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1.
Chempluschem ; : e202400101, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822555

ABSTRACT

Mussel-inspired coating is a substrate-independent surface modification technology. However, its application is limited by time-consuming, tailoring specific functions require tedious secondary reaction. To overcome those drawbacks, a strategy for the rapid fabrication of diverse coatings by expanding the library of precursors using oxidation coupled with polyamine was proposed. Based on DFT simulations of the reaction pathways, a method was developed to achieve rapid deposition of coatings by coupling oxidation and polyamines, which simultaneously accelerated the oxidation of precursors and polymer chain growth. The feasibility and generalizability of the strategy was validated by the rapid coating of 10 catechol derivatives and polyamines on various substrates. The surface properties of the substrates such as functional group densities, Zeta potential and contact angles can be easily tuned. The tailored surface engineering application of the strategy was demonstrated by the heavy metal adsorbents and superwetting materials prepared through the delicate combination of different building blocks. Our strategy was flexible in terms of diverse surface engineering design which greatly enriched the connotation of mussel-inspired technique.

2.
Oncol Res ; 32(6): 1093-1107, 2024.
Article in English | MEDLINE | ID: mdl-38827320

ABSTRACT

Breast cancer is the leading cause of cancer-related deaths in women worldwide, with Hormone Receptor (HR)+ being the predominant subtype. Tamoxifen (TAM) serves as the primary treatment for HR+ breast cancer. However, drug resistance often leads to recurrence, underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates. Artemisinin (ART) has demonstrated efficacy in inhibiting the growth of drug-resistant cells, positioning art as a viable option for counteracting endocrine resistance. This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation. Five characterized genes (ar, cdkn1a, erbb2, esr1, hsp90aa1) and seven drug-disease crossover genes (cyp2e1, rorc, mapk10, glp1r, egfr, pgr, mgll) were identified using WGCNA crossover analysis. Subsequent functional enrichment analyses were conducted. Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and -sensitized patients. scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells, suggesting artemisinin's specific impact on tumor cells in estrogen receptor (ER)-positive BC tissues. Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes. These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.


Subject(s)
Artemisinins , Breast Neoplasms , Computational Biology , Drug Resistance, Neoplasm , Receptors, Estrogen , Tamoxifen , Tamoxifen/pharmacology , Tamoxifen/therapeutic use , Humans , Artemisinins/pharmacology , Artemisinins/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Drug Resistance, Neoplasm/genetics , Computational Biology/methods , Receptors, Estrogen/metabolism , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Agents, Hormonal/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Cell Line, Tumor , Molecular Docking Simulation , Cell Proliferation/drug effects
3.
Sci Total Environ ; : 173866, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38862045

ABSTRACT

The presence of certain associated bacteria has been reported to increase pest resistance to pesticides, which poses a serious threat to food security and the environment. Researches on the above microbe-derived pesticide resistance would bring innovative approaches for pest management. Investigations into the phoxim resistance of Delia antiqua, one Liliaceae crop pests, revealed the contribution of a phoxim-degrading gut bacterium, D39, to this resistance. However, how the strain degraded phoxim was unknown. In this study, the role of D39 in phoxim degradation and resistance was first confirmed. DT, which had an identical taxonomy but lacked phoxim-degrading activity, was analyzed alongside D39 via comparative genomics to identify the potential phoxim degrading genes. In addition, degradation metabolites were identified, and a potential degradation pathway was proposed. Furthermore, the main gene responsible for degradation and the metabolites of phoxim were further validated via prokaryotic expression. The results showed that D39 contributed to resistance in D. antiqua larva by degrading phoxim. Phoxim was degraded by an enzyme encoded by the novel gene phoD in D39 to O,O-diethyl hydrogen phosphorothioate and 2-hydroxyimino-2-phenylacetonitrile. Finally, downstream products were metabolized in the tricarboxylic acid cycle. Further analysis via prokaryotic expression of phoD confirmed its degradation activity. The mechanisms through which gut microbes promote pesticide resistance are elucidated in this study. These results could aid in the development of innovative pest control methods. In addition, this information could also be used to identify microbial agents that could be applied for the remediation of pesticide contamination.

