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1.
Protein Expr Purif ; 219: 106484, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38614377

RESUMO

Cancer and antibiotic resistance represent significant global challenges, affecting public health and healthcare systems worldwide. Lectin, a carbohydrate-binding protein, displays various biological properties, including antimicrobial and anticancer activities. This study focused on anticancer and antibacterial properties of Alocasia macrorrhiza lectin (AML). AML, with a molecular weight of 11.0 ± 1.0 kDa was purified using Ion-exchange chromatography, and the homotetrameric form was detected by gel-filtration chromatography. It agglutinates mouse erythrocytes, that was inhibited by 4-Nitrophenyl-α-d-mannopyranoside. Maximum hemagglutination activity was observed below 60 °C and within a pH range from 8 to 11. Additionally, it exhibited moderate toxicity against brine shrimp nauplii with LD50 values of 321 µg/ml and showed antibacterial activity against Escherichia coli and Shigella dysenteriae. In vitro experiments demonstrated that AML suppressed the proliferation of mice Ehrlich ascites carcinoma (EAC) cells by 35 % and human lung cancer (A549) cells by 40 % at 512 µg/ml concentration. In vivo experiments involved intraperitoneal injection of AML in EAC-bearing mice for five consecutive days at doses of 2.5 and 5.0 mg/kg/day, and the results indicated that AML inhibited EAC cell growth by 37 % and 54 %, respectively. Finally, it can be concluded that AML can be used for further anticancer and antibacterial studies.


Assuntos
Antibacterianos , Carcinoma de Ehrlich , Animais , Camundongos , Humanos , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Antibacterianos/farmacologia , Antibacterianos/química , Lectinas de Plantas/farmacologia , Lectinas de Plantas/química , Lectinas de Plantas/isolamento & purificação , Rizoma/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Células A549 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química
2.
Artigo em Inglês | MEDLINE | ID: mdl-39041320

RESUMO

Helicobacter pylori, a leading human pathogen associated with duodenal ulcer and gastric cancer, presents a significant threat to human health due to increasing antibiotic resistance rates. This study investigates G-quadruplexes (G4s), which are non-canonical secondary structures form in G-rich regions within the H. pylori genome. Extensive research on G4s in eukaryotes has revealed their role in epigenetically regulating cellular processes like gene transcription, DNA replication, and oncogene expression. However, understanding of G4-mediated gene regulation in other organisms, especially bacterial pathogens, remains limited. Although G4 motifs have been extensively studied in a few bacterial species such as Mycobacterium, Streptococci, and Helicobacter, research on G4 motifs in other bacterial species is still sparse. Like in other organisms such as archaea, mammals, and viruses, G4s in H. pylori display a non-random distribution primarily situated within open reading frames of various protein-coding genes. The occurrence of G4s in functional regions of the genome and their conservation across different species indicates that their placement is not random, suggesting an evolutionary pressure to maintain these sequences at specific genomic sites. Moreover, G-quadruplexes show enrichment in specific gene classes, suggesting their potential involvement in regulating the expression of genes related to cell wall/membrane/envelope biogenesis, amino acid transport, and metabolism. This indicates a probable regulatory role for G4s in controlling the expression of genes essential for H. pylori survival and virulence. Biophysical techniques such as Circular Dichroism spectroscopy and Nuclear Magnetic Resonance were used to characterize G4 motifs within selected H. pylori genes. The study revealed that G-quadruplex ligand inhibited the growth of H. pylori, with minimal inhibitory concentrations in the low micromolar range. This suggests that targeting G4 structures could offer a promising approach for developing novel anti-H. pylori drugs.

