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1.
BMC Anesthesiol ; 24(1): 226, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971731

RESUMO

BACKGROUND: Remimazolam tosilate (RT) is a new, ultrashort-acting benzodiazepine. Here, we investigated the efficacy and safety of RT for general anesthesia in patients undergoing Laparoscopic Cholecystectomy (LC). METHODS: In this study, 122 patients undergoing laparoscopic cholecystectomy were randomly allocated to receive either remimazolam tosilate (Group RT) or propofol group (Group P). RT was administered as a slow bolus of 0.3 mg kg- 1 for induction, followed by 1.0-2.0 mg kg- 1 h- 1 for maintenance of general anesthesia. Propofol was started at 2 mg kg- 1 and followed by 4-10 mg kg- 1 h- 1 until the end of surgery. The primary outcome was the time to bispectral index (BIS) ≤ 60. The secondary outcome included the time to loss of consciousness (LoC), and the time to extubation. Adverse events were also assessed. RESULTS: A total of 112 patients were recruited for study participation. Among them, the time to BIS ≤ 60 in Group RT was longer than that in Group P (Group RT: 89.3 ± 10.7 s; Group P: 85.9 ± 9.7 s, P > 0.05). While the time to LoC comparing remimazolam and propofol showed no statistical significance (Group RT: 74.4 ± 10.3 s; Group P: 74.7 ± 9.3 s, P > 0.05). The time to extubation in Group RT was significantly longer than that in Group P (Group RT: 16.0 ± 2.6 min; Group P: 8.8 ± 4.3 min, P < 0.001). Remimazolam tosilate had more stable hemodynamics and a lower incidence of hypotension during general anesthesia. CONCLUSIONS: Remimazolam tosilate can be safely and effectively used for general anesthesia in patients undergoing Laparoscopic Cholecystectomy. It maintains stable hemodynamics during induction and maintenance of general anesthesia compared with propofol. Further studies are needed to validate the findings. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2300071256 (date of registration: 09/05/2023).


Assuntos
Anestesia Geral , Anestésicos Intravenosos , Benzodiazepinas , Colecistectomia Laparoscópica , Propofol , Humanos , Propofol/administração & dosagem , Feminino , Masculino , Colecistectomia Laparoscópica/métodos , Estudos Prospectivos , Pessoa de Meia-Idade , Anestesia Geral/métodos , Adulto , Benzodiazepinas/administração & dosagem , Anestésicos Intravenosos/administração & dosagem
2.
Sci Rep ; 14(1): 15122, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956289

RESUMO

Natalisin (NTL) is a conserved neuropeptide, only present in insects, that has been reported to regulate their sexual activity. In this study, we investigated the involvement of NTL in the reproductive behaviors of a major invasive pest, Spodoptera frugiperda. We identified NTL precursor-encoded transcripts, and evaluated their transcript levels in different stages and tissues of S. frugiperda. The results showed that the NTL transcript level was expressed in both male and female pupae and both male and female adults in the later stage. It was highly expressed in male pupae, 3-day-old male and female adults, and 5-day-old male adults. In different tissues, the expression level is higher in the male and female adult brain and male testis. Immunohistochemical staining of the brain of S. frugiperda female and male adults revealed that three pairs of brain neurons of S. frugiperda adults of both sexes secreted and expressed NTL. To study the role of NTL in reproductive behaviors, NTL was silenced in S. frugiperda male and female adults by RNA interference (RNAi) technology, the results showed that silencing NTL could significantly affect the sexual activity behavior of the adults, reducing the calling rate of females, the courtship rate of males, and the mating rate. In summary, this study emphasizes the important role of NTL in regulating the mating behavior and sexual activity of S. frugiperda in both male and female adults, potentially laying a foundation to employ NTL as a new insect-specific target to control populations of pest insects.


