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1.
Sci Rep ; 14(1): 806, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191628

RESUMO

Layered double hydroxides have recently gained wide interest as promising multifunctional nanomaterials. In this work, a multifunctional ternary Zn-Co-Fe LDH was prepared and characterized using XRD, FTIR, BET, TEM, SEM, and EDX. This LDH showed a typical XRD pattern with a crystallite size of 3.52 nm and a BET surface area of 155.9 m2/g. This LDH was investigated, for the first time, as an adsorbent for moxifloxacin, a common fluoroquinolones antibiotic, showing a maximum removal efficiency and equilibrium time of 217.81 mg/g and 60 min, respectively. Its antifungal activity, for the first time, was investigated against Penicillium notatum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucor fungi at various concentrations (1000-1.95 µg/mL). This LDH was found to be effective against a variety of fungal strains, particularly Penicillium and Mucor species and showed zones of inhibition of 19.3 and 21.6 mm for Penicillium and Mucor, respectively, with an inhibition of 85% for Penicillium species and 68.3% for Mucormycosis. The highest antifungal efficacy results were obtained at very low MIC concentrations (33.3 and 62 µg/ml) against Penicillium and Mucor, respectively. The results of this study suggest a promising multifunctional potential of this LDH for water and wastewater treatment and disinfection applications.


Assuntos
Antifúngicos , Penicillium , Antifúngicos/farmacologia , Moxifloxacina/farmacologia , Desinfecção , Hidróxidos , Mucor , Zinco
2.
RSC Adv ; 13(43): 30151-30167, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37849691

RESUMO

An advanced form of magnesium-doped hydroxyapatite (Mg HAP) was synthesized and hybridized with cellulose fibers, producing a safe biocomposite (CF/Mg HAP) as an enhanced delivery structure of traditional oxaliplatin (OXPN) chemotherapy drug during the treatment stages of colorectal cancer. The qualifications of CF/Mg HAP as a carrier for OXPN were followed based on loading, release, and cytotoxicity as compared to Mg HAP. The CF/Mg HAP composite exhibits a notably higher OXPN encapsulation capacity (256.2 mg g-1) than the Mg HAP phase (148.9 mg g-1). The OXPN encapsulation process into CF/Mg HAP displays the isotherm behavior of the Langmuir model (R2 = 0.99) and the kinetic assumptions of pseudo-first-order kinetics (R2 > 0.95). The steric studies reflect a strong increment in the quantities of the free sites after the cellulose hybridization steps (Nm = 178.58 mg g-1) as compared to pure Mg HAP (Nm = 69.39 mg g-1). Also, the capacity of each site was enhanced to be loaded by 2 OXPN molecules (n = 1.43) in a vertical orientation. The OXPN encapsulation energy into CF/Mg HAP (<40 kJ mol-1) reflects physical encapsulation reactions involving van der Waals forces and hydrogen bonding. The OXPN release profiles of CF/Mg HAP exhibit slow and controlled properties for about 100 h, either at pH 5.5 or pH 7.4. The release kinetics and diffusion exponent (>0.45) signify non-Fickian transport and a complex erosion/diffusion release mechanism. The free CF/Mg HAP particles display a considerable cytotoxic effect on the HCT-116 cancer cells (21.82% cell viability), and their OXPN-loaded product shows a strong cytotoxic effect (1.85% cell viability).

3.
Molecules ; 28(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37175102

RESUMO

Brown macroalgae (BMG) were used as carriers for ZnO (ZnO/BMG) and cobalt-doped ZnO (Co-ZnO/BMG) via facile microwave-assisted hydrothermal synthesis. The multifunctional structures of synthesized composites were evaluated as enhanced antioxidant and anti-diabetic agents based on the synergistic effects of ZnO, Co-ZnO, and BMG. BMG substrate incorporation and cobalt doping notably enhanced the bioactivity of the synthesized ZnO nanoparticles. As an antioxidant, the Co-ZnO/BMG composite exhibited highly effective scavenging properties for the common free reactive oxygen radicals (DPPH [89.6 ± 1.5%], nitric oxide [90.2 ± 1.3%], ABTS [87.7 ± 1.8%], and O2●- [46.7 ± 1.9%]) as compared to ascorbic acid. Additionally, its anti-diabetic activity was enhanced significantly and strongly inhibited essential oxidative enzymes (porcine α-amylase (90.6 ± 1.5%), crude α-amylase (84.3 ± 1.8%), pancreatic α-glucosidase (95.7 ± 1.4%), crude intestinal α-glucosidase (93.4 ± 1.8%), and amyloglucosidase (96.2 ± 1.4%)). Co-ZnO/BMG inhibitory activity was higher than that of miglitol, and in some cases, higher than or close to that of acarbose. Therefore, the synthetic Co-ZnO/BMG composite can be used as a commercial anti-diabetic and antioxidant agent, considering the cost and adverse side effects of current drugs. The results also demonstrate the impact of cobalt doping and BMG integration on the biological activity of ZnO.


