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Journal of Cellular and Molecular... Jun 2024TNKS is a new target for the treatment of lung adenocarcinoma, the synergistic effects of the TCM compound Xiaoyan decoction and the TNKS inhibitor E7449 in the...
TNKS is a new target for the treatment of lung adenocarcinoma, the synergistic effects of the TCM compound Xiaoyan decoction and the TNKS inhibitor E7449 in the intervention on TNKS were investigated, and the possible underlying mechanisms involved were clarified. Immunohistochemistry was used to analyse TNKS expression in tumour tissues. The impact of targeting TNKS on cell growth, invasion, apoptosis, key genes and signalling pathways was investigated in tumour cells by Western blotting, rescue experiments, colony formation assays, flow cytometry and label-free experiments. Tumour xenografts with A549 cells were then transplanted for in vivo study. We found that TNKS high expression was closely related to the advanced tumour stage and tumour size in lung adenocarcinom. After TNKS was knocked down in vitro, the growth, proliferation, migration and invasion were markedly reduced in A549 and H1975 cells. We subsequently applied the Xiaoyan decoction and TNKS inhibitors to intervene in lung adenocarcinoma. Xiaoyan decoction and E7449 suppressed TNKS expression and inhibited adenocarcinoma cell proliferation, migration, invasion and apoptosis in vitro. Proteomic analysis revealed that E7449 treatment may be most closely associated with the classic Wnt/β-catenin pathway, whereas Xiaoyan decoction treatment may be related to the WNT/PLAN pathway. Xenograft studies confirmed that E7449 or Xiaoyan decoction inhibited lung tumour growth in vivo and attenuated the Wnt signalling pathway in adenocarcinoma. These findings suggest that TNKS is a novel therapeutic target. TCM preparations and small molecule inhibitors are expected to constitute an effective combination strategy.
Topics: Humans; Animals; Drugs, Chinese Herbal; Cell Proliferation; Adenocarcinoma of Lung; Apoptosis; Lung Neoplasms; Cell Movement; Xenograft Model Antitumor Assays; Wnt Signaling Pathway; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Mice; Carcinogenesis; A549 Cells; Mice, Nude; Male; Female; Proteomics; Mice, Inbred BALB C
PubMed: 38898581
DOI: 10.1111/jcmm.18467 -
BMC Biotechnology Jun 2024γ-Hexachlorocyclohexane (γ-HCH), an organochlorine insecticide of anthropogenic origin, is a persistent organic pollutant (POP) that causes environmental pollution...
BACKGROUND
γ-Hexachlorocyclohexane (γ-HCH), an organochlorine insecticide of anthropogenic origin, is a persistent organic pollutant (POP) that causes environmental pollution concerns worldwide. Although many γ-HCH-degrading bacterial strains are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the low survival rate of the exogenous bacteria. Another strategy for the bioremediation of γ-HCH involves the use of transgenic plants expressing bacterial enzyme for γ-HCH degradation through phytoremediation.
RESULTS
We generated transgenic Arabidopsis thaliana expressing γ-HCH dehydrochlroninase LinA from bacterium Sphingobium japonicum strain UT26. Among the transgenic Arabidopsis T2 lines, we obtained one line (A5) that expressed and accumulated LinA well. The A5-derived T3 plants showed higher tolerance to γ-HCH than the non-transformant control plants, indicating that γ-HCH is toxic for Arabidopsis thaliana and that this effect is relieved by LinA expression. The crude extract of the A5 plants showed γ-HCH degradation activity, and metabolites of γ-HCH produced by the LinA reaction were detected in the assay solution, indicating that the A5 plants accumulated the active LinA protein. In some A5 lines, the whole plant absorbed and degraded more than 99% of γ-HCH (10 ppm) in the liquid medium within 36 h.
CONCLUSION
The transgenic Arabidopsis expressing active LinA absorbed and degraded γ-HCH in the liquid medium, indicating the high potential of LinA-expressing transgenic plants for the phytoremediation of environmental γ-HCH. This study marks a crucial step toward the practical use of transgenic plants for the phytoremediation of POPs.
