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1.
Mol Biol Rep ; 51(1): 648, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727802

RESUMEN

BACKGROUND: Polygonatum kingianum holds significant importance in Traditional Chinese Medicine due to its medicinal properties, characterized by its diverse chemical constituents including polysaccharides, terpenoids, flavonoids, phenols, and phenylpropanoids. The Auxin Response Factor (ARF) is a pivotal transcription factor known for its regulatory role in both primary and secondary metabolite synthesis. However, our understanding of the ARF gene family in P. kingianum remains limited. METHODS AND RESULTS: We employed RNA-Seq to sequence three distinct tissues (leaf, root, and stem) of P. kingianum. The analysis revealed a total of 31,558 differentially expressed genes (DEGs), with 43 species of transcription factors annotated among them. Analyses via gene ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that these DEGs were predominantly enriched in metabolic pathways and secondary metabolite biosynthesis. The proposed temporal expression analysis categorized the DEGs into nine clusters, suggesting the same expression trends that may be coordinated in multiple biological processes across the three tissues. Additionally, we conducted screening and expression pattern analysis of the ARF gene family, identifying 12 significantly expressed PkARF genes in P. kingianum roots. This discovery lays the groundwork for investigations into the role of PkARF genes in root growth, development, and secondary metabolism regulation. CONCLUSION: The obtained data and insights serve as a focal point for further research studies, centred on genetic manipulation of growth and secondary metabolism in P. kingianum. Furthermore, these findings contribute to the understanding of functional genomics in P. kingianum, offering valuable genetic resources.


Asunto(s)
Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Proteínas de Plantas , Plantas Medicinales , Polygonatum , Transcriptoma , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Polygonatum/genética , Polygonatum/metabolismo , Transcriptoma/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica/métodos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ontología de Genes , Hojas de la Planta/genética , Hojas de la Planta/metabolismo
2.
Biometrics ; 80(1)2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38488465

RESUMEN

Age-related hearing loss has a complex etiology. Researchers have made efforts to classify relevant audiometric phenotypes, aiming to enhance medical interventions and improve hearing health. We leveraged existing pattern analyses of age-related hearing loss and implemented the phenotype classification via quadratic discriminant analysis (QDA). We herein propose a method for analyzing the exposure effects on the soft classification probabilities of the phenotypes via estimating equations. Under reasonable assumptions, the estimating equations are unbiased and lead to consistent estimators. The resulting estimator had good finite sample performances in simulation studies. As an illustrative example, we applied our proposed methods to assess the association between a dietary intake pattern, assessed as adherence scores for the dietary approaches to stop hypertension diet calculated using validated food-frequency questionnaires, and audiometric phenotypes (older-normal, metabolic, sensory, and metabolic plus sensory), determined based on data obtained in the Nurses' Health Study II Conservation of Hearing Study, the Audiology Assessment Arm. Our findings suggested that participants with a more healthful dietary pattern were less likely to develop the metabolic plus sensory phenotype of age-related hearing loss.


Asunto(s)
Pérdida Auditiva , Humanos , Causalidad , Análisis de Regresión , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/etiología , Fenotipo
3.
Phytomedicine ; 128: 155338, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38520835

