Evaluation of the Immunomodulatory Effects of a Probiotics and Natural Extract-Based Formulation in Bacterial-Induced Prostatitis.

Among the many factors inducing prostate inflammation, bacterial contribution is potentially underrated according to the scientific community. Bacterial prostatitis is characterized by modifications of the prostatic microenvironment, mainly driven by the immune system. Macrophages play a major role in bacterial prostatitis, secreting a plethora of proinflammatory and chemoattractive cytokines and proteolytic enzymes able to degrade the ECM, so facilitating the invasion of other immune cells. Consequently, macrophages represent a link between bacterial infection and prostate inflammation, as well as being the main target of prostate anti-inflammatory drugs and dietary supplements. This study aims to investigate the effect of a formulation composed of active principles and a probiotic strain with a particular focus on the anti-inflammatory effect in an in vitro bacterial prostatitis model. The results obtained showed that the formulation reduces the inflammatory response of prostatic epithelium induced by bacterial infection. This effect is mediated by the modulation of activated macrophages. Analysis of the cytokines released highlights that the tested formulation is able to reduce the expression of key proinflammatory cytokines involved in the pathogenesis of prostate diseases, in particular prostate cancer, and represents a valuable tool to prevent bacterial prostatitis and ensure favorable prostate health.

Micronized Palmitoylethanolamide, Hempseed Oil, and Maritime Pine Bark Dry Extract (Pelvipea®) for Pelvic Pain: An In Vitro Study for Urothelial Inflammation Treatment.

Urothelial inflammation plays a key role in the pathogenesis of chronic pelvic pain due to its origin in the bladder. The aim of this study was to evaluate the efficacy of a patent-pending formulation (Pelvipea®) composed of micronized palmitoylethanolamide (PEA), hempseed oil, and maritime pine bark dry extract in reducing urothelial inflammation, as well as the effect of each ingredient individually, in order to define the synergistic effect of the three ingredients. An in vitro bladder urothelium model composed of the T24 cell line was exposed to a conditioned media obtained by treating macrophage-differentiated THP-1 cells with different concentrations of the functional ingredients and a mixture of them in the presence of the pro-inflammatory stimulus of Escherichia coli. Cells exposed only to the inflammatory stimulus in the absence of pre-treatment were considered as a positive control for inflammation. The impact of each functional ingredient and their mixture on inflammation was evaluated by the determination of transcription factor NF-kB and of pro-inflammatory cytokine expression. Statistical analysis was performed using the t-test, comparing the mixture and the single ingredients for every condition tested. All results were reported as fold change (mean ± standard deviation), the ratio between the values obtained from the respective treatments for inflammation control. The three functional ingredients did not induce negative effects on THP-1 cell vitality. The levels of NF-kB were reduced following treatment with hempseed oil, maritime pine bark dry extract, and the mixture at all tested concentrations, and with micronized PEA from 25 to 200 µg/mL. Treatment with the mixture resulted in the lowest expression levels of interleukins (IL)-1ß, IL-6, and IL-8 compared to the single functional ingredients at a concentration of 230 µg/mL, with values of 0.08 (±0.00), 0.01 (±0.00), and 0.32 (±0.01), respectively. The mixture of micronized PEA, hempseed oil, and maritime pine bark dry extract (Pelvipea®) at 230 µg/mL showed the best efficacy in urothelial IL-1ß, IL-6, and IL-8 reduction compared with the singular components. This formulation may represent a promising therapeutic option to relieve painful symptoms originating in the bladder. However, in vivo studies are needed to confirm these results.

Nano- and microplastics: a comprehensive review on their exposure routes, translocation, and fate in humans.