3.
Mol Divers ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722455

RESUMO

Visceral Leishmaniasis (VL), the second neglected tropical disease caused by various Leishmania species, presents a significant public health challenge due to limited treatment options and the absence of vaccines. The agent responsible for visceral leishmaniasis, also referred to as "black fever" in India, is Leishmania donovani. This study focuses on L. donovani Minichromosome maintenance 10 (LdMcm10), a crucial protein in the DNA replication machinery, as a potential therapeutic target in Leishmania therapy using in silico and in vitro approaches. We employed bioinformatics tools, molecular docking, and molecular dynamics simulations to predict potential inhibitors against the target protein. The research revealed that the target protein lacks homologues in the host, emphasizing its potential as a drug target. Ligands from the DrugBank database were screened against LdMcm10 using PyRx software. The top three compounds, namely suramin, vapreotide, and pasireotide, exhibiting the best docking scores, underwent further investigation through molecular dynamic simulation and in vitro analysis. The observed structural dynamics suggested that LdMcm10-ligand complexes maintained consistent binding throughout the 300 ns simulation period, with minimal variations in their backbone. These findings suggest that these three compounds hold promise as potential lead compounds for developing new drugs against leishmaniasis. In vitro experiments also demonstrated a dose-dependent reduction in L. donovani viability for suramin, vapreotide, and pasireotide, with computed IC50 values providing quantitative metrics of their anti-leishmanial efficacy. The research offers a comprehensive understanding of LdMcm10 as a drug target and provides a foundation for further investigations and clinical exploration, ultimately advancing drug discovery strategies for leishmaniasis treatment.

4.
J Toxicol Environ Health A ; 87(6): 266-273, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38166509

RESUMO

Benzophenone-3 (BP-3, 2-hydroxy-4-methoxybenzophenone, oxybenzone) is one of the most widely used types of benzophenone organic sunscreen. However, this compound is a potentially harmful toxicant. The aim of this study was 2-fold to: (1) utilize a Hershberger bioassay in vivo in castrated male Sprague-Dawley rats to investigate the anti-androgenic activities of BP-3, and (2) use in vitro a methyl tetrazolium assay to compare the toxicity between Leydig cells (TM3 cells) and mouse fibroblast (NIH-3T3) cell lines. In the Hershberger assay, rats were divided into 6 groups (each of n = 7): a vehicle control, negative control, positive control, PB-3 low (40 mg/kg), BP-3 intermediate (200 mg/kg), and BP-3 high (1000 mg/kg)-dose. The weight of the ventral prostate was significantly decreased at BP-3 doses of 200 or 1,000 mg/kg/day. In addition, the levator anibulbocavernosus muscle weights were also significantly reduced at BP-3 doses of 40, 200, or 1,000 mg/kg/day. In the MTT assay, the viability of NIH-3T3 mouse fibroblast cells was within the normal range. However, the TM3 mouse testis Leydig cell viability was significantly lowered in a concentration-dependent manner. Therefore, data indicate that BP-3 might exert in vivo anti-androgenic and in vitro cytotoxic effects in cells associated with the male reproductive system compared to normal non-reproductive cells.Abbreviation: BP-3: benzophenone-3; CG: Cowper's gland; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; GP: glans penis; LABC: levator anibulbocavernosus muscle; MTT: methyl tetrazolium; NC: negative control; PC: positive control; SV: seminal vesicle; TP: testosterone propionate; VC: vehicle control; VP: ventral prostate.


Assuntos
Antineoplásicos , Orquiectomia , Camundongos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Antagonistas de Androgênios/farmacologia , Benzofenonas/toxicidade , Antineoplásicos/farmacologia , Tamanho do Órgão , Genitália Masculina
5.
Biochem Genet ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536569

RESUMO

Non-alcoholic fatty liver disease is a multifactorial disorder with complicated pathophysiology ranging from simple steatosis to steatohepatitis and liver fibrosis. Trimethylamine-N-oxide (TMAO) production is believed to be correlated with choline deficiency. This study investigated the expression of miRNA-34a, miRNA-122, and miRNA-192 in the fatty liver cell model treated with different concentrations of TMAO. A fatty liver cell model was developed by exposing HepG2 cells to a mixture of palmitate and oleate in a ratio of 1:2 at a final concentration of 1200 µM for 24 h. The confirmed fatty liver cells were treated with 37.5, 75, 150, and 300 µM of TMAO for 24 h. RT-qPCR was used to quantify the expression of microRNAs in a cellular model. The cellular expression of all microRNAs was significantly higher in treated fatty liver cells compared to normal HepG2 cells (P < 0.05). Only 75 and 150 µM of TMAO significantly increased the expression of miRNA-34a and miRNA-122 compared to both fatty and normal control cells (P < 0.05). Our results provided an experimental documentation for the potential effect of TMAO to change the expression of miR-34a and miR-22 as a mechanism for contributing to the pathogenesis of non-alcoholic fatty liver disease.

