Plant-Derived Bioactive Compounds in Colorectal Cancer: Insights from Combined Regimens with Conventional Chemotherapy to Overcome Drug-Resistance.

Acquired drug resistance represents a major clinical problem and one of the biggest limitations of chemotherapeutic regimens in colorectal cancer. Combination regimens using standard chemotherapeutic agents, together with bioactive natural compounds derived from diet or plants, may be one of the most valuable strategies to overcome drug resistance and re-sensitize chemoresistant cells. In this review, we highlight the effect of combined regimens based on conventional chemotherapeutics in conjunction with well-tolerated plant-derived bioactive compounds, mainly curcumin, resveratrol, and EGCG, with emphasis on the molecular mechanisms associated with the acquired drug resistance.

Breast Cancer-Delivered Exosomal miRNA as Liquid Biopsy Biomarkers for Metastasis Prediction: A Focus on Translational Research with Clinical Applicability.

Metastasis represents the most important cause of breast cancer-associated mortality. Even for early diagnosed stages, the risk of metastasis is significantly high and predicts a grim outcome for the patient. Nowadays, efforts are made for identifying blood-based biomarkers that could reliably distinguish patients with highly metastatic cancers in order to ensure a closer follow-up and a more personalized therapeutic method. Exosomes are nano vesicles secreted by cancer cells that can transport miRNAs, proteins, and other molecules and deliver them to recipient cells all over the body. Through this transfer, cancer cells modulate their microenvironment and facilitate the formation of the pre-metastatic niche, leading to sustained progression. Exosomal miRNAs have been extensively studied due to their promising potential as prognosis biomarkers for metastatic breast cancer. In this review, we tried to depict an overview of the existing literature regarding exosomal miRNAs that are already validated as potential biomarkers, and which could be immediately available for the clinic. Moreover, in the last section, we highlighted several miRNAs that have proven their function in preclinical studies and could be considered for clinical validation. Considering the lack of standard methods for evaluating exosomal miRNA, we also discussed the challenges and the technical aspects underlying this issue.

Bioactive Compounds and Functional Properties of Herbal Preparations of Cystus creticus L. Collected From Rhodes Island.

The members of Cystus genus are perenial shrubs with a well-established use in traditional medicine. Among these, C. creticus is the most popular, herbal preparations obtained from its aerial parts being recognized as antimicrobial, antitumor and anti-inflammatory agents. The present study aimed to evaluate phytochemical profile and bioactive potential of aqueous and hydroethanolic extracts of C. creticus aerial parts harvested from two different areas of Rhodes island. LC-DAD-ESI/MSn analysis revealed the presence of myricetin and quercetin glycosides as main compounds, especially in aqueous extracts, being probably responsible for their enhanced antioxidant and antimicrobial potential. On the other side, hydroethanolic preparations exerted a strong anti-inflammatory and anti-biofilm activity. Our findings suggest that the use of solvents with intermediate polarity can assure the best recovery of bioactive compounds from C. creticus, increasing the extraction yield for other non-phenolic compounds which can enhance therapeutic potential of the extract through a synergistic action.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.

Breastfeeding Practices and Determinant Factors of Exclusive Breastfeeding among Mothers of Children Aged 0-23 Months in Northwestern Romania.

In terms of breastfeeding (BF) practices in Romania, there is a lack of up-to-date data. The aim of the present study was to assess current BF practices, and to investigate the factors associated with exclusive BF (EBF) under 6 months of age in northwestern Romania. A structured questionnaire was used to collect data among 1399 mothers of children aged 0-23 months, recruited between March and June 2019, from the community. BF practices were evaluated based on the World Health Organization indicators for assessing infant and young child feeding practices, whereas determinants of EBF were explored using logistic regression models. Almost all mothers (95.7%) breastfed their child at least once. The EBF rate was 46.7%, the continued BF rate at one year of age was 54.2%, and the continued BF rate at 2 years of age was 30.3%. The place of delivery and parental leave duration were strong determinants of EBF. The improving rates observed in this study for all the BF practices assessed suggest the continuation of efforts to develop effective national policies and programs for promoting, protecting, and supporting BF in Romania. Particular emphasis should be given to the creation in maternity hospitals of an environment that is supportive towards breastfeeding.

Determinants of Early Initiation of Breastfeeding among Mothers of Children Aged Less than 24 Months in Northwestern Romania.

