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A new matrix framework is presented in this study for the improved ionization efficiency of complex mixtures by matrix-assisted laser desorption ionization (MALDI) mass spectrometry/imaging. Five nitro indole (NI) derivatives [3-methyl-4-nitro-1H-indole (3,4-MNI), 3-methyl-6-nitro-1H-indole (3,6-MNI), 2,3-dimethyl-4-nitro-1H-indole (2,3,4-DMNI), 2,3-dimethyl-6-nitro-1H-indole (2,3,6-DMNI), and 4-nitro-1H-indole (4-NI)] were synthesized and shown to produce both positive and negative ions with a broad class of analytes as MALDI matrices. NI matrices were compared to several common matrices, such as 2,5-dihydroxybenzoic acid (DHB), alpha-cyano-4-hydroxylcinnamic acid (CHCA), sinapinic acid (SA), 1,5-diaminonaphthelene (1,5-DAN), and 9-aminoacridine (9-AA), for the analysis of lipid, peptide, protein, glycan, and perfluorooctanesulfonic acid (PFOS) compounds. 3,4-MNI demonstrated the best performance among the NI matrices. This matrix resulted in reduced ion suppression and better detection sensitivity for complex mixtures, for example, egg lipids/milk proteins/PFOS in tap water, while 2,3,6-DMNI was the best matrix for blueberry tissue imaging. Several important aspects of this work are reported: (1) dual-polarity ion production with NI matrices and complex mixtures; (2) quantitative analysis of PFOS with a LOQ of 0.5 ppb in tap water and 0.05 ppb in MQ water (without solid phase extraction enrichment), with accuracy and precision within 5%; (3) MALDI imaging with 2,3,6-DMNI as a matrix for plant metabolite/lipid identification with ionization enhancement in the negative ion mode m/z 600-900 region; and (4) development of a thin film deposition under/above tissue method for MALDI imaging with a vacuum sublimation matrix on a high-vacuum MALDI instrument.
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Ácidos Alcanesulfónicos , Fluorocarburos , Indoles , Lípidos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Lípidos/análisis , Mezclas Complejas , AguaRESUMEN
Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.
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Apolipoproteínas E , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Pakistán/epidemiología , Masculino , Femenino , Apolipoproteínas E/genética , Persona de Mediana Edad , Enfermedades Cardiovasculares/genética , Adulto , Polimorfismo Genético , Anciano , Factores de Riesgo , Dislipidemias/genética , Dislipidemias/complicaciones , Genotipo , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/complicacionesRESUMEN
Background and Objectives: The main objective of the present study was to determine the role of oxidative markers (glutathione (GSH), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and malondialdehyde (MDA)) and inflammatory biomarkers (interleukin-6 IL-6, tumor necrosis factor α (TNF-α), myeloperoxide (MPO)) in the development of diabetic nephropathy along with routinely used biochemical parameters. Materials and Method: This was a case control study. All the selected patients were screened and enrolled by convenient non-probability sampling technique at the Jinnah hospital in Lahore. Informed consent was obtained before enrollment of the study subjects. A total of 450 patients enrolled in the study, and they were divided into three groups, 150 subjects with type 2 diabetes and 150 diagnosed diabetic nephropathy (DN) vs. 150 healthy individuals as a control group. Five mL of venous blood sample was taken from the antecubital vein of each participant. Statistical analysis was performed by SPSS. The results of all variables were evaluated by using one way ANOVA. Results: The mean value of biochemical parameters (WBCs, platelets, prothrombin time, HbA1c, glucose, urinary albumin-to creatinine ratio (UACR), triglycerides, LDL, HDL, serum creatinine, urinary albumin (creatinine)) were increased and Hb (g/dL), red blood cells (RBCs), hematocrit (Hct), free serum insulin levels, and estimated glomerular filtration rate (eGFR) were decreased in the nephropathy group compared to the control and type 2 diabetes groups. The mean values of MDA, AGE, and AOPPs in type 2 diabetes and diabetic nephropathy were significantly increased compared to the control group. GSH level was decreased in type 2 diabetics and DN patients as compared to the control group. In addition, IL-6, TNFα, and MPO levels were also increased in case of diabetes nephropathy compared to controls. Conclusions: ROS mediated injuries can be prevented by the restoration of an antioxidant defense system, through the administration of antioxidant agents. Moreover, increased levels of inflammatory mediators are responsible for enhancing inflammation in patients with diabetic nephropathy.