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1.
Nat Prod Res ; : 1-8, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38934460

RESUMEN

One previously undescribed abietane diterpene alkaloid containing an oxazole ring (1), one unreported abietane diterpene (2), and nine known abietane diterpenes (3-11) were isolated from the roots and rhizomes of Salvia castanea Diels. Their structures and absolute configurations were elucidated by a combination of HRESIMS, 1D and 2D NMR, and ECD. All compounds were evaluated for their cytotoxic activity against several human cancer cell lines (HepG2, A549, H460, MCF7, PC3, and Hela). The results showed that 1 exhibited a moderate cytotoxic effect on HepG2 cells (IC50: 14.22 ± 1.05 µM) and was able to inhibit the cell growth of MCF7 and Hela cells by 35.08% and 47.26% respectively, at a concentration of 20 µM, while other compounds showed low cytotoxic activity.

2.
J Cell Mol Med ; 28(12): e18449, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38924214

RESUMEN

Mitochondrial dynamics has emerged as an important target for neuronal protection after cerebral ischaemia/reperfusion. Therefore, the aim of this study was to investigate the mechanism by which ARMC10 regulation of mitochondrial dynamics affects mitochondrial function involved in ischaemic stroke (IS). Mitochondrial morphology was detected by laser scanning confocal microscopy (LSCM), and mitochondrial ultrastructural alterations were detected by electron microscopy. The expression of mitochondrial dynamics-related genes Drp1, Mfn1, Mfn2, Fis1, OPA1 and ARMC10 and downstream target genes c-Myc, CyclinD1 and AXIN2 was detected by RT-qPCR. Western blot was used to detect the protein expression of ß-catenin, GSK-3ß, p-GSK-3ß, Bcl-2 and Bax. DCFH-DA fluorescent probe was to detect the effect of ARMC10 on mitochondrial ROS level, Annexin V-FITC fluorescent probe was to detect the effect of ARMC10 on apoptosis, and ATP assay kit was to detect the effect of ARMC10 on ATP production. Mitochondrial dynamics was dysregulated in clinical IS samples and in the OGD/R cell model, and the relative expression of ARMC10 gene was significantly decreased in IS group (p < 0.05). Knockdown and overexpression of ARMC10 could affect mitochondrial dynamics, mitochondrial function and neuronal apoptosis. Agonist and inhibitor affected mitochondrial function and neuronal apoptosis by targeting Wnt/ß-Catenin signal pathway. In the OGD/R model, ARMC10 affected mitochondrial function and neuronal apoptosis through the mechanism that regulates Wnt/ß-catenin signalling pathway. ARMC10 regulates mitochondrial dynamics and protects mitochondrial function by activating Wnt/ß-catenin signalling pathway, to exert neuroprotective effects.


Asunto(s)
Apoptosis , Proteínas del Dominio Armadillo , Accidente Cerebrovascular Isquémico , Mitocondrias , Dinámicas Mitocondriales , Vía de Señalización Wnt , Mitocondrias/metabolismo , Humanos , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/patología , Proteínas del Dominio Armadillo/metabolismo , Proteínas del Dominio Armadillo/genética , Masculino , beta Catenina/metabolismo , beta Catenina/genética , Especies Reactivas de Oxígeno/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/patología , Animales
3.
Nanoscale ; 16(25): 11849-11862, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38836376

RESUMEN

Atherosclerosis, as a chronic cardiovascular disease driven by inflammation, can lead to arterial stenosis and thrombosis, which seriously threatens human life and health. Achieving the timely monitoring of atherosclerosis is an important measure to reduce acute cardiovascular diseases. Compared with other imaging platforms, fluorescence imaging technology has the characteristics of excellent sensitivity, high spatiotemporal resolution and real-time imaging, which is very suitable for direct visualization of molecular processes and abnormalities of atherosclerosis. Recently, researchers have strived to design a variety of fluorescent probes, from single-mode fluorescent probes to fluorescent-combined dual/multimode probes, to enrich the imaging and detection of atherosclerosis. Therefore, this review aims to provide an overview of currently investigated fluorescent probes in the context of atherosclerosis, summarize relevant published studies showing applications of different types of fluorescent probes in the early-stage and other stages to detect atherosclerosis, give effective biological targets and discuss the latest progress and some limitations. Finally, some insights are provided for the development of a new generation of more accurate and efficient fluorescent probes.


