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A comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bonds (H-bonds) on the obscure reaction of a hydroxyl radical (HOË) and guanine (G) by selecting the building block of parallel triplex DNA, C(H+)GC, as the model. By mapping the energy profiles for addition and hydrogen abstraction reactions, the favorable pathway is predicted. The results reveal that in the C(H+)GC context, barrierless hydrogen abstraction from N2 of G leading to a neutral radical G(N2-H)Ë appears to become significant, but electrophilic attack by HOË on C8 of G resulting in 8-oxoG is the most thermodynamically favorable course. This shows a strong structural dependence due to the context constrained by the H-bond, which is dramatically different from the situation in unencumbered G. More interestingly, it proves that the stability order of resulting adduct radicals is not altered by H-bonding, but the activity for possible sites of the hydroxylation reaction changes. The significant influence of the H-bond on elementary reactions involved in the reaction is emphasized in the C(H+)GC context but is not restricted to the H-abstraction reaction. It is greatly anticipated that the present study could provide thoughtful insights into the vague hydroxyl radical-induced oxidation chemistry.
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With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.
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Envelhecimento , Sequestradores de Radicais Livres , Nanoestruturas , Estresse Oxidativo , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Nanoestruturas/química , Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
Fluorescence imaging can improve surgical accuracy in ovarian cancer, but a high signal-to-noise ratio is crucial for tiny metastatic cancers. Meanwhile, intraoperative fluorescent surgical navigation modalities alone are still insufficient to completely remove ovarian cancer lesions, and the recurrence rate remains high. Here, we constructed a cancer-associated fibroblasts (CAFs)-mimetic aggregation-induced emission (AIE) probe to enable full-cycle management of surgery that eliminates recurrence. AIE molecules (P3-PPh3) were packed in hollow mesoporous silica nanoparticles (HMSNs) to form HMSN-probe and then coated with a CAFs membrane to prepare CAF-probe. First, due to the negative potential of the CAF-probe, the circulation time in vivo is elevated, which facilitates passive tumor targeting. Second, the CAF-probe avoids its clearance by the immune system and improves the bioavailability. Finally, the fibronectin on the CAF-probe specifically binds to integrin α-5 (ITGA5), which is highly expressed in ovarian cancer cells, enabling fluorescence imaging with a contrast of up to 8.6. CAF-probe-based fluorescence imaging is used to evaluate the size and location of ovarian cancer before surgery (preoperative evaluation), to guide tumor removal during surgery (intraoperative navigation), and to monitor tumor recurrence after surgery (postoperative monitoring), ultimately significantly improving the efficiency of surgery and completely eliminating tumor recurrence. In conclusion, we constructed a CAFs mimetic AIE probe and established a full-cycle surgical management model based on its precise imaging properties, which significantly reduced the recurrence of ovarian cancer.
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Semaphorins are a family of evolutionarily conserved morphogenetic molecules that were initially found to be associated with axonal guidance. Semaphorin 4C (Sema4C), a member of the fourth subfamily of semaphorins, has been demonstrated to play multifaceted and important roles in organ development, immune regulation, tumor growth, and metastasis. However, it is completely unknown whether Sema4C is involved in the regulation of ovarian function. We found that Sema4C was widely expressed in the stroma, follicles, and corpus luteum of mouse ovaries, and its expression was decreased at distinct foci in ovaries of mice of mid-to-advanced reproductive age. Inhibition of Sema4C by the ovarian intrabursal administration of recombinant adeno-associated virus-shRNA significantly reduced oestradiol, progesterone, and testosterone levels in vivo. Transcriptome sequencing analysis showed changes in pathways related to ovarian steroidogenesis and the actin cytoskeleton. Similarly, knockdown of Sema4C by siRNA interference in mouse primary ovarian granulosa cells or thecal interstitial cells significantly suppressed ovarian steroidogenesis and led to actin cytoskeleton disorganization. Importantly, the cytoskeleton-related pathway RHOA/ROCK1 was simultaneously inhibited after the downregulation of Sema4C. Furthermore, treatment with a ROCK1 agonist after siRNA interference stabilized the actin cytoskeleton and reversed the inhibitory effect on steroid hormones described above. In conclusion, Sema4C may play an important role in ovarian steroidogenesis through regulation of the actin cytoskeleton via the RHOA/ROCK1 signaling pathway. These findings shed new light on the identification of dominant factors involved in the endocrine physiology of female reproduction.
