ABSTRACT
Drought, especially terminal drought, severely limits wheat growth and yield. Understanding the complex mechanisms behind the drought response in wheat is essential for developing drought-resistant varieties. This study aimed to dissect the genetic architecture and high-yielding wheat ideotypes under terminal drought. An automated high-throughput phenotyping platform was used to examine 28 392 image-based digital traits (i-traits) under different drought conditions during the flowering stage of a natural wheat population. Of the i-traits examined, 17 073 were identified as drought-related. A genome-wide association study (GWAS) identified 5320 drought-related significant single-nucleotide polymorphisms (SNPs) and 27 SNP clusters. A notable hotspot region controlling wheat drought tolerance was discovered, in which TaPP2C6 was shown to be an important negative regulator of the drought response. The tapp2c6 knockout lines exhibited enhanced drought resistance without a yield penalty. A haplotype analysis revealed a favored allele of TaPP2C6 that was significantly correlated with drought resistance, affirming its potential value in wheat breeding programs. We developed an advanced prediction model for wheat yield and drought resistance using 24 i-traits analyzed by machine learning. In summary, this study provides comprehensive insights into the high-yielding ideotype and an approach for the rapid breeding of drought-resistant wheat.
Subject(s)
Droughts , Genome-Wide Association Study , Phenotype , Polymorphism, Single Nucleotide , Triticum , Triticum/genetics , Triticum/physiology , Polymorphism, Single Nucleotide/genetics , Haplotypes/genetics , Quantitative Trait, Heritable , Adaptation, Physiological/genetics , Drought ResistanceABSTRACT
BACKGROUND: Currently, there is limited understanding of the specific humoral immune response in BA.5-infected hemodialysis patients (BA.5-CHDPs) with previous COVID-19 vaccination. Additionally, the relevant risk factors for reinfection with XBB variants in BA.5-CHDPs have yet to be elucidated. METHOD: A total of 178 BA.5-CHDPs were enrolled in this study among 53 patients who had previous vaccination. To compare hemodialysis patients in both unvaccinated and vaccinated for their immune response to the BA.5 subtype infection, we assessed serum levels of anti-ancestral-S1-IgG, anti-BA.5-receptor binding domain (RBD)-IgG, and anti-XBB.1.16-RBD-IgG using enzyme-linked immunosorbent assay, the neutralizing antibody titer against BA.5 and XBB.1.16 was determined using pseudovirus neutralization assays. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with severe infection, the magnitude of specific humoral immunity and susceptibility to XBB variants reinfection. RESULT: Our findings indicate that BA.5-CHDPs with full or booster vaccinations have higher levels of anti-ancestral-S1-IgG than unvaccinated individuals. However, levels of anti-BA.5-RBD-IgG and anti-XBB.1.16-RBD-IgG are much lower. Booster-vaccinated BA.5-CHDPs have significantly higher levels of BA.5 and XBB.1.16 specific antibodies and neutralizing antibodies than unvaccinated patients. Low globulin levels and shorter hemodialysis duration are independent risk factors for XBB reinfection in BA.5-CHDPs. CONCLUSION: Although XBB.1.16 specific neutralizing antibody levels were low in BA.5-CHDPs, these levels cannot predict the risk of reinfection; other potential risk factors need to be investigated in the future.
ABSTRACT
OBJECTIVES: Robots are increasingly being used for surgical procedures in various specialties. However, information about the accuracy of robot-assisted dental implant surgery is lacking. This pilot clinical study aimed to investigate the accuracy of an autonomous dental implant robotic (ADIR) system in partially edentulous cases. MATERIAL AND METHODS: The ADIR system was used to place a total of 20 implants in 13 participants. Implant deviation from the planned positions was assessed to determine accuracy. The entry, apex, and angular deviations were described as means ± standard deviation. A two-sample t test was used to compare implant deviation between the flap and flapless groups and between maxillary and mandibular implants (α = .05). RESULTS: The entry, apex, and angular deviations were 0.65 ± 0.32 mm, 0.66 ± 0.34 mm, and 1.52 ± 1.01°, respectively, with no statistically significant difference between the flap and flapless approaches (P > .05). No adverse events were encountered in any of the participants. CONCLUSIONS: DIR accuracy in this clinical series was comparable to that reported for static and dynamic computer-assisted implant surgery. Robotic computer-assisted implant surgery may be useful for dental implant placement, potentially improving the quality and safety of the procedure. CLINICAL RELEVANCE: The findings of this study showed that the ADIR system could be useful for dental implant surgery.
