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1.
Front Pharmacol ; 15: 1399829, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974033

RESUMO

Ethnopharmacological relevance: Pulsatilla decoction (PD) is a classical prescription for the treatment of ulcerative colitis. Previous studies have demonstrated that the therapeutic efficacy of PD is closely associated with the activation of Farnesoid X receptor (FXR). The activity of FXR is regulated by apical sodium-dependent bile acid transporter (ASBT), and the FXR-ASBT cascade reaction, centered around bile acid receptor FXR, plays a pivotal role in maintaining bile acid metabolic homeostasis to prevent the occurrence and progression of ulcerative colitis (UC). Aim of the study: To elucidate the underlying mechanism by which PD exerts its proteactive effects against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis, focusing on the modulation of FXR and ASBT. Materials and methods: To establish a model of acute ulcerative colitis, BALB/C mice were administered 3.5% DSS in their drinking water for consecutive 7 days. The disease activity index (DAI) was employed to evaluate the clinical symptoms exhibited by each group of mice. Goblet cell expression in colon tissue was assessed using glycogen schiff periodic acid-Schiff (PAS) and alcian blue staining techniques. Inflammatory cytokine expression in serum and colonic tissues was examined through enzyme-linked immunosorbent assay (ELISA). A PCR Array chip was utilized to screen 88 differential genes associated with the FXR-ASBT pathway in UC treatment with PD. Western blotting (WB) analysis was performed to detect protein expression levels of differentially expressed genes in mouse colon tissue. Results: The PD treatment effectively reduced the Disease Activity Index (DAI) score and mitigated colon histopathological damage, while also restoring weight and colon length. Furthermore, it significantly alleviated the severity of ulcerative colitis (UC), regulated inflammation, modulated goblet cell numbers, and restored bile acid balance. Additionally, a PCR Array analysis identified 21 differentially expressed genes involved in the FXR-ASBT pathway. Western blot results demonstrated significant restoration of FXR, GPBAR1, CYP7A1, and FGF15 protein expression levels following PD treatment; moreover, there was an observed tendency towards increased expression levels of ABCB11 and RXRα. Conclusion: The therapeutic efficacy of PD in UC mice is notable, potentially attributed to its modulation of bile acid homeostasis, enhancement of gut barrier function, and attenuation of intestinal inflammation.

2.
Front Vet Sci ; 11: 1390473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835897

RESUMO

Objective: Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies. Methods: The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method. Results: For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result. Conclusion: GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

3.
Comput Biol Med ; 178: 108785, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925089

RESUMO

Variational Autoencoders (VAEs) are an efficient variational inference technique coupled with the generated network. Due to the uncertainty provided by variational inference, VAEs have been applied in medical image registration. However, a critical problem in VAEs is that the simple prior cannot provide suitable regularization, which leads to the mismatch between the variational posterior and prior. An optimal prior can close the gap between the evidence's real and variational posterior. In this paper, we propose a multi-stage VAE to learn the optimal prior, which is the aggregated posterior. A lightweight VAE is used to generate the aggregated posterior as a whole. It is an effective way to estimate the distribution of the high-dimensional aggregated posterior that commonly exists in medical image registration based on VAEs. A factorized telescoping classifier is trained to estimate the density ratio of a simple given prior and aggregated posterior, aiming to calculate the KL divergence between the variational and aggregated posterior more accurately. We analyze the KL divergence and find that the finer the factorization, the smaller the KL divergence is. However, too fine a partition is not conducive to registration accuracy. Moreover, the diagonal hypothesis of the variational posterior's covariance ignores the relationship between latent variables in image registration. To address this issue, we learn a covariance matrix with low-rank information to enable correlations with each dimension of the variational posterior. The covariance matrix is further used as a measure to reduce the uncertainty of deformation fields. Experimental results on four public medical image datasets demonstrate that our proposed method outperforms other methods in negative log-likelihood (NLL) and achieves better registration accuracy.

4.
Phytochemistry ; 225: 114192, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901624

RESUMO

Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC50 values ranging from 1.35 to 5.93 µM, which were more effective than the positive control indomethacin (IC50 = 13.18 µM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα.


