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Studies indicate that the lysine-specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C-C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post-SNT resulted in a higher paw withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV-EGFP-KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV-EGFP-KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV-EGFP-KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP-PCR analysis revealed that increased binding of p-STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV-EGFP-KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs.
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Kupffer cells (KCs) are liver-resident macrophages involved in hepatic inflammatory responses, including nonalcoholic fatty liver disease (NAFLD) development. However, the contribution of KC subsets to liver inflammation remains unclear. Here, using high-dimensional single-cell RNA sequencing, we characterized murine embryo-derived KCs and identified two KC populations with different gene expression profiles: KC-1 and KC-2. KC-1 expressed CD170, exhibiting immunoreactivity and immune-regulatory abilities, while KC-2 highly expressed lipid metabolism-associated genes. In a high-fat diet-induced NAFLD model, KC-1 cells differentiated into pro-inflammatory phenotypes and initiated more frequent communications with invariant natural killer T (iNKT) cells. In KC-1, interleukin (IL)-10 expression was unaffected by the high-fat diet but impaired by iNKT cell ablation and upregulated by iNKT cell adoptive transfer in vivo. Moreover, in a cellular co-culture system, primary hepatic iNKT cells promoted IL-10 expression in RAW264.7 and primary KC-1 cells. CD206 signal blocking in KC-1 or CD206 knockdown in RAW264.7 cells significantly reduced IL-10 expression. In conclusion, we identified two embryo-derived KC subpopulations with distinct transcriptional profiles. The CD206-mediated crosstalk between iNKT and KC-1 cells maintains IL-10 expression in KC-1 cells, affecting hepatic immune balance. Therefore, KC-based therapeutic strategies must consider cellular heterogeneity and the local immune microenvironment for enhanced specificity and efficiency.
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Células T Matadoras Naturais , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Células de Kupffer , Interleucina-10 , Fígado , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The cell endocrine pathway is a critical physiological process composed of the endoplasmic reticulum, Golgi apparatus and associated vesicles. Loss of enzymes or proteins can cause dysfunction of endoplasmic reticulum and Golgi apparatus and affect secretion pathways leading to a variety of human diseases, including cancer. METHODS: The single-cell RNA sequencing and single nucleotide variant principal component analysis data of ovarian cancer were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Eighty-four genes from SECRETORY_PATHWAYs were obtained from the gene set enrichment analysis (GSEA) website. Univariate cox regression analyses and ConsensusClusterPlus were used to identify prognostic genes and molecular subtypes, which were validated using the tumor immune dysfunction and exclusion (i.e. TIDE) analysis and gene mutation analysis. A prognosis model was established by randomForestSRC. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ssGSEA, ESTIMATE, MCP-counter and GSEA. The drug sensitive analysis was performed using pRRophetic package. Immunotherapy datasets and pan-carcinoma analysis were used to examine the performance of prognostic model. RESULTS: Eighteen prognostic genes from SECRETORY_PATHWAYs were found in both TCGA and GEO datasets. Next, two clusters (C1 and C2) were determined, for which C1 with a poor prognosis had higher immune infiltration. Tumor-related pathways, such as PATHWAYS_IN_CANCER and B_CELL_RECEPTOR_SIGNALING_PATHWAY, were enriched in C1. Moreover, C2 was suitable for immunotherapy. A four-gene (DNAJA1, NDRG3, LUZP1 and ZCCHC24) signature was developed and successfully validated. RiskScore of higher levels were significantly associated with worse prognoses. An enhanced immune infiltration, increased pathways score and inappropriate immunotherapy were observed in the high RiskScore group. The high- and low-RiskScore groups had different drug sensitivities. Immunotherapy datasets and pan-carcinoma analysis indicated that the low RiskScore group may benefit from immunotherapy. CONCLUSIONS: Based on the perspective of the secretory signaling pathway, a robust prognostic signature with great performances was determined, which may provide clues for clinical precision treatment of ovarian cancer.