RESUMEN

BACKGROUND: Liver cancer, one of the most common types of cancer worldwide, accounts for millions of cases annually. With its multi-target and wide-ranging therapeutic effects, traditional Chinese medicine has emerged as a potential approach for treating various tumors. Codonopsis pilosula, a traditional herb, is known for its anti-inflammatory and antioxidant properties. In this study, we investigated the potential molecular mechanisms of Codonopsis pilosula in regulating the inhibition of CDK1 and the modulation of PDK1/ß-catenin, which are involved in hepatocellular carcinoma growth and metastasis. STUDY DESIGN/METHODS: Firstly, we screened the active chemical constituents of Codonopsis pilosula and identified their respective target proteins using the Herb database. Then, we applied the GeneCards database and transcriptome sequencing analysis to screen for critical genes associated with the occurrence and development of liver cancer. The intersection of the target proteins and disease-related genes was used to determine the potential targets of Codonopsis pilosula in hepatocellular carcinoma. Protein-protein interaction analysis and GO/KEGG analysis were subsequently performed to uncover the pathways through which Codonopsis pilosula acts on liver cancer. The Huh-7 cell line, exhibiting the highest sensitivity to Codonopsis pilosula polysaccharide solution (CPP) intervention, was chosen for subsequent studies. Cell viability was evaluated using the CCK-8 assay, colony formation assay was conducted to determine cell proliferation capacity, flow cytometry was used to analyze cell cycle, TUNEL staining was performed to assess cell apoptosis, scratch assay was carried out to evaluate cell migration ability, the expression of EMT-related proteins was detected and analyzed, and cell sphere formation assay was conducted to investigate cell stemness. Finally, a liver cancer animal model was established, and different doses of CPP were administered via gavage the next day. The expression levels of CDK1, PDK1, and ß-catenin in mouse liver tissues were detected and analyzed, immunohistochemistry staining was performed to assess the expression of tumor cell proliferation-related proteins Ki67 and PCNA in mouse xenografts, and TUNEL staining was carried out to evaluate cell apoptosis in mouse liver tissues. After intervention with CDK1 expression, the expression levels of CDK1, PDK1, and ß-catenin proteins and mRNA in each group of cells were detected using Western blot and RT-qPCR. RESULTS: Through network pharmacology analysis, transcriptome sequencing, and bioinformatics analysis, 35 target genes through which Codonopsis pilosula acts on liver cancer were identified. Among them, CDK1, with the highest degree in the PPI network, was considered an essential target protein for Codonopsis pilosula in treating liver cancer. In vitro cell experiments revealed that CPP could inhibit the expression of CDK1/PDK1/ß-catenin signaling axis factors, suppress cell proliferation, decrease cell migration ability, influence the EMT process, and reduce cell stemness by inhibiting CDK1 and affecting the PDK1/ß-catenin signaling axis. Similarly, in vivo experiments demonstrated that CPP could regulate the CDK1/PDK1/ß-catenin signaling axis, inhibit tumor growth, and induce cell apoptosis. CONCLUSION: Codonopsis pilosula may inhibit hepatocellular carcinoma growth by suppressing CDK1 and affecting the PDK1/ß-catenin signaling axis, limiting cell EMT and reducing cell stemness. These findings provide insights into the potential therapeutic role of Codonopsis pilosula in liver cancer.


Asunto(s)
Proteína Quinasa CDC2 , Carcinoma Hepatocelular , Codonopsis , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Humanos , Codonopsis/química , Línea Celular Tumoral , Proteína Quinasa CDC2/metabolismo , Ratones , Proliferación Celular/efectos de los fármacos , beta Catenina/metabolismo , Antineoplásicos Fitogénicos/farmacología , Ratones Desnudos , Ratones Endogámicos BALB C , Masculino , Movimiento Celular/efectos de los fármacos , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Ensayos Antitumor por Modelo de Xenoinjerto , Medicamentos Herbarios Chinos/farmacología
4.
Heliyon ; 10(5): e26732, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38449666

RESUMEN

Ganoderma lucidum polysaccharides (G. PS) have been recognized for their immune-modulating properties. In this study, we investigated the impact of G. PS in a sepsis mouse model, exploring its effects on survival, inflammatory cytokines, Treg cell differentiation, bacterial load, organ dysfunction, and related pathways. We also probed the role of macrophages through chlorphosphon-liposome pretreatment. Using the cecal ligation and puncture (CLP) model, we categorized mice into normal, PBS, and G. PS injection groups. G. PS significantly enhanced septic mouse survival, regulated inflammatory cytokines (TNF-α, IL-17A, IL-6, IL-10), and promoted CD4+Foxp3+ Treg cell differentiation in spleens. Additionally, G. PS reduced bacterial load, mitigated organ damage, and suppressed the NF-κB pathway. In vitro, G. PS facilitated CD4+ T cell differentiation into Treg cells via the p-STAT5 pathway. Chlorphosphon-liposome pretreatment heightened septic mortality, bacterial load, biochemical markers, and organ damage, emphasizing macrophages' involvement. G. PS demonstrated significant protective effects in septic mice by modulating inflammatory responses, enhancing Treg cell differentiation, diminishing bacterial load, and inhibiting inflammatory pathways. These findings illuminate the therapeutic potential of G. PS in sepsis treatment.

