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Background: There is a paucity of data evaluating whether positive deviance (PD) can sustain improvement in hand hygiene compliance. Methods: An observational study comparing the effect of PD on compliance with hand hygiene was conducted in two 20-bed step-down units (SDUs) at a private tertiary care hospital. In a 3-month baseline period (April-June 2008), hand hygiene counts were performed by electronic handwashing counters. Between July 1, 2008, and November 30, 2009, (East SDU) and between September 30, 2008, and December 2009 (West SDU), PD was applied in both units. Results: There was more than a 2-fold difference in the number of alcohol gel aliquots dispensed per month from April 2008 (before PD) to November 2009 (last month in PD) in the East SDU. There was also a 2-fold difference in the number of alcohol gel aliquots dispensed per month from September 2008 (before PD) to December 2009 (last month in PD) in the West SDU. The difference in the rate of health care‒associated infections (HAIs) between the baseline period and 2009 was statistically significant in the East SDU (5.8 vs 2.8 per 1,000 device-days; P = .008) and in the West SDU (3.7 vs 1.7 per 1,000 device-days; P = .023). Conclusions: PD was responsible for a sustained improvement in hand hygiene in the inpatient setting and was associated with a decrease in the incidence of device-associated HAIs. [ABSTRACT FROM AUTHOR]

Aim: To describe the self-reported mental health of nurses from 35 countries who worked during the COVID-19 pandemic., Background: There is little occupationally specific data about nurses' mental health worldwide. Studies have documented the impact on nurses' mental health of the COVID-19 pandemic, but few have baseline referents., Methods: A descriptive, cross-sectional design structured the study. Data reflect a convenience sample of 9,387 participants who completed the opt-in survey between July 31, 2022, and October 31, 2023. Descriptive statistics were run to analyze the following variables associated with mental health: Self-reports of mental health symptoms, burnout, personal losses during the pandemic, access to mental health services, and self-care practices used to cope with pandemic-related stressors. Reporting of this study was steered by the STROBE guideline for quantitative studies., Results: Anxiety or depression occurred at rates ranging from 23%-61%, with country-specific trends in reporting observed. Approximately 18% of the sample reported experiencing some symptoms of burnout. The majority of nurses' employers did not provide mental health support in the workplace. Most reported more frequently engaging with self-care practices compared with before the pandemic. Notably, 20% of nurses suffered the loss of a family member, 35% lost a friend, and 34% a coworker due to COVID-19. Nearly half (48%) reported experiencing public aggression due to their identity as a nurse., Conclusions: The data obtained establish a basis for understanding the specific mental health needs of the nursing workforce globally, highlighting key areas for service development., Implications for Nursing Policy: Healthcare organizations and governmental bodies need to develop targeted mental health support programs that are readily accessible to nurses to foster a resilient nursing workforce., (© 2025 International Council of Nurses.)

The development of new drugs is a lengthy and complex process regarding its conception and ideation, passing through in silico studies, synthesis, in vivo studies, clinical trials, approval, and commercialization, with an exceptionally low success rate. The lack of efficacy, safety, and suboptimal pharmacokinetic parameters are commonly identified as significant challenges in the discovery of new drugs. To help address these challenges, various approaches have been explored in medicinal chemistry, including the use of prodrug strategies. As a well-established approach, prodrug design remains the best option for improving physicochemical properties, reducing toxicity, and increasing selectivity, all while minimizing costs and saving on biological studies. This review article aims to analyze the current advances using the prodrug approach that has allowed the advance of drug candidates to clinical trials in the last 10 years. The approaches presented here aim to inspire further molecular optimization processes and highlight the potential of this strategy to facilitate the advancement of new compounds to clinical study phases.

