DN4 questionnaire as a useful tool for evaluating the pharmacotherapeutic response to opioid pharmacotherapy in malignant neuropathy.

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Self-assembled metal-phenolic network nanoparticles for delivery of a cisplatin prodrug for synergistic chemo-immunotherapy.

Despite cisplatin's pivotal role in clinically proven anticancer drugs, its application has been hampered by severe side effects and a grim prognosis. Herein, we devised a glutathione (GSH)-responsive nanoparticle (PFS-NP) that integrates a disulfide bond-based amphiphilic polyphenol (PP-SS-DA), a dopamine-modified cisplatin prodrug (Pt-OH) and iron ions (Fe3+) through coordination reactions between Fe3+ and phenols. After entering cells, the responsively released Pt-OH and disulfide bonds eliminate the intracellular GSH, in turn disrupting the redox homeostasis. Meanwhile, the activated cisplatin elevates the intracellular H2O2 level through cascade reactions. This is further utilized to produce highly toxic hydroxyl radicals (˙OH) catalyzed by the Fe3+-based Fenton reaction. Thus, the amplified oxidative stress leads to immunogenic cell death (ICD), promoting the maturation of dendritic cells (DCs) and ultimately activating the anti-tumor immune system. This innovative cisplatin prodrug nanoparticle approach offers a promising reference for minimizing side effects and optimizing the therapeutic effects of cisplatin-based drugs.

Intranasal Tapentadol Versus Intravenous Paracetamol for Postoperative Analgesia in Lower Limb Orthopaedic Surgeries Under Spinal Anaesthesia: A Single Blind RCT.

OBJECTIVE: We aimed to compare the analgesic effectiveness of intranasal tapentadol nasal spray 44.5 mg and intravenous (IV) paracetamol 1 gm during the postoperative period in patients undergoing lower limb orthopedic surgeries under spinal anesthesia. METHODS: This prospective, randomized, single-blind clinical trial was carried out in a tertiary care teaching hospital. Patients aged between 18 and 60 years of physical status ASA grade 1-3 were included in the study. Postoperative pain scores were measured using the visual analog scale (VAS) in centimeters (cm) every 12 hours in 37 patients per group. The patients were administered either intranasal tapentadol or IV paracetamol every 6 hours for 72 hours, beginning 3 hours after surgery. RESULTS: There was a significant group by intervention effect favoring intranasal tapentadol, suggesting a greater reduction in VAS pain scores after the intervention at 72 hours (estimate: -1.58 cm; SE:0.2; P<0.001). Group by time effect for all the measured time frames, except for 36 hours, favored intranasal tapentadol with estimated values for greater reduction in VAS pain scores ranging from -0.8 cm to -1.6 cm. DISCUSSION: The results of the present study suggests that intranasal tapentadol results in a greater reduction of postoperative pain compared with IV paracetamol in lower limb orthopedic surgeries. The ease of administration of tapentadol may make it a preferred option over IV paracetamol in such surgeries.

The preventive and therapeutic consumption of meat enriched with carob fruit extract, rich in phenolic compounds, improves colonic antioxidant status in late-stage T2DM rats.

Oxidative stress is prevalent in Type 2 Diabetes Mellitus (T2DM) and has been associated with high meat consumption. Carob Fruit Extract (CFE) contains phenolic compounds, making it a suitable functional ingredient. Current study aims to evaluate the effect of CFE-enriched meat (CFE-meat) consumption on the antioxidant status of proximal and distal colon, and its relationship with fecal phenolic compounds in late-stage T2DM rats. Three groups of eight rats were studied: 1) D, fed control-meat; 2) ED, fed CFE-meat since the beginning of the study; 3) DE, fed CFE-meat after confirming T2DM. CFE-meat consumption reduces colonic oxidative stress mainly in the proximal section and helps to ameliorate glutathione metabolism and antioxidant score. Difference between ED and DE groups were associated with colon homeostasis and T2DM progression suggesting greater fermentation but lower absorption in the DE group. CFE appears as a promising tool to improve the antioxidant status observed in late-stage T2DM.

Inhalation of 2, 4-di-tert-butylphenol-Loaded micelles suppresses respiratory syncytial virus infection in mice.

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.

Randomised clinical trial to test the phenolization in sacrococcygeal pilonidal disease.