Contamination of the environment with nano-and microplastic particles (NMPs) and its putative adverse effects on organisms, ecosystems, and human health is gaining increasing scientific and public attention. Various studies show that NMPs occur abundantly within the environment, leading to a high likelihood of human exposure to NMPs. Here, different exposure scenarios can occur. The most notable exposure routes of NMPs into the human body are via the airways and gastrointestinal tract (GIT) through inhalation or ingestion, but also via the skin due to the use of personal care products (PCPs) containing NMPs. Once NMPs have entered the human body, it is possible that they are translocated from the exposed organ to other body compartments. In our review article, we combine the current knowledge on the (1) exposure routes of NMPs to humans with the basic understanding of the potential (2) translocation mechanisms into human tissues and, consequently, their (3) fate within the human body. Regarding the (1) exposure routes, we reviewed the current knowledge on the occurrence of NMPs in food, beverages, personal care products and the air (focusing on indoors and workplaces) and found that the studies suggest an abundant presence of MPs within the exposure scenarios. The overall abundance of MPs in exposure matrices relevant to humans highlights the importance of understanding whether NMPs have the potential for tissue translocation. Therefore, we describe the current knowledge on the potential (2) translocation pathways of NMPs from the skin, GIT and respiratory systems to other body compartments. Here, particular attention was paid to how likely NMPs can translocate from the primary exposed organs to secondary organs due to naturally occurring defence mechanisms against tissue translocation. Based on the current understanding, we conclude that a dermal translocation of NMPs is rather unlikely. In contrast, small MPs and NPs can generally translocate from the GIT and respiratory system to other tissues. Thus, we reviewed the existing literature on the (3) fate of NMPs within the human body. Based on the current knowledge of the contamination of human exposure routes and the potential translocation mechanisms, we critically discuss the size of the detected particles reported in the fate studies. In some cases, the particles detected in human tissue samples exceed the size of a particle to overcome biological barriers allowing particle translocation into tissues. Therefore, we emphasize the importance of critically reading and discussing the presented results of NMP in human tissue samples.

Prostatic Therapeutic Efficacy of LENILUTS®, a Novel Formulation with Multi-Active Principles.

Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH etiology is still unclear. Recent works highlighted a relevant inflammation role in BPH onset and development. Consequently, to complement the 5-α reductase (and α-adrenergic receptor agonists-based therapy, an anti-inflammatory therapy should be devised. To reduce potential adverse effects of multi-drug treatment, plant extract-based therapies are becoming increasingly common. Serenoa repens, the main phytotherapic treatment for BPH, is not sufficient to front the multi-faceted etiology of BPH. In response to this, a novel, multiple phytotherapic agents-based formulation, LENILUTS®, was developed. In the present work, we compared, using an in vitro approach, the prostatic safety and efficacy of LENILUTS® with a commercial formulation, based only on Serenoa repens, and a 5αR inhibitor, Dutasteride. Furthermore, preliminary in vitro experiments to investigate the active principles, bioaccessibility and bioavailability of LENILUTS® were performed. Our results showed a better prostatic safety and therapeutic efficacy of LENILUTS® compared to the commercial formulation and Dutasteride, with increased anti-inflammatory, and pro-apoptotic activity, and a stronger inhibitory effect on the release of the key enzyme 5αR and Prostatic-Specific Antigen (PSA). The limited bioaccessibility and bioavailability of the active principles of LENILUTS® were highlighted. Considering the results obtained, the LENILUTS® formulation is more promising for BPH and LUTs therapy compared to formulations based on Serenoa repens only, but further efforts should be made to improve the bioaccessibility and bioavailability of the active principles.

Effects of short chain fructo-oligosaccharides on selected skin bacteria.

The human skin microbiota plays a key role in the maintenance of healthy skin, ensuring protection and biological barrier by competing with pathogens and by closely communicating with the immune system. The development of approaches which preserve or restore the skin microbiota represents a novel target for skincare applications. Prebiotics could be applied to balance almost any microbial community to achieve advantageous effects. However, information about their effectiveness as skin microbiota modulators is limited. The objective of the current study was to evaluate the effects of short chain fructo-oligosaccharides (scFOS) from sugar beet (DP 3-5), well-recognised prebiotics, on some representative bacterial strains of the skin microbiota. We measured the growth and competitive activity of these specific bacteria for the use of scFOS as energy source in minimal medium and in a reconstructed human epithelium (RHE) in vitro model. In minimal growth medium, scFOS promoted and sustained the growth of Staphylococcus epidermidis up to 24 h, considered a beneficial skin commensal bacterium, while inhibiting both Cutibacterium acnes and Staphylococcus aureus growth, regarded as opportunistic pathogens. S. epidermidis showed the highest colonization potential and 1% scFOS was effective in shifting the competition in favour of S. epidermidis with respect to C. acnes in the RHE model. This latter effect was observed following 24 h of exposure, suggesting a long-term effect of scFOS in a highly skin dynamic environment. Therefore, scFOS could be effectively implemented in skincare formulations for recovering skin microbiota homeostasis.

