Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.

Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation.

Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti-inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately. Colitis was induced in mice by 2,4-dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC-MS-IT-TOF). Endocannabinoids and related mediators were assessed by LC-MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin-1ß, and intestinal permeability. CBG, but not CBD, given by oral gavage, ameliorated DNBS-induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti-inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon. By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.

TNF-Stimulated Gene-6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are well established to have promising therapeutic properties. TNF-stimulated gene-6 (TSG-6), a potent tissue-protective and anti-inflammatory factor, has been demonstrated to be responsible for a significant part of the tissue-protecting properties mediated by MSCs. Nevertheless, current knowledge about the biological function of TSG-6 in MSCs is limited. Here, we demonstrated that TSG-6 is a crucial factor that influences many functional properties of MSCs. The transcriptomic sequencing analysis of wild-type (WT) and TSG-6-/- -MSCs shows that the loss of TSG-6 expression leads to the perturbation of several transcription factors, cytokines, and other key biological pathways. TSG-6-/- -MSCs appeared morphologically different with dissimilar cytoskeleton organization, significantly reduced size of extracellular vesicles, decreased cell proliferative rate, and loss of differentiation abilities compared with the WT cells. These cellular effects may be due to TSG-6-mediated changes in the extracellular matrix (ECM) environment. The supplementation of ECM with exogenous TSG-6, in fact, rescued cell proliferation and changes in morphology. Importantly, TSG-6-deficient MSCs displayed an increased capacity to release interleukin-6 conferring pro-inflammatory and pro-tumorigenic properties to the MSCs. Overall, our data provide strong evidence that TSG-6 is crucial for the maintenance of stemness and other biological properties of murine MSCs.

Comparing the influence of exercise intensity on brain-derived neurotrophic factor serum levels in people with Parkinson's disease: a pilot study.

INTRODUCTION: Endogenous brain-derived neurotrophic factor (BDNF) is thought to be protective against the neurodegeneration seen in Parkinson's disease (PD), and is thought to increase during exercise. This has been proposed as a possible mechanism by which exercise improves outcomes for people with PD. We conducted a pilot study to investigate the role of exercise intensity on BDNF levels in people with PD. METHODS: Participants of early- to mid-stage disease were recruited from a single PD service in north-east England, UK into two separate studies of exercise in PD, one involving moderate-intensity continuous training (MICT) and one involving high-intensity interval training (HIIT), both had control groups. In both the interventions, participants exercise three times per week for 12 weeks. Blood samples were taken for BDNF analysis at the start and end of the first session and the start and end of the final session, with corresponding samples taken in controls. RESULTS: Data were available for 27 participants (13 intervention, 14 control) in the MICT intervention and 17 (9 intervention, 8 control) in the HIIT intervention. BDNF level did not rise significantly from the start to end of individual sessions. Across the 12 week period, they rose significantly in the HIIT intervention group, but not in controls or the MICT intervention group. CONCLUSIONS: High-intensity interval training appears to have a greater impact on BDNF than MICT. Future work should directly compare exercise modalities and investigate the impact of BDNF levels on disease progression and quality of life.

Caesalpinia ferrea C. Mart. (Fabaceae) Phytochemistry, Ethnobotany, and Bioactivities: A Review.

Caesalpinia ferrea C. Mart., popularly known as "Jucá" or "Pau-ferro", belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of C. ferrea. The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from C. ferrea are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of C. ferrea most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of C. ferrea.

The clinical efficacy of curcumin-containing nutraceuticals: An overview of systematic reviews.

BACKGROUND: The clinical efficacy of curcumin-containing nutraceuticals (e.g. turmeric preparations, curcumin, curcuminoids) for a range of conditions has been assessed by several systematic reviews, in some instances with contradictory conclusions. Our aim was to provide an up-to-date and rigorous synthesis of these data and to evaluate the quality of the available systematic reviews. METHODS: Electronic searches were conducted (up to December 2017) to locate all systematic reviews (SRs) related to the use of curcumin-containing nutraceuticals for any condition. The quality of the retrieved SRs was assessed by using AMSTAR an OQAQ tolls. RESULTS: Twenty-two SRs met our inclusion criteria. Overall, four SRs were of high quality using the AMSTAR scale, whereas twelve SRs achieved an high quality classification according to the OQAQ score. There is some evidence that curcumin-containing nutraceuticals can exert systemic antioxidant actions (1 SR) and may be effective i) in inflammatory conditions such as arthritis-related diseases and inflammatory bowel disease (12 SRs), ii) in reducing lipid levels and cardiovascular risk factors (5 SRs) as well as iii) in skin diseases (1 SR). Cautious preliminary positive results were reported for depressive disorders (3 SRs), while no efficacy was observed in Alzheimer's disease patients (1 SR). Curcumin-containing nutraceuticals appear to be safe, as assessed by the adverse events reported in twelve SRs. CONCLUSIONS: Based on the currently available SRs, the efficacy of curcumin-containing nutraceuticals has been demonstrated for several conditions; however, due to the poor quality of the primary trials and the low-to-moderate level of some SRs, there is still some uncertainty.

