Synthesis of polymeric nanoparticles by double emulsion and pH-driven: encapsulation of antibiotics and natural products for combating Escherichia coli infections.

The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.

Cannabidiol-loaded microparticles embedded in a porous hydrogel matrix for biomedical applications.

In this study, poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with cannabidiol (CBD) were synthesized (PLGA@CBD microparticles) and embedded up to 10 wt% in a chondroitin sulfate/polyvinyl alcohol hydrogel matrix. In vitro chemical, physical, and biological assays were carried out to validate the potential use of the modified hydrogels as biomaterials. The microparticles had spherical morphology and a narrow range of size distribution. CBD encapsulation efficiency was around 52%, loading was approximately 50%. Microparticle addition to the hydrogels caused minor changes in their morphology, FTIR and thermal analyses confirmed these changes. Swelling degree and total porosity were reduced in the presence of microparticles, but similar hydrophilic and degradation in phosphate buffer solution behaviors were observed by all hydrogels. Rupture force and maximum strain at rupture were higher in the modified hydrogels, whereas modulus of elasticity was similar across all materials. Viability of primary human dental pulp cells up to 21 days was generally not influenced by the addition of PLGA@CBD microparticles. The control hydrogel showed no antimicrobial activity against Staphylococcus aureus, whereas hydrogels with 5% and 10% PLGA@CBD microparticles showed inhibition zones. In conclusion, the PLGA@CBD microparticles were fabricated and successfully embedded in a hydrogel matrix. Despite the hydrophobic nature of CBD, the physicochemical and morphological properties were generally similar for the hydrogels with and without the CBD-loaded microparticles. The data reported in this study suggested that this original biomaterial loaded with CBD oil has characteristics that could enable it to be used as a scaffold for tissue/cellular regeneration.

Panorama of Bacterial Infections Caused by Epidemic Resistant Strains.

Antimicrobial resistance (AMR) represents a critical obstacle to public health worldwide, due to the high incidence of strains resistant to available antibiotic therapies. In recent years, there has been a significant increase in the prevalence of resistant epidemic strains, associated with this, public health authorities have been alarmed about a possible scenario of uncontrolled dissemination of these microorganisms and the difficulty in interrupting their transmission, as nosocomial pathogens with resistance profiles previously considered sporadic. They become frequent bacteria in the community. In addition, therapy for infections caused by these pathogens is based on broad-spectrum antibiotic therapy, which favors an increase in the tolerance of remaining bacterial cells and is commonly associated with a poor prognosis. In this review, we present the current status of epidemic strains of methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), MDR Mycobacterium tuberculosis, extended-spectrum ß-lactamase-producing Enterobacterales (ESBL), Klebsiella pneumoniae carbapenemase (KPC), and-New Delhi Metallo-beta-lactamase-producing Pseudomonas aeruginosa (NDM).

Chemokines in Leishmaniasis: Map of cell movements highlights the landscape of infection and pathogenesis.

Pathogen interactions with the host immune response components are critical for establishing protective immunity and pathological responses against Leishmania parasites. A predominant proinflammatory profile associated with enhanced phagocytosis trigger a cell-mediated immune response that is relevant to infection control. On the other hand, an anti-inflammatory phenotype, correlated with a predominant modulated/regulatory response, favors intracellular proliferation of Leishmania parasites and disease progression. In this context, chemokines play an important role in determining cellular composition at inflammatory sites. Leishmania infection induces the expression of various chemokines and chemokine receptors in the mammalian host, which can subvert the host immune responses. Indeed, the balance and dynamic changes in cytokines and chemokines may control or predict the disease outcome. In this review, we address our current knowledge regarding the chemokines and chemokines receptors' role in the immunopathogenesis of Tegumentary and Visceral Leishmaniasis.

Swimming training improves cardiovascular autonomic dysfunctions and prevents renal damage in rats fed a high-sodium diet from weaning.