Intestinal Absorption Study of a Granular Form of Ferric Pyrophosphate.

Iron deficiency is one of the most prevalent nutritional disorders worldwide. The standard treatment involves iron supplementation, but this task is challenging because of poor solubility and organoleptic issues. Moreover, the need to increase iron bioavailability represents a challenge for treating iron-related disorders. In this study, gastroresistance and iron intestinal absorption of an innovative granular formulation composed of ferric pyrophosphate, modified starch and phospholipids branded as Ferro Fosfosoma® was investigated. Gastroresistant properties were studied using standard protocols, and a bioaccessible fraction was obtained by exposing a food supplement to in vitro digestion. This fraction was used for investigating iron absorption in Caco-2 and human follicle-associated intestinal epithelium (FAE) models. Ferro Fosfosoma® showed an improved resistance to gastric digestion and higher intestinal absorption than ferric pyrophosphate salt used as a control in both models. In the FAE model, Ferro Fosfosoma® induces larger iron absorption than in the Caco-2 monolayer, most likely due to the transcytosis ability of M cells. The larger iron absorption in the Ferro Fosfosoma®-treated FAE model corresponds to higher ferritin level, proving physiological iron handling that was once delivered by granular formulation. Finally, the formulation did not induce any alterations in viability and barrier integrity. To conclude, Ferro Fosfosoma® favors iron absorption and ferritin expression, while preserving any adverse effects.

Role of a Novel Silver Fir (Abies alba) Extract, Abigenol®/AlbiPhenol®, in Modulating Cardiovascular Disorders: Key Factors.

Cardiovascular diseases (CVDs) represent the leading cause of death worldwide, being responsible for about one third of deaths. Among CVDs, coronary artery diseases (CADs) are characterized by vascular endothelium dysfunction due to oxidative and inflammatory damages, the oxidation of circulating low-density lipoproteins (LDL) and high-density lipoproteins (HDL), and the production of ROS in the steatotic liver with the consequent increase of lipids and cholesterol. Together with CADs, heart failure (HF) represents another high-mortality rate CVD. A major risk factor for HF is hypertension that is accompanied by oxidative stress. Phytoextracts, rich in antioxidant and anti-inflammatory compounds, may have therapeutic value as they can interfere with several CVDs risk factors. In this work, a novel silver fir (Abies alba) bark extract, Abigenol®/AlbiPhenol®, was studied. First, Abigenol®/AlbiPhenol® cytotoxicity, bioaccessibility and bioavailability were evaluated by using an in vitro digestion model. Abigenol®/AlbiPhenol® was shown to be non-cytotoxic and showed good bioaccessibility. Then, by using in vitro hepatic, cardiac and vascular models, its antioxidant and anti-steatotic properties were assessed. Abigenol®/AlbiPhenol® showed an effective antioxidant action, and it was able to inhibit LDL and HDL oxidation, the main actors in atherosclerotic plaque formation. In steatotic conditions, Abigenol®/AlbiPhenol® induces decreased lipid and cholesterol accumulation in hepatocytes. In addition, in a cardiac model, the formulation reduced the activity of the hypertension-related angiotensin-converting enzyme (ACE). Altogether, these findings reveal a potential application of Abigenol®/AlbiPhenol® in the prevention and treatment of CVDs.

An investigation on [5 fluorouracil and epigallocatechin-3-gallate] complex activity on HT-29 cell death and its stability in gastrointestinal fluid.