Assuntos
Diabetes Mellitus , Nanopartículas Metálicas , Sargassum , Alga Marinha , Óxido de Zinco , Animais , Suínos , Antioxidantes/farmacologia , Antioxidantes/química , Sargassum/metabolismo , Óxido de Zinco/farmacologia , Óxido de Zinco/química , alfa-Glucosidases , Hipoglicemiantes/farmacologia , alfa-Amilases , Cobalto/química , Nanopartículas Metálicas/química , Alga Marinha/metabolismo
4.
Int J Biol Macromol ; 242(Pt 2): 124713, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148946

RESUMO

The chitosan matrix was used as a substrate for ZnO nanoflowers (ZnO/CH) and Ce-doped ZnO nanoflowers (Ce-ZnO/CH) by microwave-induced hydrothermal synthesis processes. The obtained hybrid structures were assessed as enhanced antioxidant and antidiabetic agents considering the synergetic effect of the different components. The integration of chitosan and cerium induced significantly the biological activity of ZnO flower-like particles. Ce-doped ZnO nano-flowers show higher activities than both ZnO nanoflowers and ZnO/CH composite reflecting the strong effect of surface electrons that were formed by the doping process as compared to the high interactive interface of the chitosan substrate. As an antioxidant the synthetic Ce-ZnO/CH composite achieved remarkable scavenging efficiencies for DPPH (92.4 ± 1.33 %), nitric oxide (95.2 ± 1.81 %), ABTS (90.4 ± 1.64 %), and superoxide (52.8 ± 1.22 %) radicals which are significantly higher values than Ascorbic acid as standard and the commercially used ZnO nanoparticles. Also, its antidiabetic efficiency enhanced greatly achieving strong inhibition effects on porcine α-amylase (93.6 ± 1.66 %), crude α-amylase (88.7 ± 1.82 %), pancreatic α-glucosidase (98.7 ± 1.26 %), crude intestinal α-glucosidase (96.8 ± 1.16 %), and amyloglucosidase (97.2 ± 1.72 %) enzymes. The recognized inhibition percentages are notably higher than the determined percentages using miglitol drug and slightly higher than acarbose. This recommends the Ce-ZnO/CH composite as a potential antidiabetic and antioxidant agent compared with the high cost and the reported side effects of the commonly used chemical drug.


Assuntos
Quitosana , Óxido de Zinco , Animais , Suínos , Antioxidantes/farmacologia , Quitosana/química , Óxido de Zinco/química , alfa-Glucosidases , Micro-Ondas , Hipoglicemiantes/farmacologia , alfa-Amilases
5.
J Funct Biomater ; 14(4)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37103288

RESUMO

Green ZnO-decorated acid-activated bentonite-mediated curcumin extract (ZnO@CU/BE) was prepared as a multifunctional antioxidant and antidiabetic agent based on the extract of curcumin, which was used as a reducing and capping reagent. ZnO@CU/BE showed notably enhanced antioxidant properties against nitric oxide (88.6 ± 1.58%), 1,1-diphenyl-2-picrylhydrazil (90.2 ± 1.76%), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (87.3 ± 1.61%), and superoxide (39.5 ± 1.12%) radicals. These percentages are higher than the reported values of ascorbic acid as a standard and the integrated components of the structure (CU, BE/CU, and ZnO). This signifies the impact of the bentonite substrate on enhancing the solubility, stability, dispersion, and release rate of the intercalated curcumin-based phytochemicals, in addition to enhancing the exposure interface of ZnO nanoparticles. Therefore, effective antidiabetic properties were observed, with significant inhibition effects on porcine pancreatic α-amylase (76.8 ± 1.87%), murine pancreatic α-amylase (56.5 ± 1.67%), pancreatic α-glucosidase (96.5 ± 1.07%), murine intestinal α-glucosidase (92.5 ± 1.10%), and amyloglucosidase (93.7 ± 1.55%) enzymes. These values are higher than those determined using commercial miglitol and are close to the values measured using acarbose. Hence, the structure can be applied as an antioxidant and antidiabetic agent.

