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1.
J Proteome Res ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39253780

RESUMEN

Platinum resistance in ovarian cancer poses a significant challenge, substantially impacting patient outcomes. Developing an accurate predictive model is crucial for improving clinical decision-making and guiding treatment strategies. Proteomic data from 217 high-grade serous ovarian cancer (HGSOC) biospecimens obtained from JHU, PNNL, and PTRC were used to construct a prediction model for identifying individuals who are resistant to platinum-based chemotherapy. A total of 6437 common proteins were detected across all data sets, with 26 proteins overlapping between the development cohorts JHU and PNNL. Using LASSO and logistic regression analysis, a six-protein model (P31323_PRKAR2B, Q13309_SKP2, Q14997_PSME4, Q6ZRP7_QSOX2, Q7LGA3_HS2ST1, and Q7Z2Z2_EFL1) was developed, which accurately predicted platinum resistance, with an AUC of 0.964 (95% CI, 0.929-0.999). Internal validation by resampling resulted in a C-index of 0.972 (95% CI 0.894-0.988). External validation performed on the PTRC cohort achieved an AUC of 0.855 (95% CI 0.748-0.963). Calibration curves showed good consistency, and DCA indicated superior clinical utility. The model also performed well in predicting PFS and OS at various time points. Based on these proteins, our predictive model can precisely predict platinum response and survival outcomes in HGSOC patients, which can assist clinicians in promptly identifying potentially platinum-resistant individuals.

2.
Environ Sci Technol ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145972

RESUMEN

This study delves into the unexplored distribution and accumulation of chlorinated paraffins (CPs), pervasive industrial contaminants used as flame retardants and plasticizers, within the hadal trenches, some of Earth's most isolated marine ecosystems. Analysis of sediments from the Mussau (MS) and Mariana trench (MT) reveals notably high total CP concentrations (∑SCCPs + ∑MCCPs) of 10,963 and 14,554 ng g-1 dw, respectively, surpassing those in a reference site in the western Pacific abyssal plain (8533 ng g-1 dw). In contrast, the New Britain Trench (NBT) exhibits the lowest concentrations (2213-5880 ng g-1 dw), where CP distribution correlates with clay content, δ13C and δ15N values, but little with total organic carbon and depth. Additionally, amphipods from these trenches display varying CP levels, with MS amphipods reaching concerning concentrations (8681-16,138 ng g-1 lw), while amphipods in the MT-1 site show the lowest (4414-5010 ng g-1 lw). These bioaccumulation trends appear to be primarily influenced by feeding behaviors (δ13C) and trophic levels (δ15N). Utilizing biota-sediment accumulation factor values and principal component analysis, we discern that CPs in sediment may come from surface-derived particulate organic matters, while those in amphipods may come from the above carrion. Our findings elucidate the profound impacts of the emerging pollutants on the Earth's least explored marine ecosystems.

3.
Adv Mater ; 36(33): e2400178, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38843462

RESUMEN

The incorporation of functionalized nanofillers into polymers via photopolymerization approach has gained significant attention in recent years due to the unique properties of the resulting composite materials. Surface modification of nanofillers plays a crucial role in their compatibility and polymerization behavior within the polymer matrix during photopolymerization. This review focuses on the recent developments in surface modification of various nanofillers, enabling their integration into polymer systems through photopolymerization. The review discusses the key aspects of surface modification of nanofillers, including the selection of suitable surface modifiers, such as photoinitiators and polymerizable groups, as well as the optimization of modification conditions to achieve desired surface properties. The influence of surface modification on the interfacial interactions between nanofillers and the polymer matrix is also explored, as it directly impacts the final properties of the nanocomposites. Furthermore, the review highlights the applications of nanocomposites prepared by photopolymerization, such as sensors, gas separation membranes, purification systems, optical devices, and biomedical materials. By providing a comprehensive overview of the surface modification strategies and their impact on the photopolymerization process and the resulting nanocomposite properties, this review aims to inspire new research directions and innovative ideas in the development of high-performance polymer nanocomposites for diverse applications.

