Natural compounds-based nanomedicines for cancer treatment: Future directions and challenges.

Several efforts have been extensively accomplished for the amelioration of the cancer treatments using different types of new drugs and less invasives therapies in comparison with the traditional therapeutic modalities, which are widely associated with numerous drawbacks, such as drug resistance, non-selectivity and high costs, restraining their clinical response. The application of natural compounds for the prevention and treatment of different cancer cells has attracted significant attention from the pharmaceuticals and scientific communities over the past decades. Although the use of nanotechnology in cancer therapy is still in the preliminary stages, the application of nanotherapeutics has demonstrated to decrease the various limitations related to the use of natural compounds, such as physical/chemical instability, poor aqueous solubility, and low bioavailability. Despite the nanotechnology has emerged as a promise to improve the bioavailability of the natural compounds, there are still limited clinical trials performed for their application with various challenges required for the pre-clinical and clinical trials, such as production at an industrial level, assurance of nanotherapeutics long-term stability, physiological barriers and safety and regulatory issues. This review highlights the most recent advances in the nanocarriers for natural compounds secreted from plants, bacteria, fungi, and marine organisms, as well as their role on cell signaling pathways for anticancer treatments. Additionally, the clinical status and the main challenges regarding the natural compounds loaded in nanocarriers for clinical applications were also discussed.

Correction: Bufalo et al. Human Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compounds. Cells 2022, 11, 247.

In the original publication [...].

Marine waste derived carbon materials for use as sulfur hosts for Lithium-Sulfur batteries.

Lithium-sulfur batteries are a promising alternative to lithium-ion batteries as they can potentially offer significantly increased capacities and energy densities. The ever-increasing global battery market demonstrates that there will be an ongoing demand for cost effective battery electrode materials. Materials derived from waste products can simultaneously address two of the greatest challenges of today, i.e., waste management and the requirement to develop sustainable materials. In this study, we detail the carbonisation of gelatin from blue shark and chitin from prawns, both of which are currently considered as waste biproducts of the seafood industry. The chemical and physical properties of the resulting carbons are compared through a correlation of results from structural characterisation techniques, including electron imaging, X-ray diffraction, Raman spectroscopy and nitrogen gas adsorption. We investigated the application of the resulting carbons as sulfur-hosting electrode materials for use in lithium-sulfur batteries. Through comprehensive electrochemical characterisation, we demonstrate that value added porous carbons, derived from marine waste are promising electrode materials for lithium-sulfur batteries. Both samples demonstrated impressive capacity retention when galvanostatically cycled at a rate of C/5 for 500 cycles. This study highlights the importance of looking towards waste products as sustainable feeds for battery material production.

Trends in primary percutaneous coronary intervention for the treatment of acute coronary ST-elevation myocardial infarction in Latin American countries: insights from the CECI consortium.

Background: ST-elevation myocardial infarction (STEMI) requires revascularization treatment, preferably via primary percutaneous coronary interventions (pPCI). There is a lack of data about contemporary management of STEMI in Latin America. Methods: This was a multicenter, multinational, prospective, and dynamic registry of patients undergoing pPCI in Latin America for STEMI (STEMI/LATAMI Registry) that was carried out in nine centers from five countries (Argentina, Ecuador, Venezuela, Bolivia, and the Dominican Republic) between June 2021 and June 2023. All interventionalists involved in the study were originally trained at the same institution (Centro de Estudios en Cardiología Intervencionista, Buenos Aires, Argentina). The primary objective was to evaluate procedural and in-hospital outcomes of pPCI in STEMI and in-hospital outcome in the Latin America (LATAM) region; as secondary endpoints, we analyzed the following subgroups: differences between pPCI vs. pharmaco-invasive or late presenters, gender, elderly and very elderly patients, cardiogenic shock outcomes, and causes of STEMI. Results: In total, 744 STEMI patients who underwent PCI between June 2021 and June 2023 in five countries (nine centers) in our continent were included; 76.3% had a pPCI, 8.1% pharmaco-invasive PCI, and 15.6% had late STEMI PCI. There were no differences in region or center when we evaluated in-hospital and 30 days of death. The rate of procedural success was 96.2%, and the overall in-hospital mortality rate was 2.2%. In the subgroup of pPCI, mean symptom onset-to-balloon time was 295.3 ± 246 min, and mean door-to-balloon time was 55.8 ± 49.9 min. The femoral approach was chosen in 60.5%. In 3.0% of patients, the left main disease was the culprit artery, with 1.63 ± 1.00 stents per patient (564 drug-eluting stents and 652 bare metal stents), with 34 patients receiving only plain optimal balloon angioplasty. Definitive stent thrombosis was related to the infarct artery as the primary cause of STEMI in 7.5% of patients. The use of assistant mechanical devices was low, at 2.1% in the pPCI group. Women were older, with large numbers in very elderly age (≥90 years), greater mortality, and incidence of spontaneous coronary dissection as a cause of STEMI (p < 0.001, p < 0.001, p < 0.001, and p < 0.003, respectively). Conclusion: In suitable LATAM Centers from low/medium-income countries, this prospective registry in patients with STEMI, PCI performed by well-trained operators has comparable results to those reported in well-developed countries.

