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International Journal of Molecular... May 2024While edible algae might seem low in fat, the lipids they contain are crucial for good health and preventing chronic diseases. This study introduces a binary matrix to...
While edible algae might seem low in fat, the lipids they contain are crucial for good health and preventing chronic diseases. This study introduces a binary matrix to analyze all the polar lipids in both macroalgae (Wakame-, Dulse-, and Nori- spp.) and microalgae (Spirulina-, and Chlorella-) using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The key lies in a new dual matrix made by combining equimolar amounts of 1,5-diaminonaphthalene (DAN) and 9-aminoacridine (9AA). This combination solves the limitations of single matrices: 9AA is suitable for sulfur-containing lipids and acidic phospholipids, while DAN excels as an electron-transfer secondary reaction matrix for intact chlorophylls and their derivatives. By employing the equimolar binary matrix, a wider range of algal lipids, including free fatty acids, phospholipids, glycolipids, pigments, and even rare arsenosugarphospholipids were successfully detected, overcoming drawbacks related to ion suppression from readily ionizable lipids. The resulting mass spectra exhibited a good signal-to-noise ratio at a lower laser fluence and minimized background noise. This improvement stems from the binary matrix's ability to mitigate in-source decay effects, a phenomenon often encountered for certain matrices. Consequently, the data obtained are more reliable, facilitating a faster and more comprehensive exploration of algal lipidomes using high-throughput MALDI-MS/MS analysis.
Topics: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Lipids; Seaweed; Microalgae; 2-Naphthylamine; Aminacrine; Pigments, Biological; Spirulina
PubMed: 38892117
DOI: 10.3390/ijms25115919 -
Luminescence : the Journal of... Jun 2024Various 9-(substituted phenoxycarbonyl)-10-methylacridinium trifluoromethanesulfonates possessing electron-withdrawing substituents have been synthesized. The effect of...
Various 9-(substituted phenoxycarbonyl)-10-methylacridinium trifluoromethanesulfonates possessing electron-withdrawing substituents have been synthesized. The effect of substituents on the stability of the acridinium esters (AEs) at various temperatures in different buffers and the chemiluminescent properties have been examined. There was little correlation between the chemiluminescent properties of AEs and the pKa values of their associated phenols, but the steric effects of the ortho-substituents in the phenoxy group, as well as their electron-withdrawing natures, seem to play an important role in determining the properties. In general, when two identical substituents are present in the 2- and 6-positions, the compound is significantly more stable than when only a single substituent is present, presumably because of greater steric hindrance from the second group. The exception is the 2,6-difluorophenyl ester, which is less stable than the 2-fluorophenyl ester, presumably because the fluoro group is small. Addition of a third electron-withdrawing substituent at the 4-position, where it has no steric influence, typically increases susceptibility to decomposition. The presence of a nitro group has a significant destabilizing effect on AEs. Of the AEs studied, the 4-chlorophenyl ester showed the greatest chemiluminescent yield, while the 2-iodo-6-(trifluoromethyl)phenyl ester group showed the greatest stability in low pH buffers.
Topics: Acridines; Mesylates; Luminescence; Molecular Structure; Luminescent Measurements
PubMed: 38887175
DOI: 10.1002/bio.4794 -
Journal of Ethnopharmacology Jun 2024Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic...
ETHNOPHARMACOLOGICAL RELEVANCE
Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of β cells.
AIM OF THE STUDY
We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used.
MATERIALS AND METHODS
The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 μg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining.
RESULT
28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic β-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKβ/AMPK pathway.
CONCLUSIONS
The present study findings show that JTTF may protects β-cells by inhibiting the CaMKKβ/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM.
PubMed: 38885916
DOI: 10.1016/j.jep.2024.118440 -
Molecular Biology Reports Jun 2024The present study aimed to elucidate the potential anticancer activity and mechanism of P. harmala's alkaloid extract, harmine (HAR), and harmaline (HAL) in HCT-116...
BACKGROUND
The present study aimed to elucidate the potential anticancer activity and mechanism of P. harmala's alkaloid extract, harmine (HAR), and harmaline (HAL) in HCT-116 colorectal cancer cells.
