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1.
Fitoterapia ; 176: 106010, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740341

RESUMEN

Flowers of Hosta plantaginea (H. plantaginea), a widely utilized medicinal herb in Mongolian medicine, holds a significant historical background in terms of its medicinal applications. This herb is renowned for its ability to clear heat and detoxify the body, alleviate cough, and provide relief to the throat. However, the active ingredients and the potential mechanism of action remain ambiguity. The objective of this study was to conduct a comprehensive analysis of the efficacy of H. plantaginea in treating pneumonia, identify its active ingredients and unveil the pharmacological mechanism in the treatment of pneumonia. In vivo experiments demonstrate the plant's anti-pneumonia properties, while mass spectrometry analysis identifies 62 chemicals, with 14 absorbed into the bloodstream. Network pharmacology and Venn analysis reveal 195 targets of 52 active ingredients, with 49 gene targets common to H. plantaginea and pneumonia. Protein-protein interaction (PPI) network construction and enrichment analysis highlight the key targets and pathways such as AKT, EGFR, IL-17. Western blotting confirms downregulation of these pathways, indicating the anti-inflammatory effects of H. plantaginea in treating acute lung injury. Our findings showed that the treatment of ALI with the H. plantaginea exerts its anti-inflammatory effects through multiple components, targets, and pathways. This study established a solid experimental foundation for investigating the various components, targets, and pathways involved in the treatment of pneumonia using H. plantaginea. It offers valuable insights from multiple perspectives and can serve as a reference for the clinical application of this plant in pneumonia treatment.

2.
J Med Chem ; 67(9): 7569-7584, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38690687

RESUMEN

PTP1B, a promising target for insulin sensitizers in type 2 diabetes treatment, can be effectively degraded using proteolysis-targeting chimera (PROTAC). This approach offers potential for long-acting antidiabetic agents. We report potent bifunctional PROTACs targeting PTP1B through the E3 ubiquitin ligase cereblon. Western blot analysis showed significant PTP1B degradation by PROTACs at concentrations from 5 nM to 5 µM after 48 h. Evaluation of five highly potent PROTACs revealed compound 75 with a longer PEG linker (23 atoms), displaying remarkable degradation activity after 48 and 72 h, with DC50 values of 250 nM and 50 nM, respectively. Compound 75 induced selective degradation of PTP1B, requiring engagement with both the target protein and CRBN E3 ligase, in a ubiquitination and proteasome-dependent manner. It significantly reduced blood glucose AUC0-2h to 29% in an oral glucose tolerance test and activated the IRS-1/PI3K/Akt signaling pathway in HepG2 cells, showing promise for long-term antidiabetic therapy.


Asunto(s)
Hipoglucemiantes , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteolisis , Animales , Humanos , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Descubrimiento de Drogas , Células Hep G2 , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/síntesis química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteolisis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo
3.
ACS Chem Neurosci ; 15(10): 2042-2057, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38656184

RESUMEN

Based on the neuroprotection of butylphthalide and donepezil, a series of indanone/benzofuranone and piperidine hybrids were designed and synthesized for assessment of their neuroprotective activities, aiming to enhance the bioavailability and therapeutic efficacy of natural phthalide analogues. Within this study, it was observed that most indanone derivatives bearing 1-methylpiperidine in the tail segment demonstrated superior neuroprotective effects on the oxygen glucose deprivation/reperfusion (OGD/R)-induced rat primary neuronal cell injury model in vitro compared to benzofuranone compounds. Among the synthesized compounds, 11 (4, 14, 15, 22, 26, 35, 36, 37, 48, 49, and 52) displayed robust cell viabilities in the OGD/R model, along with favorable blood-brain barrier permeability as confirmed by the parallel artificial membrane permeability assay. Notably, compound 4 showed significant neuronal cell viabilities within the concentration range of 3.125 to 100 µM, without inducing cytotoxicity. Further results from in vivo middle cerebral artery occlusion/R experiments revealed that 4 effectively ameliorated ischemia-reperfusion injury, reducing the infarct volume to 18.45% at a dose of 40 mg/kg. This outcome suggested a superior neuroprotective effect compared to edaravone at 20 mg/kg, further highlighting the potential therapeutic efficacy of compound 4 in addressing neurological disorders.


