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Synthesis, anti-amoebic activity and molecular docking simulation of eugenol derivatives against sp.Saudi Pharmaceutical Journal : SPJ :... Sep 2023Amoebae of the genus can cause diseases such as amoebic keratitis and granulomatous amoebic encephalitis. Until now, treatment options for these diseases have not been...
Amoebae of the genus can cause diseases such as amoebic keratitis and granulomatous amoebic encephalitis. Until now, treatment options for these diseases have not been fully effective and have several drawbacks. Therefore, research into new drugs is needed for more effective treatment of infections. Eugenol, a phenolic aromatic compound mainly derived from cloves, has a variety of pharmaceutical properties. In this study, nine eugenol derivatives (K1-K9), consisting of five new and four known compounds, were synthesized and screened for their antiamoebic properties against sp. The structure of these compounds was characterized spectroscopically by Fourier transform infrared (FTIR), Ultraviolet-Visible (UV-Vis), H and C Nuclear Magnetic Resonance (NMR) and mass spectrometer (MS). The derived molecules were screened for antiamoebic activity by determining IC values based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and observation of amoeba morphological changes by light and fluorescence microscopy. Most of the tested compounds possessed strong to moderate cytotoxic effects against trophozoite cells with IC values ranging from 0.61 to 24.83 μg/mL. Observation of amoebae morphology by light microscopy showed that the compounds caused the transformed cells to be roundish and reduced in size. Furthermore, fluorescence microscopy observation using acridine orange (AO) and propidium iodide (PI) (AO/PI) staining showed that the cells have damaged membranes by displaying a green cytoplasm with orange-stained lysosomes. Acidification of the lysosomal structure indicated disruption of the internal structure of cells when treated with eugenol derivatives. The observed biological results were also confirmed by interaction simulations based on molecular docking between eugenol derivatives and profilin. These interactions could affect the actin-binding ability of the protein, disrupting the shape and mobility of The overall results of this study demonstrate that eugenol derivatives can be considered as potential drugs against infections caused by
PubMed: 37546528
DOI: 10.1016/j.jsps.2023.101703 -
Biomedicine & Pharmacotherapy =... May 2024Diabetic nephropathy is a type of kidney disorder that develops as a complication of multifactorial diabetes. Diabetic nephropathy is characterized by microangiopathy,...
INTRODUCTION
Diabetic nephropathy is a type of kidney disorder that develops as a complication of multifactorial diabetes. Diabetic nephropathy is characterized by microangiopathy, resulting from glucose metabolism, oxidative stress, and changes in renal hemodynamics. This study strived to evaluate the in vitro cytoprotective activity of atorvastatin (ATR), and quercetin (QCT) alone and in combination against diabetic nephropathy.
METHODS
The MTT assay was utilized to analyze the effects of the test compounds on NRK-52E rat kidney epithelial cells. The detection of apoptosis and ability to scavenge free radicals was assessed via acridine orange-ethidium bromide (AO-EB) dual fluorescence staining, and 2,2-diphenyl-1-picrylhydrazyfree assay (DPPH), respectively. The ability of anti-inflammatory effect of the test compounds and western blot analysis against TGF-β, TNF-α, and IL-6 further assessed to determine the combinatorial efficacy.
RESULTS
Atorvastatin and quercetin treatment significantly lowered the expression of TGF-β, TNF-α, and IL-6 indicating the protective role in Streptozotocin-induced nephrotoxicity. The kidney cells treated with a combination of atorvastatin and quercetin showed green fluorescing nuclei in the AO-EB staining assay, indicating that the combination treatment restored cell viability. Quercetin, both alone and in combination with atorvastatin, demonstrated strong DPPH free radical scavenging activity and further encountered an anti-oxidant and anti-inflammatory effect on the combination of these drugs.
CONCLUSION
Nevertheless, there is currently no existing literature that reports on the role of QCT as a combination renoprotective drug with statins in the context of diabetic nephropathy. Hence, these findings suggest that atorvastatin and quercetin may have clinical potential in treating diabetic nephropathy.