4.
J Agric Food Chem ; 72(20): 11341-11350, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38713071

ABSTRACT

Insect neuropeptides play an essential role in regulating growth, development, reproduction, nerve conduction, metabolism, and behavior in insects; therefore, G protein-coupled receptors of neuropeptides are considered important targets for designing green insecticides. Cockroach-type allatostatins (ASTs) (FGLamides allatostatins) are important insect neuropeptides in Diploptera punctata that inhibit juvenile hormone (JH) synthesis in the corpora allata and affect growth, development, and reproduction of insects. Therefore, the pursuit of novel insecticides targeting the allatostatin receptor (AstR) holds significant importance. Previously, we identified an AST analogue, H17, as a promising candidate for pest control. Herein, we first modeled the 3D structure of AstR in D. punctata (Dippu-AstR) and predicted the binding mode of H17 with Dippu-AstR to study the critical interactions and residues favorable to its bioactivity. Based on this binding mode, we designed and synthesized a series of H17 derivatives and assessed their insecticidal activity against D. punctata. Among them, compound Q6 showed higher insecticidal activity than H17 against D. punctata by inhibiting JH biosynthesis, indicating that Q6 is a potential candidate for a novel insect growth regulator (IGR)-based insecticide. Moreover, Q6 exhibited insecticidal activity against Plutella xylostella, indicating that these AST analogs may have a wider insecticidal spectrum. The underlying mechanisms and molecular conformations mediating the interactions of Q6 with Dippu-AstR were explored to understand its effects on the bioactivity. The present work clarifies how a target-based strategy facilitates the discovery of new peptide mimics with better bioactivity, enabling improved IGR-based insecticide potency in sustainable agriculture.


Subject(s)
Insect Proteins , Insecticides , Neuropeptides , Peptidomimetics , Insecticides/chemistry , Insecticides/pharmacology , Insecticides/chemical synthesis , Animals , Neuropeptides/chemistry , Neuropeptides/pharmacology , Neuropeptides/metabolism , Insect Proteins/chemistry , Insect Proteins/metabolism , Insect Proteins/genetics , Peptidomimetics/chemistry , Peptidomimetics/pharmacology , Peptidomimetics/chemical synthesis , Drug Design , Juvenile Hormones/chemistry , Juvenile Hormones/pharmacology , Juvenile Hormones/metabolism , Cockroaches/drug effects , Cockroaches/chemistry
5.
Curr Microbiol ; 81(7): 192, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801460

ABSTRACT

The plant-colonized microbial communities have closely micro-ecological effects on host plant growth and health. There are many medicinal plants in the genus Hedyotis, but it is yet unclear about the shoot-assembled bacterial and fungal communities (SBFC) of Hedyotis plants. Hence, eight plant populations of Hedyotis diffusa (HD) and H. corymbosa (HC) were evaluated with 16S rRNA gene and ITS sequences, for comparing the types, abundance, or/and potential functions of SBFC at plant species- and population levels. In tested HD- and HC-SBFC, 682 fungal operational taxonomic units and 1,329 bacterial zero-radius operational taxonomic units were identified, with rich species compositions and varied alpha diversities. Notably, the SBFC compositions of HD and HC plant populations were exhibited with partly different types and abundances at phylum and genus levels but without significantly different beta diversities at plant species and population levels. Typically, the SBFC of HD and HC plant populations were presented with abundance-different biomarkers, such as Frankiaceae and Bryobacteraceae, and with similar micro-ecological functions of microbial metabolisms of lipids, terpenoids,and xenobiotics. Taken together, HD- and HC-SBFC possessed with varied rich compositions, conservative taxonomic structures, and similar metabolic functions, but with small-scale type and abundance differences at plant species- and population- levels.


