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1.
J Environ Sci (China) ; 147: 22-35, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003042

RESUMEN

High temperatures and providing sufficient time for the thermal desorption of persistent organic pollutants (POPs) from contaminated clay soils can lead to intensive energy consumption. Therefore, this article provides a critical review of the potential additives which can improve soil texture and increase the volatility of POPs, and then discusses their enhanced mechanisms for contributing to a green economy. Ca-based additives have been used to reduce plasticity of bentonite clay, absorb water and replenish system heat. In contrast, non-Ca-based additives have been used to decrease the plasticity of kaolin clay. The soil structure and soil plasticity can be changed through cation exchange and flocculation processes. The transition metal oxides and alkali metal oxides can be applied to catalyze and oxidize polycyclic aromatic hydrocarbons, petroleum and emerging contaminants. In this system, reactive oxygen species (•O2- and •OH) are generated from thermal excitation without strong chemical oxidants. Moreover, multiple active ingredients in recycled solid wastes can be controlled to reduce soil plasticity and enhance thermal catalysis. Alternatively, the alkali, nano zero-valent iron and nano-TiN can catalyze hydrodechlorination of POPs under reductive conditions. Especially, photo and photo-thermal catalysis are discussed to accelerate replacement of fossil fuels by renewable energy in thermal remediation.


Asunto(s)
Arcilla , Restauración y Remediación Ambiental , Contaminantes del Suelo , Suelo , Arcilla/química , Suelo/química , Catálisis , Contaminantes del Suelo/química , Restauración y Remediación Ambiental/métodos , Calor
2.
Redox Biol ; 75: 103273, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39142180

RESUMEN

Malic enzymes (MEs) are metabolic enzymes that catalyze the oxidation of malate to pyruvate and NAD(P)H. While researchers have well established the physiological metabolic roles of MEs in organisms, recent research has revealed a link between MEs and carcinogenesis. This review collates evidence of the molecular mechanisms by which MEs promote cancer occurrence, including transcriptional regulation, post-transcriptional regulation, post-translational protein modifications, and protein-protein interactions. Additionally, we highlight the roles of MEs in reprogramming energy metabolism, suppressing senescence, and modulating the tumor immune microenvironment. We also discuss the involvement of these enzymes in mediating tumor resistance and how the development of novel small-molecule inhibitors targeting MEs might be a good therapeutic approach. Insights through this review are expected to provide a comprehensive understanding of the intricate relationship between MEs and cancer, while facilitating future research on the potential therapeutic applications of targeting MEs in cancer management.


Asunto(s)
Metabolismo Energético , Malato Deshidrogenasa , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/genética , Malato Deshidrogenasa/metabolismo , Malato Deshidrogenasa/antagonistas & inhibidores , Malato Deshidrogenasa/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Microambiente Tumoral , Animales , Procesamiento Proteico-Postraduccional , Oxidación-Reducción
3.
World J Psychiatry ; 14(8): 1174-1181, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39165560

RESUMEN

BACKGROUND: Bipolar disorder (BD) is a severe mental illness. BD often coexists with borderline personality disorders, making the condition more complex. AIM: To explore the differences in cognitive impairment between patients with BD and those with BD comorbid with borderline personality disorder. METHODS: Eighty patients with BD and comorbid borderline personality disorder and 80 patients with BD alone were included in groups A and B, respectively, and 80 healthy volunteers were included as controls. Cognitive function in each group was evaluated using the Chinese version of the repeatable battery for the assessment of neuropsychological status (RBANS), the Stroop color-word test, and the Wechsler intelligence scale-revised (WAIS-RC). RESULTS: The indices of the RBANS, Stroop color-word test, and WAIS-RC in groups A and B were significantly lower than those of the control group (P < 0.05). Group A had significantly longer Stroop color-word test times for single-character, single-color, double-character, and double-color, lower scores of immediate memory, visual breadth, verbal function dimensions and total score of the RBANS, as well as lower scores of verbal IQ, performance IQ, and overall IQ of the WAIS-RC compared with group B (P < 0.05). Compared to group B, group A exhibited significantly longer single-character time, single-color time, double-character time, and double-color time in the Stroop color-word test (P < 0.05). CONCLUSION: The cognitive function of patients with BD complicated with borderline personality disorder is lower than that of patients with BD.