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Ovário , Semaforinas , Animais , Feminino , Camundongos , Citoesqueleto de Actina/metabolismo , Ovário/metabolismo , RNA Interferente Pequeno/genética , Semaforinas/genética , Semaforinas/metabolismo , Transdução de SinaisRESUMO
A theoretical investigation was performed to disclose the transformation mechanism of 8-oxo-7,8-dihydroguanine radical cation (8-oxoGâ + ) to protonated 2-amino-5-hydroxy-7,9-dihydropurine-6,8-dione (5-OH-8-oxoG) in base pair. The energy profiles for three possible pathways of the events were mapped. It is shown that direct loss of H7 from base paired 8-oxoGâ + is the only energetically favorable pathway to generate neutral radical, 8-oxoG(-H7)â . Further oxidation of 8-oxoG(-H7)â : C to 8-oxoG(-H7)+ : C is exothermic. However, the 8-oxoG(-H7)+ : C deprotonation from all possible active sites is infeasible, indicating the inaccessible second proton loss and the lack of essential intermediate 2-amino-7,9-dihydropurine-6,8-dione (8-oxoGOX ). This makes 8-oxoG(-H7)+ act as the precursor of hydration leading to the generation of protonated 5-HO-8-oxoG by stepwise fashion in base pair, which would initiate the step down guanidinohydantoin (Gh) pathway. These results clearly specify the structure-dependent transformation for 8-oxoGâ + and verify the emergence of protonated 5-HO-8-oxoG in base pair.
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Guanina , Prótons , Pareamento de Bases , Oxirredução , Guanina/químicaRESUMO
A DFT investigation was performed to illuminate the obscure mechanism of hydroxyl radical (OHË) and guanine in G-quadruplex by mapping the energy profiles for both addition and hydrogen abstraction reactions. Results revealed that in G-quadruplex, the electrophilic attack of OHË to C8 (G) leading to 8-oxoG is the most energetically favorable course, where direct hydrogen abstraction from N2 of G to furnish neutral radicals could compete with that. Although the addition of OHË to C4 and C5 positions could provide stable OH-adducts, the subsequent dehydration of C4-OH adduct and hydrogen transfer of C5-OH adduct, which is a prerequisite for neutral radical formation, is rate-limited due to the high barrier manifesting the inaccessibility for these courses. Intriguingly, the identity of the decisive neutral radical was confirmed to be G(N2-H)Ë rather than the familiar G(N1-H)Ë, where the hydrogen bond plays significant roles by blocking tautomerizations.
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Quadruplex G , Radical Hidroxila , Radical Hidroxila/química , Guanina/química , Ligação de Hidrogênio , Hidrogênio/química , Radicais LivresRESUMO
AIMS: We determined the synergistic effects of tea tree essential oil nano-emulsion (nanoTTO) and antibiotics against multidrug-resistant (MDR) bacteria in vitro and in vivo. Then, the underlying mechanism of action of nanoTTO was investigated. METHODS AND RESULTS: Minimum inhibitory concentrations and fractional inhibitory concentration index (FICI) were determined. The transepithelial electrical resistance (TEER) and the expression of tight junction (TJ) protein of IPEC-J2 cells were measured to determine the in vitro efficacy of nanoTTO in combination with antibiotics. A mouse intestinal infection model evaluated the in vivo synergistic efficacy. Proteome, adhesion assays, quantitative real-time PCR, and scanning electron microscopy were used to explore the underlying mechanisms. Results showed that nanoTTO was synergistic (FICI ≤ 0.5) or partial synergistic (0.5 < FICI < 1) with antibiotics against MDR Gram-positive and Gram-negative bacteria strains. Moreover, combinations increased the TEER values and the TJ protein expression of IPEC-J2 cells infected with MDR Escherichia coli. The in vivo study showed that the combination of nanoTTO and amoxicillin improved the relative weight gain and maintained the structural integrity of intestinal barriers. Proteome showed that type 1 fimbriae d-mannose specific adhesin of E. coli was downregulated by nanoTTO. Then, nanoTTO reduced bacterial adhesion and invasion and inhibited the mRNA expression of fimC, fimG, and fliC, and disrupted bacterial membranes.
