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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic that has wreaked havoc globally, which has put a heavy toll on public health, lives, and the world economy. Vaccination is considered as one of the greatest successes in medical history. Based on prior experience with the development of SARS-CoV vaccines, all COVID-19 vaccines must be subjected to the tests for protective effects and harmful risks derived from antibody-dependent enhancement that may contribute to augmented infectivity and/or eosinophilic infiltration. The SARS-CoV-2 vaccine is now being developed urgently in several different ways. China is regarded as one of the world's leading countries in SARS-CoV-2 vaccine development, up to date the last inactivated vaccine international clinical (Phase III) trial was launched in the United Arab Emirates by Sinopharm China National Biotec Group (CNBG). In this review, we outline the current status of vaccine development against clinically relevant SARS-CoV-2 strains, anticipating that such attempts would help create efficacious and sage SARS-CoV-2 vaccines.

Nepetalactol, an iridoid with four chiral carbons, is a crucial component of aphid sex pheromones that have been employed with great success to control the insect-related diseases. Despite of agricultural usage as end products, iridoids are fundamental biosynthetic intermediates for pharmaceutically important monoterpenoid indole alkaloids such as camptothecin (CAM) and vinca alkaloids. Herein we characterized 10-hydroxygeraniol oxidoreductase (10HGO) and iridoid synthase (IS) from Camptotheca acuminata, a CAM-producing plant, and reported their application in biological preparation of nepetalactol. Ca10HGO and CaIS were respectively cloned from C. acuminata, overexpressed in Escherichia coli, and purified to homogeneity. Ca10HGO catalyzes the oxidation of 10-hydroxygeraniol into 10-oxogeranial, in which NADP+ was reduced to NADPH. CaIS catalyzes nepetalactol formation from 10-oxogeranial using NADPH cofactor. The net outcome of the two reactions generate nepetalactol from 10-hydroxygeraniol efficiently, indicating NADP+ - NADPH recycling. Ca10HGO and CaIS were co-overexpressed in E. coli under optimized fermentation conditions to prepare cell-based catalysts that catalyze the conversion of 10-hydroxygeraniol into nepetalactol. The present work shows the enzymatic conversion of 10-hydroxygeraniol into nepetalactol involved in CAM biosynthesis. Co-overexpression of Ca10HGO and CaIS in E. coli is an alternative valuable cell-based biotransformation process with regenerating recycling of NADP+ - NADPH cofactors for nepetalactol preparation.

Anthraquinone dyes, which include an anthraquinone chromophore group, are the second-largest among dye classes, which is often employed in textile manufacturing. A significant number of anthraquinone dyes get into the environment, creating severe pollution since many of these dyes have intricate and stable structures. Currently, microbiological treatment of wastewater is an economically and feasibly viable solution for treating printing and dyeing wastewater, and there are growing reports of biodegradation of anthraquinone dyes. In this review, we outline the current advances in the biodegradation of anthraquinone dyes, summarizes dyes biodegradation by bacterial, fungal, and algae strains, factors influencing dyes biodegradation, current methods in enhancing dyes biodegradation, resuscitation of viable but non-culturable (VBNC) bacteria for better microbial performance, and potentials of VBNC bacteria in degrading dyes. Finally, future directions and important areas for study are given, and such efforts are anticipated to improve the anaerobic degradation process.

A series of new naphthalimide derivatives, benzothiophenonaphthalimides (7a-7g, 8a-8g), were designed and synthesized, of which compounds 8a-8g are hydrochloride salts of corresponding compounds 7a-7g. All compounds presented different anti-tumor activities for tumor cells tested by the CCK-8 assay. In particular, compound 7c displayed the strongest anti-tumor activity with an IC

Wnt/β-catenin-mediated signaling is a key pathway regulating tissue growth and development, and tumorigenesis, and has received increasing attention in recent years. In addition to participating in healthy tissue and organ development, ectopic activation of the pathway can cause a variety of tumors and other pathologies. The pathway plays a critical role in many processes such as proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition and cancer cell stemness. The importance of the Wnt signal is self-evident. This review describes the underlying mechanism of Wnt signaling pathway and highlights the latest findings on the relationship between Wnt signaling pathway and tumorigenesis. In addition, the potential relationship between miRNAs and Wnt signaling is presented. Furthermore, we discuss the intrinsic link between Wnt signaling and cancer cell stemness, which shed light on the malignant progression of tumor cells. Finally, cancer treatment strategies based on the canonical Wnt signaling pathway are summarized, hoping to help clinical development.

