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1.
J Transl Med ; 22(1): 726, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103897

RESUMO

Accurate survival prediction for Non-Small Cell Lung Cancer (NSCLC) patients remains a significant challenge for the scientific and clinical community despite decades of advanced analytics. Addressing this challenge not only helps inform the critical aspects of clinical study design and biomarker discovery but also ensures that the 'right patient' receives the 'right treatment'. However, survival prediction is a highly complex task, given the large number of 'omics; and clinical features, as well as the high degree of freedom that drive patient survival. Prior knowledge could play a critical role in uncovering the complexity of a disease and understanding the driving factors affecting a patient's survival. We introduce a methodology for incorporating prior knowledge into machine learning-based models for prediction of patient survival through Knowledge Graphs, demonstrating the advantage of such an approach for NSCLC patients. Using data from patients treated with immuno-oncologic therapies in the POPLAR (NCT01903993) and OAK (NCT02008227) clinical trials, we found that the use of knowledge graphs yielded significantly improved hazard ratios, including in the POPLAR cohort, for models based on biomarker tumor mutation burden compared with those based on knowledge graphs. Use of a model-defined mutational 10-gene signature led to significant overall survival differentiation for both trials. We provide parameterized code for incorporating knowledge graphs into survival analyses for use by the wider scientific community.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Aprendizado de Máquina , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Análise de Sobrevida , Prognóstico , Modelos de Riscos Proporcionais , Gráficos por Computador , Mutação/genética , Conhecimento
2.
Environ Res ; 259: 119448, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38942255

RESUMO

Dye wastewater consists of high solids concentrations, heavy metals, minor contaminants, dissolved chemical oxygen demand, and microorganisms. Nanoflowers are nanoparticles that resemble flowers when viewed at a microscopic level. Inorganic metal oxide nanoflowers have been discovered to be a potential source for overcoming this situation. Their flower-like features give them a higher surface area to volume ratio and porosity structure, which can absorb a significant amount of dye. The metal oxide nanoflower synthesized from different synthesis methods is used to compare which one is cost-effective and capable of generating a large scale of nanoflower. This review has demonstrated outstanding dye removal efficiency by applying inorganic nanoflowers to dye removal. Since both adsorption and photocatalytic reactions enhance the dye degradation process, complete dye degradation could be achieved. Meanwhile, the inorganic metal oxide nanoflowers' exemplary reusability characteristics with negligible performance drop further prove that this approach is highly sustainable and may help to save costs. This review has proven the momentum of obtaining high dye removal efficiency in wastewater treatment to conclude that the metal oxide nanoflower study is worth researching.


Assuntos
Corantes , Águas Residuárias , Poluentes Químicos da Água , Corantes/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Águas Residuárias/química , Águas Residuárias/análise , Eliminação de Resíduos Líquidos/métodos , Óxidos/química , Purificação da Água/métodos , Nanopartículas Metálicas/química , Nanoestruturas/química
3.
Mol Divers ; 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39470912

RESUMO

Proteolytic enzymes are closely associated with cancer and are important in different phases, including tumor growth, angiogenesis, and metastasis. Despite efforts to target matrix metalloproteases (MMPs), clinical trials have often resulted in various side effects such as musculoskeletal pain, joint stiffness, and tendinitis, making them less optimal for chronic cancer treatment. Thus, there is a need for the identification of other protease targets that would provide different approaches towards the management of cancer. Of these targets, Cathepsin L (CatL) is a lysosomal cysteine protease that has been identified as a therapeutic target that is implicated in cancer development and metastasis. In this study, we performed an integrated approach of virtual screening and molecular dynamics (MD) simulations to identify the potential inhibitors of CatL from a library of drugs that have been used for different treatments. Towards this goal, we performed virtual screening of the DrugBank database and found two repurposed drugs, Irinotecan and Nilotinib, against CatL based on their docking profiles, favorable docking scores, and specific interaction with the CatL binding pocket. MD simulations of the Irinotecan and Nilotinib bound structures with CatL were carried out, and the analysis showed that both these compounds could function as CatL inhibitors as the protein-ligand interactions were stable for 300 ns. This study highlights the robustness of these drugs bound to CatL and indicates that they could be repurposed for the treatment of cancer. These findings endorse the use of computer-based approaches for the identification of new inhibitors, and the present study will be a useful resource for future experimental research towards the targeting of CatL in cancer therapeutics.