6.
Lasers Med Sci ; 39(1): 135, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787412

RESUMO

In this study, we assess the impact of photodynamic therapy (PDT) using aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability and cellular stress responses of MCF-7 breast cancer cells. Specifically, we investigate changes in cell viability, cytokine production, and the expression of stress-related genes. Experimental groups included control cells, those treated with AlPcS4 only, light-emitting diode (LED) only, and combined PDT. To evaluate these effects on cell viability, cytokine production, and the expression of stress-related genes, techniques such as 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT‒qPCR) were employed. Our findings reveal how PDT with AlPcS4 modulates mitochondrial activity and cytokine responses, shedding light on the cellular pathways essential for cell survival and stress adaptation. This work enhances our understanding of PDT's therapeutic potential and mechanisms in treating breast cancer.


Assuntos
Neoplasias da Mama , Sobrevivência Celular , Citocinas , Indóis , Compostos Organometálicos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fotoquimioterapia/métodos , Células MCF-7 , Citocinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Indóis/farmacologia , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Ensaio de Imunoadsorção Enzimática
7.
Chem Biodivers ; : e202401430, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031897

RESUMO

A series of resveratrol surrogate molecules were designed, synthesized and biologically evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) along with anti-oxidant activity as potential novel multifunctional agents against Alzheimer's disease (AD). Six novel compounds were synthesized by reacting (E)-4-(3,5-Dimethoxystyryl) aniline with benzaldehyde and some selected derivatives of benzaldehyde in the presence of ethanol and a few drops of glacial acetic acid which followed the general scheme involved in the formation of Schiff bases. The spectral analysis data including FT-IR, 1H-NMR, 13C-NMR, and Mass spectroscopy results were found to be in good agreement with the newly synthesized compounds (Resveratrol Surrogate Molecules 1-6). The synthesized compounds were evaluated for their dual cholinesterase inhibitory activities, cytotoxic effect, and anti-oxidant potential. The results showed that compound RSM5 showed potent inhibitory activity against AChE and BChE. In, addition the cytotoxicity of the compound RSM5 is less and found to be within the desirable limit indicating the potential safety of RSM5. Also, it possesses substantial anti-oxidant activity which qualifies RSM5 as an anti-AD agent. Taken together, these findings demonstrate that the molecule RSM5 had the most multifunctional properties and could be a promising lead molecule for the future development of drugs for Alzheimer's treatments.

8.
Chem Biodivers ; : e202401122, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39176466

RESUMO

Chalcone-incorporated pyridine-pyrimidines i.e. derivatives of (5-(6-(pyrimidin-5-yl)pyridin-3-yl)thiophen-2-yl)prop-2-en-1-one were synthesized and their structures were confirmed by analytical techniques. In addition, all the derivatives were examined for their capacity to fight against cancer towards four cell lines, including breast (MCF-7), prostate (DU-145 and PC3), and lung (A549) by utilizing the MTT technique and the clinically used chemotherapy medication, etoposide serving as a positive reference. All these results were expressed in IC50 µM, and values of synthesized compounds are compared with a reference drug, showing values ranging from 1.97 ± 0.45 µM to 3.08 ± 0.135 µM. Among those, a few compounds 10(a-e) demonstrated strong activities with corresponding cell lines.

9.
Mikrochim Acta ; 191(5): 261, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613580

RESUMO

Contrast enhancement is explored in optical coherence tomography images using core NaYF4:Ho3+/Yb3+ and core@shell NaYF4:Ho3+/Yb3+@NaGdF4 nanoparticles. Under 980 nm excitation, core@shell nanoparticles exhibited 2.8 and 3.3 times enhancement at 541 nm and 646 nm emission wavelengths of Ho3+ ions compared to core nanoparticles. Photo-thermal conversion efficiencies were 32% and 20% for core and core@shell nanoparticles. In swept-source optical coherence tomography (SSOCT), core@shell nanoparticles have shown superior contrast, while in photo-thermal optical coherence tomography (PTOCT) core nanoparticles have excelled due to their higher photo-thermal conversion efficiency. The enhancement in contrast to noise ratio obtained is 58 dB. Comparative assessments of scattering coefficients and contrast-to-noise ratios were conducted, providing insights into nanoparticle performance for contrast enhancement in optical coherence tomography.

