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Spirulina polysaccharides (PSP) possess significant biological properties. However, it is still a lack of investigation on the anti-colorectal cancer effect and mechanism. In this study, PSP showed significant effects on LoVo cell spheroids with an IC 50 value of 0.1943 mg/mL. The analysis of transcriptomics and metabolomics indicated the impact of PSP on LoVo spheroid cells through involvement in the two pathways of "glycine, serine, and threonine metabolism" and "ABC transporters". And, the q-PCR data further verified the pointed mechanism of PSP on colon cancer (CC) by regulating the expression levels of relevant genes in the synthesis pathways of serine and glycine in tumor cells. Furthermore, the anti-colon cancer effects of PSP were verified via other human colon cancer cell lines HCT116 and HT29 spheroids (IC 50  = 0.0646 mg/mL and 0.2213 mg/mL, respectively), and three patient-derived organoids (PDOs) with IC 50 values ranging from 3.807 to 7.788 mg/mL. In addition, this study found that a mild concentration of PSP cannot enhance the anti-tumor effect of 5-Fu. And a significant inhibition was found of PSP in 5-Fu resistance organoids. These results illustrated that PSP could be a treatment or supplement for 5-Fu resistant colorectal cancer (CRC)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Until now, relatively little is known about marine-derived fungal polysaccharides and their activities. Exopolysaccharide AVP141-A was isolated from the broth of marine-derived fungus Aspergillus versicolor SCAU141 and purified by Diethylaminoethyl-Sepharose Fast Flow and Sephadex G-100. The structural characteristics of AVP141-A was studied by chemical analysis together with high-performance gel permeation chromatography, ion chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The results showed that AVP141-A with the molecular weight of 5.10 kDa was mainly composed of →4)-α-D-Glcp-(1→, branched by α-D-Glcp-(1→ and →6)-α-D-Glcp-(1→ at C-6 positions of the glucan backbone. In particular, sulfate ester (approximately 3.62 %) was found in AVP141-A, which was frequently considered to occur in marine-derived microbial polysaccharides rather than other microbial polysaccharides. Furthermore, AVP141-A significantly enhanced the activity of the inflammatory factors NO, COX-2 and TNF-α in RAW264.7 macrophages by activating the MAPK/p38 and NF-κB/p65 pathways. In addition, metabolomic analysis revealed that most of the pathways with significant changes in RAW264.7 macrophages treated with AVP141-A were amino acid-related pathways, and arginine was the characteristic metabolite. In conclusion, this study identified AVP141-A as a marine fungus-derived sulfated exopolysaccharide with potential for development as an immune activator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Oxidative stress in plants caused by UV-B stress has always been a great challenge to the yield of agricultural products. Carbon dots (CDs) with enzyme-like activity have been developed, and inhibiting oxidative stress in animals has been achieved, but little is known about abiotic stress resistance in plants, especially UV-B stress. In this study, CDs were synthesized from Scutellaria baicalensis via a hydrothermal method. The ability of CDs to scavenge reactive oxygen species (ROS) in vivo and in vitro and to enhance antioxidant resistance in vivo was evaluated. The results show that CDs promoted the nutrient assimilation ability of lettuce seedlings and protected the plants from UV-B stress by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase (APX). Moreover, the antioxidant metabolism of plants can be activated by CDs and the expression levels of aquaporin (AQP) genes PIP1 and PIP2 are also up-regulated. These results facilitate the design and fabrication of CDs to meet the challenge of abiotic stress in food production., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic is a toxic heavy metal widely found in the natural environment and has adverse effects on the health of waterfowl and human. Curcumin (CUR), a natural pigment of the golden spice turmeric, exhibits excellent anti-tumor, anti-inflammatory and anti-oxidant activities. But the effects of CUR on duck spleen exposed to arsenic remain largely unknown. In this study, 75 ducks were divided randomly into Control, L-ATO, M-ATO, H-ATO and CUR + H-ATO groups to systematically analyze the underlying role of CUR. The results showed that arsenic trioxide (ATO) led to growth retardation of ducks, hyaline degeneration and sparse cell arrangement on their spleen. And in the ATO-exposed ducks, the levels of immunoglobulins (Ig; IgA, IgG, IgM) in the serum and the expression