A Surprising Repurposing of Central Nervous System Drugs against Squamous Cell Carcinoma of the Bladder, UM-UC-5.

The potential benefits of drug repurposing have gained attention as an alternative to developing de novo drugs. The potential of using central nervous system (CNS) drugs as anticancer drugs has been explored in several types of human cancers, such as breast and colon cancer, among others. Here, we examine the effect of the CNS drugs sertraline, paroxetine, and chlorpromazine on human squamous carcinoma cells of the bladder (UM-UC-5). After exposing UM-UC-5 cells to increased concentrations of each drug for 48 h, we assessed their metabolic activity using an MTT assay. Based on those results, we calculated cell viability and the half-maximal inhibitory concentration (IC50) values. The results suggest that the CNS drugs were effective against UM-UC-5 in the order of potency of sertraline > chlorpromazine > paroxetine. Interestingly, sertraline was more potent than 5-fluorouracil (5-FU), a widely used anticancer drug. This study demonstrated, for the first time, the promising anticancer activity of CNS drugs on human bladder cancer cells in vitro and supports the repurposing of CNS drugs to improve cancer treatment. Nevertheless, further studies are necessary to understand their mechanism of action and in vivo activity.

Testing motivational and self-regulatory mechanisms of action on device-measured physical activity in the context of a weight loss maintenance digital intervention: A secondary analysis of the NoHoW trial.

BACKGROUND: To date, few digital behavior change interventions for weight loss maintenance focusing on long-term physical activity promotion have used a sound intervention design grounded on a logic model underpinned by behavior change theories. The current study is a secondary analysis of the weight loss maintenance NoHoW trial and investigated putative mediators of device-measured long-term physical activity levels (six to 12 months) in the context of a digital intervention. METHODS: A subsample of 766 participants (Age = 46.2 ± 11.4 years; 69.1% female; original NoHoW sample: 1627 participants) completed all questionnaires on motivational and self-regulatory variables and had all device-measured physical activity data available for zero, six and 12 months. We examined the direct and indirect effects of Virtual Care Climate on post intervention changes in moderate-to-vigorous physical activity and number of steps (six to 12 months) through changes in the theory-driven motivational and self-regulatory mechanisms of action during the intervention period (zero to six months), as conceptualized in the logic model. RESULTS: Model 1 tested the mediation processes on Steps and presented a poor fit to the data. Model 2 tested mediation processes on moderate-to-vigorous physical activity and presented poor fit to the data. Simplified models were also tested considering the autonomous motivation and the controlled motivation variables independently. These changes yielded good results and both models presented very good fit to the data for both outcome variables. Percentage of explained variance was negligible for all models. No direct or indirect effects were found from Virtual Care Climate to long term change in outcomes. Indirect effects occurred only between the sequential paths of the theory-driven mediators. CONCLUSION: This was one of the first attempts to test a serial mediation model considering psychological mechanisms of change and device-measured physical activity in a 12-month longitudinal trial. The model explained a small proportion of variance in post intervention changes in physical activity. We found different pathways of influence on theory-driven motivational and self-regulatory mechanisms but limited evidence that these constructs impacted on actual behavior change. New approaches to test these relationships are needed. Challenges and several alternatives are discussed. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN88405328. Registered December 16, 2016, https://www.isrctn.com/ISRCTN88405328.

What goes on in digital behaviour change interventions for weight loss maintenance targeting physical activity: A scoping review.