6.
Nutrients ; 15(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37111107

RESUMO

Quercetin is a naturally existing plant pigment belonging to the flavonoid group; it is contained in a wide range of vegetables and fruits. The accumulated evidence points to the potential uses of quercetin in protection of some disease conditions. Lead is one of the highly toxicant heavy metals that are widely spread in the environment and implicated in a wide spectrum of industries. No previous study has been reported to evaluate the effect of quercetin on lead toxicity. Therefore, the present study was conducted to elucidate some aspects of quercetin bioactivities in regard to its ability to combat the oxidative stress induced by lead toxicity. For this purpose, a total of sixty male Wistar rats were randomly and equally divided into three groups of 20 animals each; untreated control animals (group 1), lead-exposed animals (group 2; exposed to lead daily by oral gavage at the dose of 80 mg/Kg b.w.), and group 3 of animals, which were exposed to lead and daily received quercetin (10 h gap time between lead exposure and the receiving of quercetin) by oral gavage at the dose of 350 mg/Kg b.w. The experiment period was 8 weeks. All the assayed hematological and biochemical parameters of animals exposed to lead were significantly altered compared with the untreated control levels. Animals exposed to lead (group 2) exhibited significant decrements of the erythrocytic and total leucocytic counts, hemoglobin concentration, packed cell volume percent, total proteins, albumin and globulin. These animals also disclosed significantly decreased levels of antioxidant markers including total thiols, catalase and glutathione. On the other hand, these animals demonstrated significant increments in the levels of bilirubin, urea, creatinine, BUN, serum enzymes, H2O2 and MDA. Animals exposed to lead and given quercetin (group 3) exhibited improvement of these parameters, which were brought back at varying degrees toward the untreated control levels. Basing on the improvements of the assayed hematological and biochemical parameters, it was concluded that quercetin as a dietary supplement can act efficiently as an antioxidant to counteract the oxidative stress induced by lead toxicity and to maintain the oxidant antioxidant balance.


Assuntos
Antioxidantes , Intoxicação por Chumbo , Ratos , Animais , Quercetina , Ratos Wistar , Chumbo/toxicidade , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo , Intoxicação por Chumbo/tratamento farmacológico
7.
J Cancer ; 14(3): 490-504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860921

RESUMO

Cancer is the major challenge across world and the adenocarcinoma of prostate malignancy is the second most prevalent male cancer. Various medicinal plants are used for the treatment and management of various cancers. Matricaria chamomilla L., is one of the extensively used Unani medicament for the treatment of various type of diseases. In the current study we evaluated most of the parameters prescribed for drug standardization using pharmacognostic approaches. The 2,2 Diphenyl-1-picryl hydrazyl (DPPH) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. Moreover, we analyzed the antioxidant and cytotoxic activity of M. chamomilla (Gul-e Babuna) through in-vitro method. DPPH (2,2-diphenyl-1-picryl-hydrazl-hydrate) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. CFU and wound healing assay were performed to determine the anti-cancer activity. The results demonstrated that various extracts of M. chamomilla fulfilled most of the parameters of drug standardization and contained good antioxidant and anticancer activities. The ethyl acetate showed higher anticancer activity followed by aqueous, hydroalcoholic, petroleum benzene and methanol by CFU method. Also, the wound healing assay demonstrated that ethyl acetate extract has more significant effect followed by methanol and petroleum benzene extract on prostate cancer cell line (C4-2). The current study concluded that the extract of M. chamomilla flowers could act as good source of natural anti-cancer compounds.

8.
J Cell Physiol ; 238(1): 32-69, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317692

RESUMO

A type of small noncoding RNAs known as microRNAs (miRNAs) fine-tune gene expression posttranscriptionally by binding to certain messenger RNA targets. Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells. The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNA-mediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver-specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.