Asunto(s)
Benzofuranos , Indanos , Fármacos Neuroprotectores , Piperidinas , Animales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/síntesis química , Piperidinas/farmacología , Piperidinas/síntesis química , Piperidinas/química , Indanos/farmacología , Indanos/síntesis química , Indanos/química , Benzofuranos/farmacología , Benzofuranos/síntesis química , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Masculino , Supervivencia Celular/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico
4.
Appl Microbiol Biotechnol ; 108(1): 292, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38592514

RESUMEN

Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.


Asunto(s)
Microbioma Gastrointestinal , Úlceras Bucales , Humanos , Animales , Ratas , ARN Ribosómico 16S/genética , Mucosa Bucal , Biomarcadores
5.
RSC Adv ; 14(18): 12556-12560, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38638814

RESUMEN

Selenium-containing compounds are important scaffolds owing to their value in medicinal chemistry, biochemistry and material chemistry. Herein, we report an electrochemical approach to access seleno-benzazepines through an oxidative radical cascade cyclization of dienes with diselenides under metal-free, external oxidant-free and base-free conditions. In a simple undivided cell, various dienes and diselenides were suitable for this transformation, generating the desired products in up to 84% yields. This method provides a green and convenient route for the synthesis of valuable selenium-containing seven-membered N-heterocycles from simple starting materials.

6.
ACS Appl Mater Interfaces ; 16(15): 19205-19213, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38591860

RESUMEN

An artificial nociceptor, as a critical and special bionic receptor, plays a key role in a bioelectronic device that detects stimuli and provides warnings. However, fully exploiting bioelectronic applications remains a major challenge due to the lack of the methods of implementing basic nociceptor functions and nociceptive blockade in a single device. In this work, we developed a Pt/LiSiOx/TiN artificial nociceptor. It had excellent stability under the 104 endurance test with pulse stimuli and exhibited a significant threshold current of 1 mA with 1 V pulse stimuli. Other functions such as relaxation, inadaptation, and sensitization were all realized in a single device. Also, the pain blockade function was first achieved in this nociceptor with over a 25% blocking degree, suggesting a self-protection function. More importantly, an obvious depression was activated by a stimulus over 1.6 V due to the cooperative effects of both lithium ions and oxygen ions in LiSiOx and the dramatic accumulation of Joule heat. The conducting channel ruptured partially under sequential potentiation, thus achieving nociceptive blockade, besides basic functions in one single nociceptor, which was rarely reported. These results provided important guidelines for constructing high-performance memristor-based artificial nociceptors and opened up an alternative approach to the realization of bioelectronic systems for artificial intelligence.


Asunto(s)
Inteligencia Artificial , Nociceptores , Humanos , Nociceptores/fisiología , Dolor , Biónica , Iones/farmacología
7.
Acta Pharm Sin B ; 14(4): 1661-1676, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38572101

RESUMEN

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this study, we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels. Our results demonstrated that RA significantly alleviated renal tubular epithelial injury, particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes, while attenuating the inflammatory response of macrophages, oxidative stress, and cytotoxicity of natural killer cells. These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage, oxidative stress, and inflammation, offering valuable guidance for the clinical application of RA in the treatment of DN.

8.
J Ethnopharmacol ; 328: 118082, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38522625

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Longdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute bronchitis and asthma. In Chinese traditional medicine, some herbal formulas with anti-inflammatory properties targeting the respiratory system are clinically adopted as supplementary therapies for chronic obstructive pulmonary disease (COPD). However, the specific anti-COPD effects of LDZK remain to be evaluated. AIM OF THE STUDY: The aim of this study is to identify the principal bioactive compounds in LDZK, and elucidate the effects and mechanisms of the LDZK on COPD. METHODS: High-resolution mass spectrometry was utilized for a comprehensive characterization of the chemical composition of LDZK. The therapeutic effects of LDZK were assessed on the LPS-papain-induced COPD mouse model, and LPS-induced activation model of A549 cells. The safety of LDZK was evaluated by orally administering a single dose of 30 g/kg to rats and monitoring physiological and biochemical indicators after a 14-day period. Network pharmacology and Western blot analysis were employed for mechanism prediction of LDZK. RESULTS: A comprehensive analysis identified a total of 45 compounds as the major constituents of LDZK. Oral administration of LDZK resulted in notable ameliorative effects in respiratory function, accompanied by reduced inflammatory cell counts and cytokine levels in the lungs of COPD mice. Acute toxicity tests demonstrated a favorable safety profile at a dose equivalent to 292 times the clinically prescribed dose. In vitro studies revealed that LDZK exhibited protective effects on A549 cells by mitigating LPS-induced cellular damage, reducing the release of NO, and downregulating the expression of iNOS, COX2, IL-1ß, IL-6, and TNF-α. Network pharmacology and Western blot analysis indicated that LDZK primarily modulated the MAPK signaling pathway and inhibited the phosphorylation of p38/ERK/JNK. CONCLUSIONS: LDZK exerts significant therapeutic effects on COPD through the regulation of the MAPK pathway, suggesting its potential as a promising adjunctive therapy for the treatment of chronic inflammation in COPD.


