IgAV-GI (19 in the acute stage and 9 in the recovery stage) and from nine children with non-abdominal involvement. Fecal specimens were selected and DNA was obtained using an extraction kit which was then subjected to high-throughput sequencing and analysis. Results: There was no significant difference in the community structure of the intestinal microbiota among the IgAV-GI acute, IgAV-GI convalescence, and IgAV-non-GI stages. The abundance of Veillonella in the acute stage of IgAV-GI was significantly higher than that in IgAV-non-GI and convalescence stages, and Ruminococcus was the most abundant in IgAV-GI convalescence. The α-diversity of children with IgAV was significantly lower than that of healthy children, and healthy children had higher intestinal microbiota richness and more evenly distributed species. In terms of changes in intestinal microbial diversity in patients with IgAV at the genus level, obligate anaerobes such as Bifidobacterium, Prevotella, Coprobacter, Prevotella_9, Blautia, Romboutsia, Parabacteroide, Subdoligranulum, and Roseburia were significantly reduced, and the enrichment of facultative anaerobe was represented by Bacteroides, Lachnoclostridium, and Alistipe. Conclusion: Different bacterial species may be involved in the pathogenesis of different types of IgAV-GI. Differences were observed in the intestinal microbiota between healthy children and children with IgAV.

Clinical analysis of asparaginase-associated pancreatitis in children.

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of asparaginase-associated pancreatitis (AAP) in children to assess the risk factors of AAP and improve its clinical prognosis. METHODS: We performed a retrospective analysis of 24 patients with AAP who suffered from acute lymphoblastic leukemia (ALL) and received asparaginase chemotherapy, and who were admitted to the Children's Hospital of Zhejiang University School of Medicine from January 2009 to January 2019. We analyzed the general situation, drug application, clinical manifestations, laboratory tests, imaging findings, treatment, and prognosis. RESULTS: In 796 patients with ALL who received asparaginase chemotherapy, the incidence of AAP was 3% (24/796). Among these patients, 11 (45.8%) developed AAP during the first application of asparaginase during the induction of remission, six cases developed AAP during the second application of asparaginase, and seven cases developed AAP during the third and above application. The median time from the diagnosis of AAP in 24 patients to the last asparaginase treatment was 8 days (1-18 days), among whom, the main clinical symptoms were abdominal pain, vomiting, nausea, bloating, and fever, which accounted for 95.8%, 37.5%, 33.3%, 20.8%, 4.0%, and 42.7%, respectively. Additionally, seven patients had peritoneal effusion. At initial diagnosis, 62.5% of the patients (15/24) had an increase in blood amylase levels to more than three times the upper limit of normal. The abdominal ultrasound results of 91.7% (22/24) of the patients were consistent with the imaging changes observed in pancreatitis. All 24 patients immediately stopped asparaginase treatment and received symptomatic supportive treatment, including fluid resuscitation, fasting, nutritional support, antibiotics, pancreatin inhibitors, and treatment of complications, as needed. Twenty-three patients were relieved after treatment, and one died. Following the resolution of symptoms in 14 patients with AAP, asparaginase chemotherapy was reintroduced, and 3 patients relapsed with AAP, all of which were mild. Symptoms were relieved 72 h after stopping asparagine chemotherapy. CONCLUSION: According to the data from this single-center study, the incidence of AAP in patients with ALL was 3%, most of which occurred during the first or second exposure to asparaginase. Abdominal pain was the most common clinical manifestation. The diagnosis of AAP should be based on clinical manifestations, laboratory tests, and imaging findings. The prognosis of AAP is good, and whether asparaginase treatment can be reintroduced requires an evaluation of the benefits of asparaginase treatment and the risk of recurrence of pancreatitis.

Blood routine examination: a simple way for differential diagnosis of immunoglobulin A vasculitis with abdominal involvement and appendicitis in children.