4.
Life Sci ; 341: 122490, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38336274

RESUMEN

AIMS: The "Warburg effect" has been developed from the discovery that hypoxia-inducible factor 1α (HIF-1α) could promote the conversion of pyruvate to lactate. However, no studies have linked hypoxia and lactate metabolism to uterine corpus endometrial carcinoma (UCEC). MAIN METHODS: Sequencing and clinical data of patients with UCEC were extracted from The Cancer Genome Atlas (TCGA) database. Hypoxia-related lactate metabolism genes (HRLGs) were screened using Spearman's correlation analysis. A prognostic signature based on HRLGs was developed using the least absolute shrinkage and selection operator (LASSO) algorithm. A comprehensive analysis was conducted on the molecular features, immune environment, mutation patterns, and response to drugs between different risk groups. In vitro and in vivo experiments were performed to verify the function of KIF23. KEY FINDINGS: A five HRLG-based prognostic signature was identified. The prognostic outcome was unfavorable for the high-risk subgroup. Observation of increased pathway activities associated with cell proliferation and DNA damage repair was noted in the high-risk subgroup. Additionally, notable correlations were observed between risk score and immune microenvironment, mutational features, and drug responsiveness. Further, we confirmed KIF23 as a novel oncogene in UCEC, whose silencing decreased proliferation and promoted apoptosis of cancer cells. KIF23 knockdown reduced tumor growth in nude mice. We demonstrated that KIF23 was upregulated under hypoxic stress in a HIF-1α dependent manner. Moreover, KIF23 regulated lactate dehydrogenase A expression. SIGNIFICANCE: The developed HRLG-related signature was associated with prognosis, immune microenvironment, and drug sensitivity in UCEC. We also revealed KIF23 as a hypoxia-regulated lactate metabolism-related oncogene.


Asunto(s)
Neoplasias Endometriales , Oncogenes , Animales , Ratones , Humanos , Femenino , Ratones Desnudos , Oncogenes/genética , Mutación , Hipoxia , Neoplasias Endometriales/genética , Microambiente Tumoral/genética , Proteínas Asociadas a Microtúbulos
5.
Environ Sci Technol ; 58(9): 4392-4403, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38362876

RESUMEN

Unraveling the mysterious pathways of pollutants to the deepest oceanic realms holds critical importance for assessing the integrity of remote marine ecosystems. This study tracks the transport of pollutants into the depths of the oceans, a key step in protecting the sanctity of these least explored ecosystems. By analyzing hadal trench samples from the Mariana, Mussau, and New Britain trenches, we found the widespread distribution of organophosphate ester (OPE) flame retardants but a complex transport pattern for the OPE in these regions. In the Mariana Trench seawater column, OPE concentrations range between 17.4 and 102 ng L-1, with peaks at depths of 500 and 4000 m, which may be linked to Equatorial Undercurrent and topographic Rossby waves, respectively. Sediments, particularly in Mariana (422 ng g-1 dw), showed high OPE affinity, likely due to organic matter serving as a transport medium, influenced by "solvent switching", "solvent depletion", and "filtering processes". Amphipods in the three trenches had consistent OPE levels (29.1-215 ng g-1 lipid weight), independent of the sediment pollution patterns. The OPEs in these amphipods appeared more linked to surface-dwelling organisms, suggesting the influence of "solvent depletion". This study highlights the need for an improved understanding of deep-sea pollutant sources and transport, urging the establishment of protective measures for these remote marine habitats.


