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1.
ACS Nano ; 18(27): 17837-17851, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38938113

RESUMEN

Currently, specific cancer-responsive fluorogenic probes with activatable imaging and therapeutic functionalities are in great demand in the accurate diagnostics and efficient therapy of malignancies. Herein, an all-in-one strategy is presented to realize fluorescence (FL) imaging-guided and synergetic chemodynamic-photodynamic cancer therapy by using a multifunctional alkaline phosphatase (ALP)-response aggregation-induced emission (AIE) probe, TPE-APP. By responding to the abnormal expression levels of an ALP biomarker in cancer cells, the phosphate groups on the AIE probe are selectively hydrolyzed, accompanied by in situ formation of strong emissive AIE aggregates for discriminative cancer cell imaging over normal cells and highly active quinone methide species with robust chemodynamic-photodynamic activities. Consequently, the activated AIE probes can efficiently destroy cancer cell membranes and lead to the death of cancer cells within 30 min. A superior efficacy in cancer cell ablation is demonstrated in vitro and in vivo. The cancer-associated biomarker response-derived discriminative FL imaging and synergistic chemodynamic-photodynamic therapy are expected to provide a promising avenue for precise image-guided cancer therapy.


Asunto(s)
Fosfatasa Alcalina , Colorantes Fluorescentes , Fotoquimioterapia , Humanos , Fosfatasa Alcalina/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Colorantes Fluorescentes/síntesis química , Animales , Imagen Óptica , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Ratones , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Ratones Desnudos , Ensayos de Selección de Medicamentos Antitumorales
2.
Behav Processes ; 220: 105059, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38878914

RESUMEN

Understanding how animal collectives and societies form and function is a fundamental goal in animal biology. To date, research examining fish shoaling behavior has focused mostly on the general principles and ecological relevance of the phenomeon, while the ways in which physiological state (e.g., nutrition) affects collective behavior remain overlooked. Here, we investigated the shoaling behavior of common minnows (Phoxinus phoxinus) with three different nutritional states (control treatment: fasting for 24 h, fasting treatment: fasting for 7 days, and digestion treatment: 1 h after satiation feeding) across two ecological contexts (i.e., without and with food). No effects of either nutritional state or context were found on swimming speed, but the acceleration was greater in the digestion group than in the control group, with that in the fasting group being intermediate. Similar to change tendency in group length and group width of shoals, both interindividual distance and nearest neighbor distance were also greater in the fasting group than in the digestion group, suggesting that fasting and digestion may exert opposite driving forces on group cohesion. However, neither nutritional state nor context influenced the group area, group speed, group percent time moving, or group polarization. Both the foraging efficiency and the percentage of food items consumed by the fish shoals were greater in the fasting and control groups than in the digestion group. Our study suggested that one week of hunger and the energetically demanding stage of food digestion tend to have opposite influences on group shape, while the social foraging context does not influence the individual and group behavior of fish.

3.
Clin Immunol ; 265: 110293, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38936523

RESUMEN

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD , Humanos , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/deficiencia , Femenino , Adulto Joven , Mutación , Neutrófilos/inmunología , Células Th17/inmunología , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/inmunología , Monocitos/inmunología , Citocinas
4.
Theor Appl Genet ; 137(6): 128, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733405

RESUMEN

KEY MESSAGE: Discovery of Rht27, a dwarf gene in wheat, showed potential in enhancing grain yield by reducing plant height. Plant height plays a crucial role in crop architecture and grain yield, and semi-dwarf Reduced Height (Rht) alleles contribute to lodging resistance and were important in "Green Revolution." However, the use of these alleles is associated with some negative side effects in some environments, such as reduced coleoptile length, low nitrogen use efficiency, and reduced yield. Therefore, novel dwarf gene resources are needed to pave an alternative route to overcome these side effects. In this study, a super-dwarf mutant rht27 was obtained by the mutagenesis of G1812 (Triticum urartu, the progenitor of the A sub-genome of common wheat). Genetic analysis revealed that the dwarf phenotype was regulated by a single recessive genetic factor. The candidate region for Rht27 was narrowed to a 1.55 Mb region on chromosome 3, within which we found two potential candidate genes that showed polymorphisms between the mutant and non-mutagenized G1812. Furthermore, the natural variants and elite haplotypes of the two candidates were investigated in a natural population of common wheat. The results showed that the natural variants affect grain yield components, and the dwarf haplotypes show the potential in improving agronomic traits and grain yield. Although the mutation in Rht27 results in severe dwarf phenotype in T. urartu, the natural variants in common wheat showed desirable phenotype, which suggests that Rht27 has the potential to improve wheat yield by utilizing its weak allelic mutation or fine-tuning its expression level.