10.
Arch Pharm (Weinheim) ; : e2400281, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058899

RESUMO

Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant-antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant-antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH-SY5Y (a human neuroblastoma cell line), HT-29 (a human colorectal adenocarcinoma cell line), and PCS-201-012 (a human primary dermal fibroblast cell line) cells. Consequently, the half-maximal inhibitory concentration (IC50) values of compound 3a were determined to be 218.72, 202.85, and 227.86 µM while the IC50 values of compound 3b were defined to be 227.42, 199.27, and 250.11 µM in PCS-201-012, HT-29, and SH-SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS-201-012 cells as compared to the other cell lines.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38935113

RESUMO

Bio-inspired zinc oxide nanoparticles are gaining immense interest due to their safety, low cost, biocompatibility, and broad biological properties. In recent years, much research has been focused on plant-based nanoparticles, mainly for their eco-friendly, facile, and non-toxic character. Hence, the current study emphasized a bottom-up synthesis of zinc oxide nanoparticles (ZnO NPs) from Psidium guajava aqueous leaf extract and evaluation of its biological properties. The structural characteristic features of biosynthesized ZnO NPs were confirmed using various analytical methods, such as UV-Vis spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM). The synthesized ZnO NPs exhibited a hydrodynamic shape with an average particle size of 11.6-80.2 nm. A significant antimicrobial efficiency with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 40 and 27 µg/ml for Enterococcus faecalis, followed by 30 and 40 µg/ml for Staphylococcus aureus, 20 and 30 µg/ml for Staphylococcus mutans, 30 µg/ml for Candida albicans was observed by ZnO NPs. Additionally, they showed significant breakdown of biofilms of Streptococcus mutans and Candida albicans indicating their future value in drug-resistance research. Furthermore, an excellent dose-dependent activity of antioxidant property was noticed with an IC50 of 9.89 µg/ml. The antiproliferative potential of the ZnO NPs was indicated by the viability of MDA MB 231 cells, which showed a drastic decrease in response to increased concentrations of biosynthesized ZnO NPs. Thus, the present results open up vistas to explore their pharmaceutical potential for the development of targeted anticancer drugs in the future.

12.
J Basic Microbiol ; 64(5): e2300490, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38227394

RESUMO

Currently, zinc oxide (ZnO) particles are used in nanotechnology to destroy a wide range of microorganisms. Although pentavalent antimony compounds are used as antileishmanial drugs, they are associated with several limitations and side effects. Therefore, it is always desirable to try to find new and effective treatments. The aim of this research is to determine the antileishmanial effect of ZnO particles in comparison to the Antimoan Meglumine compound on promastigotes and amastigotes of Leishmania major (MRHO/IR/75/ER). After the extraction and purification of macrophages from the peritoneal cavity of C57BL/6 mice, L. major parasites were cultured in Roswell Park Memorial Institute-1640 culture medium containing fetal bovine serum (FBS) 10% and antibiotic. In this experimental study, the effect of different concentrations of nanoparticles was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) colorimetric method, in comparison to the glucantime on promastigotes, amastigotes and healthy macrophages in the culture medium. The amount of light absorption of the obtained color from the regeneration of tetrazolium salt to the product color of formazan by the parasite was measured by an enzyme-linked immunosorbent assay (ELISA) reader, and the IC50 value was calculated. IC50 after 24 h of incubation was calculated as IC50 = 358.6 µg/mL. The results showed, that the efficacy of ZnO nanoparticles was favorable and dose-dependent. The concentration of 500 µg/mL of ZnO nanoparticles induced 84.67% apoptosis after 72. Also, the toxicity of nanoparticles was less than the drug. Nanoparticles exert their cytotoxic effects by inducing apoptosis. They can be suitable candidates in the pharmaceutical industry in the future.


