The Accumulative Effect of Multiple Postnatal Risk Factors with the Risk of Being Overweight/Obese in Late Childhood.

Most past studies focused on the associations of prenatal risk factors with the risks of childhood overweight/obesity. Instead, more postnatal risk factors are modifiable, with less knowledge of their cumulative effects on childhood obesity. We analyzed data of 1869 children in an Australian birth cohort. Key postnatal risk factors included: maternal and paternal overweight/obesity during the child's infancy, tobacco exposure, low family socioeconomic score, breastfeeding duration < 6 months, early introduction of solid foods, and rapid weight gain during infancy. The risk score was the sum of the number of risk factors. The primary outcome is overweight/obesity in late childhood (11-12 years); secondary outcomes are high-fat mass index (FMI), body fat percentage (BF%), and waist-to-height ratio (WHtR). Poisson regression models were used in the analyses. Children with higher risk scores had higher risks of overweight/obesity (p-for-trends < 0.001). After adjusting covariates, compared with those with 0-1 risk factors, children with 4-6 risk factors had 4.30 (95% confidence interval: 2.98, 6.21) times higher risk of being overweight/obesity; the relative risks for high FMI, BF%, and WHtR were 7.31 (3.97, 13.45), 4.41 (3.00, 6.50), and 6.52 (3.33, 12.74), respectively. Our findings highlighted that multiple postnatal risk factors were associated with increased risks of being overweight/obesity in late childhood.

Adenylate kinase 4 promotes neuronal energy metabolism and mitophagy in early cerebral ischemia via Parkin/PKM2 pathway.

Mitochondrial dysfunction is closely related to brain injury and neurological dysfunction in ischemic stroke. Adenylate kinase 4 (AK4) plays a critical role in energy metabolism and mitochondrial homeostasis. However, the underlying mechanisms remain unclear. In the present study, we demonstrated an important role of AK4 in mitochondrial dysfunction in the early cerebral ischemia. Early focal cerebral ischemia induced decrease of AK4 protein expression in ischemic hemispheric brain tissue in mice. Exposure of cultured primary neuron to oxygen-glucose deprivation (OGD) also induced AK4 downregulation. Overexpression of AK4 in neuron using adeno-associated virus (AAV-AK4) in mice promoted neuronal survival reflected by decreased infarction volume and TUNEL staining. AK4 overexpression inhibited mitochondrial decline and downregulation of energy metabolism-associated proteins (p-AMPK and ATP1A3) induced by MCAO. Moreover, AK4 knock-in using lentivirus carried AK4 vector (LV-AK4) induced energy metabolism shift from glycolysis to oxidation in neuron. Using transmission electron microscope and western blot, we revealed that AK4 overexpression promoted mitophagy and mitophagy-associated proteins expression PINK1 and Parkin after MCAO. Mass spectrometry and co-immunoprecipitation revealed an interaction between AK4 and PKM2. Mechanistically, AK4 indirectly decreased PKM2 expression via enhancing its ubiquitination by increasing the interaction between PKM2 and its ubiquitin E3 ligase Parkin, and inhibits Parkin downregulation. In conclusion, our data demonstrate that AK4/ Parkin /PKM axis prevents cerebral ischemia damage via regulation of neuronal energy metabolism model and mitophagy. AK4 was a new target for intervention of early ischemic neuron injury.

A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

Effectiveness and safety of human type 5 recombinant adenovirus (H101) in malignant tumor with malignant pleural effusion and ascites: A multicenter, observational, real-world study.