Bioimpedance Spectroscopy as a Practical Tool for the Early Detection and Prevention of Protein-Energy Wasting in Hemodialysis Patients.

OBJECTIVES: To evaluate whether body composition monitor (BCM) could be a practical instrument for nephrologists to assess nutritional status in patients on hemodialysis (HD) and whether it is more effective in identifying patients at highest risk of developing protein-energy wasting (PEW) alone or in combination with other tools currently used for that purpose. DESIGN: Observational cross-sectional study in 91 HD patients (60 ± 14 years, 70.3% male, 24 ± 4.1 kg/m2 body mass index) from 2 different locations. METHODS: Nutritional status was evaluated by anthropometric methods (biceps and triceps skinfold thickness, waist circumference, and arm muscular circumference), biochemical nutritional markers, malnutrition-inflammation score (MIS), and BCM. The patients were grouped into those with and without PEW by using classical criteria and then classified as being adequately or inadequately nourished according to a BCM flow chart to detect those requiring preferential nutritional intervention. A multivariate approach was used to calculate the risk of developing PEW. RESULTS: Anthropometric measurements revealed significantly lower body mass index (<23 kg/m2; odds ratios [OR] = 13.3 and P = 0.001) and arm muscular circumference < p10 (OR = 34, P < 0.001) in the PEW group. MIS was above 5 in all the patients classified as having PEW. BCM showed that fat tissue index < p10 was significantly lower in this group (OR = 1.52), and a decision tree using the lean tissue index < p10, fat tissue index < p10, and extracellular water > 15% revealed that 42.9% of the patients would need nutritional monitoring. On multivariate analysis, insufficient nutritional status detected by BCM decision tree was an independent prognostic factor for developing PEW. About 9.89% of the patients were classified as PEW, with MIS > 5, and insufficient nutritional status detected by BCM required preferential nutritional intervention. CONCLUSION: BCM is a practical instrument for nephrologists to assess nutritional status in patients on HD and is useful for the early prevention and detection of PEW, as is able to identify differences in body composition, predict clinically important outcomes, and classify patients requiring preferential nutritional intervention.

Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis.

Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR. MAGL and 2-AG were strongly expressed in tumor tissues. The MAGL inhibitor URB602 reduced xenograft tumor volume, this effect being associated to down-regulation of VEGF and FGF-2, reduction in the number of vessels and down-regulation of cyclin D1. In HUVEC, URB602 exerted a direct antiangiogenic effect by inhibiting FGF-2 induced proliferation and migration, and by modulating pro/anti-angiogenic agents. In experiments aiming at investigating the role of MAGL in chemoprevention, URB602 attenuated azoxymethane-induced preneoplastic lesions, polyps and tumors. MAGL, possibly through modulation of angiogenesis, plays a pivotal role in experimental colon carcinogenesis. Pharmacological inhibition of MAGL could represent an innovative therapeutic approach to reduce colorectal tumor progression.

Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages.

Historical and scientific evidence suggests that Cannabis use has immunomodulatory and anti-inflammatory effects. We have here investigated the effect of the non-psychotropic phytocannabinoid Δ9-tetrahydrocannabivarin (THCV) and of a Cannabis sativa extract with high (64.8%) content in THCV (THCV-BDS) on nitric oxide (NO) production, and on cannabinoid and transient receptor potential (TRP) channel expression in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. THCV-BDS and THCV exhibited similar affinity in radioligand binding assays for CB1 and CB2 receptors, and inhibited, via CB2 but not CB1 cannabinoid receptors, nitrite production evoked by LPS in peritoneal macrophages. THCV down-regulated the over-expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin 1ß (IL-1ß) proteins induced by LPS. Furthermore, THCV counteracted LPS-induced up-regulation of CB1 receptors, without affecting the changes in CB2, TRPV2 or TRPV4 mRNA expression caused by LPS. Other TRP channels, namely, TRPA1, TRPV1, TRPV3 and TRPM8 were poorly expressed or undetectable in both unstimulated and LPS-challenged macrophages. It is concluded that THCV - via CB2 receptor activation - inhibits nitrite production in macrophages. The effect of this phytocannabinoid was associated with a down-regulation of CB1, but not CB2 or TRP channel mRNA expression.

Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid.

Cannabigerol (CBG) is a safe non-psychotropic Cannabis-derived cannabinoid (CB), which interacts with specific targets involved in carcinogenesis. Specifically, CBG potently blocks transient receptor potential (TRP) M8 (TRPM8), activates TRPA1, TRPV1 and TRPV2 channels, blocks 5-hydroxytryptamine receptor 1A (5-HT1A) receptors and inhibits the reuptake of endocannabinoids. Here, we investigated whether CBG protects against colon tumourigenesis. Cell growth was evaluated in colorectal cancer (CRC) cells using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide and 3-amino-7-dimethylamino-2-methylphenazine hydrochloride assays; apoptosis was examined by histology and by assessing caspase 3/7 activity; reactive oxygen species (ROS) production by a fluorescent probe; CB receptors, TRP and CCAAT/enhancer-binding protein homologous protein (CHOP) messenger RNA (mRNA) expression were quantified by reverse transcription-polymerase chain reaction; small hairpin RNA-vector silencing of TRPM8 was performed by electroporation. The in vivo antineoplastic effect of CBG was assessed using mouse models of colon cancer. CRC cells expressed TRPM8, CB1, CB2, 5-HT1A receptors, TRPA1, TRPV1 and TRPV2 mRNA. CBG promoted apoptosis, stimulated ROS production, upregulated CHOP mRNA and reduced cell growth in CRC cells. CBG effect on cell growth was independent from TRPA1, TRPV1 and TRPV2 channels activation, was further increased by a CB2 receptor antagonist, and mimicked by other TRPM8 channel blockers but not by a 5-HT1A antagonist. Furthermore, the effect of CBG on cell growth and on CHOP mRNA expression was reduced in TRPM8 silenced cells. In vivo, CBG inhibited the growth of xenograft tumours as well as chemically induced colon carcinogenesis. CBG hampers colon cancer progression in vivo and selectively inhibits the growth of CRC cells, an effect shared by other TRPM8 antagonists. CBG should be considered translationally in CRC prevention and cure.

Novel insights into the pharmacology of flavonoids.

Flavonoids are widely distributed secondary metabolites and currently consumed in large amounts in the daily diet. In this article, some of the most recent developments in flavonoid - and related polyphenolic compounds - pharmacology are discussed, with particular emphasis on very recent data, most of which are published in Phytotherapy Research, which highlight new aspects in flavonoid anti-inflammatory, antilipidemic, antihyperglycemic, antiviral, hepatoprotective, gastric antiulcer, cardioprotective, neuroprotective, antioxidant and anticancer actions. These updated data confirm the well-established diverse beneficial pharmacological actions and might support the perspective for a therapeutic use.

Frailty in hemodialysis patients: results of a screening program and multidisciplinary interventions.

Background: The number of frail patients of advanced age with end-stage kidney disease (ESKD) undergoing hemodialysis is increasing globally. Here we evaluated a frailty screening program of ESKD patients starting hemodialysis, and subsequent multidisciplinary interventions. Methods: This was a prospective observational study of ESKD patients in a hemodialysis program. Patients were evaluated for frailty (Fried frail phenotype) before and after a 12-month period. Patients followed standard clinical practice at our hospital, which included assessment and multidisciplinary interventions for nutritional (malnutrition-inflammation score, protein-energy wasting), physical [short physical performance battery (SPPB)] and psychological status. Results: A total of 167 patients (mean ± standard deviation age 67.8 ± 15.4 years) were screened for frailty, and 108 completed the program. At screening, 27.9% of the patients were frail, 40.0% pre-frail and 32.1% non-frail. Nutritional interventions (enrichment, oral nutritional supplements, intradialytic parenteral nutrition) resulted in stable nutritional status for most frail and pre-frail patients after 12 months. Patients following recommendations for intradialytic, home-based or combined physical exercise presented improved or stable in SPPB scores after 12 months, compared with those that did not follow recommendations, especially in the frail and pre-frail population (P = .025). A rate of 0.05 falls/patient/year was observed. More than 60% of frail patients presented high scores of sadness and anxiety. Conclusions: Frailty screening, together with coordinated interventions by nutritionists, physiotherapists, psychologists and nurses, preserved the health status of ESKD patients starting hemodialysis. Frailty assessment helped in advising patients on individual nutritional, physical or psychological needs.