Graphical abstract, Highlights • Drug repurposing, depicting patented medicines as an effective technique to develop drugs. • Drug repurposing, compared to de novo drug discovery, could shorten the duration and reduce costs. • Remdesivir and Favipiravir, despite having side effects, were more promising drugs for SARS-CoV-2 infection. • Considering the unparalleled morbidity and deaths associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causal factor of the coronavirus disease 2019 (COVID-19). Drug repurposing, portraying patented drugs as a successful drug development technique, could shorten the period and minimize costs relative to de novo drug exploration. Recently several drugs have been used as anti-SARS-CoV-2 such as Remdesivir, Favipiravir, Hydroxychloroquine, Azithromycin, Lopinavir/Ritonavir, Nafamostat mesylate and so on. Despite such efforts, there is currently no successful broad-spectrum antiviral countermeasures to combat SARS-CoV-2 or possibly potential CoVs pandemic. Therefore it is desperately important to recognize and test widely efficient, reliable anti-CoV therapies now and in the future. Remdesivir and Favipiravir were more promising despite having side effects; it had prominent efficacy and efficiency while still not yet approved as the official anti-viral drug for SARS CoV-2. In this review, we summarizes the current drug and vaccine discovery status against SARS-CoV-2, predicting that these efforts will help create effective drugs and vaccines for SARS-CoV-2.

Immune checkpoint blockade has displayed substantial anti-tumor resistance in a variety of forms of cancer, but the fundamental regulation role remains unclear, and several questions continue to be addressed. PD-1/PD-L1 has been recognized as an anti-cancer drug target for several years, and through targeting the PD-1/PD-L1 signaling pathway, many monoclonal antibodies have thus far produced promising results in cancer therapy. The discovery of small-molecule inhibitors focused on the PD-1/PD-L1 signaling pathway is steadily reviving over decades, owing to the intrinsic shortcomings of the antibodies. PD-1 function and its PD-L1 or PD-L2 ligands are essential for the activation, proliferation, and cytotoxic secretion of T-cells in cancer to degenerate anti-tumor immune response. The axis PD-1/PD-L1 is important for the immune escape of cancer which has an immense impact on cancer treatment. In this review, we summarize the function of PD-1 and PD-L1 in cancer and aiming to enhance cancer therapy.

The outbreak of the coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pandemic apparently started in December 2019 in Wuhan, China, and has since affected many countries worldwide, turning into a major global threat. Chinese researchers reported that SARS-CoV-2 could be classified into two major variants. They suggest that investigating the variations and characteristics of these variants might help assess risks and develop better treatment and prevention strategies. The two variants were named L-type and S-type, in which L-type was prevailed in an initial outbreak in Wuhan, Central China's Hubei Province, and S-type was phylogenetically older than L-type and less prevalent at an early stage, but with a later increase in frequency in Wuhan. There were 149 mutations in 103 sequenced SARS-CoV-2 genomes, 83 of which were nonsynonymous, leading to alteration in the amino acid sequence of proteins. Much effort is currently being devoted to elucidate whether or not these mutations affect viral transmissibility and virulence. In this review, we summarize the mutations in SARS-CoV-2 during the early phase of virus evolution and discuss the significance of the gene alterations in infections.

Wnt/β-catenin-mediated signaling is a key pathway regulating tissue growth and development, and tumorigenesis, and has received increasing attention in recent years. In addition to participating in healthy tissue and organ development, ectopic activation of the pathway can cause a variety of tumors and other pathologies. The pathway plays a critical role in many processes such as proliferation, differentiation, apoptosis, migration, invasion, epithelial–mesenchymal transition and cancer cell stemness. The importance of the Wnt signal is self-evident. This review describes the underlying mechanism of Wnt signaling pathway and highlights the latest findings on the relationship between Wnt signaling pathway and tumorigenesis. In addition, the potential relationship between miRNAs and Wnt signaling is presented. Furthermore, we discuss the intrinsic link between Wnt signaling and cancer cell stemness, which shed light on the malignant progression of tumor cells. Finally, cancer treatment strategies based on the canonical Wnt signaling pathway are summarized, hoping to help clinical development.

