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ACS Applied Materials & Interfaces Jun 2024Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are...
Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.
PubMed: 38888094
DOI: 10.1021/acsami.4c05214 -
Clinical and Experimental Allergy :... Jun 2024
PubMed: 38886976
DOI: 10.1111/cea.14525 -
ACS Nano Jul 2024Biological barriers present a significant obstacle to treatment, especially when drugs are administered locally to increase their concentrations at the target site while...
Biological barriers present a significant obstacle to treatment, especially when drugs are administered locally to increase their concentrations at the target site while minimizing unintended off-target effects. Among these barriers, mucus presents a challenge, as it serves as a protective layer in the respiratory, urogenital, and gastrointestinal tracts. Its role is to shield the underlying epithelial cells from pathogens and toxic compounds but also impedes the efficient delivery of drugs. Despite the exploration of mucolytic agents to improve drug delivery, overcoming this protective barrier remains a significant hurdle. In our study, we investigate an alternative approach involving the use of catalase-powered nanobots. We use an model that simulates intestinal mucus secretion to demonstrate the dual functionality of our nanobots. This includes their ability to disrupt mucus, which we confirmed through and validation, as well as their self-propulsion to overcome the mucus barrier, resulting in a 60-fold increase compared with passive nanoparticles. Therefore, our findings highlight the potential utility of catalase-powered nanobots as carriers for therapeutic agents since they could enhance drug delivery efficiency by penetrating the mucus barrier.
Topics: Catalase; Mucus; Humans; Animals; Nanoparticles; Drug Delivery Systems; Mice
PubMed: 38885185
DOI: 10.1021/acsnano.4c01760 -
European Review For Medical and... Jun 2024Eur Rev Med Pharmacol Sci 2023; 27 (11): 5119-5127-DOI: 10.26355/eurrev_202306_32628-PMID: 37318485, published online on June 13, 2023. After publication, the authors...
Eur Rev Med Pharmacol Sci 2023; 27 (11): 5119-5127-DOI: 10.26355/eurrev_202306_32628-PMID: 37318485, published online on June 13, 2023. After publication, the authors have found some mistakes. This erratum corrects the following: In Figure 1, "4 withdrawal" has been corrected into "7 withdrawal" and "95 completed study" has been corrected into "97 corrected study" In the "Efficacy" paragraph at page 5123, "1.0 in the placebo group" has been corrected into "-1.0 in the placebo group". The legend of Table V has been corrected as follows: Table V. Published clinical studies of the mucolytic and expectorant efficacy of IV NAC in respiratory diseases. In Table V, the data regarding the Treatment groups (duration) by Grassi et al5 have been corrected as follows: NAC oral 200 mg TID NAC IM 300 mg BID NAC IV 500 mg OD (6 days) In Table V, the data regarding the Treatment groups (duration) by Henneghien et al8 have been corrected as follows: NAC oral 200 mg TID NAC IV 300 mg TID (3-10 days) NAC IV 500 mg BID (12 days) There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32628.
PubMed: 38884516
DOI: 10.26355/eurrev_202406_36388 -
Cureus May 2024Chronic obstructive pulmonary disease (COPD), a heterogeneous respiratory disease driven by various genetic and environmental factors, presents significant challenges in... (Review)
Review
Chronic obstructive pulmonary disease (COPD), a heterogeneous respiratory disease driven by various genetic and environmental factors, presents significant challenges in diagnosis and management. Traditional approaches focused on phenotypic classification, but recent paradigms emphasize identifying and addressing treatable traits to personalize treatment strategies. Treatable traits facilitate personalized interventions, optimizing symptom control, and reducing exacerbation risk. Dyspnea and exacerbations, recognized as key traits, guide treatment decisions and follow-up management. Various interventions, including bronchodilators, corticosteroids, and lifestyle modifications, target specific traits like airway inflammation, mucus overproduction, and emphysema. Strategies for assessing and addressing treatable traits during initial encounters and follow-up visits enhance disease monitoring and treatment efficacy. Comprehensive trait assessment demands resources and specialized monitoring, posing barriers to widespread implementation. The lack of standardized protocols and evolving evidence further complicates decision-making and clinical practice. Despite these challenges, the shift toward treatable traits-based management signifies a pivotal advancement in COPD care, emphasizing holistic approaches tailored to individual patient needs. Recognizing and addressing treatable traits offers personalized interventions, enhancing symptom control and disease management. Embracing treatable traits-based approaches holds promise for improving clinical outcomes and enhancing the quality of life for individuals living with COPD.