Topics: Quercetin; Atorvastatin; Animals; Diabetic Nephropathies; Rats; Cell Line; Apoptosis; Antioxidants; Kidney; Transforming Growth Factor beta; Drug Therapy, Combination; Cell Survival; Oxidative Stress; Anti-Inflammatory Agents
PubMed: 38574626
DOI: 10.1016/j.biopha.2024.116533 -
International Journal of Molecular... Feb 2024Pancreatic ductal adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis associated with this cancer is due to the absence...
Pancreatic ductal adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis associated with this cancer is due to the absence of specific biomarkers, aggressiveness, and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that result in cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory properties. Regarding the anticancer effect of CBG, up to now, there is only limited evidence in human cancers. To fill this gap, we investigated the effects of CBG on the PDAC cell lines, PANC-1 and MIAPaCa-2. The effect of CBG activity on cell viability, cell death, and EGFR-RAS-associated signaling was investigated. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate the effect of CBG on PDAC cell line viabilities. Annexin-V and Acridine orange staining, followed by cytofluorimetric analysis and Western blotting, were used to evaluate CBG's effect on cell death. The modulation of EGFR-RAS-associated pathways was determined by Western blot analysis and a Milliplex multiplex assay. Moreover, by employing the MTT data and SynergyFinder Plus software analysis, the effect of the combination of CBG and chemotherapeutic drugs was determined.
Topics: Humans; Apoptosis; Autophagic Cell Death; Cannabinoids; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Deoxycytidine; ErbB Receptors; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras)
PubMed: 38396679
DOI: 10.3390/ijms25042001 -
Heliyon Sep 2023Oral cancer is one of the leading causes of death worldwide, and its prevalence is especially high in developing countries. As an oral cancer treatment, traditional...
Oral cancer is one of the leading causes of death worldwide, and its prevalence is especially high in developing countries. As an oral cancer treatment, traditional therapies are commonly used. Nonetheless, these treatments frequently result in a variety of side effects. As a consequence, there is an urgent need to enhance oral cancer therapies. Probiotics have recently demonstrated intriguing properties as therapeutic options for cancer treatment. Thus, the purpose of this study was to investigate the anticancer effect of probiotic strains on the mouth epidermal carcinoma cells (KB) and oral squamous cell carcinoma (OSCC) cell lines. In this study, we looked at 21 strains isolated from traditional dairy products in the Kermanshah province of western Iran to see if they had any inhibitory effects on oral cancer cell lines in vitro. We isolated and characterized strains before assessing and comparing their probiotic potential and safety. Using the MTT assay, the bacterial extract was then prepared and used as an anti-proliferative agent on oral cancer (KB and OSCC) and normal (fibroblast and human umbilical vein endothelial cells (HUVEK) cell lines. Finally, acridine orange/ethidium bromide staining was used to determine whether cell death was caused by apoptosis. Four isolates (C14, M22, M42, and Y8) were shown to have beneficial probiotic qualities. extracts (of a protein nature) decreased the survival and proliferation of the KB and OSCC cancer cell lines (dose- and time-dependent) by inducing apoptosis, with no basic damaging effects on normal cells. The staining with acridine orange/ethidium bromide revealed that the cell death was caused by apoptosis. Furthermore, of the four strains examined, isolate Y8 () showed the strongest probiotic potential for suppressing KB and OSCC cell proliferation when compared to anticancer medicines (doxorubicin and paclitaxel). The current research found that extract might reduce the growth and viability of the KB and OSCC cancer cell lines by inducing apoptosis, increasing the survival rate of oral cancer patients.
PubMed: 37809760
DOI: 10.1016/j.heliyon.2023.e20147 -
Scientific Reports Nov 2023The Sperm Chromatin Structure Assay (SCSA) is a robust test with high repeatability and precision. It is a clinically accepted assay that defines risk for infertility in...