Asunto(s)
Genes de Plantas , Triticum , Alelos , Mapeo Cromosómico , Haplotipos , Fenotipo , Triticum/genética , Triticum/crecimiento & desarrollo
5.
Anal Chem ; 96(22): 9244-9253, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38773697

RESUMEN

Sensitive identification and effective inactivation of the virus are paramount for the early diagnosis and treatment of viral infections to prevent the risk of secondary transmission of viruses in the environment. Herein, we developed a novel two-step fluorescence immunoassay using antibody/streptavidin dual-labeled polystyrene nanobeads and biotin-labeled G-quadruplex/hemin DNAzymes with peroxidase-mimicking activity for sensitive quantitation and efficient inactivation of living Zika virus (ZIKV). The dual-labeled nanobeads can specifically bind ZIKV through E protein targeting and simultaneously accumulate DNAzymes, leading to the catalytic oxidation of Amplex Red indicators and generation of intensified aggregation-induced emission fluorescence signals, with a detection limit down to 66.3 PFU/mL and 100% accuracy. Furthermore, robust reactive oxygen species generated in situ by oxidized Amplex Red upon irradiation can completely kill the virus. This sensitive and efficient detection-inactivation integrated system will expand the viral diagnostic tools and reduce the risk of virus transmission in the environment.


Asunto(s)
ADN Catalítico , Virus Zika , ADN Catalítico/química , ADN Catalítico/metabolismo , Inmunoensayo/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Límite de Detección , G-Cuádruplex , Inactivación de Virus/efectos de la radiación , Humanos
6.
J Nat Prod ; 87(5): 1347-1357, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38701173

RESUMEN

A chemical investigation of a cold-seep-sediment-derived fungus, Pseudallescheria boydii CS-793, resulted in characterization of 10 novel bergamotene-derived sesquiterpenoids, pseuboyenes A-J (1-10). Their structures were elucidated by spectroscopic and X-ray crystallographic analyses as well as using the modified Mosher's method. Compound 1 represents the first example of a ß-bergamotene containing a 6-oxobicyclo[3.2.1]octane nucleus adducted with a methyl lactate unit, while 8-10 involve a skeletal rearrangement from bergamotene. Compounds 2-5 showed significant antifungal activities against Colletotrichum gloeosporioides Penz. and Fusarium oxysporum with MICs ranging from 0.5 to 8 µg/mL. Compound 4 exhibited an in vitro anti-F. proliferatum effect with an EC50 value of 1.0 µg/mL.


Asunto(s)
Antifúngicos , Pruebas de Sensibilidad Microbiana , Pseudallescheria , Sesquiterpenos , Antifúngicos/farmacología , Antifúngicos/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Estructura Molecular , Colletotrichum/efectos de los fármacos , Fusarium/efectos de los fármacos , Cristalografía por Rayos X
7.
Bioorg Chem ; 147: 107417, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701596

RESUMEN

Marine natural products play an important role in biopesticides. Seven new secondary metabolites with different structural classes, including two cycloheptapeptides, scortide A (1) and scortide B (2), two 19-nor-diterpenoids, talascortene H (3) and talascortene I (4), two diterpenoid acids, talascortene J (5) and talascortene K (6), and one triterpenoid, talascortene L (7) were isolated and identified from the sea-anemone-derived endozoic fungus Talaromyces scorteus AS-242. Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, tandem mass spectrometry, and electronic circular dichroism (ECD) calculations. The result of the antimicrobial assay demonstrated that compounds 1 - 6 have inhibitory activity against several human, aquatic, and plant pathogens with minimum inhibitory concentration (MIC) values ranging from 1 to 64 µg/mL. Specially, compounds 2 and 4 showed significant activities against the pathogenic fungus Curvularia spicifera with the MIC value of 1 µg/mL, providing an experimental basis of 2 and 4 with the potential as lead compounds to be developed into biopesticides.