To explore the value of blood routine examination indexes in the differential diagnosis of immunoglobulin A vasculitis (IgAV) with abdominal involvement and appendicitis in children. Forty-seven patients with IgAV and abdominal involvement, 95 cases with appendicitis, and 48 healthy children were enrolled in this study. Demographic and laboratory data were retrospectively recorded from medical files. The levels of serum percentage of lymphocytes (LYM%), percentage of eosinophils (E%), red cell volume distribution width (RDW) and platelet (PLT) count were higher, while blood cells (WBC) count, percentage of neutrophils (N%), percentage of monocytes (M%), mean platelet volume (MPV), platelet distribution width and C-reactive protein were lower in the group of IgAV with abdominal involvement compared to appendicitis group (P < 0.05). Multivariate logistic regression analysis showed LYM% (odds ratio (OR) = 1.34, P = 0.001) and RDW (OR = 2.96, P = 0.045) were independent risk factors for IgAV with abdominal involvement. N% (OR = 1.270, P = 0.006) and MPV (OR = 51.15, P = 0.042) were independently associated with appendicitis. Using receiver operating characteristic analysis, the optimal cut-off values (sensitivity and specificity) respectively were 42.17% (95.7%, 100.0%) for LYM%, 12.65% (83.0%, 83.2%) for RDW, 61.5% (91.6%, 97.9%) for NE% and 10.1fL (78.9%, 75.4%) for MPV, with the AUC values of 0.989, 0.881, 0.985, 0.810, respectively. Blood routine examination indices, especially the N%, LYM%, RDW, and MPV, can be used for simple differential diagnosis of IgAV with abdominal involvement and appendicitis.

Evaluation of gallic acid on membrane damage of Yersinia enterocolitica and its application as a food preservative in pork.

This study was aimed to examine the membrane damage mechanism of gallic acid (GA) on Yersinia enterocolitica BNCC 108930, and to explore whether GA can prolong the shelf life of pork. The minimal inhibitory concentration (MIC) of GA against Y. enterocolitica was determined by adopting the broth microdilution method. Second, an investigation was conducted on the morphological and physiological variations of Y. enterocolitica after the GA treatment. Finally, a response surface approach was used to establish the growth inhibition model of GA against Y. enterocolitica in pork. The MIC of GA against Yersinia enterocolitica BNCC 108930 was 2.5 mg/mL. GA affects the membrane integrity of Y. enterocolitica, as demonstrated by a significant decrease in intracellular ATP and pH. The results showed that the number of Y. enterocolitica in pork meat containing 5 mg/g of GA decreased by 2 logarithmic cycles during storage at 4 °C for 3 days. According to the obtained findings, GA could be used as a food preservative to prolong the shelf life of pork.

Serum Syndecan-1 levels in patients with immunoglobulin A vasculitis in children.

OBJECTIVE: The aim of this study was to evaluate the serum Syndecan-1 (SDC-1) levels in patients with immunoglobulin-A vasculitis (IgAV) in children and its relation with gastrointestinal involvements. METHODS: Sixty-eight children with IgAV and 48 healthy children were enrolled in this cross-sectional study. Clinical and related laboratory data were collected from a computerized hospital database. Serum SDC-1 was collected on admission prior to treatment. RESULTS: Forty-eight patients fully met the IgAV diagnostic criteria at admission (IgAV group), 20 patients with rash only and diagnosed IgAV during hospitalization (Purpura group). In IgAV group, 30 patients with gastrointestinal involvements (IgAV-GI group) and 18 patients without gastrointestinal involvements (IgAV-NGI group). SDC-1 serum levels were significantly higher in the IgAV group (86.37 ng/mL (IQR 59.16-117.14 ng/mL)) than in the controls (20.37 ng/mL (IQR 15.52-26.45 ng/mL)) and the Purpura group (32.66 ng/mL (IQR 14.87-49.89 ng/mL)). Additionally, SDC-1 (OR = 1.08) was independently associated with IgAV with a cut-off value (sensitivity and specificity) of 66.55 ng/mL (68.8%, 95.0%), and the area under the curve was 0.908. The serum SDC-1 levels of the IgAV-GI group (106.92 ± 50.12 ng/mL) were significantly higher than those in the IgAV-NGI group (67.52 ± 17.59 ng/mL). Logistic regression analysis showed that SDC-1 (OR = 1.03) was independently associated with IgAV-GI with a cut-off value of 89.39 ng/mL. CONCLUSIONS: SDC-1 serum levels may mirror vascular endothelium injury and mucosal damage in IgAV. Its applicability as a surrogate biomarker in IgAV remains to be determined.