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Biomarcadores Tumorais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Biomarcadores Tumorais/genética , Transcriptoma , Biologia Computacional/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Physiologically based pharmacokinetic (PBPK) modeling was used to predict the human pharmacokinetics and drug-drug interaction (DDI) of GDC-2394. PBPK models were developed using in vitro and in vivo data to reflect the oral and intravenous PK profiles of mouse, rat, dog, and monkey. The learnings from preclinical PBPK models were applied to a human PBPK model for prospective human PK predictions. The prospective human PK predictions were within 3-fold of the clinical data from the first-in-human study, which was used to optimize and validate the PBPK model and subsequently used for DDI prediction. Based on the majority of PBPK modeling scenarios using the in vitro CYP3A induction data (mRNA and activity), GDC-2394 was predicted to have no-to-weak induction potential at 900 mg twice daily (BID). Calibration of the induction mRNA and activity data allowed for the convergence of DDI predictions to a narrower range. The plasma concentrations of the 4ß-hydroxycholesterol (4ß-HC) were measured in the multiple ascending dose study to assess the hepatic CYP3A induction risk. There was no change in plasma 4ß-HC concentrations after 7 days of GDC-2394 at 900 mg BID. A dedicated DDI study found that GDC-2394 has no induction effect on midazolam in humans, which was reflected by the totality of predicted DDI scenarios. This work demonstrates the prospective utilization of PBPK for human PK and DDI prediction in early drug development of GDC-2394. PBPK modeling accompanied with CYP3A biomarkers can serve as a strategy to support clinical pharmacology development plans. SIGNIFICANCE STATEMENT: This work presents the application of physiologically based pharmacokinetic modeling for prospective human pharmacokinetic (PK) and drug-drug interaction (DDI) prediction in early drug development. The strategy taken in this report represents a framework to incorporate various approaches including calibration of in vitro induction data and consideration of CYP3A biomarkers to inform on the overall CYP3A-related DDI risk of GDC-2394.
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Citocromo P-450 CYP3A , Interações Medicamentosas , Modelos Biológicos , Humanos , Interações Medicamentosas/fisiologia , Citocromo P-450 CYP3A/metabolismo , Animais , Cães , Ratos , Masculino , Camundongos , Biomarcadores/sangue , Biomarcadores/metabolismo , Hidroxicolesteróis/farmacocinética , Hidroxicolesteróis/sangue , Adulto , Feminino , Indutores do Citocromo P-450 CYP3A/farmacocinética , Adulto Jovem , Midazolam/farmacocinética , Midazolam/administração & dosagem , Haplorrinos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.
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Mapeamento Cromossômico , Cromossomos de Plantas , Haplótipos , Fenótipo , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Mapeamento Cromossômico/métodos , Marcadores Genéticos , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Sementes/genética , Melhoramento Vegetal , Alelos , Genes de PlantasRESUMO
Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract.
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Nefropatias , Sirtuínas , Humanos , Sirtuínas/metabolismo , Nefropatias/tratamento farmacológico , Estresse Oxidativo , Reparo do DNARESUMO
The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight.
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Índice de Massa Corporal , Obesidade , Síndrome do Ovário Policístico , Resultado da Gravidez , Técnicas de Reprodução Assistida , Humanos , Síndrome do Ovário Policístico/complicações , Feminino , Técnicas de Reprodução Assistida/estatística & dados numéricos , Gravidez , Obesidade/complicações , Taxa de Gravidez , Infertilidade Feminina/terapia , Infertilidade Feminina/etiologia , Sobrepeso/complicaçõesRESUMO
Muscle foods, valued for their significant nutrient content such as high-quality protein, vitamins, and minerals, are vulnerable to adulteration and fraud, stemming from dishonest vendor practices and insufficient market oversight. Traditional analytical methods, often limited to laboratory-scale., may not effectively detect adulteration and fraud in complex applications. Raman spectroscopy (RS), encompassing techniques like Surface-enhanced RS (SERS), Dispersive RS (DRS), Fourier transform RS (FTRS), Resonance Raman spectroscopy (RRS), and Spatially offset RS (SORS) combined with chemometrics, presents a potent approach for both qualitative and quantitative analysis of muscle food adulteration. This technology is characterized by its efficiency, rapidity, and noninvasive nature. This paper systematically summarizes and comparatively analyzes RS technology principles, emphasizing its practicality and efficacy in detecting muscle food adulteration and fraud when combined with chemometrics. The paper also discusses the existing challenges and future prospects in this field, providing essential insights for reviews and scientific research in related fields.
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Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.
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C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.