Subject(s)
Dental Implantation, Endosseous , Jaw, Edentulous, Partially , Humans , Pilot Projects , Male , Female , Middle Aged , Dental Implantation, Endosseous/methods , Jaw, Edentulous, Partially/surgery , Adult , Robotic Surgical Procedures/instrumentation , Robotic Surgical Procedures/methods , Dental Implants , Treatment OutcomeABSTRACT
BACKGROUND: Progress is being made in the prevention and treatment of chronic obstructive pulmonary disease (COPD), but it is still unsatisfactory. With the development of genetic technology, validated genetic information can better explain COPD. OBJECTIVE: The study utilized scRNA-seq and Mendelian randomization analysis of eQTLs to identify crucial genes and potential mechanistic pathways underlying COPD pathogenesis. MEHODS: Single-cell sequencing data were used to identify marker genes for immune cells in the COPD process. Data on eQTLs for immune cell marker genes were obtained from the eQTLGen consortium. To estimate the causal effect of marker genes on COPD, we selected an independent cohort (ukb-b-16751) derived from the UK Biobank database for two-sample Mendelian randomization analysis. Subsequently, we performed immune infiltration analysis, gene set enrichment analysis (GSEA), and co-expression network analysis on the key genes. RESULTS: The 154 immune cell-associated marker genes identified were mainly involved in pathways such as vacuolar cleavage, positive regulation of immune response and regulation of cell activation. Mendelian randomization analysis screened four pairs of marker genes (GZMH, COTL1, CSTA and CD14) were causally associated with COPD. These four key genes were significantly associated with immune cells. In addition, we have identified potential transcription factors associated with these key genes using the Cistrome database, thus contributing to a deeper understanding of the regulatory network of these gene expressions. CONCLUSIONS: This eQTLs Mendelian randomization study identified four key genes (GZMH, COTL1, CSTA, and CD14) causally associated with COPD, providing new insights for prevention and treatment of COPD.
Subject(s)
Mendelian Randomization Analysis , Pulmonary Disease, Chronic Obstructive , Single-Cell Analysis , Pulmonary Disease, Chronic Obstructive/genetics , Humans , Genetic Predisposition to Disease , Quantitative Trait Loci , Male , Genetic Markers , Female , Lipopolysaccharide Receptors/genetics , Middle AgedABSTRACT
Total saikosaponins (TSS) form a group of chemically and biologically active components that can be extracted from Bupleurum, with reported antidepressive, anti-inflammatory, antiviral, antiendotoxin, antitumor, anti-pulmonary fibrosis and anti-gastric ulcer effects. Bupleurum or TSS is frequently utilized in clinical practice alongside other medications (such as entecavir, lamivudine, compound paracetamol and amantadine hydrochloride capsules), leading to an increased risk of drug-drug interactions. The cytochrome P450 (CYP) family serves a critical role in the metabolism of numerous essential drugs (such as tamoxifen, ibuprofen and phenytoin), where the majority of drug interactions involve CYP-mediated metabolism. It is therefore essential to understand the effects of key components of Bupleurum on CYPs when administering combination therapies containing TSS or Bupleurum. The present study aimed to investigate the effects of TSS on the mRNA and protein expression of CYP3A4 and CYP1A2 in HepaRG cells. The effects of TSS on the survival of HepaRG cells was investigated using the Cell Counting Kit-8 (CCK-8) method. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) analysis were used to assess the effects of different concentrations of TSS (0, 5, 10 and 15 µg/ml) on CYP3A4 and CYP1A2 mRNA and protein expression in HepaRG cells. Based on the CCK-8 assay results, it was observed that the cell viability remained above 80% when treated with 1, 5, 10 and 15 µg/ml TSS. Although there was a statistically significant reduced cell viability at TSS concentrations of 10 and 15 µg/ml compared with the control group, the findings indicated that TSS did not exhibit notable cytotoxic effects at these concentrations. Furthermore, RT-qPCR results revealed that compared with those in the control group, TSS at concentrations