Nepetalactol, an iridoid with four chiral carbons, is a crucial component of aphid sex pheromones that have been employed with great success to control the insect-related diseases. Despite of agricultural usage as end products, iridoids are fundamental biosynthetic intermediates for pharmaceutically important monoterpenoid indole alkaloids such as camptothecin (CAM) and vinca alkaloids. Herein we characterized 10-hydroxygeraniol oxidoreductase (10HGO) and iridoid synthase (IS) from Camptotheca acuminata, a CAM-producing plant, and reported their application in biological preparation of nepetalactol. Ca10HGO and CaIS were respectively cloned from C. acuminata, overexpressed in Escherichia coli, and purified to homogeneity. Ca10HGO catalyzes the oxidation of 10-hydroxygeraniol into 10-oxogeranial, in which NADP

Coronavirus (CoV) has been one of the major pandemic threats to human health in the last two decades. The human coronavirus was first identified in 1960s. CoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV have caused numerous disasters or human deaths worldwide. Recently, an outbreak of the previously unknown deadly CoV disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome CoV 2 (SARS-CoV-2, early named 2019-nCoV) occurred in Wuhan, China, and it had caused 81238 cases of confirmed infection, including 3250 deaths until March 19, 2020. Its risks and pandemic potential have brought global consideration. We summarized epidemiology, virological characteristics, clinical symptoms, diagnostic methods, clinical treatments, and prevention methods for COVID-19 to present a reference for the future wave of probable CoV outbreaks.

Aims This study aimed to evaluate the ability of compound 13d to induce autophagy and to promote apoptosis of tumor cells and its interaction mechanism. Materials and methods Using CCK-8 assay, transwell assay, fluorescence resonance energy transfer melting analysis (FRET), transmission electron microscopy, flow cytometry assay, immunofluorescence assay, Western blot analysis, and wound healing assay. Key findings The results indicated that compound 13d could induce autophagy and apoptosis of gastric cancer cells. Moreover, the findings of CCK-8 assay, colony formation, migration and invasion assay, and wound healing assay revealed that compound 13d would effectively inhibit cell proliferation, migration, and invasion. Its IC50 value is about 2.4 μM against gastric cancer cells, which is similar to positive drug‑platinum. 13d specific induction of telomere G-quadruplex formation was proved in extracellular FRET melting assay, and indirectly affected telomerase activity. G-quadruplex formation promoted cell apoptosis and autophagy. Upon incorporating the autophagy inhibitors 3-MA and HCQ, the expression of the autophagy marker protein LC3 was then checked, suggesting that the compound 13d influences the autophagy flux. Furthermore, knocking down the autophagy-related gene Atg5 to reduce the level of autophagy enhances the anti-tumor activity and increases apoptotic cells' proportion. Mechanistic experiments have shown that blocking the Akt/m-TOR signal pathway plays a crucial role in autophagy and G-quadruplex induced telomere dysfunction. DNA damage is the leading cause of autophagy. Compound 13d combined with autophagy inhibitor can inhibit tumor cells more effectively. Significance Our findings demonstrate that compound 13d as a telomeric G-quadruplex ligand induces Telomere dysfunction, DNA damage response, autophagy, and apoptosis in gastric cancer cells by blocking the Akt/m-TOR signaling pathway.

