The temporal protein signature analyses of developing human deciduous molar tooth germ.

The tooth serves as an exemplary model for developmental studies, encompassing epithelial-mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time-dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap-to-early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co-expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single-cell RNA-sequencing (scRNA-seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

Serum betaine and dimethylglycine in mid-pregnancy and the risk of gestational diabetes mellitus: a case-control study.

PURPOSE: To investigate the associations of choline, betaine, dimethylglycine (DMG), L-carnitine, and Trimethylamine-N-oxide (TMAO) with the risk of Gestational diabetes mellitus (GDM) as well as the markers of glucose homeostasis. METHODS: We performed a case-control study including 200 diagnosed GDM cases and 200 controls matched by maternal age (±2 years) and gestational age (±2 weeks). Concentrations of serum metabolites were measured by the high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). RESULTS: Compared to the control group, GDM group had significantly lower serum betaine concentration and betaine/choline ratio, and higher DMG concentration. Furthermore, decreased betaine concentration and betaine/choline ratio, increased DMG concentration showed significant association with the risk of GDM. In addition, serum betaine concentrations were negatively associated with blood glucose levels at 1-h post-glucose load (OGTT-1h), and both betaine and L-carnitine concentrations were positively associated with 1,5-anhydroglucitol levels. Betaine/choline ratio was negatively associated with OGTT-1h and blood glucose levels at 2-h post-glucose load (OGTT-2h) and serum choline concentrations were negatively associated with fasting blood glucose and positively associated with OGTT-2h. CONCLUSION: Decreased serum betaine concentrations and betaine/choline ratio, and elevated DMG concentrations could be significant risk factors for GDM. Furthermore, betaine may be associated with blood glucose regulation and short-term glycemic fluctuations.

Preeclampsia/eclampsia impacts the structure and function of neonatal hearts probably by reducing myocardial compaction.

PURPOSE: Preeclampsia/Eclampsia (PE/E) poses significant risks to neonatal cardiac health. Traditional echocardiographic methods have limitations in detailing these impacts. This study hypothesized that echocardiographic radiomics could provide a more comprehensive assessment of the cardiac changes in neonates affected by PE/E. METHOD: In a comprehensive analysis, 2594 neonates underwent echocardiographic screening. From these, 556 were selected for detailed radiomics analysis, focusing on cardiac shape, movement, and texture features. A multiblock sparse partial least squares (sPLS) model integrated these features to assess their association with PE/E. RESULTS: Newborns from PE/E-affected pregnancies displayed lower left ventricular ejection fractions compared to the control group (61.1 % vs. 66.2 %). Our radiomics approach extracted 15,494 features per neonate, with the sPLS model identifying 17 features significantly correlated with PE/E. Among these, texture features representing myocardial non-compaction were most strongly correlated with PE/E (correlation coefficient r = 0.63). Detailed visualization of these texture features suggested that PE/E might lead to more pronounced myocardial non-compaction, characterized by a thicker non-compaction layer and increased cardiac trabeculation. CONCLUSIONS: Our findings demonstrate the potential of echocardiographic radiomics as a tool for assessing the impact of PE/E on neonatal cardiac function. The correlation between PE/E and myocardial non-compaction underlines the need for enhanced cardiac monitoring in neonates born to PE/E-affected mothers. This study contributes to a better understanding of PE/E's cardiac implications, potentially guiding future clinical practices.

Randomized controlled trial comparing the impacts of Saccharomyces boulardii and Lactobacillus rhamnosus OF44 on intestinal flora in cerebral palsy rats: insights into inflammation biomarkers and depression-like behaviors.