Objective: To identify the core components of digital behaviour change interventions for weight loss maintenance targeting physical activity, in terms of: (i) behaviour change techniques, (ii) mechanisms of action, (iii) modes of delivery, (iv) dose and (v) tailoring/personalization. In addition, the links between these components were investigated. Methods: A literature search was performed in five electronic databases: PubMed, Embase, CINHAL, PsycINFO and Web of Science. Two reviewers independently screened the identified articles and extracted data related with the study characteristics and behaviour change techniques, mechanism of action, mode of delivery, dose, and tailoring, using standardized classifications whenever available (e.g. behaviour change techniques taxonomy). Results: Seventeen articles reporting 11 original studies were selected. Two studies were protocols, 9 studies presented results for weight change and all but one showed no significant differences between the intervention and control groups. Eight studies (73%) provided adequate information on behaviour change techniques. Five studies (45%) provided partial information about how the behaviour change techniques were linked to mechanisms of action, and only one study (0.9%) described these links for all the techniques. Around half of the studies reported the modes through which behaviour change techniques were delivered. Descriptions of dose were present in most studies, but with minimal information. The use of tailoring or personalization approaches was mentioned in eight studies (73%), but descriptions of what was tailored and how were minimal. Conclusions: The compilation of information regarding intervention components was difficult due to the lack of information and systematization in reporting across papers. This is particularly true for the reporting of the links between behaviour change techniques and the other core intervention components. This information is crucial to help us understand in the context of behaviour change interventions what works or does not work, how it works and why.

Control Strategies for Carcinogenic-Associated Helminthiases: An Integrated Overview.

Helminthiases are extremely prevalent in the developing world. In addition, the chronic infection with some parasitic worms are classified as carcinogenic. Therefore, it is utmost importance to understand the parasite-host interactions, the mechanisms underlay carcinogenesis and how they could be counteracted. This knowledge may ultimately guide novel control strategies that include chemotherapy-based approaches targeting these pathogens and associated pathologies caused by their infections. Little is known on how some helminthiases are associated with cancer; however, it has been hypothesized that chemical carcinogenesis may be involved in the process. Here, we summarize the current knowledge on chemical carcinogenesis associated with helminthiases, along with available therapeutic options and potential therapeutic alternatives including chemotherapy and/or immunotherapy. Ideally, the treatment of the carcinogenic helminthiases should target both the parasite and associated pathologies. The success of any chemotherapeutic regimen often depends on the host immune response during the infection and nutritional status among other factors. The close association between chemotherapy and cell-mediated immunity suggests that a dual therapeutic approach would be advantageous. In addition, there is a pressing need for complementary drugs that antagonize the carcinogenesis process associated with the helminth infections.

Synthesis, Biological Activity and In Silico Pharmacokinetic Prediction of a New 2-Thioxo-Imidazoldidin-4-One of Primaquine.

The discovery of novel antiparasitic drugs for neglected tropical diseases (NTDs) constitutes a global urgency and requires a range of innovative strategies to ensure a sustainable pipeline of lead compounds. Thus far, primaquine (PQ) is the only transmission-blocking antimalarial that is clinically available, displaying marked activity against gametocytes of all causative species of human malaria (Plasmodium spp.). Chagas disease, caused by Trypanosoma cruzi, is another PQ-sensitive illness besides malaria. One of the major drawbacks of PQ is its metabolism into carboxyprimaquine (CPQ), which is less active than the parent drug. In this study, we developed different synthetic pathways to confer N-protection to PQ through introduction of thioxo-imidazolidin-4-one. The introduction of this group prevents the formation of CPQ, counteracting one major drawback of the parent drug. After that, we evaluated the potential biological activity of the novel 2-thioxo-imidazolidin-4-one derivative of PQ, which showed relevant in vitro activity against Trypanosoma cruzi (IC50 1.4 µM) compared to PQ (IC50 1.7 µM) and the reference drug benznidazole (IC50 1.6 µM). Noting its acceptable pharmacokinetic profile, this PQ conjugate may be a potential scaffold for novel drug exploration against Chagas disease.

Urogenital Schistosomiasis-History, Pathogenesis, and Bladder Cancer.