Asunto(s)
Pruebas de Sensibilidad Microbiana , Talaromyces , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/aislamiento & purificación , Estructura Molecular , Relación Estructura-Actividad , Talaromyces/química , Talaromyces/metabolismo , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología
8.
Angew Chem Int Ed Engl ; 63(26): e202403963, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38635317

RESUMEN

(±)-Penindolenes A-D (1-4), the first representatives of indole terpenoids featuring a γ-lactam skeleton, were isolated from the mangrove-derived endophytic fungus Penicillium brocae MA-231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ-lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3-cleavage of the indole ring to generate two keto groups in 1. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase-like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids.


Asunto(s)
Sistema Enzimático del Citocromo P-450 , Indoles , Penicillium , Sistema Enzimático del Citocromo P-450/metabolismo , Indoles/química , Indoles/metabolismo , Penicillium/enzimología , Penicillium/metabolismo , Biocatálisis , Estereoisomerismo , Estructura Molecular
9.
Zhongguo Zhong Yao Za Zhi ; 49(3): 763-769, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621880

RESUMEN

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.


Asunto(s)
Compuestos Azo , Dieta Alta en Grasa , Enfermedad del Hígado Graso no Alcohólico , Ratones , Ratas , Animales , Dieta Alta en Grasa/efectos adversos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/farmacología , Caveolina 1/metabolismo , Caveolina 1/farmacología , Ratones Endogámicos C57BL , Hígado , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Triglicéridos/metabolismo , Peso Corporal , Adenosina Trifosfato/farmacología
10.
J Agric Food Chem ; 72(12): 6372-6388, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38471112

RESUMEN

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.


Asunto(s)
Oxalato de Calcio , Algas Comestibles , Cálculos Renales , Porphyra , Ratas , Animales , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Oxalato de Calcio/metabolismo , Oxalato de Calcio/farmacología , Antioxidantes/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Riñón/metabolismo , Cálculos Renales/metabolismo , Estrés Oxidativo , Oxalatos/metabolismo , Oxalatos/farmacología , Polisacáridos/metabolismo
11.
Cell Death Dis ; 15(3): 216, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485947

RESUMEN

Despite progressive improvements in the survival rate of pediatric B-cell lineage acute lymphoblastic leukemia (B-ALL), chemoresistance-induced disease progression and recurrence still occur with poor prognosis, thus highlighting the urgent need to eradicate drug resistance in B-ALL. The 6-mercaptopurine (6-MP) is the backbone of ALL combination chemotherapy, and resistance to it is crucially related to relapse. The present study couples chemoresistance in pediatric B-ALL with histidine metabolism deficiency. Evidence was provided that histidine supplementation significantly shifts the 6-MP dose-response in 6-MP-resistant B-ALL. It is revealed that increased tetrahydrofolate consumption via histidine catabolism partially explains the re-sensitization ability of histidine. More importantly, this work provides fresh insights into that desuccinylation mediated by SIRT5 is an indispensable and synergistic requirement for histidine combination therapy against 6-MP resistance, which is undisclosed previously and demonstrates a rational strategy to ameliorate chemoresistance and protect pediatric patients with B-ALL from disease progression or relapse.


Asunto(s)
Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sirtuinas , Humanos , Niño , Mercaptopurina/farmacología , Mercaptopurina/uso terapéutico , Histidina/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Linfoma de Burkitt/tratamiento farmacológico , Recurrencia , Progresión de la Enfermedad
12.
Beilstein J Org Chem ; 20: 470-478, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38440169

RESUMEN

Pseudallenes A and B (1 and 2), the new and rare examples of sulfur-containing ovalicin derivatives, along with three known analogues 3-5, were isolated and identified from the culture extract of Pseudallescheria boydii CS-793, a fungus obtained from the deep-sea cold seep sediments. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed and established the structures and absolute configurations of compounds 1-3, thus providing the first characterized crystal structure of an ovalicin-type sesquiterpenoid. In the antimicrobial assays, compounds 1-3 showed broad-spectrum inhibitory activities against several plant pathogens with MIC values ranging from 2 to 16 µg/mL.

