Enteric and diarrheal diseases are important causes of childhood death in the developing world. These diseases are responsible for more than 750 thousand deaths in children under 5 years old worldwide, ranking second cause of death, after lower respiratory diseases, in this age group. Among the major causative agents of diarrhea is Escherichia coli. There are several vaccine trials for diarrheagenic E. coli. However, diarrheagenic E. coli has seven pathotypes and vaccines are directed for one or two of the five main pathotypes-causing diarrhea. Currently, there are no combined vaccines available in the market for all five diarrheagenic E. coli pathotypes. Therefore, we aimed to develop a low-cost vaccine candidate combining the five main diarrheagenic E. coli to offer wide-spectrum protection. We formulated a formalin-killed whole-cell mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypes as a combined vaccine candidate. We immunized Balb/C mice subcutaneously with 109 CFU of combined vaccine candidate and found a significant increase in survival rate post challenge compared to unimmunized controls (100 % survival). Next we aimed to determine the immunological response of mice to the combined vaccine candidate compared to each pathotype immunization. To do so, we immunized mice groups with combined vaccine candidate and monitored biomarkers levels over 6 weeks as well as measured responses post challenge with relevant living E. coli. We found significant increase in specific systemic antibodies (IgG), interferon gamma (IFNγ) and interleukin 6 (IL-6) levels elicited by combined vaccine candidate especially in the first 2 weeks after mice immunization compared to controls (p < 0.05). We also evaluated alum and cholera toxin B subunit (CTB) as potential adjuvant systems for our candidate vaccine. We found that CTB-adjuvanted combined vaccine candidate showed significantly higher IgG and IFNγ levels than alum. Overall, our combined vaccine candidate offered protection against the five main diarrheagenic E. coli pathotypes in a single vaccine using mouse model. To the best of our knowledge, this is the first combined vaccine against the five main diarrheagenic E. coli pathotypes that is cost-effective with promise for further testing in humans.

One of the most common cancers that result in death is lung cancer. There is new hope in the fight against lung cancer thanks to the chemopreventive properties of natural dietary substances like β-caryophyllene oxide (CPO), and research is currently being done to test this theory. CPO, a sesquiterpene isolated from medicinal plant essential oils, inhibits carcinogenesis and has been effective in treating many cancers. This study examined how CPO affected proliferation of human lung cancer A549 cells. CPO was found to have an inhibitory concentration (IC50) of 124.1 g/ml. The proliferative markers Ki67 and PCNA were significantly inhibited after cells were treated with CPO at a concentration of 50 g/ml compared to controls. CPO-treated cells expressed more P21, P53, and DNA strand breaks than controls. This was accompanied by a significant cell cycle arrest in the S and G2/M phases. In treated A549 cells, this was also associated with a significant induction of apoptosis, as shown by the upregulation of the expression of caspases 3, 7, and 9, as well as Bax, and the downregulation of Bcl-2. Furthermore, the redox status of treated A549 cells revealed a marked rise in GSH and GPx activity levels and a decline in 4-HNE levels, indicating low oxidative stress following CPO treatment of A549 cells. In conclusion, cell cycle arrest and apoptosis, which are unrelated to oxidative stress, were the mechanisms by which CPO reduced cancer lung cell growth. This finding might be a potential therapeutic target for the treatment of lung cancer. Graphical abstract Hypothetical scheme of CPO anticancer effects (mechanism of signaling) in A549 cells; in vitro. CPO treatment increases expression of p21, p53 and DNA fragmentation. These events cause arrest of cell cycle which was associated with significant induction in apoptosis via increase expression of caspases (-3,-7,-9), and Bax and downregulation of Bcl-2.

