Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently found cancer in the world, and it is frequently discovered when it is already far along in its development. About 20% of cases of CRC are metastatic and incurable. There is more and more evidence that colorectal cancer stem cells (CCSCs), which are in charge of tumor growth, recurrence, and resistance to treatment, are what make CRC so different. Because we know more about stem cell biology, we quickly learned about the molecular processes and possible cross-talk between signaling pathways that affect the balance of cells in the gut and cancer. Wnt, Notch, TGF-ß, and Hedgehog are examples of signaling pathway members whose genes may change to produce CCSCs. These genes control self-renewal and pluripotency in SCs and then decide the function and phenotype of CCSCs. However, in terms of their ability to create tumors and susceptibility to chemotherapeutic drugs, CSCs differ from normal stem cells and the bulk of tumor cells. This may be the reason for the higher rate of cancer recurrence in patients who underwent both surgery and chemotherapy treatment. Scientists have found that a group of uncontrolled miRNAs related to CCSCs affect stemness properties. These miRNAs control CCSC functions like changing the expression of cell cycle genes, metastasis, and drug resistance mechanisms. CCSC-related miRNAs mostly control signal pathways that are known to be important for CCSC biology. The biomarkers (CD markers and miRNA) for CCSCs and their diagnostic roles are the main topics of this review study.

Rhamnolipids Nano-Micelles as a Potential Hand Sanitizer.

COVID-19 is a pandemic disease caused by the SARS-CoV-2, which continues to cause global health and economic problems since emerging in China in late 2019. Until now, there are no standard antiviral treatments. Thus, several strategies were adopted to minimize virus transmission, such as social distancing, face covering protection and hand hygiene. Rhamnolipids are glycolipids produced formally by Pseudomonas aeruginosa and as biosurfactants, they were shown to have broad antimicrobial activity. In this study, we investigated the antimicrobial activity of rhamnolipids against selected multidrug resistant bacteria and SARS-CoV-2. Rhamnolipids were produced by growing Pseudomonas aeruginosa strain LeS3 in a new medium formulated from chicken carcass soup. The isolated rhamnolipids were characterized for their molecular composition, formulated into nano-micelles, and the antibacterial activity of the nano-micelles was demonstrated in vitro against both Gram-negative and Gram-positive drug resistant bacteria. In silico studies docking rhamnolipids to structural and non-structural proteins of SARS-CoV-2 was also performed. We demonstrated the efficient and specific interaction of rhamnolipids with the active sites of these proteins. Additionally, the computational studies suggested that rhamnolipids have membrane permeability activity. Thus, the obtained results indicate that SARS-CoV-2 could be another target of rhamnolipids and could find utility in the fight against COVID-19, a future perspective to be considered.

Allicin mitigates hepatic injury following cyclophosphamide administration via activation of Nrf2/ARE pathways and through inhibition of inflammatory and apoptotic machinery.

Treatment with anti-neoplastic agents, including cyclophosphamide (CP), is associated with several adverse reactions. Here, we distinguished the potential protective effect of allicin against CP-mediated hepatotoxicity in rats. To assess the effect of allicin, four experimental groups were used, with 7 rats per group, including control, allicin (10 mg/kg), CP (200 mg/kg), and allicin + CP-treated groups. All groups were treated for 10 days. Blood and liver samples were collected for biochemical, molecular, and histological analyses. Treatment with CP led to deformations in the liver tissue that were associated with higher liver function markers (alanine transaminase, aspartate transaminase, and alkaline phosphatase). Additionally, a disturbance in the redox balance was observed after CP exposure, as indicated by increased levels of oxidants, including malondialdehyde and nitric oxide, and the decreased levels of endogenous antioxidants, including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. At the molecular level, CP treatment resulted in reduced expression of the Nrf2/ARE pathway and other genes related to this pathway, including NAD(P)H quinone dehydrogenase 1 and glutamate-cysteine ligase catalytic subunit. CP also led to a hyper-inflammatory response in hepatic tissue, with increased production of pro-inflammatory cytokines, including tumor necrosis factor-alpha and interlukin-1beta, and upregulation of nitric oxide synthase 2. CP also enhanced the immunoreactivity of the profibrogenic cytokine, transforming growth factor-beta, in liver tissue. Upregulation of caspase 3 and Bcl-2-associated X protein and downregulation of B-cell lymphoma 2 were also observed in response to CP treatment. Treatment with allicin reversed the molecular, biochemical, and histological changes that occurred with CP exposure. These results suggest that allicin can be used in combination with CP to avoid hepatotoxicity.

