γCyclodextrin-assisted Aqueous Extract of Cinnamon for Cancer and Stress Management.

AIM: Our goal was to investigate the use of Cyclodextrin in creating an aqueous extract of Cinnamon with a high content of its bioactive ingredients, validated by cell-based assays. BACKGROUND: Due to their safety and cost-effectiveness, natural compounds have garnered attention for cancer therapy, which often faces challenges related to drug toxicity and resistance. Cinnamon (Cinnamomum verum; also known as Ceylon Cinnamon) is a commonly used spice with a history in folk medicine for treating various ailments. However, its active ingredients suffer from poor solubility, stability, and bioavailability, which limits its use and benefits. OBJECTIVE: We prepared γCyclodextrin (γCD)-assisted aqueous extract of Cinnamon (CD-CIN) and compared its activity with the DMSO extract (DM-CIN). METHODS: The cells were exposed to CD-CIN and DM-CIN extracts under normal and stressed (oxidative, metal, and hypoxic) conditions and then analyzed for stress and cancerous phenotypes using various molecular assays. RESULTS: We found that CD-CIN possesses considerable anticancer activity that involves the activation of tumor suppressor proteins and DNA damage response. Low, non-toxic concentrations of DM-CIN and CD-CIN caused comparable inhibition of migration and invasion capability of cells, supported by molecular marker analyses. Furthermore, protection against oxidative, metal, and hypoxia stress, as well as induction of differentiation, was recorded in both DM-CIN and CD-CIN treated cells, as compared to the control. CONCLUSION: We report CD-CIN as a new economic and easy Cinnamon-derived resource that possesses considerable anticancer and antistress activities and hence warrants further chemical, in vitro, and in vivo studies.

Cucurbitacin-B inhibits cancer cell migration by targeting mortalin and HDM2: computational and in vitro experimental evidence.

Cancer metastasis, a highly complex process wherein cancer cells move from the primary site to other sites in the body, is a major hurdle in its therapeutics. A large array of synthetic chemotherapeutic molecules used for the treatment of metastatic cancers, besides being extremely expensive and unaffordable, are known to cause severe adverse effects leading to poor quality of life (QOL) of the patients. In this premise, natural compounds (considered safe, easily available and economic) that possess the potential to inhibit migration of cancer cells are deemed useful and hence are on demand. Cucurbitacin-B (19-(10→9ß)-abeo-10-lanost-5-ene triterpene, called Cuc-B) is a steroid mostly found in plants of Cucurbitaceae family. It has been shown to possess anticancer activity although the molecular mechanism remains poorly defined. We present evidence that Cuc-B has the ability to interact with mortalin and HDM2 proteins that are enriched in cancer cells, suppress wild type p53 function and promote cancer cell migration. Computational analyses showed that Cuc-B interacts with mortalin similar to MKT077 and Withanone, both have been shown to reactivate p53 function and inhibit cell migration. Furthermore, Cuc-B interacted with HDM2 similar to Y30, a well-known inhibitor of HDM2. Experimental cell and molecular analyses demonstrated the downregulation of several proteins, critically involved in cell migration in Cuc-B (low non-toxic doses)-treated cancer cells and exhibited inhibition of cell migration. The data suggested that Cuc-B is a potential natural drug that warrants further mechanistic and clinical studies for its use in the management of metastatic cancers.Communicated by Ramaswamy H. Sarma.

Erratum: CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFß1: Erratum.

[This corrects the article DOI: 10.7150/ijbs.53657.].

Bioactivity-guided fractionation of Helicteres angustifolia L. extract and its molecular evidence for tumor suppression.