The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019, and its global dissemination became the coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) on 11 March 2020. In patients undergoing immunotherapy, the effect and path of viral infection remain uncertain. In addition, viral-infected mice and humans show T-cell exhaustion, which is identified after infection with SARS-CoV-2. Notably, they regain their T-cell competence and effectively prevent viral infection when treated with anti-PD-1 antibodies. Four clinical trials are officially open to evaluate anti-PD-1 antibody administration's effectiveness for cancer and non-cancer individuals influenced by COVID-19 based on these findings. The findings may demonstrate the hypothesis that a winning strategy to combat SARS-CoV-2 infection could be the restoration of exhausted T-cells. In this review, we outline the potential protective function of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 therapy., Graphical Abstract ga1

Coumarins are naturally evolving molecules that have a wide variety of activities. In medical chemistry and chemical biology, their structural and physicochemical properties make them a suitable scaffold. Herein, we designed and synthesized novel coumarin analogues-7-O-substituted pyridyl-4-methyl naphthopyrone derivatives and initially evaluated their anti-cancer activity. RTCA profiling reveals that compounds 6, 7 and 8, in particular 7, possess stronger in vitro cytotoxicity for A549 cells. All synthesized compounds have been characterized by 1H NMR spectra, elemental analysis, and mass spectrometry.

Hepatocellular carcinoma (HCC) ranks in the top of cancers leading to death. Early diagnosis is the big challenge in the case of HCC. Our in vitro study showed that Ezrin expression in lymphatic metastasis hepatocellular carcinoma (LNM-HCC) was associated with the metastatic rate. Here we aim to evaluate Ezrin expression as diagnostic and/or prognostic biomarker of LNM-HCC in mice. Chinese inbred 615 mice, Hca-F and Hca-P cell lines were used in the study. Histological changes were determined by Hematoxylin and Eosin, while Ezrin expression was assessed by qRT-PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assay. Ezrin expression in this study gives credit to our in vitro study which Ezrin expression was positively correlated with LNM-HCC and negatively with Annexin7 (A7) expression. The highest histological changes were observed in high metastatic primary/secondary tumors combined with high Ezrin expression. Ezrin and A7 are higher in total primary tumors than in total secondary tumors (P = 0.0001, P = 0.021), respectively. Ezrin expression was enhanced in Hca-P A7 down-regulated primary/secondary tumors (P = 0.004), whereas, Ezrin expression was suppressed in Hca-F A7 upregulated primary/secondary tumors. Serum ELISA indicated differential expression of Ezrin among the study groups (P ≤ 0.0001). Ezrin expression was higher in NC-Hca-F than NC-Hca-P (P ≤ 0.0001), suppressed in Hca-F A7 upregulation (P ≤ 0.0001) and in enhanced in Hca-P A7 down-regulation (P = 0.0001). In conclusion, Ezrin level may serve as a differential diagnostic and/or prognostic biomarker for high and low LNM-HCC and may be beneficial in the diagnosis of HCC disease. © 2017 BioFactors, 43(5):662-672, 2017.

Aims This study aimed to investigate the effect of previously synthesized 4,5-diazafluorene derivative (14c) on γδ T cell-mediated cytotoxicity against renal cell carcinoma (RCC). Materials and methods A real-time cell analyzer monitored cell proliferation, and Cell Counting Kit-8 determined cell viability. A reverse transcription-polymerase chain reaction analyzed gene expression, and protein expression was determined by cellular immunofluorescence analysis and Western blot. Key findings The compound 14c induced the expression of immunomodulatory molecules, such as natural killer group 2, member D ligands (NKG2DLs), fibroblast-associated (Fas) death receptor, and tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAILRs) in RCC. In addition, 14c induced DNA damage responses in RCC. Blocking DNA damage by KU-55933 reduced the effect of γδ T cells on 14c-treated RCC, suggesting that DNA damage responses were involved in the augmentation of γδ T cell-mediated cytotoxicity. Treating 786-O cells with a nitrogen-containing bisphosphonate prodrug further enhanced the anti-tumor effect of γδ T cell plus 14c combination treatment. Significance The present evidence indicates that 14c induced DNA damage responses in RCC and augmented γδ T cell-mediated cytotoxicity primarily through NKG2D/NKG2DLs pathways, suggesting potential cancer immunotherapy for harnessing γδ T cells and small compounds that induce DNA damage responses.