Asunto(s)
Medicina Tradicional Tibetana , Enfermedad Pulmonar Obstructiva Crónica , Ratas , Ratones , Animales , Lipopolisacáridos/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Pulmón , Transducción de Señal
9.
Food Chem ; 445: 138648, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354639

RESUMEN

This research investigates the formation of amyloid fibrils using enzymatically hydrolyzed peptides from gluten, including its components glutenin and gliadin. After completing the fibrillation incubation, the gluten group demonstrated the most significant average particle size (908.67 nm) and conversion ratio (57.64 %), with a 19.21 % increase in thioflavin T fluorescence intensity due to self-assembly. The results indicated increased levels of ß-sheet structures after fibrillation. The gliadin group exhibited the highest zeta potential (∼13 mV) and surface hydrophobicity (H0 = 809.70). Around 71.15 % of predicted amyloidogenic regions within gliadin peptides showed heightened hydrophobicity. These findings emphasize the collaborative influence of both glutenin and gliadin in the formation of gluten fibrils, influenced by hydrogen bonding, hydrophobic, and electrostatic interactions. They also highlight the crucial role played by gliadin with amyloidogenic fragments such as ILQQIL and SLVLQTL, aiming to provide a theoretical basis for understanding the utilization of gluten proteins.


Asunto(s)
Amiloide , Gliadina , Amiloide/metabolismo , Gliadina/química , Péptidos/química , Glútenes/química , Conformación Proteica en Lámina beta , Fragmentos de Péptidos/química
10.
Nat Commun ; 15(1): 1132, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326298

RESUMEN

The exponential growth of various complex images is putting tremendous pressure on storage systems. Here, we propose a memristor-based storage system with an integrated near-storage in-memory computing-based convolutional autoencoder compression network to boost the energy efficiency and speed of the image compression/retrieval and improve the storage density. We adopt the 4-bit memristor arrays to experimentally demonstrate the functions of the system. We propose a step-by-step quantization aware training scheme and an equivalent transformation for transpose convolution to improve the system performance. The system exhibits a high (>33 dB) peak signal-to-noise ratio in the compression and decompression of the ImageNet and Kodak24 datasets. Benchmark comparison results show that the 4-bit memristor-based storage system could reduce the latency and energy consumption by over 20×/5.6× and 180×/91×, respectively, compared with the server-grade central processing unit-based/the graphics processing unit-based processing system, and improve the storage density by more than 3 times.

11.
Nat Prod Res ; : 1-13, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38189427

RESUMEN

Bioactivity-guided purification obtained polysaccharide BP-S1 from seeds of Brucea javanica. The results showed that BP-S1 was a homogenous polysaccharide with molecular weight of 45.7 kDa, mainly composed of arabinose and glucose in the ratio of 1.0:1.0 and the backbone of BP-S1 was deduced to be →3,4)-α-Glup-(1→ with branches of →2)-α-Arap-(1→and α-Arap-(1→, and the possible repetitive units were speculated according to result of methylation and 2D-NMR. Moreover, BP-S1 is a periodic rope-like structure. Functional analysis revealed that BP-S1 inhibited complement activation on the classic and alternative pathways with values of CH50 0.073 ± 0.012 mg/mL and AP50 0.097 ± 0.004 mg/mL, respectively. In mechanism study, using complement component depleted-sera methods indicated that BP-S1 selectively interacted with C3 and C4 components.

12.
Arch Pharm (Weinheim) ; 357(5): e2300603, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38290060

RESUMEN

Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l-tryptophan, 3a-1-3d-1, were designed, synthesized, and evaluated for their biological activity. Among them, IC50 (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a-18 and 3b-1 were 0.58 and 0.44 µM for human serum butyrylcholinesterase (hBuChE), respectively, and both of them exhibited more than 30-fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of hBuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent ß-amyloid (Aß) self-aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood-brain barrier permeation assay, compounds 3a-18 and 3b-1 showed enough blood-brain barrier permeability. In drug-likeness prediction, compounds 3a-18 and 3b-1 showed good gastrointestinal absorption and a low risk of human ether-a-go-go-related gene toxicity. Therefore, compounds 3a-18 and 3b-1 are potential multitarget anti-AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for hBuChE as well as prevent Aß self-aggregation.


