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1.
J Pharm Biomed Anal ; 245: 116194, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704878

RESUMO

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.

2.
Biochem Biophys Res Commun ; 717: 150061, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38718570

RESUMO

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.

3.
Proc Natl Acad Sci U S A ; 121(20): e2319115121, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38709931

RESUMO

The endosomal sorting complexes required for transport (ESCRTs) are responsible for membrane remodeling in many cellular processes, such as multivesicular body biogenesis, viral budding, and cytokinetic abscission. ESCRT-III, the most abundant ESCRT subunit, assembles into flat spirals as the primed state, essential to initiate membrane invagination. However, the three-dimensional architecture of ESCRT-III flat spirals remained vague for decades due to highly curved filaments with a small diameter and a single preferred orientation on the membrane. Here, we unveiled that yeast Snf7, a component of ESCRT-III, forms flat spirals on the lipid monolayers using cryogenic electron microscopy. We developed a geometry-constrained Euler angle-assigned reconstruction strategy and obtained moderate-resolution structures of Snf7 flat spirals with varying curvatures. Our analyses showed that Snf7 subunits recline on the membrane with N-terminal motifs α0 as anchors, adopt an open state with fused α2/3 helices, and bend α2/3 gradually from the outer to inner parts of flat spirals. In all, we provide the orientation and conformations of ESCRT-III flat spirals on the membrane and unveil the underlying assembly mechanism, which will serve as the initial step in understanding how ESCRTs drive membrane abscission.


Assuntos
Microscopia Crioeletrônica , Complexos Endossomais de Distribuição Requeridos para Transporte , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/ultraestrutura , Saccharomyces cerevisiae/metabolismo , Membrana Celular/metabolismo
4.
Rapid Commun Mass Spectrom ; 38(14): e9761, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38714820

RESUMO

RATIONALE: Himalayan marmot oil (SPO) has been used for pharmaceutical purposes for centuries, but its composition is still unclear. The bioactivity of SPO highly depends on the techniques used for its processing. This study focused on the comprehensive lipidomics of SPO, especially on the ones derived from dry rendering, wet rendering, cold pressing, and ultrasound-assisted solvent extraction. METHODS: We performed lipid profiling of SPO acquired by different extraction methods using ultrahigh-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry, and 17 classes of lipids (2 BMPs, 12 LysoPCs, 9 LysoPEs, 41 PCs, 24 PEs, 23 Plasmenyl-PCs, 10 Plasmenyl-PEs, 10 MGs, 63 DGs, 187 TGs, 2 MGDGs, 3 Cer[NDS]s, 22 Cer[NS]s, 2 GlcCer[NS]s, 14 SMs, 14 CEs, and 6 AcylCarnitines) were characterized. RESULTS: Fifty-five lipids were differentially altered (VIP > 1.5, p < 0.05) between the extraction techniques, which can be used as potential biomarkers to differentiate SPO extracted by various methods. Additionally, the contents of oleic acid and arachidic acid were abundant in all samples that may suggest their medicinal values and are conducive to in-depth research. CONCLUSIONS: These findings reveal the alterations of lipid profile and free fatty acid composition in SPO obtained with different extraction methods, providing a theoretical foundation for investigating its important components as functional factors in medicines and cosmetics.


Assuntos
Lipídeos , Marmota , Espectrometria de Massas , Cromatografia Líquida de Alta Pressão/métodos , Lipídeos/química , Lipídeos/análise , Espectrometria de Massas/métodos , Óleos de Plantas/química , Óleos de Plantas/análise , Lipidômica/métodos , Fracionamento Químico/métodos
5.
Technol Cancer Res Treat ; 23: 15330338241242637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584417

RESUMO

Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls (P < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. Conclusion: These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis.