BACKGROUND: The aim of this study was to analyze the effectiveness and safety of H101 in Chinese patients with malignant pleural effusion and ascites (MPE/MA) in the real world. METHODS: This multicenter, observational, real-world study recruited patients with MPE/MA caused by malignant tumor receiving H101-containing treatment between January 2020 and June 2022. Effectiveness was evaluated by overall remission rate (ORR), and safety was evaluated based on adverse events (AEs). Subgroup analysis was performed on patients grouped according to tumor type, the volume of MPE and MA, and dosage of H101. RESULTS: A total of 643 eligible patients were enrolled, and 467 received H101 monotherapy and 176 received H101 combined with chemotherapy. The ORR of total patients was60.3% with 388 case of PR. In the H101 monotherapy group, the decrease of MPE or MA was achieved in 282 (60.4%, PR) patients, 176 (37.7%, NC) patients showed no change in volume of MPE or MA, and nine (1.9%, PD) patients showed an increase, yielding an ORR of 60.4% (282/467). The ORR for the combination therapy group was 60.2% (106/176), with 106 cases of PR, 69 cases of NC and one case of PD. Subgroup analyses based on tumor type, volume of MPE and MA, and dosage of H101 all showed high ORR, approximately 60%. The main AEs associated with H101-containing regimens were fever, nausea and vomiting. No serious AEs occurred in both groups. CONCLUSION: Encouraging clinical benefits and manageable toxicity of H101 against MPE/MA were preliminarily observed in the real-world clinical setting, indicating that the H101-containing regimen is reliable, safe, and feasible, providing a novel and effective option for the treatment of this disease.

A comparison of bioelectrical impedance analysis and air displacement plethysmography to assess body composition in children.

Background: Accurate assessment of body composition (BC) is important to investigate the development of childhood obesity. A bioelectrical impedance analysis (BIA) device is portable and inexpensive compared with air displacement plethysmography (ADP) for the assessment of BC and is widely used in children. However, studies of the effectiveness of BIA are few and present different results, especially in pediatric populations. The aim of this study was to evaluate the agreement between BIA and ADP for estimating BC. Methods: The BC of 981 Chinese children (3-5 years) was measured using the BIA device (SeeHigher BAS-H, China) and ADP (BOD POD). Results: Our results showed that BIA underestimated fat mass (FM) and overestimated fat-free mass (FFM) in normal weight children (P < 0.05), but the opposite trend was shown in children with obesity (P < 0.05). The agreement between FM and FFM measured by the two methods was strong (CCC > 0.80). The linear regression equation of 5-year-old children was constructed. Conclusion: The SeeHigher BAS-H multi-frequency BIA device is a valid device to evaluate BC in Chinese preschool children compared with ADP (BOD POD), especially in 5-year-old children or children with obesity. Further research is needed to standardize the assessment of BC in children.

Impact of Early Life Factors on Metabolic Phenotypes of Obesity in Preschool Children.

OBJECTIVE: To investigate the impact of factors in the first 1,000 days of life on metabolic phenotypes of obesity in preschool children in a cohort study. RESEARCH DESIGN AND METHODS: We recruited 3-year-old children for the study. Early life factors included maternal age at delivery, maternal education, prepregnancy BMI, gestational weight gain, gravidity, history of gestational diabetes mellitus, delivery mode, gestational age, family history of metabolic disorders, paternal education, annual family income, child sex, birth weight, and breastfeeding duration. According to BMI and metabolic status, children were classified as metabolically healthy (no metabolic risk factors) with normal weight (MHNW), metabolically unhealthy (one or more metabolic risk factors) with normal weight (MUNW), metabolically healthy with overweight or obesity (MHO), and metabolically unhealthy with overweight or obesity (MUO). RESULTS: We recruited 3,822 children for the study, with 3,015 analyzed. Accelerated BMI z score growth rate between 6 and 24 months was associated with MHO (ß = 0.022; 95% CI 0.009, 0.036) and MUO (ß = 0.037; 95% CI 0.018, 0.056). Maternal overweight (odds ratio [OR] 3.16; 95% CI 1.55, 6.42) and obesity (OR 8.14; 95% CI 3.73, 17.76) before pregnancy and macrosomia (OR 2.47; 95% CI 1.32, 4.59) were associated with MHO, and maternal obesity before pregnancy (OR 6.35; 95% CI 2.17, 18.52) increased the risk of MUO. CONCLUSIONS: Early life factors, such as maternal obesity and accelerated BMI growth rate between 6 and 24 months, were related not only to MHO but also to MUO. Children with these early life factors should be given interventions for weight control to prevent metabolic abnormalities.

HNF4G accelerates glioma progression by facilitating NRP1 transcription.