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Antioxidantes/metabolismo , Creatinina , Estudios de Casos y Controles , Citocinas/metabolismo , Interleucina-6/metabolismo , Biomarcadores , Productos Avanzados de Oxidación de Proteínas , Glutatión , Albúminas , Estrés OxidativoRESUMEN
Liver is a vital organ and is routinely exposed to toxins. Carbon tetrachloride is one such noxious agent which cause toxicity in liver when CYP450 enzyme bio-activates it. Many hepatoprotective agents are available in market with severe side effects. Appropriate agent is required to combat such liver problems. Azole compounds have much therapeutic values in many diseases. Based upon this fact, present study is aimed to evaluate the repurposing of Itraconazole in the prevention of hepatic fibrosis via inhibition of cytochrome P450 pathway. For in-vitro evaluation of cyto-protective effects in HepG2 cells (untreated and treated groups), cell viability assays, antioxidant evaluation, enzyme linked immunosorbent assay (ELISA) and immunocytochemistry was used. For in-vivo evaluation, CCl4 induced liver fibrotic rat model was used and post treated evaluation was done by blood biochemistry, hematoxylin and eosin (H&E) staining and gene expression profiling. Results of the current study indicated hepatoprotective role of itraconazole via inhibition of CYP450 pathway inhibition. Therefore, Itraconazole use could be a potential therapeutic approach to prevent liver fibrosis.
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Inhibidores Enzimáticos del Citocromo P-450/farmacología , Itraconazol/farmacología , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Animales , Tetracloruro de Carbono/metabolismo , Tetracloruro de Carbono/toxicidad , Supervivencia Celular/efectos de los fármacos , Femenino , Células Hep G2 , Humanos , Itraconazol/uso terapéutico , Sustancias Protectoras/farmacología , Ratas , TranscriptomaRESUMEN
This study investigated the influence of three different organic carbon sources including sodium acetate (SOD), glucose (GLU), and starch (STAR), on soluble microbial products (SMP), which presumably have dissimilar uptake rates and metabolic pathways, in sequencing batch reactors (SBR) and their subsequent effects on membrane fouling of ultrafiltration (UF). SMP were mainly characterized by fluorescence excitation emission matrix coupled with parallel factor analysis (EEM-PARAFAC) and size exclusion chromatography (SEC). SMP produced in SOD-fed SBR showed higher abundances of protein-like fluorescent component and large sized aliphatic biopolymer (BP) than GLU- or STAR-fed counterpart did, while the STAR-based operation resulted in more SMP enriched with humic-like fluorescence. The differences in SMP exerted marked effects on UF membrane fouling as indicated by the highest fouling potential with reversibility shown for the SMP from the SOD-fed reactor. Regardless of the carbon source, BP fraction and protein-like component exhibited the greatest extent of reversible fouling, suggesting that size exclusion plays a critical role. However, notable differences in the reversible fouling propensity of relatively smaller size fractions among the three SBRs signified the possible involvement of chemical interactions as a secondary fouling mechanism and its dependency on different carbon sources. Our results provide a new insight into the roles of carbon sources in the characteristics of SMP in biological treatment systems and their effects on the post-treatment using membrane filtration, which is ultimately beneficial to the optimization of biological treatment design and membrane filtration operation.