Nanoparticles induce genetic, biochemical, and ultrastructure variations in Salvadora persica callus.

BACKGROUND: Salvadora persica is an endangered medicinal plant due to difficulties in its traditional propagation. It is rich in bioactive compounds that possess many pharmaceutical, antimicrobial activities and widely used in folk medicine. The current study aims at in vitro propagation of Salvadora persica and the application of different nanoparticles (NPs) to induce the synthesis of bioactive and secondary metabolites within the plant. The cellular and genetic responses to the application of different NPs were evaluated. RESULTS: The impact of nanoparticles NPs (ZnO, SiO2, and Fe3O4) on callus growth of Salvadora persica and the production of its active constituent benzyl isothiocyanate was examined, regarding some oxidative stress markers, antioxidant enzymes, and genetic variabilities. An encouraging impact of 0.5 mg/l ZnO NPs on benzyl isothiocyanate production was shown reaching up to 0.905 mg/g callus fresh weight in comparison to 0.539 mg/g in control callus. This was associated with decreasing hydrogen peroxide content and increasing superoxide dismutase and peroxidase activities. The deposition of the NPs on cellular organelles was detected using a transmission microscope. Fifteen Inter-Simple Sequence Repeats (ISSR) primers detected an overall, 79.1% polymorphism among different treatments. A reduction in genomic DNA template stability (GTS) was made and was more pronounced in higher doses of different NPs. CONCLUSION: This study is a stepping stone in developing a productive protocol for in vitro production of benzyl isothiocyanate from Salvadora persica using NPs as a valuable anticancer compound.

Diagnostic performances of leucine-rich α-2-glycoprotein 1 and stem cell factor for diagnosis and follow-up of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequently diagnosed tumors worldwide with high mortality and morbidity. There is an urgent need for biomarkers to improve the outcomes and early detection of CRC. The sensitivity of traditional CRC tumor markers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)) is not ideal. The levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) and stem cell factor (SCF) were evaluated, but the combined value of both markers is unclear. This case-control study included four groups: CRC patients before treatments (n = 22), CRC patients after treatments (n = 26), 20 patients with benign tumor, and 20 healthy subjects. Levels of routine biochemical and hematological markers, traditional tumor markers (CA19.9 and CEA), and candidate markers (LRG1 and SCF) were determined. Univariate and multivariate logistic regression analysis and area receiver-operating characteristic analysis (ROC) were used for evaluation the diagnostic performances of single and combined markers. RESULTS: No significance difference in traditional tumor markers CEA, CA 19.9, and neutrophil-lymphocyte ratio (NLR) were found among study groups. SCF, LRG1, and platelet-lymphocyte ratio (PLR) were significantly decreased (p < 0.05) in non-treated CRC patients than after treated CRC. The combination between SCF and LRG1 showed highly significant difference in CRC patients compared with benign, healthy subjects, and among CRC groups (treated and non-treated) (p < 0.0001). The highest areas under curve (AUCs) were observed when LRG1 was used as a single predictor for discriminating CRC from healthy (0.87), benign (0.84), and non-treated CRC vs treated CRC (0.82). AUCs were jumped to 0.90, 0.84, and 0.84 when LRG1 and SCF were combined. CONCLUSION: Our study revealed that LRG1 and SCF were potential diagnostic and follow-up markers for CRC.

Development of a novel panel based on micro-RNAs (21, 29a, 200 and 335) and alpha-fetoprotein as diagnostic biomarkers for hepatocellular carcinoma associated with hepatitis C infection.