Asunto(s)
Aterosclerosis , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Humanos , Aterosclerosis/diagnóstico por imagen , Animales , Imagen Óptica/métodos
4.
Tree Physiol ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832722

RESUMEN

Sabina chinensis is a typically heteromorphic leaf evergreen tree worldwide with both ornamental and ecological value. However, the shaping mechanism of heteromorphic leaves of Sabina chinensis and its adaptability to environment are important factors determining its morphology. The morphological change of S. chinensis which under different habitats (arbor around) and treatments (light, pruning and nutrients) was investigated. Our findings suggested that the prickle leaves proportion was associated with low light intensity and soil nutrient scarcity. Stems and leaves are pruned together to form clusters of large prickle leaves, while only pruning leaves often form alternately growing small prickle leaves and scale leaves, and the length of the prickle leaves is between 0.5 cm to 1 cm. The gene expression of prickle leaves is higher than that of scale leaves that under adverse environmental conditions, and the gene expression correlations of small prickle leaf and scale leaf were the highest. Homologous and heterologous mutants of gene structure in prickle leaves were larger than those in scale leaves. KEGG pathway showed that phenylpropanone and flavonoid biosynthesis were common enrichment pathways, and the enrichment genes were mainly related to metabolism, genetic information processing and organismal systems. Therefore, we concluded that the occurrence of the heteromorphic leaf phenomenon was related to the changes in photosynthesis, mechanical damage and nutrient supplementation. The organic matter in the S. chinensis prickle leaves was reduced under environmental stresses, and it will be allocated to the expression to the prickle leaf or protective cuticles formation.

5.
J Immunol ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856712

RESUMEN

Bats are the natural reservoir hosts of some viruses, some of which may spill over to humans and cause global-scale pandemics. Different from humans, bats may coexist with high pathogenic viruses without showing symptoms of diseases. As one of the most important first defenses, bat type I IFNs (IFN-Is) were thought to play a role during this virus coexistence and thus were studied in recent years. However, there are arguments about whether bats have a contracted genome locus or constitutively expressed IFNs, mainly due to species-specific findings. We hypothesized that because of the lack of pan-bat analysis, the common characteristics of bat IFN-Is have not been revealed yet. In this study, we characterized the IFN-I locus for nine Yangochiroptera bats and three Yinpterochiroptera bats on the basis of their high-quality bat genomes. We also compared the basal expression in six bats and compared the antiviral and antiproliferative activity and the thermostability of representative Rhinolophus bat IFNs. We found a dominance of unconventional IFNω-like responses in the IFN-I system, which is unique to bats. In contrast to IFNα-dominated IFN-I loci in the majority of other mammals, bats generally have shorter IFN-I loci with more unconventional IFNω-like genes (IFNω or related IFNαω), but with fewer or even no IFNα genes. In addition, bats generally have constitutively expressed IFNs, the highest expressed of which is more likely an IFNω-like gene. Likewise, the highly expressed IFNω-like protein also demonstrated the best antiviral activity, antiproliferative activity, or thermostability, as shown in a representative Rhinolophus bat species. Overall, we revealed pan-bat unique, to our knowledge, characteristics in the IFN-I system, which provide insights into our understanding of the innate immunity that contributes to a special coexistence between bats and viruses.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38837550

RESUMEN

PURPOSE: The present study was to investigate prevalence of suicidal ideation and its associations with biological and environmental factors in adolescents with different genotypes of rs12342 at adiponectin receptor 2 gene (ADIPOR2). METHODS: Suicidal ideation, biological and environmental factors were evaluated by questionnaires in 669 high school students after Wenchuan earthquake in China. ADIPOR2 rs12342 was genotyped by polymerase chain reaction-restriction fragment length polymorphism and verified by DNA sequencing. RESULTS: Female adolescents had higher prevalence of suicidal ideation than male students in AG heterozygote and GG homozygote, but not AA homozygote. Prevalence of suicidal ideation was different in male, but not female, subjects with different genotypes. Genotype and allele frequencies were significantly different between male students with and without suicidal ideation, but not the female counterparts. Family history of mental disorders, extent of damage to property, carbohydrate intake and protein intake were associated with suicidal ideation in female subjects, while ADIPOR2 rs12342, father's educational level and previous trauma experience were associated with suicidal ideation in male subjects. CONCLUSION: ADIPOR2 rs12342 is associated with and has potential to interact with environmental factors on suicidal ideation in a gender-dependent manner in youth. These findings pave a novel way and perspective for precision inferences of suicidal ideation in subjects with different genetic backgrounds. ADIPOR2 rs12342 needs to be considered when intervening suicidal ideation, especially in adolescents.

7.
J Agric Food Chem ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38905352

RESUMEN

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.

