Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester.

BACKGROUND: To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy. METHODS: During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 ℃. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups. RESULTS: It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05). CONCLUSION: Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.

Comparison of the inflammatory states of serum and gingival crevicular fluid in periodontitis patients with or without type 2 diabetes mellitus.

Background/purpose:There is a two-way relationship between periodontitis and type 2 diabetes mellitus. This study aimed to compare the inflammatory states in serum and gingival crevicular fluid (GCF) in periodontitis patients with or without type 2 diabetes mellitus (T2DM) and healthy subjects. Materials and methods: 20 subjects were systematic and periodontal healthy (H group), 40 subjects were with periodontitis (CP group), and other 40 were with periodontitis and type 2 diabetes mellitus (DC group). Fasting blood glucose (FBG) and HbA1c was tested. GCF and serum level of interleukin (IL) -17, visfatin, receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL)/osteoprotegerin (OPG) ratio were measured. Results: The GCF volume, total amount of IL-17, vastatin, RANKL/OPG ratio in GCF and their concentrations in serum were higher (P < 0.05) in CP and DC groups than in H group, which were also higher (P < 0.05) in DC group than in CP group except for visfatin in GCF and IL-17 in serum. At sample sites of PD ≤ 3 mm, GCF volume, IL-17, visfatin and RANKL/OPG ratio in DC and CP groups were higher (P < 0.05) than that in H group, which were also higher in DC group than in CP group either with PD ≤ 3 mm or PD > 3 mm. Inflammatory state in GCF was positively correlated to systemic inflammation, and both of them were positively correlated to FBG. Conclusion: Moderate and severe periodontitis aggravated systemic inflammation. T2DM together with periodontitis resulted in more severe systemic inflammation. The positive correlation between the periodontal and systemic inflammation and their association with FBG indicated an inflammatory link between periodontitis and T2DM.

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Auditory Sensory Gating in Children With Cochlear Implants: A P50-N100-P200 Study.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear. Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance. Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children. Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

Organ- and Age-Specific Differences of Dioscorea polystachya Compounds Measured by UPLC-QTOF/MS.

Dioscorea polystachya, named Chinese yam, is widely cultivated as a functional food and natural medicine in China. There is currently little information about the chemical characteristics of Dioscorea polystachya in different organs (tuber cortex and tuber flesh) and at various ages. In this study, an ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used to profile chemical compounds in Dioscorea polystachya. As a result, thirty-eight compounds were detected in yam tuber cortex and tuber flesh. More compounds were detected in yam tuber cortex than in tuber flesh. Compounds such as dehydroepiandrosterone, allantoin and flavonoids were selected as biomarker candidates. Dehydroepiandrosterone was found more abundant in tuber flesh, while allantoin and flavonoids showed higher levels in tuber cortex. Furthermore, the levels of dioscin, malvalic acid and sucrose differed significantly among age groups and were highest in the tubers at 2 years. While the levels of allantoin, adenosine and glutamine increased with the growing years and were highest at 4 years. Thus, 2-year old Dioscorea polystachya tubers could be harvested to prepare dioscin, malvalic acid and sucrose supplements. The 4-year-old Dioscorea polystachya tubers would be the best choice for obtaining a large amount of allantoin and adenosine in industrial production.

Sleep-related symptoms in multiple system atrophy: determinants and impact on disease severity.

BACKGROUND: Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. METHODS: This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). RESULTS: The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. CONCLUSIONS: Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

The clinical significance of the combined detection of serum Smac, HE4 and CA125 in endometriosis-associated ovarian cancer.

OBJECTIVE: This study aims to investigate the clinical significance of serum Smac, HE4 and CA125 alone or combined for detecting endometriosis-associated ovarian cancer (EAOC). METHODS: The level of serum Smac, HE4 and CA125 in 40 healthy controls, 40 cases of benign endometriosis ovarian tumor, and 60 cases of EAOC were detected by ELISA and electrochemical immune method. RESULTS: Serum Smac expression level was significantly lower in the EAOC group than in the control group and benign ovarian tumor group (P< 0.05), while HE4 and CA125 expression levels were significantly higher in the EAOC group than the other two groups. The sensitivity of Smac single detection was up to 91.67%, and the specificity of HE4 was up to 98.75%. Furthermore, the sensitivity of Smac + HE4 + CA125 combined was the highest, which reached up to 98.33%; but the specificity was low, which reached up to 75%. The serum expression level differences before and after surgery were statistically significant. As the number of chemotherapies increases, the Smac level increased, and HE4 and CA125 levels gradually decreased. Furthermore, Smac increased to normal at the end of the 2nd period of chemotherapy, while HE4 and CA125 decreased to normal in 2nd and 3rd period of chemotherapy, respectively. CONCLUSION: Serum Smac, HE4 and CA125 may play an important role in predicting EAOC and in monitoring the prognosis of postoperative EAOC.

Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening.

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

[Comparison of Laccase Activity of Different Strains of Ganoderma spp.].

Objective: To explore the relationship between the laccase activity and growth of Ganoderma spp.,to screen the highproducing laccase strains. Methods: The mycelium was cultured in PDA solid medium,and the laccase activity was measured by ABTS+method. The content of polysaccharide was determined by phenol sulfuric acid method. Results: Ganoderma gibbosum grew more rapidly in the early stage,and the laccase activity reached maximum( 1 476. 64 U/g) in the 4th day,which was 11. 37 times larger than that of sweet Ganoderma lucidum. Ganoderma gibbosum had the significant advantage after a comprehensive analysis. The polysaccharide content of Ganoderma lucidum of Shinshu was lower; the growth rate of Ganoderma lucidum strain S3 was stable, and the content of polysaccharide was medium. Conclusion: There are some differences in the growth rate of Ganoderma spp., and there is a certain correlation between the laccase activity and growth. Ganoderma gibbosum is the highest-producing laccase strain among the screening strains.

Dynamin-2 mediates heart failure by modulating Ca2+ -dependent cardiomyocyte apoptosis.

BACKGROUND: Heart failure (HF) is approaching an epidemic proportion and has become one of the leading causes of death. It imposes a great burden on the healthcare system and society. Remodeling of cardiomyocyte membranes has a profound role in the pathogenesis of HF. However, whether dynamin (DNM), a membrane-remodeling GTPase, is associated with HF remains unclear. METHODS AND RESULTS: Here, we identified that DNM2 is necessary for the maintenance of cardiac function. Endogenous DNM2 protein levels were gradually decreased in parallel with the progression of HF in different experimental animal models. Decreased DNM2 level was also observed in the end-stage failing human heart. DNM2-deficient zebrafish exhibited signs of notable cardiac apoptosis and eventually developed severe HF. Mechanistic study showed that DNM2 downregulation caused cardiomyocyte sarcoplasmic reticulum Ca(2+) overload and subsequent mitochondria-dependent apoptosis. These events were preceded by enhanced membrane translocation of the L-type Ca(2+) channel due to DNM2 deficiency-mediated membrane trafficking dysfunction. Furthermore, prevention of cardiomyocyte Ca(2+)-mishandling largely ameliorated the DNM2 deficiency-associated cardiomyocyte apoptosis and HF. CONCLUSIONS: DNM2 mediates HF by modulating Ca(2+)-dependent apoptotic death of cardiomyocyte. The finding may shed light on the new strategy of HF treatment.

Prolyl hydroxylase domain protein 2 regulates the intracellular cyclic AMP level in cardiomyocytes through its interaction with phosphodiesterase 4D.

Cyclic adenosine 3',5'-monophosphate (cAMP), which is synthesized by adenylyl cyclase (AC) and degraded by phosphodiesterase (PDE), plays crucial roles in the regulation of multiple cellular functions and physiological processes. Prolyl hydroxylase domain (PHD) proteins, which belong to a family of dioxygenases that function as oxygen sensors through their hydroxylation activity, have been implicated in multiple signaling pathways. Here, we aimed to determine whether PHD played a role in regulating intracellular cAMP level in cardiomyocytes. Through the overexpression/knockdown of the PHD gene and the measurement of the cAMP content, we found that PHD2, but not PHD1 or PHD3, acts as a regulator of intracellular cAMP. In neonatal rat cardiomyocytes and H9c2 cells, the overexpression of PHD2 increased the intracellular cAMP level, whereas the PHD2 knockdown reduced it. There was no alteration in the AC expression or activity in cells that overexpressed or downregulated PHD2. The overexpression of PHD2 decreased both the protein expression and the activity of phosphodiesterase 4D (PDE4D), whereas the PHD2 knockdown increased the PDE4D expression and activity. Co-immunoprecipitation experiments revealed a direct binding between PHD2 and PDE4D and liquid chromatography-tandem mass spectrometry analyses identified the specific hydroxylation sites on PDE4D. In conclusion, PHD2 may directly interact with PDE4D to function as a novel regulator of the intracellular cAMP levels in cardiomyocytes.