Assuntos
Neoplasias do Endométrio , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Metilação de DNA , Estudos Retrospectivos , Colo do Útero/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38581929

RESUMO

Nandrolone (NT) is a type of androgen anabolic steroid that is often illegally used in cattle farming, leading to unpredictable harm to human health via the food chain. In this study, a rapid detection method for NT in the samples of cattle farming was established using a portable mass spectrometer. The instrument parameters were optimized, including a thermal desorption temperature of 220 °C, a pump speed of 30 %, an APCI ionization voltage of 3900 v, and an injection volume of 6 µL. The samples of bovine urine, feed, sewage, and tissue were selected, and extracted using a solution of methanol:acetonitrile (1:1, v/v), followed by spiking a NT standard solution (1000 ng·mL-1) and ionization through the APCI ion source for detection. The results showed that NT could not be detected in beef and feed due to the complexity of the matrix, while clear signals of NT ions were observed in bovine urine and sewage samples, with LODs of 1000 and 100 ng·mL-1, respectively. Furthermore, quantitative analysis was attempted, and a good linear relationship (R2 = 0.9952) was observed for NT in sewage within the range of 100 to 1000 ng·mL-1. At spiked levels of 100, 500, 1000 and 2000 ng mL-1, the recovery rates ranged from 74.3 % to 92.8 %, with a relative standard deviation (n = 6) of less than 15 %. In conclusion, this detection method offers the advantages of simplicity, rapidity, strong timeliness, and specificity, making it suitable for on-site detection. It can be used for qualitative screening of nandrolone in bovine urine and quantitative analysis of nandrolone in sewage.


Assuntos
Limite de Detecção , Nandrolona , Bovinos , Animais , Nandrolona/análise , Nandrolona/urina , Modelos Lineares , Reprodutibilidade dos Testes , Espectrometria de Massas/métodos , Esgotos/química , Esgotos/análise , Ração Animal/análise , Anabolizantes/urina , Anabolizantes/análise
7.
J Agric Food Chem ; 72(15): 8859-8870, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564481

RESUMO

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.


Assuntos
Ácidos Graxos Monoinsaturados , Óleos de Peixe , Água , Triglicerídeos/química , Óleos de Peixe/química , Digestão
8.
Small Methods ; : e2400015, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607951

RESUMO

Nowadays, the extensively used lead sulfide (PbS) quantum dot (QD) hole transport layer (HTL) relies on layer-by-layer method to replace long chain oleic acid (OA) ligands with short 1,2-ethanedithiol (EDT) ligands for preparation. However, the inevitable significant volume shrinkage caused by this traditional method will result in undesired cracks and disordered QD arrangement in the film, along with adverse increased defect density and inhomogeneous energy landscape. To solve the problem, a novel method for EDT passivated PbS QD (PbS-EDT) HTL preparation using small-sized benzoic acid (BA) as intermediate ligands is proposed in this work. BA is substituted for OA ligands in solution followed by ligand exchange with EDT layer by layer. With the new method, smoother PbS-EDT films with more ordered and closer QD packing are gained. It is demonstrated stronger coupling between QDs and reduced defects in the QD HTL owing to the intermediate BA ligand exchange. As a result, the suppressed nonradiative recombination and enhanced carrier mobility are achieved, contributing to ≈20% growth in short circuit current density (Jsc) and a 23.4% higher power conversion efficiency (PCE) of 13.2%. This work provides a general framework for layer-by-layer QD film manufacturing optimization.

9.
Food Chem ; 449: 139198, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574526

RESUMO

The preparation of high specificity and affinity antibodies is challenging due to limited information on characteristic groups of haptens in traditional design strategy. In this study, we first predicted characteristic groups of flurogestone acetate (FGA) using quantitative analysis of molecular surface combined with atomic charge distribution. Subsequently, FGA haptens were rationally designed to expose these identified characteristic groups fully. As a result, seven monoclonal antibodies were obtained with satisfactory performance, exhibiting IC50 values from 0.17 to 0.45 µg/L and negligible cross-reactivities below 1% to other 18 hormones. The antibody recognition mechanism further confirmed hydrogen bonds and hydrophobic interactions involving predicted FGA characteristic groups and specific amino acids in the antibodies contributed to their high specificity and affinity. Finally, one selective and sensitive ic-ELISA was developed for FGA determination with a detection limit as low as 0.12 µg/L, providing an efficient tool for timely monitoring of FGA in goat milk samples.