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Antibacterianos , Óleo de Melaleuca , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Óleo de Melaleuca/farmacologia , Escherichia coli , Proteoma , Sinergismo Farmacológico , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common food-borne pathogen, which has the ability to infect a wide range of hosts. The increasing emergence of drug-resistant strains urgently requires new alternative therapies. Eugenol has been shown to be very effective against drug-resistant strains of Gram-negative and Gram-positive bacteria. The purpose of this study is to explore the effects of eugenol on the virulence factors and pathogenicity of S. Typhimurium. METHODS: The antibacterial activity of eugenol was investigated via the changes of cell morphology, fimbriae related-genes and virulence factors of S. Typhimurium, then the pathogenicity of S. Typhimurium pretreated by eugenol to chickens was evaluated. RESULTS: Susceptibility testing showed that eugenol possessed significant antimicrobial activity. Scanning electron microscope analysis showed eugenol treatment deformed the morphology with damaged fimbriae structure of S. Typhimurium. Real time PCR assay confirmed eugenol significantly down-regulated the expressions of virulence factors (hilA, hilD, sipA, sipC, spiC, misL) of Type III secretion system (T3SS) and adherence genes (fimA, fimH, fimD, fimY, fimZ, stm0551) of Type I fimbriae (TIF). Animal experiment proved that the pathogenicity of S. Typhimurium exposed by eugenol was reduced, which was evidenced by the higher survival rate, weight gains and organs indexes, the lower bacterial loads in organs. Meanwhile, the duodenal histopathological changes were mitigated, with a significantly decline in the expressions of TNF-α, IL-6 and IL-18. CONCLUSION: In summary, eugenol pretreatment may alleviate the pathogenicity of the S. Typhimurium to chickens via wrecking the fimbriae and inhibiting the mRNA expressions of virulence factors and adhesion molecules. These data dedicated the potential mechanisms of eugenol against S. Typhimurium in vitro.
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Galinhas , Salmonella typhimurium , Animais , Proteínas de Bactérias , Eugenol/farmacologia , Salmonella typhimurium/genética , VirulênciaRESUMO
The continuous emergence of multidrug-resistant (MDR) bacteria has posed an increasingly serious public health threat which urges people to develop some alternatives. Gallic acid (GA) is a natural ingredient in many traditional Chinese medicines, which has many biological activities, such as antibacterial, and antiseptic. Here, clinical isolates of MDR Escherichia coli (E. coli) were used to evaluate the antibacterial effect of GA and the underlying mechanism. The results revealed that GA exerted bactericidal activity and inhibited the formation of bacterial biofilm. GA enhanced the activities of ceftiofur sodium or tetracycline against E. coli, and facilitated antibiotic accumulation in bacteria. Further analysis of morphological alterations and efflux pump gene expressions confirmed that GA damaged outer and inner membranes, and suppressed the mRNA expressions of acrA, acrB, tolC, acrD and acrF involved in membrane permeability. In addition, GA showed protective effects against bacterial infection and improved the survival rates of Galleria mellonella and BALB/c mice. These data highlight a better understanding of GA against bacteria and provide an alternative strategy for MDR bacterial infection.