5.
RSC Chem Biol ; 5(3): 189-197, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38456041

RESUMEN

Proteolysis-targeting chimeras or PROTACs are hetero-bifunctional molecules designed to mediate the disposal of a target protein via recruitment of the ubiquitination-proteasome degradation machinery. Because of the chimeric nature of such molecules, their synthesis requires a key step of "assembling" whether in the lab or in situ. Furthermore, targeted PROTACs often are hetero-trifunctional and require a second "assembling" step. Click chemistry has the unique advantages of tethering two or more molecular entities of choice under near physiological conditions and therefore has been applied to the development of PROTACs in various ways. This review provides a succinct summary of this field with a critical analysis of various factors that need to be considered for optimal results. Specifically, we examine issues including applications of click chemistry in in situ assembly for improved delivery, conjugation with a targeting group for selectivity, rapid synthesis for linker optimization, and lysosomal degradation of extracellular and membrane-associated proteins. We also examine reaction kinetics issues whenever possible or warranted.

6.
Immunology ; 172(1): 163-177, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38361445

RESUMEN

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.


Asunto(s)
Antineoplásicos , Citotoxicidad Inmunológica , Humanos , Dasatinib/farmacología , Dasatinib/uso terapéutico , Dasatinib/metabolismo , Células Asesinas Naturales/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular
7.
Chem Biodivers ; : e202301477, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38415906

RESUMEN

Alkaloids are natural products that occur widely in many herbal plants. Anisodamine, widely present in the Solanaceae family, is an alkaloid extracted from the roots of the Anisodus tanguticus Maxim. It is an antagonist to M-choline receptors and exhibits diverse pharmacological effects, such as cholinolytic effect, calcium antagonist effect, anti-oxygenation effect. Anisodamine, a prominent constituent of the tropine alkaloid family, exhibits a range of pharmacological effects akin to those of atropine and scopolamine. owing to its low toxicity and moderate efficacy in clinical to wide applications, especially for varieties of shock treatment. However, there remains a dearth of research regarding the in vivo pharmacokinetics, mechanism of action, and toxicity of anisodamine. Consequently, this paper provides a comprehensive review of the anti-shock effects, toxicity, and pharmacokinetic characteristics of anisodamine to increase the understanding of its medicinal value, and provide reference and inspiration for the clinical application and further in-depth research of anisodamine.

8.
Front Aging ; 5: 1361098, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38379538

RESUMEN

China is in a period of rapid population aging. The total population of the elderly aged 60 and above in mainland China was 264 million in 2020, and is the country with the largest elderly population in the world, which is home to 1/5 of the world's older people. The urgency of actively coping with the aging population has never been greater, and China has raised it to the height of national strategy. To this end, China has issued several plans and projects on aging work. Many of them include multiple overlapping components. The management of physical illness and mental illness in the elderly is over-differentiated and segmented. However, it is common for older adults with complex health problems. The body and mind are inherently integrated and interact with each other, and should not be separated. There is an urgent need for integrated healthcare services for the physical and mental health of the elderly population. The national basic public health services play an important role in early detection and awareness of health problems for the elderly in community health services. This paper introduces the elderly health management services, one of the national basic public health projects, and the psychological care project for the elderly in Shenzhen, Guangdong Province, China. Taking Long-gang District's exploration of the joint management of physical and mental health of the elderly as an example, this review discusses the difficulties of the elderly health work, and the feasibility of integrating the elderly mental health and physical health in medical care. We outlook to build an integrated platform for physical and mental health of the elderly in China. Focus on the needs of older population, strengthen community health services, build a integrative team, fully publicize and improve health literacy of the elderly, link up and down and work together, improve coordination between providers of medical care and social services. It is of great significance to construct a strong public health system for the elderly and promote the realization of the grand goal of Healthy China.

9.
Mol Neurobiol ; 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38311654

RESUMEN

Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4 W) by utilizing a concentration of 0.5 mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side's forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI. This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries.

10.
Adv Biol (Weinh) ; 8(3): e2300593, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38221687

RESUMEN

In vitro cell culturing witnessed its applications in scientific research and industrial activities. Attempts to shorten the doubling time of cultured cells have never ceased. In plants, auxin is applied to promote plant growth, the synthetic derivative 1-Naphthaleneacetic acid (NAA) is a good example. Despite the auxin's naturally occurring receptors are not present in mammalian cells, studies suggested they may affect cell culturing. Yet the effects and mechanisms are still unclear. Here, an up to 2-fold increase in the yield of in vitro cultured human cells is observed. Different types of human cell lines and primary cells are tested and found that NAA is effective in all the cells tested. The PI staining followed by FACS suggested that NAA do not affect the cell cycling. Apoptosis-specific dye staining analysis implicated that NAA rescued cell death. Further bulk RNA sequencing is done and it is identified that the lipid metabolism-engaging and anti-apoptosis gene, ANGPTL4, is enhanced in expression upon NAA treatment. Studies on ANGPTL4 knockout cells indicated that ANGPTL4 is required for NAA-mediated response. Thus, the data identified a beneficial role of NAA in human cell culturing and highlighted its potency in in vitro cell culturing.