The Sperm Chromatin Structure Assay (SCSA) is a robust test with high repeatability and precision. It is a clinically accepted assay that defines risk for infertility in men by measuring the degree of DNA fragmentation (% DFI) in sperm. The objective of this study was to adapt and validate the SCSA for rhesus macaques (Macaca mulatta) and establish a range for % DFI in fertile males. Sperm samples from two different males were used to produce a % DFI validation curve before establishing a range using additional samples from n = 11 males. Sperm labeled with acridine orange were analyzed by flow cytometry to measure green fluorescence (native or intact DNA) and red fluorescence (fragmented DNA). Data were exported to FlowJo software to determine the % DFI for each sample. DNA fragmentation ranged from 0.1 to 2.4% DFI, with a mean ± SD = 1.1 ± 0.7% DFI (validation curve optimized to R > 0.95). In conclusion, we were able to successfully validate the SCSA in our institution and establish the first normal range for sperm DNA fragmentation in rhesus macaques. Our study provides a quantitative baseline for future evaluations to assess macaque fertility through the SCSA test.
Topics: Animals; Humans; Male; Macaca mulatta; Semen; DNA Fragmentation; Reference Values; Chromatin; Spermatozoa; Infertility, Male; DNA
PubMed: 37974016
DOI: 10.1038/s41598-023-46928-w -
Orthopaedic Surgery Jun 2024The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation...
OBJECTIVES
The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation provides a new opportunity for the development of bone implants, but it necessitates higher requirements for bone tissue differentiation and the antibacterial properties of bone implants in clinical practice.
METHODS
This study investigated the preparation, antimicrobial properties, and osteogenesis-promoting ability of the 3D printed porous Ti alloy anodic oxidized Ag-carrying (Ag@3D-TiO) scaffolds. The 3D printed porous Ti alloy (3D-Ti), anodized 3D printed porous Ti alloy (3D-TiO), and Ag@3D-TiO scaffolds were synthesized using electron beam melting. The antimicrobial properties of the scaffolds were examined using antibacterial tests and their cytocompatibility was assessed using a cell proliferation assay and acridine orange/ethidium bromide (AO/EB) staining. In vitro cellular assays were used to investigate the effects of the scaffold microstructural features on cell activity, proliferation, and osteogenesis-related genes and proteins. In vivo animal experiments were used to evaluate the anti-inflammatory and osteogenesis-promoting abilities of the scaffolds.
RESULTS
The Ag@3D-TiO scaffolds exhibited sustained anti-microbial activity over time, enhanced cell proliferation, facilitated osteogenic differentiation, and increased extracellular matrix mineralization. In addition, alkaline phosphatase (ALP), collagen type I (COL-I), and osteocalcin (OCN)-related genes and proteins were upregulated. In vivo animal implantation experiments, the anti-inflammatory effect of the Ag@3D-TiO scaffolds were observed using histology, and a large amount of fibrous connective tissue was present around it; the Ag@3D-TiO scaffolds were more bio-compatible with the surrounding tissues compared with 3D-Ti and 3D-TiO; a large amount of uniformly distributed neoplastic bone tissue existed in their pores, and the chronic systemic toxicity test showed that the 3D-Ti, 3D-TiO, and Ag@3D-TiO scaffolds are biologically safe.
CONCLUSION
The goal of this study was to create a scaffold that exhibits antimicrobial properties and can aid bone growth, making it highly suitable for use in bone tissue engineering.
Topics: Titanium; Osteogenesis; Tissue Scaffolds; Silver; Animals; Printing, Three-Dimensional; Mice; Cell Proliferation; Cell Differentiation; Anti-Bacterial Agents; Porosity
PubMed: 38706035
DOI: 10.1111/os.14081 -
Cells Mar 2024Semen handling and cryopreservation induce oxidative stress that should be minimized. In this study, human semen was supplemented during cryopreservation with...
