Single-cell RNA sequencing and transcriptomic analysis reveal key genes and regulatory mechanisms in sepsis.

The pathogenesis of sepsis, with a high mortality rate and often poor prognosis, has not been fully elucidated. Therefore, an in-depth study on the pathogenesis of sepsis at the molecular level is essential to identify key sepsis-related genes. The aim of this study was to explore the key genes and potential molecular mechanisms of sepsis using a bioinformatics approach. In addition, key genes with miRNA network correlation analysis and immune infiltration correlation analysis were investigated. The scRNA dataset (GSE167363) and RNA-seq dataset (GSE65682, GSE134347) from GEO database were used for screening out differentially expressed genes using single-cell sequencing and transcriptome sequencing. The analysis of immune infiltration was evaluated by the CIBERSORT method. Key genes and possible mechanisms were identified by WGCNA analysis, GSVA analysis, GSEA enrichment analysis and regulatory network analysis, and miRNA networks associated with key genes were constructed. Nine key genes associated with the development of sepsis, namely IL7R, CD3D, IL32, GPR183, HLA-DPB1, CD81, PEBP1, NCL, and ETS1 were screened, and the specific signaling mechanisms associated with the key genes causing sepsis were predicted. Immune profiling showed immune heterogeneity between control and sepsis samples. A regulatory network of 82 miRNAs, 266 pairs of mRNA-miRNA relationship pairs was also constructed. These nine key genes have the potential to become biomarkers for the diagnosis of sepsis and provide new targets and research directions for the treatment of sepsis.

Influence of hippophae rhamnoides on two appetite factors, gastric emptying and metabolic parameters, in children with functional dyspepsia.

Our aim was to explore in children with functional dyspepsia the effect of hippophae rhamnoides on the levels of plasma appetite factors and on their gastrointestinal motility. A hundred and twenty children with functional dyspepsia were randomly divided into three groups: Group I (treated with hippophae rhamnoides), Group II (treated with domperidone), and Group III (treated with hippophae rhamnoides plus domperidone). The treatment lasted for eight weeks. The levels of plasma leptin (LP) and neuropeptide Y (NPY) were measured before and after treatment. All patients underwent a gastric emptying (GE) test by ultrasound (US) to measure the rate of postprandial gastric antrum residual, at 30min, 60min, 90min and 120min. The average value of subcutaneous fat, body fat percentage, upper arm girth and body mass index (BMI) were also measured. To compare the US with the radionuclide GE test 14 healthy adults volunteers were tested by both GE techniques. We found that the levels of LP and NPY in plasma were markedly higher after treatment in Groups I and III than in Group II. The postprandial gastric antrum remains at 60min, 90min and 120min in Groups I and III fell greatly and the thickness of skin fold (SF), body fat percentage and arm girth increased (P<0.05). The GE half emptying time of a mixed liquid-solid food measured by B US and by the radionuclide technique in the same individuals was similar (P>0.05). In conclusion, in children's functional dyspepsia, our study showed that hippophae rhamnoides increases the levels of appetite factors, leptin and neuropeptide Y, increases gastric emptying and gastrointestinal digestive function, children's growth and development.

High-protein diets alters body composition and improves insulin resistance in a rat model of low birth weight.

OBJECTIVE: We aimed to investigate the effects of early high-protein supplementation on low birth weight (LBW)-associated adult metabolic disturbances. MATERIALS AND METHODS: This study involved 32 LBW rat pups that were fed a normal protein (20% of energy intake) diet or high-protein (30% of energy intake) diet on their first 4 weeks of life. Sixteen rat pups with normal birth weight (NBW) fed the normal-protein diet were included as control. Biochemical measurements were performed at 4 and 12 weeks of age. RESULTS: Low birth weight offspring showed significantly (P < 0.05) increased fat mass percentage and adipocyte size and decreased lean mass percentage and muscle fiber size relative to NBW offspring. These LBW-related changes in body composition were corrected by high-protein diet intervention. At 12 weeks of age, the fasting insulin level (7.14 ± 0.83 vs 9.27 ± 0.67 mU/L) and homeostasis model of insulin resistance (1.71 ± 0.35 vs 2.30 ± 0.44) were significantly lower in high protein-fed LBW offspring than in normal protein-fed LBW offspring. Low birth weight rat pups showed a significant (P < 0.05) reduction in serum adiponectin concentrations, glucose transporter 4 mRNA abundance, and phosphorylation levels of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) relative to NBW controls. These LBW-associated alterations in gene expression were reversed by early high-protein treatment. CONCLUSIONS: Early postnatal high-protein intake alters the body composition and improves insulin resistance in adults with LBW, which is associated with activation of the AMPK and mTOR pathways.

