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1.
Front Pharmacol ; 15: 1401826, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055489

RESUMEN

Pomegranate seeds (PS) are the dried seeds derived from pomegranate fruit, accounting for approximately 20% of the fruit's total weight, and are a by-product of pomegranate juice extraction. These seeds hold significance in traditional medicine among Uyghurs and Tibetan cultures, featuring diverse clinical applications within traditional Chinese medicine. These applications include management of gastric coldness and acidity, abdominal distension, liver and gallbladder fever, and pediatric enteritis. PS demonstrates properties such as stomach tonicity, qi regulation, analgesia, and anti-inflammatory effects. Extensive research underscores the richness of PS in various phytochemical compounds and metabolites, notably unsaturated fatty acids (particularly linolenic acid and linoleic acid), phenolic compounds tocopherols, proteins, and volatile oils. Notably, among these bioactive compounds, punicic acid (PA), found within PS, demonstrates potential in the prevention and treatment of cancers, diabetes, obesity, and other ailments. Despite extensive literature on pomegranate as a botanical entity, a comprehensive review focusing specifically on the chemical composition and pharmacological effects of PS remains elusive. Therefore, this review aimed to consolidate knowledge regarding the medicinal properties of PS, summarizing its chemical composition, traditional uses, and pharmacological effects in treating various diseases, thereby laying a foundation for the advancement and application of PS in the field of pharmacology.

2.
Sci Adv ; 10(31): eadn4682, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39083600

RESUMEN

G0-G1 phase alternative end joining (A-EJ) is a recently defined mutagenic pathway characterized by resected deletion and translocation joints that are predominantly direct and are distinguished from A-EJ in cycling cells that rely much more on microhomology-mediated end joining (MMEJ). Using chemical and genetic approaches, we systematically evaluate potential A-EJ factors and DNA damage response (DDR) genes to support this mechanism by mapping the repair fates of RAG1/2-initiated double-strand breaks in the context of Igκ locus V-J recombination and chromosome translocation. Our findings highlight a polymerase theta-independent Parp1-XRCC1/LigIII axis as central A-EJ components, supported by 53BP1 in the context of an Ataxia-telangiectasia mutated (ATM)-activated DDR. Mechanistically, we demonstrate varied changes in short-range resection, MMEJ, and translocation, imposed by compromising specific DDR activities, which include polymerase alpha, Ataxia-telangiectasia and Rad3-related (ATR), DNA2, and Mre11. This study advances our understanding of DNA damage repair within the 53BP1 regulatory domain and the RAG1/2 postcleavage complex.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada , Reparación del ADN por Unión de Extremidades , Proteína 1 de Unión al Supresor Tumoral P53 , Recombinación V(D)J , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Animales , Humanos , Roturas del ADN de Doble Cadena , Ratones , Daño del ADN , Translocación Genética
3.
Nat Commun ; 15(1): 6331, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068148

RESUMEN

Activation-induced cytidine deaminase (AID) is a B cell-specific mutator required for antibody diversification. However, it is also implicated in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain blood cancers is critical in assessing disease severity and treatment options. We have developed a digital PCR (dPCR) assay that allows us to quantify mutations resulting from AID modification or DNA double-strand break (DSB) formation and repair at sites known to be prone to DSBs. Implementation of this assay shows that increased AID levels in immature B cells increase genome instability at loci linked to chromosomal translocation formation. This includes the CRLF2 locus that is often involved in translocations associated with a subtype of acute lymphoblastic leukemia (ALL) that disproportionately affects Hispanics, particularly those with Latin American ancestry. Using dPCR, we characterize the CRLF2 locus in B cell-derived genomic DNA from both Hispanic ALL patients and healthy Hispanic donors and found increased mutations in both, suggesting that vulnerability to DNA damage at CRLF2 may be driving this health disparity. Our ability to detect and quantify these mutations will potentiate future risk identification, early detection of cancers, and reduction of associated cancer health disparities.