4.
RSC Adv ; 14(35): 25793-25801, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39156746

RESUMEN

MXenes as an emerging class of 2D materials have great potential in fabricating functional polymer nanocomposites. In this study, Ti3C2T x MXene as a representative MXene filler was employed to prepare sPS nanocomposites. The abundant surface groups (mainly -OH) on MXene allowed facile modification, and thus MXene nanosheets bearing -C12H25 groups were prepared using dodecyl triethoxysiloxane (DCTES) as a modifier. Grafting -C12H25 long alkyl chains onto the surface of MXene strongly affected its affinity towards hydrophobic solvent and the sPS matrix. The rheological threshold concentration (ϕ c,G' = 0.033 vol%) and exponent (ß G' = 1.51) and the conductivity threshold concentration (ϕ c,σ = 0.259 vol%) and exponent (ß σ = 2.92) were determined by applying percolation scaling laws. The influences of DCTES-modified MXene on the polymorphism, mechanical, thermal and flammability properties of nanocomposites were studied. The obtained nanocomposites displayed not only enhanced mechanical properties, but also improved thermal stability and flame retardancy to some extent. Moreover, the higher the loading level of DCTES-modified MXene, the better was the improved effect.

5.
Orthop Surg ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39139066

RESUMEN

OBJECTIVES: Cervical spondylosis may lead to changes in the sagittal parameters of the neck and trigger compensatory alterations in systemic sagittal parameters. However, there is currently a dearth of comparative research on the changes and compensatory alterations to sagittal parameters resulting from different types of cervical spondylosis. This study compared the preoperative sagittal alignment sequences among patients with cervical spondylotic radiculopathy (CSR), ossification of the posterior longitudinal ligament (OPLL), and cervical spondylotic myelopathy (CSM) caused by factors resulting from non-OPLL factors. MATERIALS AND METHODS: Full length lateral X-ray of the spine and cervical computed tomography (CT) of 256 patients (134 men, 122 women; mean age, 56.9 ± 9.5 years) were analyzed retrospectively. A total of 4096 radiomics features were measured through the lateral X-ray by two spinal surgeons with extensive experience. The clinical symptoms measures were the Japanese Orthopaedic Association (JOA) score, number of hand actions in 10 s, hand-grip strength, visual analog scale (VAS) score. Normally distributed data was compared using one-way analysis of variance (ANOVA) for parametric variables and χ2 test were used to analyze the categorical data. RESULTS: In the OPLL group, the C2-C7 Cobb angle was greater than in the CSR and CSM groups (19.8 ± 10.4°, 13.3 ± 10.3°, and 13.9 ± 9.9°, respectively, p < 0.001). Additionally, the C7-S1 SVA measure was found to be situated in the anterior portion with regards to the CSM and CSR groups (19.7 ± 58.4°, -6.3 ± 34.3° and -26.3 ± 32.9°, p < 0.001). Moreover, the number of individuals with C7-S1 SVA >50 mm was significantly larger than the CSM group (26/69, 11/83, p < 0.001). In the CSR group, the TPA demonstrated smaller values compared to the OPLL group (8.8 ± 8.5°, 12.7 ± 10.2°, p < 0.001). Furthermore, the SSA was comparatively smaller as opposed to both the OPLL and CSM groups (49.6 ± 11.2°, 54.2 ± 10.8° and 54.3 ± 9.3°, p < 0.05). CONCLUSION: Patients with OPLL exhibit greater cervical lordosis than those with CSR and CSM. However, OPLL is more likely to result in spinal imbalance when compared to the CSM group. Furthermore, OPLL and CSM patients exhibit anterior trunk inclination and worse global spine sagittal parameters in comparison to CSR patients.

