The relative importance of arthropod-borne and other disease pathogens as the cause of an outbreak of febrile illnesses was assessed during August 1988, following severe flooding in Khartoum, Sudan. A total of 200 patients with acute febrile illness and 100 afebrile controls were enrolled in the study during October and November 1988; at the Omdurman Military Hospital, Khartoum, Sudan. Sera were tested for IgM and IgG antibodies to six arthropod-borne viruses by an enzyme-linked immunoabsorbent assay, and for similar antibodies to Lassa fever, Crimean-Congo hemorrhagic fever, and Ebola and Marburg viruses by an indirect fluorescence assay. Thick and thin blood smears were examined microscopically for malaria parasites, and fecal and blood specimens were tested for bacteria by standard culture methods. Among the acute and convalescent sera collected from 67 febrile patients, five cases were caused by sandfly fever Sicilian (SFS), six by sandfly fever Naples (SFN), and 12 by unidentified phleboviruses. Of 233 remaining unpaired, acute-phase sera collected from cases and controls, 49 (21%) had IgM antibodies to SFS or SFN, RVF, West Nile (WN), and Chikungunya (CHIK) viruses. Forty-three (22%) of 192 febrile cases and two of the 100 afebrile controls were positive for Plasmodium falciparum, and bacterial enteropathogens were associated with 25 (13%) cases and four controls. These data indicated that phleboviruses and to a lesser extent, WN, P. falciparum, and enterobacterial pathogens were causes of acute febrile illnesses following the 1988 flood in Khartoum, Sudan.
Background: colorectal cancer is considered to be the third most common cause of deaths in both men and women. The incidence of colorectal cancer cases has been rising at an alarming rate. In most cases, colon cancer treatment involves chemotherapy. However, toxicity and tumor cell drug resistance are outstanding obstacles to this treatment. Scientific studies suggested that combining certain chemotherapy treatments with specific antioxidants at defined dosages can improve drug efficacy or may reduce side effects severity.5-Fluorouracil, which is used in the treatment of breast, stomach and pancreatic cancer, remains the cornerstone of CRC treatment, although widely used in combination with several other drugs. Many effective drugs, including those actually used for cancer treatment, have been developed from botanical sources. Resveratrol is a pleiotropic phytochemical which is belong to the stilbene family. Although, it is only significantly present in grape products. Many preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Aim of the work: in the present study, the anticancer effects of Resveratrol alone or combined with 5-Fu were assessed on experimentally induced colorectal cancer in rats. Results: the results of this study indicated that RES had a better therapeutic effect against N-methylnitrosourea induced colorectal cancer than 5-Fu alone and when in combination with each other they diminished the cytotoxic effect of 5-Fu and enhanced normal histological appearance of colon tissue, which could be a promising alternative for resistant colorectal cancer. However, the exact mechanisms involved needs to be further explored. Conclusion: our results suggested that both natural compounds could be in the future a possible alternative to enhance the efficiency of 5-Fu in resistant colon cancer cells. This study supports the potential of plant extracts as source of bioactive compounds with biomedical applications.
Background: MicroRNA modulation therapy has shown great promise to treat hepatocellular carcinoma (HCC), however Efficient tissue-specific and safe delivery remains a major challenge. Objective: We sought to develop an inorganic-organic hybrid vehicle for the systemic delivery of the tumor suppressor miR-34a, and to investigate the efficiency of the delivered miR-34a in the treatment of HCC in vitro and in vivo. Methods: In the present study, pEGP-miR cloning and expression vector, expressing miR-34a, was electrostatically bound to polyethyleneimine (PEI), and then loaded onto ZSM-5 zeolite nanoparticles (ZNP). Qualitative and quantitative assessment of the transfection efficiency of miR-34a construct in HepG2 cells was applied by GFP screening and qRT-PCR, respectively. The expression of miR-34a target genes was investigated by qRT-PCR in vitro and in vivo. Results: ZNP/PEI/miR-34a nano-formulation could efficiently deliver into HepG2 cells with low cytotoxicity, indicating good biocompatibility of generated nanozeolite. Furthermore, five injected doses of ZNP/PEI/miR-34a nano-formulation in HCC induced male Balb-c mice, significantly inhibited tumor growth, and demonstrated improved cell structure, in addition to a significant decrease in alphafetoprotein level and liver enzymes activities, as compared to the positive control group. Moreover, injected ZNP/PEI/miR-34a nano-formulation led to a noticeable decrease in the CD44 and c-Myc levels. Results also showed that ZNP/PEI/miR-34a nano-formulation inhibited several target oncogenes including AEG-1, and SOX-9, in vitro and in vivo. Conclusion: Our results suggested that miR-34a is a powerful candidate in HCC treatment and that AEG-1 and SOX-9 are novel oncotargets of miR-34a in HCC. Results also demonstrated that our nano-formulation may serve as a candidate approach for miR-34a restoration for HCC therapy, and generally for safe gene delivery.
Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.
Hepatocellular carcinoma is a devastating tumor which accounts for death mortality rate 94% globally, and about 780,000 new cases each year. Tumor suppressor miRNAs represent a class of noncoding RNAs, which exhibit decreased or inhibited expression in the case of carcinogenesis. Therefore, the replacement of these molecules leads to post-transcriptional regulation of tens to hundreds of oncogenic targets and limiting the tumor. Interestingly, there is a group of tumor silencer miRNAs that have been highlighted in HCC and herein, our review will discuss the prominent examples of these miRs in terms of their efficient delivery using vectors, nano-delivery systems, their successful models either in vitro or in vivo and pre-clinical trials. Collectively, tumor suppressor miRNAs can act as novel therapeutics for HCC and more studies should be directed towards these promising therapeutics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.