Improving water quality and mitigating CH4 and N2O production in urban landscape water simultaneously by optimizing calcium peroxide dosage.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO2) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO2 dosage on the production of methane (CH4) and nitrous oxide (N2O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N2O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH4 production at increased CaO2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO2/m2 achieved 41.21 % and 84.40 % reductions in CH4 and N2O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH4 and N2O, from urban landscape water but also suggests a methodology for optimizing CaO2 dosage, providing valuable insights for its practical application.

Enhancing Oral Mucosal Barrier, Mitigating Microinflammation, and Addressing Malnutrition in Dialysis Patients: The Impact of Tangerine Peel Lemon Glycerin.

Objective: This study investigates the efficacy of tangerine peel lemon glycerin extract oral spray in improving oral mucosal barrier, reducing microinflammation, and addressing malnutrition in maintenance dialysis (MHD) patients. Methods: Tangerine peel and dry lemon underwent glycerin extraction. From January 2021 to June 2022, 72 MHD patients with thirst were prospectively chosen at Sinopharm Gezhouba Central Hospital. Randomization divided them into an observation group (n=36) and a control group (n=36). Both received routine maintenance dialysis and chronic kidney disease management. Oral conditions were assessed using OHIP-14, a homemade visual thirst score scale, SFR, sAA, and saliva pH. Microinflammatory indexes (CRP, TNF-α, IL-6) and nutritional status indicators (Alb, PA, Hb) were measured. The observation group used 1ml of tangerine peel lemon glycerin extract with a pH value of 5.9~6.1 q6h, while the control group used 1ml of purified water q6h. Results: After 3 months, the observation group showed significant improvement in OHIP-14 and visual thirst score scale (P < .01). Saliva pH, CRP, TNF-α, and IL-6 levels decreased, and SAA activity, SFR, Alb, PA, and Hb levels increased significantly in the observation group compared to the control group (P < .01). Conclusions: Tangerine peel lemon glycerin spray demonstrates promise in improving the oral mucosal barrier, exhibiting antibacterial and anti-inflammatory properties that mitigate microinflammation and malnutrition. This finding suggests a connection between oral health, systemic pathology, psychological state, and social adaptability.

Characterisation and identification of chemical constituents in aqueous extract of Fomes officinalis Ames based on ultrahigh-performance liquid chromatography tandem quadrupole-Orbitrap high-resolution mass spectrometry.

INTRODUCTION: Fungal species are an attractive resource for physiologically functional food and drug precursor. Fomes officinalis Ames, a medicinal fungus, is traditionally used as a folk medicine in traditional Chinese medicine prescription for the therapy of cough and asthma. The water-soluble substances in Chinese herbal medicines are likely to play an important physiological function. However, information on probing and identifying chemical components of the aqueous extract of Fomes officinalis Ames (AFO) remains unknown. OBJECTIVE: This study was conducted to screen and characterise the chemical components of AFO. MATERIAL AND METHODS: An effective and sensitive ultrahigh-performance liquid chromatography tandem quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) method with the Full MS/PIL/dd-MS2 acquisition approach was applied for the profiling of chemical components in AFO. An HSS T3 column was used for component separation, and a strategy of simultaneous targeted and untargeted multicomponent characterisation was implemented. Multiple identification approaches were used, including accurate molecular mass and elemental composition matching, literature and database searching, and fragmentation rules elucidation. RESULTS: A total of 115 components, including 20 amino acids and derivatives, six nucleobases, nine nucleosides, 75 dipeptides, two tripeptides, and three other components, were tentatively identified. Among them, the targeted exploring method screened six nucleobases and nine nucleosides including modified nucleosides. To our best knowledge, this is the first time a report has been done on the presence of the 115 compounds in AFO. CONCLUSION: Profiling and characterisation compounds of AFO enriched its material basis, which would lay the foundation for improving potential medicinal and nutritional values and effecting comprehensive quality control of Fomes officinalis Ames.

Foliar spraying of lanthanum activates endocytosis in lettuce (Lactuca sativa L.) root cells, increasing Cd and Pb accumulation and their bioaccessibility.