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Carbono , Ultrafiltración , Reactores Biológicos , Cromatografía en Gel , Membranas Artificiales , Espectrometría de FluorescenciaRESUMEN
Much remains unknown about compositional variations in soluble microbial products (SMP) with the shift of the substrate condition from a feast to a famine phase in biological treatment systems. This study demonstrated that the formation of SMP could be suppressed by up to 75% during the famine phase with the addition of essential nutrients. In contrast, presence of electron acceptor did not play any significant role during the stress condition, showing the similar amounts of SMP (râ¯=â¯0.98, pâ¯<â¯0.05) formation between the bioreactors supplied with air and N2. The SMP formed in the famine phase was more bio-refractory in the famine versus the feast phase with a linear correlation shown between the production and their aromatic structures in the composition (R2â¯>â¯0.95). The fluorescence excitation-emission matrix coupled with parallel factor analysis (EEM-PARAFAC) revealed the presence of four different fluorescent components, including two protein-like (C1 and C4), fulvic-like (C2), and humic-like (C3) components, in the SMP and bEPS formed at different conditions. Both C1 and C4 showed increasing trends (R2â¯>â¯0.95) with the length of starvation in the bioreactors without essential nutrients. Nutrient availability was found to be a key factor to quench the production of large-sized biopolymers. This study provides a wealth of information on operation conditions of activated sludge treatment systems to minimize large sized SMP molecules (particularly proteins), which typically exert many environmental concerns to effluent organic matter quality.
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Reactores Biológicos/microbiología , Aguas del Alcantarillado/microbiología , Administración de ResiduosRESUMEN
Forward osmosis membranes are less prone to fouling with high rejection of salts, and the osmotic membrane bioreactor (OMBR) can be considered as an innovative membrane technology for wastewater treatment. In this study, a submerged OMBR having a cellulose triacetate membrane, with the active layer facing the feed solution configuration, was operated at different organic loading rates (OLRs), i.e., 0.4, 1.2 and 2.0 kg-COD/(m(3)·d) with chemical oxygen demand (COD) concentrations of 200 mg/L, 600 mg/L and 1,000 mg/L, respectively, to evaluate the performance on varying wastewater strengths. High organic content with sufficient amount of nutrients enhanced the biomass growth. High OLR caused more extrapolymeric substances production and less dewaterability. However, no significant differences in fouling trends and flux rates were observed among different OLR operational conditions.
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Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Análisis de la Demanda Biológica de Oxígeno , Reactores Biológicos , Celulosa/análogos & derivados , Celulosa/química , Membranas Artificiales , Ósmosis , Eliminación de Residuos Líquidos/instrumentaciónRESUMEN
In electrokinetic remediation (EKR), the sedimentary dissolved organic matter (DOM) could impede remediation by scavenging reactive species and generating unintended byproducts. Yet its transformation and mechanisms remained largely unknown. This study conducted molecular-level characterization of the water-extractable DOM (WEOM) in EKR using negative-ion electrospray ionization coupled to 21 tesla Fourier transform ion cyclotron resonance mass spectrometry (21 T FT-ICR MS). The results suggested that â¼55 % of the â¼7,000 WEOM compounds identified were reactive, and EKR lowered their diversity, molecular weight distribution, and double-bond equivalent (DBE) through a combination of electrochemical and microbial redox reactions. Heteroatom-containing WEOM (CHON and CHOS) were abundant (â¼ 35% of the total WEOM), with CHOS generally being more reactive than CHON. Low electric potential (1 V/cm) promoted the growth of dealkylation and desulfurization bacteria, and led to anodic CO2 mineralization, anodic cleavage of -SO and -SO3, and cathodic cleavage of -SH2; high electric potential (2 V/cm) only enriched desulfurization bacteria, and differently, led to anodic oxygenation and cathodic hydrogenation of unsaturated and phenolic compounds, in addition to cathodic cleavage of -SH2. The long-term impact of these changes on soil quality and nitrogen-sulfur-carbon flux may be need to studied to identify unknown risks and new applications of EKR.
