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BACKGROUND: This study investigated the effects of dietary plant polysaccharides on growth performance, immune status and intestinal health in broilers. We randomly divided 960 one‐day‐old Arbor Acres broiler chicks into four groups. The control (CON) group was fed a basal diet, and the remaining groups were fed a basal diet supplemented with 1000 mg kg−1Ginseng polysaccharide (GPS), Astragalus polysaccharide (APS), or Salvia miltiorrhiza polysaccharide (SMP) for 42 days. RESULTS: Dietary supplementation with SMP significantly increased body weight (BW) at 21 and 42 days of age, average daily gain (ADG) and average daily feed intake (ADFI) during the starter and whole experimental period, decreased the concentrations of interleukin‐1 beta (IL‐1β), tumor necrosis factor α (TNF‐α) and malondialdehyde (MDA), increased the levels of interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10) and catalase (CAT) activity in the serum (P < 0.05). GPS, APS, and SMP supplementation increased serum levels of immunoglobulins, activities of glutathione peroxidase (GSH‐Px), total superoxide dismutase (T‐SOD) and total antioxidant capacity (T‐AOC), and cecal concentrations of acetic acid and propionic acid of broilers (P < 0.05). Furthermore, high‐throughput sequencing results showed that the relative abundance of Firmicutes was decreased while the relative abundance of Bacteroidota, Alistipes, and Prevotellaceae_NK3B31_group were increased (P < 0.05) in the GPS, APS, and SMP groups compared with the CON group. CONCLUSION: Dietary GPS, APS, and SMP supplementation could improve growth performance, enhance immune function by increasing serum immunoglobulin and regulating cytokines, improve antioxidant function by increasing serum antioxidant enzyme activity, increase volatile fatty acid levels and improve the microbial composition in the cecum of broilers. Dietary SMP supplementation had the optimal effect in this study. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

We previously found that Lactobacillus plantarum (LP)‐derived postbiotics protected animals against Salmonella infection, but the molecular mechanism remains obscure. This study clarified the mechanisms from the perspective of autophagy. Intestinal porcine epithelial cells (IPEC‐J2) were pretreated with LP‐derived postbiotics (the culture supernatant, LPC; or heat‐killed bacteria, LPB), and then challenged with Salmonella enterica Typhimurium (ST). Results showed that LP postbiotics markedly triggered autophagy under ST infection, as indicated by the increased LC3 and Beclin1 and the decreased p62 levels. Meanwhile, LP postbiotics (particularly LPC) exhibited a strong capacity of inhibiting ST adhesion, invasion and replication. Pretreatment with the autophagy inhibitor 3‐methyladenine (3‐MA) led to a significant decrease of autophagy and the aggravated infection, indicating the importance of autophagy in LP postbiotics‐mediated Salmonella elimination. LP postbiotics (especially LPB) significantly suppressed ST‐induced inflammation by modulating inflammatory cytokines (the increased interleukin (IL)‐4 and IL‐10, and decreased tumor necrosis factor‐α (TNF), IL‐1β, IL‐6 and IL‐18). Furthermore, LP postbiotics inhibited NOD‐like receptor protein 3 (NLRP3) inflammasome activation, as evidenced by the decreased levels of NLRP3, Caspase‐1 and apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC). Deficits in autophagy resulted in an increase of inflammatory response and inflammasome activation. Finally, we found that both LPC and LPB triggered AMP‐activated protein kinase (AMPK) signaling pathway to induce autophagy, and this was further confirmed by AMPK RNA interference. The intracellular infection and NLRP3 inflammasome were aggravated after AMPK knockdown. In summary, LP postbiotics trigger AMPK‐mediated autophagy to suppress Salmonella intracellular infection and NLRP3 inflammasome in IPEC‐J2 cells. Our findings highlight the effectiveness of postbiotics, and provide a new strategy for preventing Salmonella infection. [ABSTRACT FROM AUTHOR]

Chitosan nanoparticles (CNP), widely applied as oral drug/gene/vaccine carrier, were found to have anti‐inflammatory properties. In this study, the effects of CNP on lipopolysaccharide (LPS)‐induced intestinal damage in weaned piglets and the related mechanisms were investigated. Twenty‐four weaned piglets (Duroc × Landrace × Yorkshire, 21 ± 2 day of age, initial mass: 8.58 ± 0.59 kg) were randomly assigned into four groups: control, LPS, CNP and CNP + LPS. The control and LPS groups were fed a corn–soybean meal‐based control diet, whereas the CNP and CNP + LPS groups were fed a control diet supplemented with 400 mg/kg CNP. After 28 days of feeding, piglets in LPS and CNP + LPS groups were injected with LPS (100 μg/kg); meanwhile, the piglets in control and CNP groups were injected with sterile saline. After 4 h from the LPS challenge, pigs were sacrificed to collect the intestinal samples for analysis. The results showed that CNP could attenuate the intestinal damages and inflammatory response stimulated by LPS treatment. LPS induced dramatically higher levels of CD177+ neutrophils invasion in jejunum mucosa (p < 0.01), which accompanied by increased secretion of marks of inflammation (p < 0.01) compared with the control, whereas CNP administration obviously inhibited LPS‐induced CD177+ neutrophils invasion (p < 0.01) and secretion of marks of inflammation, such as interleukin‐8 (p < 0.05), intercellular adhesion molecule‐1 (p < 0.05) secretion in jejunum mucosa compared with LPS group. Moreover, CNP was shown to inhibit IκB‐α degradation in cytoplasm, which resulted in reduced nuclear translocation of NF‐κB p65 in LPS‐challenged piglets. These findings suggest that CNP attenuates intestinal damage and inflammatory responses in LPS‐challenged weaned piglets by impairing the NF‐κB signalling pathway. [ABSTRACT FROM AUTHOR]