Asunto(s)
Acetilcolinesterasa , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Antioxidantes , Barrera Hematoencefálica , Butirilcolinesterasa , Inhibidores de la Colinesterasa , Diseño de Fármacos , Triptófano , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Antioxidantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Relación Estructura-Actividad , Barrera Hematoencefálica/metabolismo , Butirilcolinesterasa/metabolismo , Animales , Triptófano/farmacología , Triptófano/química , Triptófano/análogos & derivados , Triptófano/síntesis química , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Ratas , Acetilcolinesterasa/metabolismo , Estructura Molecular , Células PC12 , Relación Dosis-Respuesta a Droga , Modelos Moleculares
13.
Nat Prod Res ; : 1-6, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38217490

RESUMEN

A novel alkaloid with a hexa-tetra-hexa-cyclic skeleton, Bi-4-methoxycarbonyl-2-quinolone (1), was discovered during the investigation of Brucea javanica. Additionally, six known alkaloids (2-7) were also found. The chemical structures of these compounds were identified using HRESIMS and 1D and 2D NMR spectroscopic analysis. Additionally, the absolute configuration of the new compound 1 was determined through X-ray single crystal diffraction. Compound 1 exhibited significant anti-inflammatory activity in RAW264.7 cells and demonstrated promising anti-cancer effects in Lewis cells.

14.
Phytochem Anal ; 35(2): 288-307, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37814999

RESUMEN

BACKGROUND AND OBJECTIVE: The herb Rheum tanguticum (RT), a member of the Polygonaceae family, is listed in the Chinese Pharmacopoeia and has been widely used to treat cardiovascular and gastrointestinal disease. The research aimed to identify the different substances from two kinds of RT extraction methods and the in vivo biotransformation of RT components. METHODS: In this study, by using ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS), we have investigated the metabolomic variation and the in vivo metabolism of RT. A post-acquisition data processing software, PeakView, was applied to an accurate qualitative analysis of the chemical components in RT. RESULTS: Through plant metabolomics analysis, 24 related, differentially expressed metabolites of RT water extract and alcohol extract were obtained. Combined with novel identification strategies and systematic in vivo metabolism analysis, a total of 101 compounds were discovered or tentatively identified in rat serum (including 15 prototype compounds and 86 metabolites). CONCLUSION: In this study, a combination of extraction methods, liquid chromatography-mass spectrometry (LC-MS) technology, and in vivo animal metabolism studies have been established for the screening, identification, and research of chemical active components of natural medicines. LC-MS analysis combined with plant metabolomics was used to study the differential metabolites between different extraction methods of RT. Based on UHPLC-Q-TOF-MS/MS technology, the composition and metabolism of rat plasma before and after RT administration were analysed in vivo, and 15 prototype components and 86 metabolites were detected.


Asunto(s)
Etanol , Rheum , Animales , Ratas , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Metabolómica
15.
Appl Opt ; 62(30): 7960-7965, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-38038088

RESUMEN

We report on a low dark current density P-B-i-N extended short-wavelength infrared photodetector with atomic layer deposited (ALD) A l 2 O 3 passivation based on a InAs/GaSb/AlSb superlattice. The dark current density of the A l 2 O 3 passivated device was reduced by 38% compared to the unpassivated device. The cutoff wavelength of the photodetector is 1.8 µm at 300 K. The photodetector exhibited a room-temperature (300 K) peak responsivity of 0.44 A/W at 1.52 µm, corresponding to a quantum efficiency of 35.8%. The photodetector exhibited a specific detectivity (D ∗) of 1.08×1011 c m⋅H z 1/2/W with a low dark current density of 3.4×10-5 A/c m 2 under -50m v bias at 300 K. The low dark current density A l 2 O 3 passivated device is expected to be used in the fabrication of extended short-wavelength infrared focal plane arrays for imaging.