Asunto(s)
Citidina Desaminasa , Hispánicos o Latinos , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Citocinas , Humanos , Citidina Desaminasa/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Hispánicos o Latinos/genética , Receptores de Citocinas/genética , Roturas del ADN de Doble Cadena , Linfocitos B/metabolismo , Linfocitos B/inmunología , Disparidades en el Estado de Salud , Translocación Genética , Sitios Genéticos , América Latina , Femenino
4.
Genes Dev ; 38(11-12): 569-582, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38997156

RESUMEN

Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of "cell cycling" and "oxidative stress response" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.


Asunto(s)
Homeostasis , Regeneración , Telomerasa , Telomerasa/metabolismo , Telomerasa/genética , Animales , Homeostasis/genética , Homeostasis/efectos de la radiación , Ratones , Regeneración/efectos de la radiación , Regeneración/genética , Humanos , Glándulas Salivales/efectos de la radiación , Glándulas Salivales/metabolismo , Glándulas Salivales/citología , Proliferación Celular/efectos de la radiación , Proliferación Celular/genética , Supervivencia Celular/efectos de la radiación , Supervivencia Celular/genética , Glándula Submandibular/efectos de la radiación , Glándula Submandibular/metabolismo , Células Madre/efectos de la radiación , Células Madre/metabolismo , Células Madre/citología , Radioterapia/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Células Cultivadas
5.
BMC Plant Biol ; 24(1): 530, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862888

RESUMEN

BACKGROUND: Seed aging, a natural and inevitable process occurring during storage. Oats, an annual herb belonging to the Gramineae family and pooideae. In addition to being a healthy food, oats serve as ecological pastures, combating soil salinization and desertification. They also play a role in promoting grassland agriculture and supplementing winter livestock feed. However, the high lipid and fat derivatives contents of oat seeds make them susceptible to deterioration, as fat derivatives are prone to rancidity, affecting oat seed production, storage, development, and germplasm resource utilization. Comparative studies on the effects of aging on physiology and cytological structure in covered and naked oat seeds are limited. Thus, our study aimed to determine the mechanism underlying seed deterioration in artificially aged 'LongYan No. 3' (A. sativa) and 'BaiYan No. 2' (A. nuda) seeds, providing a basis for the physiological evaluation of oat seed aging and serving as a reference for scientifically safe storage and efficient utilization of oats. RESULTS: In both oat varieties, superoxide dismutase and catalase activities in seeds showed increasing and decreasing trends, respectively. Variance analysis revealed significant differences and interaction in all measured indicators of oat seeds between the two varieties at different aging times. 'LongYan No. 3' seeds, aged for 24-96 h, exhibited a germination rate of < 30%, Conductivity, malondialdehyde, soluble sugar, and soluble protein levels increased more significantly than the 'BaiYan No. 2'. With prolonged aging leading to cell membrane degradation, reactive oxygen species accumulation, disrupted antioxidant enzyme system, evident embryo cell swelling, and disordered cell arrangement, blocking the nutrient supply route. Simultaneously, severely concentrated chromatin in the nucleus, damaged mitochondrial structure, and impaired energy metabolism were noted, resulting in the loss of 'LongYan No. 3' seed vitality and value. Conversely, 'BaiYan No. 2' seeds showed a germination rate of 73.33% after 96 h of aging, consistently higher antioxidant enzyme activity during aging, normal embryonic cell shape, and existence of the endoplasmic reticulum. CONCLUSIONS: ROS accumulation and antioxidant enzyme system damage in aged oat seeds, nuclear chromatin condensation, mitochondrial structure damage, nucleic acid metabolism and respiration weakened, oat seed vigor decreased. 'LongYan No. 3' seeds were more severely damaged under artificial aging than 'BaiYan No. 2' seeds, highlighting their heightened susceptibility to aging effects.