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Sedimentos Geológicos , Sedimentos Geológicos/química , Espectrometría de Masas , Restauración y Remediación Ambiental , Análisis de Fourier , Compuestos Orgánicos/química , Compuestos Orgánicos/análisisRESUMEN
Membrane fouling and high-strength membrane concentrate production are two limitations of membrane distillation (MD) for landfill leachate treatment. In this study, activated carbon- and biochar-based adsorption processes were integrated into a conventional MD system to overcome these limitations. The organic matter fractionations of the leachate were thoroughly investigated during the treatment. Membrane-reversible and irreversible foulants differed remarkably from the inlet leachate in the non-assisted MD system. Specifically, reversible foulants were characterized by a high abundance of humic-like fluorescent components, high-molecular-weight humic-size constituents, peptides, and unsaturated compounds. In contrast, irreversible foulants were enriched with fulvic-like fluorescent components, low-molecular-weight neutrals, unsaturated compounds, and polyphenols. The adsorption-based pre-treatment effectively removed foulant precursors from landfill leachate, with a relatively higher (20%) adsorption performance for specific biochar used in this study than for activated carbon. Compared with the non-assisted MD system, the biochar-assisted MD system showed improved performance, achieving 40% overall membrane flux recovery, 42% higher filtration fluxes, and 53% lower concentrate production. In addition, a 15% higher removal of irreversible foulants was observed as compared to the reversible foulants, which can potentially increase the membrane lifespan. This study demonstrates the effectiveness of an adsorption-assisted MD system supported by increased filtration, membrane fouling alleviation, and low-strength leachate concentrate generation.
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Carbón Orgánico , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico/química , Contaminantes Químicos del Agua/análisis , DestilaciónRESUMEN
Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 - 244.5±88.24â¯nm diameter with the polydispersity index ranging from 0.20±0.03 - 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC0-∞, AUMC0-∞, t1/2, and MRT0-∞) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX.
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Disponibilidad Biológica , Portadores de Fármacos , Nanopartículas , Paclitaxel , Paclitaxel/farmacocinética , Paclitaxel/administración & dosificación , Paclitaxel/química , Paclitaxel/farmacología , Animales , Administración Oral , Portadores de Fármacos/química , Nanopartículas/química , Materiales Biocompatibles/química , Ratas , Tamaño de la Partícula , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Masculino , Poloxámero/química , Hemólisis/efectos de los fármacos , Liberación de Fármacos , Colesterol/químicaRESUMEN
In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. In this study, we aimed to assess the cytotoxic activity of Kigelia Africana (KA) extracts on breast cancer (MDA-MB-231 and MCF-7) and noncancerous kidney cells (HEK-293T) to develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS to analyze the constituents of EKA and HKA extracts meanwhile the crystal violet and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used to examine the possible cytotoxic effects of plant extracts on our cancer cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run on cell samples to evaluate the differential expression of cell proliferative markers of cancer (BCL-2 and TP53). These phytochemicals have been reported to have binding affinity for some other growth factors and receptors as well which was evaluated by the in-silico molecular docking against Bcl2, EGFR, HER2, and TP53. Our Morphological observation showed a significant difference in the cell morphology and proliferation potential which was decreased under the effect of plant extracts treatment as compared to the control samples. The ethanol extract exhibited a marked antiproliferative activity towards MDA-MB-231 and MCF-7 cell lines with IC50 = 20 and 32 µg/mL, respectively. Quantitative RT-PCR gene expression investigation revealed that the IC50 concentration of ethanolic extract regulated the levels of mRNA expression of apoptotic genes. With the target and active binding site amino acids discovered in the molecular docking investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is the best-docked ligand. The use of this plant in folk remedies justifies its high in vitro anti-cancer capabilities. This work highlights the role of phytochemicals in the inhibition of cancer proliferation. Based on all these findings, it can be concluded that EKA extract has promising anti-proliferative effect on cancerous cells but more study is required in future to further narrow down the active ingredients of total crude extract with specific targets in cancer cells.