Pyrrole-imidazole polyamide (PIP) can specifically bind in the B-DNA minor groove that has been used in several biological applications, such as anti-cancer activity, gene expression and translation control, and visualization of complex genomic areas. c-kit is a family member of the Tyrosine Kinase (RTK) type III receptor and plays a vital role in tumor growth, proliferation, differentiation, and cell apoptosis; however, its mutations and overexpression induce tumor dysfunction. Here, we designed and synthesized five matched PIPs that can recognize and bind to the DNA sequence in the oncogene c-kit promoter region, and evaluated their anti-cancer activity. The RTCA assay findings revealed that the PIPs would prevent the proliferation of cancer cells A549 and SGC-7901. EMSA assay showed that the PIPs were actively interacting with the c-kit gene target DNA. RT-PCR and Western blot assays have an effect on expression levels of the c-kit gene in the presence of PIPs. Flow cytometry and wound-healing assays showed that PIPs 4, 5 would cause apoptosis of cancer cells and inhibit the migration of cells, respectively. Overall findings indicate that PIP 5 has a relatively significant intracellular and extracellular impact on the target, contributing to migration and proliferation reduction, and cancer cell apoptosis. In addition, PIP has a certain ability to evolve into c-kit gene-targeting drugs.

Background/Aim Probiotics have been suggested as prophylactic measure in colon carcinogenesis. This study aimed at determining the potential prophylactic activity of Lactobacillus rhamnosus GG CGMCC 1.2134 (LGG) strain on colorectal carcinogenesis via measuring its effect on Nuclear factor kappa B (NFκB) inflammatory pathway and apoptosis. Materials and methods 64 Sprague Dawley rats were grouped into four as follows; Group 1 (Healthy control), Group 2 (LGG), Group 3 (cancer control Dimethyl hydrazine (DMH)) and Group 4 (LGG + DMH). LGG was administered orally to LGG and LGG + DMH groups. Colon carcinogenesis was chemically induced in LGG + DMH and DMH groups by weekly injection of 40 mg/kg DMH. Animals were sacrificed after 25 weeks of experiment and tumor characteristics assessed. The change in expression of NFκB-p65, COX-2, TNFα, Bcl-2, Bax, iNOS, VEGFα, β-catenin, Casp3 and p53 were evaluated by western blotting and qRT-PCR. Results LGG treatment significantly reduced tumor incidence, multiplicity and volume in LGG + DMH treatment group compared to DMH cancer control group. Also, LGG treatment reduced the expression of β-catenin and the inflammatory proteins NFκB-p65, COX-2 and TNFα; the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic proteins Bax, casp3 and p53 compared with DMH group. Conclusion LGG have a potential protection effect against colon carcinogenesis; inducing apoptosis and ameliorating inflammation, and may hold a promise as bio-therapeutic dietary agent.

Aims This study aimed to analyze the impact of four synthesized benzoxazinone derivatives as screening drugs on c-Myc-overexpressed cancer cells (H7402, HeLa, SK-RC-42, SGC7901, and A549) and to explore their interaction mechanisms in detail. Materials and methods Using morphological analysis, real-time cytotoxicity analysis, wound healing assay, reverse transcription PCR, electrophoretic mobility shift assay, and circular dichroism spectroscopy techniques. Key findings Results revealed that these four compounds could inhibit proliferation of SK-RC-42, SGC7901, and A549 cells in five cancer cell lines to varying degrees and significantly hinder migration. More importantly, the RT-PCR assay showed that the compounds could surprisingly downregulate the expression of c-Myc mRNA in a dose-dependent manner in the five cancer cells, which may be one of the causes of cancer cell proliferation in vitro inhibition. Further EMSA assays demonstrated that at the molecular level of DNA, four compounds can induce the formation of G-quadruplexes (G4-DNAs) in the c-Myc gene promoter. In addition, the CD result of compound 1 clearly indicates that it specifically induces a c-Myc GC-rich 36mer double-stranded DNA in the c-Myc promoter to form a G-quadruplex hybrid configuration. In conclusion, the compounds studied could dose-dependently inhibit the growth and migration of the cancer cells being investigated. This is positively associated with the reduction of overexpression of the c-Myc gene, which may be significantly regulated by the association of compounds with the G-quadruplexes produced in the c-Myc gene promoter region. Significance We conclude that three compounds merit further study, particularly against non-small-cell lung cancer, as leading compounds of anticancer drugs.