Assuntos
Neuropeptídeos , Comportamento Sexual Animal , Spodoptera , Animais , Spodoptera/genética , Spodoptera/fisiologia , Masculino , Feminino , Neuropeptídeos/metabolismo , Neuropeptídeos/genética , Comportamento Sexual Animal/fisiologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Encéfalo/metabolismo , Interferência de RNA , Reprodução
3.
Int Heart J ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39010226

RESUMO

Dementia limits timely revascularization in individuals with acute myocardial infarction (AMI). However, it remains unclear whether dementia affects prognosis negatively in older individuals with AMI in the intensive care unit (ICU). This research aimed to evaluate the dementia effect on the outcomes in individuals with AMI in ICU.Data from 3,582 patients aged ≥ 65 years with AMI in ICU from the Medical Information Mart for Intensive Care IV (MIMIC IV) database were evaluated. The independent variable was dementia at baseline, and the primary finding was death from any cause during follow-up. A 1:1 propensity score matching (PSM) showed 208 participants with and without dementia. The correlation between dementia and poor prognosis of AMI was verified using a double-robust estimation method.In the PSM cohort, the 30-day all-cause mortality was 37.50% and 33.17% in the dementia and non-dementia groups (P = 0.356), respectively, and the 1-year all-cause mortality was 61.06% and 51.44%, respectively (P = 0.048). Cox regression analysis showed no association between dementia and elevated 30-day (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84, 1.60) and 1-year (HR 1.28, 95% CI 0.99, 1.66) all-cause mortality after AMI. Similarly, dementia was not connected with in-hospital mortality, bleeding, or stroke after AMI. Interaction analysis showed that 1-year all-cause mortality was 48.00% higher in individuals with dementia and diabetic complications than in those without diabetic complications.Dementia is not an independent risk factor for adverse outcomes in AMI. Thus, it may be inappropriate to include dementia as a contraindication for invasive AMI therapy.

4.
Healthcare (Basel) ; 12(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38998892

RESUMO

The occurrence of major public health crises, like the COVID-19 epidemic, present significant challenges to healthcare systems and the management of emergency medical resources worldwide. This study, by examining the practices of emergency medical resource management in select countries during the COVID-19 epidemic, and reviewing the relevant literature, finds that emergency hierarchical diagnosis and treatment systems (EHDTSs) play a crucial role in managing emergency resources effectively. To address key issues of emergency resource management in EHDTSs, we examine the features of EHDTSs and develop a research framework for emergency resource management in EHDTSs, especially focusing on the management of emergency medical personnel and medical supplies during evolving epidemics. The research framework identifies key issues of emergency medical resource management in EHDTSs, including the sharing and scheduling of emergency medical supplies, the establishment and sharing of emergency medical supply warehouses, and the integrated dispatch of emergency medical personnel. The proposed framework not only offers insights for future research but also can facilitate better emergency medical resource management in EHDTSs during major public health emergencies.

5.
Quant Imaging Med Surg ; 14(7): 4688-4702, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022239

RESUMO

Background: Dual-energy computed tomography (DECT) and iterative metal artifact reduction (iMAR) algorithms are valuable tools for reducing metal artifacts. Different parameters of these technologies and their combination can achieve different performance. This study compared various polychromatic and monochromatic images obtained via DECT with and without using iMAR algorithm to reduce artifacts in patients with dental implants. Methods: This study included 30 patients with dental implants who underwent DECT for head and neck imaging. The computed tomography (CT) image sets comprised DECT polychromatic image sets [dual-energy (DE) polychromatic] that linearly blended 100 kV and tin-filtered 140 kV images using composition ratios of -1, -0.6, -0.3, 0, and 0.6, and virtual monochromatic images (DE monochromatic) at 90, 110, 130, 150, and 170 keV. These image sets were obtained with and without using iMAR, resulting in a total of 20 image sets. For subjective analysis, metal artifacts and image quality were assessed using a 5-point Likert scale. For objective analysis, CT attenuation, standard deviation (SD), contrast-to-noise ratio (CNR) and artifact index (AI) were evaluated. In addition, subgroup analysis was performed based on implant size. Results: In the subjective evaluation, iMAR + DE polychromatic (-0.3) images exhibited the lowest metal artifact scores [median (interquartile range): 2 (2-3)]. iMAR + DE monochromatic (110 keV) images demonstrated optimal image quality scores [median (interquartile range): 2 (2-3)]. In the objective evaluation, none of the images demonstrated a significant difference in the CNR, except polychromatic images with a composition of -1 and 0.6. iMAR + DE polychromatic (0) exhibited the lowest AI [median (interquartile range): 8.7 (5.9-14.5)]. There was no significant difference between the two groups with different implant sizes for the techniques combined with iMAR (all P>0.05). Conclusion: iMAR + DE polychromatic (-0.3 and 0) and iMAR + DE monochromatic (110 keV) images exhibited better image quality and substantial metal artifact reduction (MAR) compared with the other image sets. The performance of the techniques combined with iMAR was not affected by the size of the implant.