TRPM8 indicates poor prognosis in colorectal cancer patients and its pharmacological targeting reduces tumour growth in mice by inhibiting Wnt/ß-catenin signalling.

BACKGROUND AND PURPOSE: Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). EXPERIMENTAL APPROACH: TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8-/- mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. KEY RESULTS: TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt-Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/ß-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of ß-catenin and its target oncogenes such as C-Myc and Cyclin D1. CONCLUSION AND IMPLICATIONS: Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.

Sphingosine-1-phosphate/TGF-ß axis drives epithelial mesenchymal transition in asthma-like disease.

BACKGROUND AND PURPOSE: Airway remodelling is a critical feature of chronic lung diseases. Epithelial-mesenchymal transition (EMT) represents an important source of myofibroblasts, contributing to airway remodelling. Here, we investigated the sphingosine-1-phosphate (S1P) role in EMT and its involvement in asthma-related airway dysfunction. EXPERIMENTAL APPROACH: A549 cells were used to assess the S1P effect on EMT and its interaction with TGF-ß signalling. To assess the S1P role in vivo and its impact on lung function, two experimental models of asthma were used by exposing BALB/c mice to subcutaneous administration of either S1P or ovalbumin (OVA). KEY RESULTS: Following incubation with TGF-ß or S1P, A549 acquire a fibroblast-like morphology associated with an increase of mesenchymal markers and down-regulation of the epithelial. These effects are reversed by treatment with the TGF-ß receptor antagonist LY2109761. Systemic administration of S1P to BALB/c mice induces asthma-like disease characterized by mucous cell metaplasia and increased levels of TGF-ß, IL-33 and FGF-2 within the lung. The bronchi harvested from S1P-treated mice display bronchial hyperresponsiveness associated with overexpression of the mesenchymal and fibrosis markers and reduction of the epithelial.The S1P-induced switch from the epithelial toward the mesenchymal pattern correlates to a significant increase of lung resistance and fibroblast activation. TGF-ß blockade, in S1P-treated mice, abrogates these effects. Finally, inhibition of sphingosine kinases by SK1-II in OVA-sensitized mice, abrogates EMT, pulmonary TGF-ß up-regulation, fibroblasts recruitment and airway hyperresponsiveness. CONCLUSION AND IMPLICATIONS: Targeting S1P/TGF-ß axis may hold promise as a feasible therapeutic target to control airway dysfunction in asthma.

Prevalence of Protein-Energy Wasting in Dialysis Patients Using a Practical Online Tool to Compare with Other Nutritional Scores: Results of the Nutrendial Study.

This cross-sectional study aims to explore the prevalence of protein-energy wasting (PEW) in dialysis patients in Catalonia, Spain, using a new and practical online tool which enables rapid calculation and comparison with other nutritional scores. METHODS: A web tool (Nutrendial) was created to introduce different variables and automatically calculate PEW, Malnutrition inflammation Score (MIS) and Subjective Global Assessment (SGA) in 1389 patients (88% in haemodialysis (HD)), 12% in peritoneal dialysis (PD) from different regions of Catalonia. RESULTS: A prevalence of 23.3% (26% HD, 10.2% PD) of PEW was found, with a mean MIS score of 6 and SGA score of C in 7% of the patients. ROC analysis showed MIS as the best nutritional score to diagnose PEW (AUC 0.85). Albumin delivered lower diagnostic precision (AUC 0.77) and sensitivity (66%). A cut off point of 7 (86% sensitivity and 75% specificity) for MIS and 3.7 mg/dL for albumin were found to predict the appearance of PEW in this population. SGA B or C showed an 87% sensitivity and 55% specificity to diagnose PEW. Very low nutritional intervention (14%) was recorded with this tool in patients with PEW. CONCLUSIONS: This new online tool facilitated the calculation of PEW, enabling different professionals-including nephrologists, dieticians and nurses-to efficiently obtain insights into the nutritional status of the Catalonian dialysis population and implement the required nutritional interventions. MIS is the score with more sensitivity to diagnose PEW.

N-Acylethanolamine acid amidase (NAAA) is dysregulated in colorectal cancer patients and its inhibition reduces experimental cancer growth.