Hepatocyte nuclear factor 4γ (HNF4G) is considered to be a transcription factor and functions as an oncogene in certain types of human cancer. However, the precise functions and the potential molecular mechanisms of HNF4G in glioma remain unclear. Therefore, the present study aimed to elucidate the role of HNF4G in glioma and the underlying mechanism. Western blotting and reverse transcription-quantitative PCR (RT-qPCR) demonstrated that HNF4G was highly expressed in glioma tissues and cell lines. The overexpression of HNF4G in LN229 and U251 glioma cells promoted cell proliferation and cell cycle progression, and inhibited apoptosis, while the knockdown of HNF4G suppressed cell proliferation, cell cycle progression and tumor growth, and induced apoptosis. A significant positive association was detected between HNF4G and neuropilin-1 (NRP1) mRNA expression in glioma tissues. Bioinformatics analysis, chromatin immunoprecipitation-RT-qPCR and promoter reporter assays confirmed that HNF4G promoted NRP1 transcription in glioma by binding to its promoter. NRP1 overexpression facilitated glioma cell proliferation and cell cycle progression, and suppressed apoptosis in vitro, while the knockdown of NRP1 inhibited cell proliferation and cell cycle progression, and facilitated apoptosis. NRP1 overexpression reversed the effects induced by HNF4G knockdown on glioma cell proliferation, cell cycle progression and apoptosis. In summary, the present study demonstrated that HNF4G promotes glioma cell proliferation and suppresses apoptosis by activating NRP1 transcription. These findings indicate that HNF4G acts as an oncogene in glioma and may thus be an effective therapeutic target for glioma.

Validation of different personalized risk models of chemotherapy-induced nausea and vomiting: results of a randomized, double-blind, phase III trial of fosaprepitant for cancer patients treated with high-dose cisplatin.

BACKGROUND: Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis. The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid malignant tumors, determine risk factors and externally validate different personalized risk models for CINV. METHODS: This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy. The primary endpoint was complete response (CR) during the overall phase (OP) with a non-inferiority margin of 10.0%. Logistic regression models were used to assess the risk factors of CR and no nausea. To validate the personalized risk models, the accuracy of the risk scoring systems was determined by measuring the specificity, sensitivity and area under the receiver operating characteristic (ROC) curve (AUC), while the predictive accuracy of the nomogram was measured using concordance index (C-index). RESULTS: A total of 720 patients were randomly assigned. CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group (78.1% vs. 77.7%, P = 0.765) with a between-group difference of 0.4% (95% CI, -5.7% to 6.6%). Female sex, higher cisplatin dose (≥ 70 mg/m2 ), no history of drinking and larger body surface area (BSA) were significantly associated with nausea. The AUC for the acute and delayed CINV risk indexes was 0.68 (95% CI: 0.66-0.71) and 0.66 (95% CI: 0.61-0.70), respectively, and the C-index for nomogram CINV prediction was 0.59 (95% CI, 0.54-0.64). Using appropriate cutoff points, the three models could stratify patients with high- or low-risk CINV. No nausea and CR rate were significantly higher in the low-risk group than in the high-risk group (P < 0.001). CONCLUSIONS: Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy. Female cancer patients without a history of alcohol consumption, with larger BSA and received high-dose cisplatin might be more vulnerable to CINV. Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.

Analysis and Comparison of Early Childhood Nutritional Outcomes Among Offspring of Chinese Women Under the Chinese 2021 and US 2009 Gestational Weight Gain Guidelines.