Assuntos
Biomarcadores , Hepatopatias , Fígado , MicroRNAs , Humanos , Fígado/patologia , Fígado/fisiologia , MicroRNAs/genética , Exossomos , Inativação Gênica , Hepatopatias/patologia
9.
Semin Cancer Biol ; 86(Pt 2): 54-68, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36087856

RESUMO

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , DNA , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico
10.
J Nutr Biochem ; 109: 109101, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35777588

RESUMO

Inflammatory bowel disease (IBD) is a chronic disorder associated with the inflammation in the digestive tract. The exact cause of IBD is unknown; nevertheless, in IBD, the homeostasis of key regulatory factors involved in intestinal immunity has been documented to be disrupted. Despite the lack of a viable treatment for IBD, synthetic drugs and monoclonal antibodies are currently used to treat it. However, these treatments have side effects, and the high relapse rate limits their usage. Dietary polyphenols constitute a great variety of compounds and have shown an array of biological properties. Resveratrol is a natural polyphenol found in grapevines and berries. The therapeutic ability of resveratrol against IBD is amply demonstrated in many in vivo studies. Resveratrol can interact with several molecular targets (Nf-kB, SIRT1, mTOR, HIF-1α, miRNAs, and TNF-α) and effectively prevent/ alleviate IBD symptoms with promising results. Although resveratrol has profound anti-inflammatory properties against IBD, its therapeutic employment is limited due to its low water solubility, less chemical stability, less bioavailability, and rapid metabolism in vivo. Hence, resveratrol encapsulation using different carries and its controlled release has become a promising strategy to overcome limitations. Herein, we meticulously review, talk-over the anti-inflammatory effect and mechanisms of resveratrol in IBD. We further provide the latest information on resveratrol formulations and nano-delivery systems used in oral delivery of resveratrol for the treatment of IBD and offer our view on future research on resveratrol in IBD treatment.


Assuntos
Doenças Inflamatórias Intestinais , MicroRNAs , Medicamentos Sintéticos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , MicroRNAs/uso terapêutico , NF-kappa B , Sistemas de Liberação de Fármacos por Nanopartículas , Polifenóis/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sirtuína 1 , Medicamentos Sintéticos/uso terapêutico , Serina-Treonina Quinases TOR , Fator de Necrose Tumoral alfa , Água
11.
Nanomaterials (Basel) ; 12(3)2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35159838

RESUMO

Plumeria alba (P. alba) is a small laticiferous tree with promising medicinal properties. Green synthesis of nanoparticles is eco-friendly, cost-effective, and non-hazardous compared to chemical and physical synthesis methods. Current research aiming to synthesize silver nanoparticles (AgNPs) from the leaf extract of P. alba (P- AgNPs) has described its physiochemical and pharmacological properties in recognition of its therapeutic potential as an anticancer and antimicrobial agent. These biogenic synthesized P-AgNPs were physiochemically characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM), atomic force microscopy (AFM), X-ray diffractometry (XRD), and zeta potential analysis. Antimicrobial activity was investigated against Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Enterococcus faecalis, Bacillus subtilis, Streptococcus pneumoniae, Candida albicans, and Candida glabrata. Anticancer activity against glioblastoma U118 MG cancer lines was investigated using an MTT assay, and apoptosis activity was determined by flow cytometry. UV-visible spectroscopic analysis portrayed surface plasmon resonance at 403 nm of synthesized P-AgNPs, and FTIR suggested the presence of amines, alkanes, and phenol molecules that could be involved in reduction and capping processes during AgNPs formation. Synthesized particles were spherical in shape and poly-dispersed with an average particle size of 26.43 nm and a poly-dispersity index (PDI) of 0.25 with a zeta potential value of -24.6 mV, ensuring their stability. The lattice plane values confirm the crystalline nature as identified by XRD. These P-AgNPs exhibited potential antimicrobial activity against selected human pathogenic microbes. Additionally, the in vitro MTT assay results showed its effective anticancer activity against the glioma U118 MG cancer cell line with an IC50 value of 9.77 µg/mL AgNPs by initiating apoptosis as identified by a staining study with flow cytometric Annexin V-Fluorescein Isothiocyanate (FITC) and Propidium Iodide (PI). Thus, P. alba AgNPs can be recommended for further pharmacological and other biological research. To conclude, the current investigation developed an eco-friendly AgNPs synthesis using P. alba leaf extract with potential cytotoxic and antibacterial capacity, which can therefore be recommended as a new strategy to treat different human diseases.