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Farmacorresistência Bacteriana Múltipla , Proteínas de Escherichia coli , Escherichia coli , Ácido Gálico , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ácido Gálico/farmacologia , Lipoproteínas/genética , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismoRESUMO
Ovarian aging is characterized by a progressive decline in ovarian function. With the increase in life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Over the years, various strategies have been developed to preserve fertility in women, while there are currently no clinical treatments to delay ovarian aging. Recently, advances in biomaterials and technologies, such as three-dimensional (3D) printing and microfluidics for the encapsulation of follicles and nanoparticles as delivery systems for drugs, have shown potential to be translational strategies for ovarian aging. This review introduces the research progress on the mechanisms underlying ovarian aging, and summarizes the current state of biomaterials in the evaluation and treatment of ovarian aging, including safety, potential applications, future directions and difficulties in translation.
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Materiais Biocompatíveis , Ovário , Envelhecimento , Feminino , Fertilidade , Humanos , Impressão TridimensionalRESUMO
Tea tree oil (TTO) is a popular topical use to treat skin infections. However, its poor aqueous solubility and stability have substantially limited its widespread application, including oral administration that might be therapeutic for enteric infections. In this study, mechanical ultrasonic methods were used to prepare TTO nanoemulsion (nanoTTO) with a mean droplet diameter of 161.80 nm ± 3.97, polydispersity index of 0.21 ± 0.01, and zeta potential of -12.33 ± 0.72 mV. The potential toxicity of nanoTTO was assessed by studying the oral median lethal dose (LD50) and repeated 28-day oral toxicity to provide a reference for in vivo application. Results showed that nanoTTO had no phase separation under a centrifugation test and displayed good stability during storage at -20, 4 and 25 °C over 60 days. Repeated-dose 28-day oral toxicity evaluation revealed no significant effects on growth and behavior. Assessments of hematology, clinical biochemistry, and histopathology indicated no obvious adverse effects in mice at 50, 100 and 200 mg/mL. These data suggest that nanoTTO can be considered a potential antimicrobial agent by oral administration due to its inhibitory effect on bacteria and relatively lower toxicity.
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Nanopartículas/toxicidade , Óleo de Melaleuca/toxicidade , Administração Oral , Administração Tópica , Animais , Estabilidade de Medicamentos , Emulsões , Dose Letal Mediana , Masculino , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Óleo de Melaleuca/administração & dosagem , Óleo de Melaleuca/química , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines has been successfully realized with 2.5 mol% of B(C6F5)3 as a catalyst to furnish a variety of 3,4-dihydro-2H-1,4-benzoxazines in 93-99% yields. Up to 42% ee was also achieved for the asymmetric hydrogenation with the use of a chiral diene and HB(C6F5)2.
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Using a simple combination of tri-tert-butylphosphine and chiral borane generated in situ by the hydroboration of chiral diene with HB(C6F5)2 as a frustrated Lewis pair catalyst, a highly enantioselective metal-free hydrogenation of silyl enol ethers was successfully realized to furnish a variety of optically active secondary alcohols in 93-99% yields with 88->99% ee's.
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Clinical studies have continually referred to the involvement of drug carrier having dramatic negative influences on the biocompatibility, biodegradability, and loading efficacy of hydrogel. To overcome this deficiency, researchers have proposed to directly self-assemble natural herbal small molecules into a hydrogel without any structural modification. However, it is still a formidable challenge due to the high requirements on the structure of natural molecules, leading to a rarity of this type of hydrogel. Mangiferin (MF) is a natural polyphenol of C-glucoside xanthone with various positive health benefits, including the treatment of diabetic wounds, but its poor hydrosolubility and low bioavailability significantly restrict the clinical application. Inspired by these, with heating/cooling treatment, a carrier-free hydrogel (MF-gel) is developed by assembling the natural herbal molecule mangiferin, which is mainly governed through hydrogen bonds and intermolecular π-π stacking interactions. The as-prepared hydrogel has injectable and self-healing properties and shows excellent biocompatibility, continuous release ability, and reversible stimuli-responsive performances. All of the superiorities enable the MF-based hydrogel to serve as a potential wound dressing for treating diabetic wounds, which was further confirmed by both the vitro and vivo studies. In vitro, the MF-gel could promote the migration of healing-related cells from peripheral as well as the angiogenesis and displays the capacity of mediating inflammation response by scavenging the intracellular ROS. In vivo, the MF-gel accelerates wound contraction and healing via inflammatory adjustment, collagen deposition, and angiogenesis. This study provides a facile and effective method for diabetic wound management and emphasizes the direct self-assembly hydrogel from natural herbal small molecule.