4.
Arch Pharm (Weinheim) ; 357(11): e2400402, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39221527

RESUMO

Cancer ranks among the most life-threatening diseases worldwide and is continuously affecting all age groups. Consequently, many research studies are being carried out to develop new cancer treatments, but many of them experience resistance and cause severe toxicity to the patients. Therefore, there is a continuous need to design novel anticancer agents that are target-based, have a higher potency, and have minimal toxicity. The imidazo[1,2-a]pyridine (IP) pharmacophore has been found to be a prominent moiety in the field of medicinal chemistry due to its vast biological properties. Also, it holds immense potential for combating cancer with minimal side effects, depending on the substitution patterns of the core structure. IPs exhibit significant capability in regulating various cellular pathways, offering possibilities for targeted anticancer effects. The present review summarizes the anticancer profile of numerous IP derivatives synthesized and developed by various researchers from 2016 till now, as inhibitors of phosphoinositide-3-kinase/mammalian target of rapamycin (PI3K/mTOR), protein kinase B/mammalian target of rapamycin (Akt/mTOR), aldehyde dehydrogenase (ALDH), and tubulin polymerization. This review provides a comprehensive analysis of the anticancer activity afforded by the discussed IP compounds, emphasizing the structure-activity-relationships (SARs). The aim is also to underscore the potential therapeutic future of the IP moiety as a potent partial structure for upcoming cancer drug development and to aid researchers in the field of rational drug design.


Assuntos
Antineoplásicos , Imidazóis , Piridinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Relação Estrutura-Atividade , Imidazóis/farmacologia , Imidazóis/química , Imidazóis/síntese química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Estrutura Molecular
5.
J Environ Manage ; 353: 120170, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38308991

RESUMO

The stress of pharmaceutical and personal care products (PPCPs) discharging to water bodies and the environment due to increased industrialization has reduced the availability of clean water. This poses a potential health hazard to animals and human life because water contamination is a great issue to the climate, plants, humans, and aquatic habitats. Pharmaceutical compounds are quantified in concentrations ranging from ng/Lto µg/L in aquatic environments worldwide. According to (Alsubih et al., 2022), the concentrations of carbamazepine, sulfamethoxazole, Lutvastatin, ciprofloxacin, and lorazepam were 616-906 ng/L, 16,532-21635 ng/L, 694-2068 ng/L, 734-1178 ng/L, and 2742-3775 ng/L respectively. Protecting and preserving our environment must be well-driven by all sectors to sustain development. Various methods have been utilized to eliminate the emerging pollutants, such as adsorption and biological and advanced oxidation processes. These methods have their benefits and drawbacks in the removal of pharmaceuticals. Successful wastewater treatment can save the water bodies; integrating green initiatives into the main purposes of actor firms, combined with continually periodic awareness of the current and potential implications of environmental/water pollution, will play a major role in water conservation. This article reviews key publications on the adsorption, biological, and advanced oxidation processes used to remove pharmaceutical products from the aquatic environment. It also sheds light on the pharmaceutical adsorption capability of adsorption, biological and advanced oxidation methods, and their efficacy in pharmaceutical concentration removal. A research gap has been identified for researchers to explore in order to eliminate the problem associated with pharmaceutical wastes. Therefore, future study should focus on combining advanced oxidation and adsorption processes for an excellent way to eliminate pharmaceutical products, even at low concentrations. Biological processes should focus on ideal circumstances and microbial processes that enable the simultaneous removal of pharmaceutical compounds and the effects of diverse environments on removal efficiency.


Assuntos
Cosméticos , Poluentes Químicos da Água , Purificação da Água , Humanos , Águas Residuárias , Poluentes Químicos da Água/análise , Cosméticos/análise , Purificação da Água/métodos , Água , Preparações Farmacêuticas
6.
AAPS PharmSciTech ; 25(6): 145, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918292

RESUMO

The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after oral administration. AAHNPs were developed by microinjection technique and optimized by 3-factor 3-level Box-Behnken design. The AAHNPs were evaluated for morphology, FTIR, X-ray diffraction, in-vitro release, ex-vivo permeation, in-vitro antioxidant, and in-vivo anti-inflammatory activity. The optimized AAHNPs (AAHNPsopt) displayed 384.5 ± 6.36nm of PS, 0.376 of PDI, 23.0 mV of ZP, and 80.01 ± 1.89% of EE. FTIR and X-ray diffraction study results revealed that AA was encapsulated into a HNPs matrix. The AAHNPsopt showed significant (P < 0.05) high and sustained release of AA (86.72 ± 4.92%) than pure AA (29.87 ± 3.11%) in 24h. AAHNPsopt showed an initial fast release of AA (20.12 ± 3.07% in 2h), which succeeded in reaching the therapeutic concentration. The AAHNPsopt showed 2.49-fold higher ex-vivo gut permeation flux than pure AA due to the presence of lipid and surfactant. The AAHNPsopt exhibited significantly (P < 0.05, P < 0.01, P < 0.001) higher antioxidant activity as compared to pure AA at each concentration. AAHNPsopt formulation displayed a significantly (P < 0.05) higher anti-inflammatory effect (21.51 ± 2.23% swelling) as compared to pure AA (46.51 ± 1.74% swelling). From the in-vitro and in-vivo finding, it was concluded that HNPs might be a suitable carrier for the improvement of the therapeutic efficacy of the drug.


Assuntos
Abietanos , Anti-Inflamatórios , Antioxidantes , Portadores de Fármacos , Lipídeos , Nanopartículas , Polímeros , Nanopartículas/química , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Ratos , Polímeros/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Lipídeos/química , Portadores de Fármacos/química , Abietanos/farmacologia , Abietanos/administração & dosagem , Abietanos/química , Difração de Raios X/métodos , Liberação Controlada de Fármacos , Administração Oral , Masculino , Tamanho da Partícula , Ratos Wistar , Química Farmacêutica/métodos
7.
Saudi Pharm J ; 32(10): 102167, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39286769

RESUMO

Opuntia (Cactaceae) species are native to arid and semi-arid regions of Mexico and the southern United States and grow in various climatic zones. Opuntia dillenii is a cactus fruit with many beneficial properties, and it is used as a medicinal plant in various countries. This review paper provides updated information on the phytochemical and pharmacological aspects of O. dillenii. The fruit contains valuable compounds such as flavonoids, phenolics, ascorbic acid, betanin, and essential elements, which have been isolated and identified. The fruit also exhibits diverse pharmacological activities, such as antioxidant, anti-inflammatory, anti-tumor, neuroprotective, hepatoprotective, hypotensive, anti-diabetic, antifungal, and anticancer effects. Moreover, molecular docking and ADMET predictions were performed to evaluate the antibacterial potential of the fruit against Escherichia coli protein. This paper suggests that O. dillenii has significant potential as a complementary therapy for various pathological conditions.

8.
Funct Integr Genomics ; 23(2): 195, 2023 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-37270446

RESUMO

Noncoding RNAs (ncRNAs), which make up a significant portion of the mammalian transcriptome and plays crucial regulatory roles in expression of genes and other biological processes, have recently been found. The most extensively researched of the sncRNAs, microRNAs (miRNAs), have been characterized in terms of their synthesis, roles, and significance in the tumor development. Its crucial function in the stem cell regulation, another class of sncRNAs known as aspirRNAs, has attracted attention in cancer research. The investigations have shown that long non-coding RNAs have a crucial role in controlling developmental stages, such as mammary gland development. Additionally, it has been discovered that lncRNA dysregulation precedes the development of several malignancies, including breast cancer. The functions of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the onset and development of the breast cancer are described in this study. Additionally, future perspectives of various ncRNA-based diagnostic, prognostic, and therapeutic approaches also discussed.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Prognóstico , Prevalência , RNA não Traduzido/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Biomarcadores , Mamíferos/genética , Mamíferos/metabolismo
9.
Small ; 19(51): e2208209, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37096900