8.
Org Lett ; 26(23): 4857-4862, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38838191

RESUMEN

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

9.
Front Pharmacol ; 15: 1359939, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933676

RESUMEN

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

11.
J Nanobiotechnology ; 22(1): 330, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862987

RESUMEN

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.


Asunto(s)
Criopreservación , Ovario , Criopreservación/métodos , Femenino , Humanos , Animales
12.
Huan Jing Ke Xue ; 45(6): 3627-3637, 2024 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-38897782

RESUMEN

In order to explore the evolution law and driving mechanism of aerobic denitrification bacteria in Baiyangdian Lake under different hydrological scenarios, based on water quality survey and high-throughput sequencing technology, this study conducted a water quality factor analysis and aerobic denitrification bacteria α-diversity analysis, species composition, and network analysis. The results showed that the water body of Baiyangdian Lake was weakly alkaline, with the highest T and the lowest DO in the rainy season and the lowest T and the highest DO in the freezing season. There were significant differences between NH4+-N, NO2--N, NO3--N, TN, permanganate index, Fe, and Mn in Baiyangdian water under different hydrological scenarios (P < 0.01), and there was no significant difference in TP under different hydrological scenarios (P > 0.05). The largest category in water bodies under different hydrological scenarios was Proteobacteria, and the genera with a higher relative abundance were Magnetospirillum, Aeromonas, Pseudomonas, Azospirillum, and Bradyrhizobium. In addition, within the aerobic denitrifying bacteria community, there were significant differences in α-diversity (P < 0.001), with the highest abundance of microbial communities occurring during the freezing period, and the highest diversity and evenness of microbial communities during the dry and freezing periods. According to the RDA and Mantel analyses, the water quality driving factors of flora were different under different hydrological scenarios. The water quality driving factors of flora in the dry season were pH, NO3--N, NO2--N, and permanganate index; the driving factors of flora in the rainy season were pH, T, DO, NO2--N, and TP; the driving factors of flora in the normal season were NO2--N, Fe, and permanganate index; and the driving factors of flora in the freezing season were NO3--N and NONO2--N. Network analysis showed that there were temporal differences in species related to water quality driving factors. The genera related to water quality driving factors during the dry season were Magnetospirillum, Aeromonas, and Azoarcus, whereas the genera related to the rainy season were Magnetospirillum, Pseudomonas, and Aeromonas. The genera related to the normal season were Magnetospirillum, Pseudomonas, and Limnohabitans, and the genera related to the freezing period were Magnetospirillum, Azoarcus, and Pseudomonas. The relationship between key water quality factors (mainly T, DO, NO3--N, and permanganate index) and aerobic denitrification flora in different hydrological scenarios was gradually changing with time. In conclusion, the study on the evolution characteristics of aerobic denitrification bacteria in Baiyangdian Lake under different hydrological scenarios and the driving mechanism of environmental factors could provide a basis for understanding the evolution mechanism of aerobic denitrification bacteria in the natural environment.


Asunto(s)
Desnitrificación , Lagos , Calidad del Agua , China , Lagos/microbiología , Hidrología , Bacterias Aerobias/metabolismo , Bacterias Aerobias/aislamiento & purificación , Monitoreo del Ambiente , Proteobacteria/aislamiento & purificación , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo
13.
Environ Res ; 255: 119162, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38762003

RESUMEN

In order to evaluate the impact of salinity gradients on the aniline biodegradation system, six reactors at salinity concentrations (0%-5%) were established. The results presented the salinity except for 5% imposed negligible effects on aniline degradation performance. Nitrification had prominent resistance to salinity (0%-1.5%) while were significantly restrained when salinity increased. The total nitrogen (TN) removal efficiency of Z4 (1.5%) was 20.5% higher than Z1 (0%) during the stable operation phase. Moreover, high throughput sequencing analysis showed that halophilic bacterium, such as Halomonas, Rhodococcus, remained greater survival advantages in high salinity system. The substantial enrichment of Flavobacterium, Dokdonella, Paracoccus observed in Z4 ensured its excellent nitrogen removal performance. The close cooperation among dominant functional bacteria was strengthened when salt content was below 1.5% while exceeding 1.5% led to the collapse of metabolic capacity through integrating the toxicity of aniline and high osmotic pressure.