METHODS AND RESULTS
P. harmala's alkaloid was extracted from harmala seeds. HCT-116 cells were treated with P. harmala's alkaloid extract, HAR and HAL. Cytotoxicity was determined by MTT assay, apoptotic activity detected via flow cytometry and acridine orange (AO)/ethidium bromide (EB) dual staining, and cell cycle distribution analyzed with flow cytometry. The mRNA expression of Bcl-2-associated X protein (Bax) and glycogen synthase kinase-3 beta (GSK3β) was measured by real-time PCR. Furthermore, the expression of Bax, Bcl-2, GSK3β and p53 proteins, were determined by western blotting. The findings indicated that, P. harmala's alkaloids extract, HAR and HAL were significantly cytotoxic toward HCT116 cells after 24 and 48 h of treatment. We showed that P. harmala's alkaloid extract induce apoptosis and cell cycle arrest at G2 phase in the HCT116 cell line. Downregulation of GSK3β and Bcl-2 and upregulation of Bax and p53 were observed.
CONCLUSION
The findings of this study indicate that the P. harmala's alkaloid extract has anticancer activity and may be further investigated to develop future anticancer chemotherapeutic agents.
Topics: Humans; Peganum; HCT116 Cells; Apoptosis; Colonic Neoplasms; Seeds; Harmine; Glycogen Synthase Kinase 3 beta; bcl-2-Associated X Protein; Plant Extracts; Alkaloids; Harmaline; Antineoplastic Agents, Phytogenic; Tumor Suppressor Protein p53; Proto-Oncogene Proteins c-bcl-2; Cell Proliferation
PubMed: 38872006
DOI: 10.1007/s11033-024-09655-7 -
Scientific Reports Jun 2024Antimicrobial peptides (AMPs) have sparked significant interest as potential anti-cancer agents, thereby becoming a focal point in pursuing novel cancer-fighting...
Antimicrobial peptides (AMPs) have sparked significant interest as potential anti-cancer agents, thereby becoming a focal point in pursuing novel cancer-fighting strategies. These peptides possess distinctive properties, underscoring the importance of developing more potent and selectively targeted versions with diverse mechanisms of action against human cancer cells. Such advancements would offer notable advantages compared to existing cancer therapies. This research aimed to examine the toxicity and selectivity of the nrCap18 peptide in both cancer and normal cell lines. Furthermore, the rate of cellular death was assessed using apoptosis and acridine orange/ethidium bromide (AO/EB) double staining at three distinct incubation times. Additionally, the impact of this peptide on the cancer cell cycle and migration was evaluated, and ultimately, the expression of cyclin-dependent kinase 4/6 (CDK4/6) genes was investigated. The results obtained from the study demonstrated significant toxicity and selectivity in cancer cells compared to normal cells. Moreover, a strong progressive increase in cell death was observed over time. Furthermore, the peptide exhibited the ability to halt the progression of cancer cells in the G1 phase of the cell cycle and impede their migration by suppressing the expression of CDK4/6 genes.
Topics: Humans; Animals; Cell Line, Tumor; Breast Neoplasms; Apoptosis; Cathelicidins; Cyclin-Dependent Kinase 4; Female; Rabbits; Cell Movement; Antineoplastic Agents; Antimicrobial Cationic Peptides; Cyclin-Dependent Kinase 6; Cell Cycle; Cell Proliferation; Peptides; Gene Expression Regulation, Neoplastic
PubMed: 38866982
DOI: 10.1038/s41598-024-64400-1 -
International Journal of Pharmaceutics Jun 2024Nanomaterials have become increasingly important over time as research technology has enabled the progressively precise study of materials at the nanoscale. Developing... (Review)
Review
Nanomaterials have become increasingly important over time as research technology has enabled the progressively precise study of materials at the nanoscale. Developing an understanding of how nanomaterials are produced and tuned allows scientists to utilise their unique properties for a variety of applications, many of which are already incorporated into commercial products. Fullerenol nanoparticles C60(OH)n, 2 ≤ n ≤ 44 are fullerene derivatives and are produced synthetically. They have good biocompatibility, low toxicity and no immunological reactivity. In addition, their nanometre size, large surface area to volume ratio, ability to penetrate cell membranes, adaptable surface that can be easily modified with different functional groups, drug release, high physical stability in biological media, ability to remove free radicals, magnetic and optical properties make them desirable candidates for various applications. This review comprehensively summarises the various applications of fullerenol nanoparticles in different scientific fields such as nanobiomedicine, including antibacterial and antiviral agents, and provides an overview of their use in agriculture and biosensor technology. Recommendations are also made for future research that would further elucidate the mechanisms of fullerenols actions.
PubMed: 38857663
DOI: 10.1016/j.ijpharm.2024.124313 -
Drug Development and Industrial Pharmacy Jun 2024Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for...