Subject(s)
Bacteria , Fungi , Hedyotis , Microbiota , RNA, Ribosomal, 16S , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Fungi/classification , Fungi/genetics , Fungi/isolation & purification , RNA, Ribosomal, 16S/genetics , Hedyotis/chemistry , Hedyotis/genetics , Plant Shoots/microbiology , Plants, Medicinal/microbiology , Phylogeny , Biodiversity
6.
BMC Public Health ; 24(1): 1465, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822295

ABSTRACT

BACKGROUND: Malnutrition is related to impaired oral health and function that causes poor dietary intake, declining the general health of older adults. The role of dietary intake in the association between oral function and nutritional status of Chinese older adults (aged 75 and above) was examined in this cross-sectional study. METHODS: Through the randomized cluster sampling method, 267 older adults living in rural areas of Qingdao, Shandong (aged 81.4 ± 4.3, 75-94 years) were chosen as the primary research participants. A Mini Nutritional Assessment - Short Form was used to determine nutritional status, and Food Frequency Questionnaire and 24-hour Food Intake Recall were used to assess dietary intake. The oral function was evaluated by analyzing the teeth, oral problems, bite force, tongue pressure, lip sealing pressure, chewing function questionnaire, whole saliva flow rate, 10-Item Eating Assessment Tool, and water swallow test. RESULTS: Based on the MNA-SF score, it was divided into a well-nourished group and a malnutrition group, with the malnutrition group comprising 40.6% of participants. The participants in the malnutrition group showed a higher rate of xerostomia, lower bite force, tongue pressure, and lip sealing pressure, and higher Chewing Function Questionnaire and 10-Item Eating Assessment Tool scores. Furthermore, their plant fat, iron, cereals and potatoes, vegetables, fruits, and seafood intake were relatively low. The regression model indicated that exercise frequency, stroke, chewing and swallowing function, intake of vegetables and fruits were risk factors for nutritional status of older adults. CONCLUSION: Malnutrition was relatively common among the Chinese older adults aged 75 and above, and it was significantly correlated with exercise frequency, stroke, chewing and swallowing function, and intake of vegetables and fruits. Therefore, nutrition management should be carried out under the understanding and guidance of the oral function and dietary intake of the older adults.


Subject(s)
Nutritional Status , Humans , Cross-Sectional Studies , Aged , Male , Female , Aged, 80 and over , China/epidemiology , Malnutrition/epidemiology , Oral Health/statistics & numerical data , Diet/statistics & numerical data , Eating/physiology , Surveys and Questionnaires , Nutrition Assessment
7.
Environ Pollut ; 351: 124101, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38710361

ABSTRACT

Both nanoplastics (NPs) and 3-tert-butyl-4-hydroxyanisole (3-BHA) are environmental contaminants that can bio-accumulate through the food chain. However, the combined effects of which on mammalian female reproductive system remain unclear. Here, the female ICR-CD1 mice were used to evaluate the damage effects of ovaries and uterus after NPs and 3-BHA co-treatment for 35 days. Firstly, co-exposure significantly reduced the body weight and organ index of ovaries and uterus in mice. Secondly, combined effects of NPs and 3-BHA exacerbated the histopathological abnormalities to the ovaries and uterus and decreased female sex hormones such as FSH and LH while increased antioxidant activities including CAT and GSH-Px. Moreover, the apoptotic genes, inflammatory cytokines and the key reproductive development genes such as FSTL1 were significantly up-regulated under co-exposure conditions. Thirdly, through transcriptional and bioinformatics analysis, immunofluorescence and western blotting assays, together with molecular docking simulation, we determined that co-exposure up-regulated the FSTL1, TGF-ß and p-Smad1/5/9 but down-regulated the expression of BMP4. Finally, the pharmacological rescue experiments further demonstrated that co-exposure of NPs and 3-BHA mainly exacerbated the female reproductive toxicity through FSTL1-mediated BMP4/TGF-ß/SMAD signaling pathway. Taken together, our studies provided the theoretical basis of new environmental pollutants on the reproductive health in female mammals.