Helicteres angustifolia L. (Helicteres angustifolia) has been commonly used in folk medicine to treat cancer; however, its mechanisms of action remain obscure. In our earlier work, we reported that aqueous extract of H. angustifolia root (AQHAR) possesses attractive anticancer properties. In the present study, we isolated five ethanol fractions from AQHAR and investigated their therapeutic efficacy in human non-small cell lung cancer (NSCLC) cells. The results showed that among the five fractions, the 40% ethanol fraction (EF40) containing multiple bioactive compounds exhibited the best selective killing effect on NSCLC cells with no obvious toxicity to normal human fibroblasts. Mechanistically, EF40 reduced the expression of nuclear factor-E2-related factor 2 (Nrf2), which is constitutively expressed at high levels in many types of cancers. As a result, Nrf2-dependent cellular defense responses are suppressed, leading to the intracellular accumulation of reactive oxygen species (ROS). Extensive biochemical analyses revealed that EF40 caused cell cycle arrest and apoptosis through activation of the ROS-mediated DNA damage response. Furthermore, treatment with EF40 compromised NSCLC cell migration, as evidenced by the downregulation of matrix metalloproteinases (MMPs) and heterogeneous nuclear ribonucleoprotein K (hnRNP-K). In vivo studies using A549 xenografts in nude mice also revealed significant suppression of tumor growth and lung metastasis in the treated group. We propose that EF40 may serve as a potential natural anti-NSCLC drug that warrants further mechanistic and clinical attention.

Research Progress on Fiber-Reinforced Recycled Brick Aggregate Concrete: A Review.

The addition of fibers to strengthen recycled concrete can strengthen the inherent deficits and deficiencies of concrete containing recycled aggregates to some extent and enlarge the concrete's application range. In order to further promote the development and application of fiber-reinforced brick aggregate recycled concrete, the research results regarding its mechanical properties are reviewed in this paper. The effect of the content of broken brick on the mechanical properties of recycled concrete and the effects of different categories and contents of fiber on the basic mechanical properties of recycled concrete are analyzed. The problems to be solved in research on the mechanical properties of fiber-reinforced recycled brick aggregate concrete are presented, and the related research suggestions and prospects are summarized. This review provides a reference for further research in this field and the popularization and application of fiber-reinforced recycled concrete.

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression.

Objective: To explore the effect and molecular mechanism of Src homology region 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in tumor-associated macrophages (TAMs) repressing the migration and invasion of colorectal cancer (CRC) cells. Methods: The relevant data sets of human colon specimens were obtained from GEO database, and then the performed correlation analysis, principal component analysis and differentially expressed gene (DEGs) analysis on the samples were conducted. GO and KEGG enrichment analysis were performed on the common DEGs, and then functional interaction prediction was performed to verify the gene regulatory circuit of SHP-2. Furthermore, western blot was used to detect the effect of low expression of SHP-2 on related proteins, including the markers of promoting M2 polarization and exosome secretion, and keys proteins of the PI3K pathway. The relationship between SHP-2 and PI3K pathway was further verified by adding PI3K inhibitor LY294002. Finally, the effect of SHP-2 on the function of colon cancer cells was confirmed by wound healing assay and Transwell assay. Results: Through bioinformatics analysis, SHP-2 was screened as a possible key gene affecting CRC. The low expression of SHP-2 promoted the protein levels of Arginase-1 and IL-10 in IL-4 induced M2 macrophages, while inhibited the protein levels of IL-1ß and TNF-α. Meanwhile, low expression of SHP-2 was found to similarly promote the expression of p-PI3K, p-AKT, and the release of exosomes. Interestingly, the promotion was suppressed after the addition of the PI3K inhibitor LY294002. In terms of cellular behavior, wound healing and transwell data showed that low expression of SHP-2 enhanced the migration and invasion abilities of CRC cells. Conclusion: The low expression of SHP-2 induced by PHPS1 may regulate M2 polarization of TAMs and release of exosomes through PI3K/AKT pathway, thereby enhancing the migration and invasion ability of CRC cells.

Revealing calcium ion behavior during anaerobic phosphorus release process in aerobic granular sludge system.

