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1.
J Antimicrob Chemother ; 75(11): 3244-3247, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712655

RESUMO

BACKGROUND: The rising incidence of antimicrobial resistance in Neisseria gonorrhoeae may result in untreatable gonorrhoea in certain circumstances and development of novel antimicrobials is urgently needed. OBJECTIVES: To evaluate the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, DIS-73285, against a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates and reference strains, including various types of high-level resistant, MDR and XDR gonococcal isolates (n = 262). METHODS: MICs (mg/L) of DIS-73285 were determined by agar dilution and by Etest for ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline. RESULTS: DIS-73285 was substantially more potent than any of the currently or previously used therapeutic antimicrobials, with MICs ranging from ≤0.001 to 0.004 mg/L, and the MIC50, MIC90 and modal MIC all ≤0.001 mg/L (lowest MIC tested). No correlation with the MICs of DIS-73285 and the MICs of any of the currently or previously used antimicrobials was observed. CONCLUSIONS: The novel chemotype, small-molecule antimicrobial DIS-73285, demonstrated high in vitro potency against all tested N. gonorrhoeae isolates. Further in vitro and in vivo studies, evaluating efficacy, resistance emergence, pharmacokinetic/pharmacodynamic parameters, toxicity and safety, should be conducted to evaluate DIS-73285 as a therapy specifically for urogenital and extra-genital gonorrhoea.


Assuntos
Anti-Infecciosos , Gonorreia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae
2.
J Biomed Inform ; 111: 103586, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33049416

RESUMO

People with asthma have heterogeneous triggers and symptoms, which they need to be aware of in order to implement the strategies to manage their condition. Context-aware reasoning has the potential to provide the personalisation that is required to address the heterogeneity of asthma by helping people to define the information that is relevant considering the characteristics of their condition and delivering services based on this information. This research work proposes the Approach to Develop context-Aware solutions for Personalised asthma managemenT (ADAPT), whose aim is to facilitate the creation of solutions allowing the required customisation to address the heterogeneity of asthma. ADAPT is the result of the constant interaction with people affected by asthma throughout the research project, which was possible to achieve thanks to the collaboration formed with the Centre for Applied Research of Asthma UK. ADAPT context dimensions facilitate the development of preventive and reactive features that can be configured depending on the characteristics of the person with asthma. The approach also provides support to people not knowing their triggers through case-based reasoning and includes virtual assistant as a complementing technology supporting asthma management. ADAPT is validated by people with asthma, carers and experts in respiratory conditions, who evaluated a mobile application that was built based on the approach.


Assuntos
Asma , Cuidadores , Asma/terapia , Humanos , Monitorização Fisiológica
3.
J Antimicrob Chemother ; 74(6): 1591-1594, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30778550

RESUMO

BACKGROUND: Lack of effective treatment of gonorrhoea due to increasing antimicrobial resistance in Neisseria gonorrhoeae is a serious threat to the management and control of the infection. Novel antimicrobials are required to prevent the infection becoming untreatable. OBJECTIVES: Herein, we investigated the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, SMT-571, against a large collection of clinical N. gonorrhoeae isolates (n = 228) and international gonococcal reference strains (n = 34), including numerous MDR and XDR gonococcal isolates. METHODS: MICs of SMT-571 were determined by agar dilution and MICs of ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline were determined by Etest. RESULTS: SMT-571 showed potent in vitro activity against all the tested N. gonorrhoeae isolates (n = 262). The MICs ranged from 0.064 to 0.125 mg/L and the MIC50, MIC90 and modal MIC were all 0.125 mg/L. No cross-resistance or correlation between the MICs of SMT-571 and comparator agents was seen. CONCLUSIONS: SMT-571 demonstrated potent in vitro activity against all tested gonococcal isolates and no cross-resistance to previously and currently used antimicrobials was seen. With its promising supplementary in vitro and in vivo preclinical data, including high levels of oral bioavailability, SMT-571 could be an effective option for the oral treatment of gonorrhoea. Randomized controlled clinical trials for gonorrhoea that examine the treatment efficacy, pharmacokinetics/pharmacodynamics, toxicity and safety of SMT-571, and include urogenital and extragenital (rectal and pharyngeal) samples, are crucial.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Neisseria gonorrhoeae/efeitos dos fármacos , Administração Oral , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Relação Dose-Resposta a Droga , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana
4.
Fish Physiol Biochem ; 45(3): 1153-1165, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30847628