Asunto(s)
Anfípodos , Contaminantes Ambientales , Retardadores de Llama , Animales , Ecosistema , Organofosfatos , Ésteres , Solventes
6.
Mar Environ Res ; 195: 106354, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38224625

RESUMEN

Cold-water coral (CWC) communities are biodiversity hotspots on the world's deep seafloor. Although deep-sea corals in the South China Sea (SCS) have been reported before, they are only sporadic. A comprehensive and systematic understanding of the CWC in the SCS would forge the basis for future protection. Here we conducted the first systematic survey on the CWCs in the following six broad-scale sub-regions, from the northwest and northeast slopes to the seamounts in the western and central basins of the SCS, through twenty-four dives of the human-occupied vehicle ShenhaiYongshi. Statistical analysis provided detailed information on the distribution, abundance, size, diversity, and density of CWCs and the in situ environmental conditions supporting coral habitats. We found that the SCS hosted highly diversified coral communities, including twelve genera of gorgonians, six genera of black corals, and one genus of stony corals. The differences in the spatial distribution patterns of coral communities suggested that several environmental variables (depth, temperature, salinity, substrate, and geomorphology) might influence the development of CWCs in the SCS. The intermediate water layer of the SCS appeared to provide suitable habitat for deep-sea coral communities and potentially promoted connectivity. Furthermore, differences between sub-regions within the SCS may be an important factor responsible for the biogeographic patterns of CWCs. These sub-regions of CWCs were observed to range from 0.004 to 0.622 corals m-2, with an average of 0.139 corals m-2. The mean density of CWCs in the SCS was relatively high compared to well-studied CWC hotspots. Overall, the results revealed the significance of the SCS as an important CWC hotspot in the world. These findings provide a fundamental basis for the protection of deep-sea coral assemblages in the SCS.


Asunto(s)
Antozoos , Animales , Humanos , Ecosistema , Agua , Temperatura , China , Arrecifes de Coral
7.
Water Res ; 251: 121126, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38237461

RESUMEN

The "V"-shaped structure of hadal trenches acts as a natural collector of organic pollutants, drawing attention to the need for extensive research in these areas. Our review identifies significant concentrations of organic pollutants, including persistent organic pollutants, black carbon, antibiotic-resistant genes, and plastics, which often match those in industrialized regions. They may trace back to both human activities and natural sources, underscoring the trenches' critical role in ocean biogeochemical cycles. We highlight the complex lateral and vertical transport mechanisms within these zones. Advanced methodologies, including stable isotope analysis, biomarker identification, and chiral analysis within isotope-based mixing models, are crucial for discerning the origins and pathways of these pollutants. In forthcoming studies, we aim to explore advanced methods for precise pollutant tracing, develop predictive models to forecast the future distribution and impacts of pollutants in hadal zones and on the Earth's larger ecological systems.


Asunto(s)
Contaminantes Ambientales , Humanos , Ecosistema , Plásticos , Isótopos
8.
Zool Res ; 45(1): 215-225, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38247179

RESUMEN

A total of 10 specimens of Alcyonacea corals were collected at depths ranging from 905 m to 1 633 m by the manned submersible Shenhai Yongshi during two cruises in the South China Sea (SCS). Based on mitochondrial genomic characteristics, morphological examination, and sclerite scanning electron microscopy, the samples were categorized into four suborders (Calcaxonia, Holaxonia, Scleraxonia, and Stolonifera), and identified as 9 possible new cold-water coral species. Assessments of GC-skew dissimilarity, phylogenetic distance, and average nucleotide identity (ANI) revealed a slow evolutionary rate for the octocoral mitochondrial sequences. The nonsynonymous ( Ka) to synonymous ( Ks) substitution ratio ( Ka/ Ks) suggested that the 14 protein-coding genes (PCGs) were under purifying selection, likely due to specific deep-sea environmental pressures. Correlation analysis of the median Ka/ Ks values of five gene families and environmental factors indicated that the genes encoding cytochrome b (cyt b) and DNA mismatch repair protein ( mutS) may be influenced by environmental factors in the context of deep-sea species formation. This study highlights the slow evolutionary pace and adaptive mechanisms of deep-sea corals.