Asunto(s)
Avena , Semillas , Avena/fisiología , Avena/crecimiento & desarrollo , Semillas/fisiología , Semillas/crecimiento & desarrollo , Calor , Catalasa/metabolismo , Superóxido Dismutasa/metabolismo , Germinación/fisiología , Antioxidantes/metabolismo
7.
Nucleic Acids Res ; 52(9): 5048-5066, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38412274

RESUMEN

Two DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ involved in humans and A-EJ in mice predominantly. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation. While DNA-PKcs inhibition promotes chromosome translocations harboring microhomologies in mice, its synonymous effect in humans is not known. We find partial DNA-PKcs inhibition in human cells leads to increased translocations and the continued involvement of a dampened NHEJ. In contrast, complete DNA-PKcs inhibition substantially increased microhomology-mediated end joining (MMEJ), thus bridging the two different translocation mechanisms between human and mice. Similar to a previous study on Ku70 deletion, DNA-PKcs deletion in G1/G0-phase mouse progenitor B cell lines, significantly impairs V(D)J recombination and generated higher rates of translocations as a consequence of dysregulated coding and signal end joining. Genetic DNA-PKcs inhibition suppresses NHEJ entirely, with repair phenotypically resembling Ku70-deficient A-EJ. In contrast, we find DNA-PKcs necessary in generating the near-exclusive MMEJ associated with Lig4 deficiency. Our study underscores DNA-PKcs in suppressing illegitimate chromosome rearrangement while also contributing to MMEJ in both species.


Asunto(s)
Aberraciones Cromosómicas , Reparación del ADN por Unión de Extremidades , Proteína Quinasa Activada por ADN , Animales , Humanos , Ratones , Línea Celular , ADN Ligasa (ATP)/genética , ADN Ligasa (ATP)/metabolismo , Proteína Quinasa Activada por ADN/genética , Proteína Quinasa Activada por ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Translocación Genética , Recombinación V(D)J
8.
Biomed Pharmacother ; 170: 116059, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38154273

RESUMEN

The liver cancer has microenvironmental features such as low pH, M2 tumor-associated macrophage enrichment, low oxygen, rich blood supply and susceptibility to hematotropic metastasis, high chemokine expression, enzyme overexpression, high redox level, and strong immunosuppression, which not only promotes the progression of the disease, but also seriously affects the clinical effectiveness of traditional therapeutic approaches. However, nanotechnology, due to its unique advantages of size effect and functionalized modifiability, can be utilized to develop various responsive nano-drug delivery system (NDDS) by using these characteristic signals of the liver cancer microenvironment as a source of stimulation, which in turn can realize the intelligent release of the drug under the specific microenvironment, and significantly increase the concentration of the drug at the target site. Therefore, researchers have designed a series of stimuli-responsive NDDS based on the characteristics of the liver cancer microenvironment, such as hypoxia, weak acidity, and abnormal expression of proteases, and they have been widely investigated for improving anti-tumor therapeutic efficacy and reducing the related side effects. This paper provides a review of the current application and progress of NDDS developed based on the response and regulation of the microenvironment in the treatment of liver cancer, compares the effects of the microenvironment and the NDDS, and provides a reference for building more advanced NDDS.


Asunto(s)
Neoplasias Hepáticas , Nanopartículas , Neoplasias , Humanos , Sistemas de Liberación de Medicamentos , Sistema de Administración de Fármacos con Nanopartículas , Microambiente Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Micelas
9.
Res Sq ; 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37790327

RESUMEN

Activation-induced cytidine deaminase (AID) is a B cell-specific base editor required during class switch recombination and somatic hypermutation for B cell maturation and antibody diversification. However, it has also been implicated as a factor in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain types of blood cancers is critical in assessing disease severity and treatment options. Here, we have developed a digital PCR (dPCR) assay that allows us to track the mutational landscape resulting from AID modification or DNA double-strand break (DSB) formation and repair at sites known to be prone to DSBs. Implementation of this new assay showed that increased AID levels in immature B cells increases genome instability at loci linked to translocation formation. This included the CRLF2 locus that is often involved in chromosomal translocations associated with a subtype of acute lymphoblastic leukemia (ALL) that disproportionately affects Latin Americans (LAs). To support this LA-specific identification of AID mutation signatures, we characterized DNA from immature B cells isolated from the bone marrow of ALL patients. Our ability to detect and quantify these mutation signatures will potentiate future risk identification, early detection of cancers, and reduction of associated cancer health disparities.