RESUMO

The stress ameliorating effect of dietary supplementation of vitamin C, vitamin E, and tryptophan on rohu Labeo rohita fry was evaluated. Rohu fry (1.1 ± 0.03 g) were cultured under five different feeding regimes: enriched with 0.08% vitamin C (D1), 0.02% vitamin E (D2), 1.42% tryptophan (D3), a combination of these three ingredients at similar doses (D4), and control diet (D5). Rohu fry of D5 were divided into two groups-exposed to experimental light (D5FL) and ambient light (114 ± 4 lx, D5AL). All fry (except D5AL) were exposed at light intensity of 3442 ± 648 lx. Feeding of rohu with enriched diets significantly (P < 0.05) enhanced the survival rate and average weight. A 15-25% higher survival and 1.3-1.8-fold higher average weight were recorded in rohu fed with enriched diet compared to D5FL treatment. Supplementation of vitamin C in diet (D1) of rohu resulted in 4.1-fold and 6.9-fold higher nitric oxide synthase and reduced glutathione (GSH) levels, respectively compared to the D5FL treatment. The tryptophan-enriched diet (D3) showed 5.8-fold higher melatonin and 4.4-fold lower cortisol levels in rohu compared to the D5FL treatment. Significantly (P < 0.05) higher nitric oxide synthase, GSH and melatonin, and lower cortisol, glucose, thiobarbituric acid reactive substances, carbonyl protein, glutathione S-transferase, and glutathione peroxidase levels were found in D4 diet fed rohu compared to the other treatments. Reduced level of stress in D4 treatment resulted in best performance of rohu in terms of less swimming activity and higher survival and growth compared to the other treatments.


Assuntos
Ácido Ascórbico/farmacologia , Cyprinidae/crescimento & desenvolvimento , Suplementos Nutricionais , Triptofano/farmacologia , Vitamina E/farmacologia , Animais , Glicemia , Metabolismo Energético , Glutationa Peroxidase , Glutationa Transferase , Hidrocortisona , Larva/efeitos dos fármacos , Larva/efeitos da radiação , Longevidade , Melatonina , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Aumento de Peso
5.
J Clin Psychopharmacol ; 38(6): 590-597, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30346333

RESUMO

BACKGROUND: Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD). METHODS: Ten patients with TRD were included in an open, noncontrolled 4-week study and received a rapid intravenous dose of ketamine 0.5 mg/kg. Main outcome measure was the Montgomery-Åsberg Depression Rating Scale and suicidality was assessed using the Scale for Suicide Ideation. RESULTS: Rapid injection of ketamine elicited transient increase of blood pressure and altered states of consciousness in all patients and mild psychotomimetic effects in 4 patients, which all resolved without any intervention. Decrease of depression severity was observed from 40-minute postinjection until day 15. Eight patients became responders within 1 day and all were nonresponders after 4 weeks. The decrease of suicidal ideation was significant until day 7. Analysis indicated that higher severity of depression and anxiety at baseline predicted a larger Montgomery-Åsberg Depression Rating Scale decrease after 4 weeks. CONCLUSIONS: This study suggests that in well-controlled medical settings with adequate monitoring, a single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD. These findings are relevant to the practice of general clinical psychiatry and emergency departments were ketamine can have a place in acute management of TRD. Larger studies are necessary to confirm these results.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Ideação Suicida , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Feminino , Humanos , Injeções Intravenosas , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade
6.
Pak J Pharm Sci ; 30(6): 2085-2089, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29175777

RESUMO

A novel flavone derivative has been synthesized in good yield from ketone and aldehyde. The structure has been established by different spectroscopic techniques like 1H NMR, 13C NMR, IR and elemental analysis. The compound was then screened for its acute toxicity and antinociceptive activity studies on animal model. The novel compound was safe upto a maximum dose of 500mg/kg body weight oral dose in mice and showed 65.92 and 82.18% pheriperal analgesic activity at 15 and 30mg/kg body weight doses. Central antinociceptive activity of the compound was 53.13 and 64.44% at 15 and 30mg/kg body weight respectively.