6.
Front Chem ; 12: 1389694, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39148666

RESUMEN

The continuous preparation scheme EPO-Poly-indol-nido-carborane (E-P-INDOLCAB), L100-55-Poly-indol-nido-carborane (L-P-INDOLCAB), RS-Poly-indol-nido-carborane (S-P-INDOLCAB), and RL-Poly-indol-nido-carborane (R-P-INDOLCAB) were used to prepare the four types of acrylic resin-coated nido-carborane indole fluorescent polymers. After testing their spectral properties and the fluorescence stability curve trend at various acidic pH values (3.4 and 5.5, respectively), L-P-INDOLCAB and S-P-INDOLCAB were determined to be the best polymers. The stable states of the two polymers and the dispersion of the nanoparticles on the system's surface during Atomic Force Microscope (AFM) test are shown by the zeta potentials of -23 and -42 mV. The dispersion of nanoparticles on the system's surface and the stable condition of the two polymers were examined using zeta potential and atomic force microscopy (AFM). Transmission electron microscopy (TEM) can also confirm these findings, showing that the acrylic resin securely encases the interior to form an eyeball. Both polymers' biocompatibility with HELA cells was enhanced in cell imaging, closely enclosing the target cells. The two complexes displayed strong inhibitory effects on PC-3 and HeLa cells when the concentration was 20 ug/mL, as validated by subsequent cell proliferation toxicity studies.

7.
Food Chem ; 460(Pt 2): 140660, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39089029

RESUMEN

This study utilized computational simulation and surface molecular imprinting technology to develop a magnetic metal-organic framework molecularly imprinted polymer (Fe3O4@ZIF-8@SMIP) capable of selectively recognizing and detecting multiple fluoroquinolones (FQs). The Fe3O4@ZIF-8@SMIP material was synthesized using the "common" template-ofloxacin, identified by computational simulation, demonstrating notable adsorption capacity (88.61-212.93 mg g-1) and rapid mass-transfer features (equilibration time: 2-3 min) for all tested FQs, consistent with Langmuir adsorption model. Subsequently, this material was employed as a magnetic solid-phase-extraction adsorbent for adsorption and detection of multiple FQs by combining with high performance liquid chromatography. The developed method exhibited good linearity for various FQs within the concentration range of 0.1-500 µg L-1, with low limit of detection (0.0605-0.1529 µg L-1) and limit of quantitation (0.2017-0.5097 µg L-1). Satisfactory recoveries (88.38-103.44%) were obtained when applied to spiked food samples, demonstrating the substantial potential of this Fe3O4@ZIF-8@SMIP material for rapid enrichment and identification for multiple FQs residues.

8.
Int J Biol Macromol ; 277(Pt 4): 134515, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39106627

RESUMEN

Spherical nucleic acids (SNAs) are nanostructures with the DNA arranged radially on the surface, thus allowing specific binding with cancer cells expressing high levels of scavenger receptor-A to enhance cellular uptake. However, conventional carriers for SNAs are cytotoxic, not degradable and difficult to deliver multiple payloads. In this study, we developed charge-reversible coordination-crosslinked SNAs to deliver dual anti-cancer genes and ferroptosis payload for anti-cancer purposes. To this end, we modified poly(lactic acid) (PLA) with functionalized side chains to allow its binding with antisense oligonucleotides (ASOs) and siRNA, annealed two single-stranded RNAs to obtain double-stranded RNA, and introduced a polyethylene glycol (PEG) shell to enhance the circulation time. Additionally, the ferroptosis payload imidazole was coordinated with iron ions as a core-crosslinked group to enhance the stability of SNAs and efficiency to kill cancer cells. We demonstrated that this novel nanocomplex efficiently internalized and killed CT-26 cells in vitro. In vivo data confirmed that the dual gene delivery system successfully targeted CT-26 tumors in tumor-bearing BALB/c mice, and exhibited strong tumor suppression ability, without inducing adverse toxic effects. Taken together, our dual gene therapy system offered an enhanced anti-tumor solution by simultaneously delivering dual anti-cancer genes and ferroptosis payload in tumor microenvironment.