To test the efficacy and safety of phenolization in uncomplicated Sacrococcygeal pilonidal disease (SPD) the phenolization in uncomplicated SPD is feasible and secure in selected patients in observational studies. The greatest benefits are obtained to reduce the length of sick leave (LSL) and complications. Single-center randomised controlled clinical trial. Patients were recruited at University Hospital of Tarragona Joan XXIII of Spain. Patients were randomised into two treatment groups. All patients with uncomplicated sacrococcygeal disease, localised in the midline and with only 1 fistulous orifice. The patients were randomly assigned to the phenolization group (PhG) or conventional-surgery group (CsG). Both groups were managed without admission. The main endpoint was the recurrence of sacrococcygeal disease. Secondary endpoints included time of sick leave, complications, and readmission. 124 patients were included in the study. No disease recurrence was observed in either group. Clinical follow-up was carried out with a mean of 493.8 days (SD 6.59). The LSL was shorter in the PhG (mean 19.63 days, SD 28.15) than in the CSG (43.95 days, SD 38.60). The LSL reduction was -24.31 days (P .002). The phenolization in selected SPD is a safe and feasible procedure in selected patients. This approach could become the standard of care for patients with selected Sacrococcygeal pilonidal.

Bisphenol A Induces Histopathological, Hematobiochemical Alterations, Oxidative Stress, and Genotoxicity in Common Carp (Cyprinus carpio L.).

Bisphenol A (BPA) is one of the environmental endocrine disrupting toxicants and is widely used in the industry involving plastics, polycarbonate, and epoxy resins. This study was designed to investigate the toxicological effects of BPA on hematology, serum biochemistry, and histopathology of different organs of common carp (Cyprinus carpio). A total of 60 fish were procured and haphazardly divided into four groups. Each experimental group contained 15 fish. The fish retained in group A was kept as the untreated control group. Three levels of BPA 3.0, 4.5, and 6 mg/L were given to groups B, C, and D for 30 days. Result indicated significant reduction in hemoglobin (Hb), lymphocytes, packed cell volume (PCV), red blood cells (RBC), and monocytes in a dose-dependent manner as compared to the control group. However, significantly higher values of leucocytes and neutrophils were observed in the treated groups (P < 0.05). Results on serum biochemistry revealed that the quantity of glucose, cholesterol, triglycerides, urea, and creatinine levels was significantly high (P < 0.05). Our study results showed significantly (P < 0.05) increase level of oxidative stress parameters like reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) and lower values of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) in treated groups (4.5 mg/L and 6 mg/L)) in the brain, liver, gills, and kidneys. Our study depicted significant changes in erythrocytes (pear shaped erythrocytes, leptocytes, microcytes, spherocytes, erythrocytes with broken, lobed, micronucleus, blabbed, vacuolated nucleus, and nuclear remnants) among treated groups (4.5 mg/L and 6 mg/L). Comet assay showed increased genotoxicity in different tissues including the brain, liver, gills, and kidneys in the treated fish group. Based on the results of our experiment, it can be concluded that the BPA exposure to aquatic environment is responsible for deterioration of fish health, performance leading to dysfunction of multiple vital organs.

Anxiolytic Effect and Improved Sleep Quality in Individuals Taking Lippia citriodora Extract.

The current fast-moving, hectic lifestyle has increased the number of individuals worldwide with difficulties in managing stress, which in turn is also affecting their sleep quality. Therefore, the objective of the current study was to assess a natural plant-based dietary supplement comprised of lemon verbena (Lippia citriodora) extract, purified in phenylpropanoids, in alleviating stress and improving quality of sleep. A double-blind, placebo-controlled study was conducted for 8 weeks, followed by a 4-week washout period. Both validated questionnaires and functional tests were performed during the study, whereas questionnaires were used after the washout. As a result, the group taking the lemon verbena extract significantly reduced their perception of stress after 8 weeks, which was corroborated by a significant decrease in cortisol levels. After the washout period, the subjects reported to present even lower stress levels, due to the lasting effect of the ingredient. As for sleep quality, the subjects taking the supplement reported feeling better rested, with a stronger effect observed in women. Sleep tracking using a wearable device revealed that the supplement users improved their times in the deeper stages of sleep, specifically their percentage of time in deep sleep and REM. In conclusion, lemon verbena extract purified in phenylpropanoids is revealed as a natural solution to help individuals to improve their stress and sleep quality.

Salidroside attenuates cardiac dysfunction in a rat model of diabetes.