Importance: In 2009, the US National Academy of Medicine (NAM) released revised gestational weight gain (GWG) guidelines, which were established primarily for White North American women and may be unsuitable for Asian women. In 2021, the Chinese Nutrition Society (CNS) released its GWG guidelines, but their applicability requires re-examination. Objective: To compare the differences between the CNS and NAM recommendations for GWG in association with health outcomes in the offspring of Chinese women. Design, Setting, and Participants: In this bidirectional cohort study, children in China were recruited at age 3 years from 2017 to 2018, with 2 follow-up visits over the next 2 years (between September 2017 and September 2020). Information during pregnancy was retrieved from medical records. Data analysis was performed from October 2021 to January 2022. Main Outcomes and Measures: GWG was classified as insufficient, appropriate, or excessive according to the CNS and NAM guidelines separately. Children's height, weight, fat mass, fat-free mass, and percentage of body fat were measured at each visit. Body mass index, fat mass index, fat-free mass index, weighted κ score, risk ratio values, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: A total of 3822 children (1996 boys and 1826 girls; mean [SD] age, 3.79 [0.30] years) were enrolled; after exclusions, 3170 term singleton children were recruited and were followed at 4 and 5 years of age. According to the CNS guidelines, the prevalence rates were 14.1% for insufficient GWG, 48.1% for appropriate GWG, and 37.9% for excessive GWG, whereas the rates according to NAM guidelines were 39.7% for insufficient GWG, 37.2% for appropriate GWG, and 23.1% for excessive GWG. The weighted κ value for the classification agreement between the 2 guidelines was 0.530 (95% CI, 0.510-0.550). For the appropriate GWG group, the rates for low nutritional levels did not differ between the 2 guidelines, but the rates for high nutritional levels were significantly lower under CNS guidelines than under NAM guidelines. When the sensitivity, specificity, PPV, and NPV with respect to the mothers who maintained appropriate GWG were used to estimate the nonhigh nutritional status of their offspring, generally higher values based on the CNS guidelines were found compared with those based on the NAM recommendations. Conclusions and Relevance: These findings suggest that the GWG recommendations promulgated by the NAM are higher than the CNS guidelines, with the latter more suitable for Chinese women.

Night-to-night variability in respiratory sleep parameters to diagnose obstructive sleep apnea in children: A systematic review and meta-analysis.

PURPOSE: This systematic review aims to assess the night-to-night variability (NtNV) in respiratory sleep parameters in children and the accuracy of diagnosing obstructive sleep apnea (OSA) in children based on a single-night sleep study. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched until March 8, 2021. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021239838). RESULTS: Our study included 395 patients from 5 articles. The mean (SD) age of all included patients was 11.78 (4.05) years. AHI was reported for 325 participants in 4 studies, and the mean change between two consecutive nights was -0.13 [95% CI: -0.40, 0.14] events per hour. The mean change in OAI was -0.07 [95% CI: -0.27, 0.12] events per hour in 187 participants across 3 studies. Based on the diagnostic criteria used, three studies reported that the diagnostic rates of OSA patients in a single-night sleep study were 83%, 84.6%, and 91%. The NtNV in AHI in children with severe and moderate OSA was greater than that in children with mild OSA (3.35 [95% CI: 0.07, 6.62] events per hour vs -0.15 [95% CI: -0.42, 0.12] events per hour), and these children with more severe OSA may have shown a higher AHI on the first night. CONCLUSIONS: The NtNV in AHI was not statistically significant in the group sample of children. However, there were significant differences in NtNV in AHI between children with mild and moderate-to-severe OSA. Individual NtNV in respiratory sleep parameters may cause children to be misdiagnosed by single-night diagnostic sleep studies.

The Relationship between Fat Mass Percentage and Glucose Metabolism in Children and Adolescents: A Systematic Review and Meta-Analysis.

To assess the relationship between fat mass percentage (FMP) and glucose metabolism in children aged 0−18 years we performed a systematic review of the literature on Medline/PubMed, SinoMed, Embase and Cochrane Library using the PRISMA 2020 guidelines up to 12 October 2021 for observational studies that assessed the relationship of FMP and glucose metabolism. Twenty studies with 18,576 individuals were included in the meta-analysis. The results showed that FMP was significantly associated with fasting plasma glucose (FPG) (r = 0.08, 95% confidence interval (CI): 0.04−0.13, p < 0.001), fasting plasma insulin (INS) (r = 0.48, 95% CI: 0.37−0.57, p < 0.001), and homeostasis model assessment (HOMA)- insulin resistance (IR) (r = 0.44, 95% CI: 0.33−0.53, p < 0.001). The subgroup analysis according to country or overweight and obesity indicated that these associations remained significant between FMP and INS or HOMA-IR. Our results demonstrated that there is a positive relationship between FMP and FPG. Moreover, subgroup analysis according to country or overweight and obesity indicated that FMP is significantly associated with INS and HOMA-IR. This is the first known systematic review and meta-analysis to determine the associations of FMP with glucose metabolism in children and adolescents.