Subject(s)
Mice, Inbred ICR , Ovary , Polystyrenes , Uterus , Animals , Female , Mice , Uterus/drug effects , Uterus/metabolism , Ovary/drug effects , Ovary/metabolism , Polystyrenes/toxicity , Reproduction/drug effects , Microplastics/toxicity , Bone Morphogenetic Protein 4/genetics , Bone Morphogenetic Protein 4/metabolism , Nanoparticles/toxicity , Molecular Docking Simulation , Environmental Pollutants/toxicity , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/genetics
8.
BMC Genom Data ; 25(1): 38, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689211

ABSTRACT

BACKGROUND: Saccharum spontaneum L. is a closely related species of sugarcane and has become an important genetic component of modern sugarcane cultivars. Stem development is one of the important factors for affecting the yield, while the molecular mechanism of stem development remains poorly understanding in S. spontaneum. Phenylalanine ammonia-lyase (PAL) is a vital component of both primary and secondary metabolism, contributing significantly to plant growth, development and stress defense. However, the current knowledge about PAL genes in S. spontaneum is still limited. Thus, identification and characterization of the PAL genes by transcriptome analysis will provide a theoretical basis for further investigation of the function of PAL gene in sugarcane. RESULTS: In this study, 42 of PAL genes were identified, including 26 SsPAL genes from S. spontaneum, 8 ShPAL genes from sugarcane cultivar R570, and 8 SbPAL genes from sorghum. Phylogenetic analysis showed that SsPAL genes were divided into three groups, potentially influenced by long-term natural selection. Notably, 20 SsPAL genes were existed on chromosomes 4 and 5, indicating that they are highly conserved in S. spontaneum. This conservation is likely a result of the prevalence of whole-genome replications within this gene family. The upstream sequence of PAL genes were found to contain conserved cis-acting elements such as G-box and SP1, GT1-motif and CAT-box, which collectively regulate the growth and development of S. spontaneum. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that SsPAL genes of stem had a significantly upregulated than that of leaves, suggesting that they may promote the stem growth and development, particularly in the + 6 stem (The sixth cane stalk from the top to down) during the growth stage. CONCLUSIONS: The results of this study revealed the molecular characteristics of SsPAL genes and indicated that they may play a vital role in stem growth and development of S. spontaneum. Altogether, our findings will promote the understanding of the molecular mechanism of S. spontaneum stem development, and also contribute to the sugarcane genetic improving.


Subject(s)
Gene Expression Regulation, Plant , Phenylalanine Ammonia-Lyase , Phylogeny , Plant Stems , Saccharum , Saccharum/genetics , Saccharum/growth & development , Plant Stems/genetics , Plant Stems/growth & development , Phenylalanine Ammonia-Lyase/genetics , Phenylalanine Ammonia-Lyase/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Profiling , Genes, Plant
9.
Sci Rep ; 14(1): 9220, 2024 04 22.
Article in English | MEDLINE | ID: mdl-38649697

ABSTRACT

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.


Subject(s)
Chromosome Aberrations , Fetal Growth Retardation , Karyotyping , Pregnancy Outcome , Humans , Female , Fetal Growth Retardation/genetics , Fetal Growth Retardation/diagnosis , Pregnancy , Adult , Prenatal Diagnosis/methods
10.
Heliyon ; 10(5): e27612, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38486783

ABSTRACT

Sarcoidosis, a multisystemic immune disease, significantly impacts patients' quality of life. The complexity and diversity of its pathogenesis, coupled with limited comprehensive research, had hampered both diagnosis and treatment, resulting in an unsatisfactory prognosis for many patients. In recent years, the research had made surprising progress in the triggers of sarcoidosis (genetic inheritance, infection and environmental factors) and the abnormal regulations on immunity during the formation of granuloma. This review consolidated the latest findings on sarcoidosis research, providing a systematic exploration of advanced studies on triggers, immune-related regulatory mechanisms, and clinical applications. By synthesizing previous discoveries, we aimed to offer valuable insights for future research directions and the development of clinical diagnosis and treatment strategies.