AIM: This study aimed to investigate the therapeutic effects of salidroside on diabetes-induced cardiovascular disease. METHODS: Sprague-Dawley rats treated with 65 mg/kg of streptozotocin (STZ) on a daily basis were used to establish the diabetic rat model (blood glucose levels >13.9 mmol/L). Cardiac functions of diabetic rats were evaluated by their haemodynamic alterations. Western blot assay was performed to evaluate the protein levels of multiple signalling pathway factors. Quantitative real-time PCR assay was performed to investigate the inflammation and oxidative stress of diabetic rats. RESULTS: Salidroside treatment improved the cardiac functions of diabetic rats. In addition, salidroside therapy attenuated the cardiac oxidative stress induced by diabetes. Salidroside inhibited the diabetes-induced inflammation in diabetic rat hearts. The apoptosis of cardiomyocytes was also alleviated by the treatment of salidroside. Salidroside also upregulated the phosphorylation levels of AMPK, ACC, TSC2 and RAPTOR. CONCLUSION: Salidroside exerts protective effects against diabetes-induced cardiac dysfunction by modulating the mTOR and AMPK signalling pathways.

Chronic bisphenol A exposure triggers visual perception dysfunction through impoverished neuronal coding ability in the primary visual cortex.

Contrast perception is a fundamental visual ability that allows us to distinguish objects from the background. However, whether it is perturbed by chronic exposure to environmental xenoestrogen, bisphenol A (BPA), is still elusive. Here, we used adult cats to explore BPA-induced changes in contrast sensitivity (CS) and its underlying neuronal coding mechanism. Behavioral results showed that 14 days of BPA exposure (0.4 mg/kg/day) was sufficient to induce CS declines at the tested spatial frequencies (0.05-2 cycles/deg) in all four cats. Furthermore, based on multi-channel electrophysiological recording and interneuronal correlation analysis, we found that the BPA-exposed cats exhibited an obvious up-regulation in noise correlation in the primary visual cortex (area 17, A17), thus providing a population neuronal coding basis for their perceptual dysfunction. Moreover, single neuron responses in A17 of BPA-exposed cats revealed a slight but marked decrease in CS compared to that of control cats. Additionally, these neuronal responses presented an overt decrease in signal-to-noise ratio, accompanied by increased trial-to-trial response variability (i.e., noise). To some extent, these neuron population and unit dysfunctions in A17 of BPA-exposed cats were attributable to decreased response activity of fast-spiking neurons. Together, our findings demonstrate that chronic BPA exposure restricts contrast perception, in response to impoverished neuronal coding ability in A17.

DFMO Improves Survival and Increases Immune Cell Infiltration in Association with MYC Downregulation in the Pancreatic Tumor Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor five-year survival rate of less than 10%. Immune suppression along with chemoresistance are obstacles for PDAC therapeutic treatment. Innate immune cells, such as tumor-associated macrophages, are recruited to the inflammatory environment of PDAC and adversely suppress cytotoxic T lymphocytes. KRAS and MYC are important oncogenes associated with immune suppression and pose a challenge to successful therapies. Here, we targeted KRAS, through inhibition of downstream c-RAF with GW5074, and MYC expression via difluoromethylornithine (DFMO). DFMO alone and with GW5074 reduced in vitro PDAC cell viability. Both DFMO and GW5074 showed efficacy in reducing in vivo PDAC growth in an immunocompromised model. Results in immunocompetent syngeneic tumor-bearing mice showed that DFMO and combination treatment markedly decreased tumor size, but only DFMO increased survival in mice. To further investigate, immunohistochemical staining showed DFMO diminished MYC expression and increased tumor infiltration of macrophages, CD86+ cells, CD4+ and CD8+ T lymphocytes. GW5074 was not as effective in modulating the tumor infiltration of total CD3+ lymphocytes or tumor progression and maintained MYC expression. Collectively, this study highlights that in contrast to GW5074, the inhibition of MYC through DFMO may be an effective treatment modality to modulate PDAC immunosuppression.

Human Metabolism and Urinary Excretion Kinetics of Nonylphenol in Three Volunteers after a Single Oral Dose.