of 10 and 15 µg/ml reduced CYP3A4 mRNA expression but increased CYP1A2 mRNA expression in HepaRG cells at concentrations of 15 µg/ml. WB analysis found that TSS at concentrations of 10 and 15 µg/ml downregulated CYP3A4 protein expression in HepaRG cells while increasing CYP1A2 protein expression at concentrations of 15 µg/ml. Results in the present study suggest that TSS can inhibit CYP3A4 mRNA and protein expression, but exerts opposite effects on their CYP1A2 counterparts. These findings suggest that it is necessary to consider drug interactions between clinical preparations containing TSS or Bupleurum and drugs metabolized by CYP3A4 and CYP1A2 to avoid potential adverse drug reactions in clinical practice.
ABSTRACT
Sesame (Sesamum indicum L.) is a valuable oilseed crop with numerous nutritional benefits containing a diverse range of bioactive compounds. However, sesame is also considered an allergenic food that triggers various mild to severe adverse reactions (e.g., anaphylaxis). Strict dietary avoidance of sesame components is the best option to protect the sensitized consumers. Sesame or sesame-derived foods are always consumed after certain food processing operations, which would cause a considerable impact on the structure of sesame proteins, changing their sensitization capacity and detectability. In the review, the molecular structure properties, and immunological characteristics of the sesame allergens were described. Meanwhile, the influence of food processing techniques on sesame proteins and the relevant detection techniques used for the sesame allergens quantification are also emphasized critically. Hopefully, this review could provide valuable insight into the development and management for the new "Big Eight" sesame allergen in food industry.
ABSTRACT
Ganoderic acid A (GAA) is one of the major triterpenoids in Ganoderma lucidum (GL). Accumulating evidence has indicated that GAA demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Here, the effects and mechanisms of GAA in the treatment of neurological disorders were evaluated and discussed through previous research results. By summarizing previous research results, we found that GAA may play a neuroprotective role through various mechanisms: anti-inflammatory, anti-oxidative stress, anti-apoptosis, protection of nerve cells, and regulation of nerve growth factor. Therefore, GAA is a promising natural neuroprotective agent and this review would contribute to the future development of GAA as a novel clinical candidate drug for treating neurological diseases.
Subject(s)
Heptanoic Acids , Lanosterol/analogs & derivatives , Nervous System Diseases , Neuroprotective Agents , Humans , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Lanosterol/pharmacology , Lanosterol/therapeutic use , Nervous System Diseases/drug therapyABSTRACT
Breeding new and sustainable crop cultivars of high yields and desirable traits has been a major challenge for ensuring food security for the growing global human population. For polyploid crops such as wheat, introducing genetic variation from wild relatives of its subgenomes is a key strategy to improve the quality of their breeding pools. Over the past decades, considerable progress has been made in speed breeding, genome sequencing, high-throughput phenotyping and genomics-assisted breeding, which now allows us to realize whole-genome introgression from wild relatives to modern crops. Here, we present a standardized protocol to rapidly introgress the entire genome of Aegilops tauschii, the progenitor of the D subgenome of bread wheat, into elite wheat backgrounds. This protocol integrates multiple modern high-throughput technologies and includes three major phases: development of synthetic octaploid wheat, generation of hexaploid A. tauschii-wheat introgression lines (A-WIs) and homozygosis of the generated A-WIs. Our approach readily generates stable introgression lines in 2 y, thus greatly accelerating the generation of A-WIs and the introduction of desirable genes from A. tauschii to wheat cultivars. These A-WIs are valuable for wheat-breeding programs and functional gene discovery. The current protocol can be easily modified and used for introgressing the genomes of wild relatives to other polyploid crops.