Calcium ions (Ca2+) are important for biological phosphorus (P) removal from wastewater, but its behavior has not been well documented during the anaerobic P release process. This study is aimed to explore the mechanisms of Ca2+ release in bacterial aerobic granular sludge (AGS) system. During the non-aeration (anaerobic) phase, nearly 40 % increase in Ca2+ concentration was detected at the bottom of AGS reactor where decrease in pH and increase in Mg2+ concentration occurred. The pH decrease due to anaerobic P release caused CaCO3 dissolution inside the granules, leading to Ca2+ release. In addition, the increased Mg2+ ions from hydrolysis of polyphosphates were detected to reversibly exchange with Ca2+ in granules at a molar ΔCa/ΔMg ratio of 0.51-0.65. Results from this work revealed that dissolution of CaCO3 and ions exchange between Ca2+ and Mg2+ were the two major contributors to Ca2+ release during anaerobic P release process.

Zero-valent iron is not always effective in enhancing anaerobic digestion performance.

Liquid nitrogen was employed as a low-temperature medium to activate zero-valent iron (ZVI) powder in an attempt to strengthen its enhancement effect on anaerobic digestion (AD) of swine manure (SM). Surprisingly, it was found that both pristine ZVI and liquid nitrogen-pretreated ZVI (LZVI) did not significantly improve the AD performance or change the archaeal community structure. It was hypothesized that ZVI might not be effective at stress-free environment like in these digesters. To confirm this, an additional set of AD experiments were performed at high ammonia stress (about 4000 mg/L), results showed that ZVI and LZVI greatly alleviated ammonia inhibition and increased the CH4 yield by 11.6% and 28.2%, respectively. Apparently, ZVI mainly affected AD systems by changing the metabolism pathways and enhancing the microbial activity to overcome process inhibition, and pretreatment of liquid nitrogen could significantly accelerate the dissolution of ZVI and improve its utilization efficiency, contributing to a greater extend of process recovery and improvement.

Chemical and Biological Evidence of the Efficacy of Shengxian Decoction for Treating Human Lung Adenocarcinoma.

Shengxian Decoction (SXT) is a traditional Chinese medicine prescription comprising several anti-cancer medicinal herbs. However, the anti-cancer effect of SXT has rarely been reported. Herein, we explored the therapeutic potential of SXT for the treatment of lung adenocarcinoma (LUAD). High-performance liquid chromatography analysis of crude SXT extract revealed the abundance of mangiferin, an established anti-cancer compound. The serum pharmacological evaluation revealed that serum SXT suppressed A549 lung cancer cell proliferation in vitro. The tumor-inhibitory activity of SXT was confirmed in vivo via tumor formation assays in nude mice. We applied biochemical, histopathological and imaging approaches to investigate the cellular targets of SXT. The results indicated that the treatment with SXT induced tumor necrosis, and downregulated hypoxia-inducible factor 1 alpha in the serum. In vivo biosafety assessment of SXT revealed low levels of toxicity in mouse models. Our study provides the first scientific evidence that SXT effectively represses cancer cell growth and, thus, may serve as a safe anti-cancer agent for LUAD treatment.

Insight into aerobic phosphorus removal from wastewater in algal-bacterial aerobic granular sludge system.

This study aimed to figure out the main contributors to aerobic phosphorus (P) removal in the algal-bacterial aerobic granular sludge (AGS)-based wastewater treatment system. Kinetics study showed that aerobic P removal was controlled by macropore (contributing to 64-75% P removal) and micropore diffusion, and the different light intensity (0, 4.0, 12.3, and 24.4 klux) didn't exert significant (p > 0.05) influence on P removal. On the other hand, the increasing light intensity did promote microalgae metabolism, leading to the elevated wastewater pH (8.0-9.8). The resultant pH increase had a strongly negative relationship (R2 = 0.9723) with P uptake by polyphosphate-accumulating organisms, while promoted chemical Ca-P precipitation at a molar Ca/P ratio of 1.05. Results from this work could provide an in-depth understanding of microalgae-bacteria symbiotic interaction, which is helpful to better design and operate the algal-bacterial AGS systems.