10.
Nat Struct Mol Biol ; 30(11): 1707-1718, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37828409

RESUMEN

Using Sanger sequencing and high-throughput genome sequencing of DNA cleavage reactions, we find that the Streptococcus pyogenes SpCas9 complex responds to internal mechanical strain by robustly generating a distribution of overhanging, rather than blunt, DNA ends. Internal mechanical strain is generated by shifting (increasing or decreasing) the spacing between the RNA-DNA hybrid and the downstream canonical PAM. Up to 2-base 3' overhangs can be robustly generated via a 2-base increase in the distance between hybrid and PAM. We also use single-molecule experiments to reconstruct the full course of the CRISPR-SpCas9 reaction in real-time, structurally and kinetically monitoring and quantifying R-loop formation, the first and second DNA-incision events, and dissociation of the post-catalytic complex. Complex dissociation and release of broken DNA ends is a rate-limiting step of the reaction, and shifted SpCas9 is sufficiently destabilized so as to rapidly dissociate after formation of broken DNA ends.


Asunto(s)
Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Proteína 9 Asociada a CRISPR/metabolismo , ADN/genética , Genoma , Streptococcus pyogenes/metabolismo , Edición Génica
11.
Water Res ; 244: 120430, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37678037

RESUMEN

Anionic surfactants represented by linear alkylbenzene sulfonate (LAS) exhibit vertical heterogeneity of concentrations in aquatic environments owing to their amphiphilic structure. Field investigations showed that the concentration of anionic surfactants (mainly LAS) in the water surface microlayer (SML) of Lake Taihu reached 580 µg/L, higher than that in the lower layer. Floating Microcystis blooms overlap in space with the high concentration of anionic surfactants in SML. However, few studies have focused on the effects of anionic surfactants (e.g., LAS) on the interspecies competition between toxic and nontoxic Microcystis. In this study, coculture and monoculture experiments were conducted with both toxic and nontoxic Microcystis species to explore how the environmental concentration of LAS regulates the dominance of toxic Microcystis and toxicity from the perspective of photosynthesis, species dominance, and MC production. The results showed that LAS concentrations above 0.267 or 0.431 mg/L (depending on light conditions) selectively promoted the photosynthetic competitive advantage of toxic Microcystis, leading to its higher population proportion in the community. Additionally, LAS concentrations above 0.5 mg/L induced the synthesis and release of microcystins (MCs). The results of chlorophyll fluorescence analysis, electron microscopy and transcriptome sequencing suggested that compared with nontoxic Microcystis, toxic Microcystis can better resist LAS stress by dissipating excess light, maintaining an intact membrane structure and maintaining cellular homeostasis. Transcriptome sequencing revealed that the photosynthetic damage of nontoxic Microcystis might be attributed to the impacts of LAS on the absorption and assimilation of nitrogen, which finally resulted in the degradation of phycobilisomes. This study can provide novel insight for establishing standards and safety management of wastewater discharge.


Asunto(s)
Ácidos Alcanesulfónicos , Microcystis , Lagos , Fotosíntesis
12.
PLoS One ; 18(8): e0290714, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37624822

RESUMEN

The utilization of biogas slurry is critical for the sustainable development of animal husbandry. Biomass carbon adsorption is a feasible method for the recycling of nutrients from biogas slurry. However, research on the co-adsorption of ammonia nitrogen and phosphate is scarce. Herein, soybean straw was utilized as the raw material to prepare Ca2+-modified biochar (CaSSB), which was investigated for its ammonia nitrogen and phosphate adsorption mechanisms. Compared with natural biochar (SSB), CaSSB possesses a high H/C ratio, larger surface area, high porosity and various functional groups. Ca2+-modified soybean straw biochar exhibited excellent adsorption performance for NH4+-N (103.18 mg/g) and PO43--P (9.75 mg/g) at pH = 6, using an adsorbent dosage of 2 g/L. The experimental adsorption data of ammonia nitrogen by CaSSB corresponded to pseudo-second-order kinetics and the Langmuir isotherm model, suggesting that the adsorption process was homogeneous and that electrostatic attraction might be the primary adsorption mechanism. Meanwhile, the adsorption of phosphate conformed to pseudo-second-order kinetics and the Langmuir-Freundlich model, whose mechanism might be attributed to ligand exchange and chemical precipitation. These results reveal the potential of CaSSBs as a cost-effective, efficient adsorbent for the recovery of ammonium and phosphate from biogas slurry.