Asunto(s)
Antozoos , Genoma Mitocondrial , Animales , Antozoos/genética , Filogenia , China , Citocromos b/genética
9.
J Fish Biol ; 104(3): 887-891, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37933516

RESUMEN

This note reports on eight observations of inverted swimming behavior by species of ceratioid whipnose anglerfishes in the genus Gigantactis, from the Caribbean, tropical east Atlantic, tropical western Indian Ocean, the north-east and north-west Pacific and south-west Pacific. It covers four putative species and strongly suggests that this is the normal behavior for the genus. A possible reason is briefly discussed. In addition, a new depth record of 5866 m for the ceratioid anglerfish is recorded.


Asunto(s)
Peces , Natación , Animales , Océano Índico , Región del Caribe , Océano Pacífico
10.
Microbiol Spectr ; 11(6): e0206923, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37943079

RESUMEN

IMPORTANCE: A distinct distribution pattern was shaped by a deterministic process. Enhanced vertical connectivity expanded the previous understanding of seamount effects. Parasitism and predation were prevalent in the seamounts.


Asunto(s)
Eucariontes , Sedimentos Geológicos , Agua de Mar , Océano Pacífico , Sedimentos Geológicos/microbiología , Agua de Mar/microbiología
11.
Sci Total Environ ; 903: 166609, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-37657544

RESUMEN

Serpentinization of peridotite provides a significant source of energy for the subseafloor biosphere and abiotic organic synthesis. The presence of diverse micrometer-scale organic matter in serpentinites offers insights into deep carbon cycling and the origin of life on Earth. It is critical to maintain stringent lab protocols in analyzing serpentinite samples, limiting the contact with organic materials that could contaminate serpentinites and cause misinterpretations. However, the extent to which these organic materials (e.g. latex gloves or nylon polishing disc) can introduce contamination remains unclear. Here we subject serpentinite samples from the Yap Trench in the western Pacific Ocean to multi-stage cutting and polishing procedures prior to analysis. Our findings from electron microscopy reveal that micrometer-scale organic matter in serpentinites is randomly distributed either on the sample surface or within Cr-spinel fractures. Further analysis using Raman spectroscopy indicates that the organic matter contains several hydrogen bonding moieties, similar to those found in the latex gloves or nylon polishing disc used during the treatment of serpentinite samples. Our results suggest that the detected organic matter is likely due to contamination from the organic materials involved during sample processing. Thus, future studies need to carefully assess micrometer-scale organic contamination and limit the use of organic materials when analyzing organic compounds hosted in serpentinites, not only on Earth but also on other rocky planets.

12.
Aging (Albany NY) ; 15(16): 8275-8297, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37616056

RESUMEN

BACKGROUND: Intrauterine adhesion (IUA) is a troublesome complication characterized with endometrial fibrosis after endometrial trauma. Increasing number of investigations focused on autophagy and non-coding RNA in the pathogenesis of uterine adhesion, but the underlying mechanism needs to be further studied. METHODS: mRNA expression profile and miRNA expression profile were obtained from Gene Expression Omnibus database. The autophagy related genes were low. Venn diagram was used to set the intersection of autophagy genes and DEGs to obtain ARDEGs. Circbank was used to select hub autophagy-related circRNAs based on ARDEMs. Then, the differentially expressed autophagy-related genes, miRNAs and circRNAs were analyzed by functional enrichment analysis, and protein-protein interaction network analysis. Finally, the expression levels of hub circRNAs and hub miRNAs were validated through RT-PCR of clinical intrauterine adhesion samples. In vitro experiments were investigated to explore the effect of hub ARCs on cell autophagy, myofibroblast transformation and collagen deposition. RESULTS: 11 autophagy-related differentially expressed genes (ARDEGs) and 41 differentially expressed miRNA (ARDEMs) compared between normal tissues and IUA were identified. Subsequently, the autophagy-related miRNA-mRNA network was constructed and hub ARDEMs were selected. Furthermore, the autophagy-related circRNA-miRNA-mRNA network was established. According to the ranking of number of regulated ARDEMs, hsa-circ-0047959, hsa-circ-0032438, hsa-circ-0047301 were regarded as the hub ARCs. In comparison of normal endometrial tissue, all three hub ARCs were upregulated in IUA tissue. All hub ARDEMs were downregulated except has-miR-320c. CONCLUSIONS: In the current study, we firstly constructed autophagy-related circRNA-miRNA-mRNA regulatory network and identified hub ARCs and ARDEMs had not been reported in IUA.


