HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches.

Natural approach became a high demand for the prevention and treatment of such diseases for their proven safety and efficacy. This study is aimed to perform comparative phytochemical analysis of white pitaya (Hylocereus undatus) peel, pulp and seed extracts via determination of total flavonoid content, phenolic content, and antioxidant capacity, coupled with HPLC-ESI/MS-MS analysis. Further, we evaluated the synergistic cytotoxic potential with Cisplatin against cervical cancer cells with investigation of underlying mechanism. The highest content of phenolics and antioxidants were found in both seed and peel extracts. The HPLC-ESI/MS-MS revealed identification of flavonoids, phenolic acids, anthocyanin glycosides, lignans, stilbenes, and coumarins. The cytotoxicity effects were evaluated by MTT assay against prostate, breast and cervical (HeLa) and Vero cell lines. The seed and peel extracts showed remarkable cytotoxic effect against all tested cell lines. Moreover, the selectivity index confirmed high selectivity of pitaya extracts to cancer cells and safety on normal cells. The combined therapy with Cisplatin effectively enhanced its efficacy and optimized the treatment outcomes, through the apoptotic ability of pitaya extracts in HeLa cells, as evaluated by flow cytometry. Besides, RT-PCR and western blotting analysis showed downregulation of Bcl-2 and overexpression of P53, BAX among HeLa cells treated with pitaya extracts, which eventually activated apoptosis process. Thus, pitaya extract could be used as adjuvant therapy with cisplatin for treatment of cervical cancer. Furthermore, in-vivo extensive studies on the seed and peel extracts, and their compounds are recommended to gain more clarification about the required dose, and side effects.

CircRNA-associated ceRNA regulatory networks as emerging mechanisms governing the development and biophysiopathology of epilepsy.

The etiology of epilepsy is ascribed to the synchronized aberrant neuronal activity within the brain. Circular RNAs (circRNAs), a class of non-coding RNAs characterized by their circular structures and covalent linkage, exert a substantial influence on this phenomenon. CircRNAs possess stereotyped replication, transience, repetitiveness, and paroxysm. Additionally, MicroRNA (miRNA) plays a crucial role in the regulation of diverse pathological processes, including epilepsy. CircRNA is of particular significance due to its ability to function as a competing endogenous RNA, thereby sequestering or inhibiting miRNA activity through binding to target mRNA. Our review primarily concentrates on elucidating the pathological and functional roles, as well as the underlying mechanisms, of circRNA-miRNA-mRNA networks in epilepsy. Additionally, it explores the potential utility of these networks for early detection and therapeutic intervention.

Chemical Composition and Antimicrobial and Cytotoxic Activities of Foeniculum vulgare Mill Essential Oils.

BACKGROUND AND AIM: Foeniculum vulgare (F. vulgare) Mill, commonly known as fennel, belongs to the Umbelliferae (Apiaceae) family, biennial or perennial herbs disseminated in Mediterranean region and central Europe. This herbal medicine (HM) is considered as a traditional HM, and its parts have been studied. METHODS: In this survey, essential oils from seeds collected from three various regions (Kerman, Golestan, and East Azerbaijan Provinces) of Iran were prepared with hydro-distillation and their components were analyzed with gas chromatography (GC) and chromatography time-of-flight mass spectrometry (GC/MS). Antimicrobial and cytotoxic activities of the essential oils were examined with disk-diffusion method on Muller-Hinton agar and Subaru-dextrose Agar, respectively. Additionally, the MTT assay was assessed on breast cancer cell line (MCF-7). The expression of apoptosis-related genes, Bax and Bcl2, was determined using quantitative real-time PCR (RT-qPCR). RESULTS: The major fractions of essential oils identified by GC and GC/MS included trans-anethole (78.47%, 49.64%, 78.68%), fenchone (10.5%, 8.4%, and 10.2%), and limonene (5.9%, 6.70%, and 5.6%), respectively. Fennel oil collected from three various places exerted inhibitory effects on the bacterial growth and higher cytotoxic effects on MCF-7 cancer cell line. In addition, the essential oil increased the expression of Bax, but decreased Bcl2 gene expression significantly (P < 0.001). CONCLUSION: According to our findings, F. vulgare essential oil can be considered as a promising agent opening venues for novel antimicrobial and anticancer therapies. Owing to side effects and expensiveness of chemotherapy approaches, HM is a new remarkable insight for future therapies.

Inhibitory Traits of Dendrosome Curcumin (DNC) on Breast Cancer Compared to Curcumin Single Compound.

PURPOSE: Vast therapeutic traits and very low toxicity of curcumin compound have made it and related formulations promising for treatment purposes. The aim of this study was the assessment of dendrosome curcumin (DNC) inhibitory effects on breast cancer therapy compared to single curcumin compound. METHODS: DNC was synthesized and MCF-7 cells were prepared. The cultured cells were treated with 20 µg/ml and 25 µg/ml of DNC. Real-time quantitative PCR (RT-qPCR) was performed to measure the expression of FOXCUT and MEG3 genes. Additionally, flow cytometry was applied to measure cell death rate and apoptosis. RESULTS: The results outlined that DNC enhanced the MEG3 gene expression significantly higher than the control. Furthermore, DNC was associated with a significant decrease in the expression of FOXCUT gene as compared to the control. The application of DNC in the MCF7 cell line enhanced cell death and reduced necrosis. CONCLUSIONS: The rate of apoptosis (programmed cell death) was enhanced, but necrosis was decreased in treated cancer cells compared to those treated with single curcumin. Accordingly, the DNC can be applied to hinder the growth and dissemination of cancer cells as a preferred approach to reduce the complications of other strategies such as chemotherapy and radiation therapy. Indeed, we concluded that DNC enhanced the expression of MEG3, a tumor suppressor, at 25 µm dose, but reduced the expression of the FOXCUT gene, possibly via the methylation of the gene. Thereby, DNC exerted a promising tumor inhibitory growth potential for the eradication of cancer cells.

Bacterial l-asparaginases for cancer therapy: Current knowledge and future perspectives.

l-Asparaginases hydrolyzing plasma l-asparagine and l-glutamine has attracted tremendous attention in recent years owing to remarkable anticancer properties. This enzyme is efficiently used for acute lymphoblastic leukemia (ALL) and lymphosarcoma and emerged against ALL in children, neoplasia, and some other malignancies. Cancer cells reduce the expression of l-asparaginase leading to their elimination. The l-asparaginase anticancerous application approach has made incredible breakthrough in the field of modern oncology through depletion of plasma l-asparagine to inhibit the cancer cells growth; particularly among children. High level of l-asparaginase enzyme production by Escherichia coli, Erwinia species, Streptomyces, and Bacillus subtilis species is highly desirable as bacterial alternative enzyme sources for anticancer therapy. Thermal or harsh conditions stability of those from the two latter bacterial species is considerable. Some enzymes from marine bacteria have conferred stability in adverse conditions being more advantageous in cancer therapy. Several side effects exerted by l-asparaginases such as hypersensitivity should be hindered or decreased through alternative therapies or use of immune-suppressor drugs. The l-asparaginase from Erwinia species has displayed remarkable traits in children with this regard. Noticeably, Erwinia chrysanthemi l-asparaginase exhibited negligible glutaminase activity representing a promising efficiency mitigating related side effects. Application of software such as RSM would optimize conditions for higher levels of enzyme production. Additionally, genetic recombination of the encoding gene would indisputably help improving enzyme traits. Furthermore, the possibility of anticancer combination therapy using two or more l-asparaginases from various sources is plausible in future studies to achieve better therapeutic outcomes with lower side effects.