Coaxial Electrospun Polycaprolactone/Gelatin Nanofiber Membrane Loaded with Salidroside and Cryptotanshinone Synergistically Promotes Vascularization and Osteogenesis.

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.

Pseudomonas aeruginosa PR23 isolated from oil contaminated soil tolerate and degrades mixture of polyaromatic hydrocarbons and express novel proteins.

Pseudomonas aeruginosa PR23 isolated from the hydrocarbon contaminated soil can tolerate and degrade mixture of polyaromatic hydrocarbons (PAHs) at an initial concentration of 1300 ppm. The degradation and intermediates formed were assessed by gas chromatography-mass spectrometry (GC-MS) analysis. The isolated strain was able to degrade 59.2% of the mixture of PAHs in 3 days and 71.6% by day 15. Effect of PAHs on protein expression in Pseudomonas aeruginosa PR23 was studied using nano LC-MS/MS. Thirty-six proteins showed a more than 2-fold increase in expression in the presence of mixture of PAHs. Out of these proteins, 7 proteins have been reported for their role in degradation of naphthalene, phenanthrene, and pyrene. The data revealed the presence of 16 proteins that were uniquely expressed in the presence of mixture of PAHs. A twin-arginine translocation signal peptide (Tat system), known for the transportation of folded proteins across the cell membrane, showed more than 8-fold increased expression in the presence of mixture of PAHs. These results indicate that the isolated strain adopts the conditions in the presence of mixture of PAHs by modulating its metabolic and physiological processes. These findings suggest that Pseudomonas aeruginosa PR23 may be a suitable candidate for use in the development of strategies for bioremediation of mixtures of PAHs.

Testing the Simplified Molecular Dynamics Approach to Improve the Reproduction of ECD Spectra and Monitor Aggregation.

A simplified molecular-dynamics-based electronic circular dichroism (ECD) approach was tested on three condensed derivatives with limited conformational flexibility and an isochroman-2H-chromene hybrid, the ECD spectra of which could not be precisely reproduced by the conventional ECD calculation protocol. Application of explicit solvent molecules at the molecular mechanics (MD) level in the dynamics simulations and subsequent TDDFT-ECD calculation for the unoptimized MD structures was able to improve the agreements between experimental and computed spectra. Since enhancements were achieved even for molecules with limited conformational flexibility, deformations caused by the solvent molecules and multitudes of conformers produced with unoptimized geometries seem to be key factors for better agreement. The MD approach could confirm that aggregation of the phenanthrene natural product luzulin A had a significant contribution to a specific wavelength range of the experimental ECD. The MD approach has proved that dimer formation occurred in solution and this was responsible for the anomalous ECD spectrum. The scope and limitations of the method have also been discussed.

Sphingobium sp. SJ10-10 encodes a not-yet-reported chromate reductase and the classical Rieske dioxygenases to simultaneously degrade PAH and reduce chromate.

Both polycyclic aromatic hydrocarbons (PAHs) and heavy metals persist in the environment and are toxic to organisms. Their co-occurrence makes any of them difficult to remove during bioremediation and poses challenges to environmental management and public health. Microorganisms capable of effectively degrading PAHs and detoxifying heavy metals concurrently are required to improve the bioremediation process. In this study, we isolated a new strain, Sphingobium sp. SJ10-10, from an abandoned coking plant and demonstrated its capability to simultaneously degrade 92.6 % of 75 mg/L phenanthrene and reduce 90 % of 3.5 mg/L hexavalent chromium [Cr(VI)] within 1.5 days. Strain SJ10-10 encodes Rieske non-heme iron ring-hydroxylating oxygenases (RHOs) to initiate PAH degradation. Additionally, a not-yet-reported protein referred to as Sphingobium chromate reductase (SchR), with low sequence identity to known chromate reductases, was identified to reduce Cr(VI). SchR is distributed across different genera and can be classified into two classes: one from Sphingobium members and the other from non-Sphingobium species. The widespread presence of SchR in those RHO-containing Sphingobium members suggests that they are excellent candidates for bioremediation. In summary, our study demonstrates the simultaneous removal of PAHs and Cr(VI) by strain SJ10-10 and provides valuable insights into microbial strategies for managing complex pollutant mixtures.