Asunto(s)
MicroARNs , Enfermedades Uterinas , Femenino , Humanos , ARN Circular , Autofagia , ARN Mensajero
13.
Environ Sci Technol ; 57(16): 6550-6562, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37042785

RESUMEN

Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (<10%) of Hg as MMHg and slightly positive Δ199Hg values. These Δ199Hg values are slightly higher than those in near-field sulfides but are 1 order of magnitude lower than the trench counterparts. We suggest that deep-sea chemosynthetic food webs mainly assimilate Hg from ambient seawater/sediments and hydrothermal fluids formed by percolated seawater through magmatic/mantle rocks. The MMHg transfer from photosynthetic to chemosynthetic food webs is likely limited. The contrasting Hg sources between chemosynthetic and trench food webs highlight Hg isotopes as promising tools to trace the deep-sea Hg biogeochemical cycle.


Asunto(s)
Mercurio , Contaminantes Químicos del Agua , Isótopos de Mercurio/análisis , Cadena Alimentaria , Monitoreo del Ambiente , Mercurio/análisis , Isótopos , Océano Índico , Biota , Contaminantes Químicos del Agua/análisis
14.
Microorganisms ; 11(2)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36838501

RESUMEN

The transition areas of riverine, estuarine, and marine environments are particularly valuable for the research of microbial ecology, biogeochemical processes, and other physical-chemical studies. Although a large number of microbial-related studies have been conducted within such systems, the vast majority of sampling have been conducted over a large span of time and distance, which may lead to separate batches of samples receiving interference from different factors, thus increasing or decreasing the variability between samples to some extent. In this study, a new in situ filtration system was used to collect membrane samples from six different sampling sites along the Sanya River, from upstream freshwater to the sea, over a nine-hour period. We used high-throughput sequencing of 16S and 18S rRNA genes to analyze the diversity and composition of prokaryotic and eukaryotic communities. The results showed that the structures of these communities varied according to the different sampling sites. The α-diversity of the prokaryotic and eukaryotic communities both decreased gradually along the downstream course. The structural composition of prokaryotic and eukaryotic communities changed continuously with the direction of river flow; for example, the relative abundances of Rhodobacteraceae and Flavobacteriaceae increased with distance downstream, while Sporichthyaceae and Comamonadaceae decreased. Some prokaryotic taxa, such as Phycisphaeraceae and Chromobacteriaceae, were present nearly exclusively in pure freshwater environments, while some additional prokaryotic taxa, including the SAR86 clade, Clade I, AEGEAN-169 marine group, and Actinomarinaceae, were barely present in pure freshwater environments. The eukaryotic communities were mainly composed of the Chlorellales X, Chlamydomonadales X, Sphaeropleales X, Trebouxiophyceae XX, Annelida XX, and Heteroconchia. The prokaryotic and eukaryotic communities were split into abundant, common, and rare communities for NCM analysis, respectively, and the results showed that assembly of the rare community assembly was more impacted by stochastic processes and less restricted by species dispersal than that of abundant and common microbial communities for both prokaryotes and eukaryotes. Overall, this study provides a valuable reference and new perspectives on microbial ecology during the transition from freshwater rivers to estuaries and the sea.