RESUMO

Hydrogen peroxide (H2 O2 ) is a primary reactive oxygen species (ROS) that can act as a chemical signal in developing and progressing serious and life-threatening diseases like cancer. Due to the stressful nature of H2 O2 , there is an urgent need to develop sensitive analytical approaches to be applied to various biological matrices. Herein, a portable point-of-care electrochemical system based on MXene-Co3 O4 nanocomposites to detect H2 O2 in different cancer cell-lines is presented. The developed sensor is affordable, disposable, and highly selective for H2 O2 detection. This approach achieves a dynamic linear range of 75 µm with a LOD of 0.5 µm and a LOQ of 1.6 µm. To improve the practical application, the level of ROS is evaluated both in cancer cell lines MDA-MB-231 and DU145, respectively, to breast and prostate cancers, and in healthy HaCat cells. Moreover, the same cancer cells are treated with transforming growth factor-ß1, and MXene-Co3 O4 modified strip is capable to monitorROS variation. The results are satisfactory compared with the cellular ROS fluorescent assay based on DCFH/DCFH-DA. These results open new perspectives for real-time monitoring of cancer progression and the efficacy of the therapy.


Assuntos
Nanocompostos , Neoplasias , Masculino , Humanos , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio/metabolismo , Neoplasias/tratamento farmacológico
10.
Environ Res ; 220: 115169, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587722

RESUMO

To date, the development of renewable fuels has become a normal phenomenon to solve the problem of diesel fuel emissions and the scarcity of fossil fuels. Biodiesel production has some limitations, such as two-step processes requiring high free fatty acids (FFAs), oil feedstocks and gum formation. Hydrotreated vegetable oil (HVO) is a newly developed international renewable diesel that uses renewable feedstocks via the hydrotreatment process. Unlike FAME, FFAs percentage doesn't affect the HVO production and sustains a higher yield. The improved characteristics of HVO, such as a higher cetane value, better cold flow properties, lower emissions and excellent oxidation stability for storage, stand out from FAME biodiesel. Moreover, HVO is a hydrocarbon without oxygen content, but FAME is an ester with 11% oxygen content which makes it differ in oxidation stability. Waste sludge palm oil (SPO), an abundant non-edible industrial waste, was reused and selected as the feedstock for HVO production. Techno-economical and energy analyses were conducted for HVO production using Aspen HYSYS with a plant capacity of 25,000 kg/h. Alternatively, hydrogen has been recycled to reduce the hydrogen feed. With a capital investment of RM 65.86 million and an annual production cost of RM 332.56 million, the base case of the SPO-HVO production process was more desirable after consideration of all economic indicators and HVO purity. The base case of SPO-HVO production could achieve a return on investment (ROI) of 89.03% with a payback period (PBP) of 1.68 years. The SPO-HVO production in this study has observed a reduction in the primary greenhouse gas, carbon dioxide (CO2) emission by up to 90% and the total annual production cost by nearly RM 450 million. Therefore, SPO-HVO production is a potential and alternative process to produce biobased diesel fuels with waste oil.


Assuntos
Óleos de Plantas , Esgotos , Óleo de Palmeira , Emissões de Veículos , Biocombustíveis/análise , Gasolina/análise , Hidrogênio , Oxigênio
11.
Environ Res ; 219: 115089, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36529332

RESUMO

In the present work, the synthesis of cellulose nanowhiskers (CNW)/chitosan nanocomposite films via deep eutectic solvents (DES) changing the chemical structures were carried out. It was observed that a pure chitosan film has broadband at 3180-3400 cm-1, indicating amide and hydroxyl groups. Upon CNW incorporation, the peak gets sharper and stronger and shifts to a greater wavelength. Further, the addition of DES infuses more elements of amide into the nanocomposite films. Moreover, the mechanical properties incorporating CNW filler into a chitosan matrix show an enhancement in tensile strength (TS), Young's modulus (YM), and elongation at break. The TS and YM increase while the elongation decrease as the CNW concentration increases. The YM of biocomposite films is increased to 723 MPa at 25% CNW into chitosan films. Besides, the TS has enhanced to 11.48 MPa at 15% CNW concentration in the biocomposite films. The elongation at break has decreased to 11.7% at 25% CNW concentration. Hence, incorporating CNW into the chitosan matrix via DES can still improve the mechanical properties of the nanocomposite films. Therefore, the application of DES results in a lower YM and TS as the films are hygroscopic. In conclusion, DES can be considered the new green solvent media for synthesizing materials. It has the potential to replace ionic liquids due to its biodegradability and non-toxic properties while preserving the character of low-vapour pressure. Besides that, chitosan can be used as potential material for applications in process industries, such as the biomedical and pharmaceutical industries. Thus, DES can be used as a green solvent and aim to reduce the toxic effect of chemicals on the environment during chemical production.