13.
Sci Adv ; 10(13): eadk2152, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38552018

RESUMEN

The evolution of oxygen cycles on Earth's surface has been regulated by the balance between molecular oxygen production and consumption. The Neoproterozoic-Paleozoic transition likely marks the second rise in atmospheric and oceanic oxygen levels, widely attributed to enhanced burial of organic carbon. However, it remains disputed how marine organic carbon production and burial respond to global environmental changes and whether these feedbacks trigger global oxygenation during this interval. Here, we report a large lithium isotopic and elemental dataset from marine mudstones spanning the upper Neoproterozoic to middle Cambrian [~660 million years ago (Ma) to 500 Ma]. These data indicate a dramatic increase in continental clay formation after ~525 Ma, likely linked to secular changes in global climate and compositions of the continental crust. Using a global biogeochemical model, we suggest that intensified continental weathering and clay delivery to the oceans could have notably increased the burial efficiency of organic carbon and facilitated greater oxygen accumulation in the earliest Paleozoic oceans.

14.
Environ Sci Pollut Res Int ; 31(16): 23568-23578, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38421543

RESUMEN

Shallow urban lakes are naturally vulnerable to ecosystem degradation. Rapid urbanization in recent decades has led to a variety of aquatic problems such as eutrophication, algal blooms, and biodiversity loss, increasing the risk to lake-wide ecological sustainability. Instead of a simple binary assessment of ecological risk, holistic evaluation frameworks that consider multiple stressors and receptors can provide a more comprehensive assessment of overall ecological risk. In this study, we analyzed a combined dataset of government statistics, remote sensing images, and 1 year of field measurements to develop an index system for urban lake ecological risk assessment based on the pressure-state-response (PSR) framework. We used the developed ecological safety index (ESI) system to evaluate the ecological risk for three urban lakes in Jiangsu Province, China: Lake Yangcheng-LYC, Lake Changdang-LCD, and Lake Tashan-LTS. LYC and LTS were classified as "mostly safe" and "generally recognized as safe," respectively, while LCD was assessed as having "potential ecological risk." Our data suggest that socioeconomic pressure and aquatic health are the two main factors affecting the ecological risk in both LYC and LCD. The ecological risk of LTS could be improved more effectively if regional management plans are well implemented. Our study highlights the pressure of external wastewater loading, low forest-grassland coverage, and lake shoreline damage on the three selected urban lakes. The findings of this study can inform watershed management for lake ecosystem restoration and environmental sustainability.


Asunto(s)
Ecosistema , Monitoreo del Ambiente , Monitoreo del Ambiente/métodos , Lagos , Biodiversidad , China , Medición de Riesgo , Eutrofización
15.
Cancer Lett ; 588: 216763, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38403109

RESUMEN

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Mutación de Línea Germinal , Fosfatidilinositol 3-Quinasas/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Mutación , China
16.
Phytochemistry ; 220: 114000, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38278465

RESUMEN

Sumalarins D-G (1-4), four previously undescribed curvularin derivatives, along with two known related metabolites, curvularin (5) and dehydrocurvularin (6), were isolated and identified from the mangrove-derived fungus Penicillium sumatrense MA-325. Among them, sumalarin D (1) represents a unique example of curvularin derivative featuring a 5-methylfuran-2-yl-methyl group. Their structures were elucidated based on analysis of NMR and MS data as well as comparison of ECD spectra and quantum chemical calculations of NMR, and compound 1 was confirmed by X-ray crystallographic analysis. Compounds 1, 2, 5, and 6 are active against aquatic pathogenic bacteria Vibrio alginolyticus and V. harveyi with MIC values ranging from 4 to 64 µg/mL, while compound 6 is cytotoxic against tumor cell lines 5673, HCT 116, 786-O, and Hela with IC50 values of 3.5, 10.6, 10.9, and 14.9 µM, respectively.


Asunto(s)
Antineoplásicos , Penicillium , Zearalenona/análogos & derivados , Estructura Molecular , Penicillium/química , Antineoplásicos/química
17.
Clin Microbiol Infect ; 30(5): 660-665, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38295989

RESUMEN

OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.