9.
Med Image Anal ; 97: 103281, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39106764

RESUMEN

Imbalanced classification is a common and difficult task in many medical image analysis applications. However, most existing approaches focus on balancing feature distribution and classifier weights between classes, while ignoring the inner-class heterogeneity and the individuality of each sample. In this paper, we proposed a sample-specific fine-grained prototype learning (SFPL) method to learn the fine-grained representation of the majority class and learn a cosine classifier specifically for each sample such that the classification model is highly tuned to the individual's characteristic. SFPL first builds multiple prototypes to represent the majority class, and then updates the prototypes through a mixture weighting strategy. Moreover, we proposed a uniform loss based on set representations to make the fine-grained prototypes distribute uniformly. To establish associations between fine-grained prototypes and cosine classifier, we propose a selective attention aggregation module to select the effective fine-grained prototypes for final classification. Extensive experiments on three different tasks demonstrate that SFPL outperforms the state-of-the-art (SOTA) methods. Importantly, as the imbalance ratio increases from 10 to 100, the improvement of SFPL over SOTA methods increases from 2.2% to 2.4%; as the training data decreases from 800 to 100, the improvement of SFPL over SOTA methods increases from 2.2% to 3.8%.

11.
J Transl Med ; 22(1): 738, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103838

RESUMEN

BACKGROUND: High levels of lactate are positively associated with prognosis and mortality in pulmonary hypertension (PH). Lactate dehydrogenase A (LDHA) is a key enzyme for the production of lactate. This study is undertaken to investigate the role and molecular mechanisms of lactate and LDHA in PH. METHODS: Lactate levels were measured by a lactate assay kit. LDHA expression and localization were detected by western blot and Immunofluorescence. Proliferation and migration were determined by CCK8, western blot, EdU assay and scratch-wound assay. The right heart catheterization and right heart ultrasound were measured to evaluate cardiopulmonary function. RESULTS: In vitro, we found that lactate promoted proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in an LDHA-dependent manner. In vivo, we found that LDHA knockdown reduced lactate overaccumulation in the lungs of mice exposed to hypoxia. Furthermore, LDHA knockdown ameliorated hypoxia-induced vascular remodeling and right ventricular dysfunction. In addition, the activation of Akt signaling by hypoxia was suppressed by LDHA knockdown both in vivo and in vitro. The overexpression of Akt reversed the inhibitory effect of LDHA knockdown on proliferation in PASMCs under hypoxia. Finally, LDHA inhibitor attenuated vascular remodeling and right ventricular dysfunction in Sugen/hypoxia mouse PH model, Monocrotaline (MCT)-induced rat PH model and chronic hypoxia-induced mouse PH model. CONCLUSIONS: Thus, LDHA-mediated lactate production promotes pulmonary vascular remodeling in PH by activating Akt signaling pathway, suggesting the potential role of LDHA in regulating the metabolic reprogramming and vascular remodeling in PH.


Asunto(s)
Proliferación Celular , Hipertensión Pulmonar , L-Lactato Deshidrogenasa , Lactato Deshidrogenasa 5 , Ácido Láctico , Ratones Endogámicos C57BL , Arteria Pulmonar , Remodelación Vascular , Animales , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Lactato Deshidrogenasa 5/metabolismo , Masculino , Ácido Láctico/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Arteria Pulmonar/patología , Arteria Pulmonar/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Movimiento Celular , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Hipoxia/complicaciones , Hipoxia/metabolismo , Transducción de Señal , Técnicas de Silenciamiento del Gen , Ratones , Hipoxia de la Célula , Ratas Sprague-Dawley , Ratas , Humanos , Pulmón/patología , Pulmón/irrigación sanguínea
12.
Front Neurosci ; 18: 1407775, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108313

RESUMEN

Introduction: Noise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss. Methods: Twenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions. Results: NR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity. Discussion: Individuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.