Assuntos
Quitosana , Nanocompostos , Celulose/química , Quitosana/química , Solventes Eutéticos Profundos , Solventes , Nanocompostos/química
12.
Environ Res ; 224: 115527, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36822539

RESUMO

Bacterial strains belonging to Citrobacter spp. were reported to produce polysaccharides consisting of N-acetylglucosamine and glucosamine like chitosan, with high flocculation activity. In this work, the flocculation dewatering performance of activated sludge conditioned by a novel cationic chitosan-like bioflocculant (BF) named BF01314, produced from Citrobacter youngae GTC 01314, was evaluated under the influences of flocculant dosage, pH, and temperature. At BF dosage as low as 0.5 kg/t DS, the sludge dewaterability was significantly enhanced in comparison to the raw (untreated) sludge, featuring well-flocculated characteristic (reduction in CST from 22.0 s to 9.4 s) and good sludge filterability with reduced resistance (reduction in SRF by one order from 7.42 × 1011 to 9.59 × 1010 m/kg) and increased compactness of sludge (increase in CSC from 15.2 to 23.2%). Besides, the BF demonstrated comparable high sludge dewatering performance within the pH range between 2 and 8, and temperature range between 25 °C and 80 °C. Comparison between the BF, the pristine chitosan and the commercial cationic copolymer MF 7861 demonstrated equivalent performance with enhanced dewaterability at the dosage between 2.0 and 3.0 kg/t DS. Besides, the BF demonstrated strong flocculation activity (>99%) when added to the sludge suspension using moderate to high flocculation speeds (100-200 rpm) with at least 3-min mixing time. The BF's reaction in sludge flocculation was best fitted with a pseudo first-order kinetic model. Electrostatic charge patching and polymer bridging mechanisms are believed to be the dominant mechanistic phenomena during the BF's sludge conditioning process (coagulation-flocculation).


Assuntos
Quitosana , Esgotos , Cinética , Citrobacter , Floculação , Polímeros , Eliminação de Resíduos Líquidos , Água , Filtração
13.
Environ Res ; 236(Pt 1): 116646, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37481054

RESUMO

The mutating SARS-CoV-2 necessitates gauging the role of airborne particulate matter in the COVID-19 outbreak for designing area-specific regulation modalities based on the environmental state-of-affair. To scheme the protocols, the hotspots of air pollutants such as PM2.5, PM10, NH3, NO, NO2, SO2, and and environmental factors including relative humidity (RH), and temperature, along with COVID-19 cases and mortality from January 2020 till December 2020 from 29 different ground monitoring stations spanning Delhi, are mapped. Spearman correlation coefficients show a positive relationship between SARS-COV-2 with particulate matter (PM2.5 with r > 0.36 and PM10 with r > 0.31 and p-value <0·001). Besides, SARS-COV-2 transmission showed a substantial correlation with NH3 (r = 0.41), NO2 (r = 0.36), and NO (r = 0.35) with a p-value <0.001, which is highly indicative of their role in SARS-CoV-2 transmission. These outcomes are associated with the source of PM and its constituent trace elements to understand their overtone with COVID-19. This strongly validates temporal and spatial variation in COVID-19 dependence on air pollutants as well as on environmental factors. Besides, the bottlenecks of missing latent data, monotonous dependence of variables, and the role air pollutants with secondary environmental variables are discussed. The analysis set the foundation for strategizing regional-based modalities considering environmental variables (i.e., pollutant concentration, relative humidity, temperature) as well as urban and transportation planning for efficient control and handling of future public health emergencies.

