Oleanolic acid increases the anticancer potency of doxorubicin in pancreatic cancer cells.

Combination therapy is a novel cancer therapy approach that combines two or more chemotherapy drugs. This treatment modality enhances the efficacy of chemotherapy by targeting key pathways in an additive or synergistic manner. Therefore, we investigated the efficacy of combination therapy by widely used chemotherapy drug doxorubicin (DOX) and oleanolic acid (OA) to induction of apoptosis for pancreatic cancer (PC) therapy. The effects of DOX, OA, and their combination (DOX-OA) were investigated on proliferation and viability of PC cell line (PANC-1) by MTT assay. Moreover, migration and invasion of the cancer cells were evaluated by trans-well migration assay and wound healing assay. Flow cytometry and DAPI (4',6-diamidino-2-phenylindole) staining were employed to investigate apoptosis quantification and qualification of the treated cancer cells. Finally, mRNA expression of apoptosis-related genes was assessed by quantitative real-time polymerase chain reaction. Our results demonstrated that the proliferation and metastasis potential of PC cells significantly decreased after treatment by DOX, OA, and DOX-OA. Moreover, we observed an increase in apoptosis percentage in the treated cancer cells. The apoptosis-related gene expression was modified to increase the apoptosis rate in all of the treatment groups. However, the anticancer potency of DOX-OA combination was significantly more than that of DOX and OA treatments alone. Our study suggested that DOX-OA combination exerts more profound anticancer effects against PC cell lines than DOX or OA monotherapy. This approach may increase the efficiency of chemotherapy and reduce unintended side effects by lowering the prescribed dose of DOX.

A review of the application of fungi as an effective and attractive bio-adsorbent for biosorption of heavy metals from wastewater.

One of the most hazardous environmental pollutants is the pollution risen by heavy metal ions in effluents, which is increasing due to the increasing human activity and the development of urbanization. Notwithstanding the economic challenges to control the pollution of effluent treatment processes, it seems necessary to provide effective approaches. The sorption method is widely used due to low-cost, flexibility in design and operation, repeatability, and significant performance. Hence, the need for more environmentally friendly sorbents to eliminate metal ions is greater than ever. Due to the unique features such as the presence of chitin and chitosan in the cell wall, high absorption capacity, environmental friendliness, availability, and cheapness, the use of fungi as adsorbent has received much attention. Therefore, this work tries to address the use of fungi as biosorbents to remove these metals, the dangers of heavy metals, and their sources. Moreover, equilibrium, kinetic, and thermodynamic behaviors of the heavy metal ion adsorption process in the literature are briefly studied.

A fuzzy logic-based computational method for the repurposing of drugs against COVID-19.

Introduction: COVID-19 has spread out all around the world and seriously interrupted human activities. Being a newfound disease, not only many aspects of the disease are unknown, but also there is not an effective medication to cure the disease. Besides, designing a drug is a time-consuming process and needs large investment. Hence, drug repurposing techniques, employed to discover the hidden benefits of the existing drugs, maybe a useful option for treating COVID-19. Methods: The present study exploits the drug repositioning concepts and introduces some candidate drugs which may be effective in controlling COVID-19. The suggested method consists of three main steps. First, the required data such as the amino acid sequences of targets and drug-target interactions are extracted from the public databases. Second, the similarity score between the targets (protein/enzymes) and genome of SARS-COV-2 is computed using the proposed fuzzy logic-based method. Since the classical approaches yield outcomes which may not be useful for the real-world applications, the fuzzy technique can address the issue. Third, after ranking targets based on the obtained scores, the usefulness of drugs affecting them is examined for managing COVID-19. Results: The results indicate that antiviral medicines, designed for curing hepatitis C, may also cure COVID-19. According to the findings, ribavirin, simeprevir, danoprevir, and XTL-6865 may be helpful in controlling the disease. Conclusion: It can be concluded that the similarity-based drug repurposing techniques may be the most suitable option for managing emerging diseases such as COVID-19 and can be applied to a wide range of data. Also, fuzzy logic-based scoring methods can produce outcomes which are more consistent with the real-world biological applications than others.

Selectivity of major isoquinoline alkaloids from Chelidonium majus towards telomeric G-quadruplex: A study using a transition-FRET (t-FRET) assay.

BACKGROUND: Natural bioproducts are invaluable resources in drug discovery. Isoquinoline alkaloids of Chelidonium majus constitute a structurally diverse family of natural products that are of great interest, one of them being their selectivity for human telomeric G-quadruplex structure and telomerase inhibition. METHODS: The study focuses on the mechanism of telomerase inhibition by stabilization of telomeric G-quadruplex structures by berberine, chelerythrine, chelidonine, sanguinarine and papaverine. Telomerase activity and mRNA levels of hTERT were estimated using quantitative telomere repeat amplification protocol (q-TRAP) and qPCR, in MCF-7 cells treated with different groups of alkaloids. The selectivity of the main isoquinoline alkaloids of Chelidonium majus towards telomeric G-quadruplex forming sequences were explored using a sensitive modified thermal FRET-melting measurement in the presence of the complementary oligonucleotide CT22. We assessed and monitored G-quadruplex topologies using circular dichroism (CD) methods, and compared spectra to previously well-characterized motifs, either alone or in the presence of the alkaloids. Molecular modeling was performed to rationalize ligand binding to the G-quadruplex structure. RESULTS: The results highlight strong inhibitory effects of chelerythrine, sanguinarine and berberine on telomerase activity, most likely through substrate sequestration. These isoquinoline alkaloids interacted strongly with telomeric sequence G-quadruplex. In comparison, chelidonine and papaverine had no significant interaction with the telomeric quadruplex, while they strongly inhibited telomerase at transcription level of hTERT. Altogether, all of the studied alkaloids showed various levels and mechanisms of telomerase inhibition. CONCLUSIONS: We report on a comparative study of anti-telomerase activity of the isoquinoline alkaloids of Chelidonium majus. Chelerythrine was most effective in inhibiting telomerase activity by substrate sequesteration through G-quadruplex stabilization. GENERAL SIGNIFICANCE: Understanding structural and molecular mechanisms of anti-cancer agents can help in developing new and more potent drugs with fewer side effects. Isoquinolines are the most biologically active agents from Chelidonium majus, which have shown to be telomeric G-quadruplex stabilizers and potent telomerase inhibitors.