Background: Cerebral palsy (CP) is a unique neurological disorder which adversely affects motion. Cytokines and gut microbial composition contribute to CP and other diseases, such as reproductive tract inflammation and bone loss. Importantly, Saccharomyces boulardii (S. boulardii) reduces the degree of inflammation and improves overall health status. As our previous study showed that Lactobacillus rhamnosus (L. rhamnosus) OF44, a selected strain of gut bacteria originally used to treat reproductive tract inflammation and bone loss, has effects similar to that of S. boulardii, we decided to use L. rhamnosus OF44 on CP rats. Validation of the effects of L. rhamnosus OF44 on CP adds to its confirmed effects in treating osteoporosis and reproductive tract microbiota disorders, increasing its potential as a probiotic. The purpose of this was to ascertain whether L. rhamnosus OF44 can alleviate the symptoms of CP. Methods: CP rat models were created through left carotid artery ligation. Following this, 100-day old CP rats were exposed to L. rhamnosus OF44, S. boulardii, or normal saline gastric gavage daily for 28 days. Grouping of the rats is determined randomly. Before and after the gavage, behavioral experiments were conducted and the inflammation levels assessed via measurements of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) inflammatory markers. The efficacy of the outcome is measured by performing statistical analysis like the t-test on the data to see its significance. Additionally, variations inside gut microbiome were evaluated via 16S ribosomal RNA sequencing. Results: Before intervention, CP rats failed to exhibit depression-like behavior (P=0.6). L. rhamnosus OF44 treatment significantly reduced the level of IL-6 (P=4.8e-05), S. boulardii treatment significantly reduced the level of TNF-α (P=0.04). In addition, both treatments altered the composition and complexity of the gut microbiome. Conclusions: Our results indicated that L. rhamnosus OF44 has potential in alleviating inflammation and altering the gut microbial composition in CP, and that it has the potential to clinically treat CP. There are some limitations of this study. For example, dietary differences and their effects on gastrointestinal dysfunction are not considered in this study, and only two behavioral experiments were used.

Genetic basis of pregnancy-associated decreased platelet counts and gestational thrombocytopenia.

ABSTRACT: Platelet count reduction occurs throughout pregnancy, with 5% to 12% of pregnant women being diagnosed with gestational thrombocytopenia (GT), characterized by a more marked decrease in platelet count during pregnancy. However, the underlying biological mechanism behind these phenomena remains unclear. Here, we used sequencing data from noninvasive prenatal testing of 100 186 Chinese pregnant individuals and conducted, to our knowledge, the hitherto largest-scale genome-wide association studies on platelet counts during 5 periods of pregnancy (the first, second, and third trimesters, delivery, and the postpartum period) as well as 2 GT statuses (GT platelet count < 150 × 109/L and severe GT platelet count < 100 × 109/L). Our analysis revealed 138 genome-wide significant loci, explaining 10.4% to 12.1% of the observed variation. Interestingly, we identified previously unknown changes in genetic effects on platelet counts during pregnancy for variants present in PEAR1 and CBL, with PEAR1 variants specifically associated with a faster decline in platelet counts. Furthermore, we found that variants present in PEAR1 and TUBB1 increased susceptibility to GT and severe GT. Our study provides insight into the genetic basis of platelet counts and GT in pregnancy, highlighting the critical role of PEAR1 in decreasing platelet counts during pregnancy and the occurrence of GT. Those with pregnancies carrying specific variants associated with declining platelet counts may experience a more pronounced decrease, thereby elevating the risk of GT. These findings lay the groundwork for further investigation into the biological mechanisms and causal implications of GT.

Dietary protein in early pregnancy and gestational diabetes mellitus: a prospective cohort study.

PURPOSE: The relationship between dietary protein intake and the risk of gestational diabetes mellitus (GDM) remains inconsistent and unclear. Here, we examined the correlation between the various sources of protein intake among Chinese pregnant women and GDM. METHODS: This prospective cohort study included 1060 pregnant women at 6-13+6 weeks of gestation from Guangdong Provincial Hospital for Women and Children, South China. The participants' intake of dietary protein was assessed using a validated quantitative food frequency questionnaire during the early trimester. GDM was diagnosed via an oral glucose tolerance test performed at 24-28 gestational weeks. Logistic regression analysis was used to evaluate the association between dietary protein intake during pregnancy and GDM. Furthermore, we applied restricted cubic splines to determine their linear relationship. RESULTS: About 26.3% (n = 279) of pregnant women were diagnosed with GDM. Animal protein intake was revealed to have a positive correlation with GDM risk (Q4 vs. Q1: OR, 2.78; 95% CI, 1.46-5.34; P = 0.015), whereas high intake levels of dietary plant protein were linked to reduced GDM risk (Q4 vs. Q1: OR, 0.43; 95% CI, 0.25-0.73). In stratified analysis, the relationship between protein and GDM was stronger during early pregnancy in women with obesity. However, total protein intake did not show a significant association with GDM. CONCLUSIONS: Our study findings suggest that a plant protein-based diet was associated with reduced GDM risk, whereas the dietary intake of animal protein was positively associated with GDM risk among Chinese women during early pregnancy.