Assuntos
Analgésicos/síntese química , Analgésicos/farmacologia , Cromonas/síntese química , Cromonas/farmacologia , Dor/prevenção & controle , Ácido Acético , Analgésicos/toxicidade , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cromonas/toxicidade , Modelos Animais de Doenças , Dose Letal Mediana , Dose Máxima Tolerável , Camundongos , Estrutura Molecular , Dor/induzido quimicamente , Dor/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Testes de Toxicidade Aguda
7.
Environ Sci Pollut Res Int ; 31(16): 23535-23548, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38421542

RESUMO

The persistence and transmission of emerging pollutants such as antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) have caused concern to scientific community. Composting practises are often adapted for the reduction of organic waste or to enhance fertility in agriculture soil but its continuous usage has posed a potential risk of increased abundance of ARGs in soil. Thus, the present study scrutinises the emerging risk of ARGs and MGEs in agriculture soil and its potential mitigation using biochar owing to its proven environmental sustainability and performance. After 30 days incubation, ARG distribution of SulI, SulII, dfrA1, dfrA12, tetA, flor, and ErmA was 50, 37.5, 37.5, 62.5, 42.11, 62.5, and 52.63% in control samples whereas it was 5, 15.78, 21.05, 15.79, 10.53, 21.05, and 31.58%, respectively, for biochar amended samples. Similarly, IntI1 and IntI2 in control and biochar amended samples were 18.75 and 6.25% and 10.53 and 5.26%, respectively. Principal component analysis (PCA) factor suggests that biochar amendment samples showed enhanced value for pH, organic matter, and organic carbon over control samples. Furthermore, Pearson's correlation analysis performed between detected ARGs and MGEs demonstrated the positive and significant correlation at p < 0.05 for both control and biochar amended samples.


Assuntos
Carvão Vegetal , Compostagem , Solo , Antibacterianos/análise , Genes Bacterianos , Integrons , Agricultura , Microbiologia do Solo , Esterco/análise
8.
ACS Biomater Sci Eng ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940421

RESUMO

Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, and fluorogenic agents. Moreover, through a combination of chemical and bioengineering methodologies, exosomes are tailored to transport precise therapeutic payloads to designated cells or tissues. In this review, we summarize the strategies for exosome modification and drug loading modalities in engineered exosomes. In addition, we provide an overview of the advances in the use of engineered exosomes for targeted drug delivery. Lastly, we discuss the merits and limitations of chemically engineered versus bioengineered exosome-mediated target therapies. These insights offer additional options for refining engineered exosomes in pharmaceutical development and hold promise for expediting the successful translation of engineered exosomes from the bench to the bedside.

9.
Bioeng Transl Med ; 9(2): e10623, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435823

RESUMO

The biological barriers of the body, such as the blood-brain, placental, intestinal, skin, and air-blood, protect against invading viruses and bacteria while providing necessary physical support. However, these barriers also hinder the delivery of drugs to target tissues, reducing their therapeutic efficacy. Extracellular vesicles (EVs), nanostructures with a diameter ranging from 30 nm to 10 µm secreted by cells, offer a potential solution to this challenge. These natural vesicles can effectively pass through various biological barriers, facilitating intercellular communication. As a result, artificially engineered EVs that mimic or are superior to the natural ones have emerged as a promising drug delivery vehicle, capable of delivering drugs to almost any body part to treat various diseases. This review first provides an overview of the formation and cross-species uptake of natural EVs from different organisms, including animals, plants, and bacteria. Later, it explores the current clinical applications, perspectives, and challenges associated with using engineered EVs as a drug delivery platform. Finally, it aims to inspire further research to help bioengineered EVs effectively cross biological barriers to treat diseases.