Unambiguous Characterization of Commercial Natural (Dihydro)phenanthrene Compounds Is Vital in the Discovery of AMPK Activators.

These days, easy access to commercially available (poly)phenolic compounds has expanded the scope of potential research beyond the field of chemistry, particularly in the area of their bioactivity. However, the quality of these compounds is often overlooked or not even considered. This issue is illustrated in this study through the example of (dihydro)phenanthrenes, a group of natural products present in yams, as AMP-activated protein kinase (AMPK) activators. A study conducted in our group on a series of compounds, fully characterized using a combination of chemical synthesis, NMR and MS techniques, provided evidence that the conclusions of a previous study were erroneous, likely due to the use of a misidentified commercial compound by its supplier. Furthermore, we demonstrated that additional representatives of the (dihydro)phenanthrene phytochemical classes were able to directly activate AMPK, avoiding the risk of misinterpretation of results based on analysis of a single compound alone.

Homotypic cell membrane-camouflaged biomimetic PLGA nanoparticle loading triptolide for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1.

Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.

Bioremediation of petroleum refinery wastewater using Bacillus subtilis IH-1 and assessment of its toxicity.

Environmental contamination from petroleum refinery operations has increased due to the rapid population growth and modernization of society, necessitating urgent repair. Microbial remediation of petroleum wastewater by prominent bacterial cultures holds promise in circumventing the issue of petroleum-related pollution. Herein, the bacterial culture was isolated from petroleum-contaminated sludge samples for the valorization of polyaromatic hydrocarbons and biodegradation of petroleum wastewater samples. The bacterial strain was screened and identified as Bacillus subtilis IH-1. After six days of incubation, the bacteria had degraded 25.9% of phenanthrene and 20.3% of naphthalene. The treatment of wastewater samples was assessed using physico-chemical and Fourier-transform infrared spectroscopy analysis, which revealed that the level of pollutants was elevated and above the allowed limits. Following bacterial degradation, the reduction in pollution parameters viz. EC (82.7%), BOD (87.0%), COD (80.0%), total phenols (96.3%), oil and grease (79.7%), TKN (68.8%), TOC (96.3%) and TPH (52.4%) were observed. The reduction in pH and heavy metals were also observed after bacterial treatment. V. mungo was used in the phytotoxicity test, which revealed at 50% wastewater concentration the reduction in biomass (30.3%), root length (87.7%), shoot length (93.9%), and seed germination (30.0%) was observed in comparison to control. When A. cepa root tips immersed in varying concentrations of wastewater samples, the mitotic index significantly decreased, suggesting the induction of cytotoxicity. However, following the bacterial treatment, there was a noticeable decrease in phytotoxicity and cytotoxicity. The bacterial culture produces lignin peroxidase enzyme and has the potential to degrade the toxic pollutants of petroleum wastewater. Therefore the bacterium may be immobilised or directly used at reactor scale or pilot scale study to benefit the industry and environmental safety.

Oral exposure to phenanthrene during gestation disorders endocrine and spermatogenesis in F1 adult male mice.

Phenanthrene (Phe), a typical low-molecular-weight polycyclic aromatic hydrocarbon (PAH) of three benzene rings, is one of the most abundant PAHs detected in daily diets. Pregnant women and infants are at great risk of Phe exposure. In the present study, Phe was administered to pregnant mice at a dose of 0, 60, or 600 µg/kg body weight six times, and the F1 male mice showed significant reproductive disorders: the testicular weight and testis somatic index were significantly reduced; the levels of serum testosterone, GnRH and SHBG were increased, while the FSH levels were reduced; histological analysis showed that the amount of Sertoli cells and primary spermatocytes in seminiferous tubules was increased, while the amount of secondary spermatocytes and spermatids were decreased in Phe groups. The protein levels of PCNA and androgen receptor were reduced. Differently expressed genes in the testis screened by RNA sequence were enriched in antioxidant capacity, reproduction et al.. Further biochemical tests confirmed that the antioxidant capacity in the F1 testis was significantly inhibited by treatment with Phe during pregnancy. Those results suggested that gestational Phe exposure disordered hypothalamic-pituitary-gonadal (HPG) hormones on the one hand, and on the other hand reduced testicular antioxidant capacity and further arrested cell cycle in F1 adult male mice, which co-caused the inhibition of spermatogenesis.