Subject(s)
Aegilops , Triticum , Humans , Triticum/genetics , Aegilops/genetics , Plant Breeding , Chromosome Mapping , PolyploidyABSTRACT
Objective@#To study the impact of sleep characteristics on myopia, among lower primary school students in Shanghai, so as to provide foundation for the prevention of the onset and development of myopia.@*Methods@#A total of 636 students from the first and second grades of two primary schools in Jiading District, Shanghai, were selected through cluster random sampling for questionnaire surveys and ophthalmological examinations in October 2022. The Childrens Sleep Habits Questionnaire (CSHQ) was used to assess sleep quality at baseline. Ophthalmological examinations were conducted in October 2023(479), during which the students study time, screen time and outdoor activity time were monitored for twoweek, repeated twice. Generalized multivariable Logistic regression models and linear regression models were employed to examine the association between sleeprelated factors and myopia, as well as the strength of this association.@*Results@#The baseline survey indicated a myopia prevalence of 18.58%, with 17.18% at followup. The average CSHQ total score was (51.58±4.44), and the average daily sleep duration was (9.43±4.84)h/d, with only 11.6% of participants meeting the recommended sleep sufficiency. Multivariable regression models indicated that insufficient sleep showed positive association with myopia (OR=1.64, 95%CI=1.05-2.56), while bedtime duration was significantly negative associated with myopia (OR=0.74, 95%CI=0.63-0.91, P<0.05), adjusting for confounding factors. Inconsistency in bed rest time was a risk factor for myopia (OR=1.07, P<0.05), and the consistency of bed rest time, and wakeup time showed statistically significant correlations with SE (P<0.05). There was also statistically significant correlations between consistency in sleep time, bed rest time, and wakeup time with AL (P<0.05).@*Conclusions@#Insufficient sleep and bedtime duration are correlated with the onset and progression of myopia. It is critical to ensure sufficient sleep duration and regular sleep habits for children to reduce the occurrence of myopia in the primary school students.
ABSTRACT
The level of human chorionic gonadotropin (HCG) is an important indicator for early pregnancy, pregnancy-related diseases trophoblastic diseases and even cancer diagnosis. Therefore, sensitive detection of HCG has crucial significance in clinical, especially in gynaecology and obstetrics. Herein, a hybridization chain reaction (HCR) assisted multicolor immunosensor have been developed for HCG analysis. The proposed method introduced HCR after the immunoreaction between antibody and HCG protein, and produced long double strand DNA (dsDNA) that contain biotin sites. The streptavidin-horseradish peroxidase was linked on the dsDNA by the interaction between biotin and streptavidin, and can further mediated gold nanobipyramids (Au NBPs) etching. The localized surface plasmon resonance absorption peaks of Au NBPs blue shift and accompanied a vivid color change after etching effect. Based on this color change, HCG could be qualitative and semi-quantitative detected. Because of the introduction of HCR and enzyme amplification technique, the proposed method exhibited high sensitivity with a linear range of 0.1-2000 pg/mL and limit of detection (LOD) of 0.1 pg/mL. Finally, the proposed immunosensor was used to detect clinical serum samples. The results show there are no significant differences between clinical results and the test results by this method, indicating the practicability of the proposed method.