10.
Environ Pollut ; 328: 121552, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37075921

RESUMO

The prevalence of antibiotic traces in the aquatic matrices is a concern due to the emanation of antibiotic resistance which requires a multifaceted approach. One of the potential sources is the wastewater treatment plants with a lack of advance infrastructure leading to the dissemination of contaminants. Continuous advancements in economic globalization have facilitated the application of several conventional, advanced, and hybrid techniques for the mitigation of rising antibiotic traces in the aquatic matrices that have been thoroughly scrutinized in the current paper. Although the implementation of existing mitigation techniques is associated with several limiting factors and barriers which require further research to enhance their removal efficiency. The review further summarizes the application of the microbial processes to combat antibiotic persistence in wastewater establishing a sustainable approach. However, hybrid technologies are considered as most efficient and environmental-benign due to their higher removal efficacy, energy-efficiency, and cost-effectiveness. A brief elucidation has been provided for the mechanism responsible for lowering antibiotic concentration in wastewater through biodegradation and biotransformation. Overall, the current review presents a comprehensive approach for antibiotic mitigation using existing methods however, policies and measures should be implemented for continuous monitoring and surveillance of antibiotic persistence in aquatic matrices to reduce their potential risk to humans and the environment.


Assuntos
Antibacterianos , Poluentes Químicos da Água , Purificação da Água , Humanos , Resistência Microbiana a Medicamentos , Águas Residuárias , Poluentes Químicos da Água/análise , Purificação da Água/métodos
11.
Medicine (Baltimore) ; 102(32): e34629, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565919

RESUMO

BACKGROUND: Compound Xiao-ai-fei honey ointment (CXHO) is an anticancer preparation with a long history in Uyghur folk medicine in China and has been used for the treatment of gastric cancer (GC) in Xinjiang, China. Nevertheless, the mechanism of its anticancer effect remains to be investigated. METHODS: Bioactive ingredients of CXHO were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Target genes of ingredients were acquired via the PubChem and Swiss target prediction database. Gene expression profiling of GC was obtained from GSE54129 in the GEO database and analyzed using the limma package in R. The hub genes associated with CXHO in GC were validated using the TIMER2.0 database, GEPIA2 database and Auto Dock tools. The effect of CXHO on migration of GC cells was detected by Transwell chamber assay and Wound healing assay. The effect of CXHO on expression levels of MMP2/MMP9 and NF-κb, PI3K/AKT signaling pathway was detected by Western blot assay. RESULTS: Forty-five bioactive ingredients and their 819 related genes were found. A total of 462 differentially expressed genes were identified between GC patients and healthy controls. Seventeen common target genes were identified as hub genes CXHO against GC. Among them, MMP2 and MMP9 were significantly associated with tumor immune infiltrates and had good binding affinity with effective ingredients. Moreover, we validated the mRNA and protein expression levels and prognostic value of MMP2 and MMP9 by different databases. In addition, Kyoto encyclopedia of genes and genomes and gene ontology analyses showed that the 17 common target genes were mainly involved in steroid hormone biosynthesis and cancer-related pathways. Experimental results showed that CXHO inhibited migration of GC cells and down regulated the expression levels of MMP2/MMP9, NF-κb. In addition, CXHO can inhibited PI3K/AKT signaling pathway. CONCLUSION: We identified and experimental validated 2 pivotal target genes of CXHO against GC and preliminarily analyzed the potential mechanisms by which CXHO inhibits the development of GC. All these findings support CXHO as a promising drug for the treatment of GC.


Assuntos
Insuficiência da Valva Aórtica , Mel , Neoplasias Gástricas , Humanos , NF-kappa B , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Farmacologia em Rede , Pomadas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
12.
Chemosphere ; 311(Pt 1): 136880, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36257401

