Colorectal cancer (CRC) represents the third type of cancer in incidence and second in mortality worldwide, with the newly diagnosed case number on the rise. Among the diagnosed patients, approximately 70% have no hereditary germ-line mutations or family history of pathology, thus being termed sporadic CRC. Diet and environmental factors are to date considered solely responsible for the development of sporadic CRC; therefore; attention should be directed towards the discovery of preventative actions to combat the CRC initiation, promotion, and progression. Quercetin is a polyphenolic flavonoid plant secondary metabolite with a well-characterized antioxidant activity. It has been extensively reported as an anti-carcinogenic agent in the scientific literature, and the modulated targets of quercetin have been also characterized in the context of CRC, mainly in original research publications. In this fairly comprehensive review, we summarize the molecular targets of quercetin reported to date in in vivo and in vitro CRC models, while also giving background information about the signal transduction pathways that it up- and downregulates. Among the most relevant modulated pathways, the Wnt/β-catenin, PI3K/AKT, MAPK/Erk, JNK, or p38, p53, and NF-κB have been described. With this work, we hope to encourage further quests in the elucidation of quercetin anti-carcinogenic activity as single agent, as dietary component, or as pharmaconutrient delivered in the form of plant extracts.

Bilberries (Vaccinium myrtillus L.) have been reported to hold a plentitude of health-promoting properties beyond basic nutrition, mainly attributed to their anthocyanin content and antioxidant activity. In this article, we built the phytochemical profile of three wild bilberry fruit extract formulations (aqueous, methanolic, and hydro-methanolic) using UHPLC-ESI-MS/MS putative analysis, identifying 88 individual phytochemicals, mainly flavonoids (total content 8.41 ± 0.11 mg QE/g dw), free amino acids, polyphenols (total content 21.68 ± 0.19 mg GAE/g dw), carboxylic acids, and vitamins. Furthermore, the antioxidant activity of the extract was assessed, reaching 78.03 ± 0.16% DPPH free radical scavenging activity, comparable to literature values determined for bilberry extracts of other origin. Due to the increased prevalence of metabolic syndrome and based on the reviewed benefits of bilberries, we tested the most potent formulation of our bilberry extracts in this biological context. The in vivo rescue effect of a bilberry extract supplemented diet on Drosophila melanogaster was assessed by monitoring biochemical and genomic markers. Hemolymph trehalose levels were halved upon addition of 3% hydro-methanolic bilberry extract to a high-sugar (1.5 M sucrose) diet, as compared to the non-supplemented high-sugar diet. Noteworthy, the rescue seen for flies kept on the bilberry extract supplemented high-sugar diet appeared to parallel the trehalose levels observed in the case of the control diet (50 mM sucrose) flies. Moreover, next to the trehalose-lowering type of in vivo effects, other gene expression related rescues were also detected for genes such as InR, Akh, AstA, AstC, Irk, Npc2g, and CCHa2 upon supplementation of the high-sugar diet with our hydro-methanolic bilberry fruit extract. Our findings suggest that such a bilberry fruit extract could generate physiological and genomic type of compensatory mechanisms so that further translational approaches would advance the understanding of some human specific pathological conditions.

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress.

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder posing multifaceted challenges to global public health. Among its numerous complications, infected diabetic foot ulcers (IDFUs) represent a particularly debilitating consequence. Beyond cardiovascular implications, there is an emerging understanding of the interconnectedness among IDFUs, neuropathy, atherosclerosis, and dyslipidemia. IDFUs, peripheral neuropathy, and atherosclerosis share common risk factors and mechanistic pathways. The primary objective of this study was to characterize the lipid profiles in DM patients with IDFUs, comparing them with DM patients without foot ulcers, and with a control group of healthy subjects. The secondary objectives included evaluating apolipoprotein E (ApoE) levels across these study groups and comparing lipid profiles within IDFU subgroups. A total of 160 patients were assessed for this study. After applying exclusion criteria, 140 participants were included, divided into three groups: Group IDFU (80 patients with IDFUs), Group DM (32 patients with DM but no foot ulcers), and Group Controls (28 healthy controls). Compared to Group DM, Group IDFU demonstrated lower levels of high-density lipoprotein cholesterol (HDL-C) (30.9 ± 12.6 mg/dL vs. 40.8 ± 16.6 mg/dL, p = 0.002), but improved levels of ApoE (160.9 ± 68.4 mg/dL vs. 197.2 ± 69.6 mg/dL, p = 0.01), triglycerides (TG) (126.9 ± 56.2 mg/dL vs. 165.8 ± 79.0 mg/dL, p = 0.004), low-density lipoprotein cholesterol (LDL-C) (84.2 ± 32.3 mg/dL vs. 92.3 ± 39.3 mg/dL, p = 0.1), and total cholesterol (133.6 ± 43 mg/dL vs. 164.6 ± 44.4 mg/dL, p = 0.002). The IDFU patients exhibit improved lipid profiles, excepting HDL-C, which is unusual because IDFU follows complications related to dyslipidemia for DM patients. Anemia, impaired renal function, and elevated TG levels were identified as biomarkers for mortality among patients with IDFUs. The data suggest that a lower level of HDL-C and an improved lipid profile may indicate a systemic end-stage disease manifestation in DM patients with IDFUs.

Tussilago farfara L., a perennial species, is a medicinal herb used in traditional medicine, mainly for the treatment of respiratory tract-related pathology. In traditional Chinese medicine, flower buds are preferred; in Europe, the leaves are used; and in some parts of India, the whole plant is utilized. This preferential usage of the plant organs might be based on differences in the chemical composition due to environmental conditions, along with preferred traditional and cultural approaches. In this article, the impact of pedoclimatic growth conditions on the morpho-anatomical development and phytochemical profile of the plant were studied on T. farfara in the vegetative state, collected from two different locations in the Romanian spontaneous flora, revealing significant variations. Furthermore, the antioxidant profile of the specific extracts from the aerial and subterranean plant parts is also in accordance with these discrepancies. The plant anatomy was assessed histologically by optical microscopy, while the analytical chemistry evaluation was based on LC/MS and spectral methods for the evaluation of the antioxidant and enzyme inhibitory activity. To our knowledge, this is the first comparative analysis contextually reporting on the histology, phenolic profile, antioxidant capacity, and geographical location of the vegetative form of T. farfara.

Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) (p < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume (p = 0.002) and increased level of HDL (p = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS.