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1.
Toxicol Appl Pharmacol ; 490: 117038, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39019095

RESUMO

Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3ß/ß-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/ß-catenin signaling pathways.


Assuntos
1-Naftilisotiocianato , Colestase , Glicogênio Sintase Quinase 3 beta , NF-kappa B , Piridonas , Receptores Citoplasmáticos e Nucleares , Fator de Necrose Tumoral alfa , Via de Sinalização Wnt , Animais , Piridonas/farmacologia , NF-kappa B/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Masculino , 1-Naftilisotiocianato/toxicidade , Camundongos , Receptores Citoplasmáticos e Nucleares/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Colestase/induzido quimicamente , Colestase/metabolismo , Colestase/tratamento farmacológico , Colestase/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos Endogâmicos C57BL , beta Catenina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia
2.
Int Microbiol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767683

RESUMO

In the relentless battle against multi-drug resistant Gram-negative bacteria, piceatannol emerges as a beacon of hope, showcasing unparalleled antibacterial efficacy and a unique ability to disrupt virulence factors. Our study illuminates the multifaceted prowess of piceatannol against prominent pathogens-Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Notably, piceatannol demonstrated a remarkable ability to inhibit biofilm formation, reduce bacterial mobility, and diminish extracellular enzyme synthesis.Mechanistic insights into piceatannol's activity unraveled its impact on membrane potential, proton motive force, and ATP production. Furthermore, our study delved into piceatannol's anti-quorum sensing (QS) activity, showcasing its potential to downregulate QS-encoding genes and affirming its affinity to critical QS receptors through molecular docking. Crucially, piceatannol exhibited a low propensity for resistance development, positioning it as a promising candidate for combating antibiotic-resistant strains. Its mild effect on red blood cells (RBCs) suggests safety even at higher concentrations, reinforcing its potential translational value. In an in vivo setting, piceatannol demonstrated protective capabilities, significantly reducing pathogenesis in mice infected with P. aeruginosa and P. mirabilis. This comprehensive analysis positions piceatannol as a renaissance in antibacterial innovation, offering a versatile and effective strategy to confront the evolving challenges posed by resilient Gram-negative pathogens.

3.
J Environ Manage ; 351: 119778, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086113

RESUMO

This work was focused on the selective recovery of gold and silver from electronic wastes using a sequential process of pyrometallurgy (Qalkari) and room-temperature hydrometallurgy. In the first step, electronic wastes underwent Qalkari recycling, yielding tablets containing precious elements (Qalkari furnace product) and melting slag (Qalkari furnace waste). In the subsequent hydrometallurgy phase, the nitric acid concentration and the input solid amount were optimized for the effective room-temperature recovery of gold. Due to the successful separation of precision elements and disturbing substances in Qalkari, the gold recovery efficiency of 99.99% was obtained at the acid concentration of 50% (v/v) and the solid input of 15% (w/v). Afterwards, HCl, NH4Cl, and NaCl were used for silver recovery from the Qalkari-processed gold-recovered leaching solution, leading to the efficiency of 99.99%. But NH4Cl was recognized as the most effective precipitant as it promises the most enhanced potential for the possible subsequent recovery of palladium. In conclusion, this study draws the effectiveness of Qalkari in recycling electronic wastes, with a significant impact on the efficiency of succeeding room-temperature hydrometallurgical processes for gold and silver recovery within a reasonable leaching time.


Assuntos
Resíduo Eletrônico , Prata , Ouro , Temperatura , Reciclagem
4.
J Environ Manage ; 350: 119654, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38016232

RESUMO

China has implemented policies like Leading areas for Agricultural Green Development (LAGD) to mitigate livestock and poultry farming pollution while promoting industry growth. However, it remains uncertain whether LAGDs have successfully balanced emission reduction with stable development. This study examines 165 LAGDs to analyze changes in emissions, assess the decoupling of emission reduction from output value, and identify influencing factors. Findings reveal that emissions from livestock and poultry in LAGDs initially increased and then decreased between 2010 and 2019. Cattle were responsible for over 40% of fecal emissions, and pigs for more than 20%. Additionally, pigs contributed to over 61% of urine emissions. From 2010 to 2014, increases in chemical oxygen demand were mainly due to pigs and cattle. Total nitrogen levels were significantly impacted by cattle, while pigs were affected by total phosphorus. From 2014 to 2019, reductions in emissions were largely attributed to a decrease in pig-related pollutants. The decoupling status shifted from strong to weak and then back to strong between 2014 and 2019. Production efficiency played a crucial role in reducing emissions, while changes in industrial structure moved from supporting to hindering this reduction. Economic development was a primary factor in driving these changes. Standard emissions in Chinese regions showed a rising and then declining trend from 2010 to 2019. The Northeast and Northwest regions of China demonstrated emission trends that were in sync with the growth in rural income. This study offers insights into the successes and challenges of LAGDs in achieving a balance between reduced emissions and development, using quantitative analysis. The findings are instrumental in informing policies for a sustainable livestock and poultry industry. Recommendations include evaluating coordinated approaches to pollution reduction and industrial growth, setting decoupling goals, designing policies based on influential factors, conducting regional assessments of livestock and poultry demand, and implementing region-specific strategies.