Assuntos
Anti-Inflamatórios , Lipopolissacarídeos , Melia , NF-kappa B , Óxido Nítrico , Transdução de Sinais , Triterpenos , Camundongos , Animais , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Estrutura Molecular , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Melia/química , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Casca de Planta/química , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade
5.
Am J Case Rep ; 25: e943721, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886994

RESUMO

BACKGROUND rimary hepatic neuroendocrine neoplasms (PHNEN) are exceedingly rare tumors with atypical clinical manifestations, accounting for less than 0.5% of all neuroendocrine tumors. Currently, there is a lack of consensus on their management, and guidelines do not recommend postoperative chemotherapy for patients with stage G1/G2 disease after curative resection. We present a case report of PHNEN, outlining its diagnostic challenges, treatment strategy, and clinical outcomes. CASE REPORT A 31-year-old man presented with jaundice and was initially diagnosed with suspected IgG4-related disease, which initially appeared to respond to steroid therapy, but manifested worsening jaundice 4 months after initial treatment. Subsequent evaluation revealed a PHNEN NET G2 with lymph node metastasis and invasion of the right hepatic artery; and involvement of the hepatic duct at the hepatic hilum, primarily the left hepatic duct. The patient underwent extended left hemi-hepatectomy with caudate lobe resection, bile duct resection, and lymphadenectomy, followed by reconstruction of the right hepatic artery. Postoperatively, the patient received adjuvant chemotherapy consisting of capecitabine (1000 mg bid D1-14) and temozolomide (200 mg qn D10-14) for 6 cycles. Currently, the patient remains disease free 43 months after treatment. CONCLUSIONS PHNEN presents diagnostic challenges due to its rarity and lack of specific markers. Surgical resection remains the cornerstone of treatment, with chemotherapy being considered in select cases with high-risk features. Further research is needed to refine treatment approaches and improve outcomes for patients with PHNEN.


Assuntos
Hepatectomia , Artéria Hepática , Neoplasias Hepáticas , Tumores Neuroendócrinos , Humanos , Masculino , Adulto , Artéria Hepática/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Tumores Neuroendócrinos/cirurgia
6.
Chem Commun (Camb) ; 60(58): 7487-7490, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38940677

RESUMO

Passivation defects and reducing charge recombination are of great importance in enhancing 2D perovskite solar cells' (PSCs) performance. Herein, a novel additive (TEMPIC) is introduced into 2D PSCs to improve photovoltaic properties of the device, which are mainly attributed to passivated trap-states and reduced charge recombination in device.

7.
Adv Mater ; : e2404495, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762761

RESUMO

CsPbI3 perovskite quantum dot (PQD) shows high potential for next-generation photovoltaics due to their tunable surface chemistry, good solution-processability and unique photophysical properties. However, the remained long-chain ligand attached to the PQD surface significantly impedes the charge carrier transport within the PQD solids, thereby predominantly influencing the charge extraction of PQD solar cells (PQDSCs). Herein, a ligand-induced energy level modulation is reported for band engineering of PQD solids to improve the charge extraction of PQDSCs. Detailed theoretical calculations and systemic experimental studies are performed to comprehensively understand the photophysical properties of the PQD solids dominated by the surface ligands of PQDs. The results reveal that 4-nitrobenzenethiol and 4-methoxybenzenethiol molecules with different dipole moments can firmly anchor to the PQD surface through the thiol group to modulate the energy levels of PQDs, and a gradient band structure within the PQD solid is subsequently realized. Consequently, the band-engineered PQDSC delivers an efficiency of up to 16.44%, which is one of the highest efficiencies of CsPbI3 PQDSCs. This work provides a feasible avenue for the band engineering of PQD solids by tuning the surface chemistry of PQDs for high-performing solar cells or other optoelectronic devices.