NEW FINDINGS: What is the central question of this study? How does swimming exercise training impact hydro-electrolytic balance, renal function, sympathetic contribution to resting blood pressure and cerebrospinal fluid (CSF) [Na+ ] in rats fed a high-sodium diet from weaning? What is the main finding and its importance? An exercise-dependent reduction in blood pressure was associated with decreased CSF [Na+ ], sympathetically driven vasomotor tonus and renal fibrosis indicating that the anti-hypertensive effects of swimming training in rats fed a high-sodium diet might involve neurogenic mechanisms regulated by sodium levels in the CSF rather than changes in blood volume. ABSTRACT: High sodium intake is an important factor associated with hypertension. High-sodium intake with exercise training can modify homeostatic hydro-electrolytic balance, but the effects of this association are mostly unknown. In this study, we sought to investigate the effects of swimming training (ST) on cerebrospinal fluid (CSF) Na+ concentration, sympathetic drive, blood pressure (BP) and renal function of rats fed a 0.9% Na+ (equivalent to 2% NaCl) diet with free access to water for 22 weeks after weaning. Male Wistar rats were assigned to two cohorts: (1) fed standard diet (SD) and (2) fed high-sodium (HS) diet. Each cohort was further divided into trained and sedentary groups. ST normalised BP levels of HS rats as well as the higher sympathetically related pressor activity assessed by pharmacological blockade of ganglionic transmission (hexamethonium). ST preserved the renal function and attenuated the glomerular shrinkage elicited by HS. No change in blood volume was found among the groups. CSF [Na+ ] levels were higher in sedentary HS rats but were reduced by ST. Our findings showed that ST effectively normalised BP of HS rats, independent of its effects on hydro-electrolytic balance, which might involve neurogenic mechanisms regulated by Na+ levels in the CSF as well as renal protection.

A reduction of viral mRNA, proteins and induction of altered morphogenesis reveals the anti-HTLV-1 activity of the labdane-diterpene myriadenolide in vitro.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) has been associated with leukemia/lymphoma (ATL) and myelopathy/tropical spastic paraparesis (HAM/TSP), in addition to other inflammatory diseases as well as infection complications. Therapeutic approaches for HTLV-1-related pathologies are limited. The labdane diterpene myriadenolide (AMY) is a natural product that exhibit biological activities, such as anti-inflammatory and antiviral activity as reported for HIV and herpesvirus. RESULTS: We demonstrated that this natural product was able to inhibit the expression of gag-pol mRNA and substantially reduced the expression of the structural proteins p19 and gp46. Comparison of treated and untreated cells shows that AMY alters both the morphology and the release of viral particles. The Atomic Force Microscopy assay showed that the AMY treatment reduced the number of particles on the cell surface by 47%. CONCLUSION: We demonstrated that the labdane diterpene myriadenolide reduced the expression of the structural proteins and the budding of viral particles, besides induces altered morphogenesis of HTLV-1, conferring on AMY a new antiviral activity that may be useful for the development of new compounds with specific anti-HTLV-1 activity.

Advances in porphyrins and chlorins associated with polysaccharides and polysaccharides-based materials for biomedical and pharmaceutical applications.

Over the last decade, the convergence of advanced materials and innovative applications has fostered notable scientific progress within the biomedical and pharmaceutical fields. Porphyrins and their derivatives, distinguished by an extended conjugated π-electron system, have a relevant role in propelling these advancements, especially in drug delivery systems, photodynamic therapy, wound healing, and (bio)sensing. However, despite their promise, the practical clinical application of these macrocycles is hindered by their inherent challenges of low solubility and instability under physiological conditions. To address this limitation, researchers have exploited the synergistic association of porphyrins and chlorins with polysaccharides by engineering conjugated systems and composite/hybrid materials. This review compiles the principal advances in this growing research field, elucidating fundamental principles and critically examining the applications of such materials within biomedical and pharmaceutical contexts. Additionally, the review addresses the eventual challenges and outlines future perspectives for this poignant research field. It is expected that this review will serve as a comprehensive guide for students and researchers dedicated to exploring state-of-the-art materials for contemporary medicine and pharmaceutical applications.