Asunto(s)
Autoanticuerpos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Meningitis Criptocócica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Cryptococcus gattii/inmunología , Cryptococcus neoformans/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Meningitis Criptocócica/mortalidad , Meningitis Criptocócica/inmunología , Meningitis Criptocócica/diagnóstico , Pronóstico , Estudios Retrospectivos , Estudios Seroepidemiológicos
18.
J Antibiot (Tokyo) ; 77(1): 13-20, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37884757

RESUMEN

Three new compounds, including one steroid named penivariod A (1) and two polyketides penivarides A and B (2 and 3), as well as six known derivatives (4-9) were isolated from Penicillium variabile EN-394, a fungus afforded from the marine red alga Rhodomela confervoides. Their structures were elucidated by analysis of the HRESIMS, 1D and 2D NMR. The absolute stereochemistry was determined by X-ray crystallographic data, gauge-independent atomic orbital (GIAO) NMR shift calculation followed by DP4+ analysis combined with calculated electronic circular dichroism (ECD). Antimicrobial activities for the new compounds (1-3) were evaluated against human- and aquatic-pathogenic bacteria as well as plant pathogenic fungi. Compound 1 exhibited potent antimicrobial activity against most of the pathogenic strains, especially for Escherichia coli and Pseudomonas aeruginosa, with MIC values of 1.0 and 2.0 µg ml-1, respectively.


Asunto(s)
Antiinfecciosos , Penicillium , Policétidos , Rhodophyta , Humanos , Antiinfecciosos/farmacología , Hongos , Estructura Molecular , Penicillium/química , Policétidos/química
19.
Environ Res ; 245: 118007, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38154561

RESUMEN

Polychlorinated dibenzothiophenes (PCDTs) are a form of emerging pollutant that has attracted great attention due to their structural resemblance to dioxins, which cast detrimental influence on the ecosystem and human health. This review shows the current status of research on PCDTs, focusing on their environmental occurrence, physicochemical properties, environmental behavior, and toxicity. Studies have suggested that the steps leading to the formation of PCDTs resemble those generating polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs), indicating their probable origin from the same sources. Furthermore, they may undergo a dechlorination process as a result of their photodegradation in the environment and metabolic reaction occurring within organisms, which could result in the conversion of these substances into additional pollutants like dibenzothiophene. PCDTs exist widely in the environmental media and have high logKOW values (>4.0), indicating their tendency to bioaccumulate. Moreover, the prediction results of EPI (Estimation Program Interface) Suite demonstrated a strong accumulation capacity for tetra-CDTs in fish compared to other chlorinated PCDTs. The biotransformation half-life of PCDTs would prolong with an increasing number of substituted Cl atoms in fish. A limited number of studies have also suggested that PCDTs can cause damage to the liver and immune system in living organisms, and the toxicity of PCDTs depends on the number and position of substituted Cl atoms. Future studies should be conducted on processes causing PCDT toxicity as well as their behavior and fate in actual environments.


Asunto(s)
Benzofuranos , Dioxinas , Contaminantes Ambientales , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Tiofenos , Animales , Humanos , Dibenzodioxinas Policloradas/análisis , Dibenzofuranos , Benzofuranos/toxicidad , Benzofuranos/análisis , Ecosistema , Contaminantes Ambientales/análisis , Dibenzofuranos Policlorados , Peces/metabolismo , Monitoreo del Ambiente
20.
Nat Commun ; 14(1): 8238, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38086830

RESUMEN

The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture, but the involvement of epigenetic modifications remains unexplored. Here, we analyze the chromatin landscapes of two wheat cultivars (KN9204 and J411) that differ in NUE under varied nitrogen conditions. The expression of nitrogen metabolism genes is closely linked to variation in histone modification instead of differences in DNA sequence. Epigenetic modifications exhibit clear cultivar-specificity, which likely contributes to distinct agronomic traits. Additionally, low nitrogen (LN) induces H3K27ac and H3K27me3 to significantly enhance root growth in KN9204, while remarkably inducing NRT2 in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of H3K27me3 methyltransferase shows that changes in epigenetic modifications could alter the strategy preference for root development or nitrogen uptake in response to LN. Here, we show the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.


Asunto(s)
Nitrógeno , Triticum , Triticum/metabolismo , Nitrógeno/metabolismo , Epigénesis Genética , Histonas/genética , Histonas/metabolismo , Fitomejoramiento
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