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Journal of Pharmaceutical Sciences Aug 2022The human papillomavirus (HPV) is responsible for over 90% of all cervical cancer cases. The use of vaginal gels is often indicated for local vaginal drug delivery....
BACKGROUND
The human papillomavirus (HPV) is responsible for over 90% of all cervical cancer cases. The use of vaginal gels is often indicated for local vaginal drug delivery. Previous studies have shown that Thymus vulgaris essential oil (TEO) exhibits anticancer properties besides antifungal and antibacterial properties. Its activity derives from a specific increase in free radicals and oxidative stress caused in cancer cells. Furthermore, mitoxantrone (MTX), an anthracenedione, and C, an acridine orange derivative, were shown to inhibit the growth of the cervical cancer cell line HeLa.
RESULTS
The results showed that TEO + C is the most promising formulation in terms of viscosity and osmolality properties in vaginal fluid simulant (VFS). The combined action of TEO with the compounds MTX and C resulted in HeLa cell viability reduction compared with the effect obtained with the individual formulations containing each one of the compounds.
CONCLUSIONS
The formulation TEO + C holds promise in terms of cost-benefit and topical application of the active compound for the HeLa cells.
Topics: Alphapapillomavirus; Drug Compounding; Female; HeLa Cells; Humans; Oils, Volatile; Papillomaviridae; Uterine Cervical Neoplasms
PubMed: 35182543
DOI: 10.1016/j.xphs.2022.02.004 -
Journal of Oral and Maxillofacial... 2021Oral cancer is a major health problem and its early detection is advantageous for therapeutic purposes. According to available evidence, the risks of oral malignancies...
INTRODUCTION
Oral cancer is a major health problem and its early detection is advantageous for therapeutic purposes. According to available evidence, the risks of oral malignancies increase with the usage of tobacco and other psychoactive substances (PSs). The present study showed expression pattern of nuclear and cytoplasmic changes from normal individuals without habit to oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) in PS abusers with the help of fluorescence acridine orange (AO) stain and Papanicolaou (PAP) stain.
AIM AND OBJECTIVES
This study aimed to investigate and compare diagnostic efficacy of fluorescence microscopic evaluation of AO stain in cytological smears with PAP staining under light microscopy in PS abusers having oral potentially malignant and malignant lesions.
MATERIALS AND METHODS
Oral smears from 120 individuals among which 40 from potentially malignant disorders, 40 from oral malignancy and 40 normal buccal mucosa smears were prepared. One set of smears was stained by AO staining and the other by PAP staining and examined under fluorescence and light microscope, respectively. The results of both the stainings were evaluated by grading cytology smears in class-I to class-V cytology.
RESULTS
The AO fluorescence stain reliably demonstrated malignant cells based on the differential fluorescence. The efficacy of AO fluorescence stain was higher than PAP stain in screening of oral lesions suspicious of malignancy. The sensitivity of PAP staining and AO staining is 57.50% and 61.25%, respectively.
CONCLUSION
As compared to PAP staining method, fluorescent AO method is more effective in screening of OPMD and OSCC in PS abusers.
PubMed: 34349437
DOI: 10.4103/jomfp.JOMFP_275_20 -
Transgenic Research Dec 2021Our study was aimed to investigate the effects of lgals3a (Gal-3 encoding gene) on the development of zebrafish embryo and its underlying mechanisms. Morpholino (MO)...
Our study was aimed to investigate the effects of lgals3a (Gal-3 encoding gene) on the development of zebrafish embryo and its underlying mechanisms. Morpholino (MO) technology was used to inhibit the expression of zebrafish lgals3a, and the effect of lgals3a gene knockdown on zebrafish embryo development and the number of monocyte macrophages was observed. Effect of lgals3a-e3i3-MO on apoptosis of zebrafish was detected by acridine orange staining. In addition, the mRNA expression levels of Wnt/β-catenin signaling pathway-related genes were detected by RT-qPCR. Compared with control-MO group, the zebrafish embryos injected with lgals3a-e3i3-MO had obvious defects in the head, eyes, and tail, and pericardial edema. Lgals3a-e3i3-MO significantly reduced the number of mononuclear macrophages in zebrafish embryos compared with the control-MO group. The results of acridine orange staining showed that compared with the control-MO group, lgals3a-e3i3-MO promoted cardiomyocyte apoptosis in zebrafish. Furthermore, lgals3a-e3i3-MO significantly up-regulated the expression of dkk1b, wnt9a, lrp5, fzd7a, β-catenin, Gsk-3β, mycn, myca in the Wnt/β-catenin pathway, and decreased the expression of lef1. These results indicate that lgals3a-e3i3-MO inhibits zebrafish embryo development, reduces the number of mononuclear macrophages, activates Wnt/β-catenin signaling pathway and promotes cardiomyocyte apoptosis.