8.
Small Methods ; : e2400425, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593370

RESUMO

While the 2D/3D heterojunction is an effective method to improve the power conversion efficiency (PCE) of perovskite solar cells (PSCs), carriers are often confined in the quantum wells (QWs) due to the unique structure of 2D perovskite, which makes the charge transport along the out-of-plane direction difficult. Here, a 2D/3D ferroelectric heterojunction formed by 4,4-difluoropiperidine hydrochloride (2FPD) in inverted PSCs is reported. The enriched 2D perovskite (2FPD)2PbI4 layer with n = 1 on the perovskite surface exhibits ferroelectric response and has oriented dipoles along the out-of-plane direction. The ferroelectricity of the oriented dipole layer facilitates the enhancement of the built-in electric field (1.06 V) and the delay of the cooling process of hot carriers, reflected in the high carrier temperature (above 1400 K) and the prolonged photobleach recovery time (139.85 fs, measured at bandgap), improving the out-of-plane conductivity. In addition, the alignment of energy levels is optimized and exciton binding energy (32.8 meV) is reduced by changing the dielectric environment of the surface. Finally, the 2FPD-treated PSCs achieve a PCE of 24.82% (certified: 24.38%) with the synergistic effect of ferroelectricity and defect passivation, while maintaining over 90% of their initial efficiency after 1000 h of maximum power point tracking.

9.
Chin J Traumatol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38641468

RESUMO

PURPOSE: Intramedullary nailing is the preferred internal fixation technique for the treatment of subtrochanteric fractures because of its biomechanical advantages. However, no definitive conclusion has been reached regarding whether combined cable cerclage is required during intramedullary nailing treatment. This study was performed to compare the clinical effects of intramedullary nailing with cerclage and non-cerclage wiring in the treatment of irreducible spiral subtrochanteric fractures. METHODS: Patients with subtrochanteric fractures admitted to our center from January 2013 to December 2021 were retrospectively analyzed. The patients were enrolled in the case-control study according to the inclusion and exclusion criteria and divided into the non-cerclage group and the cerclage group. The patients' clinical data, including the operative time, intraoperative blood loss, hospital stay, reoperation rate, fracture union time, and Harris hip score, were compared between these 2 groups. Categorical variables were compared using Chi-square or Fisher's exact test. Continuous variables with normal distribution were presented as mean ± standard deviation and analyzed with Student's t-test. Non-normally distributed variables were expressed as median (Q1, Q3) and assessed using the Mann-Whitney test. A p value < 0.05 was considered significant. RESULTS: In total, 69 patients were included in the study (35 patients in the non-cerclage group and 34 patients in the cerclage group). The baseline data of the 2 groups were comparable. There were no significant difference in the length of hospital stay (z = -0.391, p = 0.696), operative time (z = -1.289, p = 0.197), or intraoperative blood loss (z = -1.321, p = 0.186). However, compared with non-cerclage group, the fracture union time was shorter (z = -5.587, p < 0.001), the rate of nonunion was lower (χ2 = 6.030, p = 0.03), the anatomical reduction rate was higher (χ2 = 5.449, p = 0.03), and the Harris hip score was higher (z = -2.99, p = 0.003) in the cerclage group, all with statistically significant differences. CONCLUSIONS: Intramedullary nailing combined with cable cerclage wiring is a safe and reliable technique for the treatment of irreducible subtrochanteric fractures. This technique can improve the reduction effect, increase the stability of fracture fixation, shorten the fracture union time, reduce the occurrence of nonunion, and contribute to the recovery of hip joint function.

10.
Medicine (Baltimore) ; 103(15): e37411, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608087

RESUMO

BACKGROUND: Colonoscopy is a commonly performed gastroenterological procedure in patients associated with anxiety and pain. Various approaches have been used to provide sedation and analgesia during colonoscopy, including patient-controlled analgesia and sedation (PCAS). This study aims to evaluate the feasibility and efficiency of PCAS administered with propofol and remifentanil for colonoscopy. METHODS: This randomized controlled trial was performed in an authorized and approved endoscopy center. A total of 80 outpatients were recruited for the colonoscopy studies. Patients were randomly allocated into PCAS and total intravenous anesthesia (TIVA) groups. In the PCAS group, the dose of 0.1 ml/kg/min of the mixture was injected after an initial bolus of 3 ml mixture (1 ml containing 3 mg of propofol and 10 µg of remifentanil). Each 1 ml of bolus was delivered with a lockout time of 1 min. In the TIVA group, patients were administered fentanyl 1 µg/kg, midazolam 0.02 mg/kg, and propofol (dosage titrated). Cardiorespiratory parameters and auditory evoked response index were continuously monitored during the procedure. The recovery from anesthesia was assessed using the Aldrete scale and the Observer's Assessment of Alertness/Sedation Scale. The Visual Analogue Scale was used to assess the satisfaction of patients and endoscopists. RESULTS: No statistical differences were observed in the Visual Analogue Scale scores of the patients (9.58 vs 9.50) and the endoscopist (9.43 vs 9.30). A significant decline in the mean arterial blood pressure, heart rate, and auditory evoked response index parameters was recorded in the TIVA group (P < 0.05). The recovery time was significantly shorter in the PCAS group than in the TIVA group (P = 0.00). CONCLUSION: The combination of remifentanil and propofol could provide sufficient analgesia, better hemodynamic stability, lighter sedation, and faster recovery in the PCAS group of patients compared with the TIVA group.