Subject(s)
Biosensing Techniques , Humans , Biosensing Techniques/methods , Biotin , Streptavidin , Immunoassay/methods , Chorionic Gonadotropin/analysis , GoldABSTRACT
BACKGROUND: Grain number per spike (GNS) is a pivotal determinant of grain yield in wheat. Pubing 3228 (PB3228), a wheat-Agropyron cristatum germplasm, exhibits a notably higher GNS. RESULTS: In this study, we developed a recombinant inbred line (RIL) population derived from PB3228/Gao8901 (PG-RIL) and constructed a high-density genetic map comprising 101,136 loci, spanning 4357.3 cM using the Wheat 660 K SNP array. The genetic map demonstrated high collinearity with the wheat assembly IWGSC RefSeq v1.0. Traits related to grain number and spikelet number per spike were evaluated in seven environments for quantitative trait locus (QTL) analysis. Five environmentally stable QTLs were detected in at least three environments. Among these, two major QTLs, QGns-4A.2 and QGns-1A.1, associated with GNS, exhibited positive alleles contributed by PB3228. Further, the conditional QTL analysis revealed a predominant contribution of PB3228 to the GNS QTLs, with both grain number per spikelet (GNSL) and spikelet number per spike (SNS) contributing to the overall GNS trait. Four kompetitive allele-specific PCR (KASP) markers that linked to QGns-4A.2 and QGns-1A.1 were developed and found to be effective in verifying the QTL effect within a diversity panel. Compared to previous studies, QGns-4A.2 exhibited stability across different trials, while QGns-1A.1 represents a novel QTL. The results from unconditional and conditional QTL analyses are valuable for dissecting the genetic contribution of the component traits to GNS at the individual QTL level and for understanding the genetic basis of the superior grain number character in PB3228. The KASP markers can be utilized in marker-assisted selection for enhancing GNS. CONCLUSIONS: Five environmentally stable QTLs related to grain number and spikelet number per spike were identified. PB3228 contributed to the majority of the QTLs associated with GNS.
Subject(s)
Agropyron , Triticum , Triticum/genetics , Agropyron/genetics , Chromosome Mapping , Phenotype , Quantitative Trait Loci/genetics , Edible Grain/genetics , Genetic LinkageABSTRACT
Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.
Subject(s)
Diabetes Mellitus, Type 2 , Saponins , Triterpenes , Saponins/chemistry , Gynostemma/chemistry , Gynostemma/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Molecular Docking Simulation , Triterpenes/chemistry , Glucose , DammaranesABSTRACT
BACKGROUND: The prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children. METHODS: Thirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed. RESULTS: A total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974-16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572-14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways. CONCLUSIONS: Differential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.
Subject(s)
MicroRNAs , Pediatric Obesity , Child , Humans , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiology , Pediatric Obesity/genetics , Reproducibility of Results , MicroRNAs/metabolism , Biomarkers , Signal Transduction/geneticsABSTRACT
Background/purpose: The success of transcrestal sinus floor elevation (TSFE) is primarily reliant upon the experience of the surgeon owing to the limited operative visibility. To evaluate the accuracy associated with the use of a dynamic navigation system when conducting posterior maxilla implant surgery with TSFE. Materials and methods: Twenty-eight implants were placed in 28 patients requiring implantation in the posterior maxilla via a TSFE approach. The drills were used to access the planned position (within 1 mm of the bottom of the maxillary sinus floor) under dynamic navigation system. TSFE was then accomplished using osteotomes and a piezoelectric device. Lastly, the implant was inserted under the dynamic navigation. Three effective deviations between planned and actual implant placement were then measured including angular deviation (AD, degrees), entry point horizontal deviation (EPHD, mm), and apical point horizontal deviation (APHD, mm). Results: The AD, EPHD, and APHD between the planned and actual implant placement were 3.656 ± 1.665°, 1.073 ± 0.686 mm, and 1.086 ± 0.667 mm, respectively. Premolar site AD values were less than those for molar sites (P = 0.004). No significant differences in these outcomes were observed in different surgeons. Obvious sinus perforation was not detected by immediate postoperative cone beam computed tomography imaging. Conclusion: The accuracy associated with using a dynamic navigation system when conducting posterior maxilla implant surgery via a TSFE approach using piezoelectric devices was comparable. This technique thus achieved appropriate interventional precision and safety while decreasing the morbidity associated with the TSFE approach.