Assuntos
Antiprotozoários , Leishmania major , Antimoniato de Meglumina , Óxido de Zinco , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Animais , Leishmania major/efeitos dos fármacos , Camundongos , Antiprotozoários/farmacologia , Antimoniato de Meglumina/farmacologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Macrófagos/parasitologia , Macrófagos/efeitos dos fármacos , Concentração Inibidora 50 , Macrófagos Peritoneais/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Nanopartículas Metálicas/química
13.
Molecules ; 29(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38257345

RESUMO

Six new compounds, (7R,8S,8'R)-balanophorone (1), (7'S,8'R,8R)-yunnanensin A (2), (3S)-thunberginol C (3), (8R,8'R)-maninsigin B (4), (7S,8R)-4,7,8-dihydroxy-9,9-dimethyl-chroman (5), and 4-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butan-1-one (6), along with eight known compounds (7-14), were isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on their spectroscopic (MS, NMR, IR, and UV) data, and their absolute configurations were determined by comparing their calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, compounds 1 and 3-6 were evaluated for their ability to protect human pulmonary epithelial cells (BEAS-2B) from injury induced by lipopolysaccharide (LPS) in vitro. The results showed that compound 6 exhibited a significant protective effect against LPS-induced injury in BEAS-2B, and compound 5 exhibited a slightly protective effect at the concentration of 10 µM.


Assuntos
Ephedra , Lipopolissacarídeos , Humanos , Cromanos , Células Epiteliais
14.
Inflammopharmacology ; 32(2): 1621-1631, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38319475

RESUMO

Aframomum melegueta K Schum (A. melegueta), an herbaceous plant renowned for its medicinal seeds, was investigated for its potential immunomodulatory effects in vitro and in vivo using ethanolic and methanolic extracts. The immunomodulatory effect was evaluated by measuring antibody titers using the agglutination technique, while anti-inflammatory activity was assessed in a carrageenan-induced mouse paw edema model. In vitro immunomodulatory activity was measured by lysozyme release from neutrophils. Additionally, white blood cell counts were analyzed post-extracts treatment. The MTT assay was employed to determine cytotoxicity, and the biochemical parameters of liver toxicity were evaluated. Remarkably, both extracts exhibited a dose-dependent reduction in paw edema (p < 0.001), with the most significant reduction observed at 1 g/kg (78.13 and 74.27% for ethanolic and methanolic extracts, respectively). Neutrophil degranulation was significantly inhibited in a dose-dependent manner (p < 0.003), reaching maximal inhibition at 100 µg/mg (60.78 and 39.7% for ethanolic and methanolic extracts, respectively). In comparison to the control group, both antibody production and white blood cell counts were reduced. Neither of the extracts showcased any cytotoxicity or toxicity. These findings suggest that A. melegueta extracts exhibit immunosuppressive and anti-inflammatory activities due to the presence of various biomolecules.


Assuntos
Extratos Vegetais , Zingiberaceae , Camundongos , Animais , Extratos Vegetais/química , Sementes/química , Anti-Inflamatórios/farmacologia , Metanol , Etanol , Zingiberaceae/química , Edema
15.
Saudi Pharm J ; 32(3): 101960, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38328794

RESUMO

Ephedra foeminea is traditionally used to treat breast cancer in several Arab countries. Scientific studies have reported different effects of this plant on some cancer cell lines. The current study determined the anti-cancer potential of the methanolic extract of Ephedra foeminea against four different types of breast cancer cell lines in-vitro. The extract was prepared by maceration and phytoconstituents were identified by LC-MS analysis. The IC50 value was determined against MDA-MB-231, MCF-7, 4 T1, and MCF-10 cell lines using the MTT assay. Further investigations were carried out using IC50 concentration of the extract (40.09 µg/ml) to determine live/dead cells by acridine orange/ethidium bromide staining. The effect on the expression of reactive oxygen species (ROS) was evaluated by flow cytometry. The results were analyzed using one-way ANOVA followed by Tukey's test. The LC-MS analysis revealed the presence of 34 and 30 phytoconstituents in positive and negative modes respectively. The Ephedra foeminea extract was most effective against 4 T1 cells in a dose-dependent manner (P < 0.001) with an IC50 value of 40.09 µg/ml and showed negligible effect against MCF-10 cells. It increased apoptosis in 77.84 % of 4 T1 cells, as determined by acridine orange/ethidium bromide staining. The extract also increased the ROS expression in the 39.57 % of 4 T1 cells. The study results showed that Ephedra foeminea extract possesses an anti-cancer effect against 4 T1 cells by increasing the expression of ROS and inducing apoptosis in the 4 T1 cells. The result suggests Ephedra foemenia methanolic extract possesses a reasonable anti-cancer effect due to its effect on apoptosis and oxidative pathways. The results confirm the traditional belief that Ephedra is effective against breast cancerز.

