ObjectiveThis study aimed to investigate the influence of potential placebo and nocebo effects on pain perception of percutaneous needle electrolysis (PNE) in individuals with patellar tendinopathy.MethodsIn this secondary analysis of a three-arm randomized double-blinded controlled trial, intra and inter-session pain perception data from 48 sporting participants with patellar tendinopathy between 18 and 45 years were investigated. Participants were divided into 3 parallel groups: “no-sham group” [PNE intervention], “single-sham group” [sham PNE by using dry needling], and “double-sham group” [sham PNE by using sham needles]. Every group received 4 sessions of the needling therapies targeting the patellar tendon over 8 weeks and was instructed to perform a unilateral eccentric exercise program of the quadriceps muscle on the affected side. Clinical and needle-related pain was assessed before, during, and after each treatment session using a visual analog scale.ResultsNo differences were found between groups intra- or inter-session in terms of pain reduction (P = 0.424) despite clinical pain decreased in all groups since the first treatment session (P < 0.001). Furthermore, although the double-sham group showed a lower percentage of participants reporting needle-related pain during needle intervention (P = 0.005), the needle-related pain intensity after needle intervention was similar between groups (P = 0.682). Moreover, there were no group differences for the duration of pain sensation after any needle intervention (P = 0.184), extending in many cases beyond 24 h.ConclusionNeedling therapies for individuals with patellar tendinopathy are prone to elicit placebo effects regarding clinical pain and nocebo effects regarding needling-related pain. Clinicians and physical therapists treating musculoskeletal pain conditions should consider the added value and potential mechanisms of action before routinely using needle techniques.
Oxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Cannabis sativa L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant's antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from Cannabis sativa L. in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100 µM). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed in silico. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-κB2, IL-6, and IL-8. In silico docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that Cannabis sativa L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis alongside metabolic comorbidities like type 2 diabetes mellitus (T2DM), dyslipidaemia, overweight, or obesity. Liver damage could be prevented promoting consumption of fruits and vegetables, the main source of phenolic compounds. These molecules have been previously related with antioxidant and anti-obesity properties. Therefore, the objective of this study is to determine the antioxidant capacity and potential preventive activity of an autochthonous apple pulp extract, Amarilla de Octubre, and its main phenolic compound, procyanidin B2 (PB2), in an in vitro model of liver steatosis. Antioxidant activity was assessed by xanthine/xanthine oxidase (X/XO) system and nitric oxide scavenging production. Monoamine oxidase A (MAO-A) inhibition was also determined due to its implication in detoxification processes in liver. Human hepatocytes (HepG2 cell line) were selected to test their potential cytotoxicity, oxidative stress situations (ROS production) and the potential effect in lipid metabolism by overloading cells with oleic acid. Fat accumulation and gene expression related to lipid metabolism (PPARγ, CD36 and FAS) were also analysed by Oil Red O and qPCR respectively. PB2 showed promising results as an antioxidant compound in scavenging and enzymatic inhibition-related experiments. However, Amarilla de Octubre not only reduce fat accumulation, but also modulates the expression of PPARγ, CD36, and FAS and demonstrates slightly lower efficacy than PB2 in scavenging and enzymatic inhibition-related experiments. These results highlight the potential of apples to mitigate pathogenic conditions associated with metabolic disorders such as obesity, emphasizing the role of dietary polyphenols in this protective effect.
Thinned apples are a common by-product of apple orchards, produced in abundant quantities through thinning or natural drop, leading to the loss of substantial amounts of phenolic compounds with potential bioactive properties. Ten thinned apple samples, representing both commercial and autochthonous cultivars, were ultrasonicated using ethanol as green solvent, with the main goal of reusing their phenolic content for industrial and nutritional applications. For this reason, the phenolic content was characterized with high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The antioxidant, antidiabetic, and cardiovascular activities were evaluated and correlated with the targeted phenolic compounds. Under non-cytotoxic conditions in Caco-2, HepG2 and HFF-1 cells, Amarilla de Octubre and Pomera de Pomes Agrias showed the strongest antioxidant-antiglycation activity as well as ACE inhibition, while Reineta and Verde Doncella excelled in HMGR and ACE inhibition. Pomera de Pomes Agrias, Vadiello-02, Reineta and Verde Doncella led digestive enzymes under Caco-2 safety.
Abstract The obligate intracellular bacterium Chlamydia trachomatis is the most common bacterial sexually transmitted infection globally, with approximately 131 million new cases each year. It contributes to widespread reproductive health issues, including infertility and chronic pelvic pain. The unique cell morphology and biphasic life cycle pose challenges to their effective eradication. Guided by the identification of essential oils (EOs) capable of suppressing C. trachomatis intracellular growth, this study evaluated the antichlamydial properties of the monoterpene limonene and its metabolites perillyl alcohol and perilic acid. The antichlamydial activity was assessed through qPCR-based quantification of bacterial genome copy numbers and immunofluorescence staining of chlamydial inclusions to monitor bacterial growth and infectious progeny production. Elementary body membrane integrity was assessed with viability PCR. Citrus limon essential oil exhibited dose-dependent inhibition of C. trachomatis growth, decreasing infectious progeny by over 90%. Pinus sylvestris EO displayed consistent but non-dose-dependent effects. Limonene, a major constituent of the EOs, exhibited significant suppression of chlamydial growth and progeny production, particularly for its R-enantiomer. While viability-PCR data indicated that the EOs and limonene affected EB membrane permeability, EB infectivity was not affected by the treatments. Perillyl alcohol suppressed chlamydial growth at a lower concentration (100 µg mL−1) than the parent compound limonene. The antichlamydial activity of both limonene and perillyl alcohol was suppressed when infected cultures were supplemented with farnesyl or geranylgeranyl, indicating that the antichlamydial mechanism of the two monoterpenes involves competitive inhibition of protein prenylation. Hence, targeting host protein prenylation may be an effective antichlamydial strategy. Graphical Abstract