11.
Chemosphere ; 352: 141356, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38309603

ABSTRACT

Naphthalene, the most abundant polycyclic aromatic hydrocarbon in the atmosphere, significantly influences OH consumption and secondary organic aerosol (SOA) formation. Naphthoquinone (NQ) is a significant contributor to ring-retaining SOA from naphthalene degradation, impacting the redox properties and toxicity of ambient particles. However, inconsistencies persist regarding concentrations of its isomers, 1,2-NQ and 1,4-NQ. In present work, our theoretical investigation into naphthalene's reaction with OH and subsequent oxygenation unveils their role in SOA formation. The reaction kinetics of initial OH and subsequent O2 oxidation was extensively studied using high-level quantum chemical methods (DLPNO-CCSD(T)/aug-ccpVQZ//M052x-D3/6-311++G(d,p)) combined with RRKM/master equation simulations. The reactions mainly proceed through electrophilic addition and abstraction from the aromatic ring. The total rate coefficient of naphthalene + OH at 300 K and 1 atm from our calculation (7.2 × 10-12 cm3 molecule-1 s-1) agrees well with previous measurements (∼1 × 10-11 cm3 molecule-1 s-1). The computed branching ratios facilitate accurate product yield determination. The largest yield of 1-hydroxynaphthalen-1-yl radical (add1) producing the major precursor of RO2 is computed to be 93.8 % in the ambient environment. Our calculated total rate coefficient (5.2 × 10-16 cm3 molecule-1 s-1) for add1 + O2 closely matches that of limited experimental data (8.0 × 10-16 cm3 molecule-1 s-1). Peroxy radicals (RO2) generated from add1 + O2 include 4-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-4OOadd-cis/trans, 66.0 %/17.5 %), 2-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-2OOadd-cis/trans, 10.3 %/6.3 %). Regarding the debated predominance of 1,4-NQ (corresponding to the parent RO2, i.e., add1-4OOadd-cis/trans) and 1,2-NQ (corresponding to the parent RO2, i.e., add1-2OOadd-cis/trans) in the atmosphere, our findings substantiate the dominance of 1,4-NQ. This study also indicates potential weakening of 1,4-NQ's dominance due to competition from decomposition reactions of add1-4OOadd-cis/trans and add1-2OOadd-cis/trans. Precise reaction kinetics data are essential for characterizing SOA transformation derived from naphthalene and assessing their climatic impacts within modeling frameworks.


Subject(s)
Naphthoquinones , Polycyclic Aromatic Hydrocarbons , Naphthalenes/chemistry , Physics , Kinetics , Oxidation-Reduction
12.
RSC Adv ; 14(9): 5863-5874, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38362082

ABSTRACT

Volatile organic compounds (VOCs) are typical air pollutants as well as gaseous wastes that contain energy. Utilization and disposition of VOCs is currently an important research hotspot in the field of atmospheric environment. In this paper, the thermal cracking and oxidation reaction processes of typical VOCs components were modelled and analyzed by combining molecular dynamics and detailed reaction mechanisms, focusing on the effects of temperature, oxygen and other conditions on the conversion of VOCs. The results of molecular dynamics studies show that improving temperature and reaction time benefit the decomposition of VOCs. High temperatures under an inert atmosphere can sufficiently crack the VOCs themselves, but other by-products are generated, which in turn cause secondary pollution. The activation energies derived by ReaxFF-MD calculation are 328 kJ mol-1, 147 kJ mol-1 and 121 kJ mol-1 for toluene, styrene and benzaldehyde respectively, which is consistent with experimental results. Under the oxygen atmosphere, the conversion rate of VOCs is greatly increased and the reaction temperature is significantly reduced. Meanwhile, the oxidation reaction fully converts VOCs into non-polluting products such as CO2 and H2O. Detailed kinetic studies show that initial oxidation of toluene molecules raised by hydrogen abstraction reaction is the dominant step during toluene oxidation, which significantly improved the decomposition efficiency of toluene.