Introduction: Epilepsy encompasses numerous syndromes characterized by spontaneous, intermittent, and abnormal electrical activity in the brain. Affecting about 1-2% of the population, it is estimated that approximately 30-40% of patients experience refractory epilepsy, which does not respond to traditional anticonvulsant drugs., Aims: Therefore, developing novel, safe, and effective antiepileptic drugs remains a medical need. In this study, we synthesized a series of isoindoline-1,3-dione derivatives and evaluated their anticonvulsant effects., Results: Compounds (2a-j) and (5) were obtained with yields ranging from 52-97%. These compounds were assessed for their protective effects on the following parameters: a) time to first seizure (seizure latency), b) seizure duration, and c) mortality rate post-seizure. The most active compound, (2a), increased seizure latency, reduced seizure duration, and lowered the mortality rate., Conclusion: These findings indicate that compound (2a) is a promising new anticonvulsant prototype, offering an alternative to current anticonvulsant drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Breast cancer stands as the most common form of malignancy among women globally, and it showcases commendable rates of cure when detected in early-stage and non-metastatic conditions. To overcome drug resistance and side effects observed in conventional chemotherapy, the present study aims to deliver rapamycin (RAP), a mTOR protein inhibitor, into a nanostructured lipid carrier (NLC) functionalized with folic acid for promoting active targeting to breast cancer cells. In the first step, the synthesis of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt) with folic acid (DSPE-PEG 2000 -FA) was successfully performed and characterized by UV spectroscopy, nuclear magnetic resonance, and infrared spectroscopy. Then, the folic acid-modified NLC loaded with RAP (FA-NLC-RAP) and the unmodified formulation (NLC-RAP) was developed and displayed a size of about 100 nm, negative surface charge, and high RAP encapsulation efficiency (94.92 % and 85.72 %, respectively). In vitro studies suggested that FA-NLC-RAP exhibited a higher degree of internalization in cancer cells (MCF-7) than in normal cells (MCF-10A), demonstrating the potential of folic acid as a ligand for promoting active targeting of RAP for breast cancer cells through folate receptors overexpressed in tumor cells FA-NLC-RAP significantly reduced tumor cell viability, similarly to that observed with the RAP solution. The release profile of the formulation was prolonged. Finally, studies in Caenorhabditis elegans evidenced the safety of FA-NLC-RAP characterized by a complete absence of toxicity in this animal model. Therefore, the findings imply that FA-NLC-RAP holds considerable promise for the treatment of breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Furoxan and benzofuroxan are compounds containing an N -oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds., Method: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes) , a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes , with a Minimum Inhibitory Concentration (MIC) value of 2 μg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine , produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 μg/mL., Results: Measurements of Interleukin-1 beta (IL1-β) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 μg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties., Conclusion: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Microplastics (MPs) have emerged as a significant class of contaminants due to their widespread presence in various environmental compartments. The ingestion of these particles poses a risk to both human health and the local biota. The investigation of the Santos estuary reveals the abundance of microplastics in the mangrove sediment. The highest concentration was 62,850-93,050 MPs·kg -1 dw, never seen before in Latin America coast. The region investigated is characterized for silting sites and low energy events, notably Rio dos Bugres, influenced by anthropic aspects, while the São Vicente e Santos channels prevail the high energy hydrodynamic regime. In consequence, the MPs are entrapped in the interior of the estuary, affecting drastically the biota of mangrove. Spectroscopic investigation identified: polymers, pigments, herbicide and additives. The hypothesis is that densely populated siltation areas combined with low-energy events serve along the estuary for MPs accumulation and hotspots formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The expression and release of cysteine proteases by Leishmania spp. and their virulence factors significantly influence the modulation of host immune responses and metabolism, rendering cysteine proteases intriguing targets for drug development. This review article explores the substantial role of cysteine protease B (CPB) in medicinal chemistry from 2001 to 2024, particularly concerning combatting Leishmania parasites. We delve into contemporary advancements and potential prospects associated with targeting cysteine proteases for therapeutic interventions against leishmaniasis, emphasizing drug discovery in this context. Computational analysis using the pkCSM tool assessed the physicochemical properties of compounds, providing valuable insights into their molecular characteristics and drug-like potential, enriching our understanding of the pharmacological profiles, and aiding rational inhibitor design. Our investigation highlights that while nonpeptidic compounds constitute the majority (69.2%, 36 compounds) of the dataset, peptidomimetic- based derivatives (30.8%, 16 compounds) also hold promise in medicinal chemistry. Evaluating the most promising compounds based on dissociation constant ( Ki ) and half maximal inhibitory concentration (IC 50 ) values revealed notable potency, with 41.7% and 80.0% of nonpeptidic compounds exhibiting values < 1 μM, respectively. On the other hand, all peptidic compounds evaluated for Ki (43.8%) and IC 50 (31.3%) obtained values < 1 μM, respectively. Further analysis identified specific compounds within both categories (nonpeptidic: 1, 2, and 4; peptidic: 48-52) as particularly promising, warranting deeper investigation into their structure-activity relationships. These findings underscore the diverse landscape of inhibitors in medicinal chemistry and highlight the potential of both nonpeptidic and peptide-based compounds as valuable assets in therapeutic development against leishmaniasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This work describes the evaluation the potentiating activity of antibiotics by campesterol (1) and its derivatives (2-11) against multiresistant strains of Staphylococcus aureus 10, Escherichia coli 06 and Pseudomonas aeruginosa 24 employing the microdilution test. When subjected to the in vitro potentiating activity bioassay, all compounds showed a potentiating effect associated with norfloxacin against E. coli and P. aeruginosa with a reduction in the MIC of the antibiotic of up to 75 %. These compounds also reduced the MIC of gentamicin by 37 % to 87 % in S. aureus and E. coli. Additionally, molecular docking studies were conducted to gain a deeper understanding of the interactions between the appropriate proteins and the most effective compounds (2, 4, 9, and 10 against E. coli; 1, 2, 3, 5, 8, and 9 against S. aureus), including antibiotics. This paper registers for the first time the in vitro and in silico studies on the action of compounds 1-11 in antibiotic potentiation., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study addresses the challenge of predicting Dalbulus maidis (DeLong & Wolcott) (Hemiptera: Cicadellidae) density in cornfields by developing an artificial neural network (ANN). Over two years, we collected data on meteorological variables (atmospheric pressure, air temperature, dew point, rainfall, relative humidity, solar irradiance, and wind speed), plant age, and density of D. maidis in cornfields located in two Brazilian biomes (Atlantic Forest and Brazilian Tropical Savannah). Out of 1056 ANNs tested, the neural network featuring a 30-day time lag, six neurons, logistic activation, and resilient propagation demonstrated the lowest root mean squared error (0.057) and a high correlation (0.919) with observed D. maidis densities. This ANN exhibited an goodness of fit in low-density (Atlantic Forest) and high-density (Brazilian Tropical Savannah) scenarios for D. maidis. Critical factors influencing D. maidis seasonal dynamics, including corn plant age, rainfall, average air temperature, and relative humidity, were identified. This study highlights the potential of the ANN as a promising tool for precise predictions of pest seasonal dynamics, positioning it as a valuable asset for integrated pest management programs targeting D. maidis., Competing Interests: Declaration. Conflict of Interest: The authors declare no conflict of interest., (© 2024. Sociedade Entomológica do Brasil.)