Cadmium (Cd) and lead (Pb) accumulate easily in leafy vegetables and can harm human health. Lanthanum (La) have been used to improve agricultural yield and quality, but the effect of La application on Cd/Pb enrichment in leafy vegetables remains incomplete currently. A previous study reported that the endocytosis in lettuce leaf cells can be activated by La, leading to an increase in Pb accumulation in lettuce leaves. However, it has not been investigated whether foliar application of La enhances root cellular endocytosis and promotes its uptake of Cd and Pb. In this study, the influence of La on the uptake of Cd and Pb, Cd bioaccessibility, and the safety risks of cultivating lettuce under Cd and Pb stress were explored. It was found that La increased Cd (16-30 % in shoot, 16-34 % in root) and Pb (25-29 % in shoot, 17-23 % in root) accumulation in lettuce. The increased accumulation of Cd and Pb could be attributed to La-enhanced endocytosis. Meanwhile, La enhanced the toxicity of both Cd and Pb, inhibited lettuce growth, and aggravated the damage to the photosynthetic and antioxidant systems. Finally, gastrointestinal simulation experiments showed that La increased the Cd bioaccessibility in both gastric and intestinal phase by 7-108 % and 9-87 %, respectively. These results offer valuable insights into the safety of REEs for agricultural applications.

Network pharmacology analysis combined with experimental validation to explore the therapeutic mechanism of salidroside on intestine ischemia reperfusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated. OBJECTIVE: The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation. METHODS: In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting. RESULTS: A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed. CONCLUSION: SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.

Pollen Molecular Identification from a Long-Distance Migratory Insect, Spodoptera exigua, as Evidenced for Its Regional Pollination in Eastern Asia.

Understanding plant-insect interactions requires the uncovering of the host plant use of insect herbivores, but such information is scarce for most taxa, including nocturnal moth species, despite their vital role as herbivores and pollinators. In this study, we determined the plant species visited by an important moth species, Spodoptera exigua, by analyzing attached pollen on migratory individuals in Northeast China. Pollen grains were dislodged from 2334 S. exigua long-distance migrants captured between 2019 and 2021 on a small island in the center of the Bohai Strait, which serves as a seasonal migration pathway for this pest species, and 16.1% of the tested moths exhibited pollen contamination, primarily on the proboscis. Subsequently, 33 taxa from at least 23 plant families and 29 genera were identified using a combination of DNA barcoding and pollen morphology, primarily from the Angiosperm, Dicotyledoneae. Moreover, the sex, inter-annual, and seasonal differences in pollen adherence ratio and pollen taxa were revealed. Notably, compared to previously reported pollen types found on several other nocturnal moths, we found that almost all of the above 33 pollen taxa can be found in multiple nocturnal moth species, providing another important example of conspecific attraction. Additionally, we also discussed the indicative significance of the pollen present on the bodies of migratory individuals for determining their migratory route. Overall, by delineating the adult feeding and pollination behavior of S. exigua, we advanced our understanding of the interactions of the moths with their host plants, and its migration pattern, as well as facilitated the design of (area-wide) management strategies to preserve and optimize ecosystem services that they provide.

Promising anticancer activities and mechanisms of action of active compounds from the medicinal herb Centipeda minima (L.) A. Braun & Asch.