Asunto(s)
Ácidos Indolacéticos , Ácidos Naftalenoacéticos , Animales , Humanos , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacología , Células Cultivadas , Ácidos Naftalenoacéticos/farmacología , Ácidos Naftalenoacéticos/metabolismo , Apoptosis , Mamíferos/metabolismo
11.
Blood ; 143(19): 1965-1979, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38271660

RESUMEN

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML. We found that although PI3Kγ is highly enriched in LSCs and critical for self-renewal, it was dispensable for normal hematopoietic stem cells. Mechanistically, PI3Kγ-AKT signaling promotes nuclear factor erythroid 2-related factor 2 (NRF2) nuclear accumulation, which induces 6-phosphogluconate dehydrogenase (PGD) and the pentose phosphate pathway, thereby maintaining LSC stemness. Importantly, genetic or pharmacological inhibition of PI3Kγ impaired expansion and stemness of murine and human AML cells in vitro and in vivo. Together, our findings reveal a key role for PI3Kγ in selectively maintaining LSC function by regulating AKT-NRF2-PGD metabolic pathway. Targeting the PI3Kγ pathway may, therefore, eliminate LSCs without damaging normal hematopoiesis, providing a promising therapeutic strategy for AML.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase Ib , Leucemia Mieloide Aguda , Células Madre Neoplásicas , Vía de Pentosa Fosfato , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Animales , Humanos , Ratones , Fosfatidilinositol 3-Quinasa Clase Ib/metabolismo , Fosfatidilinositol 3-Quinasa Clase Ib/genética , Autorrenovación de las Células , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Transducción de Señal , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética
12.
Glia ; 72(3): 607-624, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38031815

RESUMEN

Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4-week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis-related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno-associated virus (AAV)-mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise-induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin-related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.


Asunto(s)
Vaina de Mielina , Traumatismos de la Médula Espinal , Ratones , Animales , Vaina de Mielina/metabolismo , PPAR gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Hibridación Fluorescente in Situ , Traumatismos de la Médula Espinal/metabolismo , Médula Espinal/metabolismo , Recuperación de la Función/fisiología
13.
Mol Biomed ; 4(1): 44, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38015348

RESUMEN

In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.

14.
Int J Mol Sci ; 24(21)2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37958753

RESUMEN

Laccase genes produce laccase enzymes that play a crucial role in the production of lignin and oxidation reactions within plants. Lignin is a complex polymer that provides structure and toughness to the cell walls of numerous fruit plants. The LAC genes that encode laccase enzymes play vital roles in plant physiology, including the synthesis of pigments like PA that contribute to the colors of fruits, and in defending against pathogens and environmental stresses. They are crucial for fruit development, ripening, structural maintenance in plants, and adaptation to various environmental factors. As such, these genes and enzymes are essential for plant growth and development, as well as for various biotechnological applications in environmental remediation and industrial processes. This review article emphasizes the significance of genes encoding laccase enzymes during fruit growth, specifically pertaining to the strengthening of the endocarp through lignification. This process is crucial for ensuring fruit defense and optimizing seed scattering. The information gathered in this article will aid breeders in producing future fruit-bearing plants that are resistant to disease, cost-effective, and nutrient-rich.


Asunto(s)
Frutas , Lignina , Lignina/metabolismo , Lacasa/metabolismo , Operón Lac , Semillas/metabolismo , Regulación de la Expresión Génica de las Plantas
15.
Front Pharmacol ; 14: 1197418, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37790812