Although a number of theories have been suggested, including roles for oxidative stress, an abnormal maternal‐fetal interface, and genetic and environmental factors, the etiopathology of pre‐eclampsia (PE) remains unclear. Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years. The assessment of candidate genetic polymorphisms in PE could partially elucidate the mechanisms of susceptibility to disease, and contribute to seeking for new diagnosis and treatment methods of PE. PE can lead to severe complications, and even the death of both mother and fetus. Although the complex pathology is not yet clear, some evidence suggested that the occurrence of PE is related to inflammatory factors. We reviewed the current understandings of roles of cytokines in PE, and provided an extensive overview of the role of single nucleotide chain polymorphisms (SNPs) in the genes potentially underlying the pathophysiology of PE. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase‐3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF mice but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis‐related proteins. The results suggested that RA exhibited a protective effect against CP‐induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Background: The dysferlin gene or the DYSF gene encodes the Ca2+‐dependent phospholipid‐binding protein dysferlin, which belongs to the ferlin family and is associated with muscle membrane regeneration and repair. Variants in the DYSF gene are responsible for limb‐girdle muscular dystrophy type 2B (LGMD2B), also called limb‐girdle muscular dystrophy recessive 2 (LGMDR2), a rare subtype of muscular dystrophy involving progressive muscle weakness and atrophy. The present study aimed to identify the variants responsible for the clinical symptoms of a Chinese patient with limb girdle muscular dystrophies (LGMDs) and to explore the genotype–phenotype associations of LGMD2B. Methods: A series of clinical examinations, including blood tests, magnetic resonance imaging scans for the lower legs, electromyography and muscle biopsy, was performed on the proband diagnosed with muscular dystrophies. Whole exome sequencing was conducted to detect the causative variants, followed by Sanger sequencing to validate these variants. Results: We identified two compound heterozygous variants in the DYSF gene, c.1058 T>C, p.(Leu353Pro) in exon 12 and c.1461C>A/p.Cys487* in exon 16 in this proband, which were inherited from the father and mother, respectively. In silico analysis for these variants revealed deleterious results by PolyPhen‐2 (Polymorphism Phenotyping v2; http://genetics.bwh.harvard.edu/pph2), SIFT (Sorting Intolerant From Tolerant; https://sift.bii.a-star.edu.sg), PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org/seq%5fsubmit.php) and MutationTaster (http://www.mutationtaster.org). In addition, the two compound heterozygous variants in the proband were absent in 100 control individuals who had an identical ethnic origin and were from the same region, suggesting that these variants may be the pathogenic variants responsible for the LGMD2B phenotypes for this proband. Conclusions: The present study broadens our understanding of the mutational spectrum of the DYSF gene, which provides a deep insight into the pathogenesis of LGMDs and accelerates the development of a prenatal diagnosis. [ABSTRACT FROM AUTHOR]

In this study, we aimed to determine the effects of dietary supplementation with chitosan nanoparticles (CNP) on growth performance, immune status, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs. A total of 144 piglets were assigned to four groups receiving different dietary treatments, including basal diets supplemented with 0, 100, 200 and 400 mg/kg CNP fed for 28 days. Each treatment group included six pens (six piglets per pen). The increase in supplemental CNP concentration improved the average daily gain (ADG) and decreased the feed and gain (F/G) and diarrhoea rate (p <.05). However, significant differences in the average daily feed intake (ADFI) among different CNP concentrations were not observed. CNP also increased plasma immunoglobulin (Ig)A and IgG, and C3 and C4 concentrations in piglets in a dose‐dependent manner on day 28, whereas IgM concentration was not affected by CNP. A total of 24 piglets in the control diet and control diet with 400 mg/kg CNP supplementation groups were randomly selected for the experiment of immunological stress. Half of the pigs in each group (n = 6) were injected i.p. with Escherichia coli lipopolysaccharide (LPS) at a concentration of 100 μg/kg. The other pigs in each group were injected with sterile saline solution at the same volume. Plasma concentrations of cortisol, prostaglandin E2 (PEG2), interleukin (IL)‐6, tumour necrosis factor (TNF)‐α and IL‐1β dramatically increased after LPS challenge. However, CNP inhibited the increase in cortisol, PEG2, IL‐6 and IL‐1β levels in plasma, whereas TNF‐α level slightly increased. Moreover, the effects of CNP on the gut microbiota were also evaluated. Our results showed that dietary supplementation with CNP modified the composition of colonic microbiota, where it increased the amounts of some presumably beneficial intestinal bacteria and suppressed the growth of potential bacterial pathogens. These findings suggested CNP supplementation improved the growth performance and immune status, alleviated immunological stress and regulated intestinal ecology in weaned piglets. Based on these beneficial effects, CNP could be applied as a functional feed additives supplemented in piglets diet. [ABSTRACT FROM AUTHOR]

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods: Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results: Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion: Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI. [ABSTRACT FROM AUTHOR]