Flaviviruses are vector-borne RNA viruses that seriously threaten global public health due to their high transmission index in humans, mainly in endemic areas. They spread infectious diseases that affect approximately 400 million people globally, primarily in developing countries struggling with persistent epidemic diseases. Viral infections manifest as hemorrhagic fever, encephalitis, congenital abnormalities, and fatalities. Despite nearly two decades of drug discovery campaigns, researchers have not identified promising lead compounds for clinical trials to treat or prevent flavivirus infections. Although scientists have made substantial progress through drug discovery approaches and vaccine development, resolving this complex issue might need some time. New therapeutic agents that can safely and effectively target key components of flaviviruses need to be identified. NS2B-NS3pro is an extensively studied pharmacological target among viral proteases. It plays a key role in the viral replication cycle by cleaving the polyprotein of flaviviruses and triggering the formation of structural and non-structural proteins. In this review, studies published from 2014 to 2023 were examined, and the specificity profile of compounds targeting NS2B-NS3 pro proteases for treating flavivirus infections was focused on. Additionally, the latest advancements in clinical trials were discussed. This article might provide information on the prospects of this promising pharmacological target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Histone deacetylase (HDAC) enzymes 1-3 exist in several corepressor complexes and are viable drug targets. To date, proteolysis targeting chimeras (PROTACs) designed to target HDAC1-3 typically exhibit the selective degradation of HDAC3. Herein, we report cereblon-recruiting PROTACs that degrade HDAC1 with selectivity over HDAC3.

Background/Objectives: Gastrointestinal functional disorders (GFDs), including irritable bowel syndrome (IBS), are imbalances in the gut-brain axis characterized by persistence of symptoms in the abdominal area. Probiotics are live microorganisms that provide benefits to the health of their hosts when administered in adequate amounts, while prebiotics are a substrate that is selectively used by host microorganisms. This narrative review aimed to evaluate the effectiveness of prebiotics and probiotics mostly in irritable bowel syndrome, particularly on issues such as the interaction between these products and the gut microbiota, the duration of supplementation and long-term effects, the definition of ideal dosages, and the regulation and quality control of these products. Methods: A bibliographic search was carried out in indexed databases and articles published within 10 years before the beginning of the study and publications in English language, which investigated the specific theme of the study were considered. Papers dealing with topics not covered by the research questions, or presenting errors related with the wrong population or the wrong methods, as well as experimental studies and case reviews were excluded. Fifty-five articles were selected, initially in isolation by the authors and, afterward, under consensus. Results: It was possible to observe the effectiveness mainly of probiotics, in improving specific symptoms of the respective disorder; however, the available data remain unclear due to limitations concerning samples and methods of the studies evaluated. Conclusions: Despite evidence suggestive of therapeutic efficacy, additional multicenter randomized controlled trials (RCTs) with better defined protocols are still necessary to fill in the gaps in this subject, define measures to ensure the safe administration of these products, and confirm their therapeutic potential.

Tuberculosis remains a serious global health threat, exacerbated by the rise of resistant strains. This study investigates the potential of two benzofuroxan ( Bfx ) derivatives, 5n and 5b, as targeted treatments for MDR-TB using in silico , in vitro , and in vivo methodologies. In vitro analyses showed that Bfx compounds have significant activity against Mtb H37Rv, with Bfx 5n standing out with a MIC 90 of 0.09 ± 0.04 μM. Additionally, their efficacy against MDR and pre-XDR strains was superior compared to commercial drugs. These Bfx compounds have a narrow spectrum for mycobacteria, which helps avoid dysbiosis of the gut microbiota, and they also exhibit high selectivity and low toxicity. Synergism studies indicate that Bfx derivatives could be combined with rifampicin to enhance treatment efficacy and reduce its duration. Scanning electron microscopy revealed severe damage to the morphology of Mtb following treatment with Bfx 5n, showing significant distortions in the bacillary structures. Whole-genome sequencing of the 5n-resistant isolate suggests resistance mechanisms mediated by the Rv1855c gene, supported by in silico studies. In vivo studies showed that the 5n compound reduced the pulmonary load by 3.0 log 10 CFU/mL, demonstrating superiority over rifampicin, which achieved a reduction of 1.23 log 10 CFU/mL. In conclusion, Bfx derivatives, especially 5n, effectively address resistant infections caused by Mtb , suggesting they could be a solid foundation for future therapeutic developments against MDR-TB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Campos, Canales, Demarqui, Fernandes, dos Santos, Prates, da Silva, Barros-Cordeiro, Báo, de Andrade, Abichabki, Zacharias, de Campos, dos Santos and Pavan.)

Background: Nuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction., Methods: DICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality., Results: After adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study., Conclusion: Adding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting., Trial Registration: This study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259-8105., (© 2024. The Author(s).)

This study aimed to evaluate the antidepressant-like and antioxidant potential of the aqueous leaf extract of Morus nigra L. in rats subjected to unpredictable chronic mild stress (UCMS). Male Wistar rats were divided into four groups, control and stressed, and treated with saline or aqueous extract of M. nigra. The dose administered was 10 mg/kg daily by gavage for 5 weeks concurrently with UCMS. M. nigra extract which showed syringic acid, quercetin, and rutin, as major phenolic compounds decreased the immobility time without changes in locomotor activity of stressed rats, in the forced swimming and open field tests, respectively. In addition, the extract diminished carbonylated proteins, lipid peroxidation, and nitrite levels in the brains of rats subjected to UCMS. These data reinforced antidepressant-like properties with the involvement of oxidative stress modulation by M. nigra extract pointing it as a possible new adjuvant treatment for depression.