Nonylphenol (NP) is an endocrine-disrupting anthropogenic chemical that is ubiquitous in the environment. Human biomonitoring data and knowledge on internal NP exposure are still sparse, and its human metabolism is largely unknown. Therefore, in this study, we investigated human metabolism and urinary excretion of NP. Three male volunteers received a single oral dose of 1 mg 13C6-labeled NP (10.6-11.7 µg/kg body weight). Consecutive full urine voids were collected for 48 h. A metabolite screening identified nine ring- and/or side chain-oxidized metabolites. We chose the most promising hits, the alkyl chain-oxidized metabolites hydroxy-NP (OH-NP) and oxo-NP, for quantitative investigation next to the parent NP. For this purpose, we newly synthesized specific n - 1-oxidized monoisomeric analytical standards. Quantification of the polyisomeric metabolites was performed via online-solid phase extraction-LC-MS/MS with stable isotope dilution using a previously published consensus method. Alkyl chain hydroxylation (OH-NP) constituted the major metabolism pathway representing 43.7 or 62.2% (depending on the mass transition used for quantification) of the NP dose excreted in urine. The urinary excretion fraction (FUE) for oxo-NP was 6.0 or 9.3%. The parent NP, quantified via an analogous isomeric 13C6-NP standard, represented 6.6%. All target analytes were excreted predominately as glucuronic acid conjugates. Excretion was rather quick, with concentration maxima in urine 2.3-3.4 h after dosing and biphasic elimination kinetics (elimination half-times first phase: 1.0-1.5 h and second phase: 5.2-6.8 h). Due to its high FUE and insusceptibility to external contamination (contrary to parent NP), OH-NP represents a robust and sensitive novel exposure biomarker for NP. The novel FUEs enable to robustly back-calculate the overall NP intakes from urinary metabolite levels in population samples for a well-informed cumulative exposure and risk assessment.

Effect of Phenolic Compounds on Human Health.

This book, based on a Special Issue of Nutrients, contains a total of 12 papers (8 original research and 4 reviews) on the effect of phenolic compounds on human health [...].

Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness.

CONTEXT: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (Crassulaceae) is used to prevent and treat acute mountain sickness. However, the mechanisms underlying its effects on the central nervous system remain unclear. OBJECTIVE: To investigate the effect of Rhodiola crenulata on cellular metabolism in the central nervous system. MATERIALS AND METHODS: The viability and Hif-1α levels of microglia and neurons at 5% O2 for 1, 3, 5 and 24 h were examined. We performed the binding of salidroside (Sal), rhodiosin, tyrosol and p-hydroxybenzyl alcohol to Hif-1α, Hif-1α, lactate, oxidative phosphorylation and glycolysis assays. Forty male C57BL/6J mice were divided into control and Sal (25, 50 and 100 mg/kg) groups to measure the levels of Hif-1α and lactate. RESULTS: Microglia sensed low oxygen levels earlier than neurons, accompanied by elevated expression of Hif-1α protein. Salidroside, rhodiosin, tyrosol, and p-hydroxybenzyl alcohol decreased BV-2 (IC50=1.93 ± 0.34 mM, 959.74 ± 10.24 µM, 7.47 ± 1.03 and 8.42 ± 1.63 mM) and PC-12 (IC50=6.89 ± 0.57 mM, 159.28 ± 8.89 µM, 8.65 ± 1.20 and 8.64 ± 1.42 mM) viability. They (10 µM) reduced Hif-1α degradation in BV-2 (3.7-, 2.5-, 2.9- and 2.5-fold) and PC-12 cells (2.8-, 2.8-, 2.3- and 2.0-fold) under normoxia. Salidroside increased glycolytic capacity but attenuated oxidative phosphorylation. Salidroside (50 and 100 mg/kg) treatment increased the protein expression of Hif-1α and the release of lactate in the brain tissue of mice. CONCLUSIONS: These results suggest that Sal induces metabolic reprogramming by regulating the Hif-1α signalling pathway to activate compensatory responses, which may be the core mechanism underlying the effect of Rhodiola crenulata on the central nervous system.

Bisphenol A single and repeated treatment increases HDAC2, leading to cholinergic neurotransmission dysfunction and SN56 cholinergic apoptotic cell death through AChE variants overexpression and NGF/TrkA/P75NTR signaling disruption.

Bisphenol-A (BPA), a widely used plasticizer, induces cognitive dysfunctions following single and repeated exposure. Several studies, developed in hippocampus and cortex, tried to find the mechanisms that trigger and mediate these dysfunctions, but those are still not well known. Basal forebrain cholinergic neurons (BFCN) innervate hippocampus and cortex, regulating cognitive function, and their loss or the induction of cholinergic neurotransmission dysfunction leads to cognitive disabilities. However, no studies were performed in BFCN. We treated wild type or histone deacetylase (HDAC2), P75NTR or acetylcholinesterase (AChE) silenced SN56 cholinergic cells from BF with BPA (0.001 µM-100 µM) with or without recombinant nerve growth factor (NGF) and with or without acetylcholine (ACh) for one- and fourteen days in order to elucidate the mechanisms underlying these effects. BPA induced cholinergic neurotransmission disruption through reduction of ChAT activity, and produced apoptotic cell death, mediated partially through AChE-S overexpression and NGF/TrkA/P75NTR signaling dysfunction, independently of cholinergic neurotransmission disruption, following one- and fourteen days of treatment. BPA mediates these alterations, in part, through HDAC2 overexpression. These data are relevant since they may help to elucidate the neurotoxic mechanisms that trigger the cognitive disabilities induced by BPA exposure, providing a new therapeutic approach.