Assuntos
Gado , Aves Domésticas , Animais , Bovinos , Agricultura , China , Análise da Demanda Biológica de Oxigênio , Desenvolvimento Econômico , Dióxido de Carbono
5.
Environ Manage ; 73(6): 1215-1229, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38578324

RESUMO

As representative of the water-energy-food nexus, fossil fuel development and industrial agriculture are rural industries that continue to expand and increasingly occur in the same areas. Being a top agricultural export county and the fossil fuel capital of California while ranking among the worst in the US for industrial pollution, Kern County is a poster child of rural nexus development and, thus, an essential place for initiating sustainability transitions. Such transitions rely on policy support and the adoption of methods by individuals and communities who may disagree with such changes. While sense of place and impact perceptions are recognized as playing critical roles in sustainability management, they have yet to be utilized in nexus research. A survey (N = 256) of the perceived impacts of nexus industries with place meaning and place attachment as possible drivers for perceptions was conducted in nexus industry pollution exposure risk zones. Factor analysis and bivariate correlations showed that place meaning and place attachment are drivers for perceptions while also being drivers for concern for changes in nexus industries. While perceptions of impacts indicated contested place meanings, participants strongly perceive the economy and environment as being in decline. To build support for sustainability policy, directing funds from Kern County's renewable energy industry to local sectors of society, implementation of regenerative agriculture, cooperative management, and nurturing place meaning as aligned with nature's restorative quality are important paths forward. These nexus management foci could strengthen place attachment, build trust in government, and repair environmental alienation.


Assuntos
Agricultura , Conservação dos Recursos Naturais , California , Humanos , População Rural , Combustíveis Fósseis
6.
BMC Oral Health ; 24(1): 776, 2024 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992678

RESUMO

BACKGROUND: Early childhood caries (ECC) is a global public health challenge that requires innovation, infrastructure, and health system influences to bolster initiatives for its management and control. The aim of this scoping review was to investigate the published evidence on the association between ECC and the targets of the Sustainable Development Goal 9 (SDG9) concerned with industry, innovation, and infrastructure development. METHODS: The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. A search was conducted in PubMed, Web of Science, and Scopus between July and August 2023 using a search strategy related to the promotion of resilient infrastructure, sustainable industries, scientific research and innovation, access to the internet and ECC. Only English language publications were included. Studies that solely examined ECC without reference to the SDG9 targets were excluded. RESULTS: The search yielded 933 studies for review. After screening for the eligibility and removing duplicates, 916 unique articles remained for further screening. However, none of the identified studies provided data on the association between resilient infrastructure, sustainable industries, scientific research and innovation, access to the internet and ECC. CONCLUSION: There were no primary studies that assessed the association between ECC and SDG9, even though the plausibility of a potential relationship exists. Future studies are needed to generate evidence on the link between ECC and SDG9 as this link may contribute to the reduction in the proportion of children with untreated ECC.


Assuntos
Cárie Dentária , Desenvolvimento Sustentável , Humanos , Cárie Dentária/prevenção & controle , Pré-Escolar , Criança , Saúde Global
7.
Medicina (Kaunas) ; 60(3)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38541153

RESUMO

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for Cmax, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.


Assuntos
Omeprazol , Humanos , Omeprazol/química , Equivalência Terapêutica , Cápsulas , Estudos Cross-Over , Europa (Continente)
8.
Saudi Pharm J ; 32(7): 102106, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38831925

RESUMO

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol-3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy -5.33 and -4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 1-7 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer's disease (AD) and mitigating hyperglycemia.