Asunto(s)
Compuestos de Anilina , Biodegradación Ambiental , Contaminantes Químicos del Agua , Compuestos de Anilina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Estrés Salino , Bacterias/metabolismo , Bacterias/genética , Reactores Biológicos/microbiología , Salinidad
14.
Behav Brain Res ; 469: 115047, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38759799

RESUMEN

Hyperalgesia occurs in the orofacial region of rats when estrogen levels are low, although the specific mechanism needs to be investigated further. Furthermore, oxidative stress plays an important role in the transmission of pain signals. This study aimed to explore the role of oxidative stress in orofacial hyperalgesia under low estrogen conditions. We firstly found an imbalance between oxidative and antioxidant capacity within the spinal trigeminal subnucleus caudalis (SP5C) of rats after ovariectomy (OVX), resulting in oxidative stress and then a decrease in the orofacial pain threshold. To investigate the mechanism by which oxidative stress occurs, we used virus as a tool to silence or overexpress the excitatory amino acid transporter 3 (EAAT3) gene. Further investigation revealed that the regulation of glutathione (GSH) and reactive oxygen species (ROS) can be achieved by regulating EAAT3, which in turn impacts the occurrence of oxidative stress. In summary, our findings suggest that reduced expression of EAAT3 within the SP5C of rats in the low estrogen state may decrease GSH content and increase ROS levels, resulting in oxidative stress and ultimately lead to orofacial hyperalgesia. This suggests that antioxidants could be a potential therapeutic direction for orofacial hyperalgesia under low estrogen conditions, though more research is needed to understand its mechanism.


Asunto(s)
Estrógenos , Transportador 3 de Aminoácidos Excitadores , Dolor Facial , Glutatión , Hiperalgesia , Ovariectomía , Estrés Oxidativo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Animales , Hiperalgesia/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Femenino , Estrógenos/metabolismo , Estrógenos/farmacología , Dolor Facial/metabolismo , Glutatión/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transportador 3 de Aminoácidos Excitadores/metabolismo , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Núcleo Caudal del Trigémino/metabolismo , Núcleo Caudal del Trigémino/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo
15.
Proc Natl Acad Sci U S A ; 121(20): e2400610121, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38713623

RESUMEN

Chromatin replication is intricately intertwined with the recycling of parental histones to the newly duplicated DNA strands for faithful genetic and epigenetic inheritance. The transfer of parental histones occurs through two distinct pathways: leading strand deposition, mediated by the DNA polymerase ε subunits Dpb3/Dpb4, and lagging strand deposition, facilitated by the MCM helicase subunit Mcm2. However, the mechanism of the facilitation of Mcm2 transferring parental histones to the lagging strand while moving along the leading strand remains unclear. Here, we show that the deletion of Pol32, a nonessential subunit of major lagging-strand DNA polymerase δ, results in a predominant transfer of parental histone H3-H4 to the leading strand during replication. Biochemical analyses further demonstrate that Pol32 can bind histone H3-H4 both in vivo and in vitro. The interaction of Pol32 with parental histone H3-H4 is disrupted through the mutation of the histone H3-H4 binding domain within Mcm2. Our findings identify the DNA polymerase δ subunit Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication.


Asunto(s)
Replicación del ADN , ADN Polimerasa Dirigida por ADN , Proteínas de Saccharomyces cerevisiae , ADN Polimerasa III/metabolismo , ADN Polimerasa III/genética , Histonas/metabolismo , Componente 2 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Componente 2 del Complejo de Mantenimiento de Minicromosoma/genética , Unión Proteica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , ADN Polimerasa Dirigida por ADN/metabolismo
16.
Appl Radiat Isot ; 209: 111338, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38714137

RESUMEN

- Innovative methods were developed for direct 90Sr and 137Cs determination in soils by radiochemical separation and ß-counting. Studies focused on: (1) the suitability of PEG to remove silica by coating, (2) the decontamination effect of Cs from 40K, (3) iron elimination with Microthene-TOA column instead of oxalate complex, and (4) the effective separation of Y and Sr from Pb by a Microthene-TOA column which made the direct 90Sr determination possible in less time with just one resin-column. The methods were validated by analysing the IAEA reference materials, showing good agreement with the recommended values. The methods were used to determine 90Sr and 137Cs in 21 soil samples. The obtained 90Sr concentrations in the soils were in the range of 0.46-2.95 Bq kg-1, while 137Cs 1.24-35.5 Bq kg-1. The yields of yttrium and caesium were 73.4 ± 8.0% and 79.0 ± 9.1%, respectively.

17.
Heliyon ; 10(10): e30967, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38778971

RESUMEN

Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (p-IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro. Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.