Sickle Cell Anemia (SCA), is an inherited hemoglobinopathy characterized by the presence of an abnormal hemoglobin (HbS), being the most prevalent sickle cell disease (SCD). SCA is characterized by vascular endothelial dysfunction, which contributes significantly to various clinical conditions, including but not limited to pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke. The pathophysiology of endothelial dysfunction (ED) in SCA is a multifaceted process involving a chronic inflammatory and hypercoagulable state. Key factors include hemolysis-associated elements like reduced arginine and nitric oxide (NO) availability, elevated levels of vascular adhesion molecules, the uncoupling effect of NO synthase, heightened arginase activity, an environment characterized by oxidative stress with the production of reactive oxygen and nitrogen species, and occurrences of ischemia-reperfusion injury, along with apolipoprotein A-1 depletion. The urgency for novel interventions addressing ED is evident. Presently, there is a focus on investigating small molecules that disrupt the arginine-nitric oxide pathway, exhibiting anti-inflammatory and antioxidant properties while diminishing levels of cellular and vascular adhesion molecules. In this mini-review article, we delve into the progress made in strategies for treating ED in SCD with the aim of cultivating insights for drug design., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients., Methods: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs a survey-type, cross-sectional, descriptive-analytical method to evaluate the profile of bodybuilding athletes in the State of Sergipe, Brazil, and verify the level of knowledge/awareness about the health risks and impacts resulting from the use of such substances. Finite- and convenience-type populations are assessed, including individuals of both sexes, aged older than 18 years, self-declared bodybuilding athletes residing in the State of Sergipe, Brazil, and participating in regional and/or state competitions. As a result, no significant relationships were determined between sex ( p = 0.492), age ( p = 0.460), family income ( p = 0.141), and medical follow-up sessions. For the variables level of education and medical follow-up vs. no follow-up sessions, a significant result was achieved ( p = 0.01), with 74.3% of individuals reporting having follow-up treatment and 25.7% responding that they had no follow-up treatment, a percentage representing the group that completed their higher education. The substances most used by the athletes were Sustanon 250 or Durateston, Nandrolone Decanoate (Deca or Deca-Durabolin), and Testosterone. The most-reported acute side effects were acne at 33.8% ( n = 20), irritability at 32.1% ( n = 19), alopecia (hair loss), and nervousness at 23.7% ( n = 14). The most-reported chronic side effects were arterial hypertension at 36.0% ( n = 9), liver disease at 28.0% ( n = 7), and cancer (non-specific) at 8.0% ( n = 2). We concluded that, regardless of the athletes' socioeconomic profiles, the use of AASs was high, with two or more substances being used in combination and for a prolonged period. Thus, it is necessary to promote awareness campaigns regarding the use of AASs and their effects on high-performance and recreational athletes.

Introduction: Tuberculosis remains a significant concern in global public health due to its intricate biology and propensity for developing antibiotic resistance. Discovering new drugs is a protracted and expensive endeavor, often spanning over a decade and incurring costs in the billions. However, computer-aided drug design (CADD) has surfaced as a nimbler and more cost-effective alternative. CADD tools enable us to decipher the interactions between therapeutic targets and novel drugs, making them invaluable in the quest for new tuberculosis treatments., Areas Covered: In this review, the authors explore recent advancements in tuberculosis drug discovery enabled by in silico tools. The main objectives of this review article are to highlight emerging drug candidates identified through in silico methods and to provide an update on the therapeutic targets associated with Mycobacterium tuberculosis., Expert Opinion: These in silico methods have not only streamlined the drug discovery process but also opened up new horizons for finding novel drug candidates and repositioning existing ones. The continued advancements in these fields hold great promise for more efficient, ethical, and successful drug development in the future.

Microorganisms, such as yeasts, filamentous fungi, bacteria, and microalgae, have gained significant attention due to their potential in producing commercially valuable natural carotenoids. In recent years, Phaffia rhodozyma yeasts have emerged as intriguing non-conventional sources of carotenoids, particularly astaxanthin and β-carotene. However, the shift from academic exploration to effective industrial implementation has been challenging to achieve. This study aims to bridge this gap by assessing various scenarios for carotenoid production and recovery. It explores the use of ionic liquids (ILs) and bio-based solvents (ethanol) to ensure safe extraction. The evaluation includes a comprehensive analysis involving Life Cycle Assessment (LCA), biocompatibility assessment, and Techno-Economic Analysis (TEA) of two integrated technologies that utilize choline-based ILs and ethanol (EtOH) for astaxanthin (+β-carotene) recovery from P. rhodozyma cells. This work evaluates the potential sustainability of integrating these alternative solvents within a yeast-based bioeconomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

(1) Background: Species of the genus Cymbopogon and its essential oil are known for their antioxidant and hypoglycemic effects. This study aimed to investigate the impact of the essential oil of Cymbopogon flexuosus (EOCF), and its major component, citral, on glycemic, lipid, antioxidant parameters, and oxidative stress in a type 1 diabetes (DM1) rat model. (2) Methods: Initially, EOCF was analyzed by Gas chromatography-mass spectrometry (GC-MS) and the antioxidant activity of EOCF and citral was evaluated. Next, male Wistar rats (3 months old, 200-250 g) induced with DM1 using Streptozotocin (STZ) were divided into four groups: negative control supplemented with an 80% Tween solution, two groups of animals supplemented with EOCF (32 mg/kg and 64 mg/kg) and with citral (32 mg/kg), and treated for 14 days. Measurements of blood glucose levels and body weight were taken; after euthanasia, biochemical markers, including lipid profile, uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated. (3) Results: The predominant compounds in EOCF were α-citral (53.21%) and neral (19.42%), constituting 72.63% citral. EOCF showed good antioxidant activity, significantly greater than citral. EOCF supplementation demonstrated a mitigating effect on glycemic, lipid, and hepatic abnormalities induced by DM1. (4) Conclusions: EOCF emerges as a promising therapeutic option for the management of DM1.

Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can generate photoproducts and reactive oxygen species (ROS). Adding antioxidants, such as resveratrol, to enhance the action of UV filters in sunscreens is an interesting strategy for reducing the damage caused by UV radiation exposure. However, new compounds must have their stability, safety and efficacy guaranteed. Avobenzone, a commonly used UV filter, stands out as a promising candidate for structural modification to enhance its stability. Its molecular hybridization with other UV filters and antioxidants can lead to safer and more effective compounds. In this study, the photoprotective and antioxidant potential of a derivative of avobenzone, hybridized with resveratrol's molecule, was evaluated using in vitro models of cells in monolayer and reconstructed human skin (RHS). Phototoxic potential was assessed using fibroblasts, while the antioxidant activity was measured using the DCFH 2 -DA probe in HaCaT keratinocytes and in-house RHS. The derivative exhibited UV absorption and demonstrated photostability. It did not exhibit any phototoxic nor photoreactivity potential. Additionally, it was able to photo stabilize a combination of photounstable UV filters, avobenzone and octyl methoxycinnamate, and to reduce their phototoxic potential. In terms of antioxidant activity, the derivative successfully protected against UVA-induced ROS production in the HaCaT keratinocytes model, showing statistical equivalence to the antioxidant control, quercetin (10 μg/mL). Furthermore, experiments conducted in the RHS model demonstrated a significant reduction of 30.7% in ROS generation compared to the irradiated control. This study demonstrated that structural modifications of avobenzone can lead to the development of a broad spectrum (absorbing UVB and UVA II radiation, as well as a portion of the UVA I radiation), non-phototoxic, non-photoreactive and photostable derivative for sunscreen and anti-aging formulations. This derivative enhances protection against oxidative stress induced by UV radiation and improves the effectiveness of sun protection. In addition to the monolayer model, the use of a standardized in-house RHS model was highly relevant for evaluating the effects of UV radiation and skin aging. This model closely mimics human physiological conditions and enables the testing of new compounds and the investigation of protective mechanisms against skin damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pasuch Gluzezak, Dos Santos, Maria-Engler and Gaspar.)

Tuberculosis (TB) has claimed more lives over the course of two millennia than any other infectious disease worldwide. In 2021, the World Health Organization (WHO) estimated that 10.6 million people were diagnosed with TB, resulting in the deaths of 1.4 million HIV-negative individuals. The emergence of multidrug-resistant TB (MDR-TB), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), and extensively drug-resistant TB (XDR-TB), poses the primary challenge to overcome in the coming years. We have recently conducted an extensive analysis of investments and research endeavours in the field, with the overarching objective of achieving the established milestone of TB eradication by the year 2030. Over the past several years, there has been notable progress in advancing a multitude of promising compounds, each possessing distinct mechanisms of action, into clinical phases of development. However, it is worth noting that strains of mycobacteria resistant to current antitubercular drugs have already emerged for some of these compounds The exploration of the innovative Proteolytic Target Chimeras (PROTACs) protein degradation approach has emerged as a viable avenue for the discovery of novel antimicrobials. While the ubiquitin system is exclusive to eukaryotic cells, certain bacteria use a similar degradation system that relies on the recognition of phosphorylated arginine residues (pArg) by the ClpC:ClpP (ClpCP) protease, thereby leading to protein degradation. In this opinion article, we have described and analized the advances in the use of PROTACs that leverage bacterial proteolytic machinery (BacPROTACs) to design new antitubercular agents. Scope Statement. The development of novel pharmaceuticals for tuberculosis treatment is deemed urgently necessary due to the emergence of resistant strains. In this context, the introduction of new technologies capable of alleviating the disease and attaining the objectives outlined by the World Health Organization is imperative. Among the innovative strategies, the degradation of proteins that are crucial for the survival of the bacillus holds promise for generating new medications, particularly those that are effective at treating latent (non-replicating) Mycobacterium tuberculosis . Within this perspective, we present the advancements and obstacles encountered in the exploration of new BacPROTAC compounds, with the intention of encouraging research and illuminating challenges associated with the implementation of BacPROTACs to address to the global tuberculosis crisis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bonjorno, Pavan, Fernandes, Scarim, Castagnolo and Dos Santos.)

Chagas disease (CD) is a parasitic disease endemic in several developing countries. According to the World Health Organization, approximately 6-8 million people worldwide are inflicted by CD. The scarcity of new drugs, mainly for the chronic phase, is the main reason for treatment limitation in CD. Therefore, there is an urgent need to discover new targets for which new therapeutical agents could be developed. Cruzain cysteine protease (CCP) is a promising alternative because this enzyme exhibits pleiotropic effects by acting as a virulence factor, modulating host immune cells, and interacting with host cells. This systematic review was conducted to discover new compounds that act as cruzain inhibitors, and their effects in vitro were studied through enzymatic assays and molecular docking. Additionally, the advances and perspectives of these inhibitors are discussed. These findings are expected to contribute to medicinal chemistry in view of the design of new, safe, and efficacious inhibitors against Trypanosoma cruzi CCP detected in the last decade (2013-2022) to provide scaffolds for further optimization, aiming toward the discovery of new drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bioanalytical methods are used to quantify drugs and their metabolites in biological samples in order to determine bioequivalence, perform pharmacokinetic and bioavailability studies, and complete therapeutic drug monitoring. The objective of this review paper is to describe bioanalytical methods based on Liquid Chromatography that are used to quantify antitubercular drugs and their metabolites in different biological samples, utilizing scientific literature from 1992 to 2021.

Antiretroviral Therapy (ART) is an effective treatment for human immunodeficiency virus (HIV) which has transformed the highly lethal disease, acquired immunodeficiency syndrome (AIDS), into a chronic and manageable condition. However, better methods need to be developed for enhancing patient access and adherence to therapy and for improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS.