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Simulación del Acoplamiento Molecular , Extractos Vegetales , Proteína p53 Supresora de Tumor , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células MCF-7 , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Femenino , Células HEK293 , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
Utilizing medicinal plants and other natural resources to prevent different types of human cancers is the prime focus of attention. Cervical cancer in women ranks as the fourth most common type of malignancy. The current study used gas chromatography-mass spectrometry (GC-MS) to identify the active phytochemical constituents from Caladium lindenii leaf extracts using ethanol (ECL) and n-hexane (HCL) solvents. Plant extracts were tested for potential cytotoxic effects on HeLa and HEK-293 T cells using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and the crystal violet assays. SYBR Green-based real-time PCR was performed to assess the mRNA expression profile of the apoptosis biomarkers (BCL-2 and TP53). The molecular interaction of the compounds with the targeted proteins (TP53, BCL2, EGFR, and HER2) was determined using molecular docking. GC-MS analysis revealed a total of 93 compounds in both extracts. The ECL extract significantly reduced the proliferation of HeLa cervical cancer cells, with an IC50 value of 40 µg/mL, while HEK-293 T cells showed less effect (IC50 = 226 µg/mL). The quantitative RT-PCR gene expression analysis demonstrated the ethanol extract regulated TP53 and BCL2 mRNA expressions in treated cancer cell samples. Heptanediamide, N,N'-di-benzoyloxy-(- 10.1) is the best-docked ligand with a TP53 target found in the molecular docking study, whereas EGFR/Clionasterol had the second highest binding affinity (- 9.7), followed by EGFR/Cycloeucalenol (- 9.6). It is concluded that ECL extract has promising anti-cervical cancer potential and might be valued for developing new plant-derived anticancer agents after further investigations.
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Apoptosis , Cromatografía de Gases y Espectrometría de Masas , Simulación del Acoplamiento Molecular , Extractos Vegetales , Neoplasias del Cuello Uterino , Humanos , Células HeLa , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Células HEK293 , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Objectives: This study was conducted to evaluate the effects of vitamin C on apoptotic and proliferative genes in injured HepG2 cells. Methods: In silico analysis was performed using molecular docking of chemical compounds with vascular endothelial growth factor (VEGF). The different computational tools used were AutoDock Vina, BIOVIA DISCOVERY studio, and PyMOL. Drug likeness and toxicity were analyzed by SWISS ADMET. Cells that were 60-70% confluent were treated with different concentrations of hydrogen peroxide (H2O2) (100-2000 µM) and ascorbic acid (30, 60, 90 µg/mL). The MTT cell proliferation assay was performed to compare the proliferative potential of HepG2 cells treated with H2O2 or ascorbic acid with untreated HepG2 cells using 96-well plates. Results: The lowest binding energy of VEGF with vitamin C -5.2 kcal/mol and L-ascorbic acid-2 glycoside -4.7 kcal/mol was observed by in silico analysis. Vitamin C was selected because it exhibited a high interaction with VEGF and fulfilled Lipinski's rule, and had better oral viability and pharmacokinetics compared to L-ascorbic acid-2 glycoside. Cell viability assays showed that vitamin C had significant apoptotic effects (P < 0.0001). After treating HepG2 cells with ascorbic acid, reduced VEGF (angiogenesis) was observed as determined by apoptotic and proliferative gene expression. Ascorbic acid treatment of HepG2 cells led to downregulation of the proliferation markers, proliferating cell nuclear antigen, Ki67, and DNA topoisomerase II alpha. Increased apoptosis after treatment with vitamin C was observed due to upregulation of p53 and annexin V. Conclusion: The results of this study showed that vitamin C inhibited the growth of cancer cells, thus protecting HepG2 cells from oxidative stress. Vitamin C exhibited antiproliferative activity as observed in silico and in vitro, as well as by the inhibited expression of genes involved in protein synthesis.