Taxifolin Inhibits the Growth of Non-Small-Cell Lung Cancer via Downregulating Genes Displaying Novel and Robust Associations with Immune Evasion Factors.

Using an LL2 cell-based syngeneic mouse LC model, taxifolin suppressed allografts along with the appearance of 578 differentially expressed genes (DEGs). These DEGs were associated with enhancement of processes related to the extracellular matrix and lymphocyte chemotaxis as well as the reduction in pathways relevant to cell proliferation. From these DEGs, we formulated 12-gene (TxflSig) and 7-gene (TxflSig1) panels; both predicted response to ICB (immune checkpoint blockade) therapy more effectively in non-small-cell lung cancer (NSCLC) than numerous well-established ICB biomarkers, including PD-L1. In both panels, the mouse counterparts of ITGAL, ITGAX, and TMEM119 genes were downregulated by taxifolin. They were strongly associated with immune suppression in LC, evidenced by their robust correlations with the major immunosuppressive cell types (MDSC, Treg, and macrophage) and multiple immune checkpoints in NSCLC and across multiple human cancer types. ITGAL, ITGAX, and IIT (ITGAL-ITGAX-TMEM119) effectively predicted NSCLC's response to ICB therapy; IIT stratified the mortality risk of NSCLC. The stromal expressions of ITGAL and ITGAX, together with tumor expression of TMEM119 in NSCLC, were demonstrated. Collectively, we report multiple novel ICB biomarkers-TxflSig, TxflSig1, IIT, ITGAL, and ITGAX-and taxifolin-derived attenuation of immunosuppressive activities in NSCLC, suggesting the inclusion of taxifolin in ICB therapies for NSCLC.

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.

Background: Recently years have seen the increasing evidence identifying that OXPHOS is involved in different processes of tumor progression and metastasis and has been proposed to be a potential therapeutical target for cancer treatment. However, the exploration in oxidative phosphorylation-mediated chemoresistance is still scarce. In our study, we identify exosomal transfer leads to chemoresistance by reprogramming metabolic phenotype in recipient cells. Methods: RNA sequencing analysis was used to screen altered targets mediating exosome transfer-induced chemoresistance. Seahorse assay allowed us to measure mitochondrial respiration. Stemness was measured by spheroids formation assay. Serum exosomes were isolated for circ_0001610 quantification. Results: The induced oxidative phosphorylation leads to more stem-like properties, which is dependent on the transfer of exosomal circ_0001610. Exosome transfer results in the removal of miR-30e-5p-mediated suppression of PGC-1a, a master of mitochondrial biogenesis and function. Consequently, increased PGC-1a reshapes cellular metabolism towards oxidative phosphorylation, leading to chemoresistance. Inhibition of OXPHOS or exosomal si-circ_0001610 increases the sensitivity of chemotherapy by decreasing cell stemness in vitro and in vivo. Conclusion: Our data suggests that exosomal circ_0001610-induced OXPHOS plays an important role in chemoresistance and supports a therapeutical potential of circ_0001610 inhibitors in the treatment of oxaliplatin-resistant colorectal cancer by manipulating cell stemness.

Chromosome instability region analysis and identification of the driver genes of the epithelial ovarian cancer cell lines A2780 and SKOV3.

Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers worldwide. The molecular mechanisms of serous ovarian cancer (SOC) remain unclear and not well understood. SOC cases are primarily diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to obtain a better understanding of precise molecular mechanisms and to identify the chromosome instability region and key driver genes in the carcinogenesis and progression of SOC. Whole-exome sequencing was performed on the normal ovarian cell line IOSE80 and the EOC cell lines SKOV3 and A2780. The single-nucleotide variation burden, distribution, frequency and signature followed the known ovarian mutation profiles, without chromosomal bias. Recurrently mutated ovarian cancer driver genes, including LRP1B, KMT2A, ARID1A, KMT2C and ATRX were also found in two cell lines. The genome distribution of copy number alterations was found by copy number variation (CNV) analysis, including amplification of 17q12 and 4p16.1 and deletion of 10q23.33. The CNVs of MED1, GRB7 and MIEN1 located at 17q12 were found to be correlated with the overall survival of SOC patients (MED1: p = 0.028, GRB7: p = 0.0048, MIEN1: p = 0.0051), and the expression of the three driver genes in the ovarian cell line IOSE80 and EOC cell lines SKOV3 and A2780 was confirmed by western blot and cell immunohistochemistry.