ABSTRACT
With the development of molecular biology and genomics technology, mushroom breeding methods have changed from single traditional breeding to molecular breeding. Compared with traditional breeding methods, molecular breeding has the advantages of short time and high efficiency. It breaks through the restrictive factors of conventional breeding and improves the accuracy of breeding. Molecular breeding technology is gradually applied to mushroom breeding. This paper summarizes the concept of molecular breeding and the application progress of various molecular breeding technologies in mushroom breeding, in order to provide reference for future research on mushroom breeding.
Subject(s)
Agaricales , Agaricales/genetics , DNA ShufflingABSTRACT
OBJECTIVES: To gauge the relative accuracy of the use of passive and active dynamic navigation systems when placing dental implants, and to determine how registration areas affect the performance of these systems. MATERIALS AND METHODS: Eighty implants were assigned to be placed into 40 total resin mandible models missing either the left or right first molars using either passive or active dynamic navigation system approaches. U-shaped tube registration devices were fixed in the edentulous site for 20 models each on the left or right side. Planned and actual implant positions were superimposed to assess procedural accuracy, and parameters including 3D entry deviation, angular deviation, and 3D apex deviation were evaluated with Mann-Whitney U tests and Wilcoxon signed-rank tests. RESULTS: Respective angular, entry, and apex deviation values of 1.563 ± 0.977°, 0.725 ± 0.268 mm, and 0.808 ± 0.284 mm were calculated for all included implants, with corresponding values of 1.388 ± 1.090°, 0.789 ± 0.285 mm, and 0.846 ± 0.301 mm in the active group and 1.739 ± 0.826°, 0.661 ± 0.236 mm, and 0.769 ± 0.264 mm in the passive group. Only angular deviation differed significantly among groups, and the registration area was not associated with any significant differences among groups. CONCLUSIONS: Passive and active dynamic navigation approaches can achieve comparable in vitro accuracy. Registration on one side of the missing single posterior tooth area in the mandible can complete single-tooth implantation on both sides of the posterior teeth, highlighting the promise of further clinical research focused on this topic.
ABSTRACT
Spermidine is a type of important growth regulator, which involved in the biosynthesis of photosynthetic pigments, and has the function of promoting cell proliferation. In this study, Isochrysis sp. was selected as the research object to explore the effects of spermidine supplementation on the growth of algal cells and fucoxanthin synthesis under different light intensities. The results showed that the cell density (5.40 × 106 cells/mL) of algae were the highest at 11 days under the light intensity of 200 µmol·m-2·s-1 and spermidine content of 150 µM. The contents of diadinoxanthin (1.09 mg/g) and fucoxanthin (6.11 mg/g) were the highest when spermidine was added under low light intensity, and the growth of algal cells and fucoxanthin metabolism were the most significant. In the carotenoid synthesis pathway, PDS (phytoene desaturase) was up-regulated by 1.96 times and VDE (violaxanthin de-epoxidase) was down-regulated by 0.95 times, which may promote fucoxanthin accumulation.
Subject(s)
Haptophyta , Spermidine/pharmacology , Light , CarotenoidsABSTRACT
Protein kinase C (PKC) is a family of serine/threonine protein kinases that play an important role in many organs and systems and whose activation contributes significantly to endothelial dysfunction in diabetes. The increase in diacylglycerol (DAG) under high glucose conditions mediates PKC activation and synthesis, which stimulates oxidative stress and inflammation, resulting in impaired endothelial cell function. This article reviews the contribution of PKC to the development of diabetes-related endothelial dysfunction and summarizes the drugs that inhibit PKC activation, with the aim of exploring therapeutic modalities that may alleviate endothelial dysfunction in diabetic patients.