Assuntos
Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática , Contaminação de Alimentos , Cabras , Haptenos , Leite , Animais , Leite/química , Haptenos/química , Haptenos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Contaminação de Alimentos/análise , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Feminino , Formação de Anticorpos
10.
Adv Sci (Weinh) ; : e2308589, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491742

RESUMO

Hexagonal MAB phases (h-MAB) have attracted attention due to their potential to exfoliate into MBenes, similar to MXenes, which are predicted to be promising for Li-ion battery applications. However, the high cost of synthesizing MBenes poses challenges for their use in batteries. This study presents a novel approach where a simple ball-milling treatment is employed to enhance the purity of the h-MAB phase Ti2 InB2 and introduce significant indium defects, resulting in improved conductivity and the creation of abundant active sites. The synthesized Ti2 InB2 with indium defects (VIn -Ti2 InB2 ) exhibits excellent electrochemical properties, particularly exceptional long-cycle stability at current densities of 5 A g-1 (5000 cycles, average capacity decay of 0.0018%) and 10 A g-1 (15 000 cycles, average capacity decay of 0.093%). The charge storage mechanism of VIn -Ti2 InB2 , involving a dual redox reaction, is proposed, where defects promote the In-Li alloy reaction and a redox reaction with Li in the TiB layer. Finally, a Li-ion full cell demonstrates cycling stability at 0.5 A g-1 after 350 cycles. This work presents the first accessible and scalable application of VIn -Ti2 InB2 as a Li-ion anode, unlocking a wealth of possibilities for sustainable electrochemical applications of h-MAB phases.

12.
J Cell Mol Med ; 28(8): e18244, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520211

RESUMO

To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to assess cell proliferation. Immunofluorescence was used to detect the expression of CD68 and Vimentin in primary synovial fibroblasts (SFs). Haematoxylin and eosin staining and Safranin O/Fast green were used to evaluate the pathological damage of synovial and cartilage tissue in rats. TRIM52 was upregulated in the synovial tissue and SFs in patients with TMJOA. Interleukin (IL)-1ß treatment upregulated TRIM52 expression in TMJOA SFs and normal SF (NSF), promoting cell proliferation, inflammatory response and oxidative stress in NSF, SFs. Silence of TRIM52 relieved the cell proliferation, inflammatory response and oxidative stress induced by IL-1ß in SFs, while overexpression of TRIM52 enhanced IL-1ß induction. Meanwhile, IL-1ß induction activated toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, which was augmented by upregulation of TRIM52 in NSF, and was attenuated by TRIM52 knockdown in SFs. Besides, pyrrolidinedithiocarbamic acid ameliorated IL-1ß-induced proliferation and inflammatory response by inhibiting TLR4/NF-κB signalling. Meanwhile, TRIM52 knockdown inhibited cell proliferation, oxidative stress and inflammatory response in IL-1ß-induced SFs through downregulation of TLR4. TRIM52 promoted cell proliferation, inflammatory response, and oxidative stress in IL-1ß-induced SFs. The above functions were mediated by the activation of TLR4/NF- κB signal pathway.