6.
PeerJ ; 12: e17527, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948205

RESUMO

Objective: Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra cost. However, up to now, there is not a high-quality VTE model to steadily predict the risk for VTE in China. Consequently, setting up a prediction model to predict the VTE risk is imperative. Methods: Data from 3,092 patients from December 15, 2017, to December 31, 2022, were retrospectively analyzed. Multiple logistic regression analysis was performed to assess risk factors for GC, and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) and calibration plot was created to evaluate the accuracy of the nomogram. Results: The risk factors of suffering from VTE were older age (OR = 1.02, 95% CI [1.00-1.04]), Karnofsky Performance Status (KPS) ≥ 70 (OR = 0.45, 95% CI [0.25-0.83]), Blood transfusion (OR = 2.37, 95% CI [1.47-3.84]), advanced clinical stage (OR = 3.98, 95% CI [1.59-9.99]), central venous catheterization (CVC) (OR = 4.27, 95% CI [2.03-8.99]), operation (OR = 2.72, 95% CI [1.55-4.77]), fibrinogen degradation product (FDP) >5 µg/mL (OR = 1.92, 95% CI [1.13-3.25]), and D-dimer > 0.5 mg/L (OR = 2.50, 95% CI [1.19-5.28]). The area under the ROC curve (AUC) was 0.82 in the training set and 0.85 in the validation set. Conclusion: Our prediction model can accurately predict the risk of the appearance of VTE in gastric cancer patients and can be used as a robust and efficient tool for evaluating the possibility of VTE.


Assuntos
Nomogramas , Neoplasias Gástricas , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Neoplasias Gástricas/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , China/epidemiologia , Medição de Risco/métodos , Curva ROC , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Adulto
7.
J Asian Nat Prod Res ; : 1-13, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958633

RESUMO

Sesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation.

8.
Medicine (Baltimore) ; 103(25): e38687, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905396

RESUMO

Role conflict is defined as pressures resulting from multiple job requirements that are perceived as incompatible. The purpose of this population-based cross-sectional study was to explore the current situation and influencing factors of high-level role conflict among clinical teachers at 4 affiliated hospitals of 3 medical universities in southern China. A self-administered online questionnaire was used for data collection through an online survey platform. Chi-square tests were used to determine significant differences for categorical variables. Binary logistic regression analysis models were performed for exploring the influencing factors of role conflict in clinical teachers. A total of 208 clinical teachers successfully completed the questionnaires. Of the respondents, 41.3% reportedly had high-level role conflict, and 58.7% had low-level role conflict. The study found that primary, intermediate, and deputy senior professional title, having a leadership position in the department, and devoting a lot of time to teaching work were associated with an increasing risk of the occurrence of high-level role conflict (all P < .05). However, undertaking moderate or few/very few clinical teaching workloads, keeping clinical teachers informed of the teaching requirements, getting guidance and help from colleagues, and thinking of the teaching work as their obligation were significantly associated with decreasing risks of high-level role conflict (all P < .05). Teaching management departments in hospitals might carry out regular and systematic professional training for clinical teachers to effectively decrease role conflict and improve the quality of clinical teaching.


Assuntos
Docentes de Medicina , Humanos , Estudos Transversais , Masculino , Feminino , Adulto , Docentes de Medicina/psicologia , Docentes de Medicina/estatística & dados numéricos , China , Inquéritos e Questionários , Papel Profissional/psicologia , Conflito Psicológico , Carga de Trabalho/psicologia , Pessoa de Meia-Idade , Conflito de Papéis
9.
RSC Adv ; 14(28): 20020-20031, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911829