12.
Molecules ; 27(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35164383

RESUMO

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.


Assuntos
Fibronectinas/metabolismo , Doenças Metabólicas/metabolismo , Neoplasias/metabolismo , Animais , Carcinogênese/metabolismo , Exercício Físico , Fibronectinas/análise , Humanos , Doenças Metabólicas/fisiopatologia , Modelos Moleculares , Neoplasias/fisiopatologia , Conformação Proteica , Comportamento Sedentário , Transdução de Sinais
13.
Saudi J Biol Sci ; 29(1): 228-238, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35002413

RESUMO

The current study described the systematic and detailed extracellular synthesis method of silver nanoparticles (AgNPs) using Streptomyces hirsutus strain SNPGA-8 by green synthesis method. The AgNPs were subjected for characterizations using UV-Vis, FTIR, TGA, TEM, EDX, XRD, and zeta-potential analyses. The antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli, Candida albicans, Alternaria alternata, Candida glabrata and Fusarium oxysporum was determined by the agar well diffusion technique. The cytotoxicity of AgNPs against human lung cancer (A549) was studied by MTT and ROS assays and capping of proteins of AgNPs from SDS-PAGE. In the UV-Vis., absorption peak was found at 418 nm, FTIR analysis revealed the infrared bands of specific functional groups from 3273 cm-1 to 428 cm-1; TEM data confirmed the spherical shape, smallest size of particle as 18.99 nm, while EDX analysis confirmed the elemental composition of AgNPs with 22.24% Ag. The XRD pattern confirmed the nature of AgNPs as crystalline, and zeta potential peak was found at -24.6 mV indicating the higher stability. The AgNPs exhibited increased antimicrobial activity with increase in dosage volume and considerable MIC and MBC values against microbial pathogens. In the MTT cytotoxicity assay, the IC50 value of 31.41 µg/mL is obtained against A549 cell line, suggesting the potential of AgNPs to inhibit the tumour cells; and ROS assay displayed increased ROS production with increase in treatment time. Based on the results, it is evident that Streptomyces hirsutus strain SNPGA-8 AgNPs are potentially promising to be applied for biomedical uses.

14.
Environ Res ; 204(Pt B): 112031, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34534522

RESUMO

In the present investigation, the effect of mercuric chloride on gestation and lactation periods in mice was studied. The animals were treated with 10 ppm of HgCl2 and its complications were evaluated by supplementing 150 and 300 ppm of curcumin, respectively. Results indicated that HgCl2 increased depression-like behavior in treated animals compared to control and effects of depression in offspring significantly (p˂0.001) enhanced. Interestingly, the Tail suspension test clearly confirmed that the administration of curcumin enhanced the immobility (p˂0.001). The results confirmed that the curcumin administered mice spent less time in the closed arm (P < 0.001), whereas spent a very long time (P < 0.001) in the open arm. Related to the locomotor behaviors, number of squares crossed, wall rear, rear, and locomotion duration were decreased significantly (P < 0.001) while immobility duration was increased (P < 0.001) significantly compared to control. The anxiety and depression behaviors disorder due to mercuric chloride exposure indicated its availability via placenta or/and milk during lactation. The treatment with curcumin improved anxiety and depression behaviors compared to Hg experimental group.