Dihydrotanshinone I targets ESR1 to induce DNA double-strand breaks and proliferation inhibition in hepatocellular carcinoma.

BACKGROUND: Due to its high incidence and elevated mortality, hepatocellular carcinoma (HCC) has emerged as a formidable global healthcare challenge. The intricate interplay between gender-specific disparities in both incidence and clinical outcomes has prompted a progressive recognition of the substantial influence exerted by estrogen and its corresponding receptors (ERs) upon HCC pathogenesis. Estrogen replacement therapy (ERT) emerged for the treatment of HCC by administering exogenous estrogen. However, the powerful side effects of estrogen, including the promotion of breast cancer and infertility, hinder the further application of ERT. Identifying effective therapeutic targets for estrogen and screening bioactive ingredients without E2-like side effects is of great significance for optimizing HCC ERT. METHODS: In this study, we employed an integrative approach, harnessing data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, clinical paraffin sections, adenoviral constructs as well as in vivo studies, to unveil the association between estrogen, estrogen receptor α (ESR1) and HCC. Leveraging methodologies encompassing molecular dynamics simulation and cellular thermal shift assay (CETSA) were used to confirm whether ESR1 is a molecular target of DHT. Multiple in vitro and in vivo experiments were used to identify whether i) ESR1 is a crucial gene that promotes DNA double-strand breaks (DSBs) and proliferation inhibition in HCC, ii) Dihydrotanshinone I (DHT), a quinonoid monomeric constituent derived from Salvia miltiorrhiza (Dan shen) exerts anti-HCC effects by regulating ESR1 and subsequent DSBs, iii) DHT has the potential to replace E2. RESULTS: DHT could target ESR1 and upregulate its expression in a concentration-dependent manner. This, in turn, leads to the downregulation of breast cancer type 1 susceptibility protein (BRCA1), a pivotal protein involved in the homologous recombination repair (HRR) process. The consequence of this downregulation is manifested through the induction of DSBs in HCC, subsequently precipitating a cascade of downstream events, including apoptosis and cell cycle arrest. Of particular significance is the comparative assessment of DHT and isodose estradiol treatments, which underscores DHT's excellent HCC-suppressive efficacy without concomitant perturbation of endogenous sex hormone homeostasis. CONCLUSION: Our findings not only confirm ESR1 as a therapeutic target in HCC management but also underscores DHT's role in upregulating ESR1 expression, thereby impeding the proliferation and invasive tendencies of HCC. In addition, we preliminarily identified DHT has the potential to emerge as an agent in optimizing HCC ERT through the substitution of E2.

Quantitative proteomic analysis of circulating exosomes reveals the mechanism by which Triptolide protects against collagen-induced arthritis.

INTRODUCTION: Triptolide (TP), a natural product derived from the herbal medicine Tripterygium wilfordii, exhibits potent immunosuppressive activity. However, the mechanisms underlying its effects in rheumatoid arthritis remain incompletely understood. METHODS: Collagen-induced arthritis (CIA) model was induced in Sprague-Dawley rats by immunization with bovine type II collagen, and TP was administrated as treatment. The therapeutic effect of TP was evaluated based on paw swelling, histopathology, and serum levels of inflammatory factors. Exosomes isolated from rat serum were characterized by transmission electron microscopy, dynamic light scattering, and western blot analysis. Proteomic profiling of exosomes was analyzed by direct DIA quantitative proteomics analysis. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes databases were employed for enrichment analysis related to molecular function, biological processes, and signaling pathways. Western blot analysis was used to analyze differentially expressed proteins. RESULTS: TP treatment ameliorated arthritic phenotypes in CIA rats as evidenced by reduced arthritis score, paw swelling, pathological injury severity scores, and serum levels of inflammatory cytokines. The proteomic analysis revealed that TP treatment significantly inhibited complement and coagulation cascades, interleukin-17 signaling pathway, and cholesterol metabolism, which were reactivated in CIA rats. Importantly, lipocalin 2 (LCN2) and myeloperoxidase (MPO) levels were markedly upregulated in the CIA group but suppressed upon TP administration. Furthermore, in synovial tissues, LCN2 and MPO expression levels were also elevated in the CIA group but decreased following TP treatment. CONCLUSION: Our findings demonstrate that TP alleviates CIA, possibly through modulation of exosomal LCN2 and MPO proteins.