Asunto(s)
Amoníaco , Glycine max , Animales , Fosfatos , Biocombustibles , Calcio , Adsorción , Nitrógeno
13.
Cancer Chemother Pharmacol ; 92(5): 341-355, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37507485

RESUMEN

BACKGROUND: The anti-HER2 antibody trastuzumab is a standard treatment for gastric carcinoma with HER2 overexpression, but not all patients benefit from treatment with HER2-targeted therapies due to intrinsic and acquired resistance. Thus, more precise predictors for selecting patients to receive trastuzumab therapy are urgently needed. METHODS: We applied mass spectrometry-based proteomic analysis to 38 HER2-positive gastric tumor biopsies from 19 patients pretreated with trastuzumab (responders n = 10; nonresponders, n = 9) to identify factors that may influence innate sensitivity or resistance to trastuzumab therapy and validated the results in tumor cells and patient samples. RESULTS: Statistical analyses revealed significantly lower phosphorylated ribosomal S6 (p-RPS6) levels in responders than nonresponders, and this downregulation was associated with a durable response and better overall survival after anti-HER2 therapy. High p-RPS6 levels could trigger AKT/mTOR/RPS6 signaling and inhibit trastuzumab antitumor efficacy in nonresponders. We demonstrated that RPS6 phosphorylation inhibitors in combination with trastuzumab effectively suppressed HER2-positive GC cell survival through the inhibition of the AKT/mTOR/RPS6 axis. CONCLUSIONS: Our findings provide for the first time a detailed proteomics profile of current protein alterations in patients before anti-HER2 therapy and present a novel and optimal predictor for the response to trastuzumab treatment. HER2-positive GC patients with low expression of p-RPS6 are more likely to benefit from trastuzumab therapy than those with high expression. However, those with high expression of p-RPS6 may benefit from trastuzumab in combination with RPS6 phosphorylation inhibitors.


Asunto(s)
Carcinoma , Neoplasias Gástricas , Humanos , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Neoplasias Gástricas/patología , Proteínas Proto-Oncogénicas c-akt , Proteómica/métodos , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/metabolismo , Receptor ErbB-2/metabolismo , Resistencia a Antineoplásicos
14.
Technol Cancer Res Treat ; 22: 15330338231185285, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37394872

RESUMEN

OBJECTIVES: Primary tumor tissue is often analyzed to search for predictive biomarkers and DNA-guided personalized therapies, but there is an incomplete understanding of the discrepancies in the genomic profiles between primary tumors and metastases, such as liver and lung metastases. METHODS: We performed in-depth targeted next-generation sequencing of 520 key cancer-associated genes for 47 matched primary and metastatic tumor samples which were retrospectively collected. RESULTS: A total of 699 mutations were detected in the 47 samples. The coincidence rate of primary tumors and metastases was 51.8% (n = 362), and compared to patients with liver metastases, patients with lung metastases had a significantly greater coincidence rate (P = .021). The number of specific mutations for the primary tumors and liver and lung metastases was 186 (26.6%), 122 (17.5%), and 29 (4.1%), respectively. Analysis of a patient with all three occurrences, including a primary tumor, liver metastasis, and lung metastasis, indicated a possible polyclonal seeding mechanism for liver metastases. Remarkably, multiple samples from patients with primary and metastatic tumors supported a mechanism of synchronous parallel dissemination from primary tumors to metastatic tumors that were not mediated through pre-metastatic tumors. We also found that the PI3K-Akt signaling pathway significantly altered lung metastases compared to matched primary tumors (P = .001). In addition, patients with mutations in CTCF, PIK3CA, or TP53 and LRP1B, AURKA, FGFR1, ATRX, DNMT3B, or GNAS had larger primary tumor sizes and metastases, especially patients with both LRP1B and AURKA mutations. Interestingly, CRC patients with TP53-disruptive mutations were more likely to have liver metastases (P = .016). CONCLUSION: In this study, we demonstrate significant differences in the genomic landscapes of colorectal cancer patients based on the site of metastasis. Notably, we observe a larger genomic variation between primary tumors and liver metastasis compared to primary tumors and lung metastasis. These findings can be used for tailoring treatments based on the specific metastatic site.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Fosfatidilinositol 3-Quinasas/genética , Aurora Quinasa A/genética , Mutación , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Metástasis de la Neoplasia/patología
15.
Sci Total Environ ; 892: 164540, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37270020