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BACKGROUND: Cardiac implantable electronic devices (CIEDs) has proven to be an invaluable tool in the practice of cardiology. Patients who have undergone CIED surgery with local anesthesia may result in fear, insecurity and suffering. Some studies have put efforts on ways to improve intraoperative experience of patients with local anesthesia, but researches concerning experiences of CIED patients during surgery is in its infancy. METHODS: Based on semi-structured and in-depth interviews, a qualitative design was conducted in a tertiary general hospital in China from May 2022 to July 2023.Purposeful sampling of 17 patients received CIED surgery and 20 medical staff were interviewed. Thematic analysis with an inductive approach was used to identify dominant themes. RESULTS: Four themes emerged from the data: (1) Safety and success is priority; (2) Humanistic Caring is a must yet be lacking; (3) Paradox of surgery information given; (4) Ways to improve surgery experiences in the operation. CONCLUSIONS: Intraoperative care is significant for CIED surgery. To improve care experience during surgery, healthcare professionals should pay attention to patients' safety and the factors that affecting humanistic caring in clinical practice. In addition, information support should consider information-seeking styles and personal needs. Besides, the four approaches presented in this study are effective to improve the intraoperative care experience.
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Pessoal de Saúde , Humanos , Pesquisa Qualitativa , ChinaRESUMO
Hypertrophic scar (HS) is one of the most common sequelae of patients, especially after burns and trauma. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating HS remain underexplored. Human hypertrophic scar-derived fibroblasts (HSFBs) have been shown to exert more potent promoting effects on extracellular matrix (ECM) accumulation than normal skin-derived fibroblasts (NSFBs) and are associated with enhanced HS formation. The purpose of this study is to search for lncRNAs enriched in HSFBs and investigate their roles and mechanisms. LncRNA MSTRG.59347.16 is one of the most highly expressed lncRNAs in HS detected by lncRNA-seq and qRT-PCR and named as hypertrophic scar fibroblast-associated lncRNA (HSFAS). HSFAS overexpression significantly induces fibroblast proliferation, migration, and myofibroblast trans-differentiation and inhibits apoptosis in HSFBs, while knockdown of HSFAS results in augmented apoptosis and attenuated proliferation, migration, and myofibroblast trans-differentiation of HSFBs. Mechanistically, HSFAS suppresses the expression of A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8). ADAMTS8 knockdown rescues downregulated HSFAS-mediated fibroblast proliferation, migration, myofibroblast trans-differentiation and apoptosis. Thus, our findings uncover a previously unknown lncRNA-dependent regulatory pathway for fibroblast function. Targeted intervention in the HSFAS-ADAMTS8 pathway is a potential therapy for HS.
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Cicatriz Hipertrófica , RNA Longo não Codificante , Humanos , Cicatriz Hipertrófica/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fibroblastos/metabolismo , Apoptose/genética , Proliferação de Células/genética , Transdiferenciação Celular/genética , Proteínas ADAMTS/metabolismoRESUMO
Antimicrobial peptides (AMPs) are an important part of non-specific immunity and play a key role in the cellular host defense against pathogens and tissue injury infections. We investigated the effects of AMP supplementation on the antioxidant capacity, non-specific immunity, and gut microbiota of tsinling lenok trout. 240 fish were fed diets (CT, A120, A240 and A480) containing different amounts of AMP peptides (0, 120 mg kg-1, 240 mg kg-1, 480 mg kg-1) for 8 weeks. Our results showed that the activity of total antioxidant capacity (T-SOD) and glutathione peroxidase (GSH-Px), lysozyme (LZM), catalase (CAT) and acid phosphatase (ACP) in the A240 and A480 group were higher than that in the CT group (P < 0.05). The content of malondialdehyde (MDA) in AMP group was significantly lower than that in CT group (P < 0.05). Furthermore, we harvested the mid-gut and applied next-generation sequencing of 16S rDNA. The results showed that the abundance of Halomonas in AMP group was significantly lower than that in CT group. Functional analysis showed that the abundance of chloroalkane and chloroalkene degradation pathway increased significantly in AMP group. In conclusion, AMP enhanced the antioxidant capacity, non-specific immunity, and intestinal health of tsinling lenok trout.
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This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen-induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid-like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA.