Assuntos
Agnosia , Propofol , Humanos , Remifentanil , Midazolam , Analgesia Controlada pelo Paciente , Fentanila , Anestesia Intravenosa , Anestesia Geral , Colonoscopia , Dor
11.
Angew Chem Int Ed Engl ; 63(18): e202401751, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38436532

RESUMO

CsPbI3 perovskite receives tremendous attention for photovoltaic applications due to its ideal band gap and good thermal stability. However, CsPbI3 perovskite solar cells (PSCs) significantly suffer from photovoltage deficits because of serious interfacial energy losses within the PSCs, which to a large extent affects the photovoltaic performance of PSCs. Herein, a dipolar chemical bridge (DCB) is constructed between the perovskite and TiO2 layers to lower interfacial energy losses and thus improve the charge extraction of PSCs. The results reveal that the DCB could form a beneficial interfacial dipole between the perovskite and TiO2 layers, which could optimize the interfacial energetics of perovskite/TiO2 layers and thus improve the energy level alignment within the PSCs. Meanwhile, the constructed DCB could also simultaneously passivate the surface defects of perovskite and TiO2 layers, greatly lowering interfacial recombination. Consequently, the photovoltage deficit of CsPbI3 PSCs is largely reduced, leading to a record efficiency of 21.86 % being realized. Meanwhile, the operation stability of PSCs is also largely improved due to the high-quality perovskite films with released interfacial tensile strain being obtained after forming the DCB within the PSCs.

12.
Front Immunol ; 15: 1368203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545108

RESUMO

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.


Assuntos
Células Espumosas , Traumatismos da Medula Espinal , Humanos , Células Espumosas/patologia , Traumatismos da Medula Espinal/metabolismo , Macrófagos/metabolismo , Sistema Nervoso Central/metabolismo
13.
Chem Biodivers ; 21(5): e202400030, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38511964

RESUMO

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.


Assuntos
Amidas , Ciclo-Oxigenase 2 , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Sulfonamidas , Animais , Camundongos , Células RAW 264.7 , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Estrutura Molecular , Relação Dose-Resposta a Droga , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química
14.
Biomed Chromatogr ; 38(5): e5840, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38402901

RESUMO

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides' intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1-day-old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10-day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high-dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features.


Assuntos
Angelica sinensis , Galinhas , Fígado , Polissacarídeos , Proteômica , Espectrometria de Massas em Tandem , Animais , Angelica sinensis/química , Proteômica/métodos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/análise , Espectrometria de Massas em Tandem/métodos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteoma/análise , Proteoma/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
15.
Chem Biodivers ; 21(3): e202400184, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38372676

RESUMO

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.


Assuntos
Cumarínicos , NF-kappa B , NF-kappa B/metabolismo , Cumarínicos/farmacologia , Cumarínicos/metabolismo , Anti-Inflamatórios/farmacologia , Extratos Vegetais/química , Transdução de Sinais , Lipopolissacarídeos/farmacologia
16.
BMC Complement Med Ther ; 24(1): 47, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245694

RESUMO

BACKGROUND: Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance. METHODS: The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets - LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding. RESULTS: We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells. CONCLUSIONS: Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.


Assuntos
Alcaloides , Neoplasias Pulmonares , Sophora , Neoplasias Pulmonares/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicina Tradicional Tibetana , Fosfatidilinositol 3-Quinases , Alcaloides/farmacologia
17.
Chem Biodivers ; 21(2): e202301703, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38055204

RESUMO

Three undescribed limonoids (1-3), named aglaians G-I, and one new natural product azedaralide (4), together with nine known analogues (5-13) were isolated from the branches and leaves of Aglaia lawii by RP C18 column, silica gel column, Sephadex LH-20 column chromatography and preparative HPLC. The structures of the new compounds were elucidated by IR, HRESIMS, 1D, 2D NMR, electronic circular dichroism (ECD) calculations and X-ray crystallography diffraction analysis. The results of bioassay showed that the compound 12 exhibited potential inhibitory activity against six human tumor cell lines (MDA-MB-231, MCF-7, Ln-cap, A549, HeLa and HepG-2) with IC50 values as 8.0-18.6 µM.