9.
Saudi Pharm J ; 32(5): 102041, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38558886

RESUMO

The rise of antibiotic resistance in bacteria is becoming a global concern, particularly due to the dwindling supply of new antibiotics. This situation mandates the discovery of new antimicrobial candidates. Plant-derived natural compounds have historically played a crucial role in the development of antibiotics, serving as a rich source of substances possessing antimicrobial properties. Numerous studies have supported the reputation of 6-gingerol, a prominent compound found in the ginger family, for its antibacterial properties. In this study, the antibacterial activities of 6-gingerol were evaluated against Gram-negative bacteria, Acinetobacter baumannii and Klebsiella pneumoniae, with a particular focus on the clinically significant Gram-negative Pseudomonas aeruginosa and Gram-positive bacteria Staphylococcus aureus. Furthermore, the anti-virulence activities were assessed in vitro, in vivo, and in silico. The current findings showed that 6-gingerol's antibacterial activity is due to its significant effect on the disruption of the bacterial cell membrane and efflux pumps, as it significantly decreased the efflux and disrupted the cell membrane of S. aureus and P. aeruginosa. Furthermore, 6-gingerol significantly decreased the biofilm formation and production of virulence factors in S. aureus and P. aeruginosa in concentrations below MICs. The anti-virulence properties of 6-gingerol could be attributed to its capacity to disrupt bacterial virulence-regulating systems; quorum sensing (QS). 6-Gingerol was found to interact with QS receptors and downregulate the genes responsible for QS. In addition, molecular docking, and molecular dynamics (MD) simulation results indicated that 6-gingerol showed a comparable binding affinity to the co-crystalized ligands of different P. aeruginosa QS targets as well as stable interactions during 100 ns MD simulations. These findings suggest that 6-gingerol holds promise as an anti-virulence agent that can be combined with antibiotics for the treatment of severe infections.

10.
Saudi Pharm J ; 32(6): 102073, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38681737

RESUMO

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1ß (interleukine-1ß) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein-protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of -9.576 and -6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (-67.25 Kcal/mol) surpassed that of the reference inhibitor (-56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.

11.
Molecules ; 28(3)2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36770958

RESUMO

Dihydrofolate reductase (DHFR) is a crucial enzyme that maintains the levels of 5,6,7,8-tetrahydrofolate (THF) required for the biological synthesis of the building blocks of DNA, RNA, and proteins. Over-activation of DHFR results in the progression of multiple pathological conditions such as cancer, bacterial infection, and inflammation. Therefore, DHFR inhibition plays a major role in treating these illnesses. Sesquiterpenes of various types are prime metabolites derived from the marine sponge Dactylospongia elegans and have demonstrated antitumor, anti-inflammation, and antibacterial capacities. Here, we investigated the in silico potential inhibitory effects of 87 D. elegans metabolites on DHFR and predicted their ADMET properties. Compounds were prepared computationally for molecular docking into the selected crystal structure of DHFR (PDB: 1KMV). The docking scores of metabolites 34, 28, and 44 were the highest among this series (gscore values of -12.431, -11.502, and -10.62 kcal/mol, respectively), even above the co-crystallized inhibitor SRI-9662 score (-10.432 kcal/mol). The binding affinity and protein stability of these top three scored compounds were further estimated using molecular dynamic simulation. Compounds 34, 28, and 44 revealed high binding affinity to the enzyme and could be possible leads for DHFR inhibitors; however, further in vitro and in vivo investigations are required to validate their potential.


Assuntos
Antagonistas do Ácido Fólico , Poríferos , Sesquiterpenos , Animais , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Tetra-Hidrofolato Desidrogenase/química , Antagonistas do Ácido Fólico/química , Poríferos/metabolismo , Sesquiterpenos/farmacologia
12.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1137-1144, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-37005799

RESUMO

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Invenções , China
13.
J Environ Manage ; 310: 114735, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35202950