18.
Ann Surg Oncol ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814549

RESUMEN

BACKGROUND: The mechanism underlying the formation of gastric tumor deposits (TDs) is unclear. We aimed to explore the risk factors for the formation and prognostic value of TDs. METHODS: This retrospective analysis included 781 locally advanced gastric cancer (LAGC) patients from four medical institutions in China, from June 2014 to June 2018. The risk factors for TD formation and prognostic value were determined through univariate and multivariate analyses. RESULTS: Univariate analysis revealed that TD positivity was closely related to tumor diameter, Borrmann classification, differentiation degree, pT stage, pN stage, pTNM stage, and nerve and vascular invasion (p < 0.05). Multivariate logistic regression revealed that tumor diameter ≥ 5 cm (odds ratio [OR] 1.836, 95% confidence interval [CI] 1.165-2.894, p = 0.009) and vascular invasion (OR 2.152, 95% CI 1.349-3.433, p = 0.001) were independent risk factors for TD positivity. Multivariate Cox analysis revealed that TD positivity (OR 1.533, 95% CI 1.101-2.134, p = 0.011), tumor diameter ≥ 5 cm (OR 1.831, 95% CI 1.319-2.541, p < 0.001), pT4a stage (OR 1.652, 95% CI 1.144-2.386, p = 0.007), and vascular invasion (OR 1.458, 95% CI 1.059-2.008, p = 0.021) were independent risk factors for GC prognosis. The 5-year overall and disease-free survival of the TD-positive group showed significant effects among patients in the pT4a and pN3b stages (p < 0.05). CONCLUSIONS: TDs are closely related to tumor diameter and vascular invasion in LAGC patients, and TD positivity is an independent prognostic factor for LAGC patients, especially those at pT4a and pN3b stages.

19.
Am J Reprod Immunol ; 91(5): e13855, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38745499

RESUMEN

Endometriosis (EM) is one of the diseases related to retrograded menstruation and hemoglobin. Heme, released from hemoglobin, is degraded by heme oxygenase-1 (HO-1). In EM lesions, heme metabolites regulate processes such as inflammation, redox balance, autophagy, dysmenorrhea, malignancy, and invasion, where macrophages (Mø) play a fundamental role in their interactions. Regulation occurs at molecular, cellular, and pathological levels. Numerous studies suggest that heme is an indispensable component in EM and may contribute to its pathogenesis. The regulatory role of heme in EM encompasses cytokines, signaling pathways, and kinases that mediate cellular responses to external stimuli. HO-1, a catalytic enzyme in the catabolic phase of heme, mitigates heme's cytotoxicity in EM due to its antioxidant, anti-inflammatory, and anti-proliferative properties. Certain compounds may intervene in EM by targeting heme metabolism, guiding the development of appropriate treatments for all stages of endometriosis.


Asunto(s)
Endometriosis , Hemo-Oxigenasa 1 , Hemo , Endometriosis/metabolismo , Endometriosis/tratamiento farmacológico , Femenino , Humanos , Hemo/metabolismo , Hemo-Oxigenasa 1/metabolismo , Animales , Transducción de Señal , Macrófagos/metabolismo , Macrófagos/inmunología , Autofagia , Citocinas/metabolismo
20.
Front Plant Sci ; 15: 1326345, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756962

RESUMEN

Phragmites australis is a prevalent species in the Chongming Dongtan wetland and is capable of thriving in various tidal flat environments, including high salinity habitats. P. australis population displays inconsistent ecological performances, highlighting the need to uncover their survival strategies and mechanisms in tidal flats with diverse soil salinities. Upon comparing functional traits of P. australis at multiple tidal flats (low, middle, and high) and their responses to soil physicochemical properties, this study aimed to clarify the salt-tolerant strategy of P. australis and the corresponding mechanisms. These results showed that leaf characteristics, such as specific leaf area and leaf dry matter content, demonstrated more robust stability to soil salinity than shoot height and dry weight. Furthermore, as salt stress intensified, the activities of superoxide dismutase (SOD), catalase (CAT) and peroxisome (POD) in P. australis leaves at low tidal flat exhibited an increased upward trend compared to those at other tidal flats. The molecular mechanism of salt tolerance in Phragmites australis across various habitats was investigated using transcriptome sequencing. Weighted correlation network analysis (WGCNA) combined with differentially expressed genes (DEGs) screened out 3 modules closely related to high salt tolerance and identified 105 core genes crucial for high salt tolerance. Further research was carried out on the few degraded populations at low tidal flat, and 25 core genes were identified by combining WGCNA and DEGs. A decrease in the activity of ferroptosis marker gonyautoxin-4 and an increase in the content of Fe3+ in the degenerated group were observed, indicating that ferroptosis might participate in degradation. Furthermore, correlation analysis indicated a possible regulatory network between salt tolerance and ferroptosis. In short, this study provided new insights into the salt tolerance mechanism of P. australis population along tidal flats.

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