RESUMO

Groundwater which is an essential source of freshwater for various domestic, agricultural, industrial applications is facing a severe deterioration in quality due to demographic pressure and intense industrial activities. Present study appraises the influence of human induced activities on groundwater quality of Agra-Firozabad industrial belts of Western Uttar Pradesh, Yamuna basin, India. The maximum concentrations of metals and anions found during pre and post monsoon are as follows: Lead 0.302; 0.086, calcium 672; 1260, magnesium 215; 16.8, cadmium 0.0; 0.066, chromium 0.016; 0.005, manganese 0.340; 0.076, nickel 0.044; 0.028, sulfate 514; 286, nitrate 66.7; 3.56 and fluoride 1.17; 2.02 mg/L respectively. Based on results of Water Quality Index, groundwater samples were classified under 'Poor water' category in 34.2% and 52.63% during pre and post-monsoon period, respectively. Accordingly, higher concentrations of bicarbonate and sulfate might have attributed to excess hardness, instrumental in making it unsuitable for industrial usage. However, values of Percent Sodium, Sodium Adsorption Ratio, Magnesium Hazard and Permeability Index signified that groundwater from majority of locations was fit for agricultural use. Health risk assessment studies revealed that children consuming polluted water were affected more as compared to adults. Timely action and strict compliance of regulation is recommended towards groundwater management for defined usage to avert severe health effects and to meet sustainable development goals.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Humanos , Criança , Adulto , Rios , Magnésio/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Qualidade da Água , Sulfatos/análise , Medição de Risco , Sódio , Índia
13.
J Cancer Res Clin Oncol ; 149(11): 8467-8481, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37087696

RESUMO

PURPOSE: Esophageal squamous cell carcinoma (ESCC), is a frequent digestive tract malignant carcinoma with a high fatality rate. Daphne altaica (D. altaica), a medicinal plant that is frequently employed in Kazakh traditional medicine, and which has traditionally been used to cure cancer and respiratory conditions, but research on the mechanism is lacking. Therefore, we examined and verified the hub genes and mechanism of D. altaica treating ESCC. METHODS: Active compounds and targets of D. altaica were screened by databases such as TCMSP, and ESCC targets were screened by databases such as GeneCards and constructed the compound-target network and PPI network. Meantime, data sets between tissues and adjacent non-cancerous tissues from GEO database (GSE100942, GPL570) were analyzed to obtain DEGs using the limma package in R. Hub genes were validated using data from the Kaplan-Meier plotter database, TIMER2.0 and GEPIA2 databases. Finally, AutoDock software was used to predict the binding sites through molecular docking. RESULTS: In total, 830 compound targets were obtained from TCMSP and other databases. In addition, 17,710 disease targets were acquired based on GeneCards and other databases. In addition, we constructed the compound-target network and PPI network. Then, 127 DEGs were observed (82 up-regulated and 45 down-regulated genes). Hub genes were screened including TOP2A, NUF2, CDKN2A, BCHE, and NEK2, and had been validated with the help of several publicly available databases. Finally, molecular docking results showed more stable binding between five hub genes and active compounds. CONCLUSIONS: In the present study, five hub genes were screened and validated, and potential mechanisms of action were predicted, which could provide a theoretical understanding of the treatment of ESCC with D. altaica.


Assuntos
Carcinoma , Daphne , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Daphne/genética , Farmacologia em Rede , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Simulação de Acoplamento Molecular , Biologia Computacional , Quinases Relacionadas a NIMA
14.
Biomed Pharmacother ; 160: 114330, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36746094