New artificial hematophagy system with attractive polymeric biofilm for maintenance of Culex quinquefasciatus (Diptera: Culicidae) in the laboratory.

BACKGROUND: Maintaining mosquito colonies in the laboratory requires a blood supply so that females' oocytes can mature and oviposition can take place. In this study, a new artificial hematophagy system for colonization and maintenance of Culex quinquefasciatus in the laboratory was developed and tested. METHODS: We developed an attractive polymeric biofilm including 25% L-lactic acid for use as a membrane in an artificial hematophagy system and compared the feeding rate of females with Parafilm-M®. We also evaluated the oviposition rate, larval survival and adult emergence of females fed through the attractive biofilm. RESULTS: The average percentage of female Cx. quinquefasciatus fed through the attractive biofilm was 87%, while only 20% became engorged with Parafilm-M® (p < 0.0001). Feeding through the attractive biofilm developed in this study produced high levels of evaluated biological parameters; the percentage of egg laying by females that underwent artificial hematophagy through the biofilm was 90%, with an average of 158 eggs per raft. From these eggs, 97% of the larvae hatched, of which 95% reached the pupal stage. The adult emergence rate corresponded to 93% of pupae. CONCLUSIONS: Insects fed with attractant through the biofilm system had a higher engorgement rate compared to those fed through Parafilm-M®. Our study is preliminary and suggests that polymeric biofilm has great potential for artificially feeding mosquitoes in the laboratory. Based on this research, new studies will be carried out with biofilm and different systems.

Prevalence and implications of pKs-positive Escherichia coli in colorectal cancer.

Colorectal cancer (CRC) remains a significant global health concern, necessitating continuous investigation into its etiology and potential risk factors. Recent research has shed light on the potential role of pKs-positive Escherichia coli (pKs + E. coli) and colibactin in the development and progression of CRC. Therefore, this review aimed to provide an updated analysis of the prevalence and implications of pKs + E. coli in colorectal cancer. We conducted a literature review search in major scientific databases to identify relevant studies exploring the association between pKs + E. coli and CRC. The search strategy included studies published up to the present date, and articles were carefully selected based on predefined inclusion criteria. Thus, the present study encompasses scientific evidence from clinical and epidemiological studies supporting the presence of pKs + E. coli in CRC patients, demonstrating a consistent and significant association in multiple studies. Furthermore, we highlighted the potential mechanisms by which colibactin may promote tumorigenesis and cancer progression within the colorectal mucosa, including the production of genotoxic virulence factors. Additionally, we explored current diagnostic methods for detecting pKs + E. coli in clinical settings, emphasizing the importance of accurate identification. Moreover, we discussed future strategies that could utilize the presence of this strain as a biomarker for CRC diagnosis and treatment. In conclusion, this review consolidated existing evidence on the prevalence and implications of pKs + E. coli in colorectal cancer. The findings underscore the importance of further research to elucidate the precise mechanisms linking this strain to CRC pathogenesis and to explore its potential as a therapeutic target or diagnostic marker. Ultimately, a better understanding of the role of pKs + E. coli in CRC may pave the way for innovative strategies in CRC management and patient care.

Antimicrobial activity of geranium (Pelargonium graveolens) essential oil and its encapsulation in carioca bean starch ultrafine fibers by electrospinning.