13.
Small ; : e2311740, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38412430

ABSTRACT

Metal oxides with conversion and alloying mechanisms are more competitive in suppressing lithium dendrites. However, it is difficult to simultaneously regulate the conversion and alloying reactions. Herein, conversion and alloying reactions are regulated by modulation of the zinc oxide bandgap and oxygen vacancies. State-of-the-art advanced characterization techniques from a microcosmic to a macrocosmic viewpoint, including neutron diffraction, synchrotron X-ray absorption spectroscopy, synchrotron X-ray microtomography, nanoindentation, and ultrasonic C-scan demonstrated the electrochemical gain benefit from plentiful oxygen vacancies and low bandgaps due to doping strategies. In addition, high mechanical strength 3D morphology and abundant mesopores assist in the uniform distribution of lithium ions. Consequently, the best-performed ZnO-2 offers impressive electrochemical properties, including symmetric Li cells with 2000 h and full cells with 81% capacity retention after 600 cycles. In addition to providing a promising strategy for improving the lithiophilicity and mechanical strength of metal oxide anodes, this work also sheds light on lithium metal batteries for practical applications.

14.
Front Immunol ; 15: 1228235, 2024.
Article in English | MEDLINE | ID: mdl-38404588

ABSTRACT

Background: Ovarian cancer (OC) has the highest mortality rate among gynecological malignancies. Current treatment options are limited and ineffective, prompting the discovery of reliable biomarkers. Exosome lncRNAs, carrying genetic information, are promising new markers. Previous studies only focused on exosome-related genes and employed the Lasso algorithm to construct prediction models, which are not robust. Methods: 420 OC patients from the TCGA datasets were divided into training and validation datasets. The GSE102037 dataset was used for external validation. LncRNAs associated with exosome-related genes were selected using Pearson analysis. Univariate COX regression analysis was used to filter prognosis-related lncRNAs. The overlapping lncRNAs were identified as candidate lncRNAs for machine learning. Based on 10 machine learning algorithms and 117 algorithm combinations, the optimal predictor combinations were selected according to the C index. The exosome-related LncRNA Signature (ERLS) model was constructed using multivariate COX regression. Based on the median risk score of the training datasets, the patients were divided into high- and low-risk groups. Kaplan-Meier survival analysis, the time-dependent ROC, immune cell infiltration, immunotherapy response, and immune checkpoints were analyzed. Results: 64 lncRNAs were subjected to a machine-learning process. Based on the stepCox (forward) combined Ridge algorithm, 20 lncRNA were selected to construct the ERLS model. Kaplan-Meier survival analysis showed that the high-risk group had a lower survival rate. The area under the curve (AUC) in predicting OS at 1, 3, and 5 years were 0.758, 0.816, and 0.827 in the entire TCGA cohort. xCell and ssGSEA analysis showed that the low-risk group had higher immune cell infiltration, which may contribute to the activation of cytolytic activity, inflammation promotion, and T-cell co-stimulation pathways. The low-risk group had higher expression levels of PDL1, CTLA4, and higher TMB. The ERLS model can predict response to anti-PD1 and anti-CTLA4 therapy. Patients with low expression of PDL1 or high expression of CTLA4 and low ERLS exhibited significantly better survival prospects, whereas patients with high ERLS and low levels of PDL1 or CTLA4 exhibited the poorest outcomes. Conclusion: Our study constructed an ERLS model that can predict prognostic risk and immunotherapy response, optimizing clinical management for OC patients.


