Antibody-drug conjugates (ADCs) are used in anticancer therapy with some limitations due to their molecular properties. An alternative to monoclonal antibodies is the affibody, composed of 58 aminoacids, with lower binding affinities, small size, and rapid blood clearance and tissue distribution. We investigated the in vitro efficacy of a novel anti-HER2 ZHER2:2891 affibody conjugated to a cytotoxic drug auristatin E (MMAE) in HER2-positive human cancer cells. Adenocarcinoma cell line SK-BR-3, expressing high levels of HER2, and mammary gland adenocarcinoma MDA-MB-231, expressing basal levels of HER2, were treated with ZHER2:2891DCS-MMAE and trastuzumab (as reference compound).

ZHER2:2891DCS-MMAE induced a significant time-dependent toxic effect in SK-BR-3 cells. A 30% reduction in cell viability was found after 10 min exposure at 7 nM with an IC50 of 80.2 nM. On the contrary, MDA-MB-231 cells were not affected by the affibody complex. The HER2-specific cytotoxic effect of the ZHER2:2891DCS-MMAE has been also confirmed by measuring apoptosis by flow cytometry. In SK-BR-3 cells, increasing concentrations of conjugated affibody, induced cell death after 10 min of treatment with the strongest effect observed after 48 hours. Also, treatment with ZHER2:2891DCS-MMAE reduced (up to 50%) HER2 expression at both mRNA and protein levels in SK-BR-3 cells after 24 hours of treatment.

In conclusion, the cytotoxic conjugate based on the anti-HER2 affibody and MMAE efficiently interacts with HER2 over-expressing cancer cells, allowing the selective and specific delivery of the cytotoxic payload. The basal HER2 expressing cells are not affected most probably due to a lower uptake of drug conjugate. This confirms that affibody may be used to target HER2 overexpressing cells while sparing normal cells.

The metabolic syndrome is a cluster of conditions that occur together, increasing the risk of chronic diseases such as obesity, type II diabetes, or cardiovascular disease. Nutritional interventions improving inflammation, bioenergetics, and oxidative stress are proposed as effective tools in preventing metabolic syndrome. The cocoa shell is a by-product generated in large amounts during cocoa production. This by-product contains alkaloids and phenolic compounds as main compounds and has been investigated as an anti-obesity and anti-diabetic agent. Here, we used network pharmacology to explore the potential mechanism of the phytochemicals from the cocoa shell. We searched the cocoa shell's phytochemical composition, and oral bioavailability and drug-likeness were screened. We predicted the cocoa shell phytochemicals' targets and used different databases to search for compound-protein and compound-gene interactions, and then protein-protein interaction networks were constructed. Moreover, pathway enrichment analysis was performed, and biological processes and signaling pathways were identified and illustrated through bioinformatics analyses. Theobromine, caffeine, procyanidin B2, (−)-epicatechin, (+)-catechin, and protocatechuic acid were identified in the cocoa shell as main components. Those phytochemicals were associated with inflammation- (TNF-α, NF-κB, JNK), oxidative stress (CAT, SOD), obesity- (adiponectin, leptin, FASN, PPAR-α), and diabetes- (insulin, AKT,) related pathways. Results demonstrated that cocoa shell phytochemicals could modulate multiple biological processes and signaling pathways in a multimechanistic manner. Hence, cocoa shell consumption could support the nutritional prevention of metabolic syndrome. Future in vivo and clinical investigations will be needed to validate this potential nutraceutical and healthy ingredient's effects and mechanisms.

Chronic pain changes brain connectivity, brainwave organization, and volume, often resulting in disability, anxiety and depression. Opioid pain relievers impair function, with risk of addiction. Music analgesia research suggests that music for long-term analgesia includes slow tempo, pleasantness, and self-choice. We hypothesized that volunteers listening to self-chosen music with beats embedded, for ½ hour twice a day, could show brainwave entrainment (BWE) at frequencies of healthy descending pain modulatory system (DPMS). Over time such BWE may change brain activity, and restore organization in DPMS altered by chronic pain.

Volunteers with chronic pain > 1year participated in a study of 4 weeks of listening to one half hour of prepared music twice a day, and four weeks of non-listening, reporting pain and analgesic use during the study. Assessments used visual analog scale (VAS) and 0-10 numerical pain scores (NPS), medication types and dosage.

A mobile app provided a menu of 27 half-hour pieces of music in several genres to choose from. Isochronic beats were embedded in the music with tempo, key, and isochronic pulsed theta frequencies proportional to each other, to enhance the brain’s perception of rhythmic patterns and harmonics.

Results: Mean NPS showed a 26% reduction (p = .018). More significantly, mean medication dosage declined by over 60% (p = .008). Larger populations and longer trial periods are needed to determine the efficacy of music vs the music with brainwave beats.

Polysaccharide-based carriers have become attractive materials for the delivery of therapeutics targeted to colon. Ferulated arabinoxylans (AX), polysaccharides with gelling and antioxidant capacities that can be degraded by colonic microbiota are ideal candidates for use as oral drug delivery systems. Recently, AX-based microspheres have demonstrated potential applications as colon-targeted drug carriers. The non-cytotoxicity of AX-based microspheres is a required property for their use as a colon-targeted biomaterial. This study reports the antioxidant activity and cytotoxicity on human colon cells of covalently cross-linked particles based on AX (AXP). The in vitro antioxidant activity of AX before and after gelation was measured using the ABTS+, DPPH, and FRAP methods. Besides, the effect of AX and AXP on the proliferation of human colon cells (CCD 841 CoN) was evaluated using the MTT assay. AXP presented a spherical shape and rough surface with a three-dimensional and porous network. Gelation decreased the antioxidant activity of AX by 61–64 %. AX and AXP did not affect proliferation or show any toxic effect on the regular human colon cell line CCD 841 CoN. The results indicate that AXP are promising biocompatible materials with antioxidant activity. AXP could be suitable materials for the development of drug delivery systems targeted to colon.

Some studies demonstrate that gallic acid (GA) and myricetin (MYR) isolated from Rhus trilobata provide the therapeutic activity of the plant against cancer. However, few reports demonstrate that both compounds also could have therapeutic potential in ovarian cancer treatment. Therefore, to evaluate the cytotoxic activity of GA and MYR against ovarian cancer cells and to determine the possible action mechanism present is important. With this purpose, SKOV-3 ovarian adenocarcinoma cells (HTB-77™, ATCC®) were cultivated at 37°C with 5% CO₂ according to supplier's instructions for determine the biological activity of GA and MYR by confocal/transmission electron microscopy, PI-flow cytometry, H₂DCF-DA, MTT and Annexin V/PI assays. Possible molecular targets of the compounds were determined by Similarity Ensemble Approach model. Results showed that GA and Myr treatments decreased viability of SKOV-3 cells at 50 and 166 μg/mL respectively (p ≤ 0.05, ANOVA vs vehicle group); As well as morphological changed (cytoplasmatic reduction, nuclear chromatin condensation, cytoplasmic vesicles increment, polymerized actin, and stabilized tubulin), cell cycle arrest (GA: 8.3% G₂/M and MYR: 78% G₁), and apoptosis induction (GA: 18.9% and MYR: 8.1%), because to ROS generation (34 to 42%) for 24 h (p ≤ 0.05, ANOVA vs vehicle group). In silico studies demonstrated that GA and MYR interact with carbonic anhydrase and PI3K, respectively. As conclusions, GA and MYR show cytotoxic activity against SKOV-3 cells through ROS production, which modify the cytoskeleton and induce apoptosis mainly. Therefore, GA and Myr could be considered as a starting point for the development of novel anticancer agents.