Geranium (Pelargonium graveolens) is known for being an aromatic plant rich in bioactive compounds with antibacterial properties. In this study, geranium essential oil (GEO) was extracted and encapsulated in ultrafine bean starch fibers produced by electrospinning as an antibacterial agent. GEO revealed a composition rich in volatile compounds, including citronellol, cis-geraniol, ß-linalool, citronellyl formate, and linalool formate. In its free form, GEO exhibited high antibacterial activity against pathogenic bacteria strains (L. monocytogenes, S. aureus, and E. coli). The bean starch fibers, produced with and without the addition of GEO, were uniform and continuous, with an average diameter ranging from 249 to 373 nm. Confocal analysis indicated a uniform distribution of GEO in the fibers, with a loading capacity of 54.0 %, 42.9 %, and 36.5 % for 20 %, 30 %, and 40 % GEO concentrations, respectively. Remarkably, fibers containing 40 % GEO showed a significant reduction in tested bacteria (L. monocytogenes, S. aureus, and E. coli), suggesting promising applications in preventing losses and extending the shelf life of food through active packaging.

Antihypertensive effect of a nanoemulsion of baccharis dracunculifolia leaves extract in sodium-dependent hypertensive rats.

Baccharis dracunculifolia (DC) is an important botanical source of Brazilian green propolis and have many compounds with potential antihypertensive activity. However, little is known about the specific antihypertensive properties of DC, or the mechanisms involved. Here we aimed to chemically characterise an ethanolic DC extract (eDC), test its antihypertensive properties and the involvement of neurogenic mechanisms using an animal model of salt-dependent hypertension. The chemical analysis of the eDC revealed the presence of many antihypertensive compounds. Administering the eDC in a nanoemulsion formulation (25 to 50 mg/kg) effectively normalised blood pressure in hypertensive rats. The result also suggested that neurogenic mechanisms are involved in the antihypertensive action of eDC. The treatment with p-coumaric acid (0.32 to 3 mg/kg), a polyphenol abundant in the eDC, produced no significant antihypertensive effect. The findings indicate that the eDC has antihypertensive properties, and that these effects may be mediated through neurogenic pressor mechanisms.

Ceftazidime and Usnic Acid Encapsulated in Chitosan-Coated Liposomes for Oral Administration against Colorectal Cancer-Inducing Escherichia coli.

Escherichia coli has been associated with the induction of colorectal cancer (CRC). Thus, combined therapy incorporating usnic acid (UA) and antibiotics such as ceftazidime (CAZ), co-encapsulated in liposomes, could be an alternative. Coating the liposomes with chitosan (Chi) could facilitate the oral administration of this nanocarrier. Liposomes were prepared using the lipid film hydration method, followed by sonication and chitosan coating via the drip technique. Characterization included particle size, polydispersity index, zeta potential, pH, encapsulation efficiency, and physicochemical analyses. The minimum inhibitory concentration and minimum bactericidal concentration were determined against E. coli ATCC 25922, NCTC 13846, and H10407 using the microdilution method. Antibiofilm assays were conducted using the crystal violet method. The liposomes exhibited sizes ranging from 116.5 ± 5.3 to 240.3 ± 3.5 nm and zeta potentials between +16.4 ± 0.6 and +28 ± 0.8 mV. The encapsulation efficiencies were 51.5 ± 0.2% for CAZ and 99.94 ± 0.1% for UA. Lipo-CAZ-Chi and Lipo-UA-Chi exhibited antibacterial activity, inhibited biofilm formation, and preformed biofilms of E. coli. The Lipo-CAZ-UA-Chi and Lipo-CAZ-Chi + Lipo-UA-Chi formulations showed enhanced activities, potentially due to co-encapsulation or combination effects. These findings suggest potential for in vivo oral administration in future antibacterial and antibiofilm therapies against CRC-inducing bacteria.

Treadmill exercise induces hippocampal astroglial alterations in rats.