Background: Resistance to antibiotics and anticancer therapy is a serious global health threat particularly in immunosuppressed cancer patients. Current study aimed to estimate the antibacterial and anticancer potentials of short-term exposure to extremely low frequency electromagnetic field (ELF-EMF) and silver nanoparticles (AgNPs) either in sole or combined form. Methods: Antibacterial activity was evaluated via determination of the bacterial viable count reduction percentage following exposure, whereas their ability to induce apoptosis in breast cancer (MCF-7) cell line was detected using annexin V-fluorescein isothiocyanate and cell cycle analysis. Also, oxidative stress potential and molecular profile were investigated. Results: ELF-EMF and AgNPs significantly (p < 0.01) reduced K. pneumonia viable count of compared to that of S. aureus in a time dependent manner till reaching 100% inhibition when ELF-EMF was applied in combination to 10 µM/ml AgNPs for 2 h. Apoptosis induction was obvious following exposure to either ELF-EMF or AgNPs, however their apoptotic potential was intensified when applied in combination recording significantly (p < 0.001) induced apoptosis as indicated by elevated level of MCF-7 cells in the Pre G1 phase compared to control. S phase arrest and accumulation of cells in G2/M phase was observed following exposure to AgNPs and EMF, respectively. Up-regulation in the expression level of p53, iNOS and NF-kB genes as well as down-regulation of Bcl-2 and miRNA-125b genes were detected post treatment. Conclusions: The antibacterial and anticancer potentials of these agents might be related to their ability to induce oxidative stress, suggesting their potentials as novel candidates for controlling infections and triggering cancer cells towards self-destruction.

Cancer is known to be a fierce disease that causes a large percentage of the deaths worldwide. The common cancer treatments; chemotherapy, radiotherapy and surgery are known for their severe side effects; therefore scientists are working on finding solutions to reduce these drawbacks. One of these treatment systems is the sustained released drugs formulations, these systems depend on the encapsulation of the chemotherapy within an emulsifying agent, in order to obtain a slow drug release of low doses over long time intervals. In this study, the anti-cancer effects of free and encapsulated sinapic acid was tested against lung (A549), and colon (CaCo2) cancer cell lines, along with normal fibroblast cells (HFB4) as a negative control. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed for IC₅₀ evaluation, also cell cycle assay was performed to detect cell cycle arrest status and related anti-apoptotic and pro-apoptotic; Blc-2, BAX, and P53 gene profile fold changes post cellular treatment. Data recorded revealed that encapsulated SA showed a lower toxicity than the free form to both cell lines and also to the normal cells. The cell cycle analysis showed a cell cycle arrest at the G2/M phase post cell treatment with the free and encapsulated sinapic acid accompanied with up regulation of Bax and P53 and a down regulation of Blc-2 genes in both cell lines. The data suggest a promising anti-cancer and anti-proliferative potential of free and encapsulated sinapic acid. Also they show that the anti-cancer effect of free and encapsulated sinapic acid is quite close.

Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or Danshensu (DSS, 3-(3, 4-dihydroxyphenyl)-(2R)-lactic acid), derived from the root of Danshen (Salvia miltiorrhiza), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of Danshensu alone and in combination with different agents, such as probiotic bacteria (Lactobacillus casei and Lactobacillus acidophilus), against several assays. The inhibition mechanism of the methylation gene biomarkers, such as DNMT-1, MS, STAT-3, and TET-1, against DSS was evaluated by molecular docking and RT-PCR techniques. The physicochemical and pharmacokinetic ADMET properties of DSS were determined by SwissADME and pkCSM. The results indicated that all lipid blood test profiles, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were reduced after the oral administration of Danshensu combined with probiotics (L. casei and L. acidophilus) that demonstrated good, efficient free radical scavenging activity, measured using anti-oxidant assays. ADMET and drug-likeness properties certify that the DSS could be utilized as a feasible drug since DSS showed satisfactory physicochemical and pharmacokinetic ADMET properties.

The present work aimed to evaluate the reactivity of natural bioflavonoid hesperidin (HSP) and synthetically derived XAV939 (XAV) against human hepatocellular carcinoma (HepG2), human breast cancer (MDA-MB231) cancer cell lines, and related molecular and pathological profiles. Data recorded revealed that the cytotoxic potential of the tested products was found to be cell type- and concentration-dependent. The half-maximal inhibitory concentration (IC₅₀) value of the HSP-XAV mixture against MDA-MB231 was significantly decreased in the case of using the HSP-XAV mixture against the HepG2 cell line. Also, there was a significant upregulation of the phosphotumor suppressor protein gene (P53) and proapoptotic genes such as B-cell lymphoma-associated X-protein (Bax, CK, and Caspase-3), while antiapoptotic gene B-cell lymphoma (Bcl-2) was significantly downregulated compared with the untreated cell control. The cell cycle analysis demonstrated that DNA accumulation was detected mainly during the G2/M phase of the cell cycle accompanied with the elevated reactive oxygen species level in the treatment of HepG2 and MDA-MB231 cell lines by the HSP-XAV mixture, more significantly than that in the case of cell control. Finally, our finding suggests that both HSP and XAV939 and their mixture may offer an alternative in human liver and breast cancer therapy.