Oligomer Formation and Insecticidal Activity of Bacillus thuringiensis Vip3Aa Toxin.

Bacillus thuringiensis (Bt) Vip3A proteins are important insecticidal proteins used for control of lepidopteran insects. However, the mode of action of Vip3A toxin is still unclear. In this study, the amino acid residue S164 in Vip3Aa was identified to be critical for the toxicity in Spodoptera litura. Results from substitution mutations of the S164 indicate that the insecticidal activity of Vip3Aa correlated with the formation of a >240 kDa complex of the toxin upon proteolytic activation. The >240 kDa complex was found to be composed of the 19 kDa and the 65 kDa fragments of Vip3Aa. Substitution of the S164 in Vip3Aa protein with Ala or Pro resulted in loss of the >240 kDa complex and loss of toxicity in Spodoptera litura. In contrast, substitution of S164 with Thr did not affect the >240 kDa complex formation, and the toxicity of the mutant was only reduced by 35%. Therefore, the results from this study indicated that formation of the >240 kDa complex correlates with the toxicity of Vip3Aa in insects and the residue S164 is important for the formation of the complex.

What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis.

OBJECTIVE: The use of IVIG plus high- or low-dose aspirin for the initial treatment of Kawasaki disease remains controversial. The aim of this study was to evaluate the efficacy of IVIG plus high-dose aspirin compared with IVIG plus low-dose aspirin in the treatment of Kawasaki disease. METHODS: Studies related to aspirin therapy for Kawasaki disease were selected by searching the databases of Medline (PubMed), Embase and the Cochrane Library before March 2019. Statistical analyses were performed by using a Review Manager Software package and STATA v.15.1. RESULTS: Eight retrospective cohort studies, characterizing 12 176 patients, were analysed. Overall, no significant difference was found in the incidence of coronary artery abnormalities between the high- and low-dose aspirin groups [relative risk (RR) 1.15; 95% CI: 0.93, 1.43; P = 0.19; random-effects model]. The patients treated with high-dose aspirin had slightly faster resolution of fever [mean difference (MD) -0.30; 95% CI: -0.58, -0.02; P = 0.04; random-effects model]. but the rates of IVIG resistance (RR, 1.26; 95% CI: 0.55, 2.92; P = 0.59; random-effects model) and days in hospital (MD, 0.22; 95% CI: -0.93, 1.37; P = 0.71; random-effects model) were similar between the two groups. CONCLUSION: Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.

Analysis of risk factors and development of scoring system to predict severity of upper gastrointestinal bleeding in children.

BACKGROUND AND AIM: Upper gastrointestinal bleeding is a rare and potentially life-threatening condition in children. Herein, clinical features and risk factors in children with upper gastrointestinal bleeding were analyzed, and a clinical scoring system was constructed to assess severity. METHODS: This retrospective cohort study involved 224 children hospitalized with upper gastrointestinal bleeding between January 2012 and April 2018. Demographic data, clinical information, and laboratory test results on admission were statistically examined. RESULTS: Out of 224 upper gastrointestinal bleeding cases, 76 were diagnosed as severe and 148 as mild cases according to the rate of blood loss and severity. Severe group was significantly different from mild group in 23 items including age, number of patients aged more than 7 years, and so forth (P < 0.01 or P < 0.05). Positive detection rate of bleeding etiology was gradually decreased (P < 0.01) in relation to delay in timing of endoscopy. Analysis of logistic regression evinced five independent risk factors for severe cases to be associated with poor consciousness, hemoglobin < 80 g/L, hemoglobin drop of > 20 g/L, hematochezia, and anemic appearance (P < 0.01 or P < 0.05). Using these five parameters, a number of scoring models were tested. The most predictive resulted in a scoring system constructed with a total of 16 and a cutoff for intervention of 8. CONCLUSIONS: Amalgamation of risk factors with the scoring system plays an important role in assessing upper gastrointestinal bleeding severity in children.