Schistosomiasis is the most important helminthiasis worldwide in terms of morbidity and mortality. Most of the infections occurs in Africa, which about two thirds are caused by Schistosoma haematobium. The infection with S. haematobium is considered carcinogenic leading to squamous cell carcinoma (SCC) and urothelial carcinoma of the urinary bladder. Additionally, it is responsible for female genital schistosomiasis leading to infertility and higher risk of human immunodeficiency virus (HIV) transmission. Remarkably, a recent outbreak in Corsica (France) drew attention to its potential re-mergence in Southern Europe. Thus far, little is known related to host-parasite interactions that trigger carcinogenesis. However, recent studies have opened new avenues to understand mechanisms on how the parasite infection can lead cancer and other associated pathologies. Here, we present a historical perspective of schistosomiasis, and review the infection-associated pathologies and studies on host-parasite interactions that unveil tentative mechanisms underlying schistosomiasis-associated carcinogenesis.

Cell-penetrating peptides in oncologic pharmacotherapy: A review.

Cancer is the second leading cause of death in the world and its treatment is extremely challenging, mainly due to its complexity. Cell-Penetrating Peptides (CPPs) are peptides that can transport into the cell a wide variety of biologically active conjugates (or cargoes), and are, therefore, promising in the treatment and in the diagnosis of several types of cancer. Some notable examples are TAT and Penetratin, capable of penetrating the central nervous system (CNS) and, therefore, acting in cancers of this system, such as Glioblastoma Multiforme (GBM). These above-mentioned peptides, conjugated with traditional chemotherapeutic such as Doxorubicin (DOX) and Paclitaxel (PTX), have also been shown to induce apoptosis of breast and liver cancer cells, as well as in lung cancer cells, respectively. In other cancers, such as esophageal cancer, the attachment of Magainin 2 (MG2) to Bombesin (MG2B), another CPP, led to pronounced anticancer effects. Other examples are CopA3, that selectively decreased the viability of gastric cancer cells, and the CPP p28. Furthermore, in preclinical tests, the anti-tumor efficacy of this peptide was evaluated on human breast cancer, prostate cancer, ovarian cancer, and melanoma cells in vitro, leading to high expression of p53 and promoting cell cycle arrest. Despite the numerous in vitro and in vivo studies with promising results, and the increasing number of clinical trials using CPPs, few treatments reach the expected clinical efficacy. Usually, their clinical application is limited by its poor aqueous solubility, immunogenicity issues and dose-limiting toxicity. This review describes the most recent advances and innovations in the use of CPPs in several types of cancer, highlighting their crucial importance for various purposes, from therapeutic to diagnosis. Further clinical trials with these peptides are warranted to examine its effects on various types of cancer.

Activity of Combinations of Antioxidants and Anthelmintic Drugs against the Adult Stage of Schistosoma mansoni.

Schistosomiasis remains a major neglected tropical disease. The treatment and control of schistosomiasis rely on a single drug, praziquantel (PZQ). Despite its efficacy, treatment with PZQ presents some major drawbacks including an inability of the chemotherapy to reverse disease-induced fibrosis and the prospect of the emergence of drug resistance. Here, we investigated a novel therapeutic approach with antioxidant biomolecules in combination with PZQ against the adult developmental stage of Schistosoma mansoni and oviposition in vitro, given that this therapeutic approach achieved synergistic/additive activity against larval schistosomes. The antioxidants curcumin and oxadiazole per se exhibited antischistosomal activity against adult worms leading to severe morphological alterations and death. Additionally, the antioxidant flavone combined with vandetanib or imatinib improved antischistosomal activity against adult forms. By contrast, however, these antioxidant-anthelmintic combinations were not as effective against adults in comparison to larval schistosomes. Nevertheless, the antioxidants alone or combined with drugs inhibited oviposition.

Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation.

Estrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERß expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERß was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17ß-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis.

Oxysterols of helminth parasites and pathogenesis of foodborne hepatic trematodiasis caused by Opisthorchis and Fasciola species.