INTRODUCTION
Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy.
SIGNIFICANCE
Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy.
METHODS
CoFeO magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated.
RESULTS
The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). , experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery.
CONCLUSIONS
Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.
PubMed: 38832870
DOI: 10.1080/03639045.2024.2363231 -
BMC Complementary Medicine and Therapies Jun 2024Cervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS)...
BACKGROUND
Cervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS) possesses an antiproliferative effect on several tumors in vitro. Therefore, in this study, we assessed the impact of EESMS on human cervical carcinoma (HeLa) cell proliferation.
METHODS
The proliferation and apoptotic effects of HeLa cells treated with EESMS were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, dual acridine orange/ethidium bromide double staining, flow cytometry, and western blotting. Single-cell level atomic force microscopy (AFM) was conducted to detect the mechanical properties of HeLa cells, and proteomics and bioinformatics methods were used to elucidate the molecular mechanisms of EESMS.
RESULTS
EESMS treatment inhibited HeLa cell proliferation by blocking the G0/G1 phase, increasing the expression of Caspase-3 and affecting its mechanical properties, and the EESMS indicated no significant inhibitory effect on mouse fibroblasts L929 cell line. In total, 218 differentially expressed proteins were identified using two-dimensional electrophoresis, and eight differentially expressed proteins were successfully identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The differentially expressed proteins were involved in various cellular and biological processes.
CONCLUSION
This study provides a perspective on how cells change through biomechanics and a further theoretical foundation for the future application of Sophora moorcroftiana as a novel low-toxicity chemotherapy medication for treating human cervical cancer.
Topics: Humans; Sophora; HeLa Cells; Uterine Cervical Neoplasms; Female; Cell Proliferation; Plant Extracts; Apoptosis; Antineoplastic Agents, Phytogenic; Mice; Ethanol
PubMed: 38831394
DOI: 10.1186/s12906-024-04502-5 -
Biomedicine & Pharmacotherapy =... Jul 2024Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine...
Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies for the target proteins (K1578 and K1599) or increased potency for AChE (K1592 and K1594) were studied to identify the most promising pro-cognitive compound. Their effects were studied in cholinergic (scopolamine-induced) and glutamatergic (MK-801-induced) rat models of cognitive deficits in the Morris water maze. Moreover, the impacts on locomotion in the open field and AChE activity in relevant brain structures were investigated. The effect of the most promising compound on NMDA receptors was explored by in vitro electrophysiology. The cholinergic antagonist scopolamine induced a deficit in memory acquisition, however, it was unaffected by the compounds, and a deficit in reversal learning that was alleviated by K1578 and K1599. K1578 and K1599 significantly inhibited AChE in the striatum, potentially explaining the behavioral observations. The glutamatergic antagonist dizocilpine (MK-801) induced a deficit in memory acquisition, which was alleviated by K1599. K1599 also mitigated the MK-801-induced hyperlocomotion in the open field. In vitro patch-clamp corroborated the K1599-associated NMDA receptor inhibitory effect. K1599 emerged as the most promising compound, demonstrating pro-cognitive efficacy in both models, consistent with intended dual effect. We conclude that tacrine has the potential for development of derivatives with dual in vivo effects. Our findings contributed to the elucidation of the structural and functional properties of tacrine derivatives associated with optimal in vivo pro-cognitive efficacy.
Topics: Animals; Tacrine; Cholinesterase Inhibitors; Receptors, N-Methyl-D-Aspartate; Male; Rats; Dizocilpine Maleate; Maze Learning; Cognition; Rats, Wistar; Acetylcholinesterase; Scopolamine; Excitatory Amino Acid Antagonists; Memory
PubMed: 38823278
DOI: 10.1016/j.biopha.2024.116821 -
Anticancer Research Jun 2024The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel...
BACKGROUND/AIM
The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC.
MATERIALS AND METHODS
RENCA cells (1.0×10 cells/10 μl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively.
RESULTS
The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05).
CONCLUSION
AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.
Topics: Zoledronic Acid; Animals; Carcinoma, Renal Cell; Bone Neoplasms; Kidney Neoplasms; Male; Acridine Orange; Mice; Mice, Inbred BALB C; Apoptosis; Cell Line, Tumor; Humans; Vascular Endothelial Growth Factor A; Imidazoles; X-Ray Microtomography; Xenograft Model Antitumor Assays
PubMed: 38821618
DOI: 10.21873/anticanres.17055