Effect of the Flame Retardants and Glass Fiber on the Polyamide 66/Polyphenylene Oxide Composites.

In this work, polyamide 66/polyphenylene oxide (PA66/PPO) composites, including the flame retardants 98 wt% aluminum diethylphosphinate + 2 wt% polydimethylsiloxane (P@Si), Al(OH)3-coated red phosphorus (RP*), and glass fiber (GF), were systematically studied, respectively. The limiting oxygen index (LOI), UL-94 vertical burning level, and thermal and mechanical properties of the PA66/PPO composites were characterized. The results showed that the P@Si and RP flame retardants both improved the LOI value and UL-94 vertical burning level of the PA66/PPO composites, and PA66/PPO composites passed to the UL-94 V-0 level when the contents of P@Si and RP* flame retardants were 16 wt% and 8 wt%. On the other hand, the mechanical properties of the PA66/PPO composites were reduced from a ductile to a brittle fracture mode. The addition of GF effectively made up for these defects and improved the mechanical properties of the PA66/PPO composites containing the P@Si and RP*, but it did not change the fracture mode. P@Si and RP* flame retardants improved the thermal decomposition of PA66/PPO/GF composites and reduced the maximum mass loss rates, showing that the PA66/PPO/GF composites containing the P@Si and RP* flame retardants could be used in higher-temperature fields.

Current status of total neoadjuvant therapy for locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) plus total mesorectal excision (TME) has been the standard regimen for treatment of patients with locally advanced rectal cancer (LARC), because it significantly reduces the rate of local recurrence and enables sphincter preservation. However, distant metastasis remains the major reason for treatment failure, and the value of postoperative chemotherapy is still controversial. Recent studies have examined the use of total neoadjuvant therapy (TNT), defined as induction and/or consolidation chemotherapy (CONCT) with radiotherapy (RT) or nCRT prior to surgery. The results indicated that TNT may increase the rates of chemotherapy compliance and pathological complete response (pCR), and probably improve the success rate of sphincter preservation surgery. TNT may also improve disease-free survival and overall survival, and even reduce the rate of relapse. Here, we critically appraise the existing literature on three different TNT schemes used for LARC patients.

Combined effect of zero valent iron and magnetite on semi-dry anaerobic digestion of swine manure.

Combined effect of zero valent iron (ZVI) and magnetite on semi-dry anaerobic digestion of swine manure was studied. Compared with control, the addition of 5 g/L ZVI, magnetite and their mixture (1:1 wt) increased the CH4 yield by 17.6%, 22.7% and 21.9%, respectively. The three additives improved CH4 production through altering the metabolism pathways, rather than improving the solid degradation efficiency. ZVI promoted interspecies hydrogen transfer (IHT) by enriching H2-comsuming Methanolinea and acetate-oxidizing bacteria (Sedimentibacter and Clostridium). Magnetite enriched dissimilatory iron reduction bacteria (Acinetobacter) to accelerate organic hydrolysis and established direct interspecies electron transfer (DIET) by enriching Methanothrix and Methanospirillum. Key microorganisms relative to IHT (Clostridium) and DIET (Methanothrix and Methanospirillum) were simultaneously enriched with ZVI + magnetite, but they only showed an additive effect on methanogenesis, the lack of synergetic effect was attributable to the possible trade-off between IHT and DIET, or the little improvement effect of additives on substrate biodegradability.

Therapy Strategy of CD47 in Diffuse Large B-Cell Lymphoma (DLBCL).