Physiology and comparative genomics of the haloalkalitolerant and hydrocarbonoclastic marine strain Rhodococcus ruber MSA14.

Marine hydrocarbonoclastic bacteria can use polycyclic aromatic hydrocarbons as carbon and energy sources, that makes these bacteria highly attractive for bioremediation in oil-polluted waters. However, genomic and metabolic differences between species are still the subject of study to understand the evolution and strategies to degrade PAHs. This study presents Rhodococcus ruber MSA14, an isolated bacterium from marine sediments in Baja California, Mexico, which exhibits adaptability to saline environments, a high level of intrinsic pyrene tolerance (> 5 g L- 1), and efficient degradation of pyrene (0.2 g L- 1) by 30% in 27 days. Additionally, this strain demonstrates versatility by using naphthalene and phenanthrene as individual carbon sources. The genome sequencing of R. ruber MSA14 revealed a genome spanning 5.45 Mbp, a plasmid of 72 kbp, and three putative megaplasmids, lengths between 110 and 470 Kbp. The bioinformatics analysis of the R. ruber MSA14 genome revealed 56 genes that encode enzymes involved in the peripheral and central pathways of aromatic hydrocarbon catabolism, alkane, alkene, and polymer degradation. Within its genome, R. ruber MSA14 possesses genes responsible for salt tolerance and siderophore production. In addition, the genomic analysis of R. ruber MSA14 against 13 reference genomes revealed that all compared strains have at least one gene involved in the alkanes and catechol degradation pathway. Overall, physiological assays and genomic analysis suggest that R. ruber MSA14 is a new haloalkalitolerant and hydrocarbonoclastic strain toward a wide range of hydrocarbons, making it a promising candidate for in-depth characterization studies and bioremediation processes as part of a synthetic microbial consortium, as well as having a better understanding of the catabolic potential and functional diversity among the Rhodococci group.

Determination of soil phenanthrene degradation through a fungal-bacterial consortium.

Fungal-bacterial consortia enhance organic pollutant removal, but the underlying mechanisms are unclear. We used stable isotope probing (SIP) to explore the mechanism of bioaugmentation involved in polycyclic aromatic hydrocarbon (PAH) biodegradation in petroleum-contaminated soil by introducing the indigenous fungal strain Aspergillus sp. LJD-29 and the bacterial strain Pseudomonas XH-1. While each strain alone increased phenanthrene (PHE) degradation, the simultaneous addition of both strains showed no significant enhancement compared to treatment with XH-1 alone. Nonetheless, the assimilation effect of microorganisms on PHE was significantly enhanced. SIP revealed a role of XH-1 in PHE degradation, while the absence of LJD-29 in 13C-DNA indicated a supporting role. The correlations between fungal abundance, degradation efficiency, and soil extracellular enzyme activity indicated that LJD-29, while not directly involved in PHE assimilation, played a crucial role in the breakdown of PHE through extracellular enzymes, facilitating the assimilation of metabolites by bacteria. This observation was substantiated by the results of metabolite analysis. Furthermore, the combination of fungus and bacterium significantly influenced the diversity of PHE degraders. Taken together, this study highlighted the synergistic effects of fungi and bacteria in PAH degradation, revealed a new fungal-bacterial bioaugmentation mechanism and diversity of PAH-degrading microorganisms, and provided insights for in situ bioremediation of PAH-contaminated soil.IMPORTANCEThis study was performed to explore the mechanism of bioaugmentation by a fungal-bacterial consortium for phenanthrene (PHE) degradation in petroleum-contaminated soil. Using the indigenous fungal strain Aspergillus sp. LJD-29 and bacterial strain Pseudomonas XH-1, we performed stable isotope probing (SIP) to trace active PHE-degrading microorganisms. While inoculation of either organism alone significantly enhanced PHE degradation, the simultaneous addition of both strains revealed complex interactions. The efficiency plateaued, highlighting the nuanced microbial interactions. SIP identified XH-1 as the primary contributor to in situ PHE degradation, in contrast to the limited role of LJD-29. Correlations between fungal abundance, degradation efficiency, and extracellular enzyme activity underscored the pivotal role of LJD-29 in enzymatically facilitating PHE breakdown and enriching bacterial assimilation. Metabolite analysis validated this synergy, unveiling distinct biodegradation mechanisms. Furthermore, this fungal-bacterial alliance significantly impacted PHE-degrading microorganism diversity. These findings advance our understanding of fungal-bacterial bioaugmentation and microorganism diversity in polycyclic aromatic hydrocarbon (PAH) degradation as well as providing insights for theoretical guidance in the in situ bioremediation of PAH-contaminated soil.

