Search Results (13)

Triptolide (TPL), the core active component of the traditional Chinese medicinal herb Tripterygium wilfordii Hook F (TwHF), possesses a wide spectrum of pharmacological activities, including anti-inflammatory, neuroprotective, immunosuppressive, and anti-tumor activities. However, its clinical application is severely limited by significant reproductive toxicity, the mechanism of which remains poorly understood. Using an integrated analysis of MeRIP-seq and mRNA-seq data, coupled with experimental validation in HTR-8/SVneo cells, we systematically elucidated the molecular mechanism by which TPL induces trophoblast cell injury. Our findings revealed that TPL significantly altered intracellular N⁶-methyladenosine (m⁶A) modification and gene expression profiles, with 1774 genes displaying hypomethylation concurrent with mRNA upregulation. According to the functional enrichment analysis, these genes showed significant enrichment in several key pathways associated with reproduction, including autophagy, DNA damage response, mitochondrial outer membrane, and positive regulation of apoptotic process. Molecular docking further demonstrated direct and stable binding of TPL to key m⁶A regulators, leading to specific demethylation of targets including E2F1 and PPP1CC. This study uncovers a novel post-transcriptional mechanism where TPL disrupts m⁶A modification, thereby perturbing essential trophoblast functions and driving reproductive toxicity. Full article

Organic anion transporting polypeptide 1B1 (OATP1B1) is specifically expressed at the basolateral membrane of human liver cells and transports a wide range of endogenous compounds, toxins, and drugs, making it a crucial factor in determining the pharmacokinetics of many clinically important medications. Triptergium wilfordii Hook. f. (TWHF) is a traditional Chinese medicine known for its long history of therapeutic effects. A previous study conducted in our laboratory found that major components of TWHF, including wilforine (WFR), wilforgine (WFG), celastrol (CL), and triptolide (TPL), directly suppressed the function of OATP1B1. In the current study, we investigated the long-term (24 h) effects of these TWHF components on the transporter. It was found that TPL was the most potent compound exhibiting inhibitory effects. Mechanistically, TPL accelerated the degradation of OATP1B1, which is likely mediated by serum and glucocorticoid-induced kinase 1 (SGK1). TPL downregulated the mRNA expression of SGK1 and reduced the nuclear accumulation of nuclear factor kappa B (NFκB). Further analysis of the upstream sequence of SGK1 identified three potential binding sites for NFκB. Both luciferase activity assays and chromatin immunoprecipitation (ChIP) analyses confirmed the binding of NFκB to two specific sites located at −1015 bp~−1006 bp and −319 bp~−310 bp. Full article

Macrobrachium rosenbergii, commonly known as giant freshwater prawns (GFPs), is an economically and nutritionally important decapod crustacean species in China. Understanding the genetic diversity of selective breeding populations is crucial in breeding plans for selecting genetically diverse broodstocks and maintaining genetic diversity. The genetic structure of six breeding populations (Hefu (HF), Nantaihu No.2 (NTH), Jiaxin (JX), Shufeng (SF), Taiwan (TW), and Guangxi (GX)) of GFP in China was examined using 16 newly developed microsatellite loci and the mitochondrial control region (D-loop). The microsatellite data revealed that all 16 loci have high diversity, with all values of polymorphism information content (PIC) more than 0.5. The average expected heterozygosity (He, 0.89) and the number of alleles (Na, 18.25) of SF were the highest, followed by He (0.89) and Na (14.75) of the JX, and GX has the lowest He (0.83) and Na (11.31). The average PIC value for the six stocks ranged from 0.80 to 0.87. Pairwise comparisons revealed that Fst ranged from 0.03541 to 0.09637 and was significant (p < 0.05) between most populations, indicating from low to moderate genetic differentiation among the six populations. The D-loop analysis identified 114 variable sites and 29 haplotypes, with an average haplotype diversity (Hd) and nucleotide diversity (π) of 0.640 and 0.01247, respectively. Genetic differentiation among the six populations based on the D-loop was from moderate to high, with Fst values of 0.05603–0.80788, and all p < 0.05. This study demonstrates that selective breeding stocks of M. rosenbergii in China show moderate to high genetic diversity and have the potential for further selective breeding, providing a theoretical basis for conserving and utilizing M. rosenbergii genetic resources. Full article