BACKGROUND: Centipeda minima (L.) A. Braun & Asch (C. minima) has been used as a traditional Chinese herbal medicine to treat multiple diseases, including sinusitis, rhinitis, headache, and allergy. To date, the anticancer properties of C. minima have drawn considerable attention owing to the anticancer potential of C. minima extracts, the identification of active components, and the elucidation of underlying molecular mechanisms. However, the anticancer properties and significance of active components in C. minima have rarely been summarized. PURPOSE: This review presents a comprehensive summary of the anticancer properties exhibited by active components of C. minima. METHODS: An extensive search for published articles on the anticancer activities and active components of C. minima was performed using Web of Science, PubMed, Science Direct, and Google Scholar. RESULTS: C. minima extracts exhibited both anticancer and chemosensitizing effects. Phytochemical studies have identified the active anticancer components of C. minima extracts. Sesquiterpene lactones, such as 6-O-angeloylplenolin (6-OAP, or brevilin A) and arnicolide D, have similar structures and anticancer mechanisms. As the most abundant sesquiterpene lactone in C. minima, 6-OAP exhibits anticancer activities mainly by targeting Skp1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase and signal transducers and activators of transcription 3 (STAT3). Clinical trials have assessed the potential of 6-OAP in patients with vertex balding and alopecia areata, given its effect on JAK-STATs signaling. Chlorogenic acid, a representative organic acid in C. minima, reportedly possesses anticancer potential and inhibits tumor growth by affecting tumor microenvironment and has been approved for phase II clinical trials in patients with glioma in China. CONCLUSION: In the present review, we highlight intriguing anticancer properties mediated by active compounds isolated from C. minima extracts, particularly sesquiterpene lactones, which might provide clues for developing novel anticancer drugs. Relevant clinical trials on chlorogenic acid and 6-OAP can promote anticancer clinical applications. Therefore, it is worth comprehensively elucidating underlying anticancer mechanisms and conducting clinical trials on C. minima and its active components.

Chemical profiling of composite prescription caraway and quantification of three pairs isomeric components in caraway administered rat plasma by tandem mass spectrometry.

Caraway, a well-known traditional Uyghur medicine, has been used to treat vitiligo for centuries. Its biological effects on melanin synthesis of caraway have been investigated. However, beyond psoralen and isopsoralen alone, no further chemical component of caraway has been revealed. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry was employed to comprehensively characterize the chemical components present in caraway. Based on accurate mass measurements, key fragmental ions and comparison with reference standards, 75 chemical components were identified in caraway. Moreover, a tandem mass spectrometry method was developed and validated for quantitative analysis of three pairs isomeric components, namely psoralen/isopsoralen, bavachin/isobavachalcone and bavachromene/isobavachromene in rat plasma. Psoralen, isopsoralen, bavachin, and isobavachalcone showed linearity with concentration ranging of 1.0-500.0 ng/ml. The linear ranges for bavachromene and isobavachromene were 0.2-500.0 ng/ml. The accuracies were in ranges of 85%-115% with coefficient of variation errors of less than 15%. Furthermore, the method was applied to quantify the three pairs isomeric components in rats after oral administration of caraway.

Windborne migration amplifies insect-mediated pollination services.

Worldwide, hoverflies (Syrphidae: Diptera) provide crucial ecosystem services such as pollination and biological pest control. Although many hoverfly species exhibit migratory behavior, the spatiotemporal facets of these movement dynamics, and their ecosystem services implications are poorly understood. In this study, we use long-term (16-year) trapping records, trajectory analysis, and intrinsic (i.e., isotope, genetic, pollen) markers to describe migration patterns of the hoverfly Episyrphus balteatus in northern China. Our work reveals how E. balteatus migrate northward during spring-summer and exhibits return (long-range) migration during autumn. The extensive genetic mixing and high genetic diversity of E. balteatus populations underscore its adaptive capacity to environmental disturbances, for example, climate change. Pollen markers and molecular gut analysis further illuminate how E. balteatus visits min. 1012 flowering plant species (39 orders) over space and time. By thus delineating E. balteatus transregional movements and pollination networks, we advance our understanding of its migration ecology and facilitate the design of targeted strategies to conserve and enhance its ecosystem services.

Visiting Plants of Mamestra brassicae (Lepidoptera: Noctuidae) Inferred From Identification of Adhering Pollen Grains.

Numerous lepidopteran adults frequently pick up plant pollen when feeding. Identifying plant species visited by Mamestra brassicae moths could further strengthen our knowledge of their migratory trajectory and the interactions of M. brassicae moths with these plant species. Here, with morphological analysis and DNA metabarcoding of pollen carried by the moths, we determined these plant species visited by M. brassicae during 2015-2018. Pollen grains removed from M. brassicae moths were identified from 25 species (18 were identified to genus), representing at least 19 families, including Pinaceae, Oleaceae, Rosaceae, and Asteraceae, but mainly belonging to Angiospermae, Dicotyledoneae. There were noticeable interannual differences (maximum value: 35.31% in 2018) and seasonal differences (maximum value: 33.28% in April-(including May)-June) in the frequency of M. brassicae moths with adhering pollen, but no noticeable difference based on sex. Meanwhile, we also found pollen from some species such as Citrus sinensis (Rutales: Rutaceae) and Melia azedarach (Rutales: Meliaceae) that grow in southern China, indicating that M. brassicae moths might migrate northward in spring. Our results demonstrate that the M. brassicae moth visits a variety of plant species during migration, and these findings promote our understanding of the interaction between moths and these plant species.