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Artrite Reumatoide , Medicamentos de Ervas Chinesas , Metaboloma , Metabolômica , Animais , Metabolômica/métodos , Medicamentos de Ervas Chinesas/farmacologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Ratos , Metaboloma/efeitos dos fármacos , Metaboloma/fisiologia , Masculino , Ratos Sprague-Dawley , Artrite Experimental/metabolismo , Artrite Experimental/tratamento farmacológicoRESUMO
In the global effort to reduce CO2 emissions, the concurrent enhancement of pollutant degradation and reductions in fossil fuel consumption are pivotal aspects of microalgae-mediated wastewater treatment. Clarifying the degradation mechanisms of bacteria and microalgae during pollutant treatment, as well as regulatory biolipid production, could enhance process sustainability. The synergistic and inhibitory relationships between microalgae and bacteria are introduced in this paper. The different stimulators that can regulate microalgal biolipid accumulation are also reviewed. Wastewater treatment technologies that utilize microalgae and bacteria in laboratories and open ponds are described to outline their application in treating heavy metal-containing wastewater, animal husbandry wastewater, pharmaceutical wastewater, and textile dye wastewater. Finally, the major requirements to scale up the cascade utilization of biomass and energy recovery are summarized to improve the development of biological wastewater treatment.
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Microalgas , Eliminação de Resíduos Líquidos , Águas Residuárias , Microalgas/metabolismo , Eliminação de Resíduos Líquidos/métodos , Bactérias/metabolismo , Biomassa , Metais Pesados , Biodegradação AmbientalRESUMO
Food waste and byproducts (FWBP) are a global issue impacting economies, resources, and health. Recycling and utilizing these wastes, due to processing and economic constraints, face various challenges. However, valuable components in food waste inspire efficient solutions like active intelligent packaging. Though research on this is booming, its material selectivity, effectiveness, and commercial viability require further analysis. This paper categorizes FWBP and explores their potential for producing packaging from both animal and plant perspectives. In addition, the preparation/fabrication methods of these films/coatings have also been summarized comprehensively, focusing on the advantages and disadvantages of these methods and their commercial adaptability. Finally, the functions of these films/coatings and their ultimate performance in protecting food (meat, dairy products, fruits, and vegetables) are also reviewed systematically. FWBP provide a variety of methods for the application of edible films, including being made into coatings, films, and fibers for food preservation, or extracting active substances directly or indirectly from them (in the form of encapsulation) and adding them to packaging to endow them with functions such as barrier, antibacterial, antioxidant, and pH response. In addition, the casting method is the most commonly used method for producing edible films, but more film production methods (extrusion, electrospinning, 3D printing) need to be tried to make up for the shortcomings of the current methods. Finally, researchers need to conduct more in-depth research on various active compounds from FWBP to achieve better application effects and commercial adaptability.
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Perda e Desperdício de Alimentos , Eliminação de Resíduos , Animais , Conservação de Alimentos , Antibacterianos , FrutasRESUMO
Over half of cancer patients are subjected to radiotherapy, but owing to the deficient amount of reactive oxygen radicals (ROS) and DNA double-strand breaks (DSBs), a fair number of them suffer from radiotherapy resistance and the subsequent short-term survival opportunity. To overcome it, many successes have been achieved in radiosensitizer discovery using physical strategy and/or biological strategy, but significant challenges remain regarding developing clinically translational radiosensitizers. Herein, a peptide-Au(I) infinite coordination supermolecule termed PAICS is developed that combined both physical and biological radiosensitization and possessed pharmaceutical characteristics including adequate circulatory stability, controllable drug release, tumor-prioritized accumulation, and the favorable body eliminability. As expected, monovalent gold ion endowed this supermolecule with high X-ray absorption and the subsequent radiosensitization. Furthermore, a peptide targeting CRM1, is assembled into the supermolecule, which successfully activates p53 and apoptosis pathway, thereby further sensitizing radiotherapy. As a result, PAICS showed superior ability for radiotherapy sensitization in vivo and maintained a favorable safety profile. Thus, the PAICS reported here will offer a feasible solution to simultaneously overcome both the pharmaceutical obstacles of physical and biological radiosensitizers and will enable the development of a class of nanomedicines for tumor radiotherapy sensitization.