Triptolide, a bioactive diterpene tri-epoxide extracted from Tripterygium wilfordii Hook F (TWHF), exhibits notable pharmacological activities, including anti-inflammatory, immunosuppressive, antifertility, and anticancer effects. Despite its promising therapeutic potential, clinical applications of triptolide are significantly limited by its poor water solubility and substantial toxicity, particularly hepatotoxicity, nephrotoxicity, and cardiotoxicity. These toxic effects are difficult to separate from many of its desired therapeutic effects, the Yin and Yang of triptolide applications. Triptolide’s therapeutic and toxic effects are linked to its inhibitory interactions with XPB, a DNA helicase essential for transcription by RNA polymerase II (RNAPII) and nucleotide excision repair (NER). By irreversibly binding to XPB, triptolide inhibits its ATPase activity, leading to global repression of transcription and impaired NER, which underlies its cytotoxic and antitumor properties. Recent developments, including triptolide prodrugs such as Minnelide and derivatives like glutriptolides, aim to enhance its pharmacokinetic properties and reduce toxicity. This review critically examines triptolide’s chemical structure, therapeutic applications, toxicological profile, and molecular interactions with XPB and other protein targets to inform future strategies that maximize therapeutic efficacy while minimizing adverse effects. Full article

Triptolide (TP), a bioactive compound extracted the from traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has been shown to be effective in treating several autoimmune diseases, and has suppressive effects in several key immune cells such as dendritic cells, T cells, and macrophages. However, it is unknown whether TP has an impact on natural killer (NK) cells. Here, we report that TP has suppressive effects on human NK cell activity and effector functions. The suppressive effects were observed in human peripheral blood mononuclear cell cultures and purified NK cells from healthy donors, as well as in purified NK cells from patients with rheumatoid arthritis. TP treatment induced downregulation of NK-activating receptor (CD54, CD69) expression and IFN-gamma secretion, in a dose-dependent manner. When exposed to K562 target cells, TP treatment induced inhibition of surface expression of CD107a and IFN-gamma synthesis in NK cells. Furthermore, TP treatment induced activation of inhibitory signaling (SHIP, JNK) and inhibition of MAPK signaling (p38). Thus, our findings demonstrate a previously unknown role for TP in NK cell functional suppression and reveal several key intracellular signaling that can be regulated by TP. Our findings also offer new insight into mechanisms of TP therapeutic treatment in autoimmune disease. Full article

In treatment wetlands (TWs), solids accumulation can result in hydraulic malfunction, reducing the operation life, and it could enhance biological activity by favoring biofilm development. It is still unknown whether the solids accumulation can affect greenhouse gas (GHG) emissions. This study aims to evaluate the solid concentration along a horizontal flow (HF) TW, and its role in GHG emissions, hydraulics, treatment performance, and vegetation development (Phragmites australis (Cav.) Trin. ex Steud.). The study was carried out in an eight-year-old full-scale HF-TW located in the Mediterranean region (Sicily, Italy). To collect data inside the HF unit, nine observation points (besides the inlet and the outlet) along three 8.5-m-long transects (T1, T2, and T3) were identified. The first transect (close to the inlet zone) showed a hydraulic conductivity (Ks) reduction approximately one order of magnitude higher than the other two. Results highlighted that GHG emissions increased during the summer, when the temperature and solar radiation were higher than in the rest of the year, matching the macrophyte growth rate. Theoretical methane (CH₄) emissions followed the trend of volatile solids (VS), which was around 3.5 and 4 times in T1 to T2 and T3. Pore clogging affected carbon dioxide (CO₂) emissions, which decreased from T1 to T3, with maximum monthly values in T1 (21.4 g CO₂·m⁻²·d⁻¹) being approximately double with respect to T2 (12.6 g CO₂·m⁻²·d⁻¹) and T3 (10.7 g CO₂·m⁻²·d⁻¹) observed in July. The same trend for chemical oxygen demand (COD) removal efficiency, decreasing from T1 to T3, was observed. Notwithstanding this behavior, the final effluent quality was very satisfactory, with an average value of COD removal efficiency above 90%. Full article