Topics: Arabidopsis; Plants, Genetically Modified; Biodegradation, Environmental; Hexachlorocyclohexane; Sphingomonadaceae; Soil Pollutants; Bacterial Proteins; Lyases
PubMed: 38898480
DOI: 10.1186/s12896-024-00867-0 -
Scientific Reports Jun 2024Oxidative stress is considered one of the main challenges for in vitro maturation (IVM) and makes assisted reproductive technology (ART), including IVF and embryonic... (Comparative Study)
Comparative Study
Oxidative stress is considered one of the main challenges for in vitro maturation (IVM) and makes assisted reproductive technology (ART), including IVF and embryonic development less effective. Reducing free radicals via biocompatible nanoparticles (NPs) is one of the most promising approaches for developing IVM. We investigated the comparative effect of green and chemically synthesized iron oxide nanoparticles (IONPs) with an aqueous extract of date palm pollen (DPP) on oocyte parameters related to the IVM process. To this end, IONPs were synthesized by chemical (Ch-IONPs) and green methods (G-IONPs using DPP) and characterized. The mature oocyte quality of the Ch-IONPs and G-IONPs groups was evaluated by JC1 and Hoechst staining, Annexin V-FITC-Propidium Iodide, 2', 7'-dichlorofluorescein diacetate, and dihydroethidium staining compared to the control group. Eventually, the mature oocytes were fertilized, promoted to blastocysts (BL), and evaluated in vitro. Compared with the control and G-IONPs groups, the Ch-IONPs-treated group produced more hydrogen peroxide and oxygen radicals. Compared with the Ch-IONPs group, the fertilization rate in the G-IONPs and control groups increased significantly. Finally, the G-IONPs and control groups exhibited a significant increase in the 2PN, 2-cell, 4-cell, 8-cell, compacted morula (CM), and BL rates compared with the Ch-IONPs group. Green synthesis of IONPs can reduce the toxicity of chemical IONPs during the IVM process. It can be concluded that G-IONPs encased with DPP compounds have the potential to protect against exogenous reactive oxygen species (ROS) production in an IVM medium, which can have a crucial effect on oocyte maturation and fertilization efficiency.
Topics: Oocytes; Embryonic Development; Fertilization in Vitro; Magnetic Iron Oxide Nanoparticles; Animals; In Vitro Oocyte Maturation Techniques; Female; Reactive Oxygen Species; Green Chemistry Technology; Oxidative Stress; Mice; Ferric Compounds
PubMed: 38898126
DOI: 10.1038/s41598-024-65121-1 -
Fitoterapia Jun 2024The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology....
The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology. Extracts prepared from certain plant species native to Canadian prairie and montane cordillera ecosystems have previously been shown to have anti-mitotic activity on human cancer cell lines. In this study, we investigated the glacier lily, Erythronium grandiflorum (Liliaceae), in which the species was the most taxonomically distant from Asteraceae and had anti-mitotic activity. When added to cell lines, E. grandiflorum extracts induced rounded cell morphology and arrested cells in the G2/M phase of the cell cycle. Of the cells that displayed a rounded phenotype, all were positive for phospho-histone H3 and contained a distorted mitotic spindle. This anti-mitotic activity was distinct from that of the compound colchicine, which has been previously isolated from the Liliaceae family. By biology-guided fractionation, we isolated the natural product (+)-6-tuliposide A and are the first to report its anti-mitotic activity. These results reveal a chemical motif in secondary metabolites and expand the range of Canadian prairie plants with anti-mitotic activity that can become new scientific tools or used in the development of anti-proliferative medicines.
PubMed: 38897244
DOI: 10.1016/j.fitote.2024.106075 -
Brazilian Journal of Biology = Revista... 2024Terminalia argentea tree, native to Brazil, is widely used in landscaping, recovering degraded areas, its wood, coal production, and the bark or leaf extracts has...