Identification and field verification of an aggregation pheromone from the white-spotted flower chafer, Protaetia brevitarsis Lewis (Coleoptera: Scarabaeidae).

The white-spotted flower chafer (WSFC), Protaetia brevitarsis Lewis, is native to East Asia. Although their larvae are considered a potential resource insect for degrading plant residues, producing protein fodder, and processing to traditional medicine, adult WSFCs inflict damage to dozens of fruit and economic crops. The control of the WSFC still relies heavily on pesticides and the inefficient manual extraction of adults. Here, we report the identification and evaluation of the aggregation pheromone of WSFCs. From the headspace volatiles emitted from WSFC adults, anisole, 4-methylanisole, 2-heptanone and 2-nonanone were identified as WSFC-specific components. However, only anisole and 4-methylanisole elicited positive dose-response relationship in electroantennography tests, and only 4-methylanisole significantly attracted WSFCs of both sexes in olfactometer bioassays and field experiments. These results concluded that 4-methylanisole is the aggregation pheromone of WSFCs. Furthermore, we developed polyethylene vials as long-term dispensers of 4-methylanisole to attract and kill WSFCs. The polyethylene vial lures could effectively attracted WSFCs for more than four weeks. Pheromone-based lures can be developed as an environmentally friendly protocol for monitoring and controlling WSFC adults.

Centipeda minima extract sensitizes lung cancer cells to DNA-crosslinking agents via targeting Fanconi anemia pathway.

BACKGROUND: Intrinsic and acquired chemoresistance remains a critical challenge in lung cancer chemotherapy. Fanconi anemia (FA) pathway plays an important role in antagonizing the cytotoxic effects of chemotherapeutics by repairing DNA damage. We recently demonstrated that the traditional Chinese medicinal herb, Centipeda minima (C. minima), possessed anti-inflammatory and antioxidant properties. However, the potential anticancer application of C. minima and the underlying mechanisms remain unclear. PURPOSE: We aimed to investigate the combined anticancer effects of the ethanol extract of C. minima (ECM) and DNA-crosslinking agents on non-small cell lung cancer (NSCLC) and elucidate the underlying mechanisms. METHODS: Cell viability and flow cytometry assay were performed to determine the synergistic cytotoxicity of ECM and DNA-crosslinking agents, cisplatin (CDDP) or mitomycin C (MMC), in NSCLC cells. Western blotting and immunofluorescence were conducted to examine the effects of ECM on protein expression in DNA damage repair pathway. Comet assay was applied to evaluate DNA damage levels. Subcutaneous xenografts of NSCLC were established to evaluate the combined anticancer effects of ECM and CDDP. RESULTS: Combined treatments with ECM and DNA-crosslinking agents exhibited synergistic cytotoxic effects against A549 and H1299 cells. FANCD2 was highly expressed in NSCLC that correlates with poor prognosis of NSCLC patients, based on the online database analysis. ECM significantly inhibited DNA damage-induced monoubiquitination and nuclear foci formation of FANCD2, thereby sensitizing NSCLC to CDDP- or MMC-induced DNA damage and apoptosis, as evidenced by increased expression of γ-H2AX, increased cleavage of caspases-3 and PARP, and enhanced Annexin V-FITC/PI staining. Further, ECM can also decrease the protein level of FANCD2 that contributes to the chemosensitizing effects. Moreover, ECM significantly attenuated CDDP-mediated S-phase arrest by antagonizing the activation of ATR/Chk1 pathway in NSCLC cells. Animal experiments further demonstrated that ECM and CDDP combination treatment synergistically inhibited tumor growth by decreasing FANCD2 protein level in tumor tissues. CONCLUSION: Our results demonstrated that ECM can inhibit DNA-crosslinking agents-induced activation of FA pathway by attenuating both the expression and monoubiquitination of FANCD2. ECM and CDDP combination therapy exhibited synergistic anticancer effects both in vitro and in vivo, indicating that ECM and its active components might serve as novel anticancer drugs in the combination chemotherapy.

Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Novel inhibitors that target both the wild-type and mutant SMO are in high demand. In this study, we identified a novel Hh pathway inhibitor, pseudolaric acid B (PAB), which significantly inhibited the expression of Gli1 and its transcriptional target genes, such as cyclin D1 and N-myc, thus inhibiting the proliferation of DAOY and Ptch1+/- primary MB cells. Mechanistically, PAB can potentially bind to the extracellular entrance of the heptahelical transmembrane domain (TMD) of SMO, based on molecular docking and the BODIPY-cyclopamine binding assay. Further, PAB also efficiently blocked ciliogenesis, demonstrating the inhibitory effects of PAB on the Hh pathway at multiple levels. Thus, PAB may overcome drug-resistance induced by SMO mutations, which frequently occurs in clinical setting. PAB markedly suppressed tumor growth in the subcutaneous allografts of Ptch1+/- MB cells. Together, our results identified PAB as a potent Hh pathway inhibitor to treat Hh-dependent MB, especially cases resistant to SMO antagonists.

Traditional Chinese medicines and their active ingredients sensitize cancer cells to TRAIL-induced apoptosis.

The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.

Acupoint catgut embedding improves senescence in a rat model of ageing by regulating mitophagy via the PINK1 pathway.

Ageing population is a tough task worldwide, and the aggravating trend of ageing population in China brings enormous pressure to healthcare system. Chinese acupuncture has shown definite anti-ageing effect as arthralgia relief, movement improvement, energy increase and immunity enhancement; however, the mechanisms underlying are far away from illumination. Increasing literature has highlighted the role of alterations in mitochondrial function as a potential central regulator in ageing biology; mitophagy plays a critical role in mitochondrial quality control. In the present study, we demonstrated that acupoint catgut embedding treatment ameliorated ageing-related alterations in appearance, muscle function and spatial memory in rats, reduced degenerated cells in hippocampus, and maintained relatively normal structures in the hippocampus tissue and neurons. These changes were proved to be associated with the regulation of mitochondrial function and autophagic activity. Furthermore, we investigated part of the molecular mechanisms and demonstrated that the PINK1 other than PINK1-Parkin signalling pathway involved in the effects of acupoint catgut embedding, and the imbalancement between mitochondrial fusion and fission and stimulation of mitochondrial biogenesis may aggravate or compensate for impaired mitochondria. The factors act downstream PINK, and the interaction between them for mitochondrial homeostasis in this process remains to be identified.

Effect of pristimerin on apoptosis through activation of ROS/ endoplasmic reticulum (ER) stress-mediated noxa in colorectal cancer.

BACKGROUND: Pristimerin, a natural quinonemethid triterpenoid found in different spp. of Celastraceae and Hippocrateaceae families, has been reported to exhibit potent antitumor activities against colorectal cancer (CRC). However, the mechanisms underlying pristimerin-induced apoptosis in CRC is not clear. PURPOSE: This study aimed to investigate the mechanisms of pristimerin-induced apoptosis against CRC in vitro and in vivo. METHODS: Cell viability and cell apoptosis analyses were conducted to assess the effects of pristimerin on CRC. Western blotting was performed to detect the expression of proteins affected by pristimerin in vitro and in vivo. HCT116 colon cancer xenografts and APCmin/+ mouse models were used to evaluate the anti-CRC effect of pristimerin in vivo. RESULTS: Our data showed that pristimerin induced apoptosis by regulating proapoptotic proteins of which Noxa showed higher expression. Pristimerin triggered reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress signaling activation. Pristimerin significantly elevated the expression of ER stress-related proteins, resulting in activation of the IRE1α and c-Jun N-terminal kinase (JNK) signal pathway through the formation of the IRE1α-TRAF2-ASK1 complex. Pristimerin exhibited apoptosis-inducing activities in HCT116 colon cancer xenografts and APCmin/+ mice. CONCLUSION: Both in vitro and in vivo data demonstrated that pristimerin induced Noxa expression and apoptosis through activation of the ROS/ER stress/JNK axis in CRC. Thus, pristimerin may be a promising antitumor agent for CRC.