Numerical simulation is very useful for understanding the hydraulic fracture (HF) re-orientation mechanism from artificial weaknesses. In this paper, the UDEC T-W (Trigon–Weibull distribution) modeling method is adopted to simulate the hydraulic fracturing process in heterogeneous rocks. First, the reliability of this method is validated against previous laboratory experiments and numerical simulations. Then the effects of fluid rate, fluid viscosity, perforation angle and natural fracture (NF) on the HF re-orientation process in heterogeneous rocks are studied independently. The results show that the HF re-orientation process depends on the combined effect of these factors. The HF re-orientation distance increases significantly, the final HF re-orientation trajectory becomes more complex and the guiding effect of perforation on the HF propagation path is more evident with the increase of fluid rate, fluid viscosity, and perforation angle if the hydraulic fracturing is performed in relatively heterogeneous rocks, while the differential stress is the main influencing factor and is more likely to dictate the HF propagation path if the rocks become relatively homogeneous. However, increasing the fluid viscosity and fluid rate can attenuate the impact of differential stress and can promote HF propagation along the perforation direction. Besides, NFs are also the important factor affecting HF re-orientation and induce secondary HF re-orientation in some cases in heterogeneous rocks. Full article

Improving the transdermal delivery efficiency of medicine is a crucial measure to improve the treatment efficiency of psoriasis. This paper developed a low-cost, highly active, and large-action-area low-temperature plasma (LTP) jet array. The two components of plasma—the high concentration of reactive oxygen and nitrogen species and the strong electric field—easily changed the structural integrity of the stratum corneum, which enhanced the transdermal delivery of the medicine. Tripterygium wilfordii Hook F (TwHF) is a medicine used to treat autoimmune and inflammatory conditions. The enhanced transdermal delivery of TwHF significantly alleviated the severed psoriasiform dermatitis induced by the imiquimod. Unlike the TwHF treatment alone, the LTP + TwHF treatment was more efficient at suppressing epidermal thickening and inhibiting systemic inflammation without noticeable side effects. LTP + TwHF treatment provides a potential new solution for psoriasis treatment. Full article

This paper focuses on solving a problem of green location-routing with cold chain logistics (GLRPCCL). Considering the sustainable effects of the economy, environment, society, and cargos, we try to establish a multi-objective model to minimize the total cost, the full set of greenhouse gas (GHG) emissions, the average waiting time, and the total quality degradation. Several practical demands were considered: heterogeneous fleet (HF), time windows (TW), simultaneous pickup and delivery (SPD), and a feature of mixed transportation. To search the optimal Pareto front of such a nondeterministic polynomial hard problem, we proposed an optimization framework that combines three multi-objective evolutionary algorithms (MOEAs) and also developed two search mechanisms for a large composite neighborhood described by 16 operators. Extensive analysis was conducted to empirically assess the impacts of several problem parameters (i.e., distribution strategy, fleet composition, and depots’ time windows and costs) on Pareto solutions in terms of the performance indicators. Based on the experimental results, this provides several managerial insights for the sustainale logistics companies. Full article

Triptolide (TP), a major extract of the herb Tripterygium wilfordii Hook F (TWHF), has been shown to exert potent pharmacological effects, especially an immunosuppressive effect in the treatment of rheumatoid arthritis (RA). However, its multiorgan toxicity prevents it from being widely used in clinical practice. Recently, several attempts are being performed to reduce TP toxicity. In this review, recent progress in the use of TP for RA, including its pharmacological effects and toxicity, is summarized. Meanwhile, strategies relying on chemical structural modifications, innovative delivery systems, and drug combinations to alleviate the disadvantages of TP are also reviewed. Furthermore, we also discuss the challenges and perspectives in their clinical translation. Full article