Terminalia argentea tree, native to Brazil, is widely used in landscaping, recovering degraded areas, its wood, coal production, and the bark or leaf extracts has medicinal use. Despite of its importance, the arthropod fauna associated to this plant and its interspecific relationships still needs further studies. The objectives of this study were to evaluate the arthropods, their ecological indices and the distribution in the leaf faces on T. argentea saplings. The numbers of phytophagous insects (e.g., Cephalocoema sp.), pollinators (e.g., Tetragonisca angustula), and natural enemies (e.g., Oxyopidae), and their ecological indices (e.g., species richness), were higher on the adaxial leaf faces on T. argentea saplings. Aggregated distribution of phytophagous insects (e.g., Aphis spiraecola), pollinators (e.g., Trigona spinipes), and natural enemies (e.g., Camponotus sp.) on T. argentea saplings was observed. Abundance, diversity, and species richness of natural enemies correlated, positively, with those of phytophagous and pollinators insects. Predators and tending ants followed their prey and sucking insects, respectively. Tending ants protected sucking insects against predators, and reduced chewing insects. The high number of Cephalocoema sp. on T. argentea saplings is a problem, because this insect can feed on leaves of this plant, but its preference for the adaxial leaf face favors its control. The aggregation behavior of arthropods on T. argentea saplings favors the control of potential pests of this plant. There seems to be competition between tending ants for space and food resources on T. argentea saplings.
Topics: Animals; Plant Leaves; Arthropods; Terminalia; Population Density; Biodiversity; Brazil; Insecta
PubMed: 38896730
DOI: 10.1590/1519-6984.281588 -
Brazilian Journal of Biology = Revista... 2024It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and...
It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 μg/ml, with the flower extract having an even lower value of less than 50 μg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.
Topics: Humans; Antioxidants; Plant Extracts; Lantana; Anti-Inflammatory Agents; Cell Line, Tumor; Antineoplastic Agents, Phytogenic
PubMed: 38896728
DOI: 10.1590/1519-6984.279899 -
Immunity, Inflammation and Disease Jun 2024The sequelae of pelvic inflammatory disease (SPID) are major causes of secondary infertility. Modified Hongteng Baijiang decoction (MHTBD) has produced positive results...
OBJECTIVE
The sequelae of pelvic inflammatory disease (SPID) are major causes of secondary infertility. Modified Hongteng Baijiang decoction (MHTBD) has produced positive results in the treatment of patients with chronic pelvic inflammatory disease; however, its role in SPID remains elusive. Therefore, this study clarified the role of MHTBD in SPID pathogenesis.
METHODS
The main components in MHTBD were analyzed by using liquid chromatography‒mass spectrometry (LC/MS). An SPID rat model was established, and the rats were treated with different doses of MHTBD (0.504 g of raw drug/kg, 1.008 g of raw drug/kg, and 2.016 g of raw drug/kg). Endometrial pinopodes were observed via scanning electron microscopy, endometrial thickness and inflammatory cell infiltration were assessed via HE staining, and the expression of estrogen receptor (ER), progesterone receptor (PR), integrin β3 (ITGB3), and CD31 in the endometrium was detected by using immunohistochemistry. Western blot analysis was used to detect the protein expression of LIF, JAK2, p-JAK2, STAT3, and p-STAT3 in the endometrium. Moreover, the changes in the gut microbiota were analyzed via 16S rRNA sequencing.
RESULTS
MHTBD improved endometrial receptivity, attenuated endometrial pathologic damage, reduced inflammatory cell infiltration, decreased ER and PR expression in the endometrium, and promoted the expression of LIF, p-JAK2, and p-STAT3 in the endometrium (p < .05) in SPID rats. Additionally, MHTBD treatment affected the composition of the gut microbiota in SPID rats. Furthermore, MHTBD attenuated endometrial receptivity and pathological damage in SPID rats by promoting the LIF/JAK2/STAT3 pathway.