of autophagy-related genes (Atg5, P62, LC3I, LC3II, LC3II/I, Beclin-1) were significantly upregulated compared with the control ducks. Moreover, ATO also activated NF-κB signal pathway and upregulated the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-18). Meanwhile, application of CUR alleviated the ATO toxicity with the release of growth inhibition, and the reduced hyaline degeneration and distortion of the spleen capsule. CUR also suppressed ATO-induced NF-κB activation, pro-inflammatory cytokine addition and expression of autophagy-related genes. Overall, these results suggested that CUR might exert a protective effect against ATO-induced immunosuppression in ducks via anti-inflammation and autophagy restoring., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The gut microbiota dysbiosis is a state which the physiological combinations of flora are transformed into pathological combinations caused by factors such as diets, pollution, and drugs. Increasing evidence shows that dysbiosis is closely related to many diseases. With the continuous development and utilization of marine resources, marine polysaccharides have been found to regulate dysbiosis in many studies. In this review, we introduce the types of dysbiosis and the degree of it caused by different factors. We highlight the regulating effects of marine polysaccharides on dysbiosis as a potential prebiotic. The mechanisms of marine polysaccharides to regulate dysbiosis including protection of intestinal barrier, regulatory effect on gut microbiota, alteration for related metabolites, and some other possible mechanisms were summarized. And we aim to provide some references for the high-value utilization of marine polysaccharides and new targets for the treatment of gut microbiota dysbiosis by this review., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

A polysaccharide obtained from Spirulina (PSP) and its effect on lung cancer in mice was investigated. Our results indicate that the tumor volume and weight of the lung cancer-bearing mice treated with PSP decreased significantly. Metabolite analysis showed that 27 differential accumulated metabolites (DAMs) changed significantly, in which 24 DAMs increased while 3 DAMs decreased. KEGG enrichment results showed that these differential metabolites were enriched significantly in the high-affinity IgE receptor (FcεRI) signaling pathway and arachidonic acid metabolism. In addition, PSP modulated gut microbiota of the lung cancer-bearing mice. PSP increased the abundance of Lactobacillus , Allobaculum , Alloprevotella , and Olsenella , decreasing Bacteroides and Acinetobacter . The results might be related to suppressing lung cancer. Based on our study, we hypothesized that PSP inhibited lung cancer through FcεRI signaling pathway and arachidonic acid metabolism and regulated the balance of gut microbiota. Nevertheless, the relationship between these two pathways and gut microbiota needs further study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V.)

Ducklings is one of the most susceptible poultry to Aflatoxin B1 (AFB1) which widely existed in duckling products will also in turn affect human health. Curcumin (CUR) has significant effects on immune regulation and anti-oxidation. But whether CUR alleviates toxic effects on duckling spleen induced by AFB1 remains largely unknown. In this study we treated duckings with AFB1 and CUR for 21 days before harvesting serum and spleen tissue for analyses. The results showed that AFB1 damaged the spleen tissue of ducklings by activating the NF-κB signaling pathway. And the addition of CUR not only promoted the growth of ducklings, but also enhanced the immune function of the spleen and reduced the damage of AFB1 to the spleen tissue. At the same time, CUR activated the Nrf2 signaling pathway, upregulated the expression of related antioxidant enzymes, inhibited the NF-kB signaling pathway, and ultimately reducing the inflammation of the duckling spleen induced by AFB1. It has been suggested from these results that Nrf2 pathway might be a potential therapeutic target for CUR to treat AFB1-induced immunosuppression in ducklings., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Arsenic trioxide (ATO) has confirmed as a global pollutant, the toxic effect of which was not fully understood and lack effective therapies to against its associated toxicities. Curcumin (Cur) is a beneficial natural pigment for its antioxidant and anti-inflammatory properties. The purpose of this paper was to illustrate the antagonism of Cur against ATO-induced neurotoxicity. A total of 40 ducks were divided randomly into 4 groups and conducted via bite and sup for 28 days: control group (Control); 2 mg/kg ATO