Recently an enhancement of the sensitivity of colorectal cancer (CRC) cells by 5-fluorouracil (5FU) due to the concurrent treatment with epigallocatechin-3-gallate (EGCG) has been found. In the present paper, to investigate on this aspect, adenocarcinoma cells HT29 were treated with 5FU, EGCG and an equimolar mixture of 5FU and EGCG ([5FU+EGCG]) and cell viability was determined. While 5FU exhibits a clear activity, EGCG alone does not express any activity. However by treating the cells with [5FU+EGCG] a strong effect of EGCG is evidenced: the sensitivity of HT29 cells to 5FU was increased by 12-fold. A simulation of the behavior of [5FU+EGCG] in different compartments of the gastrointestinal digestion model was also performed. 5FU and EGCG solubilized into a mixture of digestive fluids analyzed by mass spectrometry did not lead to signals of 5FU, EGCG and the related complex, while by diluting the solution they become detectable. On the contrary, when 5FU and EGCG are submitted to the step-by-step digestion model procedure, the analysis did not show the presence of 5FU, EGCG and [5FU+EGCG]. This behaviour could be ascribed to the instability of these compounds due to the too severe digestion conditions and/or to the complexity of the matrix which could lead in ESI conditions to the suppression of the signals of the analytes of interest.

Detection and Characterization of TiO2 Nanomaterials in Sludge from Wastewater Treatment Plants of Chihuahua State, Mexico.

TiO2 nanoparticles (TiO2-NPs) have a wide range of industrial applications (paintings, sunscreens, food and cosmetics) and is one of the most intensively used nanomaterials worldwide. Leaching from commercial products TiO2-NPs are predicted to significantly accumulate in wastewater sludges, which are then often used as soil amendment. In this work, sludge samples from four wastewater treatment plants of the Chihuahua State in Mexico were obtained during spring and summer (2017). A comprehensive characterization study was performed by X-ray based (laboratory and synchrotron) techniques and electron microscopy. Ti was detected in all sludge samples (1810-2760 mg/kg) mainly as TiO2 particles ranging from 40 nm up to hundreds of nm. Micro-XANES data was analyzed by principal component analysis and linear combination fitting enabling the identification of three predominant Ti species: anatase, rutile and ilmenite. Micro-XANES from the smaller Ti particles was predominantly anatase (68% + 32% rutile), suggesting these TiO2-NPs originate from paintings and cosmetics. TEM imaging confirmed the presence of nanoscale Ti with smooth surface morphologies resembling engineered TiO2-NPs. The size and crystalline phase of TiO2-NPs in the sludge from this region suggest increased reactivity and potential toxicity to agro-systems. Further studies should be dedicated to evaluating this.

Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend.

Hepatic-related diseases, in particular hyperlipidemia and hypercholesterolemia, are a thorn on the side of the national health institutes around the globe. Indeed, liver lipid and cholesterol dysregulation could lead to atherosclerotic plaque formation and cardiovascular diseases. Currently, statin administration and monacolin K consumption are the main therapies proposed to counter this alarming connection, but relevant side effects are known. To overcome this issue, safe nutraceutical formulations and/or vegetal extracts, endowed with anticholesterolemic activity, could be instrumental in hypercholesterolemia prevention and treatment. In the present work, the anticholesterolemic efficacy of three vegetal extracts used in traditional medicine (artichoke, caigua, and fenugreek), their unique blend (ACFB), and the monacolin K-containing red yeast extract (RYR), was investigated with an in vitro approach based on hepatic cell line HepG2. The impact on cholesterol of the three extracts, their blend, and RYR were investigated by determining hepatocyte total and free cholesterol and bile acids biosynthesis. According to our results, the anticholesterolemic activity of the vegetal extracts was confirmed, and a novel choleretic activity of caigua extract was evidenced. ACFB showed to be safer than RYR while showing a similar effect on total and free cholesterol and bile acids synthesis compared to it. The anticholesterolemic activity of the blend was obtained with lower vegetal extract concentrations compared with the single vegetal extract, potentially indicating an additive effect between the extracts. In conclusion, the vegetal extracts and their blend, ACFB, are safe and are endowed with anticholesterolemic activity, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.

Correction: Spatiotemporal distribution and speciation of silver nanoparticles in the healing wound.

Correction for 'Spatiotemporal distribution and speciation of silver nanoparticles in the healing wound' by Marco Roman et al., Analyst, 2020, 145, 6456-6469, DOI: 10.1039/D0AN00607F.

Capryloyl glycine and soy isoflavonoids in hypertrichosis: An experimental and placebo-controlled clinical study.