Early initiation of breastfeeding (EIBF), defined as putting newborns to the breast within 1 h of birth, may have important benefits for both infant and mother. The aim of this study was to assess EIBF practices and its determinants in northwestern Romania. This cross-sectional study was conducted from March to June 2019, based on a sample of 1399 mothers of children aged less than 24 months. The sample was recruited from the community, from 29 cities and 41 communes distributed across the six counties of the northwestern region of Romania. Mothers responded by face-to-face interviews to a structured questionnaire. Multivariate logistic regression was used to identify factors independently associated with EIBF. Only 24.3% of the mothers initiated breastfeeding within 1 h of birth. Delivering at a private hospital (adjusted odds ratio (AOR): 5.17, 95% confidence interval (CI) 3.87, 6.91), vaginal delivery (AOR: 4.39, 95% CI 3.29, 5.88), mother-newborn skin-to-skin contact for 1 h or more (AOR: 55.6, 95% CI 23.0, 134.2), and breastfeeding counseling during antenatal visits (AOR: 1.48, 95% CI 1.12, 1.97) were factors associated with increased likelihood of EIBF. Overall, the practice of EIBF was poor. Targeting modifiable factors associated with EIBF may be used to improve early initiation practice.

Pro-apoptotic genes as new targets for single and combinatorial treatments with resveratrol and curcumin in colorectal cancer.

Colorectal cancer (CRC) represents the third most diagnosed type of cancer worldwide with high mortality and an increased incidence rate. Bioactive dietary components such as curcumin and resveratrol have great therapeutic potential as they can modulate a plethora of signaling pathways related to colorectal carcinogenesis. Previous data have demonstrated that curcumin and resveratrol can induce apoptosis in different types of cancer cells. Considering the lack of data on the combinatorial effect of curcumin and resveratrol associated with the induction of apoptosis in colorectal pathology, the main objective of this study is to investigate the impact of single vs. combinatorial treatment of resveratrol and curcumin on their cytotoxic effects, as well as the modulation of several essential pro-apoptotic genes, on two colorectal cancer cell lines (DLD-1 and Caco-2) different in terms of chromosomal stability (MSI and MSS). The cytotoxic effects were evaluated by the MTT assay, the nature of the interaction between curcumin and resveratrol was assessed by the combination index method and the expression levels of key genes involved in the modulation of pro-apoptotic mechanisms were evaluated by RT-qPCR. Our data indicate that the combination treatment of curcumin and resveratrol is more effective in inhibiting the proliferation in a dose-dependent manner, with a synergistic effect for the DLD-1 cell line (CI < 1) and an additive effect for the Caco-2 cell line (CI ≥ 1). The IC50 values for the combination treatment were 71.8 µM (20.5 µM curcumin + 51.3 µM resveratrol) for the DLD-1 cell line and 66.21 µM (18.9 µM curcumin + 47.3 µM resveratrol) for the Caco-2 cell line, respectively. Our data pointed out, for the first time, that several genes involved in the modulation of apoptosis, including PMAIP1, BID, ZMAT3, CASP3, CASP7, and FAS, represent new targets of both singular and combinatorial treatments with resveratrol and curcumin, and also the combinatorial approach of curcumin and resveratrol exhibits a more powerful gene regulating effect compared to single treatment. Considering the beneficial aspects of the combinatorial approach with curcumin and resveratrol on colorectal cancer cells further studies should address the possible pharmacological benefits of using a combination of both dietary agents with different chemotherapeutic drug approaches.

The Role of Bioactive Dietary Components in Modulating miRNA Expression in Colorectal Cancer.

Colorectal cancer is the third most common cancer in the world and considered to be one of the most diet-related types of cancer. Extensive research has been conducted but still the link between diet and colorectal cancer is complex. Recent studies have highlight microRNAs (miRNAs) as key players in cancer-related pathways in the context of dietary modulation. MicroRNAs are involved in most biological processes related to tumor development and progression; therefore, it is of great interest to understand the underlying mechanisms by which dietary patterns and components influence the expression of these powerful molecules in colorectal cancer. In this review, we discuss relevant dietary patterns in terms of miRNAs modulation in colorectal cancer, as well as bioactive dietary components able to modify gene expression through changes in miRNA expression. Furthermore, we emphasize on protective components such as resveratrol, curcumin, quercetin, α-mangostin, omega-3 fatty acids, vitamin D and dietary fiber, with a focus on the molecular mechanisms in the context of prevention and even treatment. In addition, several bioactive dietary components that have the ability to re-sensitize treatment resistant cells are described.