RESUMEN

Background: Ganoderma lucidum (G. lucidum) is a popular traditional remedy medicine used in Asia to promote health and longevity, which has also been highlighted for anti-cancer effects. This study investigated the molecular pharmacological mechanism of G. lucidum triterpenes in influencing intestinal flora imbalance in non-hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) based on 16S rRNA sequencing technology and network pharmacology analysis. Methods: 16S rRNA sequencing data of fecal samples from normal controls and HCC patients were obtained from the SRA database. G. lucidum triterpenes and HCC-related targets were screened by BATMAN-TCM, ETCM, and GeneCards databases. The TCGA-LIHC dataset was downloaded through the TCGA database to analyze the differential expression of key genes. NHBV-related HCC-related transcriptome RNA sequencing dataset was downloaded via the GEO database. Results: Abundance of intestinal flora in the HBV-related HCC and NHBV-related samples was higher than that of control samples. The intestinal flora of NHBV samples was mainly enriched in apoptosis and p53 pathways. Totally, 465 G. lucidum triterpenes-related targets were intersected with 4186 HCC-related targets, yielding 176 intersected targets. Among them, apoptosis and p53 pathway factors were located at the core of the protein-protein interactions network. Ganosporelactone B, the active component of G. lucidum triterpenes, had the lowest binding free energy to CASP3. CASP3 expression were upregulated in HCC tissue samples, and had higher predictive value in NHBV-related HCC patients. Conclusion: Therefore, Ganosporelactone B, the active ingredient of G. lucidum triterpenes, improves the imbalance of intestinal flora and ultimately curtails development of NHBV-related HCC.

16.
Medicine (Baltimore) ; 102(38): e35029, 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37746970

RESUMEN

The severe respiratory syndrome 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread explosively, raising global health concerns. Luteolin shows antiviral properties, but its effect on SARS-CoV-2 and the associated mechanisms are not elucidated. We used network pharmacology, molecular docking and molecular dynamics to provide potential molecular support of luteolin (3,4,5,7-tetrahydroxyflavone) (LUT) against COVID-19. We employed network pharmacology, molecular docking, and molecular dynamics techniques to investigate how LUT affected COVID-19. Several databases were queried to determine potential target proteins related to LUT and COVID-19. Protein-protein interaction network was constructed, and core targets were filtered by degree value. Following that, functional enrichment was conducted. Molecular docking was utilized to ensure LUT was compatible with core target proteins. Finally, molecular dynamics was used to analyze the effects of the LUT on the optimal hub target. A total of 64 potential target genes for treating COVID-19 were identified, of which albumin, RAC-alpha serine/threonine-protein kinase, caspase-3, epidermal growth factor receptor, heat shock protein HSP 90-alpha, and mitogen-activated protein kinase 1 might be the most promising. In addition, molecular docking results showed that LUT could interact with SARS-CoV-2 major protease 3CL. LUT can bind to the active sites of 3CL protease and mitogen-activated protein kinase 1, showing an anti-SARS-CoV-2 potential.


Asunto(s)
COVID-19 , Luteolina , Humanos , Luteolina/farmacología , Luteolina/uso terapéutico , Proteína Quinasa 1 Activada por Mitógenos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Péptido Hidrolasas , Endopeptidasas
17.
Accid Anal Prev ; 192: 107272, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37683567

RESUMEN

Transportation-related harms have developed into a social disease, threatening public safety and health in China. We aimed to increase the global understanding of traffic safety and public health in China from past knowledge, current status, and future directions by collecting, collating, and analyzing the Chinese traffic incidents reported in the published literature. A systematic search of China National Knowledge Infrastructure, Weipu, and published articles referenced in PubMed, Web of Science and ProQuest between January 1, 1988 and April 30, 2023 was performed. China encountered the first recorded traffic accident as early as three thousand years ago in the Shang Dynasty. An increase in vehicle capacity and velocity increased the traffic risks during the transition from rickshaws and livestock to motor vehicles in varying traffic environments. Humans are not only the decisive factor of a large number of vehicles, traffic routes, and environmental variables, but also the victims at the end and starting point of traffic accidents. Injuries (mechanical force, burns) and diseases (traffic-related air pollution, noise) caused by traffic activities not only threaten public health, but also cause risks to safe driving. Analysis of traffic activities and biomarkers promotes the treatment of traffic injuries in ethology and medicine. China prepared for the construction of healthy transportation in the "decade of road safety" toward an estimation of worldwide road traffic injuries in 2030. Improvement of traffic safety concerning public health under the "Outline of the National Comprehensive Three-dimensional Transportation Network Planning" in China will propel the realization of worldwide traffic environmental advancement.