13.
Int J Rheum Dis ; 27(8): e15285, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39114972

RESUMEN

OBJECTIVE: To investigate the age-standardized prevalence rate (ASPR) and temporal trends for hip, knee, hand, and other osteoarthritis (OA) at a global, continental, and national level. DESIGN: The estimates and 95% uncertainty intervals (UIs) for case number and ASPR of OA were derived from the Global Burden of Diseases Study (GBD) 2019. The joinpoint regression analysis was utilized to examine the temporal trends from 1990 to 2019. RESULTS: In 2019, the global ASPR of hip, knee, hand, and other OA was 400.95 (95% UI: 312.77-499.41), 4375.95 (95% UI: 3793.04-5004.9), 1726.38 (95% UI: 1319.91-2254.85), and 745.62 (95% UI: 570.16-939.8). As for the ASPR of hip OA, hand OA, and other OA, Europe and America had higher rates than Asia and Africa, and Asia was second only to America in knee OA ASPRs. The period 1990-2019, the ASPR at global level dropped significantly for hand OA (AAPC = -0.4%, 95% CI: -0.47 to -0.34) and increased significantly for hip OA (AAPC = 0.43%, 95% CI: 0.39-0.46), knee OA (AAPC = 0.17%, 95% CI: 0.09-0.24) and other OA (AAPC = 0.16%, 95% CI: 0.15-0.17). Different continents, countries, and periods demonstrated significant changes. CONCLUSIONS: Globally, America has the highest OA burden and Asia has a higher knee OA burden. Appropriate prevention and control measures to reduce modifiable risk factors are needed to reduce the burden of OA.


Asunto(s)
Carga Global de Enfermedades , Osteoartritis , Humanos , Prevalencia , Carga Global de Enfermedades/tendencias , Femenino , Masculino , Persona de Mediana Edad , Anciano , Osteoartritis/epidemiología , Osteoartritis/diagnóstico , Factores de Tiempo , Adulto , Salud Global , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/diagnóstico , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/diagnóstico , Distribución por Edad , Distribución por Sexo
14.
Nanomaterials (Basel) ; 14(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39120387

RESUMEN

Manganese dioxide (MnO2) nanomaterials have shown excellent performance in catalytic degradation and other fields because of their low density and great specific surface area, as well as their tunable chemical characteristics. However, the methods used to synthesize MnO2 nanomaterials greatly affect their structures and properties. Therefore, the present work systematically illustrates common synthetic routes and their advantages and disadvantages, as well as examining research progress relating to electrochemical applications. In contrast to previous reviews, this review summarizes approaches for preparing MnO2 nanoparticles and describes their respective merits, demerits, and limitations. The aim is to help readers better select appropriate preparation methods for MnO2 nanomaterials and translate research results into practical applications. Finally, we also point out that despite the significant progress that has been made in the development of MnO2 nanomaterials for electrochemical applications, the related research remains in the early stages, and the focus of future research should be placed on the development of green synthesis methods, as well as the composition and modification of MnO2 nanoparticles with other materials.

15.
Food Chem ; 460(Pt 3): 140774, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39121765

RESUMEN

The development of a highly selective and sensitive method for detecting chlortetracycline (CTC) is crucial for safeguarding public health and food safety. Herein, a novel ratiometric fluorescence sensor called SiC@ZIF-8@MIP was constructed to specifically recognize and sensitively detect CTC. The sensor has the advantages of fast response speed (7 min), wide linear range (0.1-18 µg mL-1), and low limit of detection (4.56 ng mL-1). With the addition of CTC, the fluorescence of SiC@ZIF-8@MIP is quenched at 410 nm due to the internal filtration effect (IFE) and a new fluorescence signal is generated at 515 nm by CTC due to the aggregation induced emission effect (AIE). Additionally, for rapid on-site detection of CTC, a smartphone is applied to digitize fluorescence images of SiC@ZIF-8@MIP, helping individuals read and analyze the images. This detection method is a promising strategy for on-site assessments of food safety and public health safety.