Assuntos
Osteoartrite , Receptor 4 Toll-Like , Animais , Humanos , Ratos , Proliferação de Células , Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Estresse Oxidativo , Articulação Temporomandibular/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
13.
JAMA Psychiatry ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446452

RESUMO

Importance: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders. Objective: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding. Design, Setting, and Participants: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023. Exposures: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey. Main Outcomes and Measures: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register. Results: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11). Conclusions and relevance: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

14.
Acta Pharmacol Sin ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467717

RESUMO

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

15.
Nanomaterials (Basel) ; 14(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38392749

RESUMO

Cs2NaInCl6 double perovskites, which have excellent photoelectric conversion properties and are non-toxic and lead-free, have recently gained significant attention. In particular, double-perovskite quantum dots (QDs) are viewed as a promising material for optoelectronic device applications. Ligands such as oleic acid (OA) and oleylamine (OAm) are essential for the synthesis of perovskite QDs, but their specific roles in double-perovskite QDs remain unclear. In this study, we have investigated the binding of OA and OAm to Cs2NaInCl6 QDs through FTIR and NMR and their effects on the surface defect reduction and stability improvement for Cs2NaInCl6 QDs. We found that only OAm was bound to the QD surfaces while OA was not. The OAm has a significant effect on the photoluminescence quantum yield (PLQY) improvement by passivating the QD surface defects. The stability of the QDs was also evaluated, and it was observed that OA played a significant role in the stability of the QDs. Our findings provide valuable insights into the roles of ligands in influencing the photophysical properties and stability of lead-free double-perovskite QDs.

16.
Curr Mol Pharmacol ; 17: e18761429282063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389418

RESUMO

BACKGROUND: Nicosulfuron, a widely used herbicide in crops, has raised concerns due to its escalating presence as an environmental pollutant, particularly in soil and water. The potential adverse effects of nicosulfuron on animals, including reproductive toxicity, have garnered attention. OBJECTIVE: The study aimed to evaluate the reproductive toxicity of nicosulfuron in male mice. METHODS: Male mice were orally administrated with three different concentration gradients (350, 700, and 1400 mg/kg) of nicosulfuron for 35 days. The investigation delved into sperm quality, testicular structures, and expression of cleaved caspase-3 and NF-κB p65 of the testes. RESULTS: The finding unveiled a correlation between nicosulfuron exposure and detrimental effects on sperm quality and alteration of testicular structure. Notably, parameters, such as sperm survival rate (SUR) and sperm motility (MOT), exhibited a decline in relation to increasing nicosulfuron dosages. Moreover, in the mice subjected to higher doses of nicosulfuron, elevated expression of cleaved caspase-3 and NF-κB p65 was observed in the testes. Interestingly, we also observed an increase of NF-κB p65 expression in the mice exposed to the nicosulfuron. CONCLUSION: Our research revealed that exposure to nicosulfuron resulted in compromised sperm quality and alterations in testicular structure. The correlation between nicosulfuron and apoptosis, especially via the NF-κB pathway, provided significant insights into the mechanisms underpinning these detrimental effects. These findings significantly enhance our comprehension of the potential hazards associated with nicosulfuron exposure and its impacts on the reproductive health of animals.


Assuntos
NF-kappa B , Piridinas , Compostos de Sulfonilureia , Testículo , Masculino , Camundongos , Animais , NF-kappa B/metabolismo , Caspase 3/metabolismo , Caspase 3/farmacologia , Estresse Oxidativo , Motilidade dos Espermatozoides , Sêmen/metabolismo , Espermatozoides/metabolismo , Transdução de Sinais , Apoptose
17.
Eur J Med Chem ; 267: 116223, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38342013

RESUMO

Acute lung injury (ALI) is a clinically high mortality disease, which has not yet been effectively treated. The development of anti-ALI drugs is imminent. ALI can be effectively treated by inhibiting the inflammatory cascade and reducing the inflammatory response in the lung. Forsythia suspense is a common Chinese herbal medicine with significant anti-inflammatory activity. Using forsythin as the parent, 27 Forsythin derivatives were designed and synthesized, and the anti-AIL activity of these compounds was evaluated. Among them, compound B5 has the best activity to inhibit the release of IL-6, and the inhibition rate reaches 91.79% at 25 µM, which was 7.5 times that of the parent forsythin. In addition, most of the compounds have no significant cytotoxicity in vitro. Further studies showed that compound B5 had a concentration-dependent inhibitory effect on NO, IL-6 and TNF-α. And the IC50 values of compound B5 for NO and IL-6 are 10.88 µM and 4.93 µM, respectively. We also found that B5 could significantly inhibit the expression of some immune-related cytotoxic factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, B5 inhibits NF-κB/MAPK signaling pathway. In vivo experiments showed that B5 could alleviate lung inflammation in LPS-induced ALI mice and inhibit IL-6, TNF-α, COX-2 and iNOS. In summary, B5 has anti-inflammatory effects and alleviates ALI by regulating inflammatory mediators and inhibiting MAPK and NF-κB signaling pathways.