Topics: Acridine Orange; Animals; Embryo, Nonmammalian; Embryonic Development; Glycogen Synthase Kinase 3 beta; Receptors, Cell Surface; Wnt Proteins; Wnt Signaling Pathway; Zebrafish; Zebrafish Proteins; beta Catenin
PubMed: 34347236
DOI: 10.1007/s11248-021-00276-5 -
Cell Biology International Nov 2023Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased... (Review)
Review
Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased resistance of the tumor to existing treatments, which is a direct result of apoptotic defects. Calculating an alternative to cell death (autophagy) may be the ultimate solution to maximizing cancer cell death. Our aim in this study was to investigate the potential of free nanoparticles (un-drug-loaded) in the induction or inhibition of autophagy and consider this effect on the therapy process. When the studies met the inclusion criteria, the full texts of all relevant articles were carefully examined and classified. Of the 25 articles included in the analysis, carried out on MCF-7, MDA-MB-231, MDA-MB-231-TXSA, MDA-MB-468, SUM1315, and 4T1 cell lines. Twenty in vitro studies and five in vivo/in vitro studies applied five different autophagy tests: Acridine orange, western blot, Cyto-ID Autophagy Detection Kit, confocal microscope, and quantitative polymerase chain reaction. Nanoparticles (NPs) in the basic format, including Ag, Au, Y O , Se, ZnO, CuO, Al, Fe, vanadium pentoxide, and liposomes, were prepared in the included articles. Three behaviors of NPs related to autophagy were seen: induction, inhibition, and no action. Screened and presented data suggest that most of the involved free NPs (metallic NPs) in this systematic review had reactive oxygen species-mediated pathways with autophagy induction (36%). Also, PI3K/Akt/mTOR and MAPK/ERK signaling pathways were mentioned in just four studies (16%). An impressive percentage of studies (31%) did not examine the NP-related autophagy pathway.
PubMed: 37671447
DOI: 10.1002/cbin.12081 -
Evidence-based Complementary and... 2022This article investigated the role and the specific mechanism of Ruscogenin in Sjögren's syndrome (SS). NOD/ShiLtJ mice were treated with Ruscogenin, and acinar cells...
This article investigated the role and the specific mechanism of Ruscogenin in Sjögren's syndrome (SS). NOD/ShiLtJ mice were treated with Ruscogenin, and acinar cells isolated from submandibular glands were treated with TNF-, Ruscogenin and transfected with NLRP3 overexpression plasmid. Salivary flow rate (SFR) was measured at weeks 11, 13, 15, 17, and 20. Histological analysis of the submandibular glands was conducted by hematoxylin-eosin staining assay. IL-6, IL-17, TNF-, and IL-1 mRNA expression was detected through qRT-PCR. AQP 5, AQP 4, P2X7R, NLRP3, caspase 1, IL-1, Bax, and Bcl-2 protein levels were tested by western blot. Cell apoptosis was assessed through acridine orange and propidium iodide (AO/PI) staining assay and flow cytometry assay. Ruscogenin ameliorated the SFR and submandibular gland inflammation of NOD/ShiLtJ mice. Ruscogenin promoted the preservation of acinar cells and suppressed inflammation-related factors (P2X7R, NLRP3, caspase 1, and IL-1) in submandibular gland tissues of NOD/ShiLtJ mice. Ruscogenin inhibited acinar cell apoptosis in NOD/ShiLtJ mice and reversed TNF--induced apoptosis and inflammation of acinar cells. NLRP3 overexpression reversed the repressive effect of Ruscogenin on TNF--induced inflammation and apoptosis of acinar cells. Ruscogenin ameliorated SS by inhibiting NLRP3 inflammasome activation.
PubMed: 35800007
DOI: 10.1155/2022/6425121 -
Spectrochimica Acta. Part A, Molecular... Jul 2023Chemotherapy-phototherapy (CTPT) combination drugs co-loaded by targeted DNA nanostructures can achieve controlled drug delivery, reduce toxic side effects and overcome...