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Clinical profiles and treatment outcomes of outpatients with interstitial lung disease and mechanic's hands: A retrospective and observational cohort.

Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.

Boosting Supercapacitor Efficiency with Amorphous Biomass-Derived C@TiO2 Composites.

Carbon materials are readily available and are essential in energy storage. One of the routes used to enhance their surface area and activity is the decoration of carbons with semiconductors, such as amorphous TiO2, for application in energy storage devices.

Multivariate analysis applied to X-ray fluorescence to assess soil contamination pathways: case studies of mass magnetic susceptibility in soils near abandoned coal and W/Sn mines.

Determining the origin and pathways of contaminants in the natural environment is key to informing any mitigation process. The mass magnetic susceptibility of soils allows a rapid method to measure the concentration of magnetic minerals, derived from anthropogenic activities such as mining or industrial processes, i.e., smelting metals (technogenic origin), or from the local bedrock (of geogenic origin). This is especially effective when combined with rapid geochemical analyses of soils. The use of multivariate analysis (MVA) elucidates complex multiple-component relationships between soil geochemistry and magnetic susceptibility. In the case of soil mining sites, X-ray fluorescence (XRF) spectroscopic data of soils contaminated by mine waste shows statistically significant relationships between magnetic susceptibility and some base metal species (e.g., Fe, Pb, Zn, etc.). Here, we show how qualitative and quantitative MVA methodologies can be used to assess soil contamination pathways using mass magnetic susceptibility and XRF spectra of soils near abandoned coal and W/Sn mines (NW Portugal). Principal component analysis (PCA) showed how the first two primary components (PC-1 + PC-2) explained 94% of the sample variability, grouped them according to their geochemistry and magnetic susceptibility in to geogenic and technogenic groups. Regression analyses showed a strong positive correlation (R2 > 0.95) between soil geochemistry and magnetic properties at the local scale. These parameters provided an insight into the multi-element variables that control magnetic susceptibility and indicated the possibility of efficient assessment of potentially contaminated sites through mass-specific soil magnetism.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients.

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8 days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1ß levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.

Eugenia uniflora (pitanga) juice as a new alternative vehicle for Limosilactobacillus fermentum ATCC 23271: evaluation of antioxidant and anti-infective effects.

Probiotic-containing foods are among the most appreciated functional foods; however, probiotic-based dairy products cannot be consumed by people who are lactose intolerant, allergic to milk, or vegetarian or vegan individuals. Thus, new non-dairy matrices have been tested for probiotics delivery. This study evaluated the growth and viability of Limosilactobacillus fermentum ATCC 23271 and Lacticaseibacillus rhamnosus ATCC 9595 in Pitanga juice (Eugenia uniflora L.). The effects of the fermentation on the antioxidant and anti-infective properties of the juice were also analyzed. The E. uniflora juice allowed lactobacilli growth without supplementation, reaching rates around 8.4 Log CFU/mL and producing organic acids (pH values < 4) after 72 h of fermentation. The strain remained viable after 35 days of refrigerated storage. Fermentation by these bacteria increases the antioxidant capacity of the juice. The central composite rotational design was employed to evaluate the effects of bacterial inoculum and pulp concentration on growth and organic acids production by L. fermentum ATCC 23271. The strain was viable and produced organic acids in all tested combinations. L. fermentum-fermented juice and its cell-free supernatant significantly increased the survival of Tenebrio molitor larvae infected by enteroaggregative Escherichia coli 042. The results obtained in this study provide more insights into the potential of Pitanga juice to develop a functional non-dairy probiotic beverage with antioxidant and anti-infective properties.

Whey Cheeses Containing Probiotic and Bioprotective Cultures Produced with Ultrafiltrated Cow's Whey.