Assuntos
Lesão Pulmonar Aguda , Glucosídeos , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Ciclo-Oxigenase 2/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo
18.
Proc Natl Acad Sci U S A ; 121(9): e2311160121, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38377189

RESUMO

Glioblastomas (GBMs) are the most lethal primary brain tumors with limited survival, even under aggressive treatments. The current therapeutics for GBMs are flawed due to the failure to accurately discriminate between normal proliferating cells and distinctive tumor cells. Mitochondria are essential to GBMs and serve as potential therapeutical targets. Here, we utilize cryo-electron tomography to quantitatively investigate nanoscale details of randomly sampled mitochondria in their native cellular context of GBM cells. Our results show that compared with cancer-free brain cells, GBM cells own more inter-mitochondrial junctions of several types for communications. Furthermore, our tomograms unveil microtubule-dependent mitochondrial nanotunnel-like bridges in the GBM cells as another inter-mitochondrial structure. These quantified inter-mitochondrial features, together with other mitochondria-organelle and intra-mitochondrial ones, are sufficient to distinguish GBM cells from cancer-free brain cells under scrutiny with predictive modeling. Our findings decipher high-resolution inter-mitochondrial structural signatures and provide clues for diagnosis and therapeutic interventions for GBM and other mitochondria-related diseases.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Tomografia com Microscopia Eletrônica , Encéfalo/patologia , Mitocôndrias/patologia
19.
Curr Med Chem ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38415438

RESUMO

The current review was undertaken to collate data on Gpx4 inhibitors and the regulatory proteins related to Gpx4. Gpx4 plays an essential role in ferroptosis; it can be used to determine the Gpx4 as an indicator for determining tumor occurrence and as a means of treating cancer. Although there is no market for Gpx4 inhibitors, many researchers have conducted extensive research, and some compounds have entered clinical research. This article summarizes all papers related to Gpx4; hope this review can provide some new insights and ideas for researchers aiming to develop efficient and low-- toxicity Gpx4 inhibitors and provide some new ideas for cancer treatment.

20.
Dalton Trans ; 53(11): 5291-5300, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38411208

RESUMO

Noble metal-based catalysts such as RuO2 and IrO2 are widely used in the catalysis of the OER. However, because of their high price and poor stability, it is urgent to develop transition metal-based electrocatalysts with low precious metal doping as an alternative. Layered double hydroxides (LDHs) grown on 3D metal-organic frameworks (MOFs) are ideal for doping precious metals owing to abundant defects at the heterointerface, large surface area, and intrinsic oxygen evolution activity. In this study, a novel FeNi LDH/MOF heterostructure was prepared via a two-step solvothermal method using Fe-soc-MOFs as the substrate. Subsequently, Ru was introduced through a hydrothermal process. The as-synthesized Ru@FeNi LDH/MOF has an overpotential of only 242 mV at a current density of 10 mA cm-2 and can be used in continuous electrolysis for 48 h. Its unique nanocubic core-shell structure and flower-like LDHs on its surface provide a large number of active sites, which become the key to ensuring high activity and stability. With the doping of Ru, the electronic structure was adjusted and electron transfer was accelerated, further improving electrochemical activity. This study provides a new idea for developing transition metal-based catalysts with low noble metal loading.

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