At present, the use of the common chemotherapy regimen CHOP/R-CHOP for diffuse large B-cell lymphoma (DLBCL) has some shortcomings, especially for relapsed and refractory DLBCL. CD47 is now considered as a prominent target in cancer therapies, and CD47 blockade mainly inhibits the CD47-SIRPα axis to prevent tumor immune escape. Here, we evaluated the effects of the latest CD47 antibodies reported and the correlations of closely related genes with CD47 in this disease. In the future, therapeutic strategies for DLBCL will focus on multitarget antibody combined treatment and multigene joint attacks.

Plasma Lipidomics Profiling Reveals Biomarkers for Papillary Thyroid Cancer Diagnosis.

The objective of this study was to identify potential biomarkers and possible metabolic pathways of malignant and benign thyroid nodules through lipidomics study. A total of 47 papillary thyroid carcinomas (PTC) and 33 control check (CK) were enrolled. Plasma samples were collected for UPLC-Q-TOF MS system detection, and then OPLS-DA model was used to identify differential metabolites. Based on classical statistical methods and machine learning, potential biomarkers were characterized and related metabolic pathways were identified. According to the metabolic spectrum, 13 metabolites were identified between PTC group and CK group, and a total of five metabolites were obtained after further screening. Its metabolic pathways were involved in glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, Phosphatidylinositol signaling system and the metabolism of arachidonic acid metabolism. The metabolomics method based on PROTON nuclear magnetic resonance (NMR) had great potential for distinguishing normal subjects from PTC. GlcCer(d14:1/24:1), PE-NME (18:1/18:1), SM(d16:1/24:1), SM(d18:1/15:0), and SM(d18:1/16:1) can be used as potential serum markers for the diagnosis of PTC.

Comparison of decabromodiphenyl ether degradation in long-term operated anaerobic bioreactors under thermophilic and mesophilic conditions and the pathways involved.

Anaerobic digestion of decabromodiphenyl ether was carried out and compared in two continuously stirred anaerobic bioreactors for 210 days under thermophilic and mesophilic conditions. Results show that the degradation of decabromodiphenyl ether followed the first-order reaction kinetics, which exhibited a higher removal rate in the thermophilic reactor when compared to the mesophilic one, reaching its maximum of 1.1 µg·day-1. The anaerobic digestion of decabromodiphenyl ether was found to involve the replacement of bromines from polybrominated diphenyl ether by hydrogen atoms, gradually forming nona-, octa- and hepta-brominated diphenyl ether, respectively. Under the thermophilic condition, the reactors were dominated by Bacillus sp. and Methanosarcina sp. with high bioactivity and high concentrations of debromination microorganisms.

Low Dose of Fluoride in the Culture Medium of Cordyceps militaris Promotes Its Growth and Enhances Bioactives with Antioxidant and Anticancer Properties.

Cordyceps militaris possesses several compounds with medicinal properties, and is commonly used in traditional Chinese functional food and medicine for a variety of health benefits. Because of its rare occurrence in nature, the market demand for artificial C. militaris is on the rise. Furthermore, efforts to increase its bioactive ingredients have also been considered in research. In this study, we aimed to investigate the effect of fluoride on the growth and enrichment of bioactive compounds in C. militaris. A wide range of potassium fluoride concentrations (0, 0.001, 0.01, 0.1, and 1 mM) were added to the culture media as a source of fluoride during the cultivation of C. militaris fruiting bodies. The contents of fluorine and bioactive substances of the fruiting bodies in normal (NM) and fluorine-supplemented (FM) media were measured and compared. C. militaris raised in the growth medium supplemented with 0.01 mM potassium fluoride led to a 44.86% (1.55 ± 0.14 g/bottle) increase in biomass and a 23.43% (3161.38 ± 35.71 µg/g) increase in total carotenoid content in the fruiting bodies. Furthermore, a remarkable increase in superoxide dismutase-like activity (84.75 U/mg) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (IC50 = 2.59 mg/mL) was recorded. In human cancer cell-based assays, C. militaris raised in FM caused stronger cytotoxicity, apoptosis, and cell cycle arrest in human osteosarcoma cells. These results demonstrated that a low dose of fluoride could stimulate the growth of C. militaris fruiting bodies and enhance the production of bioactive ingredients that possess useful antioxidant and anticancer activities.

CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFß1.

CD151 impacts various signaling pathways in different cancers, and promotes colorectal cancer (CRC) cell malignancy by yet undefined mechanisms. This study aimed to comprehensively assess CD151's function in CRC. CD151 levels were significantly higher in CRC tissues and cells compared with controls in the tissue microarray. Cell viability, migration and invasion were suppressed by CD151 downregulation in CRC cells. Consistently, mouse xenografts were inhibited by CD151 silencing. RNA-seq revealed that multiple genes were significantly altered by CD151 knockdown in cultured CRC cells and xenografts. Particularly, transforming growth factor ß1 (TGFß1), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) alongside CD151 were downregulated both in vitro and in vivo. Co-immunoprecipitation and mass spectrometry results were validated by qRT-PCR and immunoblot. Moreover, pull-down assay and immunofluorescence confirmed the associations of TGFß1, CEACAM6 and LGR5 with CD151. This study demonstrated CEACAM6, LGR5 and Wnt pathway suppression by CD151 silencing might occur through TGFß1 regulation, offering a comprehensive view of CD151's roles in colorectal carcinogenesis. Our findings provide an insight into the CD151-involved signaling network in CRC oncogenesis, which could be utilized to design novel targeted therapies against CD151-based signaling in treatment for CRC.

Novel insight into enhanced recoverability of acidic inhibition to anaerobic digestion with nano-bubble water supplementation.

Nano-bubble water (NBW) has been proven to be effective in promoting organics utilization and CH4 production during anaerobic digestion (AD) process, suggesting its potential in improving the stability of the AD process and thereby alleviating acidic inhibition. In this work, the effect of NBW on digestion stability and CH4 production was investigated to evaluate the ability of NBW on AD recovery from acidic inhibition. Results showed that NBW supplementation increased the total alkalinity (TA) and partial alkalinity (PA), and reduced the ratio of VFA/TA, thus maintained the stability of the AD process. Generation/consumption of VFAs was also enhanced with NBW supplementation under acidic inhibition with pH values of 5.5, 6.0 and 6.5. The cumulative CH4 production was 246-257 mL/g-VS in NBW groups, which was 12.1-17.2% higher than the control. Moreover, with NBW supplementation, the maximum CH4 production rate was raised according to the modeling results.

DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3.

Dual oxidase 2 (DUOX2) is an important regulatory protein in the organic process of thyroid hormone iodine. Mounting evidence suggests that DUOX2 plays a crucial role in the occurrence and development of cancers. However, the function and mechanism of DUOX2 in colorectal cancer (CRC) have not been fully clarified. In the present study, the relationship between the expression of DUOX2 and the clinicopathological features and prognosis of CRC patients was analyzed. Furthermore, the effects of DUOX2 on proliferation and invasion in vitro and in vivo were examined. DUOX2-associated proteins were identified by immunoprecipitation (IP). Next-generation sequencing detection was performed to illustrate the mechanism of DUOX2 in CRC cells. It was found that the expression levels of DUOX2 in metastatic sites were significantly higher than those in primary tumor tissues, and this was demonstrated to be associated with poor prognosis. The knockdown of DUOX2 inhibited the invasion and migration of CRC cells. Furthermore, DUOX2 regulated the stability of ribosomal protein uL3 (RPL3) by affecting the ubiquitination status of RPL3, and the invasion and migration ability of DUOX2 can be reversed by the overexpression of RPL3. The downregulation of DUOX2 can affect the expression level of a large number of genes, and a number of these are enriched in the PI3K-AKT pathway. Some of the changes caused by DUOX2 can be reversed by RPL3. In summary, DUOX2 exhibits a significantly higher expression in CRC tumor samples, and facilitates the invasion and metastasis ability of CRC cells by interacting with RPL3.