Subject(s)
Exosomes , Ovarian Neoplasms , RNA, Long Noncoding , Humans , Female , RNA, Long Noncoding/genetics , CTLA-4 Antigen , Exosomes/genetics , Prognosis , Biomarkers , Immunotherapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy
15.
Aging (Albany NY) ; 16(3): 2591-2616, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38305808

ABSTRACT

BACKGROUND: Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. Our study focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers. METHODS: Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. To delineate distinct molecular subtypes, we employed the non-negative matrix factorization (NMF)method. The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis. For external validation, we employed the GSE31684 dataset. CIBERSORT was utilized to examine the tumor immune microenvironment (TIME). A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures. We examined variations in clinical characteristics and tumor mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score. In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications. RESULTS: In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database. As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA). We found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score. According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorized as low-risk (P<0.001). The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6. Our model showed consistent distribution of samples from both the GEO database and TCGA data. Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001). According to our research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin. In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk. CONCLUSIONS: Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalized treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Prognosis , Urinary Bladder , Urinary Bladder Neoplasms/genetics , Cisplatin , Tumor Microenvironment/genetics
16.
BMC Womens Health ; 24(1): 68, 2024 01 24.
Article in English | MEDLINE | ID: mdl-38267981

ABSTRACT

BACKGROUND: Cervical cancer is strongly associated with human papillomavirus (HPV) infection. In this retrospective study, we analyzed the data of postmenopausal women who were tested for HPV in Nanjing First Hospital from 2019 to 2021. METHODS: We retrospectively analyzed the data of 14,608 postmenopausal women aged 45-90 years, who underwent HPV examination in Nanjing First Hospital between January 2019 and December 2021. All participants were tested for 23 HPV genotypes. We subsequently analyzed the infection rate and evaluated the distribution of HPV using the chi-square test. RESULTS: Our results showed that the HPV infection rate in postmenopausal women in Nanjing, China was 22.36%. In terms of age group, the infection rate was 19.54%, 24.30%, 26.58%, and 14.99% in those aged ≤ 50, 51-60, 61-70, and ≥ 71 years, respectively. The most common HPV subtypes were HPV52 (22.1 3%), HPV58 (15.86%), HPV53 (14.17%), HPV16 (12.61%), and HPV81 (11.66%), in that order. The single-HPV infection rate was 14.23%, and the multiple-genotype infection rate was 8.14% (1189/14,608). CONCLUSIONS: This study showed that in Nanjing, China, the different age groups of post-menopausal women could have different rates of HPV infection, and the most common types were HPV52, HPV58, HPV53, HPV16 and HPV81. These findings highlighted the importance of understanding the epidemiology of HPV infection in specific populations, such as postmenopausal women in Nanjing, China. The results could provide valuable information for healthcare professionals and policymakers to develop targeted prevention and screening strategies for reducing the burden of HPV-related diseases in this population.


Subject(s)
Alphapapillomavirus , Human Papillomavirus Viruses , Papillomavirus Infections , Humans , Female , Young Adult , Adult , Papillomavirus Infections/epidemiology , Postmenopause , Prevalence , Retrospective Studies , China/epidemiology , Human papillomavirus 16 , Papillomaviridae/genetics
17.
Mini Rev Med Chem ; 2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38288817

ABSTRACT

Anthriscus sylvestris (L.) Hoffm. Gen. is a biennial or perennial herb commonly found in China. It has a long history of use in traditional Chinese medicine to treat various ailments such as cough, gastric disorders, spleen deficiency, and limb weakness. Recently, its potential as an anticancer agent has gained considerable attention and has been the subject of extensive research focusing on extract efficacy, identification of active compounds, and proposed molecular mechanisms. Nevertheless, further high-quality research is still required to fully evaluate its potential as an anticancer drug. This review aims to comprehensively summarize the anticancer properties exhibited by the active components found in Anthriscus sylvestris. We conducted a comprehensive search, collation, and analysis of published articles on anticancer activity and active compounds of A. sylvestris using various databases that include, but are not limited to, PubMed, Web of Science, Science Direct and Google Scholar. The primary chemical composition of A. sylvestris consists of phenylpropanoids, flavonoids, steroids, fatty acids, and organic acids, showcasing an array of pharmacological activities like anticancer, antioxidant, anti-aging, and immunoregulatory properties. Thus, this review highlights the active compounds isolated from A. sylvestris extracts, which provide potential leads for the development of novel anticancer drugs and a better understanding of the plant's pharmacological effects, particularly its anticancer mechanism of action.