[The effect of birth weight and early growth on body fat composition and insulin sensitivity].

OBJECTIVE: To investigate the effect of birth weight and early growth on body fat composition and insulin sensitivity. METHODS: The birth and growth data of 258 children of 6 to 7 years old in Guangzhou were collected from Jun.2009 to Feb. 2010. Physical and laboratory examination were preformed, which included body weight, body height and body fat composition index (body mass index (BMI), percentage of body fat (PBF), waist circumference to height ratio (WtHR), etc). Fasting blood glucose and insulin were measured. The homeostasis model assessment model for insulin resistance index (HOMA-IR) was calculated. According to birth weight, the children were divided into three groups from light to heavy: BW-I, BW-II, BW-III group. Then according to change in weight SDS between 0 and 36 months, the children were divided into three groups: changers up (CU), non-changers (NC), changers down (CD) group. The effect of birth weight and early growth on body fat composition and insulin sensitivity were analyzed. RESULTS: Change in weight SDS between 0 and 36 months was higher in BW-I group (1.06 ± 1.29) than in the BW-II group (-0.19 ± 0.94) and BW-III group (-0.10 ± 1.20) (all P values < 0.01). Birth weight of the CU group ((2.90 ± 0.47) kg) was lower than that of the NC group ((3.22 ± 0.34) kg) and the CD group ((3.57 ± 0.37) kg) (all P values < 0.01). The body fat composition index of BMI, PBF and WtHR were higher in the BW-III group ((16.35 ± 2.13) kg/m(2), (17.03 ± 5.88)%, (0.479 ± 0.033)) than in the BW-I group ((15.46 ± 2.06) kg/m(2), (14.06 ± 5.25)%, (0.459 ± 0.032)) and BW-II group ((15.47 ± 1.58) kg/m(2), (14.09 ± 5.01)%, (0.460 ± 0.025)) (P < 0.01), while there was no significant difference between the BW-I group and the BW-II group (P > 0.05). The body fat composition index of BMI, PBF and WtHR were higher in the CU group ((16.44 ± 2.20) kg/m(2), (16.51 ± 5.78)%, (0.473 ± 0.034)) than in the NC group ((15.62 ± 1.74) kg/m(2), (14.49 ± 5.30)%, (0.463 ± 0.030)) and the CD group ((15.26 ± 1.85) kg/m(2), (14.24 ± 5.54)%, (0.462 ± 0.031)) (all P values < 0.05). In the CU group, BMI, PBF and WtHR were higher in the BW-III-CU group ((18.76 ± 2.56) kg/m(2), (22.19 ± 8.28)%, (0.512 ± 0.029)) than in the BW-I-CU group ((16.04 ± 2.14) kg/m(2), (15.54 ± 5.28)%, (0.467 ± 0.034)) and BW-II-CU group ((16.70 ± 1.36) kg/m(2), (17.12 ± 4.44)%, (0.474 ± 0.017)) (all P values < 0.05), while there was no significant difference between the BW-I-CU group and the BW-II-CU group (P > 0.05). HOMA-IR was higher in the CU group (1.27 ± 0.44) than in the NC group (1.08 ± 0.31) and the CD group (1.00 ± 0.36) (all P values < 0.01). In the CU group, HOMA-IR was higher in the BW-III-CU group (1.69 ± 0.48) than in the BW-I-CU group (1.21 ± 0.41) and the BW-II-CU group (1.27 ± 0.44) (all P values < 0.01), while there was no significant difference between the BW-I-CU and BW-II-CU group (P > 0.05). CONCLUSION: According to birth weight tertile, both lower birth weight individuals with more weight change-up growth postnatal early and higher birth weight individuals had greater body fat composition in childhood. They were high-risk people of insulin resistance.