Bovine whey cheese (WC) is a product from southern European countries that presents some challenges: its production process involves high energy inputs; the yield is low; and WC has a short shelf life. The application of ultrafiltration (UF) to bovine whey before manufacture of WC and the employment of protective cultures can reduce these disadvantages. The objective of this research was the production of whey cheeses using ultrafiltrated bovine cheese whey with added probiotics or probiotics plus protective cultures. Three types of WC were produced: control CW without any addition (C); CW with the addition of the probiotic Lactobacillus acidophilus (LA5); and CW with the addition of Lactobacillus acidophilus plus a protective culture containing Lacticaseibacillus paracasei and Lacticaseibacillus rhamnosus (LA5FQ4). The WCs were stored under refrigerated conditions for 28 days. The products with added cultures presented lower pH values and higher titratable acidities when compared to the control. Sample LA5 presented the lowest pH and the highest titratable acidity, while LA5FQ4 presented intermediate values. Slight differences were observed between products regarding color parameters, chiefly resulting from storage time. The samples with added cultures were firmer when compared to the control, with LA5 cheeses showing the highest values at the end of the storage. Lactic acid bacteria (LAB) counts were on the order of log 8-9 CFU/g for the products with added cultures. Lower levels of yeasts and molds were detected on the sample with the protective culture (LA5FQ4), so that by the end of storage they presented counts one log cycle lower than C and LA5. Hence, the beneficial impact of the protective culture on the shelf life of the product is evident. Regarding sensory evaluation, LA5FQ4 cheeses obtained the highest scores for all parameters evaluated. It can be concluded that the use of UF associated with the addition of protective cultures can be very useful to reduce the energy consumption of the manufacturing process, to prolong the shelf life of WC and to improve its sensory properties.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses.

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

Effects of Ivabradine on Myocardial Perfusion in Chronic Angina: A Prospective, Preliminary, Open-Label, Single-Arm Study.

INTRODUCTION: Ivabradine reduces heart rate (HR), episodes of angina, and nitrate consumption, and increases exercise capacity in patients with chronic angina (CA). In this exploratory study, myocardial perfusion scintigraphy (MPS) was used to evaluate changes in the percentage of myocardial ischemia after ivabradine therapy in patients with CA. METHODS: This prospective, open-label, single-arm study included patients with CA receiving maximum tolerated doses of beta blockers, who had a resting HR ≥ 70 bpm and had experienced ischemia according to MPS during an exercise test at baseline. Participants received ivabradine 5 mg twice daily (titrated according to HR) concomitant with beta blockers. A second MPS was performed after 3 months, without interruption of treatment with beta blockers or ivabradine. The primary outcome was change in the percentage of myocardial ischemia from baseline to 3 months. Time to ischemia during the exercise test, the proportion of patients presenting angina during the exercise test, and health status, assessed using the seven-item Seattle Angina Questionnaire-7 (SAQ-7), were also evaluated. RESULTS: Twenty patients (3 females) with a mean (± standard deviation [SD]) age of 62.2 ± 6.5 years were included in the study, of whom 55% had diabetes, 70% had previous myocardial revascularization, and 45% had previous myocardial infarction. The percentage of patients with myocardial ischemia significantly decreased from baseline to 3 months after initiation of treatment with ivabradine (- 2.9%; 95% confidence interval [CI] - 0.3 to - 5.5; p = 0.031). Mean time to appearance of ischemia increased from 403 ± 176 s at baseline to 466 ± 136 s at 3 months after initiation of ivabradine (Δ62 s; 95% CI 18-106 s; p = 0.008), and the proportion of patients experiencing angina during the exercise test decreased from 40% at baseline to 5% also at 3 months (p = 0.016). Mean resting HR decreased from 76 ± 7 bpm at baseline to 55 ± 8 bpm at 3 months (p < 0.001). The mean SAQ-7 summary score improved from 69 ± 21 at baseline to 83 ± 12 at 3 months (p = 0.001). No serious adverse effects were reported. CONCLUSION: Ivabradine added to beta blockers was associated with a reduction in detectable myocardial ischemia by MPS in patients with CA. Infographic available for this article. TRIAL REGISTRATION: The trial has been retrospectively registered with the Brazilian Registry of Clinical Trials (REBEC) under the following number RBR-5fysqrh (date of registration: 30 November 2023).

Connective tissue disease-associated interstitial lung disease.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Relative incidence of interstitial lung diseases in Brazil.

OBJECTIVE: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. METHODS: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. RESULTS: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). CONCLUSIONS: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.