Figure S3. Grx6 catalyses for the chemical reduction of glutathione (GSH) and NADP(+), which forms glutathione disulfide (GSSG), NADPH and FAD. The Grx6s contain cysteine in their active site making them suitable for oxidation/reduction reactions (Fig. 2). Whereas ScGrx6 can reduce ROS in the cytoplasm, ScGrx6 has the ability to reduce NADP(+) and ScGrx6 catalyses S-glutathionylation to protect SH-groups from oxidation and restore functionally active thiols. ScGrx6 catalyses the reaction only via a monothiol mechanism. Additionally, it has been suggested to have antioxidant capabilities, but their mechanisms are less understood. (PDF 3599 kb)

Figure S1. Hydrophobic interaction between the two subunit of ScGrx6. The distance between two Tyr138 residues is approximately 4.1Â Ă , which is small enough for their hydrophobic interaction. The hydrophobic interaction between hydrophobic side chains of Tyr138 from both subunits in the interface contributes to the formation of the dimeric interface and helps to stabilize the cluster by reducing the solvent accessibility. (PDF 148 kb)

Table S2. Enzymes cleaving ScGrx6 and the positions of cleavage sites. (DOCX 16 kb)

Figure S2. Ramachandran plot for the predicted model of dimer (A) and monomer (B) of ScGrx6. All residues are in the allowed regions. The Ramachandran plots were performed for quality assessment. Only 120 (52%) of the total 231 residues were present for both dimer and monomer in the disallowed region, whereas no other residues were present in the generously allowed regions (Fig. 2). G-factors provide a measure of how unusual a stereochemical property is. Values below − 1.0 represent high unusualness, while values below − 0.5 represent the unusual property. The G-factors for main chain covalent forces and dihedral angles were calculated to be 0.42 and − 0.44, respectively for the dimer, while the G-factors for main chain covalent forces and dihedral angles were calculated to be 0.50 and − 0.41, respectively for the monomer. The overall average G-factor for the dimer was 0.19, and it was 0.28 for the monomer. The Ramachandran plot and G-factors indicate that the backbone dihedral angles, phi, and psi, in the 3D model of dimer and monomer are well within acceptable limits. The Root Mean Square Deviation (RMSD) indicates the degree to which two 3D structures are similar; the lower the value, the more similar the structures. Both template and query structures were superimposed for the calculation of RMSD (Fig. 4). The RMSD value obtained from the superimposition of dimer and monomer using PyMOL view was found to be 0.3 Å over a total of 120 aligned residues. The overall quality factor, Ramachandran plot characteristics, G-factors and RMSD values confirm the quality of the dimer. (PDF 2886 kb)

Table S1. Site-directed mutagenesis primers. (DOCX 14 kb)

Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-α and -γ at the doses of 100 (P 0.05), when compared with cyclophosphamide treatment, as a positive control. Additionally, cytokine production associated with T helper (Th)2 and Th17 cells was enhanced compared with that of Th1 cytokines, and the immunomodulatory function of CVG appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has promise in supporting cancer therapies.

Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, −4, −6, −10, −17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, −4, −6, −10, −17A and IFN-α and -γ at the doses of 100 (P0.05), when compared with cyclophosphamide treatment, as a positive control. Additionally, cytokine production associated with T helper (Th)2 and Th17 cells was enhanced compared with that of Th1 cytokines, and the immunomodulatory function of CVG appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has promise in supporting cancer therapies.