RESUMO

We identified the effective components and the underlying mechanisms of Quince (Cydonia oblonga Mill, COM) extract against atherosclerosis. The effective components of COM extract were identified with UHPLC-Q-TOF-MS/MS. Network pharmacology was performed. A rat model of atherosclerosis induced by high-fat emulsion combined with vitamin D3 was established. The anti-atherosclerosis effect of COM extract was evaluated from various aspects such as blood lipid regulation, anti-oxidative stress, anti-inflammatory response, and vascular protection function. We identified 14 serum components of COM extract using UHPLC-Q-TOF-MS/MS. Through prediction, 573 targets were obtained, among which 224 targets were atherosclerosis specific targets. The key targets included GSK3ß, ESR1, EGFR, and HSP90AA1. The key signaling pathway was PI3K-Akt signaling pathway. Pharmacodynamics analysis showed that COM extract reduced the levels of TC, TG, and LDL-C as well as ALT and AST, while increased the level of HDL-C. Mechanistically, COM extract significantly increased serum SOD and GSH-Px activities, but decreased MDA content in atherosclerosis rats, showing antioxidant effects. Meanwhile, COM extract significantly down-regulated the levels of pro-inflammatory factors IL-1ß, IL-6, TNF-α and CRP, but up-regulated anti-inflammatory factor IL-10. Additionally, COM extract increased the levels of NO, eNOS, and 6-keto-PGF1α; whereas, decreased the levels of ET-1 and TXB2. Furthermore, COM extract significantly inhibited the mRNA and protein levels of EGFR, p-PI3K, p-AKT, GSK-3ß, Bax, and Caspase-3 as well as the Bax/Bcl-2 ratio. Conclusively, COM extract exerts hypolipidemic, anti-oxidative, anti-inflammatory, anti-thrombotic and vascular endothelium protective effects on atherosclerosis rat model, which may be related to the inhibition of EGFR/PI3K/AKT/GSK-3ß signaling pathway.


Assuntos
Aterosclerose , Rosaceae , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta , Fosfatidilinositol 3-Quinases/metabolismo , Espectrometria de Massas em Tandem , Proteína X Associada a bcl-2 , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores ErbB
15.
JAMA Netw Open ; 6(2): e230147, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36808239

RESUMO

Importance: Immune-metabolic disturbances have been implicated in the pathophysiology of major depressive disorder and may be more prominent in individuals with treatment-resistant depression (TRD). Preliminary trials suggest that lipid-lowering agents, including statins, may be useful adjunctive treatments for major depressive disorder. However, no adequately powered clinical trials have assessed the antidepressant efficacy of these agents in TRD. Objective: To assess the efficacy and tolerability of adjunctive simvastatin compared with placebo for reduction of depressive symptoms in TRD. Design, Setting, and Participants: This 12-week, double-blind, placebo-controlled randomized clinical trial was conducted in 5 centers in Pakistan. The study involved adults (aged 18-75 years) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) major depressive episode that had failed to respond to at least 2 adequate trials of antidepressants. Participants were enrolled between March 1, 2019, and February 28, 2021; statistical analysis was performed from February 1 to June 15, 2022, using mixed models. Intervention: Participants were randomized to receive standard care plus 20 mg/d of simvastatin or placebo. Main Outcomes and Measures: The primary outcome was the difference between the 2 groups in change in Montgomery-Åsberg Depression Rating Scale total scores at week 12. Secondary outcomes included changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, and the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. C-reactive protein and plasma lipids were measured at baseline and week 12. Results: A total of 150 participants were randomized to simvastatin (n = 77; median [IQR] age, 40 [30-45] years; 43 [56%] female) or placebo (n = 73; median [IQR] age, 35 [31-41] years; 40 [55%] female). A significant baseline to end point reduction in Montgomery-Åsberg Depression Rating Scale total score was observed in both groups and did not differ significantly between groups (estimated mean difference for simvastatin vs placebo, -0.61; 95% CI, -3.69 to 2.46; P = .70). Similarly, there were no significant group differences in any of the secondary outcomes or evidence for differences in adverse effects between groups. A planned secondary analysis indicated that changes in plasma C-reactive protein and lipids from baseline to end point did not mediate response to simvastatin. Conclusions and Relevance: In this randomized clinical trial, simvastatin provided no additional therapeutic benefit for depressive symptoms in TRD compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT03435744.