Chemotherapy-phototherapy (CTPT) combination drugs co-loaded by targeted DNA nanostructures can achieve controlled drug delivery, reduce toxic side effects and overcome multidrug resistance. Herein, we constructed and characterized a DNA tetrahedral nanostructure (MUC1-TD) linked with the targeting aptamer MUC1. The interaction of daunorubicin (DAU)/acridine orange (AO) alone and in combination with MUC1-TD and the influence of the interaction on the cytotoxicity of the drugs were evaluated. Potassium ferrocyanide quenching analysis and DNA melting temperature assays were used to demonstrate the intercalative binding of DAU/AO to MUC1-TD. The interactions of DAU and/or AO with MUC1-TD were analyzed by fluorescence spectroscopy and differential scanning calorimetry. The number of binding sites, binding constant, entropy and enthalpy changes of the binding process were obtained. The binding strength and binding sites of DAU were higher than those of AO. The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. In vitro cytotoxicity studies demonstrated that the loading of MUC1-TD augmented the inhibitory effects of DAU and AO and the synergistic cytotoxic effects of DAU + AO on MCF-7 cells and MCF-7/ADR cells. Cell uptake studies showed that the loading of MUC1-TD was beneficial in promoting the apoptosis of MCF-7/ADR cells due to its enhanced targeting to the nucleus. This study has important guiding significance for the combined application of DAU and AO co-loaded by DNA nanostructures to overcome multidrug resistance.
Topics: Daunorubicin; Acridine Orange; Antineoplastic Agents; Drug Delivery Systems; DNA
PubMed: 36905740
DOI: 10.1016/j.saa.2023.122583 -
Journal of Ginseng Research May 2023Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available...
BACKGROUND
Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology.
MATERIALS AND METHODS
Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins.
RESULTS
We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy.
CONCLUSION
RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.
PubMed: 37252280
DOI: 10.1016/j.jgr.2023.02.002 -
Biological Research May 2021The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of...
BACKGROUND
The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish.
METHODS
Morpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP) transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo.
RESULTS
As expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants.
CONCLUSIONS
These findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.
Topics: Animals; Animals, Genetically Modified; Cell Differentiation; Humans; Morphogenesis; Phenotype; Zebrafish
PubMed: 34051853
DOI: 10.1186/s40659-021-00341-7 -
Molecular Diversity Jun 2023A detailed computational analysis of acridine derivatives viz. acridone, 9-amino acridine hydrochloride hydrate, proflavin, acridine orange and acridine yellow is done...
A detailed computational analysis of acridine derivatives viz. acridone, 9-amino acridine hydrochloride hydrate, proflavin, acridine orange and acridine yellow is done in terms of conceptual density functional theory (CDFT). CDFT-based global descriptors-ionization potential, electron affinity, HOMO-LUMO gap, hardness, softness, electronegativity and electrophilicity index of acridine derivatives for ground state as well as excited state are estimated with the help of different hybrid functionals B3LYP/6-31G (d, p), B3LYP/6-311G (d, p), B3LYP/DGDZVP and B3LYP/LANL2DZ. Acridine derivatives show higher values of ionization potential and electron affinity in excited state as compared to ground state, indicating that these compounds are willing to accept electrons in excited state rather than donating electron. Acridone shows the maximum HOMO-LUMO energy gap in ground and excited state which implies that one-way electron transfer is most feasible with this compound. Our computed results emphasize the pronounced electron acceptor behaviour of the acridine derivatives in the excited state which has already been experimentally verified. It is observed that the trend in the computed values of the descriptors is not much improved on refinement of the basis set.
Topics: Density Functional Theory; Acridines
PubMed: 35781180
DOI: 10.1007/s11030-022-10486-6 -
Anatomical Record (Hoboken, N.J. : 2007) Jul 2020The current study investigated the macroscopic and microscopic differences between pennaceous and plumulaceous feathers. The morphology of the barbules distinguished...
The current study investigated the macroscopic and microscopic differences between pennaceous and plumulaceous feathers. The morphology of the barbules distinguished pennaceous and plumulaceous feathers, particularly the shape of barbules during their development. In pennaceous feathers, the initial barbules were large and elongated or pyriform in shape, while plumulaceous feathers had small, thin, elongated initial barbules. The spinous barbules were characteristic of pennaceous feathers. The histochemical reactivity of both feather types for Mallory trichrome, orange G, and acridine orange, safranin O, PAS, and methylene blue was determined. Keratin was detected by Mallory trichrome, orange G, and acridine orange. In conclusion, the histochemical properties of pennaceous and plumulaceous feathers of quail, particularly the distribution and nature of keratin during development, should be considered in future studies. The unique morphological features of pennaceous and plumulaceous feathers could be used as a guide for phylogenetic identification. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1865-1883, 2020. © 2019 American Association for Anatomy.
Topics: Animals; Feathers; Phylogeny; Quail
PubMed: 31581344
DOI: 10.1002/ar.24276