BACKGROUND AND PURPOSE: N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamines (NAEs) and its pharmacological inhibition has beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism, whereas its contribution to colorectal cancer (CRC) is unknown to date. EXPERIMENTAL APPROACH: CRC xenograft and azoxymethane models were used to assess the in vivo effect of NAAA inhibition. Further, the tumour secretome was evaluated by an oncogenic array, CRC cell lines were used for in vitro studies, cell cycle was analysed by cytofluorimetry, NAAA was knocked down with siRNA, human biopsies were obtained from surgically resected CRC patients, gene expression was measured by RT-PCR and NAEs were measured by LC-MS. KEY RESULTS: The NAAA inhibitor AM9053 reduced CRC xenograft tumour growth and counteracted tumour development in the azoxymethane model. NAAA inhibition affected the composition of the tumour secretome inhibiting the expression of EGF family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-α and TRPV1. AM9053 induced cell cycle arrest in the S phase associated with cyclin A2/CDK2 down-regulation. NAAA knock-down mirrored the effects of NAAA inhibition with AM9053. NAAA expression was down-regulated in human CRC tissues, with a consequential augmentation of NAE levels and dysregulation of some of their targets. CONCLUSION AND IMPLICATIONS: Our results show novel data on the functional importance of NAAA in CRC progression and the mechanism involved. We propose that this enzyme is a valid drug target for the treatment of CRC growth and development.

Topical Collection "Pharmacology of Medicinal Plants".

The use of remedies based on medicinal plants continues to expand rapidly around the world, with many people now resorting to this type of product for the treatment and prevention of several pathologies [...].

Triterpenoids from Vitellaria paradoxa Stem Barks Reduce Nitrite Levels in LPS-Stimulated Macrophages.

Vitellaria paradoxa C. F. Gaertn is widely used in African traditional medicine as an anti-inflammatory remedy to treat rheumatism, gastric problems, diarrhea, and dysentery. The phytochemical investigation of the ethyl acetate extract of V. paradoxa stem bark collected in Burkina Faso led to the isolation of eight known and two triterpenes undescribed to date (7 and 10), in the free alcohol form or as acetyl and cinnamyl ester derivatives. The stereostructures of the new compounds were elucidated using HR-ESIMS and 1D and 2D NMR data. The isolated compounds were evaluated in vitro for their inhibitory effect on nitrite levels on murine macrophages J774 stimulated with the lipopolysaccharide (LPS). Among all the compounds tested, lupeol cinnamate (3) and betulinic acid (5) showed a beneficial effect in reducing nitrite levels produced after LPS stimulation.

Ethnomedicinal uses, phytochemistry, and biological activities of plants of the genus Gynura.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Gynura (Compositae) includes around 46 species and is native to the tropical regions of Southeast Asia, Africa and Australia. Many species within this genus are used in ethnomedicine to treat various disorders including skin diseases, injuries, ulcers, wounds, burns, sores, scalds, as well as for the management of diabetes, hypertension, hyperlipidemia, constipation, rheumatism, bronchitis and inflammation. AIM OF THE REVIEW: This review is an attempt to provide scientific information regarding the ethnopharmacology, phytochemistry, pharmacological and toxicological profiles of Gynura species along with the nomenclature, distribution, taxonomy and botanical features of the genus. A critical analysis has been undertaken to understand the current and future pharmaceutical prospects of the genus. MATERIALS & METHODS: Several electronic databases, including Google scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE and CNKI Scholar, were explored as information sources. The Plant List Index was used for taxonomical authentications. SciFinder and PubChem assisted in the verification of chemical structures. RESULTS: A large number of phytochemical analyses on Gynura have revealed the presence of around 342 phytoconstituents including pyrrolizidine alkaloids, phenolic compounds, chromanones, phenylpropanoid glycosides, flavonoids, flavonoid glycosides, steroids, steroidal glycosides, cerebrosides, carotenoids, triterpenes, mono- and sesquiterpenes, norisoprenoids, oligosaccharides, polysaccharides and proteins. Several in vitro and in vivo studies have demonstrated the pharmacological potential of Gynura species, including antidiabetic, anti-oxidant, anti-inflammatory, antimicrobial, antihypertensive and anticancer activities. Although the presence of pyrrolizidine alkaloids within a few species has been associated with possible hepatotoxicity, most of the common species have a good safety profile. CONCLUSIONS: The importance of the genus Gynura both as a prominent contributor in ethnomedicinal systems as well as a source of promising bioactive molecules is evident. Only about one fourth of Gynura species have been studied so far. This review aims to provide some scientific basis for future endeavors, including in-depth biological and chemical investigations into already studied species as well as other lesser known species of Gynura.