Phthalimide, a pharmacophore exhibiting diverse biological activities, holds a prominent position in medicinal chemistry. In recent decades, numerous derivatives of phthalimide have been synthesized and extensively studied for their therapeutic potential across a wide range of health conditions. This comprehensive review highlights the latest developments in medicinal chemistry, specifically focusing on phthalimide-based compounds that have emerged within the last decade. These compounds showcase promising biological activities, including anti-inflammatory, anti-Alzheimer, antiepileptic, antischizophrenia, antiplatelet, anticancer, antibacterial, antifungal, antimycobacterial, antiparasitic, anthelmintic, antiviral, and antidiabetic properties. The physicochemical profiles of the phthalimide derivatives were carefully analyzed using the online platform pkCSM, revealing the remarkable versatility of this scaffold. Therefore, this review emphasizes the potential of phthalimide as a valuable scaffold for the development of novel therapeutic agents, providing avenues for the exploration and design of new compounds., (© 2023 Wiley Periodicals LLC.)

Macrophages represent a crucial line of defense and are responsible for preventing the growth and colonization of pathogens in different tissues. Conidial phagocytosis is a key process that allows for the investigation of the cytoplasmic and molecular events involved in macrophage-pathogen interactions, as well as for the determination of the time of death of internalized conidia. The technique involving the phagocytosis of fungal conidia by macrophages is widely used for studies evaluating the modulation of the immune responses against fungi. The evasion of phagocytosis and escape of phagosomes are mechanisms of fungal virulence. Here, we report the methods that can be used for the analysis of the phagocytosis, clearance, and viability of T. stromaticum conidia, a fungus which is used as a biocontrol and biofertilizer agent and is capable of inducing human infections. The protocol consists of 1) Trichoderma culture, 2) washing to obtain conidia, 3) the isolation of peripheral blood mononuclear cells (PBMCs) using the polysucrose solution method and the differentiation of the PBMCs into macrophages, 4) an in vitro phagocytosis method using round glass coverslips and coloration, and 5) a clearance assay to assess the conidia viability after conidia phagocytosis. In summary, these techniques can be used to measure the fungal clearance efficiency of macrophages.

The emergence of multidrug-resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC 90 values of 0.18-1.63 μM against Mtb H37Rv. Compounds 47-49, 51-53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC 90 values below 0.5 μM. In Mtb-infected macrophages, several compounds demonstrated a 1-log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1-b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin-dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB., (© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

ICU patients are exposed to several factors that can lead to muscle structural and functional changes, and ultrasonography can identify them. Although several studies have analyzed the reliability of muscle ultrasonography assessment, a protocol with more muscle assessments becomes a challenge. The aim of this study was to analyze the inter and intra-examiner reliability of peripheral and respiratory muscle ultrasonography assessment in critically ill patients. The sample size was 10 individuals aged ≥ 18 years who were admitted to the ICU. Practical training of four health professionals from different backgrounds was performed. After training, each examiner acquired three images to assess the thickness and echogenicity of the muscle groups: biceps brachii, forearm flexor group, quadriceps femoris, tibialis anterior and diaphragm. For the reliability analysis, an intraclass correlation coefficient was performed. Six hundred US images were analyzed for muscle thickness and 150 for echogenicity. Excellent intra-examiner reliability for echogenicity (ICC: 0.867-0.973) and inter-examiner reliability for thickness were found in all muscle groups (ICC: 0.778-0.942). For muscle thickness intra-examiner reliability, excellent results were found (ICC: 0.798-0.988), with a "good" correlation in one diaphragm assessment (ICC: 0.718). Excellent inter- and intra-examiner reliability of the thickness assessment and intra-examiner echogenicity of all muscles analyzed were found.

Trichoderma is a saprophytic fungus that is used worldwide as a biocontrol and biofertilizer agent. Although considered nonpathogenic until recently, reports of human infections produced by members of the Trichoderma genus are increasing. Numerous sources of infection were proposed based upon patient data and phylogenetic analysis, including air, agriculture, and healthcare facilities, but the deficit of knowledge concerning Trichoderma infections makes patient treatment difficult. These issues are compounded by isolates that present profiles which exhibit high minimum inhibitory concentration values to available antifungal drugs. The aim of this review is to present the global distribution and sources of infections that affect both immunocompetent and immunocompromised hosts, clinical features, therapeutic strategies that are used to treat patients, as well as highlighting treatments with the best responses. In addition, the antifungal susceptibility profiles of Trichoderma isolates that have emerged in recent decades were examined and which antifungal drugs need to be further evaluated as potential candidates to treat Trichoderma infections are also indicated.

Introduction: Sickle cell anemia (SCA) is a hematological genetic disorder caused by a mutation in the gene of the β-globin. Pharmacological treatments will continue to be an important approach, including the strategy to induce fetal hemoglobin (HbF)., Areas Covered: Here, we analyzed the articles described in the literature regarding the drug discovery of HbF inducers. The main approaches for such strategy will be discussed, highlighting those most promising., Expert Opinion: The comprehension of the mechanisms involved in the β-globin regulation is the main key to design new drugs to induce HbF. Among the strategies, gamma-globin regulation by epigenetic enzymes seems to be a promising approach to be pursued, although the comprehension of the selectivity role for those new drugs is crucial to reduce adverse effects. The low druggability of transcription factors and their vital role in embryonic human development are critical points that should be taken in account for drug design. The guanylate cyclase and the NO/cGMP signaling pathway seem to be promising not only for HbF induction, but also for the protective effects in the cardiovascular system. The association of drugs acting through different mechanisms to induce HbF seems to be promising for the discovery of new drugs.