BACKGROUND: The management of acquired hypertrichosis (HT) is based on the search of the causes and subsequent specific treatment. However, simultaneous hair removal is important. No single method for hair removal is appropriate for all patients and skin areas. Treatment options are actually limited and clinical results are often unsatisfactory. Ornithine decarboxylase 1 (ODC1), an enzyme present in hair follicles, is considered as a potential target to inhibit hair growth. Only eflornithine hydrochloride, an inhibitor of ODC1, showed to be partially effective in the management of acquired HT. AIMS: The aim of our study was to evaluate the potential inhibition of ODC1 activity by a cream containing 4% capryloyl glycine, an ODC1 inhibitor, and 1% glycine soy-fermented extract (soy isoflavonoids). Furthermore, we present the results of a placebo-controlled clinical study that evaluated the efficacy and tolerability of this cream. METHODS: The ODC1 activity was detected by measuring absorbance at 340 nm. In the presence of ODC1 inhibitors, absorbance decreases as a function of inhibition. Difluoromethylornithine (DFMO) was provided as an inhibitor control. ODC1 activity inhibition was expressed as percentage of control (untreated sample). All data were presented as mean ± standard deviation of three independent experiments. To determine if statistically significant differences between treatments were present, a t test analysis was performed. The differences between groups were considered significant at p < 0.05. Twelve Caucasian female adult patients, with HT located on the forearms, were enrolled. The study cream (product A) was applied twice/day for four months on the right forearm. A placebo cream (product B) was applied twice/day for four months on the left forearm. Clinical efficacy was evaluated by means of macrophotography. RESULTS: The cream significantly inhibited ODC1 activity (35.1 ± 0.5% inhibition, equivalent to a 64.9 ± 0.5% ODC1 activity). DFMO completely abolished the enzymatic activity (100 ± 5% inhibition, equivalent to 0 ± 5% ODC1 activity). All patients were considered evaluable. In 11 out of 12 patients (91.7%), who were treated with product A, an improvement was observed. No improvement was observed in patients treated with product B. The global assessment showed good efficacy in 7 patients (58.3%) and moderate efficacy in 5 patients (41.7%) treated with the product A. No efficacy was detected in patients treated with product B. CONCLUSIONS: The study cream showed to be effective in Caucasian, adult, female patients with hypertrichosis located on the forearms.

MINI OPCAB Operation: Surgical Technique.

INTRODUCTION: We describe how to perform left internal mammary artery (LIMA) bypass to the left anterior descending (LAD) artery, the so-called MINI Off-pump Coronary Artery Bypass (MINI OPCAB). MATERIALS AND METHODS: We included patients with a demonstrated predominant ischemia related to the LAD territory. Of 70 patients who were operated upon at the Benetti Foundation, 10 received hybrid revascularization. SURGICAL TECHNIQUE: The patient is prepared as for a standard coronary bypass operation through sternotomy. The sternum is opened to the 3rd or 4th intercostal space depending on the anatomy, and a retractor is put in place. The left mammary artery is generally dissected to about 8 cm and isolated without the veins. Importantly, the angle of the superior part, where the mammary artery is attached to the sternum, needs to be below 20% to avoid any potential kinking. The pericardium is cleaned to identify the area of the pulmonary artery. The pericardium is opened to the apex and towards the right to around 5 to 6 cm initially. In most cases, the area of the LAD can be seen and the potential area of the anastomosis is defined. The patient is heparinized and the LAD is occluded with 5-0 Proline. A mechanical stabilizer is put in place and the anastomosis is performed. When the bypass is finished, and before sutures are tied, the stitches of 5-0 polypropylene around the artery are released, along with the clamp of the mammary artery; the anastomosis is then tied. The mechanical stabilizer is removed, the stitches of the pericardium are released and the flow of the graft is measured, while ensuring that there is no kinking. If the flow and Pulsatility and Resistance (PR) are acceptable, the mammary is fixed with 2 stitches of 7-0 polypropylene on both sides around 1 cm from the anastomosis. The heparin is reverted with protamine and a drain is put in place, while taking care to avoid any chance of touching the mammary artery or the anastomosis. The sternum is closed with 1 or 2 wires. RESULTS: Operative mortality in this series was 0%; one patient was converted to sternotomy off-pump (1.4%). None of the grafts were revised after measurement with a Medistim system (Medistim ASA, Oslo, Norway). Fifty five patients (79%) were extubated in the operating room The average hospitalization stay was 60 hours (SD 17, 95% CI). Sixteen patients who underwent the LIMA-to-LAD procedure were restudied, with 100% patency. At 144 months, 82% of the patients were alive and 68% were asymptomatic. CONCLUSION: Additional clinical experience is required to be able to reproduce this operation on a large scale and expand the MINI OPCAB operation in hybrid revascularization.