The foodborne trematodiases refer to a cluster of zoonotic neglected tropical diseases caused by trematodes, with transmission involving ingestion of contaminated plants, fishes, and crustaceans. Over 40 million people are infected with foodborne trematodes and 750 million are at risk of infection. From a public health point of view, important species include Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, Fasciola hepatica, and Fasciola gigantica. Infection with C. sinensis and O. viverrini is classified as a group 1 biological carcinogen and a major risk factor for cholangiocarcinoma. The carcinogenic potential of the infection with O. felineus is less clear but recent biochemical and histopathological findings revealed that opisthorchiasis felinea also fits this pattern. By contrast, evidence of carcinogenic potential of infection with F. hepatica or F. gigantica, close phylogenetics relatives of Opisthorchis, is less certain. Oxysterols have been essentially described in animal model of opisthorchiasis and associated cholangiocarcinoma. Several oxysterol-like metabolites have been detected not only on developmental stages of O. viverrini and O. felineus but also on biofluids from experimentally infected hamsters as products of the activities of the liver flukes. These sterol derivatives are metabolized to active quinones that can modify host DNA. We have postulated that helminth parasite-associated sterols might induce tumor-like phenotypes in biliary epithelia, the cells of origin of liver fluke infection-associated cholangiocarcinoma, through the formation of DNA adducts, dysregulation of apoptosis, and other homeostatic pathways. Here we review, interpret, and discuss findings of oxysterol-like metabolites detected in liver flukes and their role in carcinogenesis, aiming to enhance understanding the pathogenesis of foodborne trematodiasis caused by Opisthorchis and Fasciola species. In future, further investigations will be necessary in order to comprehend relationship between liver flukes' oxysterols and their role in infection-associated diseases in humans.

Current and Novel Therapies Against Helminthic Infections: The Potential of Antioxidants Combined with Drugs.

Infections caused by Schistosoma haematobium and Opisthorchisviverrini are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.

Breast cancer: insights in disease and influence of drug methotrexate.

According to the World Health Organization, cancer is one of the leading causes of morbidity and mortality worldwide. The previously estimated 14 million new cases in the year of 2012 are expected to rise, yearly, over the following 2 decades. Among women, breast cancer is the most common one. In 2012, almost 1.7 million people were diagnosed worldwide and half a million died from the disease. Despite having several treatments available, from surgery to chemotherapy, most of these treatments have severe adverse effects. Chemotherapy has a narrow therapeutic window and requires high dosage treatment in patients with advanced-stage cancers and further need innovative treatment strategies. Although methotrexate (MTX) is not a first line drug used against breast cancer, however, it might be valuable to fight the disease. MTX is an effective and cheap drug that might impair malignant growth without irreversible damage to normal tissues. Nevertheless, while MTX does present some disadvantages including poor solubility and low permeability, several strategies are being used to discover and provide novel and effective targeted treatment against breast cancer. In this review, we analyze the chemotherapy of breast cancer and its relationship with drug MTX.

Infection with carcinogenic helminth parasites and its production of metabolites induces the formation of DNA-adducts.