RESUMO

China produces a large amount of industrial effluent with multiple pollutants contained, along with a flourishing economy. This study aims to examine the dynamics between China's industrialization and accompanying environmental pressure based on the gray water footprint (GWF) concept. A newly proposed net GWF (NetGWF) and the decoupling index (DI) are applied to evaluate China's industrial activities during 2002-2015 in different modes considering typical, all, and individual pollutants. The NetGWF dynamics are further quantitatively decomposed into 17 effects of not only commonly assessed drivers but also industrial fixed capital formation, inventory variation, and import, using an advanced dynamic decomposition analysis approach. Results show NetGWF is an effective indicator measuring domestic water pollution stress from industrialization, with NetGWF-AllPlt (estimated using all pollutants) validated to be more reliable and sensitive than NetGWF-COD&NH3N (estimated using Chemical oxygen demand and Ammonia nitrogen). An overall decoupling between China's industrialization and wastewater pollution is identified with most of DIs less than 1.0 caused mainly by decreased (by around 40%) industrial NetGWFs for 2002-2015. Industrial fixed capital formation and export have caused main components of China's industrial GWF, with proportions of 37.3% and 30.8%, respectively, followed by urban household consumption (16.8%). Volatile phenol, Petroleum, and Ammonia nitrogen are recognized as three decisive contaminants to the industrial NetGWFs. Technological development is the dominant contributor (-50%) to decreasing China's industrial NetGWFs, while fixed capital formation (18%) and export (16%) are principal drivers increasing the NetGWFs. Based on these, we expect to provide informative findings for building a pollution-decoupled industrialization.


Assuntos
Poluentes Ambientais , Desenvolvimento Industrial , Análise da Demanda Biológica de Oxigênio , China , Água , Poluição da Água
14.
Molecules ; 28(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36615238

RESUMO

Cannabinoid receptor ligands are renowned as being therapeutically crucial for treating diverse health disorders. Phenylspirodrimanes are meroterpenoids with unique and varied structural scaffolds, which are mainly reported from the Stachybotrys genus and display an array of bioactivities. In this work, 114 phenylspirodrimanes reported from Stachybotrys chartarum were screened for their CB2 agonistic potential using docking and molecular dynamic simulation studies. Compound 56 revealed the highest docking score (-11.222 kcal/mol) compared to E3R_6KPF (native agonist, gscore value -12.12 kcal/mol). The molecular docking and molecular simulation results suggest that compound 56 binds to the putative binding site in the CB2 receptor with good affinity involving key interacting amino acid residues similar to that of the native ligands, E3R. The molecular interactions displayed π-π stacking with Phe183 and hydrogen bond interactions with Thr114, Leu182, and Ser285. These findings identified the structural features of these metabolites that might lead to the design of selective novel ligands for CB2 receptors. Additionally, phenylspirodrimanes should be further investigated for their potential as a CB2 ligand.


Assuntos
Agonistas de Receptores de Canabinoides , Simulação de Dinâmica Molecular , Receptor CB2 de Canabinoide , Terpenos , Sítios de Ligação , Agonistas de Receptores de Canabinoides/farmacologia , Agonistas de Receptores de Canabinoides/química , Ligantes , Simulação de Acoplamento Molecular , Receptor CB2 de Canabinoide/metabolismo , Terpenos/química , Terpenos/farmacologia
15.
Molecules ; 27(19)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36235247

RESUMO

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC50 = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC50 = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Apoptose , Cumarínicos/farmacologia , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
16.
Yi Chuan ; 44(10): 824-839, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384721

RESUMO

Diabetes mellitus is a kind of metabolic disease characterized by hyperglycemia resulting from insulin insufficiency and insulin resistance. It has become one of the major diseases threatening human health. In this paper, we analyze the current R&D status of diabetes from the aspects of papers, patents, drugs and industrial development. The results show that scientific outcomes are increasing steadily and the hot topics are diabetic complications and epidemiological research. In terms of technology development, large pharmaceutical companies, such as Janssen Pharmaceutical, Lilly pharmaceutical, Boehringer Ingelheim, are actively engaged in diagnosis, treatment and management of diabetes. By March 23 2022, 207 drugs have been launched and a large number of candidate drugs are in the pre-clinical and clinical stage. In terms of industrial development, the potential diabetes market is huge and the digital management of diabetes is developing rapidly. China has certain strength in diabetes research and development. In the future, measures should be taken to strengthen the transformation of research outcomes, and promote product development to meet China's huge needs of diabetes cares.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Humanos , Diabetes Mellitus/etiologia , Pesquisa , Preparações Farmacêuticas , China
17.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1190-1195, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35343144