Body Composition in Preschool Children and the Association With Prepregnancy Weight and Gestational Weight Gain: An Ambispective Cohort Study.

Objective: To describe the body composition in preschool children and to evaluate the association with prepregnancy BMI and gestational weight gain (GWG). Methods: Children were recruited in their first year in kindergarten (3 years old) and followed up for the next 2 years. Information during pregnancy and birth was retrieved from medical records. Height, weight, fat mass, fat-free mass, and percentage of body fat (FM%) were measured through a bioelectrical impedance analysis for each child visit, and BMI, fat mass index (FMI), and fat-free mass index (FFMI) were calculated. Generalized linear mixed models (GLMMs) were used to evaluate the associations between prepregnancy weight, GWG, and adiposity indicators. Results: A total of 3,329 single-birth 3-year-old children were recruited as the baseline population and were followed at 4 and 5 years old. During the 3 years of follow-up, the mean (±SD) values of BMI, FMI, FFMI, and FM% of the children were 15.6 (±1.6) kg/m2, 2.8 (±1.3) kg/m2, 12.8 (±0.7) kg/m2, and 17.2% (±5.8%), respectively. The prevalence rates of overweight and obesity in mothers before pregnancy were 16.6 and 3.2%, respectively. Mothers were divided into three groups based on GWG: appropriate (1,233, 37.0%), excessive (767, 23.0%), and insufficient (1,329, 39.9%). GLMMs analyses showed that the preschool children's BMI, FMI, FFMI, and FM% were all significantly positively related to maternal prepregnancy BMI and GWG (all P < 0.001); the children of mothers who were overweight/obese before pregnancy were more likely to be overweight/obese, high FMI, high FFMI, and high FM% at preschool age (all P < 0.001); although maternal excessive GWG was not correlated with offspring's overweight/obese (P = 0.156), the children of mothers with excessive GWG are more likely to have higher FMI, but not to be with a higher FFMI status than the children of mothers with appropriate GWG. For prepregnancy overweight/obese women, compared with the GWG-appropriate group, maternal excessive GWG was related to the risk of high FMI (coefficient = 0.388, 95% CI: 0.129-0.647) and high FM% (coefficient = 0.352, 95% CI: 0.097-0.607), but was not related to the risk of overweight/obese or high FFMI of the offspring at preschool age. Conclusion: Fat mass index decreased with age, while FFMI increased with age among 3- to 5-year-old children. It is necessary to optimize maternal weight prior to conception and GWG management to improve the health outcomes of the offspring.

Characteristics of Body Composition Estimated by Air-Displacement Plethysmography in Chinese Preschool Children.

Objective: To describe the characteristics of body composition by air-displacement plethysmography (ADP) among Chinese preschool children. Methods: Preschool children were recruited from three kindergartens. Adiposity indices were evaluated using the ADP method. BMI, fat mass index (FMI), fat-free mass index (FFMI) and waist-to-height ratio (WHtR) were calculated. Overweight and obesity were diagnosed using the WHO reference. Analyses were executed by SPSS and MedCalc software. Smoothed curves were constructed using the lambda-mu-sigma (LMS) method. Results: This study evaluated the growth trend for body composition of ADP-based body fat indices based on a relatively large sample of preschool children, the first ever reported in China. A total of 1,011 children aged 3-5 years comprised our study population. BMI and FFMI increased with age, but the slope (P = 0.710) and y intercept (P = 0.132) in the BMI trend analysis demonstrated no differences between boys and girls. For the FFMI trend lines, the slope was significantly higher for boys than for girls (P = 0.013). The percentage of fat mass (FM%), FMI, and WHtR were negatively correlated with age for both sexes, except for FMI in girls (P = 0.094). The 95% CI regression lines for FM% according to different weight statuses intersected. Conclusions: ADP is applicable to estimating body composition among Chinese preschool children. Misclassifications might occur when overweight/obese status is defined based on surrogate indices.

Association of Cesarean Delivery with Trajectories of Growth and Body Composition in Preschool Children.