RESUMO

The structure and properties of graphene/alumina composites are affected by the interface interaction. To demonstrate the influence of interface interaction on the structure of composite materials, a composite without graphene/matrix alumina interface was designed and prepared. We introduced a nano transition layer into the composite by pre-fabricating nano alumina coating on the surface of graphene, thus regulating the influence of interface interaction on the structure of the composite. According to the analysis of laser micro Raman spectroscopy, the structure of graphene was not seriously damaged during the modification process, and graphene was subjected to tensile or compressive stress along the 2D plane. The fracture behavior of the modified graphene/alumina composites is similar to that of pure alumina, but significantly different from that of pure graphene/alumina composites. The elastic modulus and hardness of composite material G/A/A are higher, while its microstructure has better density and uniformity. In situ HRSEM observation showed that there was a transition layer of alumina in the modified graphene/alumina composite. The transition layer blocks or buffers the interfacial stress interaction, therefore, the composite material exhibits a fracture behavior similar to that of pure alumina at this time. This work demonstrates that interface interactions have a significant impact on the structure and fracture behavior of graphene/alumina composites.

10.
Front Chem ; 12: 1381835, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915902

RESUMO

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

11.
Comput Struct Biotechnol J ; 23: 2230-2239, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38827230

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Transgenic and pharmacological AD models are extensively studied to understand AD mechanisms and drug discovery. However, they are time-consuming and relatively costly, which hinders the discovery of potential anti-AD therapeutics. Here, we established a new model of AD in larval zebrafish by co-treatment with aluminum chloride (AlCl3) and D-galactose (D-gal) for 72 h. In particular, exposure to 150 µM AlCl3 + 40 mg/mL D-gal, 200 µM AlCl3 + 30 mg/mL D-gal, or 200 µM AlCl3 + 40 mg/mL D-gal successfully induced AD-like symptoms and aging features. Co-treatment with AlCl3 and D-gal caused significant learning and memory deficits, as well as impaired response ability and locomotor capacity in the plus-maze and light/dark test. Moreover, increased acetylcholinesterase and ß-galactosidase activities, ß-amyloid 1-42 deposition, reduced telomerase activity, elevated interleukin 1 beta mRNA expression, and enhanced reactive oxygen species production were also observed. In conclusion, our zebrafish model is simple, rapid, effective and affordable, incorporating key features of AD and aging, thus may become a unique and powerful tool for high-throughput screening of anti-AD compounds in vivo.

12.
Ren Fail ; 46(2): 2357746, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38832498

RESUMO

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.


Assuntos
Nefropatias Diabéticas , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Nefropatias Diabéticas/microbiologia , Microbioma Gastrointestinal/genética
13.
Nat Commun ; 15(1): 4790, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839752

RESUMO

Cancer cells are often addicted to serine synthesis to support growth. How serine synthesis is regulated in cancer is not well understood. We recently demonstrated protein arginine methyltransferase 1 (PRMT1) is upregulated in hepatocellular carcinoma (HCC) to methylate and activate phosphoglycerate dehydrogenase (PHGDH), thereby promoting serine synthesis. However, the mechanisms underlying PRMT1 upregulation and regulation of PRMT1-PHGDH axis remain unclear. Here, we show the E3 ubiquitin ligase F-box-only protein 7 (FBXO7) inhibits serine synthesis in HCC by binding PRMT1, inducing lysine 37 ubiquitination, and promoting proteosomal degradation of PRMT1. FBXO7-mediated PRMT1 downregulation cripples PHGDH arginine methylation and activation, resulting in impaired serine synthesis, accumulation of reactive oxygen species (ROS), and inhibition of HCC cell growth. Notably, FBXO7 is significantly downregulated in human HCC tissues, and inversely associated with PRMT1 protein and PHGDH methylation level. Overall, our study provides mechanistic insights into the regulation of cancer serine synthesis by FBXO7-PRMT1-PHGDH axis, and will facilitate the development of serine-targeting strategies for cancer therapy.