RESUMEN

Phosphorus is a key nutrient that causes eutrophication in lakes. Our investigation of 11 eutrophic lakes found that the concentrations of soluble reactive phosphorus (SRP) in the water column and EPC0 in sediments decreased with aggravated eutrophication. There was a significant negative correlation between the SRP concentrations and eutrophication parameters such as chlorophyll a (Chl-a), total phosphorus (TP) and algal biomass (P < 0.001). In addition, SRP concentrations were significantly affected by EPC0 (P < 0.001), while EPC0 was significantly affected by the content of cyanobacterial organic matter (COM) in sediments (P < 0.001). Based on these findings, we hypothesized that COM can alter the phosphorus release characteristics of sediments, including the phosphorus adsorption parameters of sediment (PAPS) and the phosphorus release rate of sediment (PRRS), thereby stabilizing SRP concentrations at lower levels and rapidly replenishing them when depleted by phytoplankton, which in turn benefits cyanobacteria due to their low SRP adaptation strategies. Simulation experiments were conducted to confirm this hypothesis by adding higher plant OM and COM to sediments. The results showed that all types of OM could significantly increase the maximum phosphorus adsorption capacity (Qmax), but only COM could reduce sediment EPC0 and promote PRRS (P < 0.001). Changes in these parameters (i.e., Qmax, EPC0, and PRRS) resulted in a larger SRP adsorption quantity and faster SRP release rate at low SRP concentrations. This promotes the competitive edge of cyanobacteria due to they have a higher affinity for phosphorus than other algae. As an important component of cyanobacteria, EPS can change the phosphorus release characteristics (i.e., PAPS and PRRS) by reducing sediment particle size and increasing sediment surface functional groups. This study revealed the positive feedback effect of COM accumulation in sediments on lake eutrophication from the perspective of phosphorus release characteristics of sediments, which provides a basic reference for the risk assessment of lake eutrophication.


Asunto(s)
Cianobacterias , Síndrome Respiratorio y de la Reproducción Porcina , Contaminantes Químicos del Agua , Porcinos , Animales , Fósforo/análisis , Lagos/microbiología , Clorofila A , Retroalimentación , Sedimentos Geológicos/microbiología , Contaminantes Químicos del Agua/análisis , Eutrofización , China
16.
Int Immunopharmacol ; 121: 110516, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37369159

RESUMEN

In this research, we sought to examine the effectiveness of S-allylmercapto-N-acetylcysteine (ASSNAC) on LPS-provoked acute respiratory distress syndrome (ARDS) and its potential mechanism based on network pharmacology. To incorporate the effective targets of ASSNAC against ARDS, we firstly searched DisGeNET, TTD, GeneCards and OMIM databases. Then we used String database and Cytoscape program to create the protein-protein interaction network. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis both identified the potential pathways connected to genes. Cytoscape software was used to build the network of drug-targets-pathways and the SwissDock platform was applied to dock the molecule of ASSNAC with the key disease targets. Correspondingly, an ARDS model was established by instillation of LPS in mice to confirm the underlying action mechanism of ASSNAC on ARDS as indicated by the network pharmacology analysis. Results exhibited that 27 overlapping targets, including TLR4, ICAM1, HIF1A, MAPK1, NFKB1, and others, were filtered out. The in vivo experiments showed that ASSNAC alleviated LPS-induced lung injury by downregulating levels of pro-inflammatory mediators and lung dry-wet ratio. Also, ASSNAC attenuated oxidative stress evoked by LPS via diminishing MDA production and SOD consumption as well as upregulating HO-1 level through Nrf2 activation. Results from western blot, quantitative real-time PCR and immunohistochemistry suggested that ASSNAC developed its therapeutic effects by regulating TLR4/MyD88/NF-κB signaling pathway. In conclusion, our research presented the efficacy of ASSNAC against ARDS. Furthermore, the mechanism of ASSNAC on ARDS was clarified by combining network pharmacology prediction with experimental confirmation.