Assuntos
Curcumina , Cloreto de Mercúrio , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Comportamento Animal , Curcumina/farmacologia , Curcumina/uso terapêutico , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Feminino , Lactação , Cloreto de Mercúrio/toxicidade , Camundongos , Gravidez
15.
PLoS One ; 16(8): e0256141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34407143

RESUMO

SARS-CoV-2 requires serine protease, transmembrane serine protease 2 (TMPRSS2), and cysteine proteases, cathepsins B, L (CTSB/L) for entry into host cells. These host proteases activate the spike protein and enable SARS-CoV-2 entry. We herein performed genomic-guided gene set enrichment analysis (GSEA) to identify upstream regulatory elements altering the expression of TMPRSS2 and CTSB/L. Further, medicinal compounds were identified based on their effects on gene expression signatures of the modulators of TMPRSS2 and CTSB/L genes. Using this strategy, estradiol and retinoic acid have been identified as putative SARS-CoV-2 alleviation agents. Next, we analyzed drug-gene and gene-gene interaction networks using 809 human targets of SARS-CoV-2 proteins. The network results indicate that estradiol interacts with 370 (45%) and retinoic acid interacts with 251 (31%) human proteins. Interestingly, a combination of estradiol and retinoic acid interacts with 461 (56%) of human proteins, indicating the therapeutic benefits of drug combination therapy. Finally, molecular docking analysis suggests that both the drugs bind to TMPRSS2 and CTSL with the nanomolar to low micromolar affinity. The results suggest that these drugs can simultaneously target both the entry pathways of SARS-CoV-2 and thus can be considered as a potential treatment option for COVID-19.


Assuntos
Catepsina B/genética , Catepsina L/genética , Estradiol/farmacologia , Genômica/métodos , SARS-CoV-2/fisiologia , Serina Endopeptidases/genética , Tretinoína/farmacologia , Catepsina B/química , Catepsina L/química , Bases de Dados Genéticas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Mapas de Interação de Proteínas/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Serina Endopeptidases/química , Proteínas Virais/genética , Proteínas Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos
16.
J Cancer ; 12(16): 4891-4900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234859

RESUMO

Pathogenic bacterial strains can alter the normal function of cells and induce different levels of inflammatory responses that are connected to the development of different diseases, such as tuberculosis, diarrhea, cancer etc. Chlamydia trachomatis (C. trachomatis) is an intracellular obligate gram-negative bacterium which has been connected with the cervical cancer etiology. Nevertheless, establishment of causality and the underlying mechanisms of carcinogenesis of cervical cancer associated with C. trachomatis remain unclear. Studies reveal the existence of C. trachomatis in cervical cancer patients. The DNA repair pathways including mismatch repair, nucleotide excision, and base excision are vital in the abatement of accumulated mutations that can direct to the process of carcinogenesis. C. trachomatis recruits DDR proteins away from sites of DNA damage and, in this way, impedes the DDR. Therefore, by disturbing host cell-cycle control, chromatin and DDR repair, C. trachomatis makes a situation favorable for malignant transformation. Inflammation originated due to infection directs over production of reactive oxygen species (ROS) and consequent oxidative DNA damage. This review may aid our current understanding of the etiology of cervical cancer in C. trachomatis-infected patients.

17.
Biomolecules ; 12(1)2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-35053201

RESUMO

BACKGROUND: Epithelial ovarian cancer remains one of the leading variants of gynecological cancer with a high mortality rate. Feasibility and technical competence for screening and detection of epithelial ovarian cancer remain a major obstacle and the development of point of care diagnostics (POCD) may offer a simple solution for monitoring its progression. Cathepsins have been implicated as biomarkers for cancer progression and metastasis; being a protease, it has an inherent tendency to interact with Cystatin C, a cysteine protease inhibitor. This interaction was assessed for designing a POCD module. METHODS: A combinatorial approach encompassing computational, biophysical and electron-transfer kinetics has been used to assess this protease-inhibitor interaction. RESULTS: Calculations predicted two cathepsin candidates, Cathepsin K and Cathepsin L based on their binding energies and structural alignment and both predictions were confirmed experimentally. Differential pulse voltammetry was used to verify the potency of Cathepsin K and Cathepsin L interaction with Cystatin C and assess the selectivity and sensitivity of their electrochemical interactions. Electrochemical measurements indicated selectivity for both the ligands, but with increasing concentrations, there was a marked difference in the sensitivity of the detection. CONCLUSIONS: This work validated the utility of dry-lab integration in the wet-lab technique to generate leads for the design of electrochemical diagnostics for epithelial ovarian cancer.


Assuntos
Inibidores de Cisteína Proteinase , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Catepsina L , Inibidores de Cisteína Proteinase/química , Endopeptidases , Humanos , Neoplasias Ovarianas/diagnóstico , Inibidores de Proteases
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