Assuntos
Carcinoma Hepatocelular , Proteínas F-Box , Neoplasias Hepáticas , Fosfoglicerato Desidrogenase , Proteína-Arginina N-Metiltransferases , Serina , Ubiquitinação , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Serina/metabolismo , Serina/biossíntese , Fosfoglicerato Desidrogenase/metabolismo , Fosfoglicerato Desidrogenase/genética , Linhagem Celular Tumoral , Animais , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Camundongos , Proliferação de Células , Metilação , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Masculino , Células HEK293 , Feminino , Células Hep G2
14.
Biomed Opt Express ; 15(6): 3962-3974, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38867767

RESUMO

Adjuvants are indispensable ingredients in vaccine formulations. Evaluating the in vivo transport processes of adjuvants, particularly for inhalation formulations, presents substantial challenges. In this study, a nanosized adjuvant aluminum hydroxide (AlOOH) was synthesized and labeled with indocyanine green (ICG) and bovine serum albumin (BSA) to achieve strong optical absorption ability and high biocompatibility. The adjuvant nanomaterials (BSA@ICG@AlOOH, BIA) were delivered as an aerosol into the airways of mice, its distribution was monitored using photoacoustic imaging (PAI) in vivo. PAI results illustrated the gradual cross-layer transmission process of BIA in the tracheal layer, traversing approximately 250 µm from the inner layer of the trachea to the outer layer. The results were consistent with pathology. While the intensity of the BIA reduced by approximately 46.8% throughout the transport process. The ability of PAI for quantitatively characterized the dynamic transport process of adjuvant within the tracheal layer may be widely used in new vaccine development.

15.
Adv Mater ; : e2405930, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924191

RESUMO

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency.

16.
Chem Biol Drug Des ; 103(6): e14572, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923686

RESUMO

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti-inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based-virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down-regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE-411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE-411/41415610 play a role in regulating JAK-STAT and AKT-mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR-targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages.


Assuntos
Citocromo P-450 CYP1A1 , Simulação de Acoplamento Molecular , Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Receptores de Hidrocarboneto Arílico/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Animais , Ligantes , Camundongos , Humanos , Transdução de Sinais/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Sítios de Ligação
17.
Neuroscience ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944149

RESUMO

Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice-Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.

18.
Curr Drug Deliv ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38847257

RESUMO

BACKGROUND: Ovarian cancer presents a substantial risk to women's health and lives, with early detection and treatment proving challenging. Targeted nanodelivery systems are viewed as a promising approach to enhance the effectiveness of ovarian cancer treatment and ultrasonic imaging outcomes. OBJECTIVE: A phase-shifted nanodelivery system (NPs) loaded with paclitaxel (PTX) and further conjugated with avidin (Ab) was studied, with the goal of investigating the effects of targeted nanodelivery strategies on the in vitro therapeutic efficacy and ultrasonic imaging of ovarian cancer. This study provides a foundation for future in vivo treatments utilizing this approach. METHODS: PTX-NPs were prepared using the single water-in-oil (O/W) emulsion solvent evaporation method, with avidin coupling achieved through biotin-avidin affinity. The encapsulation efficiency and release profile of PTX were analyzed using UV spectrophotometry. The phase-shift properties of the Ab-PTX-NPs delivery system were evaluated, and the targeting efficiency, cytotoxicity against SKOV3 cells, and in vivo biosafety of various nanodelivery systems were assessed. RESULTS: The prepared nanodelivery system showed a stable and uniform structure with a good particle size distribution and exhibited favorable release characteristics under ultrasound exposure. In vitro experiments revealed that the nanodelivery system displayed excellent targeting and cytotoxic effects against SKOV3 cells, indicating the potential of the Ab-PTX-NPs delivery system for targeted ovarian cancer therapy. In vivo safety studies demonstrated the high biosafety of the prepared nanodelivery system. CONCLUSION: A novel nanodelivery system was developed, and the experimental results obtained provide a solid experimental basis for further research on in vivo ultrasound molecular imaging technology, offering new insights into targeted ultrasound molecular imaging and the treatment of ovarian cancer.

20.
Ren Fail ; 46(2): 2363589, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38874093

RESUMO

PURPOSE: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators. METHODS: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy. RESULTS: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females. CONCLUSIONS: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.


Assuntos
Ingestão de Energia , Estado Nutricional , Diálise Renal , Humanos , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Proteínas Alimentares/administração & dosagem , Adulto , Modelos Lineares , Falência Renal Crônica/terapia , Falência Renal Crônica/fisiopatologia , Força da Mão , Registros de Dieta , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/fisiopatologia
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