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Nanopartículas Metálicas , Neoplasias , Radiossensibilizantes , Humanos , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Radiossensibilizantes/química , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Peptídeos , Preparações Farmacêuticas , Ouro/química , Nanopartículas Metálicas/uso terapêuticoRESUMO
Sperm development, maturation, and successful fertilization within the female reproductive tract are intricate and orderly processes that involve protein translation and post-translational modifications. Among these modifications, sialylation plays a crucial role. Any disruptions occurring throughout the sperm's life cycle can result in male infertility, yet our current understanding of this process remains limited. Conventional semen analysis often fails to diagnose some infertility cases associated with sperm sialylation, emphasizing the need to comprehend and investigate the characteristics of sperm sialylation. This review reanalyzes the significance of sialylation in sperm development and fertilization and evaluates the impact of sialylation damage on male fertility under pathological conditions. Sialylation serves a vital role in the life journey of sperm, providing a negatively charged glycocalyx and enriching the molecular structure of the sperm surface, which is beneficial to sperm reversible recognition and immune interaction. These characteristics are particularly crucial during sperm maturation and fertilization within the female reproductive tract. Moreover, enhancing the understanding of the mechanism underlying sperm sialylation can promote the development of relevant clinical indicators for infertility detection and treatment.
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Infertilidade Masculina , Maturação do Esperma , Animais , Masculino , Humanos , Feminino , Sêmen/metabolismo , Espermatozoides/metabolismo , Infertilidade Masculina/metabolismo , Mamíferos , Fertilização , Fertilidade , Capacitação EspermáticaRESUMO
Infertility is a challenging health problem that affects 8-15% of couples worldwide. Establishing pregnancy requires successful embryo implantation, but about 85% of unsuccessful pregnancies are due to embryo implantation failure or loss soon after. Factors crucial for successful implantation include invasive blastocysts, receptive endometrium, invasion of trophoblast cells, and regulation of immune tolerance at the maternal-fetal interface. Maternal-fetal crosstalk, which relies heavily on protein-protein interactions, is a critical factor in implantation that involves multiple cellular communication and molecular pathways. Glycosylation, a protein modification process, is closely related to cell growth, adhesion, transport, signal transduction, and recognition. Protein glycosylation plays a crucial role in maternal-fetal crosstalk and can be divided into N-glycosylation and O-glycosylation, which are often terminated by sialylation or fucosylation. This review article examines the role of protein glycosylation in maternal-fetal crosstalk based on two transcriptome datasets from the GEO database (GSE139087 and GSE113790) and existing research, particularly in the context of the mechanism of protein glycosylation and embryo implantation. Dysregulation of protein glycosylation can lead to adverse pregnancy outcomes, such as missed abortion and recurrent spontaneous abortion, underscoring the importance of a thorough understanding of protein glycosylation in the diagnosis and treatment of female reproductive disorders. This knowledge could have significant clinical implications, leading to the development of more effective diagnostic and therapeutic approaches for these conditions.
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Aborto Habitual , Implantação do Embrião , Gravidez , Feminino , Humanos , Glicosilação , Implantação do Embrião/fisiologia , Endométrio/fisiologia , Resultado da GravidezRESUMO
MAIN CONCLUSION: This review summarizes the anti-stress effects of flavonoids in plants and highlights its role in the regulation of polar auxin transport and free radical scavenging mechanism. As secondary metabolites widely present in plants, flavonoids play a vital function in plant growth, but also in resistance to stresses. This review introduces the classification, structure and synthetic pathways of flavonoids. The effects of flavonoids in plant stress resistance were enumerated, and the mechanism of flavonoids in plant stress resistance was discussed in detail. It is clarified that plants under stress accumulate flavonoids by regulating the expression of flavonoid synthase genes. It was also determined that the synthesized flavonoids are transported in plants through three pathways: membrane transport proteins, vesicles, and bound to glutathione S-transferase (GST). At the same time, the paper explores that flavonoids regulate polar auxin transport (PAT) by acting on the auxin export carrier PIN-FORMED (PIN) in the form of ATP-binding cassette subfamily B/P-glycoprotein (ABCB/PGP) transporter, which can help plants to respond in a more dominant form to stress. We have demonstrated that the number and location of hydroxyl groups in the structure of flavonoids can determine their free radical scavenging ability and also elucidated the mechanism by which flavonoids exert free radical removal in cells. We also identified flavonoids as signaling molecules to promote rhizobial nodulation and colonization of arbuscular mycorrhizal fungi (AMF) to enhance plant-microbial symbiosis in defense to stresses. Given all this knowledge, we can foresee that the in-depth study of flavonoids will be an essential way to reveal plant tolerance and enhance plant stress resistance.