The field of treatment wetlands (TWs) is rapidly expanding and, arguably, is tasked with studying and understanding one of the most complex water treatment systems available. Microbial communities are generally considered to be responsible for the majority of wastewater constituent degradation in TWs. However, they are also known to be spatially heterogeneous, temporally dynamic, as well as structurally and functionally diverse. Presented here is a meta-analysis of all peer reviewed TW journal articles which utilized a microbial community assessment methodology over the period of 1988 to July 2016. A total of 1101 papers were reviewed, 512 from 1988 to 2012, 215 of which included a microbial community assessment aspect and were subsequently classified as representing past research, and 589 from 2013 to July 2016, 196 of which were classified as representing current TW microbial community research. In general, TW microbial community research has increased over time, with a marked surge in the past four years. Microbial community structure is currently the most commonly used methodological type followed by activity, enumeration and function, respectively. Areas of research focus included nitrogen transformations (156), organic degradation (33), and emerging contaminants (32), with general characterization studies also accounting for a significant proportion (243). Microbial communities from a range of TW systems have been investigated over the last four years with meso-scale (10–1000 L) being the most commonly studied system size followed by large-scale (>100,000 L), micro-scale (<10 L), and pilot-scale (1000–100,000 L). Free water surface flow (SF), horizontal subsurface flow (HF), and vertical flow (VF) systems are being studied in approximately equal proportions with the majority of studies focused on gaining fixed media/biofilm samples for analysis (rather than from the rhizosphere or interstitial water). Looking at efforts from a regional perspective shows Asia to be publishing the majority of research with a main focus on VF systems and structural community assessment. European and North American studies are generally more evenly distributed among structure, function, activity, and enumeration with the majority of studies completed on HF systems. South America, Africa, and Oceania published fewer studies but focused on structural community assessment with a selection of HF, SF and VF investigations. Great strides are being made in the field of microbial community assessment in TWs with functional assessment methods being developed, better utilized, and being related directly to water treatment. The use of high-powered metagenomics sequencing such as Illumina HiSeq instrumentation is on the rise, as is the development and utilization of functional assays such as DNA microarrays and community level physiological profiling allowing for more complete community assessment. Used in concert with activity, enumeration and newly implemented stable isotope methodologies, the field of TWs is certainly moving away from the black-box understanding of the past. Full article

The commercial preparation named “Tripterygium glycosides” prepared by column chromatography has been used for the treatment of inflammatory and autoimmune diseases with significant efficacy but concurrent toxicity. The aim of this study was to reduce the toxicity of Tripterygium extracts, using cytotoxicity and anti-inflammatory activity of the three principal active components of Tripterygium wilfordii Hook. F. (TWHF) as guiding parameters. Column chromatography was replaced by sodium carbonate extraction for removing the acidic compounds and enriching epoxyditerpenoids and alkaloids in the extract. Results showed that the therapeutic index (IC₅₀/EC₅₀) on murine macrophage Raw 264.7 cells and rat mesangial HBZY-1 cells of the extract prepared by sodium carbonate extraction was significantly higher than that of Tripterygium glycosides (0.8 and 5.2 vs. 0.3 and 2.6, p < 0.05), while its cytotoxicity on human liver HL7702 cells was significantly lower (14.5 ± 1.4 vs. 6.8 ± 0.9, p < 0.05). Further acute oral toxicity experiments showed that the LD₅₀ value of this extract was 1,210 mg/kg compared to 257 mg/kg for Tripterygium glycosides. All the above results suggest that Tripterygium extract prepared by sodium carbonate extraction may represent a potentially optimal source of medicine with good therapeutic index. Full article