Physical exercise effects on brain health and cognitive performance have been described. Synaptic remodeling in hippocampus induced by physical exercise has been described in animal models, but the underlying mechanisms remain poorly understood. Changes in astrocytes, the glial cells involved in synaptic remodeling, need more characterization. We investigated the effect of moderate treadmill exercise (20 min/day) for 4 weeks on some parameters of astrocytic activity in rat hippocampal slices, namely, glial fibrillary acidic protein (GFAP), glutamate uptake and glutamine synthetase (GS) activities, glutathione content, and S100B protein content and secretion, as well as brain-derived neurotrophic factor (BDNF) levels and glucose uptake activity in this tissue. Results show that moderate treadmill exercise was able to induce a decrease in GFAP content (evaluated by ELISA and immunohistochemistry) and an increase in GS activity. These changes could be mediated by corticosterone, whose levels were elevated in serum. BDNF, another putative mediator, was not altered in hippocampal tissue. Moreover, treadmill exercise caused a decrease in NO content. Our data indicate specific changes in astrocyte markers induced by physical exercise, the importance of studying astrocytes for understanding brain plasticity, as well as reinforce the relevance of physical exercise as a neuroprotective strategy.

Impact of Chemotherapy Regimens on Body Composition of Breast Cancer Women: A Multicenter Study across Four Brazilian Regions.

This study aimed to investigate the effect of chemotherapy (CT) and its different types of regimens on the anthropometry and body composition of women with breast cancer. Three-hundred-and-four women with breast cancer were enrolled in this multicenter study. The participants were evaluated before the infusion of the first cycle of CT (pre-CT), and until two weeks after CT completion (post-CT), regarding body weight, body mass index (BMI); waist circumference (WC); waist-to-height ratio (WHtR); conicity index (C-index); fat mass index (FMI); and fat-free mass index (FFMI). CT regimens were classified as anthracycline-based (AC-doxorubicin or epirubicin); anthracyclines and taxane (ACT); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); or isolated taxanes (paclitaxel or docetaxel). Women significantly increased BMI and FMI post-CT (p < 0.001 and p = 0.007, respectively). The ACT regimen increased FMI (p < 0.001), while FFMI increased after AC (p = 0.007). It is concluded that the CT negatively impacted body composition and the type of regime had a strong influence. The ACT regimen promoted an increase in FMI compared to other regimens, and the AC increased FFMI. These findings reinforce the importance of nutritional monitoring of breast cancer patients throughout the entire CT treatment.

Strategies for the treatment of colorectal cancer caused by gut microbiota.

Colorectal cancer (CRC), also named as colon and rectal or bowel cancer, is one of the leading neoplasia diagnosed in the world. Genetic sequencing studies of microorganisms from the intestinal microbiota of patients with CRC revealed that changes in its composition occur with the development of the disease, which can play a fundamental role in its development, being mediated by the production of metabolites and toxins that damage enterocytes. Some microorganisms are frequently reported in the literature as the main agents of this process, such as the bacteria Fusobacterium nucleatum, Escherichia coli and Bacteroides fragilis. Thus, understanding the mechanisms and function of each microorganism in CRC is essential for the development of treatment tools that focus on the gut microbiota. This review verifies current research aimed at evaluating the microorganisms present in the microbiota that can influence the development of CRC, as well as possible forms of treatment that can prevent the initiation and/or spread of this disease. Due to the incidence of CRC, alternatives have been launched considering factors beyond those already known in the disease development, such as diet, fecal microbiota transplantation, use of probiotics and antibiotics, which have been widely studied for this purpose. However, despite being promising, the studies that focus on the development of new therapeutic approaches targeting the microorganisms that cause CRC still need to be improved and better developed, involving new techniques to elucidate the effectiveness and safety of these new methods.

Association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone.