14.
Molecules ; 28(13)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37446854

RESUMO

Ionogels are hybrid materials comprising an ionic liquid confined within a polymer matrix. They have garnered significant interest due to their unique properties, such as high ionic conductivity, mechanical stability, and wide electrochemical stability. These properties make ionogels suitable for various applications, including energy storage devices, sensors, and solar cells. However, optimizing the electrochemical performance of ionogels remains a challenge, as the relationship between specific capacitance, ionic conductivity, and electrolyte solution concentration is yet to be fully understood. In this study, we investigate the impact of electrolyte solution concentration on the electrochemical properties of ionogels to identify the correlation for enhanced performance. Our findings demonstrate a clear relationship between the specific capacitance and ionic conductivity of ionogels, which depends on the availability of mobile ions. The reduced number of ions at low electrolyte solution concentrations leads to decreased ionic conductivity and specific capacitance due to the scarcity of a double layer, constraining charge storage capacity. However, at a 31 vol% electrolyte solution concentration, an ample quantity of ions becomes accessible, resulting in increased ionic conductivity and specific capacitance, reaching maximum values of 58 ± 1.48 µS/cm and 45.74 F/g, respectively. Furthermore, the synthesized ionogel demonstrates a wide electrochemical stability of 3.5 V, enabling diverse practical applications. This study provides valuable insights into determining the optimal electrolyte solution concentration for enhancing ionogel electrochemical performance for energy applications. It highlights the impact of ion pairs and aggregates on ion mobility within ionogels, subsequently affecting their resultant electrochemical properties.


Assuntos
Eletrólitos , Líquidos Iônicos , Capacitância Elétrica , Condutividade Elétrica , Polímeros
15.
Molecules ; 28(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36770968

RESUMO

Cisplatin (CP) is a platinum compound of the alkylating agent class that is used for the treatment of various types of cancer. However, CP treatments in cancer patients are accountable for nephrotoxicity, as it is a major adverse effect. Hence, this research study was proposed to investigate the nephroprotective effect of diosmin, a flavonoid glycoside of hesperidin derivatives against cisplatin-induced kidney damage. Wistar rats received a single intraperitoneal (i.p) injection of CP (7.5 mg/kg, i.p) to induce nephrotoxicity. The administration of CP significantly (p < 0.001) increased the markers of kidney function test (creatinine, blood urea nitrogen, and uric acid) and demonstrated histopathological changes in the kidney of the CP-treated nephrotoxic group. In addition, the CP-treated nephrotoxic group demonstrated a significant (p < 0.001) increase in lipid peroxidation (LPO) levels and depleted activities of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT).However, diosmin (100 and 200 mg/kg) treatments significantly reduced the elevated levels of kidney function test parameters and restored structural changes in the kidney (p < 0.001). The administration of diosmin (100 and 200 mg/kg) significantly (p < 0.001) reduced LPO levels, increased GSH content and showed improvements in the activities of GPx, GR, SOD and CAT. The markers of inflammatory cytokines such as IL-1ß, IL-6 and TNFα significantly (p < 0.001) increased in the CP-treated nephrotoxic group, whereas diosmin (100 and 200 mg/kg) treatments significantly (p < 0.001) reduced the elevated levels of these cytokines. The findings of this research demonstrate the nephroprotective effect of diosmin against CP-induced kidney damage. Therefore, we conclude that diosmin may be used as a supplement in the management of nephrotoxicity associated with CP treatments in cancer patients.