This study aimed to examine the association of cesarean delivery with trajectories of growth and body composition in preschool children. This ambidirectional cohort study was conducted between 2017 and 2020 in China. Information on the delivery mode, weight, and length/height of the children measured at routine healthcare visits was obtained from maternal and child health records. For three years while in kindergarten, children's body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and percentage of body fat (FM%) were repeatedly measured. A BMI z score (zBMI) was calculated and standardized to WHO measures, and overweight and obesity were defined using the WHO reference. After adjustment for maternal age, maternal education, annual family income, prepregnancy BMI, gestational weight gain, gravidity, parity, gestational age, child sex, birthweight, breastfeeding duration, and the parent-reported dietary intake of the children, children born via cesarean delivery (n = 1992) versus those born vaginally (n = 1578) had higher zBMI growth rates beyond 36 months (ß: 0.003; 95% CI: 0.001, 0.005 SD units/month) and elevated levels of FMI (ß: 0.097; 95% CI: 0.026, 0.168 kg/m2), FM% (ß: 0.402; 95% CI: 0.058, 0.745%) and zBMI (ß: 0.073; 95% CI: 0.012, 0.133 units), but not FFMI (ß: 0.022; 95% CI: -0.022, 0.066 kg/m2). The adjusted OR of overweight and obesity was 1.21 (95% CI: 1.04, 1.40). Cesarean delivery likely elevated zBMI growth rates and increased the risk of overweight and obesity in preschool children, with the elevation of fat mass but not fat-free mass.

The Relationship Between Fat-Free Mass and Glucose Metabolism in Children and Adolescents: A Systematic Review and Meta-Analysis.

Purpose: To assess the relationship between fat-free mass (FFM) and glucose metabolism in children 0-18 years of age. Methods: We performed a systematic review of the literature on Medline/PubMed, SinoMed, Embase, and the Cochrane Library using the PRISMA 2020 guidelines to 12 October 2021; this encompassed observational studies in which the relationship between FFM and glucose metabolism was assessed. Correlation coefficient (r), regression coefficient (ß), and odds ratio (OR) values in the studies were extracted and recorded as the primary data. "Agency for Healthcare Research and Quality" quality-assessment forms recommended for cross-sectional/prevalence studies were applied to evaluate the quality of the selected studies, and we executed R software to combine the pooled data. Results: We included eight studies comprising 13,282 individuals, five of which involved the assessment of the relationship between FFM and blood glucose, and four on the relationship between FFM and insulin resistance (IR). Our results showed that FFM was significantly associated with fasting plasma insulin levels (r = 0.34, 95% CI: 0.30-0.39, P < 0.001). Due to high heterogeneity or insufficient quantity of data, the studies of the relationship between FFM and fasting plasma glucose, HOMA-IR, or HbA1c were not congruent, and were therefore not suitable for meta-analysis. Conclusion: Our results indicated that FFM was significantly associated with fasting plasma insulin levels. As far as we have determined, this is the first-ever systematic review and meta-analysis of the associations between FFM and glucose metabolism in children and adolescents; and our results thus provide novel information to fill a gap in the literature in this area. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020150320, PROSPERO CRD42020150320.

Combined Analysis of Surface Protein Profile and microRNA Expression Profile of Exosomes Derived from Brain Microvascular Endothelial Cells in Early Cerebral Ischemia.

Endothelial cell damage is an important pathological basis for the deterioration of acute ischemia stroke. Our previous studies have been exploring the mechanism of blood-brain barrier (BBB) endothelial cell injury in the early stage of cerebral ischemia. Exosomes act as an important intercellular player in neurovascular communication. However, the characteristic of exosomes derived from BBB endothelial cells in early ischemic stroke is poorly understood. We exposed cultured brain microvascular endothelial cells (bEnd.3) to 3 h oxygen glucose deprivation (OGD) to mimic early cerebral ischemia in vitro and compared miRome and surface protein contents of exosomes derived from bEnd.3 cells by miRNA sequencing and the proximity barcoding assay (PBA). A total of 346 differentially miRNA (159 upregulated and 187 downregulated) were identified via miRNA-Seq in bEnd.3 cells after exposure to OGD for 3 h. Moreover, Gene Ontology (GO) and KEGG pathway analyses showed that cell proliferation- and angiogenesis-associated miRNAs were significantly affected. The abnormal changes in top eight miRNAs were further verified by a quantitative polymerase chain reaction (qPCR). PBA experiments showed that the numbers of exosomes carrying the following proteins increased significantly under ischemia, including bFGF, CD146, EPHA2, ABCB5, and ITGB2. These proteins were related to angiogenesis, cell proliferation, and cell inflammation. The network analysis combining PBA data with miRNA-Seq data showed that 79 miRNAs were related to 24 membrane proteins and predicted that there were surface proteins associated with a variety of miRNA molecules, such as ITGA9, XIAP, ADAM1, ITGA2, ITGA3, PDPN, and ITGB1. Meanwhile, there were miRNAs related to various surface proteins including miR-410-3p, miR-378b, and miR-1960. Taken together, our data demonstrated for the first time the changes of exosomal miRNAs and surface protein profiles derived from ischemic microvascular endothelial cells, which may provide new therapeutic targets for BBB protection in ischemic stroke.