Assuntos
Depressão , Transtorno Depressivo Maior , Adulto , Humanos , Feminino , Masculino , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Sinvastatina , Proteína C-Reativa , Quimioterapia Combinada , Antidepressivos/uso terapêutico , Método Duplo-Cego , Lipídeos
16.
Chemosphere ; 287(Pt 1): 132112, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34523464

RESUMO

Soils functions, fertility, and microbial abundance may alter in various ways by the biochar amendments to the soil. This study revealed the way of pyrolysis temperature influences the biochar quality and its addition for improving soil properties. The SS biochar was synthesized via pyrolysis and characterized by SEM and FTIR for studying surface images and chemical functional groups. The biochar upon addition with soil was studied for physiological parameters of plants like seed germination index, root length, shoot length, biomass, metal (loid) analysis of soil, SS and SS biochar, total organic content, C: N ratio, NPK values, etc. Besides, combinations of biochar: soil {1:3 (25% + 75%), 1:1 (50% + 50%), and 3:1 (75% + 25%)} ratios were used for studying the effect of biochar on soil microbial community. The 16S rRNA metagenomic analysis revealed the dominance of phyla: Proteobacteria, Actinobacteria, and Acidobacteria that influence the soil nutrient cycle when applied at ratio 1:3. This study highlights the valorization of SS into biochar and studied the effect of biochar augmentation with soil; its impact on soil nutrients, microbial abundance, and plant biomass enhancement. The greener approach also mitigates and helps in the sustainable management of solid wastes, thus reducing GHGs emissions and improves nutrient cycling.


Assuntos
Esgotos , Solo , Biomassa , Carvão Vegetal , Nutrientes , RNA Ribossômico 16S , Resíduos Sólidos
17.
Chemosphere ; 293: 133474, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34979200

RESUMO

The increasing agro-demands with the burgeoning population lead to the accumulation of lignocellulosic residues. The practice of burning agri-residues has consequences viz. Release of soot and smoke, nutrient depletion, loss of soil microbial diversity, air pollution and hazardous effects on human health. The utilization of agricultural waste as biomass to synthesize biochar and biofuels, is the pertinent approach for attaining sustainable development goals. Biochar contributes in the improvement of soil properties, carbon sequestration, reducing greenhouse gases (GHG) emission, removal of organic and heavy metal pollutants, production of biofuels, synthesis of useful chemicals and building cementitious materials. The biochar characteristics including surface area, porosity and functional groups vary with the type of biomass consumed in pyrolysis and the control of parameters during the process. The major adsorption mechanisms of biochar involve physical-adsorption, ion-exchange interactions, electrostatic attraction, surface complexation and precipitation. The recent trend of engineered biochar can enhance its surface properties, pH buffering capacity and presence of desired functional groups. This review focuses on the contribution of biochar in attaining sustainable development goals. Hence, it provides a thorough understanding of biochar's importance in enhancing soil productivity, bioremediation of environmental pollutants, carbon negative concretes, mitigation of climate change and generation of bioenergy that amplifies circular bioeconomy, and concomitantly facilitates the fulfilment of the United Nation Sustainable Development Goals. The application of biochar as seen is primarily targeting four important SDGs including clean water and sanitation (SGD6), affordable and clean energy (SDG7), responsible consumption and production (SDG12) and climate action (SDG13).


Assuntos
Recuperação e Remediação Ambiental , Solo , Carvão Vegetal/química , Mudança Climática , Humanos , Solo/química
18.
Medicine (Baltimore) ; 101(1): e28286, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35029877

RESUMO

ABSTRACT: This study investigates the active components and mechanism of Shufeng Jiedu Capsules (SFJDC) against novel coronavirus through network pharmacology and molecular docking.The TCMSP, TCMID, and BATMAN-TCM databases were used to retrieve the components of SFJDC. The active components were screened by ADME (absorption, distribution, metabolism, and excretion) parameters, and identified by Pubchem, Chemical Book, and ChemDraw softwares. The molecular docking ligands were constructed. SARS Coronavirus-2 Major Protease (SARS-CoV-2-Mpro) and angiotension converting enzyme 2 (ACE2) were used as molecular docking receptors. AutoDock software was used for molecular docking. Cytoscape 3.7.1 software was used to generate an herbs-active components-targets network. Gene Ontology gene function and Kyoto Encyclopedia of Genes and Genomes signal pathway analysis were performed by DAVID data.A total of 1244 components were identified from SFJDC, and 210 active components were obtained. Among them, 97 active components were used as docking ligands to dock with SARS-CoV-2-Mpro and ACE2. There were 48 components with good binding activity to SARS-CoV-2-Mpro. Ten active components (including 7-Acetoxy-2-methylisoflavone, Kaempferol, Quercetin, Baicalein, Glabrene, Glucobrassicin, Isoglycyrol, Wogonin, Petunidin, and Luteolin) combined with SARS-CoV-2-Mpro and ACE2 simultaneously. Among them, Kaempferol, Wogonin, and Baicalein showed higher binding activity. The herbs-active components-targets network contained 7 herbs, 10 active components, and 225 targets. The 225 target targets were involved in 653 biological processes of Gene Ontology analysis and 130 signal pathways (false discovery rate ≤ 0.01) of Kyoto Encyclopedia of Genes and Genomes analysis.The active components of SFJDC (such as Kaempferol, Wogonin, and Baicalein) may combine with ACE2 and act on multiple signaling pathways and targets to exert therapeutic effect on novel coronavirus.