Design and anticancer behaviour of cationic/neutral half-sandwich iridium(III) imidazole-phenanthroline/phenanthrene complexes.

Considerable attention has been devoted to the exploration of organometallic iridium(III) (IrIII) complexes for their potential as metallic anticancer drugs. In this study, twelve half-sandwich IrIII imidazole-phenanthroline/phenanthrene complexes were prepared and characterized. Complexes exhibited promising in-vitro anti-proliferative activity, and some are obviously superior to cisplatin towards A549 cells. These complexes possessed suitable fluorescence, and a non-energy-dependent uptake pathway was identified, subsequently leading to their accumulation in the lysosome and the lysosomal damage. Additionally, complexes could inhibit the cell cycle (G1-phase) and catalyze intracellular NADH oxidation, thus substantiating the elevation of intracellular reactive oxygen species (ROS) level, which confirming the oxidative mechanism. Western blotting further confirmed that complexes could induce A549 cell apoptosis through the lysosomal-mitochondrial anticancer pathway, which was inconsistent with cisplatin. In summary, these complexes offer fresh concepts for the development of organometallic non­platinum anticancer drugs.

Triptolide exposure triggers testicular vacuolization injury by disrupting the Sertoli cell junction and cytoskeletal organization via the AKT/mTOR signaling pathway.

BACKGROUND: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure. METHODS: Male mice were subjected to TP at doses of 15, 30, and 60 µg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood-testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining. RESULTS: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells. CONCLUSION: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.

Minnelide exhibits antileukemic activity by targeting the Ars2/miR-190a-3p axis.

BACKGROUND: The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear. PURPOSE: To explore the molecular mechanisms by which minnelide exhibits antileukemic activity. METHODS: AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis. RESULTS: Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis. CONCLUSIONS: Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials.

Phenanthrene metabolism in Panicum miliaceum: anatomical adaptations, degradation pathway, and computational analysis of a dioxygenase enzyme.

Polycyclic aromatic compounds (PAHs) are persistent organic pollutants of environmental concern due to their potential impacts on food chain, with plants being particularly vulnerable. While plants can uptake, transport, and transform PAHs, the precise mechanisms underlying their localization and degradation are not fully understood. Here, a cultivation experiment conducted with Panicum miliaceum exposed different concentrations of phenanthrene (PHE). Intermediate PHE degradation compounds were identified via GC-MS analysis, leading to the proposal of a phytodegradation pathway featuring three significant benzene ring cleavage steps. Our results showed that P. miliaceum exhibited the ability to effectively degrade high levels of PHE, resulting in the production of various intermediate products through several chemical changes. Examination of the localization and anatomical characteristics revealed structural alterations linked to PHE stress, with an observed enhancement in PHE accumulation density in both roots and shoots as treatment levels increased. Following a 2-week aging period, a decrease in the amount of PHE accumulation was observed, along with a change in its localization. Bioinformatics analysis of the P. miliaceum 2-oxoglutarate-dependent dioxygenase (2-ODD) DAO-like protein revealed a 299 amino acid structure with two highly conserved domains, namely 2OG-FeII_Oxy and DIOX_N. Molecular docking analysis aligned with experimental results, strongly affirming the potential link and direct action of 2-ODD DAO-like protein with PHE. Our study highlights P. miliaceum capacity for PAHs degradation and elucidates the mechanisms behind enhanced degradation efficiency. By integrating experimental evidence with bioinformatics analysis, we offer valuable insights into the potential applications of plant-based remediation strategies for PAHs-contaminated environments.

Mechanisms and extended kinetic model of thermal desorption in organic-contaminated soil.