group (Low ATO); 4 mg/kg ATO group (Middle ATO); 8 mg/kg ATO group (High ATO); 400 mg/kg Cur group + 8 mg/kg ATO (Cur+ATO). The results showed that ATO exposure can hinder the duck growth and arsenic element accumulation rate increased in a dose-dependent manner. We observed neuronal shrinkage and vacuolize of HE staining in the ATO-treated group. In addition, SOD activity and T-AOC level reduced while MDA content increased in the ATO-exposed group. ATO exposure can decrease the expression of anti-oxidation related mRNA and proteins (Nrf2, SOD-1, GPX-1, CAT, Trx and HO-1) and anti-inflammatory makers (IL-4, IL-10), increased the expression of Keap1, NF-κB and pro-inflammatory makers (TNF-α, IL-1β, IL-18, IL-2, IL-6, INOS and COX-2). ATO treated might cause blood-brain barrier (BBB) damage through degradation of the tight junction proteins (TJs) occludin and ZO-1. Importantly, the experimental results also showed that Cur can alleviate oxidative stress, inflammatory response and BBB injury caused by ATO exposure through Nrf2 and NF-κB signaling pathway. The results suggested Cur exerted as a food additive and provided novel potential benefits of ATO toxicology in inflammation of the brain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic trioxide (ATO) and antimony (Sb) are well-known ubiquitous environmental contaminants and cause unpromising male reproductive effects in target and non-target exposed organisms. The main objective of this study was to investigate the effects of ATO or/and Sb on process of autophagy, apoptosis, and reproductive organ in adult mice. For this reason, a total of 32 adult mice were randomly divided into different groups like control group, ATO-treated group, Sb-treated group, and combined group. The duration of current experimental trial was 2 months. Various adverse effects of ATO or/and Sb on sperm parameters, oxidative stress, autophagy, and apoptosis were determined in testis of mice. Results indicated that parameters of sperm quality for organ coefficient, sperm count, ratio of sperm survival, testosterone level, and germ cells were significantly decreased, while malformation rate and vacuolization significantly increased in mice exposed to different treatments. Furthermore, the status of antioxidant index of T-AOC, SOD, and MsrB1 levels was reduced, while MDA increased significantly in ATO + Sb group. Results on TEM investigation determined that the autophagosomes, autolysosome, nuclear pyknosis, and chromatin condensation were prominent ailments, and the levels of autophagy and pro-apoptosis indictors including Beclin1, Atg-5, LC3B/LC3A, caspase-8, cytc, cleaved caspase-3, p53, and Bax were up-regulated in treated group, while the content of an anti-apoptosis maker (Bcl-2) was down-regulated. In conclusion, the results of our experiment suggested that abnormal process of autophagy and apoptosis was triggered by arsenic and antimony, and intensity of toxic effects increased in combined treatments of ATO and Sb., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with As 2 O 3 (4 mg/kg), SbCl 3 (15 mg/kg) and co-treat with SbCl 3 (15 mg/kg) and As 2 O 3 (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca 2+ release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca 2+ uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Two novel polysaccharides, namely CMPP-1 and CMPP-2, from kiwano (Cucumis metuliferus) peels were isolated through hot-water extraction, followed by ethanol precipitation and column chromatography. The results showed that CMPP-1 and CMPP-2 were hetero-galacturonans with different molecular weights of 7.35 kDa and 6.90 kDa, respectively. Both of CMPP-1 and CMPP-2 were mainly composed of glucuronic acid (45.93 % and 51.75 %, respectively), and other monosaccharides including rhamnose, arabinose, galactose, glucose, xylose, fucose, mannose, galacturonic acid, and mannuronic acid. The results of structural characterization from FT-IR and NMR confirmed that CMPP-1 and CMPP-2 were pectin with highly branched structure. Furthermore, both CMPP-1 and CMPP-2 possessed immune-enhancing activity and could enhance the secretion of nitric oxide and cytokines (TNF-α, IL-6) in a dose-dependent manner. Especially, CMPP-1 had higher immune activity than CMPP-2 as the minimum effective concentration were 0.78 μg/mL and 6.25 μg/mL, respectively. These findings provide a scientific basis for further utilization of polysaccharide from kiwano peels., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known., Methods: The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model., Results: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway., Conclusions: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.