RESUMO

Cannabis sativa,with a long history of cultivation, is a traditional industrial crop widely used for food, textiles, and me-dicine. This study discussed industrial C. sativa and medicinal C. sativa. According to the characteristics of management policies of C. sativa in different periods, we divided the development stages of C. sativa into three stages and analyzed the changes in breeding and cultivation goals under the influence of policies. Meanwhile, a comprehensive analysis was carried out based on the breeding conditions of industrial C. sativa in China. Because of the vast territory of China, the differences in agricultural planting environment, economic development, and social development in the southern and northern areas result in different used parts of C. sativa. To be speci-fic, flowers and leaves are used in Yunnan, fiber in Heilongjiang, and seeds in Shanxi. The breeding of C. sativa varieties highlights fiber, seeds, or both of them. As the value of cannabidiol is explored, medicinal C. sativa has been approved in recent years. Based on the cultivation characteristics and value of industrial C. sativa, it is proposed that industrial C. sativa has a broad application prospect as an important industrial crop, and the existing products contain almost no tetrahydrocannabinol. The cultivation of C. sativa should be rationally guided to promote the development of the C. sativa industry. Moreover, it is recommended to actively apply advanced breeding techniques such as molecular breeding to overcome the problems of the uncertainty of the existing induced breeding and the excessively long hybrid breeding cycle, and develop high value-added applications such as medicinal products of C. sativa to enhance the exploitation of the economic value of C. sativa.


Assuntos
Canabidiol , Cannabis , Canabidiol/análise , Cannabis/genética , China , Dronabinol , Melhoramento Vegetal
18.
Environ Res ; 195: 110788, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33508258

RESUMO

Worry is influenced by environmental pollution and affects individual health and well-being; however, little is known about this association in Indigenous communities. Using logistic regression models, we examined self-reported responses among Cree adults to the question "Are you worried about the pollution of the environment (land, water or air) in Iiyiyiu Aschii?" to assess if increased worry was associated with proximity to industrial and hydroelectric development, whether increased worry was associated with self-reported behavioural changes of water consumption type in the community or bush, and days spent on-the-land. Proximity to multiple industrial and hydroelectric development sites was associated with increased worry about pollution. Notably, the decreased consumption of tap water in the community was significantly associated with increased worry, but time-on-the land was not. Overall, our study provides new findings concerning development in a Cree territory in northern Quebec, Canada, and the worry about pollution's association with self-reported behavioural changes.


Assuntos
Poluição Ambiental , Indústrias , Canadá , Quebeque , Autorrelato
19.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(6): 591-593, 2021 Nov 30.
Artigo em Zh | MEDLINE | ID: mdl-34862767

RESUMO

This study summarizes the status of domestic industries of medical devices for assisted reproductive technology, product category, the status of product classification management, the status of technical review, the progress of quality evaluation technology, and the progress of standardization. The domestic industry of medical devices for assisted reproductive technology in my country has begun to take shape, and a solid foundation has been laid for standardization and supervision technology. These will become an important driving force and guarantee for the subsequent development of medical devices for assisted reproductive technology. Under the guidance of the new development concept and the trend of accelerating the construction of the main body of the domestic cycle, my country's independent and controllable assisted reproductive medical device industry is gaining momentum.


Assuntos
Indústrias , Técnicas de Reprodução Assistida , China , Humanos , Padrões de Referência , Tecnologia
20.
J Environ Manage ; 276: 111294, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896823

RESUMO

In the context of tremendously promoting bioenergy utilization, regional suitability for industrial development of biomass power generation is a critical factor when deploying region-specific strategies. An integrated framework is developed incorporating resource potential, development demands and development conditions to evaluate the suitability for regional industrial development of power generation utilizing agricultural bioresources. Twelve indicators reflecting local resource, environmental and socioeconomic features are used to measure the suitability of 31 provincial regions in China. An improved matter-element extension model combined with the entropy weight method is adopted to attain holistic and hierarchical suitability ranks. The results reveal that the distribution of holistic suitability ranks among regions is imbalanced with the eastern regions presenting more advantages compared with the western regions. Three regions belonging to Rank I (optimum) are Henan, Shandong and Xinjiang. Hainan, Tibet, Qinghai are classified into Rank V (unsuited). Moreover, there are great differences in the limiting factors of the suitability among regions. Resource potential is a limiting factor for Beijing, Shanghai, Fujian, Hainan and Guizhou; Development demands refrain Fujian, Guangxi and Yunnan; Tianjin and Ningxia are limited by development conditions. Tibet and Qinghai have the worst performance on each criterion. The results and region-targeted policy recommendations can provide insights for bioenergy utilization development in accordance with local conditions closely.


Assuntos
Fontes de Energia Bioelétrica , Pequim , Biomassa , China , Tibet
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