Thermal desorption is a preferred technology for site remediation due to its various advantages. To ensure the effective removal of different pollutants in practical applications, it is necessary to understand the kinetic behaviors and removal mechanisms of pollutants in thermal desorption process. This paper explored the thermal desorption processes of five organic pollutants (nitrobenzene, naphthalene, n-dodecane, 1-nitronaphthalene, and phenanthrene) at 50-350 °C in two different subsoils with 6-18% moisture content. The results suggested that the thermal desorption process was well-fitted by the exponential decay model (R2 = 0.972-0.999) and could be divided into two distinct stages. The first stage was relatively fast and highly influenced by soil moisture, while the second stage showed a slower desorption rate due to the constraints imposed by the soil texture and structure. The influence of soil moisture on thermal desorption depended on the octanol/water partition coefficient (KOW) of pollutants. Pollutants with log KOW values lower than the critical value exhibited enhanced thermal desorption, while those with log KOW values higher than the critical value were inhibited. The critical value of log KOW might be between 3.33 and 4.46. Changes in soil texture and structure caused by heating promoted thermal desorption, especially for naphthalene, 1-nitronaphthalene and phenanthrene. The differences in texture and structure between the two soils diminished as the temperature increased. Finally, an extended kinetic model under changing temperature conditions was derived, and the simulation results for the two subsoils were very close to the actual thermogravimetric results, with the differences ranging from -1.28% to 0.94% and from -0.67% to 1.35%, respectively. These findings propose new insights into the influencing mechanisms of soil moisture and structure on the thermal desorption of organic pollutants. The extended kinetic model can provide reference for future kinetic research and guide practical site remediation.

Suppression of retinal neovascularization by intravitreal injection of cryptotanshinone.

Neovascular eye diseases, including proliferative diabetic retinopathy and retinopathy of prematurity, is a major cause of blindness. Laser ablation and intravitreal anti-VEGF injection have shown their limitations in treatment of retinal neovascularization. Identification of a new therapeutic strategies is in urgent need. Our study aims to assess the effects of Cryptotanshinone (CPT), a natural compound derived from Salvia miltiorrhiza Bunge, in retina neovascularization and explore its potential mechanism. Our study demonstrated that CPT did not cause retina tissue toxicity at the tested concentrations. Intravitreal injections of CPT reduced pathological angiogenesis and promoted physical angiogenesis in oxygen-induced retinopathy (OIR) model. CPT improve visual function in OIR mice and reduced cell apoptosis. Moreover, we also revealed that CPT diminishes the expression of inflammatory cytokines in the OIR retina. In vitro, the administration of CPT effectively inhibited endothelial cells proliferation, migration, sprouting, and tube formation induced by the stimulation of human retinal vascular endothelial cells (HRVECs) with VEGF165. Mechanistically, CPT blocking the phosphorylation of VEGFR2 and downstream targeting pathway. After all, the findings demonstrated that CPT exhibits potent anti-angiogenic and anti-inflammatory effects in OIR mice, and it has therapeutic potential for the treatment of neovascular retinal diseases.

Importance of soil ecoenzyme stoichiometry for efficient polycyclic aromatic hydrocarbon biodegradation.

Efficient remediation of soil contaminated by polycyclic aromatic hydrocarbons (PAHs) is challenging. To determine whether soil ecoenzyme stoichiometry influences PAH degradation under biostimulation and bioaugmentation, this study initially characterized soil ecoenzyme stoichiometry via a PAH degradation experiment and subsequently designed a validation experiment to answer this question. The results showed that inoculation of PAH degradation consortia ZY-PHE plus vanillate efficiently degraded phenanthrene with a K value of 0.471 (depending on first-order kinetics), followed by treatment with ZY-PHE and control. Ecoenzyme stoichiometry data revealed that the EEAC:N, vector length and angle increased before day five and decreased during the degradation process. In contrast, EEAN:P decreased and then increased. These results indicated that the rapid PAH degradation period induced more C limitation and organic P mineralization. Correlation analysis indicated that the degradation rate K was negatively correlated with vector length, EEAC:P, and EEAN:P, suggesting that C limitation and relatively less efficient P mineralization could inhibit biodegradation. Therefore, incorporating liable carbon and acid phosphatase or soluble P promoted PAH degradation in soils with ZY-PHE. This study provides novel insights into the relationship between soil ecoenzyme stoichiometry and PAH degradation. It is suggested that soil ecoenzyme stoichiometry be evaluated before designing bioremeiation stragtegies for PAH contanminated soils.