Arsenic trioxide (ATO), a trivalent arsenic compound, is known to disrupt redox homeostasis. Methionine sulfoxide reductases (Msrs), a group of antioxidant proteins, convert methionine sulfoxide back to methionine in living organisms exposed to oxidative stress. The objective of this study was to determine the effects of ATO on oxidative stress and the expressions of Msrs in mouse liver. Sixty male mice were randomly divided into six equal groups: one control group and five groups that received ATO treatment (0.3, 1, 3, 6, and 9 mg/kg, respectively). After a 4-week treatment, livers specimens were collected and assayed for malonyldialdehyde (MDA) content, superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) activity. In addition, the mRNA expressions of SOD-1 and HO-1 and the mRNA and protein expressions of Msrs were also determined. Results showed that the T-AOC activity, SOD activity, and SOD-1 mRNA expression were significantly decreased (P < 0.01), while the GSH-Px level, MDA content, and HO-1 mRNA expression were significantly increased in mice treated with ATO compared with control. Levels of MsrB2 mRNA and MsrA protein were significantly increased by ATO treatment, except in the highest dose group. There were no significant changes in MsrB3 mRNA level. ATO, at 1 or 3 mg/kg, increased MsrB1 expression. Modifications in MsrA protein level were consistent with changes in mRNA levels. Collectively, our results suggest that ATO induced oxidative stress and then led to the variations in Msrs activity in mouse liver.

Copper (Cu) is an essential trace element for most organisms. However, excessive Cu can be highly toxic. The purpose of this study was to elucidate the mechanism underlying Cu toxicity in the kidneys of rats after treatment with CuCl 2 (15 [control], 30, 60, or 120 mg/kg in the diet) for 180 days. Histological and ultrastructural changes, antioxidant enzyme activity, and the mRNA and protein levels of apoptosis and autophagy-related genes were measured. The results showed that Cu exposure led to significant accumulation of copper in kidneys and disorganized kidney morphology. The activities of total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) in the kidneys decreased significantly, while the malondialdehyde (MDA) content increased. Furthermore, excessive Cu markedly upregulated the expression of autophagy and apoptosis-related genes (LC3A, LC3B, ATG-5, Beclin-1, Caspase3, CytC, P53, Bax), but downregulated the expression of P62, mTOR and BCL-2. Moreover, the LC3B/LC3A, ATG-5, Beclin-1, P53, Caspase3 proteins were up-regulated while P62 was down-regulated in the kidney tissues of the treatment groups. Overall, these findings provide strong evidence that excess Cu can trigger autophagy and apoptosis via the mitochondrial pathway by inducing oxidative stress in rat kidneys., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aflatoxin B 1 (AFB 1 ) causes hepatotoxic, genotoxic, and immunotoxic effects in a variety of species. Although various neutralizing agents of AFB 1 toxicity have been studied, the egg yolk immunoglobulin (IgY) detoxification of small molecular toxins and the mechanisms underlying such effects have not yet been reported. In this investigation, anti-AFB 1 IgY against AFB 1 was successfully raised, and a competitive indirect enzyme-linked immunosorbent assay was established with a sensitive half-maximal inhibitory concentration (IC 50, 2.4 ng/mL) and dynamic working range (0.13-43.0 ng/mL). The anti-AFB 1 IgY obtained reduced AFB 1 -induced cytotoxicity, cellular dysfunction, and genotoxicity by protecting cells against apoptotic body formation and DNA strand breaks, preventing G2/M phase cell cycle arrest, reducing AFB 1 -DNA adduct and reactive oxygen species production and maintaining cell migration and invasion and the mitochondrial membrane potential. Anti-AFB 1 IgY significantly inhibited the AFB 1 -induced expression of proteins related to antioxidative, pro-apoptotic, and antiapoptotic processes in a strong dose-dependent manner. These experiments demonstrated that the anti-AFB 1 IgY-bound AFB 1 could not enter cells. This is the first time that IgY has been found to reduce the effects of small molecular toxins, which will be beneficial for the development of antibodies as detoxication agents.