Vascular endothelium is a protective layer of cells lining the lumen of blood vessels that plays important roles by releasing factors responsible for controlling the vascular tone, regulating the expression of pro-inflammatory cytokines, and expressing adhesion molecules involved in vascular hemostasis. Imbalance of vascular properties leads to endothelial dysfunction (ED) and cardiovascular damage. Some diseases, such as sickle cell anemia, are characterized by ED with reduction in the levels of nitric oxide (NO). Previously, we have shown that the fetal hemoglobin inducer agent 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate ( Lapdesf-4c ) could act as NO donor, inhibiting platelet aggregation and reducing the inflammation associated with SCA. However, the vascular effect of this compound was not yet studied. Herein, we evaluated the effects of Lapdesf-4c in vascular reactivity experiments using aortic rings from male Wistar rats (300 g/90 days). We have found that Lapdesf-4c induced vasodilation in the presence (E+) or absence of endothelium (E-) with an average of EMax values of 101.8 ± 3.33% and 111.8 ± 3.21%. The mechanism of action was studied using 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), L -N G -nitroarginine methyl ester ( L -NAME), and hydroxocobalamin. The EMax values for those pathways were hydroxocobalamin (30.6 ± 2.21%), ODQ (4.75 ± 0.51%), and L -NAME (109 ± 3.65), suggesting that Lapdesf-4c exhibits NO-dependent mechanisms. Lapdesf-4c was able to prevent angiotensin-induced ED after incubation of aorta rings for 1 h. We found based on the concentration-effect curve using acetylcholine (ACh) that pEC50 values for the control, Ang II, and combination of (Ang II + Lapdesf-4c ) were 6.73, 6.46, and 7.15, respectively. In conclusion, Lapdesf-4c has emerged as a new drug candidate that can promote vasodilation and act as a protective agent against ED, being useful to prevent vascular damage.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good in vivo efficacy against Mycobacterium tuberculosis . Additionally, we highlight the main challenges and strategies for developing new TB drugs and the current global pipeline of drug candidates in clinical studies to foment fresh research perspectives.

Background: Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis., Aim: This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice., Methods: Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks)., Outcomes: Hematological parameters, concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as to electrical field stimulation (EFS), were obtained in mice corpus cavernosum strips., Results: Corpus cavernosum relaxations to SNP and EFS were increased in eNOS-/- group, which were normalized by RVT-FxMe treatment. SCD mice exhibited an excessive CC relaxant response induced by ACh, EFS and SNP RVT-FxMe treatment did not change the increased relaxant responses to ACh, EFS and SNP in corpus cavernosum from SCD group., Clinical Translation: Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds., Strength/limitations: While mechanistic data with promising potential is showed, the current study is not without limitations. RVT-FxMe effects in the mid- and long-term warrant complementary studies., Conclusion: Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS-/- mice, but not in SCD mice; it is likely that excess of plasma hemoglobin in SCD mice act to inactivate NO before it reaches soluble guanylyl cyclase, avoiding restoration of NO bioavailability in penis., Competing Interests: The authors have declared that no competing interests exist.

Background/objectives: The influence of cardioprotective foods on nontraditional indexes related to dysglycemia and body fat distribution is unknown in individuals with coronary artery disease (CAD). This study aimed to evaluate the effect of a healthy diet supplemented with pecan nuts or extra-virgin olive oil on glycemic profile and adipose tissue dysfunction assessed by anthropometric indexes in patients with stable CAD., Subjects/methods: In a randomized, pragmatic, parallel clinical trial lasting 12 weeks, 204 individuals were allocated to three interventions: a healthy diet (control group [CG], n = 67), a healthy diet plus 30 g/day of pecan nuts (pecan nut group [PNG], n = 68), or a healthy diet plus 30 mL/day of extra-virgin olive oil (olive oil group [OOG], n = 69). Triglyceride-glucose (TyG) index (primary outcome) and other markers of glycemic profile were evaluated, and nontraditional anthropometric indexes as well. Diet quality was assessed according to the Alternate Healthy Eating Index (mAHEI)., Results: After adjustment for baseline values, use of antidiabetic drugs and insulin, there were no differences in both glycemic and anthropometric profiles according to groups at the end of the study. PNG improved the quality of the diet in comparison to other groups (final mAHEI scores: CG: 19 ± 7.5; PNG: 26 ± 8; OOG: 18.9 ± 6; P < 0.001)., Conclusions: There was no difference regarding glycemic and anthropometric parameters according to interventions in patients with stable CAD. However, adding pecan nuts to a healthy diet may improve its quality. Further studies must be conducted considering dietary interventions on secondary cardiovascular prevention setting., Clinical Trials Identifier Number: NCT02202265. First Posted: July 2014; Last Update: September 2020., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi , which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage-characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease's progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Resveratrol (RVT) and curcumin (CUR) are natural compounds with potent antioxidant and anti-inflammatory properties and their cardioprotective effect have been proposed to have benefits to treat CD. Such effects could decrease or block the progression of the disease's severity. The purpose of this systematic review is to analyze the effectiveness of RVT and CUR in animal and clinical research for the treatment of CD. The study was performed according to PRISMA guidelines and it was registered on PROSPERO (CDR42021293495). The results did not find any clinical study, and the animal research was analyzed according to the SYRCLES risk of bias tools and ARRIVE 2.0 guidelines. We found 9 eligible reports in this study. We also discuss the potential RVT and CUR derivatives for the treatment of CD as well.