Assuntos
Diosmina , Nefropatias , Ratos , Animais , Cisplatino/farmacologia , Interleucina-6/metabolismo , Diosmina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Rim , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Estresse Oxidativo , Antioxidantes/farmacologia , Citocinas/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo
16.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 14-21, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36495525

RESUMO

The current article deals with the in-silico along with enzyme kinetics approach to search for a prominent AChE enzyme inhibitor among the known natural compounds. The computational tools were involved for this purpose and eventual vincamine, a monoterpenoid indole alkaloid, was selected based on several parameters, including free energy of binding (-10.77 kcal/mol) and ADME parameter. Computationally, it confirmed the interaction between vincamine and AChE at an indistinguishable locus from that of substrate AChI (-3.94 kcal/mol) but with much higher binding energy. Interestingly, amino acid residues Gly120, Gly121, Gly122, Glu202, Trp86, Tyr133, Ser203, Phe297, and His447 of AChE were found to be common in these interactions. Further, these findings were approved with wet lab tests where detailed kinetics was studied. It was found that vincamine inhibited AChE with the inhibition constant Ki (239 µM). The value of  IC50 (239 µM) and KM (0.598 mM) was determined and further confirmed by Dixon, Lineweaver- Burk reciprocal, Hanes, and Eadie- Hofstee plots, respectively. The mode of interaction of the compound was found to be competitive for AChE. Thus, the present computational and enzyme kinetics studies conclude that vincamine can be a promising inhibitor of AChE for the effective management of AD.


Assuntos
Acetilcolinesterase , Vincamina , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Cinética , Inibidores Enzimáticos
17.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 106-114, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809297

RESUMO

Alzheimer's disease is a chronic neurodegenerative ailment and the most familiar type of dementia in the older population with no effective cure to date. It is characterized by a decrease in memory, associated with the mutilation of cholinergic neurotransmission. Presently, acetylcholinesterase inhibitors have emerged as the most endorsed pharmacological medications for the symptomatic treatment of mild to moderate Alzheimer's disease. This study aimed to research the molecular enzymatic inhibition of human brain acetylcholinesterase by a natural compound emetine and I3M. Molecular docking studies were used to identify superior interaction between enzyme acetylcholinesterase and ligands. Furthermore, the docked acetylcholinesterase-emetine complex was validated statistically using an analysis of variance in all tested conformers. In this interaction, H-bond, hydrophobic interaction, pi-pi, and Cation-pi interactions played a vital function in predicting the accurate conformation of the ligand that binds with the active site of acetylcholinesterase. The conformer with the lowest free energy of binding was further analyzed. The binding energy for acetylcholinesterase complex with emetine and I3M was -9.72kcal/mol and -7.09kcal/mol, respectively. In the current study, the prediction was studied to establish a relationship between binding energy and intermolecular energy (coefficient of determination [R2 linear = 0.999), and intermolecular energy and Van der wall forces (R2 linear = 0.994). These results would be useful in gaining structural insight for designing novel lead compounds against acetylcholinesterase for the effective management of Alzheimer's disease.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Sítios de Ligação , Encéfalo/metabolismo , Domínio Catalítico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Emetina/química , Emetina/metabolismo , Humanos , Indóis , Ligantes , Simulação de Acoplamento Molecular
18.
Environ Res ; 214(Pt 4): 114149, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36007570

RESUMO

Biodiesel is renewable, biodegradable, biocompatible (non-toxic) and environmentally friendly, which emits less pollution than traditional fossil-based diesel, making it the most promising and ideal option. However, biodiesel is facing many current issues, mostly related to the utilisation of homogeneous catalytic technology, and this circumstance obstructs its potential development and advancement. Therefore, new pathways for biodiesel production need to be explored, and the aforementioned issues need to be addressed. Recently, a study was conducted on the impregnated magnetic biochar derived from a waste palm kernel shell (PKS) catalyst that can replace conventional catalysts due to its reusability property. Nevertheless, the environmental impacts of impregnated magnetic biochar derived from waste PKS catalyst for biodiesel production are yet to be studied. This study focuses on the evaluation of the life cycle assessment (LCA) of palm-based cooking oil for biodiesel production catalysed by impregnated magnetic biochar derived from waste PKS. Simapro was used in this study to evaluate the impact assessment methodologies. Case 1 (6.64 × 102 Pt) has contributed less to environmental impacts than Case 2 (1.83 × 103 Pt). This indicates purchasing refined palm oil for biodiesel production may reduce environmental impacts by 64% compared to producing biodiesel from raw fruit bunches. In the midpoint assessment, the transesterification process was identified as the hotspot and marine aquatic ecotoxicity as the highest impact category with a value of 1.00 × 106 kg 1,4-DB eq for 1 tonne of biodiesel produced. The endpoint results showed that Case 1 revealed the greatest impact on the transesterification process, with cumulative damage of 461 Pt. Scenario without processing the raw palm fruit bunches to obtained palm oil was better than Case 2. Further research should be conducted on life cycle cost and sensitivity analysis to evaluate the economic feasibility and promote sustainable biodiesel production.