HSD17B6 delays type 2 diabetes development via inhibiting SREBP activation.

BACKGROUND: The SREBP/SCAP/INSIG complex plays an essential role in SREBP activation and de novo lipogenesis. Whether the activation process is affected by hydroxysteroid 17-beta dehydrogenase 6 (HSD17B6) remains unknown. METHODS: SREBP's transcriptional activities were analyzed using an SRE-luciferase (SRE-luc) reporter in 293T cells, Huh7 hepatoma cells, and primary human hepatocytes following a variety of conditions, including ectopic expression of HSD17B6, HSD17B6 mutants defective in its enzymatic activities, knockdown of HSD17B6, and cholesterol starvation. The interaction between HSD17B6 and SREBP/SCAP/INSIG complex was analyzed in 293T cells, Huh7 cells and mouse liver upon ectopic expression of HSD17B6 and its mutants; the interaction was also analyzed using endogenous proteins. The impacts of HSD17B6 on SREBP target expression, glucose tolerance, diet-induced obesity, and type 2 diabetes (T2D) were examined using Huh7 cells in vitro, and with C57BL/6 and NONcNZO10/LtJ T2D mice in vivo. RESULTS: HSD17B6 binds to the SREBP/SCAP/INSIG complex and inhibits SREBP signaling in cultured hepatocytes and mouse liver. Although HSD17B6 plays a role in maintaining the equilibrium of 5α-dihydrotestosterone (DHT) in the prostate, a mutant defective in androgen metabolism was as effective as HSD17B6 in inhibiting SREBP signaling. Hepatic expression of both HSD17B6 and the defective mutant improved glucose intolerance and reduced hepatic triglyceride content in diet-induced obese C57BL/6 mice, while hepatic knockdown of HSD17B6 exacerbated glucose intolerance. Consistent with these results, liver-specific expression of HSD17B6 in a polygenic NONcNZO10/LtJ T2D mice reduced T2D development. CONCLUSIONS: Our study unveils a novel role of HSD17B6 in inhibiting SREBP maturation via binding to the SREBP/SCAP/INSIG complex; this activity is independent of HSD17B6's sterol oxidase activity. Through this action, HSD17B6 improves glucose tolerance and attenuates the development of obesity-induced T2D. These findings position HSD17B6 as a potential therapeutic target for T2D therapy.

Shorter telomere length in children with autism spectrum disorder is associated with oxidative stress.

Objective: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD. Methods: In this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits. Results: The TL of the ASD group was shorter than the TD group (p < 0.01) and had some accurate predictive significance for the identification of ASD (AUC = 0.632, 95% CI: 0.533-0.710, p = 0.002). Both 8-OHdG content and SOD activity in the ASD group were significantly higher than those in the TD group (p < 0.05). Shortened TL (Monofactor: 2.20 (1.22, 3.96), p = 0.009; Multifactor: 2.22 (1.22, 4.00), p = 0.008) and reduced CAT activity (Monofactor: 2.31 (1.28, 4.17), p = 0.006; Multifactor: 2.31 (1.28, 4.18), p = 0.006) are risk factors for the development of ASD, while reduced 8-OHdG content (Monofactor: 0.29 (0.14, 0.60), p = 0.001; Multifactor: 0.27 (0.13, 0.57), p = 0.001) and reduced SOD activity (Monofactor: 0.55 (0.31, 0.98), p = 0.042; Multifactor: 0.54 (0.30, 0.98), p = 0.042) are protective factors for the development of ASD. Conclusion: In this study, TL and OS were significantly different between the ASD group and the TD group. As guanine-rich telomere sequences were likely damaged by oxygen free radicals, creating OS, which is a factor in the incidence and progression of ASDs. In conclusion, oxidative damage occurs in the bodies of children with ASD, which may lead to sustained disease progression and severe clinical manifestations. We assume that timely supplementation of antioxidants is very likely to be a potential treatment for early intervention in children with ASD. Identification and detection of OS-related biomarkers may contribute to early diagnosis and timely interventions in young patients with ASD.