Asunto(s)
Medicamentos Herbarios Chinos , Síndrome de Dificultad Respiratoria , Animales , Ratones , Lipopolisacáridos , Farmacología en Red , Receptor Toll-Like 4 , Simulación del Acoplamiento Molecular
17.
J Gene Med ; 25(9): e3529, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37194408

RESUMEN

BACKGROUND: Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS: A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS: The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS: We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Nódulo Pulmonar Solitario , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Nódulo Pulmonar Solitario/diagnóstico , Nódulo Pulmonar Solitario/patología , Células Neoplásicas Circulantes/patología , Biomarcadores de Tumor
18.
BMC Plant Biol ; 23(1): 208, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37081377

RESUMEN

BACKGROUND: Artemisia is important medicinal plants in China and are widely used in medicine, agriculture, and food. Pharmacologically active components of the plants remain to be investigated. METHODS: This study sought to identify and compare the chemical constituents of three species of Artemisia in Tibet using a widely-targeted metabolomics approach and their antibacterial and antioxidant capacities were determined. RESULT: A total of 1109 metabolites within 10 categories were detected from the three species of Artemisia, including lipids, amino acids, nucleotides, flavonoids, terpenes, coumarins, organic acids, and phenolic acids. 732 different metabolites have been identified between Artemisia sieversiana and Artemisia annua, 751 different metabolites were identified between Artemisia wellbyi and A. sieversiana, and 768 differential metabolites were differentially detected from A. wellbyi and A. annua. Differentially identified compounds included flavonoids, phenolic acids, artemisinins and coumarin. A. annua contained the highest relative content of artemisinin among three Artemisia. The antimicrobial experiments showed that the three Artemisia species had strong antibiotic activities against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Proteus mirabilis and Pseudomonas aeruginosa. The biochemical analysis showed that the three species of Artemisia have strong antioxidant capacity. CONCLUSIONS: This is the first reported attempt to comparatively determine the types of the metabolites of the three widely distributed Artemisia species in Tibet. The information should help medicinal research and facilitate comprehensive development and utilization of Artemisia species in Tibet.


Asunto(s)
Artemisia annua , Artemisia , Antioxidantes/metabolismo , Tibet , Artemisia annua/química , Antibacterianos/farmacología , Flavonoides/metabolismo
19.
J Ethnopharmacol ; 312: 116440, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37023838

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Uyghur medicine, diaphragma juglandis fructus (DJF) has been conventionally used in treating insomnia and nourishing the kidneys. According to traditional Chinese medicine, DJF can boosts kidney and astringent essence, strengthen the spleen and kidney, exert diuretic effect, clear heat, stop eructation, and treat vomiting. AIM OF THE REVIEW: Research on DJF has increased gradually in recent years, but reviews of its traditional uses, chemical composition, and pharmacological activities are scarce. The purpose of this review is to analyze the traditional uses, chemical composition, and pharmacological activities of DJF and provide an overview of the findings for further research and development of DJF resources. MATERIALS AND METHODS: Data on DJF were obtained from different databases, including Scifinder, PubMed, Web of Science, Science Direct, Springer, Wiley, ACS, CNKI, Baidu Scholar, and Google Scholar; books; and Ph.D. and MSc theses. RESULTS: According to traditional Chinese medicine, DJF has astringent properties, inhibits bleeding and banding, strengthens the spleen and kidneys, acts as a sleeping aid by reducing anxiety, and relieves dysentery due to heat exposure. The components of DJF include flavonoids, phenolic acids, quinones, steroids, lignans, and volatile oils, which exhibit good antioxidant, antitumor, antidiabetic, antibacterial, anti-inflammatory, and sedative-hypnotic properties, and present therapeutic potential for kidney diseases. CONCLUSIONS: Based on its traditional use, chemical composition, and pharmacological activities, DJF is a promising source of natural medicine in the development of functional foods, drugs, and cosmetics.