Assuntos
Biocombustíveis , Óleos de Plantas , Animais , Catálise , Carvão Vegetal , Estágios do Ciclo de Vida , Fenômenos Magnéticos , Óleo de Palmeira
19.
Drug Dev Res ; 83(1): 194-207, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34350600

RESUMO

Nuclear factor kappa B cells (NF-κB) activation causes induction of the noncanonical IκB kinases (I-kappa-B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) in liver and fat after high fat diet which followed activating of cascade of counter-inflammation that conserves energy storage. Chrysin (5,7-dihydroxyflavone), a natural flavonoid, present in many plants, honey and propolis, used conventionally to treat numerous ailments. The present study was aimed to identify the protective role of chrysin on the glucose lowering and insulin sensitivity in diet induced obese (DIO) mice by regulating IKKε/TBK1. Chrysin administered therapeutically (60, 100, 200 mg/kg body weight) and preventive mode (200 mg/kg body weight) for 4 and 10 weeks respectively to DIO mice. At last fasting blood glucose, oral glucose tolerance test, serum lipid profile, as well as the expression level of IKKε/TBK1 and triglyceride in the liver tissue were assessed. DIO mice showed impaired glucose tolerance, reduced weight gain, elevated hepatic IKKε/TBK1 expression, fatty acid infiltration triglyceride and increased in plasma insulin and glucose. Chrysin in both therapeutic and preventive mode normalized the altered levels of the same. Overall chrysin improves glycemic control and insulin sensitivity through regulating expression of IKKε/TBK1 in liver of DIO mice.


Assuntos
Quinase I-kappa B , Resistência à Insulina , Animais , Dieta Hiperlipídica/efeitos adversos , Flavonoides/farmacologia , Quinase I-kappa B/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Obesos , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases
20.
BMC Oral Health ; 22(1): 304, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35870965

RESUMO

BACKGROUND: Oral health-related quality of life, a prominent topic in dentistry, has been studied extensively. However, the comparison between various self-perceived and clinical oral health measures still needs to be explored. The purpose of the current study is; first, to report the self-perceived and clinically examined oral health measures that are associated with the oral impacts on daily performances. Second, to identify the oral health measure that best predicts greater oral impact scores. Third, to investigate the difference in findings related to the disease experience measures and the treatment measures. METHODS: A cross-sectional study was carried out on children aged 12-14 years. The prevalence, frequency, and oral impact scores of each daily performance were calculated. Thirteen self-perceived OH conditions were assessed. Clinically examined oral health measures included gingival health, oral hygiene status, DMFT, DT, MT, and FT scores and, one or more decay (1 + D), missing (1 + M) and filled (1 + F) teeth. Simple linear and multiple linear regressions were carried out to report the associations. RESULTS: At least one oral health impacted daily performance was reported by 40% of the total sample of schoolchildren (N = 700). Based on the magnitude and precision of adjusted regression coefficients (RC), decay severity (DT) was identified as a better predictor of a greater oral impact score with regression coefficient values ranging between 0.3 (social contact) and 2.4 (1 + performance). Contrariwise, MT and FT components of DMFT were associated with lower oral impact scores. The self-perceived measures were also associated with oral impact scores and presented similar findings to that of the clinical oral health measures. CONCLUSIONS: Untreated decay significantly impacted daily performances, especially eating, sleeping, studying, and social contact. The findings are of importance to public health practitioners for reporting, treating, and preventing oral health problems in children, and eventually contributing to better oral health-related quality of life.


Assuntos
Cárie Dentária , Saúde Bucal , Adolescente , Criança , Estudos Transversais , Cárie Dentária/epidemiologia , Humanos , Prevalência , Qualidade de Vida , Inquéritos e Questionários
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