Machine and Deep Learning for Prediction of Subcellular Localization.

Protein subcellular localization prediction (PSLP), which plays an important role in the field of computational biology, identifies the position and function of proteins in cells without expensive cost and laborious effort. In the past few decades, various methods with different algorithms have been proposed in solving the problem of subcellular localization prediction; machine learning and deep learning constitute a large portion among those proposed methods. In order to provide an overview about those methods, the first part of this article will be a brief review of several state-of-the-art machine learning methods on subcellular localization prediction; then the materials used by subcellular localization prediction is described and a simple prediction method, that takes protein sequences as input and utilizes a convolutional neural network as the classifier, is introduced. At last, a list of notes is provided to indicate the major problems that may occur with this method.

Phragmunis a suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Glioblastoma (GBM) is a highly aggressive brain tumor. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Studies investigating the mechanism revealed that PGA diminished the binding efficiency of ETS family of transcription factor (ELK1) and Serum response factor (SRF), and suppressed ELK1-SRF complex-dependent transcription, which decreased the transcriptional levels of downstream genes Early growth response protein 1 (EGR1)-Polycomb ring finger (BMI1), thus inducing the imbalanced regulation between Myeloid cell leukaemia-1 (MCL1) and F-Box and WD repeat domain containing 7 (FBXW7). Finally, orthotopic xenograft models were established to confirm the anti-glioma effect of PGA on tumour growth. We showed, for the first time, that the cytotoxic effects of PGA occurred by inducing MCL1 inhibition and FBXW7 activation by blocking ELK1-SRF complex-dependent transcription. The blockage of ELK1-mediated transcription resulted in the suppression of EGR1-BMI1, which led to the upregulation of FBXW7 expression and downregulation of MCL1. These findings suggested that PGA could be a therapeutic drug candidate for the treatment of recurrent GBM by targeting the ELK1-SRF complex.

Moschamindole induces glioma cell apoptosis by blocking Mia40-dependent mitochondrial intermembrane space assembly and oxidative respiration.

Glioblastoma multiforme (GBM) is the most frequent, lethal, and aggressive tumor of the central nervous system in adults. In this study, we found for the first time that moschamindole (MCD), a rare phenolic amide with 8/6/6/5/5 rings, is a major bioactive constituent derived from Phragmites communis Trin (Poaceae) that exhibits a potential cytotoxic effect on both TMZ-resistant GBM cell lines and xenograft models. MCD-induced intrinsic apoptosis signals and mitochondrial dysfunction were confirmed by cell cycle arrest, caspase-3/7 activation, and membrane potential depolarization. Furthermore, investigations exploring the mechanism showed that MCD specifically inhibits Mia40-mediated oxidative folding of mitochondrial intermembrane space (IMS) proteins via PCR assay and immunoblot analysis. MCD relies on its positive charge to associate with mitochondrial oxidative respiration, thus blocking energy metabolism and inducing apoptosis. Overexpression and upregulation of Mia40 were proven to reverse MCD-induced apoptosis and were correlated with the chemoresistance of GBM in vitro and in vivo, respectively. Taken together, our study demonstrates that Mia40 is a potential target of the chemoresistance of glioblastoma and suggests that MCD might be a potential agent for the individualized treatment of chemoresistant GBM based on mitochondrial metabolic characteristics and Mia40 expression.