Semen handling and cryopreservation induce oxidative stress that should be minimized. In this study, human semen was supplemented during cryopreservation with formulations of handmade liposomes and chlorogenic acid (CGA), an antioxidant compound. Zwitterionic (ZL), anionic (AL), and cationic (CL) liposomes were synthesized and characterized. Three aliquots of swim-up-selected sperm were incubated with ZL, AL, and CL (1:10,000), respectively. The percentages of sperm with progressive motility, high mitochondrial membrane potential (MMP; JC-1), double-stranded DNA (dsDNA acridine orange), and acrosome integrity ( agglutinin) were assessed. Then, human semen was frozen using both 1:10,000 ZL and CGA as follows: freezing medium/empty ZL (EL), freezing medium/empty ZL/CGA in the medium (CGA + EL), freezing medium/CGA loaded ZL (CGA), freezing medium (CTR). The same sperm endpoints were evaluated. ZL were the most tolerated and used for semen cryopreservation protocols. All the supplemented samples showed better endpoints versus CTR ( < 0.001). In particular, spermatozoa from the CGA and CGA + EL A samples showed increased motility, dsDNA, and acrosome integrity versus CTR and EL ( < 0.001; motility EL vs. CGA + EL < 0.05). ZL and CGA can improve post-thaw sperm quality, acting on both cold shock effect management and oxidative stress. These findings open new perspectives on human and animal reproduction.
Topics: Animals; Humans; Male; Freezing; Chlorogenic Acid; Liposomes; Fertility Preservation; Cryoprotective Agents; Semen Preservation; Seeds; Spermatozoa; Cryopreservation; Dietary Supplements
PubMed: 38534386
DOI: 10.3390/cells13060542 -
International Journal of Molecular... Jul 2023Great effort has been devoted to the synthesis of novel multi-target directed tacrine derivatives in the search of new treatments for Alzheimer's disease (AD). Herein we...
Great effort has been devoted to the synthesis of novel multi-target directed tacrine derivatives in the search of new treatments for Alzheimer's disease (AD). Herein we describe the proof of concept of MBA121, a compound designed as a tacrine-ferulic acid hybrid, and its potential use in the therapy of AD. MBA121 shows good -amyloid (A) anti-aggregation properties, selective inhibition of human butyrylcholinesterase, good neuroprotection against toxic insults, such as A, A, and HO, and promising ADMET properties that support translational developments. A passive avoidance task in mice with experimentally induced amnesia was carried out, MBA121 being able to significantly decrease scopolamine-induced learning deficits. In addition, MBA121 reduced the A plaque burden in the cerebral cortex and hippocampus in APP/PS1 transgenic male mice. Our in vivo results relate its bioavailability with the therapeutic response, demonstrating that MBA121 is a promising agent to treat the cognitive decline and neurodegeneration underlying AD.
Topics: Male; Mice; Humans; Animals; Alzheimer Disease; Tacrine; Butyrylcholinesterase; Hydrogen Peroxide; Amyloid beta-Peptides; Mice, Transgenic; Disease Models, Animal; Cholinesterase Inhibitors
PubMed: 37569630
DOI: 10.3390/ijms241512254 -
Poultry Science Jun 2024Sertoli cells (SC) are a type of important cells in the testes, which can provide transport proteins, regulatory proteins, growth factors, and other cytokines for the...