INTRODUCTION: The association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone is still scarcely addressed in the literature. OBJECTIVE: To evaluate whether the intensity of obstructive sleep apnea is associated with craniofacial alterations and the position of the hyoid bone in children with mixed dentition. METHODS: 76 children aged 7 to 10 years old were examined by otorhinolaryngological evaluation, polysomnography, and orthodontic assessment, including cephalometry. The participants were divided in 3 groups: primary snoring, mild obstructive sleep apnea and moderate to severe obstructive sleep apnea. Cephalometric measures of the face and hyoid bone were assessed. These measures were compared among the different groups by unpaired Student's t test. Moreover, these measures were correlated with the patient's obstructive apnea and hypopnea index variable using Pearson's correlation test. RESULTS: Of the 76 children, 14 belonged to group 1, with primary snoring; 46 to group 2, with mild obstructive sleep apnea; and 16 to group 3, with moderate-severe obstructive sleep apnea. There was no difference between the groups regarding the craniofacial variables. Children with obstructive sleep apnea showed a longer distance from the hyoid bone to the mandibular plane when compared to the primary snoring group (p<0.05). Between the two obstructive sleep apnea subgroups, patients with moderate or severe disease showed significantly shorter horizontal distance between the hyoid bone and the posterior pharyngeal wall (p<0.05), when compared to the groups with mild obstructive sleep apnea. We also observed a significant positive correlation between obstructive apnea and hypopnea index and the distance from the hyoid to the mandibular plane (p<0.05) as well as a significant negative association between obstructive apnea and hypopnea index and the horizontal distance from the hyoid to the posterior pharyngeal wall (p<0.01). CONCLUSION: We did not observe any association between obstructive sleep apnea and linear lateral alterations of the face. In contrast, there is a direct association between obstructive sleep apnea severity and the inferior and posterior position of the hyoid bone in children aged 7 to 10 years old.

Effects of Psidium guajava L. leaves extract on blood pressure control and IL-10 production in salt-dependent hypertensive rats.

Psidium guajava (guava) leaves extract displays anti-hypertensive properties by mechanisms not yet fully understood. Here, we investigated whether sympathetic drive and immune signaling mechanisms are involved with the antihypertensive effect of the guava extract in a model of salt-dependent hypertension. Raw guava extract (rPsE) was characterized by colorimetric and UPLC-MS techniques. Two doses of rPsE (100 and 200 mg/kg) were evaluated for anti-hypertensive effect using a suspension system (PsE). Weaned male Wistar rats were put on a high-salt diet (HSD, 0.90 % Na+) for 16 weeks and received gavages of PsE for the last 4 weeks. Blood pressure (BP) was measured at the end of treatment in conscious rats. The neurogenic pressor effect was assessed by ganglionic blockade with hexamethonium. Autonomic modulation of heart rate was evaluated by spectral analysis. The effects of orally administered PsE on lumbar sympathetic nerve activity (LSNA) were assessed in anesthetized rats. Blood IL-10, IL-17A, and TNF were measured. The increased neurogenic pressor effect of HSD rats was reduced by PsE 100 mg/kg, but not by 200 mg/kg. PsE (200 mg/kg) administration in anesthetized rats produced a greater fall in BP of HSD rats compared to standard salt diet (SSD) rats. PsE hypotensive response elicited an unproportionable increase in LSNA of HSD rats compared to SSD rats. PsE (200 mg/kg) increased plasma concentrations of IL-10 but had no effect on TNF or IL-17A. Our data indicate that the antihypertensive effects of PsE may involve autonomic mechanisms and immunomodulation by overexpression of IL-10 in salt-dependent hypertensive rats.

Magnetic microspheres based on pectin coated by chitosan towards smart drug release.

This study reports the preparation of microspheres of pectin and magnetite nanoparticles coated by chitosan to encapsulate and deliver drugs. Magnetic-pectin microspheres were obtained by ionotropic gelation followed by polyelectrolyte complexation with chitosan. Characterization data show that magnetite changes the physicochemical and morphological properties of the microspheres compared to the non-magnetic samples. Using metamizole (Mtz) as a drug model, the magnetic microspheres showed appreciable encapsulation efficiency (85 %). Release experiments performed in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids suggested that the release process is pH-dependent. At pH 6.8, the Mtz release is favored achieving 75 % after 12 h. The application of an external magnetic field increased the release to 91 % at pH 6.8, indicating that the release also is magnetic-dependent. The results suggest that the magnetic microspheres based on pectin/chitosan biopolymers show the potential to be used as a multi-responsive drug delivery system.