Developmental toxicity of bisphenol S in Caenorhabditis elegans and NODEF mice.

The growing concern surrounding bisphenol A (BPA) has led to increased industrial production and application of its analog bisphenol S (BPS). The goals of this study were: (1) To examine the generational effects in the nematode C. elegans for up to three generations following developmental exposure to BPS (0.1, 1.0, 5.0 and 10.0 µM), and (2) To examine the neurotoxicity and metabolic toxicity in NODEF mouse offspring exposed to BPS (3 µg/kg BW) in utero throughout gestation once/day via oral pipette. First, worms were exposed to BPS developmentally for a single period of 48 hours and then propagated for 2 additional generations. Exposure to 0.1 and 1.0 µM BPS decreased lifespan and the number of progeny with an ability to recover in subsequent generations. In contrast, worms exposed to 5.0 or 10.0 µM BPS exhibited a continuous effect in the second generation, e.g., decreased lifespan and reduced number of progeny. Only worms exposed to 10.0 µM BPS continued to have a significant long-term effect (e.g., decreased lifespan) through the third generation. In addition, worms developmentally exposed to BPS at 5.0 µM and 10.0 µM also showed decreases in body bends. In contrast, worms exposed to 0.1 µM BPS exhibited a significant increase in head thrashes. When the multigenerational effects were examined by exposing worms to BPS for 48 hours developmentally at each generation for three generations, an accumulative effect was observed in worms treated with 0.1 or 1.0 µM BPS for two generations, but not for three generations, suggesting a threshold existed. Worms exposed to either 5.0 or 10.0 µM BPS demonstrated accumulative effects through two and three generations. When the developmental effects of BPS were studied in NODEF mice, offspring exposed gestationally exhibited behavioral deficits at 12, but not at 3, weeks of age. Specifically, female offspring had decreases in working and short-term memories while male offspring showed increases in hyperactivity and anxiety-like behaviors. In summary, this study demonstrates the sex-related effects of BPS in NODEF mouse offspring exposed in utero, along with the generational effects observed in C. elegans.

Sesamol supplementation alleviates nonalcoholic steatohepatitis and atherosclerosis in high-fat, high carbohydrate and high-cholesterol diet-fed rats.

Sesamol, a major ingredient in sesame seeds (Sesamum indicum L.) and its oil, is considered a powerful functional food ingredient. However, few studies have investigated its effects on high-fat, high carbohydrate and high-cholesterol (HF-HCC) diet-induced nonalcoholic steatohepatitis (NASH) complicated with atherosclerosis. The present study elucidates the protective effects of sesamol against NASH and atherosclerosis in HF-HCC diet-fed rats. Sprague-Dawley rats were supplemented with or without sesamol in drinking water (0.05 mg mL-1, 0.1 mg mL-1 and 0.2 mg mL-1) from the beginning to end. At the end of the experiment, sesamol supplementation suppressed HF-HCC diet-induced body weight gain and increased absolute liver and adipose tissue weights in rats. Serum biochemical analyses showed that sesamol supplementation improved HF-HCC diet-induced metabolism disorders and damaged vascular endothelial function. Histological examinations displayed that dietary sesamol not only alleviated hepatic balloon degeneration, steatosis, inflammation and fibrosis, but also mitigated lipid accumulation and fibrous elements in the aorta arch in HF-HCC diet-fed rats. In addition, sesamol supplementation inhibited hepatic NOD-like receptor protein 3 (NLRP3) expression and ERS-IRE1 signaling pathway activation. Moreover, sesamol treatment decreased uric acid levels both in serum and the liver by its effect on the inhibition of xanthine oxidase (XO) activity and/or its expression, which might be closely associated with the inhibitions of NLRP3 expression and ERS-IRE1 signaling pathway activation in HF-HCC diet-fed rats. These findings demonstrated that sesamol alleviated NASH and atherosclerosis in HF-HCC diet-fed rats, and may be a potent dietary supplement for protection against these diseases.