Taxifolin Inhibits Breast Cancer Growth by Facilitating CD8+ T Cell Infiltration and Inducing a Novel Set of Genes including Potential Tumor Suppressor Genes in 1q21.3.

Taxifolin inhibits breast cancer (BC) via novel mechanisms. In a syngeneic mouse BC model, taxifolin suppressed 4T-1 cell-derived allografts. RNA-seq of 4T-1 tumors identified 36 differentially expressed genes (DEGs) upregulated by taxifolin. Among their human homologues, 19, 7, and 2 genes were downregulated in BCs, high-proliferative BCs, and BCs with high-fatality risks, respectively. Three genes were established as tumor suppressors and eight were novel to BC, including HNRN, KPRP, CRCT1, and FLG2. These four genes exhibit tumor suppressive actions and reside in 1q21.3, a locus amplified in 70% recurrent BCs, revealing a unique vulnerability of primary and recurrent BCs with 1q21.3 amplification with respect to taxifolin. Furthermore, the 36 DEGs formed a multiple gene panel (DEG36) that effectively stratified the fatality risk in luminal, HER2+, and triple-negative (TN) equivalent BCs in two large cohorts: the METABRIC and TCGA datasets. 4T-1 cells model human TNBC cells. The DEG36 most robustly predicted the poor prognosis of TNBCs and associated it with the infiltration of CD8+ T, NK, macrophages, and Th2 cells. Of note, taxifolin increased the CD8+ T cell content in 4T-1 tumors. The DEG36 is a novel and effective prognostic biomarker of BCs, particularly TNBCs, and can be used to assess the BC-associated immunosuppressive microenvironment.

Noninvasive preeclampsia prediction using plasma cell-free RNA signatures.

BACKGROUND: Preeclampsia, especially preterm preeclampsia and early-onset preeclampsia, is a life-threating pregnancy disorder, and the heterogeneity and complexity of preeclampsia make it difficult to predict risk and to develop treatments. Plasma cell-free RNA carries unique information from human tissue and may be useful for noninvasive monitoring of maternal, placental, and fetal dynamics during pregnancy. OBJECTIVE: This study aimed to investigate various RNA biotypes associated with preeclampsia in plasma and to develop classifiers to predict preterm preeclampsia and early-onset preeclampsia before diagnosis. STUDY DESIGN: We performed a novel, cell-free RNA sequencing method termed polyadenylation ligation-mediated sequencing to investigate the cell-free RNA characteristics of 715 healthy pregnancies and 202 pregnancies affected by preeclampsia before symptom onset. We explored differences in the abundance of different RNA biotypes in plasma between healthy and preeclampsia samples and built preterm preeclampsia and early-onset preeclampsia prediction classifiers using machine learning methods. Furthermore, we validated the performance of the classifiers using the external and internal validation cohorts and assessed the area under the curve and positive predictive value. RESULTS: We detected 77 genes, including messenger RNA (44%) and microRNA (26%), that were differentially expressed in healthy mothers and mothers with preterm preeclampsia before symptom onset, which could separate participants with preterm preeclampsia from healthy samples and that played critical functional roles in preeclampsia physiology. We developed 2 classifiers for predicting preterm preeclampsia and early-onset preeclampsia before diagnosis based on 13 cell-free RNA signatures and 2 clinical features (in vitro fertilization and mean arterial pressure), respectively. Notably, both classifiers showed enhanced performance when compared with the existing methods. The preterm preeclampsia prediction model achieved 81% area under the curve and 68% positive predictive value in an independent validation cohort (preterm, n=46; control, n=151); the early-onset preeclampsia prediction model had an area under the curve of 88% and a positive predictive value of 73% in an external validation cohort (early-onset preeclampsia, n=28; control, n=234). Furthermore, we demonstrated that downregulation of microRNAs may play vital roles in preeclampsia through the upregulation of preeclampsia-relevant target genes. CONCLUSION: In this cohort study, a comprehensive transcriptomic landscape of different RNA biotypes in preeclampsia was presented and 2 advanced classifiers with substantial clinical importance for preterm preeclampsia and early-onset preeclampsia prediction before symptom onset were developed. We demonstrated that messenger RNA, microRNA, and long noncoding RNA can simultaneously serve as potential biomarkers of preeclampsia, holding the promise of prevention of preeclampsia in the future. Abnormal cell-free messenger RNA, microRNA, and long noncoding RNA molecular changes may help to elucidate the pathogenic determinants of preeclampsia and open new therapeutic windows to effectively reduce pregnancy complications and fetal morbidity.