BACKGROUND: Infections classified as group 1 biological carcinogens include the helminthiases caused by Schistosoma haematobium and Opisthorchis viverrini. The molecular mediators underlying the infection with these parasites and cancer remain unclear. Although carcinogenesis is a multistep process, we have postulated that these parasites release metabolites including oxysterols and estrogen-like metabolites that interact with host cell DNA. How and why the parasite produce/excrete these metabolites remain unclear. A gene encoding a CYP enzyme was identified in schistosomes and opisthorchiids. Therefore, it is reasonable hypothesized that CYP 450 might play a role in generation of pro-inflammatory and potentially carcinogenic compounds produced by helminth parasites such as oxysterols and catechol estrogens. Here, we performed enzymatic assays using several isoforms of CYP 450 as CYP1A1, 2E1 and 3A4 which are involved in the metabolism of chemical carcinogens that have been associated with several cancer. The main aim was the analysis of the role of these enzymes in production of helminth-associated metabolites and DNA-adducts. METHOD: The effect of cytochrome P450 enzymes CYP 1A1, 2E1 and 3A4 during the interaction between DNA, glycocholic acid and taurochenodeoxycholate sodium on the formation of DNA-adducts and metabolites associated with urogenital schistosomiasis (UGS) and opisthorchiasis was investigated in vitro. Liquid chromatography/mass spectrometry was used to detect and identify metabolites. MAIN FINDINGS: Through the enzymatic assays we provide a deeper understanding of how metabolites derived from helminths are formed and the influence of CYP 450. The assays using compounds similar to those previously observed in helminths as glycocholic acid and taurochenodeoxycholate sodium, allowed the detection of metabolites in their oxidized form and their with DNA. Remarkably, these metabolites were previously associated with schistosomiaisis and opisthorchiasis. Thus, in the future, it may be possible to synthesize this type of metabolites through this methodology and use them in cell lines to clarify the carcinogenesis process associated with these diseases. PRINCIPAL CONCLUSIONS: Metabolites similar to those detected in helminths are able to interact with DNA in vitro leading to the formation of DNA adducts. These evidences supported the previous postulate that imply helminth-like metabolites as initiators of helminthiases-associated carcinogenesis. Nonetheless, studies including these kinds of metabolites and cell lines in order to evaluate its potential carcinogenic are required.

Inhibition of the Formation In Vitro of Putatively Carcinogenic Metabolites Derived from S. haematobium and O. viverrini by Combination of Drugs with Antioxidants.

Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.

The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni.

BACKGROUND: Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and control of schistosomiasis and other platyhelminth infections, praziquantel has some shortcomings and the inability of this drug to counteract disease sequelae prompts the need for novel therapeutic strategies. METHODS: Using a host-parasite model involving Biomphalaria glabrata and Schistosoma mansoni we established mechanical transformation of S. mansoni cercariae into newly transformed schistosomula (NTS) and characterized optimal culture conditions. Thereafter, we investigated the antischistosomal activity and ability of the antioxidants N-acetylcysteine (NAC) and resveratrol (RESV) to augment the performance of praziquantel and/or artesunate (AS) against larval stages of the parasite. Drug effects were evaluated by using an automated microscopical system to study live and fixed parasites and by transmission electron microscopy (TEM). RESULTS: Transformation rates of cercariae to schistosomula reached ~ 70% when the manipulation process was optimized. Several culture media were tested, with M199 supplemented with HEPES found to be suitable for S. mansoni NTS. Among the antioxidants studied, RESV alone or combined with anthelminthic drugs achieved better results rather N-acetylcysteine (NAC). TEM observations demonstrated that the combination of AS + RESV induced severe, extensive alterations to the tegument and subtegument of NTS when compared to the constituent compounds alone. Two anthelmintic-antioxidant combinations, praziquantel-resveratrol [combination index (CI) = 0.74] and artesunate-resveratrol (CI = 0.34) displayed moderate and strong synergy, respectively. CONCLUSIONS: The use of viability markers including staining with propidium iodide increased the accuracy of drug screening assays against S. mansoni NTS. The synergies observed might be the consequence of increased action by RESV on targets of AS and PZQ and/or they may act through concomitantly on discrete targets to enhance overall antischistosomal action. Combinations of active agents, preferably with discrete modes of action including activity against developmental stages and/or the potential to ameliorate infection-associated pathology, might be pursued in order to identify novel therapeutic interventions.

Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni.

Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.

Is Mindful Parenting Associated With Adolescents' Emotional Eating? The Mediating Role of Adolescents' Self-Compassion and Body Shame.