16.
Antioxidants (Basel) ; 12(8)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37627572

RESUMEN

Proteins have been extensively studied for their outstanding functional properties, while polyphenols have been shown to possess biological activities such as antioxidant properties. There is increasing clarity about the enhanced functional properties as well as the potential application prospects for the polyphenol-protein complexes with antioxidant properties. It is both a means of protein modification to provide enhanced antioxidant capacity and a way to deliver or protect polyphenols from degradation. This review shows that polyphenol-protein complexes could be formed via non-covalent or covalent interactions. The methods to assess the complex's antioxidant capacity, including scavenging free radicals and preventing lipid peroxidation, are summarized. The combination mode, the type of protein or polyphenol, and the external conditions will be the factors affecting the antioxidant properties of the complexes. There are several food systems that can benefit from the enhanced antioxidant properties of polyphenol-protein complexes, including emulsions, gels, packaging films, and bioactive substance delivery systems. Further validation of the cellular and in vivo safety of the complexes and further expansion of the types and sources of proteins and polyphenols for forming complexes are urgently needed to be addressed. The review will provide effective information for expanding applications of proteins and polyphenols in the food industry.

17.
PLoS One ; 18(7): e0288876, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37467292

RESUMEN

Proteinuria is an important hallmark of diabetic nephropathy models, however it takes a long time for the proteinuria and is not stable. Therefore, low-dose lipopolysaccharide (LPS) was investigated in this work to induce rapid and stable proteinuria in hyperglycemic rats and the underlying mechanism was studied. Hyperglycemia rats was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ). After 21 days, the model rats received a subinjury dose of 0.8 mg / kg LPS intraperitoneally (i.p.). We detected related biochemical indexes at different time periods after LPS injection and examined the expression of glomerular podocyte-associated proteins. Simultaneously, we measured expression of inflammatory factors, apoptotic proteins and albumin (ALB) in the renal cortex and renal medulla, respectively. PAS (Periodic Acid Schiff) staining was used to observe renal pathology. After LPS injection, urinary microalbumin (umALB) increased significantly and lasted longer. The expression of Nephrin, Podocin and necroptosis factor kappa B (NF-κB) in rennal cortex and Interleukin 18 (IL-18), Caspase-1, NF-κB and ALB in the renal medulla was significantly changed. Pathologically, the glomerular basement membrane was observed to be significantly thickened, the renal tubules were dilated, and the epithelial cells fell off in a circle. LPS promoted the continuous increase in urinary microalbumin in hyperglycemic rats, which was related to the damage to the glomerular basement membrane and renal tubular epithelial cells and to the inflammatory reaction in the kidney involved in NF-κB signaling, and this pathological damage can help to establish a stable model of diabetic nephropathy with increased proteinuria.


Asunto(s)
Nefropatías Diabéticas , Ratas , Animales , Nefropatías Diabéticas/patología , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , FN-kappa B/metabolismo , Riñón/patología , Proteinuria/patología
18.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2325-2333, 2023 May.
Artículo en Chino | MEDLINE | ID: mdl-37282861

RESUMEN

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and ß-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.


Asunto(s)
Neoplasias Asociadas a Colitis , Colitis , Neoplasias del Colon , Ratones , Animales , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , PPAR alfa/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Colon , Azoximetano , ARN Mensajero , Sulfato de Dextran , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/tratamiento farmacológico , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
19.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2904-2918, 2023 Jun.
Artículo en Chino | MEDLINE | ID: mdl-37381972

RESUMEN

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.


Asunto(s)
Antimaláricos , Asteraceae , Chrysanthemum , Alquinos , Antioxidantes/farmacología
20.
ACS Appl Mater Interfaces ; 15(26): 31617-31626, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37339447

RESUMEN

Negative capacitance field effect transistors made of Hf0.5Zr0.5O2 (HZO) are one of the most promising candidates for low-power-density devices because of the extremely steep subthreshold swing and high open-state currents resulting from the addition of ferroelectric materials in the gate dielectric layer. In this paper, HZO thin films were prepared by magnetron sputtering combined with rapid thermal annealing. Their ferroelectric properties were adjusted by changing the annealing temperature and the thickness of HZO. Two-dimensional MoS2 back-gate negative capacitance field-effect transistors (NCFETs) based on HZO were prepared as well. Different annealing temperatures, thicknesses of HZO thin films, and Al2O3 thicknesses were studied to achieve optimal capacitance matching, aiming to reduce both the subthreshold swing of the transistor and the hysteresis of the NCFET. The NCFET exhibits a minimum subthreshold swing as low as 27.9 mV/decade, negligible hysteresis (∼20 mV), and the ION/IOFF of up to 1.58 × 107. Moreover, a negative drain-induced barrier lowering effect and a negative differential resistance effect have been observed. This steep-slope transistor is compatible with standard CMOS manufacturing processes and attractive for 2D logic and sensor applications as well as future energy-efficient nanoelectronic devices with scaled power supplies.

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