Asunto(s)
Medicamentos Herbarios Chinos , Aceites Volátiles , Etnofarmacología , Astringentes , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Medicina Tradicional , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/química
20.
Se Pu ; 41(5): 409-416, 2023 May 08.
Artículo en Chino | MEDLINE | ID: mdl-37087606

RESUMEN

In this work, carbon nanotubes (CNTs) on silica rod (SiO2) composite materials were prepared to extract six perfluorinated compounds (PFCs) in real environmental water samples by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The as-synthesized sorbents, hereafter referred to as CNT@SiO2, were employed for dispersive solid-phase extraction (d-SPE). Perfluoroheptanoic acid (PFHpA), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonate (PFOS), and perfluorodecanoic acid (PFDA) were selected as target analytes. The main extraction parameters were systematically optimized using the single-factor optimization method. The optimum adsorption parameters were as follows: adsorption time of 30 min, sorbent amount of 10 mg, pH 6 and NaCl concentration of 1.7 mol/L for sample solution, and 4 mL acetone as desorption solvent, desorption for 4 min. LC-triple quadrupole MS was conducted to quantify the selected PFCs in water samples. The mobile phase was 5 mmol/L ammonium acetate and methanol, the flow rate was set to 0.4 mL/min, the column temperature was set to 40 ℃, and the injection volume was 5.0 µL. The chromatographic separation system was equipped with a Kinetex C18 column (100 mm×2.1 mm, 1.7 µm). The mass spectrometer was operated with negative electrospray ionization in multi-reaction monitoring mode. CNT@SiO2 was prepared in five batches and used as the d-SPE sorbent, and the relative standard deviations (RSDs) of the PFC recoveries among these five batches ranged from 4.9% to 9.3%. The reusability of the CNT@SiO2 sorbent was assessed. After eight d-SPE cycles using the same sorbent, the RSDs of the PFC recoveries were 3.7%-8.2%. These results indicated that the sorbent had good stability and reusability for d-SPE. Excellent results were achieved under optimal extraction conditions. The method validation results indicated that the linear ranges were 0.4-1000 ng/L for PFNA, PFOS, and PFDA, 0.9-1000 ng/L for PFHpA, 0.7-1000 ng/L for PFHxS, and 0.6-1000 ng/L for PFOA. The correlation coefficients were 0.973-0.997. The limit of detection (LOD) and limit of quantification of the method were 0.10-0.26 ng/L and 0.33-0.87 ng/L, respectively. At 20 ng/L, the RSDs of the intra- and inter-day precisions were 2.73%-7.75% and 3.38%-8.21%, respectively. At 100 ng/L, the RSDs of the intra- and inter-day precisions were 2.95%-8.46% and 4.16%-9.14%, respectively. Finally, at 500 ng/L, the RSDs of the intra- and inter-day precisions were 2.51%-7.48% and 3.59%-9.63%, respectively. The developed method was applied to analyze six PFCs in tap water, barreled drinking water, and river water samples. PFOA and PFOS were determined in tap water at mass concentrations of 5.6 and 8.7 ng/L, respectively. No PFCs were found in barreled drinking water and river water. Satisfactory recoveries of 72.1%-109.6% at low, middle, and high spiking levels were also obtained. In conclusion, the d-SPE-LC-MS/MS method based on CNT@SiO2 composite sorbents is accurate and sensitive. The results of this study demonstrate that CNT@SiO2 is a good choice for the rapid and effective determination of PFCs from water samples. Further exploration of the use of CNT@SiO2 sorbents for the extraction and determination of trace organic pollutions in environmental samples is in progress.

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