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Hidrogéis , Cicatrização , Xantonas , Xantonas/química , Xantonas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Humanos , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , MasculinoRESUMO
Bi-based YbMg2Bi1.98 Zintl compounds represent promising thermoelectric materials. Precise composition and appropriate doping are of great importance for this complex semiconductor. Here, the influence of Zn substitution for Mg on the microstructure and thermoelectric properties of p-type YbMg1.85-xZnxBi1.98 (x = 0, 0.05, 0.08, 0.13, 0.23) was investigated. Polycrystalline samples were prepared using induction melting and densified with spark plasma sintering. X-ray diffraction confirmed that the major phase of the samples possesses the trigonal CaAl2Si2-type crystal structure, and SEM/EDS indicated the presence of minor secondary phases. The electrical conductivity increases and the lattice thermal conductivity decreases with more Zn doping in YbMg1.85-xZnxBi1.98, whereas the Seebeck coefficient has a large reduction. The band gap decreases with increasing Zn concentration and leads to bipolar conduction, resulting in an increase in the thermal conductivity at higher temperatures. Figure of merit ZT values of 0.51 and 0.49 were found for the samples with x = 0 and 0.05 at 773 K, respectively. The maximum amount of Zn doping is suggested to be less than x = 0.1.
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Enzyme catalytic cascade reactions based on peroxidase nanozymes and natural enzymes have aroused extensive attention in analytical fields. However, a majority of peroxidase nanozymes perform well only in acidic environments, resulting in their optimal pH mismatch with a neutral pH of natural enzymes, further restricting their application in biochemical sensing. Herein, Mn-doped CeO2 (Mn/CeO2) performing enhanced peroxidase-like activity at neutral conditions was prepared via a facile and feasible strategy. An effective enzyme cascade catalysis system via integrating glucose oxidase (GOx) with Mn/CeO2 was developed for one-pot detection of glucose in serum at neutral conditions. Using one-pot multistep catalytic reactions, this work provided a detection platform that allows for faster detection and easier operations than traditional methods. Under optimized conditions, our assay performed a sensitive detection of glucose ranging from 2.0 µΜ to 300 µΜ and a low detection limit of 0.279 µΜ. Notably, favorable analytical outcomes for glucose detection in serum samples were obtained, exhibiting potential applications in clinical diagnosis.
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Oral delivery of chitosan-coated artesunate (CPA) has been proven to be effective at preventing ulcerative colitis (UC) in mice. However, the anti-inflammatory mechanism is not fully understood. STAT6 is a key transcription factor that promotes anti-inflammatory effects by inducing M2 and Th2 dominant phenotypes, therefore we hypothesized STAT6 might play a key role in the process. To prove it, a STAT6 gene knockout macrophage cell line (STAT6-/- RAW264.7, by CRISPR/Cas9 method), and its corresponding Caco-2/RAW264.7 co-culture system combined with the STAT6 inhibitor (AS1517499, AS) in a mouse UC model were established and studied. The results showed that CPA remarkably suppressed the activation of TLR-4/NF-κB pathway and the mRNA levels of proinflammatory cytokines, while increased the IL-10 levels in RAW264.7. This effect of CPA contributed to the protection of the ZO-1 in Caco-2 which was disrupted upon the stimulation to macrophages. Simultaneously, CPA reduced the expression of CD86 but increase the expression of CD206 and p-STAT6 in LPS-stimulated RAW264.7 cells. However, above alterations were not obvious as in STAT6-/- RAW264.7 and its co-culture system, suggesting STAT6 plays a key role. Furthermore, CPA treatment significantly inhibited TLR-4/NF-κB activation, intestinal macrophage M1 polarization and mucosal barrier injury induced by DSS while promoted STAT6 phosphorylation in the UC mouse model, but this effect was also prominently counteracted by AS. Therefore, our data indicate that STAT6 is a major regulator in the balance of M1/M2 polarization, intestinal barrier integrity and then anti-colitis effects of CPA. These findings broaden our understanding of how CPA fights against UC and imply an alternative treatment strategy for UC via this pathway.