17.
J Biol Chem ; : 107672, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128723

RESUMEN

The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinases (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.

18.
Food Chem ; 461: 140864, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173255

RESUMEN

The frequent intake of ultra-processed, heat-processed, and fat-enriched foods rich in dietary advanced lipoxidation end-products (ALEs) has been correlated with cognitive decline; however, the underlying mechanisms of action remain unexplored. This study investigated the impact of a 12-month dietary exposure to ALEs on learning, memory, and Aß1-42 accumulation in mice, with a focus on the AMPK/SIRT1 signaling pathway and ADAM10 expression. The gut microbiota and metabolomic profiles revealed ALEs-induced gut dysbiosis and cognitive impairment, highlighting modulation through the microbiota-gut-brain axis. Key findings include increased pathogenic bacteria and decreased beneficial bacteria, linked to metabolite profile changes that affect neurotoxic Aß1-42 peptide accumulation. This long-term comprehensive study underscores the need for dietary guidelines to reduce ALE intake and mitigate neurodegenerative disease risk, highlighting the intricate interplay between diet, gut microbiota, and cognitive health.

19.
Eur J Med Chem ; 277: 116784, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39178727

RESUMEN

Antimicrobial resistance has emerged as a significant threat to global public health. To develop novel, high efficiency antibacterial alternatives to combat multidrug-resistant bacteria, A total of thirty-two novel amphiphilic benzopyran derivatives by mimicking the structure and function of antimicrobial peptides were designed and synthesized. Among them, the most promising compounds 4h and 17e displayed excellent antibacterial activity against Gram-positive bacteria (MICs = 1-4 µg/mL) with weak hemolytic activity and good membrane selectivity. Additionally, compounds 4h and 17e had rapid bactericidal properties, low resistance frequency, good plasma stability, and strong capabilities of inhibiting and eliminating bacterial biofilms. Mechanistic studies revealed that compounds 4h and 17e could effectively disrupt the integrity of bacterial cell membranes, and accompanied by an increase in intracellular reactive oxygen species and the leakage of proteins and DNA, ultimately leading to bacterial death. Notably, compound 4h exhibited comparable in vivo antibacterial potency in a mouse septicemia model infected by Staphylococcus aureus ATCC43300, as compared to vancomycin. These findings indicated that 4h might be a promising antibacterial candidate to combat antimicrobial resistance.

20.
Fitoterapia ; 178: 106189, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39154852

RESUMEN

Swertia Mussotti is used as febrifuge, analgesic and to treat calculous cholecystitis, however, the underling mechanism remains unclear. This study investigates the therapeutic effect of the active fraction named iridoid and xanthone glycoside (IXG) extracted from S. mussotii on six animal models related to calculous cholecystitis and its complications, and to explore its potential target proteins. Four main compounds including swertiamarin (STR), sweroside (SRS), gentiopicroside (GPS) and mangiferin (MGR) were identified from the IXG by UHPLC-TOF-MS. The in vivo experiments results confirmed that IXG significantly decreased the level of total bilirubin (TBIL), direct bilirubin (DBIL) and cyclooxygenase-2 (COX2) in calculous cholecystitis. IXG treatment dramatically reduced the number of twists and the time of clicking foot in 2nd phase induced by glacial acetic acid and formalin, however, no effect was showed on central pain established by hot plate test. IXG also significantly decreased the anal temperature induced by yeast and 2,4-dinitrophenol. These results indicated that IXG alleviate calculous cholecystitis and its clinical symptom. In addition, IXG suppressed the expression of Prostaglandin E2 (PGE2) in vitro. Mechanistically, COX2 was identified as the direct target of IXG in RAW264.7 cells, and downregulated the protein levels of COX2. The results confirmed that IXG ameliorates calculous cholecystitis and its clinical symptom (pain and fever) by suppressing the production of PGE2 through targeting COX2.

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