18.
BMC Med Genomics ; 17(1): 15, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38191380

ABSTRACT

PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.


Subject(s)
Abortion, Spontaneous , Turner Syndrome , Pregnancy , Humans , Female , Abortion, Spontaneous/genetics , DNA Copy Number Variations , Trisomy/genetics , Chromosome Aberrations
19.
Sci Rep ; 14(1): 1982, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38263420

ABSTRACT

Epidemiological studies have reported a positive association between chronic inflammation and cancer risk. However, the causal association between chronic inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of chronic inflammation in BC risk. We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1a, IL-1b, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies and the Breast Cancer Association Consortium). Next, we conducted the two-sample Mendelian randomization study to investigate the relationship of the abovementioned inflammatory factors with the incidence of BC. We found that genetically predicted CRP, IL-6, and IL-1a levels did not increase BC incidence (odds ratio (OR)CRP 1.06, 95% confidence interval (CI) 0.98-1.12, P = 0.2059, ORIL-6 1.05, 95% CI 0.95-1.16, P = 0.3297 and ORIL-1a 1.01, 95% CI 0.99-1.03, P = 0.2167). However, in subgroup analysis, genetically predicted IL-1b levels increased ER + BC incidence (OR 1.15, 95% CI 1.03-1.27, P = 0.0088). Our study suggested that genetically predicted IL-1b levels were found to increase ER + BC susceptibility. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, which deserves further research.


Subject(s)
Inflammatory Breast Neoplasms , Interleukin-1alpha , Humans , Interleukin-1beta , C-Reactive Protein , Interleukin-6 , Genome-Wide Association Study , Mendelian Randomization Analysis , Inflammation
20.
Gene ; 895: 148005, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-37977315

ABSTRACT

The study aimed to assess chromosomal abnormalities in twin pregnancies using karyotyping and SNP array analysis. The research involved 530 twin pregnancies from two prenatal diagnosis centers between October 2012 and October 2022. Two types of twin pregnancies were considered: monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA), with a total of 177 MCDA and 353 DCDA cases. Chromosomal abnormalities were examined based on chorionic and amniotic sac properties and clinical indications. Among 42 twin pregnancies, 50 fetuses showed chromosomal abnormalities by karyotyping, with 35 cases of aneuploidy in DCDA and 10 in MCDA. Trisomy 21 was the most common aberration, affecting 15 fetuses in DCDA and 4 in MCDA. The rate of discordant karyotypes in MCDA and DCDA groups was 1.1% and 8.8%, respectively. Ultrasound abnormalities and advanced maternal age were frequent indications (55.3% and 39.2%, respectively). Aneuploidy frequencies in DCDA and MCDA pregnancies with advanced maternal age were 10.6% and 4.5%. Cardiac defects and increased nuchal translucency were common anomalies, with higher incidences of chromosomal abnormalities in DCDA (12.5% and 6.9%) and MCDA groups (23.5% and 3.7%). SNP array identified 1.6% clinically significant copy number variants in DCDA fetuses with ultrasound abnormalities, while no significant CNVs were found in MCDA pregnancies. Chromosomal aneuploidies were the primary abnormalities in twin pregnancies, with detectable abnormalities and clinically significant CNVs more likely in DCDA pregnancies, especially those with ultrasound abnormalities.


Subject(s)
Polymorphism, Single Nucleotide , Pregnancy, Twin , Pregnancy , Female , Humans , Pregnancy, Twin/genetics , Karyotyping , Chromosome Aberrations , Aneuploidy , Retrospective Studies , Ultrasonography, Prenatal
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