Additional file 1 of Metabolomics analysis of serum and urine in type 1 diabetes patients with different time in range derived from continuous glucose monitoring

Additional file 1: Method S1. Table S1. Characteristics of T1D patients and healthy control. Table S2. 15 characteristic metabolites identified in serum. Table S3. 7 characteristic metabolites identified in urine. Table S4. 15 characteristic metabolites identified in serum. Table S5. 19 characteristic metabolites identified in urine. Table S6. Metabolic pathway analysis. Table S7. The Spearman analysis of the screened metabolites related to TIR

Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis

Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism. Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS). This meta-analysis was registered with PROSPERO (CRD42022298439). Sixteen RCTs, involving 10,155 patients with advanced NSCLC, was collected in this meta-analysis. The pooled HR comparing immunotherapy vs non-immunotherapy were 0.76 (95%CI 0.71–0.81) for males and 0.74 (95%CI 0.63–0.87) for females. The pooled HRs comparing immune-checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy were 0.79 (95%CI 0.70–0.89) for males and 0.63 (95%CI 0.42–0.92) for females. The pooled HRs comparing ICIs versus chemotherapy were 0.74 (95%CI 0.67–0.81) for males and 0.83 (95%CI 0.73–0.95) for females. In squamous NSCLC, the pooled HRs comparing immunotherapy vs non-immunotherapy were 0.73 (95%CI 0.58–0.91) for males and 0.74 (95%CI 0.37–1.48) for females. In non-squamous NSCLC, the pooled HRs comparing immunotherapy versus non-immunotherapy were 0.62 (95%CI 0.71–0.94) for males and 0.59 (95%CI 0.39–0.89) for females. Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy.KEY MESSAGECompared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC.The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC. Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC.</p

DataSheet1_The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials.docx

Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs).Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4.Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: −1.21; 95% CI: −1.91, −0.52, p Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.</p

Table_5_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_1_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.DOCX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_2_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_4_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_3_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Association of a reduction of G-protein coupled receptor 30 expression and the pathogenesis of preeclampsia

Preeclampsia is a pregnancy-specific disorder, which is a leading cause of maternal and perinatal mortality and morbidity. A lower increase of estrogen, compared with the increase in progesterone, is associated with pathogenesis of the disease during pregnancy. G-protein-coupled receptor 30 (GPR30) mediates the action of estrogen, however remains to be investigated in preeclampsia. The levels of GPR30 were measured in placentae from uncomplicated pregnancies and pregnancies complicated by preeclampsia using immunohistochemistry and western blotting. GPR30 expression was additionally measured in placental HTR8/SVneo cells following 17β-estrogen (E2) treatment in normal or hypoxia-reoxygenation conditions by western blotting. In addition, the outgrowth of HTR8/SVneo cells following E2 treatment in hypoxia-reoxygenation conditions was measured. Levels of GPR30 were significantly reduced in placentae from women with preeclampsia as compared with uncomplicated pregnancies. Treatment with E2 significantly increased the expression of GPR30 in HTR8/SVneo cells, in normal and hypoxia-reoxygenation conditions. Furthermore, treatment with E2 increased the outgrowth of HTR8/SVneo cells in hypoxia-reoxygenation conditions. The present study demonstrated lowered placental expression of GPR30 in preeclampsia. Estrogen treatment increases GPR30 expression in extravillous trophoblast and GPR30 may be involved in extravillous trophoblast invasion

G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia

BACKGROUND: Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown. METHOD: We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo). RESULTS: The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-β-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia. CONCLUSION: The present study suggests that GPR30 is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic interventional target for preeclampsia and other pregnancy complications resulting from impaired trophoblast invasion