Regular, but not acute, green tea supplementation increases total antioxidant status and reduces exercise-induced oxidative stress: a systematic review.

This systematic review aims to investigate the effects of green tea supplementation on exercise-induced oxidative stress. Four electronic databases were searched from inception to December 2020: SPORTDiscuss, PubMed, Scopus, and Web of Science. The search strategy was established in the following manner: (green tea) (Title/Abstract) AND (exercise OR training) (Title/Abstract) AND (oxidative stress OR antioxidant OR oxidation) (Title). After the application of inclusion and exclusion criteria 11, randomized or non-randomized control trials were included, 6 with a parallel design and 5 with a crossover design. Study methodological quality was assessed with the PEDro scale, and all studies were considered of moderate quality. Overall, acute green tea ingestion does not appear to influence antioxidant status or reduce exercise-induced oxidative stress. In contrast, green tea supplementation before exercise, for periods of more than 1 week, in a dose range of 400 to 800 mg of catechins per day, appears to be efficacious to increase total antioxidant status and protect cells against exercise-induced oxidative stress. Future investigations should focus on beginning green tea supplementation more than 7 days before exercise and completing it 2 or 3 days after while monitoring the change of markers of oxidative stress up to 48-72 h after exercise.

Design and Engineering of "Green" Nanoemulsions for Enhanced Topical Delivery of Bakuchiol Achieved in a Sustainable Manner: A Novel Eco-Friendly Approach to Bioretinol.

In the present work, we establish novel "environmentally-friendly" oil-in-water nanoemulsions to enhance the transdermal delivery of bakuchiol, the so-called "bioretinol" obtained from powdered Psoralea corylifolia seeds via a sustainable process, i.e., using a supercritical fluid extraction approach with pure carbon dioxide (SC-CO2). According to Green Chemistry principles, five novel formulations were stabilized by "green" hybrid ionic surfactants such as coco-betaine-surfactin molecules obtained from coconut and fermented rapeseed meal. Preliminary optimization studies involving three dispersion stability tests, i.e., centrifugation, heating, and cooling cycles, indicated the most promising candidates for further physicochemical analysis. Finally, nanoemulsion colloidal characterization provided by scattering (dynamic and electrophoretic light scattering as well as backscattering), microscopic (transmission electron and confocal laser scanning microscopy), and spectroscopic (UV-Vis spectroscopy) methods revealed the most stable nanocarrier for transdermal biological investigation. In vitro, topical experiments provided on human skin cell line HaCaT keratinocytes and normal dermal NHDF fibroblasts indicated high cell viability upon treatment of the tested formulation with a final 0.02-0.2 mg/mL bakuchiol concentration. This excellent biocompatibility was confirmed by ex vivo and in vivo tests on animal and human skin tissue. The improved permeability and antiaging potential of the bakuchiol-encapsulated rich extract were observed, indicating that the obtained ecological nanoemulsions are competitive with commercial retinol formulations.

Sesamol induces cytotoxicity via mitochondrial apoptosis in SCC-25 cells.

Sesamol is the main constituent of sesame seed oil and is obtained from Sesamum indicum. Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms affecting the oral cavity. In this study, we investigated the cytotoxic potentials of sesamol on human oral squamous carcinoma (SCC-25) cells. Human oral squamous carcinoma cells were treated with different concentrations (62.5, 125, and 250 µM/mL) of sesamol for 24 h. Cytotoxicity was analyzed by 3- (4, 5- dimethylthiazol -2- yl) -2, 5-diphenyltetrazolium bromide (MTT) assay. Intracellular reactive oxygen species (ROS) expression was investigated by dichloro-dihydro-fluorescein diacetate assay. Apoptosis-related morphology was analyzed by acridine orange/ethidium bromide staining. Caspase-9 expression was analyzed by confocal microscopic double immunofluorescence staining. Mitochondrial apoptosis-related markers are analyzed using qPCR. Sesamol treatment caused a significant cytotoxic effect in OSCC cells. Sesamol-induced cytotoxic effect was associated with intracellular ROS generation. Sesamol treatments induced a significant increase in the early and late apoptotic cells. This treatment also induced caspase-9 expression in OSCC cells. Sesamol treatments caused downregulation of Harvey rat sarcoma viral oncogene homolog (HRAS) expression at protein and gene levels. Sesamol treatment modulates intrinsic apoptotic marker gene expression in OSCC cells. Overall results confirm the anti-cancer potential of sesamol and it seems to be a promising candidate for OSCC.