Hepatocellular carcinoma (HCC) ranks in the top of cancers leading to death. Early diagnosis is the big challenge in the case of HCC. Our in vitro study showed that Ezrin expression in lymphatic metastasis hepatocellular carcinoma (LNM-HCC) was associated with the metastatic rate. Here we aim to evaluate Ezrin expression as diagnostic and/or prognostic biomarker of LNM-HCC in mice. Chinese inbred 615 mice, Hca-F and Hca-P cell lines were used in the study. Histological changes were determined by Hematoxylin and Eosin, while Ezrin expression was assessed by qRT-PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assay. Ezrin expression in this study gives credit to our in vitro study which Ezrin expression was positively correlated with LNM-HCC and negatively with Annexin7 (A7) expression. The highest histological changes were observed in high metastatic primary/secondary tumors combined with high Ezrin expression. Ezrin and A7 are higher in total primary tumors than in total secondary tumors (P = 0.0001, P = 0.021), respectively. Ezrin expression was enhanced in Hca-P A7 down-regulated primary/secondary tumors (P = 0.004), whereas, Ezrin expression was suppressed in Hca-F A7 upregulated primary/secondary tumors. Serum ELISA indicated differential expression of Ezrin among the study groups (P ≤ 0.0001). Ezrin expression was higher in NC-Hca-F than NC-Hca-P (P ≤ 0.0001), suppressed in Hca-F A7 upregulation (P ≤ 0.0001) and in enhanced in Hca-P A7 down-regulation (P = 0.0001). In conclusion, Ezrin level may serve as a differential diagnostic and/or prognostic biomarker for high and low LNM-HCC and may be beneficial in the diagnosis of HCC disease. © 2017 BioFactors, 43(5):662-672, 2017.

Cancer is one of the most common causes of deaths worldwide. Herein, we report an efficient natural anticancer glucan (CVG) extracted from Coriolus Versicolar (CV). CVG was extracted by the hot water extraction method followed by ethanol precipitation and purified using gas exclusion chromatography. Structural analysis revealed that CVG has a linear α-glucan chain composed of only (1→ 6)-α-D-Glcp. The antitumor activity of CVG on Sarcoma-180 cells was investigated in vitro and in vivo. Mice were treated with three doses of CVG (40, 100, 200 mg/kg body weight) for 9 days. Tumor weight, relative spleen, thymus weight, and lymphocyte proliferation were studied. A significant increase (P< 0.01) in relative spleen and thymus weight and a decrease (P< 0.01) in tumor weight at the doses of 100 and 200 mg/kg were observed. The results obtained demonstrate CVG has antitumor activity towards Sarcoma-180 cells by its immunomodulation activity.

The physicochemical properties of the natural Gum are very important in determining their commercial value and their use. Herein, the present study aims to identify differences in physicochemical properties of Kakamut Gum (Acacia polyacntha) and Hashab Gum (Acacia Senegal). Samples of Gums were collected as follows: Kakamut Gum from Um fakarin forest and Hashab Gum from Eldemokeya forest, North Kordofan State 2008 – 2009. The two samples were subjected to laboratory analyzed in Warm Seas Agro Business, Elobeid Agricultural Research Station, and Sudanese Standards and Metrology Organization. The study revealed that there were significant differences (p < 0.01) in moisture (dry matter) and optical rotation. Also, significant differences (p < 0.05) were found in the percentage of ash content and viscosity. However, there were no significant differences found in the percentage of the crude fiber, nitrogen (protein), pH, and purity between the two samples. The results obtained demonstrate clearly the physical and chemical characteristics of the two Gums samples and also, throw lights on their nutritional purposes. As well as the study of the physicochemical properties of Kakamut Gum and compare it with Hashab Gum, proved the potential contribution of the Kakamut tree (Acacia Polyacantha) in the Gum production and not depend solely on the Gum produced from the Hashab tree (Acacia Senegal).

Structural change in the gut microbiota is implicated in cancer. The beneficial modulation of the microbiota composition with probiotics and prebiotics prevents diseases. We investigated the effect of oligofructose–maltodextrin-enriched Lactobacillus acidophilus, Bifidobacteria bifidum, and Bifidobacteria infantum (LBB), on the gut microbiota composition and progression of colorectal cancer. Sprague Dawley rats were acclimatized, given ampicillin (75 mg/kg), and treated as follows; GCO: normal control; GPR: LBB only; GPC: LBB+ 1,2-dimethylhydrazine dihydrochloride (DMH); and GCA: DMH only (cancer control). 16S V4 Pyrosequencing for gut microbiota analysis, tumor studies, and the expression of MUC2, ZO-1, occludin, TLR2, TLR4, caspase 3, COX-2, and β-catenin were conducted at the end of experiment. Probiotic LBB treatment altered the gut microbiota. The relative abundance of genera Pseudomonas, Congregibacter, Clostridium, Candidactus spp., Phaeobacter, Escherichia, Helicobacter, and HTCC was decreased (P