Assuntos
Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular/métodos , Farmacologia em Rede , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2 , Humanos , Quempferóis , Ligantes , SARS-CoV-2/genética
19.
Chemosphere ; 307(Pt 4): 136124, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35995194

RESUMO

The rapid growth of the industrial sector has expedited the accumulation of heavy metal(loid)s in the environment at hazardous levels. The elements such as arsenic, lead, mercury, cadmium and chromium are lethal in terms of toxicity with severe health impacts. With issues like water scarcity, limitations in wastewater treatment, and costs pertaining to detection in environmental matrices; their rapid and selective detection for reuse of effluents is of the utmost priority. Biosensors are the futuristic tool for the accurate qualitative and quantitative analysis of a specific analyte and integrate biotechnology, microelectronics and nanotechnology to fabricate a miniaturized device without compromising the sensitivity, specificity and accuracy. The characteristic features of supporting matrix largely affect the biosensing ability of the device and incorporation of highly sensitive and durable metal organic frameworks (MOFs) are reported to enhance the efficiency of advanced biosensors. Electrochemical biosensors are among the most widely developed biosensors for the detection of heavy metal(loids), while direct electron transfer approach from the recognition element to the electrode has been found to decrease the chances of interference. This review provides an insight into the recent progress in biosensor technologies for the detection of prevalent heavy metal(loid)s; using advanced support systems such as functional metal-based nanomaterials, carbon nanotubes, quantum dots, screen printed electrodes, glass beads etc. The review also delves critically in comparison of various techno-economic studies and the latest advances in biosensor technology.


Assuntos
Arsênio , Técnicas Biossensoriais , Mercúrio , Estruturas Metalorgânicas , Metais Pesados , Nanotubos de Carbono , Cádmio , Cromo , Metais Pesados/análise , Água
20.
Bioresour Technol ; 361: 127605, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35835423

RESUMO

The enormous use of synthetic antibiotic and personal care products has impacted the natural microbiome and ecosystem. Overtime, treatment technologies developed suffered due to incomplete removal hence, a pilot dual-chambered microbial peroxide-producing cell that degrades ampicillin catalyzed by homogenous Fenton-reaction was designed. The system reported maximum current at 16.714 ± 0.048 µAcm-2, power output of 1.956 ± 0.015 mW m-2; 88 ± 2.90 mM of H2O2 generation with Na2SO4 that degraded 95.9 ± 3.00 to 97.8 ± 3.20% of 10 mg L-1ampicillin within 72 hrs with electro-active Shewanella putrefaciens. An E. coli bioactivity assay with ampicillin exhibited no sensitivity zone due to the loss of activity. Analytical spectroscopic studies reveal ß-Lactam ring deformation; Liquid Chromatography-Mass Spectroscopy clearly shows the presence of degradation metabolites. A sustainable wastewater treatment with 72 ± 4.5% reduction in anodic chemical oxygen demand was achieved. Present results designate the technology, as promising for effective antibiotics removal for wastewater treatment concomitant with electricity generation.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água , Ampicilina , Antibacterianos/farmacologia , Ecossistema , Eletrodos , Escherichia coli/metabolismo , Peróxido de Hidrogênio/química , Oxirredução , Peróxidos , Águas Residuárias , beta-Lactamas
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