BACKGROUND AND STUDY AIMS: MicroRNAs (miRNAs) play key roles in cancer biology; they are used as potential tools in cancer diagnosis. This study investigated the microRNA expression profile of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Serum microRNA expression profiles (miRNA-29a, miRNA-200, miRNA-335 and miRNA-21) were analysed in 137 patients with HCC and liver cirrhosis and 49 healthy subjects (used as negative controls) using real-time quantitative reverse transcription polymerase chain reaction. Alpha-fetoprotein (AFP), as a routine tumour marker, was also assessed using enzyme-linked immunosorbent assay. RESULTS: The expression levels of miRNA-21, miRNA-335 and miRNA-200 were significantly up-regulated, whereas those of miRNA-29a were remarkably down-regulated in patients with HCC compared with those in healthy subjects. miRNA-200 had the most elevated area under the receiver operating characteristic curve (AUC) among single miRNAs used to predict HCC occurrence (AUC = 0.72). The highest discriminatory power was recorded using a panel based on the combination of four miRNAs, miRNA-200, miRNA-29a, miRNA-21 and miRNA-355, and AFP levels (AUC = 0.92). The four-miRNA panel combined with AFP levels exhibited high accuracy in predicting HCC with small tumour sizes of <2 cm (AUC = 0.90) and ≥2 cm (AUC = 0.93). The combination of the four-miRNA panel and AFP resulted in an AUC value of 0.83 for single lesions, which was lesser than that recorded for ≥2 lesions (AUC = 0.94, 0.95, respectively). CONCLUSION: The combination of the four-miRNA panel and AFP levels can be used as a sensitive and specific biomarker for HCC.

Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium-induced oxidative challenge, inflammation, and apoptosis in rats.

Here, we examined the protective effect of ferulic acid (FA) on cadmium chloride (CdCl2 )-mediated reproductive toxicity in male rats. Animals were divided into four groups: control, FA (20 mg/kg), CdCl2 (6.5 mg/kg), and FA + CdCl2 . CdCl2 treatment evoked a significant increase in testis cadmium concentration in addition to obvious increase in testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Moreover, CdCl2 -induced oxidative damage through exhausting the cellular defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) and downregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression accompanied by increases of malondialdehyde and nitric oxide contents. Testicular inflammation was evident indicated by increased levels of interleukin-1ß and tumor necrosis factor-α in CdCl2 -treated rats. CdCl2 exposure also decreased the expression of the proliferating cell nuclear antigen and augmented apoptotic events associated with prominent histopathological alterations. However, FA coadministration mitigated the impaired hormonal level, apoptotic and inflammatory injuries elicited by CdCl2, and maintained the oxidant/antioxidant balance in testicular tissue via Nrf2 activation. PRACTICAL APPLICATIONS: Cadmium is an environmental toxicant and known to cause adverse effects including reproductive toxicity. However, antioxidant application has been found to protect against heavy metals-mediated toxic effects. Here, we examined the potential protective efficacy of ferulic acid against cadmium-mediated testicular impairments through estimating the amount of cadmium in the testis, hormonal profile, oxidative status, inflammatory response, apoptotic and proliferating markers in addition to the histopathological alterations. The obtained findings revealed that ferulic acid supplementation was able to abolish the testicular damages coupled with cadmium exposure. The protective efficiency of ferulic acid may correlated with its strong antioxidant, anti-inflammatory, and antiapoptotic activities; suggesting that ferulic acid may be used to ameliorate cadmium-induced testicular deficits.

The protective efficacy of soursop fruit extract against hepatic injury associated with acetaminophen exposure is mediated through antioxidant, anti-inflammatory, and anti-apoptotic activities.

In the current report, we examined the potential beneficial role of soursop fruit extract (SSFE) on liver injury induced by a single paracetamol (APAP) overdose (2000 mg/kg). Thirty-five Wistar albino rats were randomly divided into five groups as follows: control, SSFE, APAP, SSFE+APAP, and silymarin (SIL)+APAP. APAP intoxication was found to elevate alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels. Moreover, it increased the levels of malondialdehyde, nitrites, and nitrates and depleted glutathione, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. APAP intoxication inactivated the nuclear factor erythroid 2-related factor 2 (Nrf2) defense pathway and upregulated the expression of heme oxygenase-1 (HO-1). APAP administration enhanced the activation of nuclear factor-kappa B (NF-κB), the elevation of tumor necrosis factor-alpha and interleukin 1-beta levels, and the upregulation of inducible nitric oxide synthase mRNA expression. In addition, APAP activated the overexpression of Bax protein, increased release of cytochrome c, and the downregulation of Bcl-2 protein. Finally, APAP-induced overexpression of transforming growth factor-beta (TGF-ß) further suggested enhanced liver damage. On the other hand, SSFE pretreatment attenuated these biochemical, molecular, and histopathological alterations in the liver, which might be partially due to the regulation of hepatic Nrf2/HO-1 and downregulation of NF-κB and TGF-ß.