15.
Carbohydr Polym ; 298: 120081, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36241273

RESUMEN

Self-healing natural hydrogels still suffer from some issues such as unfit stiffness, poor healing efficiency, and lack of biocompatibility and hydrolytic stability, although they have been used to treat spinal cord injury (SCI). Herein, we develop the injectable, self-healing hyaluronate hydrogels based on multiple dynamic covalent bonds. The hydrogels exhibit fast gelation and excellent self-healing capability as well as injectability, favoring in situ formation for the hydrogels in target sites and maintaining their structural stability. Furthermore, the hydrogels are compatible with neural stem cells and various tissues and possess proper stiffness similar to nervous tissue. Interestingly, the hydrogel can induce neural differentiation of neural stem cells. In vivo experiment further illustrates that the hydrogels promote angiogenesis and remyelination as well as neuron regeneration, leading to the significant locomotor recovery of the SCI model rats. This injectable self-healing hyaluronic acid-based hydrogel is a potential candidate for nerve repair.


Asunto(s)
Hidrogeles , Traumatismos de la Médula Espinal , Animales , Glicosaminoglicanos , Ácido Hialurónico/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Ratas , Traumatismos de la Médula Espinal/tratamiento farmacológico
16.
Materials (Basel) ; 15(16)2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36013871

RESUMEN

Prefabricated composite shear walls (PCSW) consisting of steel plate clapped by single-sided or double-sided prefabricated reinforced concrete (RC) panels have enormous advantages for application as lateral-resisting structures in prefabricated high-rising residential buildings. In this paper, three 1/3-scaled PCSW were manufactured and tested to investigate the seismic performance of PCSW with single-sided or double-sided prefabricated RC panels. The experimental results, including hysteretic and skeleton curves, stiffness and strength degradation, ductility, energy dissipation capability and steel frame effects, were interpreted, compared and summarized. In spite of the RC panels being the same thickness, PCSW with double-sided RC panels had the most outstanding lateral-resisting properties: the highest yield strength and bearing capacity, adequate ductility, plumper and stable hysteresis loop and excellent energy absorption capacity. Finally, a simple predicting equation with a modification coefficient to calculate the effects of boundary steel frame was summarized and proposed to calculate the lateral yield load of the PCSW. All efforts were made to give reliable technical references for the design and construction of the PCSW.

17.
ACS Nano ; 16(7): 11346-11359, 2022 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-35848721

RESUMEN

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP (e.g., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.


Asunto(s)
Ácido Hialurónico , Plasma Rico en Plaquetas , Animales , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Nanogeles , Plasma Rico en Plaquetas/química , Cicatrización de Heridas , Hidrogeles/farmacología , Hidrogeles/química , Aldehídos/análisis
18.
Front Bioeng Biotechnol ; 10: 856745, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35392402

RESUMEN

Uterine fibroids (UF) are the most common benign gynecologic tumors and lead to heavy menstrual bleeding, severe anemia, abdominal pain, and infertility, which seriously harm a women's health. Unfortunately, the regulatory mechanisms of UF have not been elucidated. Recent studies have demonstrated that miRNAs play a vital role in the development of uterine fibroids. As a high-throughput technology, microarray is utilized to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between UF and myometrium. We identified 373 candidate DEGs and the top 100 DEMs. Function enrichment analysis showed that candidate DEGs were mainly enriched in biological adhesion, locomotion and cell migration, and collagen-containing extracellular matrix. Subsequently, protein-protein interaction (PPI) networks are constructed to analyze the functional interaction between DEGs and screen hub DEGs. Subsequently, the expression levels of hub DEGs were validated by real-time PCR of clinical UF samples. The DGIdb database was used to select candidate drugs for hub DEGs. Molecular docking was applied to test the affinity between proteins and drugs. Furthermore, target genes for 100 candidate DEMs were predicted by miRwalk3.0. After overlapping with 373 candidate DEGs, 28 differentially expressed target genes (DEGTs) were obtained. A miRNA-mRNA network was constructed to investigate the interactions between miRNA and mRNA. Additionally, two miRNAs (hsa-miR-381-3p and hsa-miR-181b-5p) were identified as hub DEMs and validated through RT-PCR. In order to better elucidate the pathogenesis of UF and the synergistic effect between miRNA and transcription factor (TF), we constructed a miRNA-TF-mRNA regulatory network. Meanwhile, in vitro results suggested that dysregulated hub DEMs were associated with the proliferation, migration, and apoptosis of UF cells. Our findings provided a novel horizon to reveal the internal mechanism and novel targets for the diagnosis and treatment of UF.