This study aimed to explore whether parents' mindful parenting skills were associated with adolescents' emotional eating through adolescents' levels of self-compassion and body shame. The sample included 572 dyads composed of a mother or a father and his/her child (12-18 years old), with normal weight (BMI = 5-85th percentile) or with overweight/obesity with or without nutritional treatment (BMI ≥ 85th percentile) according to the WHO Child Growth Standards. Parents completed self-report measures of mindful parenting (Interpersonal Mindfulness in Parenting Scale), and adolescents completed measures of self-compassion (Self-Compassion Scale-Short Form), body shame (Experience of Shame Scale), and emotional eating (Dutch Eating Behavior Questionnaire). Two path models, one with the total score for mindful parenting and the other with its dimensions, were tested in AMOS. Mindful parenting, specifically the dimension of compassion for the child, was indirectly associated with emotional eating through adolescents' self-compassion (point estimate = -0.27, p = 0.03, CI 95% [-0.61, -0.06]) and through self-compassion and body shame sequentially (point estimate = -0.19, p = 0.03, CI 95% [-0.37, -0.05]). The path model was invariant across weight groups but not across adolescents' sex (the indirect effects were significant among girls only). This study provides a novel comprehensive model of how mindful parenting, especially the dimension of compassion for the child, can be associated with adolescents' emotional eating behaviors by suggesting a potential sequence of mechanisms that may explain this association. This study suggests the beneficial effect of both mindful parenting and adolescents' self-compassion skills for adolescent girls struggling with feelings of body shame and emotional eating behaviors.

Amino Acids in the Development of Prodrugs.

Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.

Drug Repurposing for Schistosomiasis: Combinations of Drugs or Biomolecules.

Schistosomiasis is a major neglected tropical disease. Control of schistosomiasis currently relies on a single drug, praziquantel, and despite its efficacy against the all schistosome species that parasitize humans, it displays some problematic drawbacks and alone is ineffective in counteracting adverse pathologies associated with infection. Moreover, due to the development of the potential emergence of PZQ-resistant strains, the search for additional or alternative antischistosomal drugs have become a public health priority. The current drug discovery for schistosomiasis has been slow and uninspiring. By contrast, repurposing of existing approved drugs may offer a safe, rapid and cost-effective alternative. Combined treatment with PZQ and other drugs with different mode of action, i.e., antimalarials, shows promise results. In addition, a combination of anthelminthic drugs with antioxidant might be advantageous for modulating oxidative processes associated with schistosomiasis. Herein, we review studies dealing with combination therapies that involve PZQ and other anthelminthic drugs and/or antioxidant agents in treatment of schistosomiasis. Whereas PZQ combined with antioxidant agents might or might not interfere with anthelminthic efficacy, combinations may nonetheless ameliorate tissue damage and infection-associated complications. In fact, alone or combine with other drugs, antioxidants might be a valuable adjuvant to reduce morbidity and mortality of schistosomiasis. Therefore, attempting new combinations of anthelmintic drugs with other biomolecules such as antioxidants provides new avenues for discovery of alternatives to PZQ.

Is Mindful Parenting Associated with Adolescents' Well-being in Early and Middle/Late Adolescence? The Mediating Role of Adolescents' Attachment Representations, Self-Compassion and Mindfulness.

There is some evidence that mindful parenting, a parenting approach that involves the practice of bringing mindful awareness to the parent-child relationship, is associated with several positive psychosocial outcomes in adolescents. However, only a few studies have investigated the mechanisms that may underlie that association. This study explores whether the link between mindful parenting and adolescents' well-being is mediated by adolescents' attachment representations, self-compassion and mindfulness skills. The sample comprised 563 parent-child dyads (95.6% mothers). Adolescents (61.5% girls) had a mean age of 14.26 years (SD = 1.66, range = 12-20). Parents completed a measure of mindful parenting, and adolescents completed measures of attachment representations, self-compassion, mindfulness, and well-being. Mindful parenting was indirectly associated with adolescents' self-compassion and mindfulness through a more secure perception of the relationship with the parents, and was indirectly associated with adolescents' well-being through perceived attachment security, self-compassion and mindfulness. The path model was invariant across stages of adolescence but some relations in the model varied across gender. Self-compassion and mindfulness seem to develop within a parent-child relationship characterized by affection, self-regulation, and mindful awareness. These two resources, along with mindful parenting and positive representations of the parent-child relationship, are associated with adolescents' well-being.