16.
Saudi Pharm J ; 32(3): 101971, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38357701

RESUMO

Triple-negative breast cancer (TNBC) comprises 10 % to 20 % of breast cancer, however, it is more dangerous than other types of breast cancer, because it lacks druggable targets, such as the estrogen receptors (ER) and the progesterone receptor (PR), and has under expressed receptor tyrosine kinase, ErbB2. Present targeted therapies are not very effective and other choices include invasive procedures like surgery or less invasive ones like radiotherapy and chemotherapy. This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. All the designed derivatives (3a-l) were subjected to extra precision molecular docking and were synthesized and spectrally characterized. In vitro enzyme inhibition assay of compounds (3a, 3b, 3e, 3 g and 3 h) revealed their nanomolar inhibitory potential against the anticancer targets, KSP and PI3Kδ. Using MTT assay, the cytotoxic potential of compounds 3a, 3b and 3e were found highest against MDA-MB-231 cells with an IC50 of 14.51 µM, 16.27 µM, and 9.97 µM, respectively. Remarkably, these compounds were recorded safe against the oral epithelial normal cells with an IC50 values of 293.60 µM, 261.43 µM, and 222 µM, respectively. The anticancer potential of these compounds against MDA-MB-231 cells was revealed to be associated with their apoptotic activity. This was established by examination with the inverted microscope that revealed the appearance of various apoptotic features like cell shrinkage, apoptotic bodies, and membrane blebbing. Using flow cytometry, the Annexin V/PI-stained cancer cells showed an increase in early and late apoptotic cells. In addition, DNA fragmentation was revealed to occur after treatment with the tested compounds by gel electrophoresis. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity.

17.
J Contemp Dent Pract ; 24(8): 610-619, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38193186

RESUMO

AIM: This review aimed to evaluate the in vitro studies done with regard to the cytotoxicity associated with mineral trioxide aggregate (MTA)-based root canal sealers. BACKGROUND: Root canal sealers are used during endodontic treatment as fillers to seal the gaps between the canal gutta-percha cone and canal walls. It is necessary to understand the cytotoxicity of these materials on human-derived cells as these materials interact with human cells periapically. REVIEW RESULTS: Six in vitro studies were chosen for review. In these selected studies, along with MTA-based root canal sealers, other sealers were tested for cytotoxicity on human periodontal ligament (PDL) stem cells, human PDL fibroblasts, and human osteoblast cells. Regarding cytotoxicity, the studies were diverse, and most were based on 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide) (MTT) assay. In general, the studies suggested that root canal sealers cause mild to severe cytotoxic effects and that several factors influence this effect, such as material setting time, concentration, and duration of exposure. CONCLUSION: All studies in the review indicated that MTA. Fillapex must be used cautiously as it exhibited the highest cytotoxic effect compared to other MTA-based and non-MTA-based sealers. CLINICAL SIGNIFICANCE: Endodontic sealers do serve the purpose of bridging the gaps between the gutta-percha cone and the canal wall but knowing its biocompatibility becomes important as the material is extruded beyond the apical foramen where it comes in contact with the surrounding tissues. The effect of sealers on the surrounding tissues affects the healing and prognosis of the treatment.