A nanoemulsion/micelles mixed nanosystem for the oral administration of hydrophobically modified insulin.

The potential of nanoemulsions for the oral administration of peptides is still in its early stage. The aim of the present work was to rationally design, develop, and fully characterize a new nanoemulsion (NE) intended for the oral administration of hydrophobically modified insulin (HM-insulin). Specific components of the NE were selected based on their enhancing permeation properties as well as their ability to improve insulin association efficiency (Miglyol 812, sodium taurocholate), stability in the intestinal fluids, and mucodiffusion (PEGylated phospholipids and poloxamer 407). The results showed that the NE co-existed with a population of micelles, forming a mixed system that exhibited a 100% of HM-insulin association efficiency. The nanosystem showed good stability and miscibility in different bio-relevant media and displayed an acceptable mucodiffusive behavior in porcine mucus. In addition, it exhibited a high interaction with cell mono-cultures (Caco -2 and C2BBe1 human colon carcinoma Caco-2 clone cells) and co-cultures (C2BBe1 human colon carcinoma Caco-2 clone/HT29-MTX cells). The internalization in Caco-2 monolayers was also confirmed by confocal microscopy. Finally, the promising in vitro behavior of the nanosystem in terms of overcoming the biological barriers of the intestinal tract was translated into a moderate, although significant, hypoglycemic response (≈ 20-30%), following intestinal administration to both healthy and diabetic rat models. Overall, this information underlines the crucial steps to address when designing peptide-based nanoformulations to successfully overcome the intestinal barriers associated to the oral modality of administration.

COVID-19: An Argentinian perspective.

At the time of this writing (July 6, 2020), the mortality rate reported for COVID-19 in Argentina was <2%. Also, the country's critical care beds are ≤63% occupied. This achievement results from the excellent coordination and action by the Argentine Ministry of Health together with the 23 provinces and the Autonomous City of Buenos Aires of the nation for now. MATERIALS AND METHODS: Regarding cardiovascular care for patients over 65 years of age, a more accurate analysis could be performed when two comparative half-yearly periods corresponding to the years 2019 and 2020 (pandemic time) were compared. The data collected regarding this age range revealed issues that had not previously been evaluated in our country. That undoubtedly proposes a different solution for the future based on a strict scientific analysis. RESULTS: The ratio of patients who received stents to those that underwent coronary surgery was 6 to 1, while the ratio of patients who had off-pump surgery to those that underwent minimally invasive surgery was 69 to 1. CONCLUSION: An Argentinian perspective regarding cardiovascular care is good because the country has an excellent level of qualified medical training in its cardiac surgery and interventional cardiology services, as well as healthcare infrastructure distributed throughout the country, which will undoubtedly be able to respond to the new challenges posed by the post-pandemic period.

Minimal access left ventricular reconstruction.

The Revivent TC™ Transcatheter Ventricular Enhancement System (BioVentrix Inc.) is intended for use in heart failure with cardiac dysfunction a previous myocardial infarction. The resultant increased left ventricular systolic volume and discrete, contiguous, noncontractile (akinetic and/or dyskinetic) scar located in the anteroseptal, apical (may extend laterally) region of the left ventricle (LV) lends itself to Revivent. The procedure, called Less Invasive Ventricular Enhancement, consists of the implantation of a series of microanchors pairs to exclude the scarred myocardium, to reduce and reshape the LV. We present the procedure step-by-step, as team coordination between the cardiac surgeon and the interventional cardiologist is essential to ensure good procedural outcomes. This is a novel and new technique to address heart failure secondary to myocardial infarction.