Peroxisome proliferator-activated receptors are promising therapeutic targets for metabolic diseases, including obesity, diabetes, and dyslipidemia. This study describes the design, synthesis and pharmacological evaluation of stilbene-based compounds as dual PPARα/γ partial agonists with potency in the nanomolar range. In vitro and in vivo assays revealed that the lead compound (E)-4-styrylphenoxy-propanamide (5b) removed 14 C-cholesterol from the foam cells through apolipoprotein A-I and High-Density Lipoprotein-2. In the high-fat diet-induced obesity mouse model, the oral administration of compound 5b increased HDL levels, paraoxonase-1 activity, and insulin sensitivity, and decreased glucose levels. Moreover, the adipogenesis pathway and triglyceride accumulation slightly changed in the adipocyte cells upon treatment with compound 5b, without affecting the body weight and adipose tissue in obese mice. Compound 5b did not affect the plasma levels of hepatic and renal injury biomarkers. Thus, stilbene-based compound 5b is a promising prototype for developing novel candidates to treat dyslipidemia and diabetes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Spider venoms induce different physio-pharmacological effects by binding with high affinity on molecular targets, therefore being of biotechnological interest. Some of these toxins, acting on different types of ion channels, have been identified in the venom of spiders of the genus Phoneutria , mainly from P. nigriventer . In spite of the pharmaceutical potential demonstrated by P. nigriventer toxins, there is limited information on molecules from venoms of the same genus, as their toxins remain poorly characterized. Understanding this diversity and clarifying the differences in the mechanisms of action of spider toxins is of great importance for establishing their true biotechnological potential. This prompted us to compare three different venoms of the Phoneutria genus: P. nigriventer (Pn-V), P. eickstedtae (Pe-V) and P. pertyi (Pp-V)., Methods: Biochemical and functional comparison of the venoms were carried out by SDS-PAGE, HPLC, mass spectrometry, enzymatic activities and electrophysiological assays (whole-cell patch clamp)., Results: The employed approach revealed that all three venoms had an overall similarity in their components, with only minor differences. The presence of a high number of similar proteins was evident, particularly toxins in the mass range of ~6.0 kDa. Hyaluronidase and proteolytic activities were detected in all venoms, in addition to isoforms of the toxins Tx1 and Tx2-6. All Tx1 isoforms blocked Nav1.6 ion currents, with slight differences., Conclusion: Our findings showed that Pn-V, Pe-V and Pp-V are highly similar concerning protein composition and enzymatic activities, containing isoforms of the same toxins sharing high sequence homology, with minor modifications. However, these structural and functional variations are very important for venom diversity. In addition, our findings will contribute to the comprehension of the molecular diversity of the venoms of the other species from Phoneutria genus, exposing their biotechnological potential as a source for searching for new active molecules., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products' most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality.

Biliary atresia is a rare inflammatory sclerosing obstructive cholangiopathy that initiates in infancy as complete choledochal blockage and progresses to the involvement of intrahepatic biliary epithelium. Growing evidence shows that biliary atresia is not a single entity with a single etiology but a phenotype resulting from multifactorial events whose common path is obliterative cholangiopathy. The etiology of biliary atresia has been explained as resulting from genetic variants, toxins, viral infection, chronic inflammation or bile duct lesions mediated by autoimmunity, abnormalities in the development of the bile ducts, and defects in embryogenesis, abnormal fetal or prenatal circulation and susceptibility factors. It is increasingly evident that the genetic and epigenetic predisposition combined with the environmental factors to which the mother is exposed are potential triggers for biliary atresia. There is also an indication that a progressive thickening of the arterial middle layer occurs in this disease, suggestive of vascular remodeling and disappearance of the interlobular bile ducts. It is suggested that the hypoxia/ischemia process can affect portal structures in biliary atresia and is associated with both the extent of biliary proliferation and the thickening of the medial layer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tuberculosis (TB), a highly fatal infectious disease, is caused by Mycobacterium tuberculosis (Mtb) that has inflicted mankind for several centuries. In 2019, the staggering number of new cases reached 10 million resulting in 1.2 million deaths. The emergence of multidrug-resistance- Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant-Mycobacterium tuberculosis (XDR-TB) is a global concern that requires the search for novel, effective, and safer short-term therapies. Nowadays, among the few alternatives available to treat resistant-Mtb strains, the majority have limitations, which include drug-drug interactions, long-term treatment, and chronic induced toxicities. Therefore, it is mandatory to develop new anti-Mtb agents to achieve health policy goals to mitigate the disease by 2035. Among the several bioactive anti-Mtb compounds, chalcones have been described as the privileged scaffold useful for drug design. Overall, this review explores and analyzes 37 chalcones that exhibited anti-Mtb activity described in the literature up to April 2021 with minimum inhibitory concentration (MIC 90 ) values inferior to 20 μM and selective index superior to 10. In addition, the correlation of some properties for most active compounds was evaluated, and the main targets for these compounds were discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Drug induced liver injury (DILI) is an adverse drug reaction that causes liver damage in a predictable (dose-dependent) or an unpredictable (idiosyncratic) fashion. We performed an assessment of DILI in Portugal, by analyzing the reports, sent to the Portuguese Pharmacovigilance System (PPS)., Methods: A search was performed on the PPS database, in a 10-year time frame, from 1 January 2010 to 31 December 2019., Results: There was not a prevalence of either sex in any age group. Most reports ( n = 1120, 55.0%) belonged to patients in the age group 19-64 years old. Hepatitis ( n = 626, 26.7%) was the most common adverse drug reaction in our study. Hepatotoxicity ( n = 362, 15.5%) and hepatitis ( n = 333, 14.2%) were more frequent in age group 19-64 years old. Cholestasis was more prevalent in adults independently of age. Hepatic fibrosis and encephalopathy were more common in the elderly. Most patients consumed between one and four suspected drugs ( n = 1867, 92%). Most patients in our study evolved to "cure" ( n = 796; 39%). Hepatotoxicity ( n = 23; 13.8%) and hepatitis ( n = 610; 25.9%) had a female predominancy while choluria ( n = 8; 4.8%) and splenomegaly ( n = 8; 4.8%) were of male predominance., Conclusions: DILI is rare but can be fatal. As such, an active search of DILI is necessary.