Subject(s)
Diabetes Mellitus , Vascular Diseases , Humans , Protein Kinase C/metabolism , Signal Transduction , Oxidative StressABSTRACT
Bisphenol S (BPS) is a novel bisphenol A (BPA) analogue, a ubiquitous environmental pollutant that disrupts male reproductive system. Whether BPS affects Leydig cell maturation in male puberty remains unclear. Male Sprague-Dawley rats (age of 35 days) were daily gavaged to 0, 1, 10, 100, and 200 mg/kg/day from postnatal days 35-56. BPS at 1-10 mg/kg/day and higher doses markedly reduced serum testosterone and progesterone levels but it at 200 mg/kg/day significantly increased estradiol level. BPS at 100 and 200 mg/kg/day significantly elevated serum luteinizing hormone (LH) levels. BPS at 1-10 mg/kg/day and higher doses significantly reduced inhibin A and inhibin B levels. BPS at 100 and 200 mg/kg/day markedly increased CYP11A1+ Leydig cell number, but did not affect HSD11B1+ (a mature Leydig cell marker) cell number. BPS at 10 mg/kg/day and higher doses significantly downregulated the expression of Cyp11a1 and at 100 and 200 mg/kg/d significantly lowered Cyp17a1, Hsd11b1, and Nr5a1 in the testes. BPS at 100 and/or 200 mg/kg/day significantly elevated Lhb in the pituitary. BPS at 100 and 200 mg/kg/day significantly increased the phosphorylation of AKT1, AKT2, and CREB without affecting total AKT1, AKT2, and CREB levels. BPS at 1-100 µM significantly suppressed testosterone production and induced proliferation of primary immature Leydig cells after 24 h of treatment and these actions were reversed by estrogen receptor α antagonist, ICI 182780, and partially reversed by vitamin E. BPS at 0.1-10 µM significantly increased oxidative stress of Leydig cells in vitro. BPS also directly inhibited 17ß-hydroxysteroid dehydrogenase 3 activity at 10-100 µM. In conclusion, BPS causes hypergonadotropic androgen deficiency in male rats during pubertal exposure via activating ESR1 and inducing ROS in immature Leydig cells and directly inhibiting 17ß-hydroxysteroid dehydrogenase 3 activity.
Subject(s)
Cholesterol Side-Chain Cleavage Enzyme , Testosterone , Rats , Male , Animals , Rats, Sprague-Dawley , Cholesterol Side-Chain Cleavage Enzyme/metabolism , Leydig Cells/metabolism , Cell Differentiation , Cell ProliferationABSTRACT
BACKGROUND: The association between antipsychotics and cardiovascular diseases (CVDs) remains significant yet unestablished, especially in Chinese populations. OBJECTIVE: To investigate the risk of CVDs associated with antipsychotics among Chinese individuals with schizophrenia. METHODS: We conducted a nested case-control study on individuals diagnosed with schizophrenia in Shandong, China. The case group included individuals diagnosed with incident CVDs between 2012 and 2020. Each case was randomly matched with up to three controls. We used weighted logistic regression models to assess the risk of CVDs associated with antipsychotics and restricted cubic spline analysis to explore the dose-response relationship. FINDINGS: In total, 2493 cases and 7478 matched controls were included in the analysis. Compared with non-users, any antipsychotics use was associated with higher risk of any CVDs (weighted OR=1.54, 95% CI 1.32 to 1.79), with the risk mainly driven by ischaemic heart diseases (weighted OR=2.26, 95% CI 1.71 to 2.99). Treatments with haloperidol, aripiprazole, quetiapine, olanzapine, risperidone, sulpiride and chlorpromazine were associated with increased risk of CVDs. A non-linear dose-response relationship between dosage of antipsychotics and risk of CVDs was observed, with a sharp increase in risk in the beginning and then flattening out with higher doses. CONCLUSIONS: Use of antipsychotics was associated with increased risk of incident CVDs among individuals with schizophrenia, and the risk varied substantially among different antipsychotics and specific CVDs. CLINICAL IMPLICATIONS: Clinicians should consider the cardiovascular risk of antipsychotics and choose the appropriate type and dose of drugs in the treatment of schizophrenia.