Asunto(s)
Accidentes de Tránsito , Salud Pública , Humanos , Accidentes de Tránsito/prevención & control , China , Estado de Salud , Conocimiento
18.
Water Res ; 244: 120447, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37574625

RESUMEN

Natural solar-powered steam generation provides a promising strategy to deal with deteriorating water resources. However, the practical applications of this strategy are limited by the tedious manufacturing of structures at micro-nano levels to concentrate heat and transport water to heat-localized regions. Herein, this work reports the fabrication of hierarchically porous aerohydrogel with enhanced light absorption and thermal localization at the air-solid interface. This aerohydrogel steam generator is fabricated by a simple yet controllable micropore generation approach to assemble air and hydrogel into hierarchically porous gas-solid hybrids. The tunable micropore size in a wide range from 99±49µm to 316±58µm not only enables contrasting sunlight absorptance (0.2 - 2.5µm) by reducing the reflection of solar light but also harnesses water transportation to the heating region via a capillary force-driven liquid flow. Therefore, a solar-vapor conversion efficiency of 91.3% under one sun irradiation was achieved using this aerohydrogel evaporator, reaching a ready evaporation rate of 2.76kg m-2 h-1 and 3.71kg m-2 h-1 under one and two sun irradiations, respectively. Our work provides a versatile and scalable approach to engineering porous hydrogels for highly efficient steam generation and opens an avenue for other potential practical applications based on this aerohydrogel.


Asunto(s)
Vapor , Agua , Porosidad , Transporte Biológico , Comercio
19.
J Integr Plant Biol ; 65(11): 2469-2489, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37635359

RESUMEN

The resultant DNA from loss-of-function mutation can be recruited in biological evolution and development. Here, we present such a rare and potential case of "to gain by loss" as a neomorphic mutation during soybean domestication for increasing seed weight. Using a population derived from a chromosome segment substitution line of Glycine max (SN14) and Glycine soja (ZYD06), a quantitative trait locus (QTL) of 100-seed weight (qHSW) was mapped on chromosome 11, corresponding to a truncated ß-1, 3-glucosidase (ßGlu) gene. The novel gene hsw results from a 14-bp deletion, causing a frameshift mutation and a premature stop codon in the ßGlu. In contrast to HSW, the hsw completely lost ßGlu activity and function but acquired a novel function to promote cell expansion, thus increasing seed weight. Overexpressing hsw instead of HSW produced large soybean seeds, and surprisingly, truncating hsw via gene editing further increased the seed size. We further found that the core 21-aa peptide of hsw and its variants acted as a promoter of seed size. Transcriptomic variation in these transgenic soybean lines substantiated the integration hsw into cell and seed size control. Moreover, the hsw allele underwent selection and expansion during soybean domestication and improvement. Our work cloned a likely domesticated QTL controlling soybean seed weight, revealed a novel genetic variation and mechanism in soybean domestication, and provided new insight into crop domestication and breeding, and plant evolution.


Asunto(s)
Domesticación , Glycine max , Glycine max/metabolismo , Alelos , Fitomejoramiento , Semillas/metabolismo , Hidrolasas/genética , Hidrolasas/metabolismo
20.
Neurochem Res ; 48(10): 3190-3201, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37395917

RESUMEN

This study aims to investigate the effect of insulin-like growth factor 1 (IGF-1) combined with osteopontin (OPN) on the protein expression levels and growth of neuronal axons and its possible mechanism. In this study, IGF-1 combined with OPN promoted neuronal axon growth through the IGF-1R/Akt/mTOR signaling pathway in lipid rafts, and the effect was better than that of either agent alone. This effect was suppressed when given the mTOR inhibitor rapamycin or the lipid raft cholesterol extraction agent methyl-ß-cyclodextrin (M-ß-CD). Rapamycin could inhibit the expression of phosphorylated ribosomal S6 protein (p-S6) and phosphorylated protein kinase B (p-Akt) and limit axon growth. In addition to the above effects, M-ß-CD significantly downregulated the expression of phosphorylated insulin-like growth factor 1 receptor (p-IR). To further investigate the changes in lipid rafts when stimulated by different recombinant proteins, membrane lipid rafts were isolated to observe the changes by western blot. The expression levels of insulin-like growth factor 1 receptor (IR) and P-IR in the IGF-1 combined with OPN group were the highest. When M-ß-CD was administered to the lipid rafts of neurons, the enrichment of IR by IGF-1 combined with OPN was weakened, and the p-IR was decreased. Our study found that IGF-1 combined with OPN could promote axon growth by activating the IGF-1R/Akt/mTOR signaling pathway in neuronal lipid rafts.


Asunto(s)
Factor I del Crecimiento Similar a la Insulina , Proteínas Proto-Oncogénicas c-akt , Axones/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Microdominios de Membrana/metabolismo , Neuronas/metabolismo , Osteopontina , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Ratas
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