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Quitosana , Colite Ulcerativa , Humanos , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Artesunato/farmacologia , Artesunato/metabolismo , Quitosana/farmacologia , NF-kappa B/metabolismo , Células CACO-2 , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Macrófagos , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Sulfato de Dextrana/efeitos adversos , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição STAT6/farmacologiaRESUMO
The human female reproductive lifespan significantly diminishes with age, leading to decreased fertility, reduced fertility quality and endocrine function disorders. While many aspects of aging in general have been extensively documented, the precise mechanisms governing programmed aging in the female reproductive system remain elusive. Recent advancements in omics technologies and computational capabilities have facilitated the emergence of multiomics deep phenotyping. Through the application and refinement of various high-throughput omics methods, a substantial volume of omics data has been generated, deepening our comprehension of the pathogenesis and molecular underpinnings of reproductive aging. This review highlights current and emerging multiomics approaches for investigating female reproductive aging, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics. We elucidate their influence on fundamental cell biology and translational research in the context of reproductive aging, address the limitations and current challenges associated with multiomics studies, and offer a glimpse into future prospects.
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Genômica , Multiômica , Feminino , Humanos , Genômica/métodos , Proteômica , Reprodução/genética , Envelhecimento/genéticaRESUMO
BACKGROUND: Surgical intervention is advisable for both asymptomatic and symptomatic CCAM children. This study aims to compare and analyze the efficacy of thoracoscopic and Da Vinci robot-assisted procedures in the management of CCAM among pediatric patients. METHODS: The clinical data of 188 pediatric patients diagnosed with CCAM and admitted to the Children's Hospital, Zhejiang University School of Medicine, from April 2019 to April 2023 were retrospectively analyzed. The Clavien-Dindo classification was employed for the systematic categorization of postoperative complications. RESULTS: The demographic and clinical characteristics of the patients were comparable between the two groups. Postoperative outcomes, such as the chest tube indwelling rate (92.6% vs 36.2%, p < 0.001∗), chest tube duration (2.0 (2.0-3.0) days vs 1.0 (1.0-2.0) days, p < 0.001∗), and length of postoperative hospital stay (6.0 (5.0-7.0) days vs 5.0 (5.0-6.0) days, p < 0.001∗), favored RATS over VATS. Additionally, there was no significant difference in complications between the two group, but the p-value is in a critical state. â ¢a complications (mainly composed of postoperative thoracentesis procedures) manifesting as a higher rate in the RATS, nearly double that observed in the VATS. CONCLUSIONS: Robot-assisted thoracoscopic lung resection is demonstrated to be safe and feasible, with notable advantages in short-term postoperative clinical outcomes. Nevertheless, the practicality and long-term benefits of this technique necessitate further refinement and dedicated study. LEVEL OF EVIDENCE: LEVEL III.
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Malformação Adenomatoide Cística Congênita do Pulmão , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Cirurgia Torácica Vídeoassistida , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Feminino , Estudos Retrospectivos , Lactente , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cirurgia Torácica Vídeoassistida/métodos , Pré-Escolar , Resultado do Tratamento , Criança , Toracoscopia/métodos , Tempo de Internação/estatística & dados numéricosRESUMO
BACKGROUND: Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. OBJECTIVE AND RATIONALE: This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. SEARCH METHODS: A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine). OUTCOMES: The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors. WIDER IMPLICATIONS: Ovarian function is determined by its 'seeds' (follicles) and 'soil' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field. REGISTRATION NUMBER: Not applicable.