CONCLUSION
MHTBD attenuates SPID in rats by promoting the LIF/JAK2/STAT3 pathway and improving the composition of the gut microbiota. MHTBD may be a valuable drug for SPID therapy.
Topics: Animals; Female; STAT3 Transcription Factor; Janus Kinase 2; Rats; Gastrointestinal Microbiome; Drugs, Chinese Herbal; Signal Transduction; Pelvic Inflammatory Disease; Rats, Sprague-Dawley; Endometrium; Disease Models, Animal
PubMed: 38896093
DOI: 10.1002/iid3.1300 -
Veterinary Medicine and Science Jul 2024Bersama abyssinica Fresen is a plant that is used in folk medicine for the treatment of mastitis and other infectious diseases.
BACKGROUND
Bersama abyssinica Fresen is a plant that is used in folk medicine for the treatment of mastitis and other infectious diseases.
OBIECTIVE
The antibacterial activity of methanol crude extract of plant was evaluated against three common bacterial pathogens, including Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli and Pseudomonas aeruginosa).
METHODS
The antibacterial activities and minimum inhibitory concentration of B. abyssinica crude extracts were evaluated using agar-well diffusion and broth dilution methods according to the National Committee for Clinical Laboratory Standards (NCCLS).
RESULTS
A significant difference in the antibacterial activity of crude extracts was observed among different levels of concentration against tested isolates. A higher mean inhibition zone diameter was recorded in E. coli (29.2 ± 1.5 mm), followed by S. aureus (27.8 ± 1.1 mm) and P. aeruginosa (18.0 ± 0.7 mm) at a concentration of 100 mg/mL. The antibacterial activity of crude plant extract at 100 mg/mL was comparable with that of a standard antibiotic (27.6 ± 2.6) against S. aureus and E. coli isolates. The findings indicated that bacterial growth inhibition increased as the concentration of the crude extracts increased. E. coli and S. aureus isolates showed significantly higher susceptibilities to crude extracts than P. aeruginosa at all concentrations. The minimum inhibitory concentrations of extracts against S. aureus, E. coli and P. aeruginosa isolates were 0.78 mg/mL, 1.56 mg/mL and 1.56 mg/mL, respectively.
CONCLUSIONS
All tested pathogenic bacterial species were susceptible to plant leaf extract and broad-spectrum activity against Gram-positive and Gram-negative bacteria. The study recommends further fractionation of the B. abyssinica plant that contributes to its antibacterial activity and understands the mode of action of this plant against bacteria and other microbes.
Topics: Plant Extracts; Anti-Bacterial Agents; Microbial Sensitivity Tests; Gram-Negative Bacteria; Gram-Positive Bacteria; Escherichia coli; Staphylococcus aureus; Pseudomonas aeruginosa
PubMed: 38896065
DOI: 10.1002/vms3.1498 -
Drug Design, Development and Therapy 2024Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients,... (Randomized Controlled Trial)
Randomized Controlled Trial
The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.
BACKGROUND
Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.
METHODS
The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.
RESULTS
As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.
CONCLUSION
We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.
Topics: Humans; Psoriasis; Autophagy; MicroRNAs; Drugs, Chinese Herbal; Network Pharmacology; Male; Double-Blind Method; Adult; Female; Middle Aged; Cell Proliferation; Apoptosis
PubMed: 38895176
DOI: 10.2147/DDDT.S459622 -
International Journal of Nanomedicine 2024Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the subsp. (Wiesb.) Vollm. (VALE) has shown promising...
BACKGROUND AND PURPOSE
Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the subsp. (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract's chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed.
METHODS
subsp. histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS.
RESULTS
The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks.
CONCLUSION
This is the first histochemistry analysis of subsp. growing on . which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE.
Topics: Plant Extracts; Viscum album; Emulsions; Plant Leaves; Drug Delivery Systems; Particle Size; Nanoparticle Drug Delivery System; Nanoparticles
PubMed: 38895147
DOI: 10.2147/IJN.S464508