Sertoli cells (SC) are a type of important cells in the testes, which can provide transport proteins, regulatory proteins, growth factors, and other cytokines for the spermatogenic process. They participate in the regulation of the maturation and differentiation of spermatogenic cells and play an important supporting role in the migration, proliferation, and differentiation of germ cells at all levels in the testes. Previous studies found differential expression of LINC9137, miR-140-3p, and Sodium/Potassium Transporting ATPase Interacting 3 (NKAIN3) genesin high and low sperm motility goose testicular tissues. This study investigated the effects of the LINC9137-miR-140-3p-NKAIN3 signal axis on the proliferation and apoptosis of goose testicular sertoli cells at the cellular level, respectively. The results showed that through acridine orange staining, oil red O staining, Alkaline phosphatase (AKP) staining, and RT qPCR assay, it was comprehensively identified that the cultured testicular sertoli cells were purified in vitro. Through the dual luciferase activity detection test, it was found that LINC9137 has a targeted binding site with miR-140-3p and NKAIN3. In addition, this study found that overexpression of miR-140-3p significantly inhibited the expression of LINC9137 and NKAIN3 in sertoli cells, and their expression was significantly increased when miR-140-3p was interfered with. By measuring cell proliferation activity and apoptosis related gene expression, it was found that overexpression of LINC9137 decreased cell proliferation activity (P > 0.05), while the expression level of apoptosis factor Bcl2 Associated X Protein (Bax)/B-cell lymphoma-2 (Bcl2) increased (P > 0.05). On the contrary, when interfering with LINC9137, the cell proliferation activity of sertoli cells was significantly increased (P < 0.01), and the expression level of apoptosis factor Bax/Bcl2 was significantly reduced (P < 0.05); The effect of miR-140-3p on the proliferation and apoptosis of sertoli cells is opposite to that of LINC9137. Meanwhile, this study co transfected overexpressed LINC9137 and miR-140-3p plasmids into sertoli cells, and found that the effect of LINC9137 overexpression on supporting cell proliferation was weakened by miR-140-3p. This study elucidates the role and function of the LINC9137 miR-140-3p-NKAIN3 signaling axis in the development of goose testes and spermatogenesis, establishes a regulatory network related to spermatogenesis, and provides a theoretical basis for studying the genetic regulation of goose spermatogenesis.
Topics: Animals; Male; Sertoli Cells; MicroRNAs; Signal Transduction; Geese; Avian Proteins; Apoptosis; Testis; Cell Proliferation; RNA, Long Noncoding
PubMed: 38701630
DOI: 10.1016/j.psj.2024.103724 -
The New Microbiologica Jan 2024The in vitro antimicrobial activity of the active ingredient in antimicrobial magistral drug formulations and plant extracts used in folk medicine were investigated...
The in vitro antimicrobial activity of the active ingredient in antimicrobial magistral drug formulations and plant extracts used in folk medicine were investigated comparatively. Borax, sulfur colloid, hydrogen peroxide, benzoic acid, rivanol, brilliant green and plant extracts as active ingredients, namely: Helianthus tuberosus tuber-H2O (aqueous extract), Cydonia oblonga leaves-H2O, Allium porrum whole plant-H2O, Cistus laurifolius leaves-EtOH, Solanum muricalum-H2O, and Fumaria cilicica leaves-EtOH were studied to determine their antimicrobial activity against different bacteria and fungi (S. pyogenes, S. aureus, S. epidermidis, E. faecalis, K. pneumonia, H. influenza, P. aeruginosa, A. baumannii, E. coli, Candida albicans, C. tropicalis, C. parapsilosis, C. krusei) by using the microdilution method. The active ingredients and plant extracts showed different activities as MIC between 1->128 μg/mL. Brilliant green and rivanol as active ingredients had MIC values of 1 μg/mL against all tested microorganisms. C. oblonga leaves-H2O as well as C. laurifolius leaves-EtOH as plant extracts were indicated as having the highest antimicrobial effect in MIC value of 16 μg/ml against A. baumannii and S. pyogenes, respectively. On the other hand, F. cilicica leaves-EtOH and C. laurifolius leaves-EtOH showed the highest antifungal activity (MIC; 16 μg/mL).
Topics: Humans; Ethacridine; Escherichia coli; Plants, Medicinal; Staphylococcus aureus; Anti-Infective Agents; Ethanol; Plant Extracts; Quaternary Ammonium Compounds
PubMed: 38252047
DOI: No ID Found