Effectiveness of Peer Support on Quality of Life and Anxiety in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Background: Breast cancer patients report high levels of psychosocial maladjustment after hospital discharge. Peer support may play an important role in improving anxiety and quality of life in breast cancer patients. This study aimed to assess the effect of peer support on quality of life and anxiety in breast cancer patients. Method: A systematic review and meta-analysis of randomized controlled studies were conducted, using data sourced from PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, SinoMed, China Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang Data for randomized controlled trials (RCTs) from inception to October 15, 2021. The RCTs reporting the effect of peer support intervention on quality of life and anxiety in breast cancer patients were included. The quality of evidence was assessed using the Cochrane risk of bias tool, that is, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for the pooled effect size. Results: A total of 14 studies were included in the systematic review and 11 in the meta-analysis. The pooled results revealed that peer support significantly improved quality of life (SMD = 0.69, 95% CI = 0.28-1.11) and anxiety (SMD = -0.45, 95% CI = -0.88 to -0.02) in breast cancer patients. The quality of evidence was low as all studies showed the risk of bias and inconsistency. Conclusion: Peer support intervention has the potential to effectively improve psychosocial adaptations in breast cancer patients. Future studies with a robust design and larger sample size are needed to investigate the potential factors associated with the beneficial effects of peer support.

Prognostic Significance of Cuproptosis-Related Gene Signatures in Breast Cancer Based on Transcriptomic Data Analysis.

Breast cancer (BRCA) remains a serious threat to women's health, with the rapidly increasing morbidity and mortality being possibly due to a lack of a sophisticated classification system. To date, no reliable biomarker is available to predict prognosis. Cuproptosis has been recently identified as a new form of programmed cell death, characterized by the accumulation of copper in cells. However, little is known about the role of cuproptosis in breast cancer. In this study, a cuproptosis-related genes (CRGs) risk model was constructed, based on transcriptomic data with corresponding clinical information relating to breast cancer obtained from both the TCGA and GEO databases, to assess the prognosis of breast cancer by comprehensive bioinformatics analyses. The CRGs risk model was constructed and validated based on the expression of four genes (NLRP3, LIPT1, PDHA1 and DLST). BRCA patients were then divided into two subtypes according to the CRGs risk model. Furthermore, our analyses revealed that the application of this risk model was significantly associated with clinical outcome, immune infiltrates and tumor mutation burden (TMB) in breast cancer patients. Additionally, a new clinical nomogram model based on risk score was established and showed great performance in overall survival (OS) prediction, confirming the potential clinical significance of the CRGs risk model. Collectively, our findings revealed that the CRGs risk model can be a useful tool to stratify subtypes and that the cuproptosis-related signature plays an important role in predicting prognosis in BRCA patients.

Correlations between gastrointestinal and oral microbiota in children with cerebral palsy and epilepsy.

We here studied the correlation between gut and oral microbiota in children with cerebral palsy and Epilepsy (CPE). We enrolled 27 children with this condition from the social welfare center of Longgang District, collected their oral plaque and stool samples, and analyzed their gut microbiota (GM) and oral microbiota (OM) through 16S rRNA gene sequencing. Taxonomical annotation revealed that the levels of Firmicutes and Bacteroides in the oral cavity were significantly lower in CPE children than in healthy children, whereas the abundance of Actinomycetes increased significantly in CPE children. In addition, Prevotella, Fusobacterium, and Neisseria were the top three abundant genera, representing 15.49%, 9.34%, and 7.68% of the OM and suggesting potential correlations with caries, periodontitis, and malnutrition. For the GM, Bifidobacterium, Bacteroides, and Prevotella were the top three abundant genera in CPE children and probably contributed to the development of chronic inflammation and malnutrition. Furthermore, the OM and GM correlated with each other closely, and the bacterial components of these microbiota in CPE children were remarkably different from those in healthy children, such as Bifidobacterium, Fusobacterium, Bacteroides, and Neisseria. Conclusively, dysbiotic OM can translocate to the intestinal tract and induce GM dysbiosis, suggesting the consistency between OM and GM variations. Altered oral and gut microbial structures have potential impacts on the occurrence of clinical diseases such as periodontitis, caries, and malnutrition.