Assuntos
Compostos de Cálcio , Guta-Percha , Humanos , Compostos de Cálcio/toxicidade , Guta-Percha/toxicidade , Projetos de Pesquisa
18.
Pathogens ; 13(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38668249

RESUMO

OBJECTIVE: The objective of this paper was to assess the airborne mold contamination, secondary metabolite profiles, and cytotoxicity of the dominant fungal species isolated from the air in selected rooms at a Zoological Garden. MATERIALS AND METHODS: Fungal concentrations were measured with MAS-100 air samplers. The collected airborne fungi were identified using a combination of morphological and molecular methods. The cytotoxicity of 84 strains belonging to two Penicillium and Aspergillus genera was determined using the quantitative colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium salt) assay. The mycotoxins were detected using high-performance liquid chromatography (HPLC) with a mass spectrometry detector. RESULTS: The ITS gene was amplified and sequenced to identify the 132 species. For mycotoxicological and cytotoxicity analyses, 52 Penicillium isolates and 32 Aspergillus representatives were selected. Cytotoxicity was confirmed in 97.6% of cases analyzed. Using the LC-MS/MS method, 42 out of 84 strains produced at least one of the following toxins: ochratoxin A, ochratoxin B, patulin, gliotoxin, roquefortine C, griseofulvin, sterigmatocystin, fumonisin B2, moniliformin, and mycophenolic acid. CONCLUSIONS: Analytical methods for assessing the presence of mycotoxins in fungal isolates collected directly from the air have proven to be an effective tool. Our research provides new information on the occurrence of potentially toxin-producing molds within a zoo.

19.
Heliyon ; 10(6): e27787, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496878

RESUMO

The current study report a convenient, simple, and low cost approach for the biogenic synthesis of CuO/Fe3O4 nanocomposites (NCs) from pumpkin seeds extract and their vitro cytotoxicity. The characterization of finally obtained CuO/Fe3O4 nanocomposites (NCs) performed using UV-Visible, FT-IR, XRD, XPS, GC-MS, SEM-EDX and TEM analysis. The formation and elemental analysis were determined using the energy-dispersive X-ray (EDX) microanalysis technique. The formation of rod-like monoclinic and spherical, having size range 5 nm-20 nm confirmed by scanning electron microscope (SEM) and transmission electron microscopy (TEM) respectively. Finally, the MTT assay of the synthesized composites was evaluated for toxicity against cancerous cell lines HCT-116 (Colon cancer cell) and A549 (human lung adenocarcinoma cell). The synthesized composite material showed moderate (IC50 = 199 µg/mL) to low (IC50 = 445 µg/mL) activity against HCT-116 and A549 cell lines, respectively.

20.
Open Vet J ; 14(2): 674-682, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38549573

RESUMO

Background: Fertility plays a great role in animal reproduction since high-quality semen improves sheep industry reproduction. The current worldwide data revealed the close relation of C-type natriuretic peptide (CNP) to the reproductive function of rams. Aims: Evaluation of the effect of CNP on cooled sperms using traditional and molecular assays. Methods: Totally, of 20 testicular samples were collected, processed to obtain the semen samples, and divided into two parts; one was treated with a suitable dose of CNP, and the other served as a control. Sperm samples of both groups were cooled for 3 days and tested at 0, 24, 48, and 72 hours. Results: The findings revealed that the suitable dose of CNP-treated sperms was 0.01 × 10-13. Values of individual motility, live sperms, and sperm concentration were reduced significantly in CNP-24h, CNP-48h, and CNP-72h when compared to control; however, abnormal sperms were increased in both control and CNP groups at 24, 48, and 72 hours when compared to values of 0 hour. Concerning turbidmetric analysis, a significant reduction in values of lag time was observed in CNP when compared to control at all times of cooling intervals. In both CNP and control groups, motility index was decreased at 24, 48, and 72 hours when compared to 0 hour. For velocity, significant increases were shown in CNP compared with control at all cooling intervals. However, values of both groups were increased significantly at 24, 48, and 72 hours times when compared to 0 hour. Fraction of rapidly moving sperm of CNP was elevated at 0 hour and decreased at 24, 48, and 72 hours when compared to control. Expression of the hNPR-B gene was reduced gradually in sperms of CNP and control groups at times of cooling intervals. Conclusion: To the best of our knowledge, this first Iraqi study targets the effect of CNP on epididymal sperms of rams. However, changes that occur after excessive CNP exposure remain unclear, and the toxicological profile of CNP requires furthermore supplements.


Assuntos
Peptídeo Natriurético Tipo C , Sêmen , Masculino , Ovinos , Animais , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/metabolismo , Peptídeo Natriurético Tipo C/farmacologia , Iraque , Sêmen/metabolismo , Espermatozoides/metabolismo , Análise do Sêmen/veterinária , Carneiro Doméstico
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