Protection against chemotherapy- and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals.

BACKGROUND: Although great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy. PURPOSE: This review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications. METHODS: We obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects. RESULTS: Representative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values. CONCLUSION: This review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.

Gambogenic acid induces Noxa-mediated apoptosis in colorectal cancer through ROS-dependent activation of IRE1α/JNK.

BACKGROUND: Gambogenic acid (GNA), an active component of Garcinia hanburyi Hook.f. (Clusiaceae) (common name gamboge), exerts anti-inflammatory and antitumor properties. However, the underlying mechanism of GNA in colorectal cancer (CRC) is still not well understood. PURPOSE: This study aimed to investigate the antitumor effects and mechanisms of GNA on CRC in vitro and in vivo. METHODS: Cell viability, colony formation and cell apoptosis assays were performed to determine the antitumor effects of GNA. qRT-PCR and Western blotting were performed to evaluate the expression of genes or proteins affected by GNA in vitro and in vivo. HCT116 colon cancer xenografts and the APCmin/+ mice model were used to confirm the antitumor effects of GNA on CRC in vivo. RESULTS: GNA induced Noxa-mediated apoptosis by inducing reactive oxygen species (ROS) generation and c-Jun N-terminal kinase (JNK) activation. Moreover, GNA triggered endoplasmic reticulum (ER) stress, which subsequently activated inositol-requiring enzyme-1α (IRE1α) leading to JNK phosphorylation. ROS scavenger attenuated GNA-induced IRE1α activation and JNK phosphorylation. Knockdown of IRE1α also prevented GNA-induced JNK phosphorylation. In vivo, GNA suppressed tumor growth and progression in HCT116 colon cancer xenografts and the APCmin/+ mices model. CONCLUSION: These findings revealed that GNA induced Noxa-mediated apoptosis by activating the ROS/IRE1α/JNK signaling pathway in CRC both in vitro and in vivo. GNA is therefore a promising antitumor agent for CRC treatment.

Upgrading a large and centralised municipal wastewater treatment plant with sequencing batch reactor technology for integrated nutrient removal and phosphorus recovery: Environmental and economic life cycle performance.

Although nutrient removal and recovery from municipal wastewater are desirable to protect phosphorus resource and water-bodies from eutrophication, it is unclear how much environmental and economic benefits and burdens it might cause. This study evaluated the environmental and economic life cycle performance of three different upgraded Processes A, B and C with commercially available technologies for nutrient removal and phosphorus recovery based on an existing Malaysian wastewater treatment plant with a sequencing batch reactor technology and diluted municipal wastewater. It is found that the integration of nutrient removal, phosphorus recovery and electricity generation in all upgraded processes reduced eutrophication potential by 62-76%, and global warming potential by 7-22%, which, however, were gained at the cost of increases in human toxicity, acidification, abiotic depletion (fossil fuel) and freshwater ecotoxicity potentials by an average of 23%. New technologies for nutrient removal and phosphorus recovery are thus needed to achieve holistic rather than some environmental benefits at the expense of others. In addition, the study on two different functional units (FU), i.e. per m3 treated wastewater and per kg struvite recovered, shows that FU affected environmental assessment results, but the upgraded Process C had the least overall environmental burden with either of FUs, suggesting the necessity to use different functional units when comparing and selecting different technologies with two functions such as wastewater treatment and struvite production to confirm the best process configuration. The total life cycle costs of Processes A, B and C were 10.7%, 29.8% and 28.1%, respectively, higher than the existing process due to increased capital and operating costs. Therefore, a trade-off between environmental benefits and cost has to be balanced for technology selection or new integrated technologies have to be developed to achieve environmentally sustainable wastewater treatment economically.