Targeted Next-Generation Sequencing Reveals a Large Novel ß-Thalassemia Deletion that Removes the Entire HBB Gene.

ß-Thalassemia (ß-thal) is one of the most common monogenic recessive inherited diseases worldwide. The mutation spectrum of ß-thal has been increasingly broadened by various genetic testing methods. The discovery and identification of novel and rare pathogenic thalassemia variants enable better disease prevention, especially in high prevalence regions. In this study, a Chinese thalassemia family with an unclear etiology was recruited to the Thalassemia Screening Program. Blood samples collected from them were primarily screened by hematology analysis and clinical routine genetic screening. Subsequently, targeted next-generation sequencing (NGS) and Sanger sequencing were performed to find and identify a novel deletion variant. The deletion, discovered by targeted NGS, was validated through real-time quantitative polymerase chain reaction (qPCR). First, a large novel ß-thal deletion (3488 bp) related to a high Hb F level, NC_000011.9: g.5245533_5249020del (Chongqing deletion) (GRCh37/hg19), was found and identified in the proband and her mother. The deletion removed the entire ß-globin gene and led to absent ß-globin (ß0). We then validated this large novel deletion in the proband and her mother by qPCR. We first discovered and identified a large novel ß-thal deletion related to elevated Hb F level, it helps broaden the spectrum of pathogenic mutants that may cause ß-thal intermedia (ß-TI) or ß-thal major (ß-TM), paving the way for effective thalassemia screening. Next-generation sequencing has the potential of finding rare and novel thalassemia mutants.

First report of a Chinese patient carrying Hb Ty Gard: A case report.

RATIONALE: More than 1300 mutations which lead to abnormal hemoglobin (Hb) have been recorded in the HbVar database. Hb Ty Gard has rarely been reported and has not been reported in China. PATIENT CONCERNS AND DIAGNOSES: A 2-year-old Chinese girl was healthy with normal physical development and hematological parameters. Capillary electrophoresis suggested that Hb F increased slightly, while Hb A2 levels were normal. Flow cytometry, fluorescence hybridization, and Sanger sequencing were used to characterize the genotypes. Sanger sequencing detected a heterozygous mutation at codon 124 of the ß-globin gene (HBB: c.374 C > A), which was previously reported as Hb Ty Gard in the HbVar database. OUTCOMES: We report the first case of HbTy Gard in a Chinese population. In areas with a high incidence of Hb diseases, sensitive detection of Hb components and accurate diagnosis of Hb variation are very important, and the combined application of capillary electrophoresis and gene sequencing can diagnose more Hb variants.

Global Research Trends in Gestational Diabetes Mellitus from 2000 to 2020: A Bibliometric Study.

AIMS: This study analyzed major trends and topics in the field of gestational diabetes mellitus research between 2000 and 2020. METHODS: Studies that investigated gestational diabetes mellitus published between 2000 and 2020 were retrieved from the Web of Science Core Collection database. Data from the identified studies were analyzed using CiteSpace software. RESULTS: A total of 22,713 publications were retrieved, among which 21,722 publications were included in this scientometric analysis. Clustering analysis revealed 13 themes across all fields. Physical activity is an emerging trend. Co-word analysis showed that subject high-frequency keywords were: risk factor, obesity, insulin resistance, prevalence, and association. Centrality indices identified the most influential keywords to be: body mass index, risk factors, gestational weight gain, and obesity. Burst keywords revealed that there were six research frontier subtopics: i) prediction of adverse neonatal outcomes in gestational diabetes mellitus; ii) postpartum period research - blood glucose levels and insulin resistance; iii) meta-analysis - understanding the best evidence in pregnancy gestational diabetes mellitus; iv) gene expression profiles and DNA methylation in gestational diabetes mellitus; v) biomarkers for predicting higher birth and children weights; and vi) discussion on diagnostic criteria for gestational diabetes mellitus classification. CONCLUSION: The number of studies on gestational diabetes mellitus is increasing. For two decades, the United States has been the global leader in the number of published studies. Studies on gestational diabetes mellitus are mainly from developed countries, with a few of them being from developing countries. An emerging field of research aims at elucidating the association between physical activity and gestational diabetes mellitus.