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Methotrexate (MTX)-induced intestinal mucositis (IM) is a common side effect in cancer treatment that impairs the immune system and gut microbes, resulting in loss of mucosal integrity and gut barrier dysfunction. The quality of life and outcomes of treatment are compromised by IM. The present study was designed to investigate the mucoprotective potential of the benzimidazole derivative N-{4-[2-(4-methoxyphenyl)-1H-benzimidazole-1-sulfonyl] phenyl} acetamide (B8) on MTX-induced IM in mice. IM was induced by a single dose of MTX in mice and assessed by physical manifestations as well as biochemical, oxidative, histological, and inflammatory parameters. B8 (1, 3, 9 mg/kg) significantly reduced diarrhea score, mitigated weight loss, increased feed intake and, survival rate in a dose-dependent manner. Notably, B8 exhibited a mucoprotective effect evident through the mitigation of villus atrophy, crypt hypoplasia, diminished crypt mitotic figures, mucin depletion, and oxidative stress markers (GSH, SOD, MDA, and catalase concentration). Gene expression analysis revealed that B8 downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1ß, and nuclear factor-κB (NF-κB) and concurrently upregulated IL-10 expression in contrast to the MTX group. Further, B8 significantly improved the luminal microflora profile by augmenting the growth of Lactobacillus spp. and reducing the number of pathogenic bacteria (E. coli). Additionally, the enzyme-linked immunoassay showed that B8 decreased the levels of pro-inflammatory cytokines. Our findings suggest that B8 had mucoprotective effects against MTX-induced IM and could be used as an adjunct in chemotherapy to deter this side effect.
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Bencimidazoles , Metotrexato , Mucositis , Estrés Oxidativo , Animales , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/metabolismo , Mucositis/patología , Ratones , Estrés Oxidativo/efectos de los fármacos , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Metotrexato/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/inducido químicamente , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Biomarcadores/metabolismo , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/antagonistas & inhibidores , Antimetabolitos Antineoplásicos/toxicidadRESUMEN
Present study was undertaken to study the prevalence of ß-haemolytic streptococci in equine of northern temperate region of Jammu and Kashmir, India. One hundred and forty one samples were collected in duplicate from nasopharyngeal tract of diseased (53) and apparently healthy equine (88) for isolation and direct PCR. A total of 77 isolates of streptococci were recovered from 141 samples with an overall prevalence rate of 54.60%. Out of these 77 isolates, 52 were from diseased and 25 from apparently healthy animals. Of the 77 isolates, 4 were identified as Streptococcus equi subsp. equi, 56 as S. equi subsp. zooepidemicus and 17 as S. dysgalactiae subsp. equisimilis. Thus the overall prevalence of S. equi subsp. equi, S. equi subsp. zooepidemicus and S. dysgalactiae subsp. equisimilis was 2.83, 39.71 and 12.05% respectively. The sensitivity of the PCR for the detection of S. equi species was found higher when attempted from direct swab samples.
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Dissolved organic matter (DOM) in the sediment matrix affects contaminant remediation through consumption of oxidants and binding with contaminants. Yet the change in DOM during remediation processes, particularly during electrokinetic remediation (EKR), remains under-investigated. In this work, we elucidated the fate of sediment DOM in EKR using multiple spectroscopic tools under abiotic and biotic conditions. We found that EKR led to significant electromigration of the alkaline-extractable DOM (AEOM) toward the anode, followed by transformation of the aromatics and mineralization of the polysaccharides. The AEOM remaining in the cathode (largely polysaccharides) was resistant to reductive transformation. Limited difference was noted between abiotic and biotic conditions, indicating the dominance of electrochemical processes when relatively high voltages were applied (1-2 V/cm). The water-extractable organic matter (WEOM), in contrast, showed an increase at both electrodes, which was likely attributable to pH-driven dissociations of humic substances and amino acid-type constituents at the cathode and the anode, respectively. Nitrogen migrated with the AEOM toward the anode, but phosphorus remained immobilized. Understanding the redistribution and transformation of DOM could inform studies on contaminant degradation, carbon and nutrient availability, and sediment structural changes in EKR.