Assuntos
Aglaia , Antineoplásicos , Limoninas , Humanos , Aglaia/química , Limoninas/farmacologia , Limoninas/química , Estrutura Molecular , Linhagem Celular Tumoral
18.
Adv Mater ; 36(1): e2306854, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37729595

RESUMO

Perovskite quantum dots (PQDs) have emerged as one of the most promising candidates for next-generation solar cells owing to its remarkable optoelectronic properties and solution processability. However, the optoelectronic properties of PQDs suffer from severe degradation in storage due to the dynamically binding ligands, predominantly affecting photovoltaic applications. Herein, an in situ defect healing treatment (DHT) is reported to effectively rejuvenate aged PQDs. Systematically, experimental studies and theoretical calculations are performed to fundamentally understand the causes leading to the recovered optoelectronic properties of aged PQDs. The results reveal that the I3 - anions produced from tetra-n-octylammonium iodide and iodine could strongly anchor on the surface matrix defects of aged PQDs, substantially diminishing the nonradiative recombination of photogenerated charge carriers. Meanwhile, an DHT could also renovate the morphology of aged PQDs and thus improve the stacking orientation of PQD solids, substantially ameliorating charge carrier transport within PQD solids. Consequently, by using a DHT, the PQD solar cell (PQDSC) yields a high efficiency of up to 15.88%, which is comparable with the PQDSCs fabricated using fresh PQDs. Meanwhile, the stability of PQDSCs fabricated using the rejuvenated PQDs is also largely improved.

19.
Math Biosci Eng ; 20(11): 19341-19359, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-38052603

RESUMO

Due to the different weed characteristics in peanut fields at different weeding periods, there is an urgent need to study a general model of peanut and weed detection and identification applicable to different weeding periods in order to adapt to the development of mechanical intelligent weeding in fields. To this end, we propose a BEM-YOLOv7-tiny target detection model for peanuts and weeds identification and localization at different weeding periods to achieve mechanical intelligent weeding in peanut fields at different weeding periods. The ECA and MHSA modules were used to enhance the extraction of target features and the focus on predicted targets, respectively, the BiFPN module was used to enhance the feature transfer between network layers, and the SIoU loss function was used to increase the convergence speed and efficiency of model training and to improve the detection performance of the model in the field. The experimental results showed that the precision, recall, mAP and F1 values of the BEM-YOLOv7-tiny model were improved by 1.6%, 4.9%, 4.4% and 3.2% for weed targets and 1.0%, 2.4%, 2.2% and 1.7% for all targets compared with the original YOLOv7-tiny. The experimental results of positioning error show that the peanut positioning offset error detected by BEM-YOLOv7-tiny is less than 16 pixels, and the detection speed is 33.8 f/s, which meets the requirements of real-time seedling grass detection and positioning in the field. It provides preliminary technical support for intelligent mechanical weeding in peanut fields at different stages.

20.
Sci Adv ; 9(48): eadj2801, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38039360

RESUMO

The analysis of proteins in the gas phase benefits from detectors that exhibit high efficiency and precise spatial resolution. Although modern secondary electron multipliers already address numerous analytical requirements, additional methods are desired for macromolecules at energies lower than currently used in post-acceleration detection. Previous studies have proven the sensitivity of superconducting detectors to high-energy particles in time-of-flight mass spectrometry. Here, we demonstrate that superconducting nanowire detectors are exceptionally well suited for quadrupole mass spectrometry and exhibit an outstanding quantum yield at low-impact energies. At energies as low as 100 eV, the sensitivity of these detectors surpasses conventional ion detectors by three orders of magnitude, and they offer the possibility to discriminate molecules by their impact energy and charge. We demonstrate three developments with these compact and sensitive devices, the recording of 2D ion beam profiles, photochemistry experiments in the gas phase, and advanced cryogenic electronics to pave the way toward highly integrated detectors.

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