19.
Front Immunol ; 13: 1050743, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36700234

RESUMEN

Osteoarthritis (OA) is a common orthopedic degenerative disease, leading to high disability in activities of daily living. There remains an urgent need to identify the underlying mechanisms and identify new therapeutic targets in OA diagnosis and treatment. Circular RNAs (circRNAs) play a role in the development of multiple diseases. Many studies have reported that circRNAs regulate microRNAs (miRNAs) through an endogenous competitive mechanism. However, it remains unclear if an interplay between circRNAs, miRNAs, and target genes plays a deeper regulatory role in OA. Four datasets were downloaded from the GEO database, and differentially expressed circRNAs (DECs), differentially expressed miRNAs (DEMs), and differentially expressed genes (DEGs) were identified. Functional annotation and pathway enrichment analysis of DEGs and DECs were carried out to determine the main associated mechanism in OA. A protein-protein network (PPI) was constructed to analyze the function of, and to screen out, hub DEGs in OA. Based on the artificial intelligence prediction of protein crystal structures of two hub DEGs, TOP2A and PLK1, digitoxin and oxytetracycline were found to have the strongest affinity, respectively, with molecular docking. Subsequently, overlapping DEMs and miRNAs targeted by DECs obtained target DEMs (DETMs). Intersection of DEGs and genes targeted by DEMs obtained target DEGs (DETGs). Thus, a circRNA-miRNA-mRNA regulatory network was constructed from 16 circRNAs, 32 miRNAs, and 97 mRNAs. Three hub DECs have the largest number of regulated miRNAs and were verified through in vitro experiments. In addition, the expression level of 16 DECs was validated by RT-PCR. In conclusion, we constructed a circRNA-miRNA-mRNA regulatory network in OA and three new hub DECs, hsa_circ_0027914, hsa_circ_0101125, and hsa_circ_0102564, were identified as novel biomarkers for OA.


Asunto(s)
MicroARNs , Osteoartritis , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Simulación del Acoplamiento Molecular , Inteligencia Artificial , Actividades Cotidianas , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Osteoartritis/genética
20.
Innovation (Camb) ; 2(2): 100109, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34557759

RESUMEN

The hadal zone, mostly comprising of deep trenches and constituting of the deepest part of the world's oceans, represents the least explored habitat but one of the last frontiers on our planet. The present scientific understanding of the hadal environment is still relatively rudimentary, particularly in comparison with that of shallower marine environments. In the last 30 years, continuous efforts have been launched in deepening our knowledge regarding the ecology of the hadal trench. However, the geological and environmental processes that potentially affect the sedimentary, geochemical and biological processes in hadal trenches have received less attention. Here, we review recent advances in the geology, biology, and environment of hadal trenches and offer a perspective of the hadal science involved therein. For the first time, we release high-definition images taken by a new full-ocean-depth manned submersible Fendouzhe that reveal novel species with an unexpectedly high density, outcrops of mantle and basaltic rocks, and anthropogenic pollutants at the deepest point of the world's ocean. We advocate that the hydration of the hadal lithosphere is a driving force that influences a variety of sedimentary, geochemical, and biological processes in the hadal trench. Hadal lithosphere might host the Earth's deepest subsurface microbial ecosystem. Future research, combined with technological advances and international cooperation, should focus on establishing the intrinsic linkage of the geology, biology, and environment of the hadal trenches.

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