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Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H2O2 radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC50 value: 22.77 µg/mL) than ANH extract (IC50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of - 7.2, - 9.2, - 7.2 and - 9.2 kcal/mol against TNF-α, TGF-ßR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Simulación del Acoplamiento Molecular , Peróxido de Hidrógeno , Neoplasias Hepáticas/tratamiento farmacológico , Fitoquímicos/farmacología , Antioxidantes/química , Flavonoides/químicaRESUMEN
A composite manganese-based catalytic ceramic membrane (Mn-CCM) was developed by a solid-state sintering method, and its effectiveness toward activation of peroxymonosulfate (PMS) for the degradation of 11 pharmaceutical and personal care products (PPCPs) mixture was tested. The optimized Mn-CCMs/PMS system showed remarkable degradation efficiencies for PPCPs mixture with total removal >90% in ultrapure water, river water and natural organic matter (NOM) solution. The Mn-CCMs/PMS system showed the contribution of different phenomena in PPCPs removal in the order of catalytic oxidation (54.7%, Mn-CCMs/PMS) > noncatalytic oxidation (42.3%, PMS oxidation) > adsorption (3.0%, by Mn-CCMs). The singlet oxygen (1O2) was the dominant reactive oxygen specie for the degradation of PPCPs in all water matrices proved by the quenching experiments and electro-paramagnetic resonance (EPR) spectroscopy. The extraordinary stability of Mn-CCMs for the activation of PMS has been noted in terms of repeatability experiments for PPCPs degradation with fewer leaching of Mn (1.9 to 3.6 µg/L). Mineralization was achieved in the range of 28-65% for different water matrices. The toxicity of the PPCPs mixture was reduced by 85.9%. The Mn-CCMs/PMS system showed a reduction (25-100%) in precursors of different carbon- and nitrogen-based disinfection by-products. This study found the Mn-CCMs/PMS system as a feasible purification unit for removing trace concentrations of PPCPs (ng/L) in real drinking water matrices.
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Cosméticos , Agua Potable , Contaminantes Químicos del Agua , Peróxidos/química , Agua Potable/química , Oxígeno , Cosméticos/análisis , Preparaciones Farmacéuticas , Contaminantes Químicos del Agua/análisisRESUMEN
In this study, we reported the synthesis of 1-(4-bromobenzoyl)-1,3-dicyclohexylurea by the reaction of DCC (N,N'-dicyclohexylcarbodiimide) with 4-bromobenzoic acid. Subsequently, we further synthesized a new series of 1-(4-arylbenzoyl)-1,3-dicyclohexylurea (5a-g) derivatives using a Suzuki cross-coupling reaction between 1-(4-bromobenzoyl)-1,3-dicyclohexylurea (3) and various aryl/heteroaryl boronic acids (4). Thus, density functional theory (DFT) calculations have been performed to examine the electronic structure of the synthesized compounds (3, 5a-g) and to calculate their spectroscopic data. Moreover, optimized geometries and thermodynamic properties, such as frontier molecular orbitals (HOMO, LUMO), molecular electrostatic potential surfaces, and reactivity descriptors, were also calculated at the PBE0-D3BJ/def2-TZVP/SMD1,4-dioxane level of theory to validate the structures of the synthesized compounds.
RESUMEN
The excess sludge generated from the activated sludge process remains a big issue. Sustainable approaches that achieve in situ sludge reduction with satisfactory effluent quality deserve attention. This study explored the sludge reduction performance of sulfidogenic anoxic-oxic-anoxic (AOA) membrane bioreactors. The dynamics of the microbial community and metabolic pathways were further analyzed to elucidate the internal mechanism of sludge reduction. Compared with the conventional anoxic-oxic-oxic membrane bioreactor (MBRcontrol), AOAS150 (150 mg/L SO42- in the membrane tank) and AOAS300 (300 mg/L SO42- in the membrane tank) reduced biomass production by 40.39% and 47.45%, respectively. The sulfide reduced from sulfate could enhance the sludge decay rate and decrease sludge production. Extracellular polymeric substances (EPSs) destruction and aerobic lysis contributed to sludge reduction in AOA bioreactors. The relative abundance of Bacteroidetes (phylum), sulfate-reducing bacteria (SRB, genus), and Ignavibacterium (genus) increased in AOA bioreactors compared with MBRcontrol. Our metagenomic analysis indicated that the total enzyme-encoding genes involved in glycolysis, denitrification, and sulfate-reduction processes decreased over time in AOAS300 and were lower in AOAS300 than AOAS150 at the final stage of operation. The excess accumulation of sulfide in AOAS300 may inactive the functional bacteria, and sulfide inhibition induced sludge reduction.