PubMed: 38882972
DOI: 10.7759/cureus.60423 -
ACS Omega Jun 2024Insulin, a pivotal anabolic hormone, regulates glucose homeostasis by facilitating the conversion of blood glucose to energy or storage. Dysfunction in insulin activity,... (Review)
Review
Insulin, a pivotal anabolic hormone, regulates glucose homeostasis by facilitating the conversion of blood glucose to energy or storage. Dysfunction in insulin activity, often associated with pancreatic β cells impairment, leads to hyperglycemia, a hallmark of diabetes. Type 1 diabetes (T1D) results from autoimmune destruction of β cells, while type 2 diabetes (T2D) stems from genetic, environmental, and lifestyle factors causing β cell dysfunction and insulin resistance. Currently, insulin therapy is used for most of the cases of T1D, while it is used only in a few persistent cases of T2D, often supplemented with dietary and lifestyle changes. The key challenge in oral insulin delivery lies in overcoming gastrointestinal (GI) barriers, including enzymatic degradation, low permeability, food interactions, low bioavailability, and long-term safety concerns. The muco-adhesive (MA) and muco-penetrative (MP) formulations aim to enhance oral insulin delivery by addressing these challenges. The mucus layer, a hydrogel matrix covering epithelial cells in the GI tract, poses significant barriers to oral insulin absorption. Its structure, composition, and turnover rate influence interactions with insulin and other drug carriers. Some of the few factors that influence mucoadhesion and mucopenetration are particle size, surface charge distribution, and surface modifications. This review discusses the challenges associated with oral insulin delivery, explores the properties of mucus, and evaluates the strategies for achieving excellent MA and MP formulations, focusing on nanotechnology-based approaches. The development of effective oral insulin formulations holds the potential to revolutionize diabetes management, providing patients with a more convenient and patient-friendly alternative to traditional insulin administration methods.
PubMed: 38882129
DOI: 10.1021/acsomega.3c10305 -
International Journal of Biological... Jun 2024This review shows the endeavors performed to prepare immobilized formulations of bromelain extract, usually from pineapple, and their use in diverse applications. This... (Review)
Review
This review shows the endeavors performed to prepare immobilized formulations of bromelain extract, usually from pineapple, and their use in diverse applications. This extract has a potent proteolytic component that is based on thiol proteases, which differ depending on the location on the fruit. Stem and fruit are the areas where higher activity is found. The edible origin of this enzyme is one of the features that determines the applications of the immobilized bromelain to a more significant degree. The enzyme has been immobilized on a wide diversity of supports via different strategies (covalent bonds, ion exchange), and also forming ex novo solids (nanoflowers, CLEAs, trapping in alginate beads, etc.). The use of preexisting nanoparticles as immobilization supports is relevant, as this facilitates one of the main applications of the immobilized enzyme, in therapeutic applications (as wound dressing and healing components, antibacterial or anticancer, mucus mobility control, etc.). A curiosity is the immobilization of this enzyme on spores of probiotic microorganisms via adsorption, in order to have a perfect in vivo compatibility. Other outstanding applications of the immobilized enzyme are in the stabilization of wine versus haze during storage, mainly when immobilized on chitosan. Curiously, the immobilized bromelain has been scarcely applied in the production of bioactive peptides.
PubMed: 38878936
DOI: 10.1016/j.ijbiomac.2024.133089 -
Journal of Hazardous Materials Aug 2024The expected increments in the production/use of bioplastics, as an alternative to petroleum-based plastics, require a deep understanding of their potential...
The expected increments in the production/use of bioplastics, as an alternative to petroleum-based plastics, require a deep understanding of their potential environmental and health hazards, mainly as nanoplastics (NPLs). Since one important exposure route to NPLs is through inhalation, this study aims to determine the fate and effects of true-to-life polylactic acid nanoplastics (PLA-NPLs), using the in vitro Calu-3 model of bronchial epithelium, under air-liquid interphase exposure conditions. To determine the harmful effects of PLA-NPLs in a more realistic scenario, both acute (24 h) and long-term (1 and 2 weeks) exposures were used. Flow cytometry results indicated that PLA-NPLs internalized easily in the barrier (∼10 % at 24 h and ∼40 % after 2 weeks), which affected the expression of tight-junctions formation (∼50 % less vs control) and the mucus secretion (∼50 % more vs control), both measured by immunostaining. Interestingly, significant genotoxic effects (DNA breaks) were detected by using the comet assay, with long-term effects being more marked than acute ones (7.01 vs 4.54 % of DNA damage). When an array of cellular proteins including cytokines, chemokines, and growth factors were used, a significant over-expression was mainly found in long-term exposures (∼20 proteins vs 5 proteins after acute exposure). Overall, these results described the potential hazards posed by PLA-NPLs, under relevant long-term exposure scenarios, highlighting the advantages of the model used to study bronchial epithelium tissue damage, and signaling endpoints related to inflammation.
Topics: Polyesters; Humans; Cell Line; Lung; Cytokines; Microplastics; DNA Damage; Nanoparticles; Epithelium; Respiratory Mucosa; Epithelial Cells; Tight Junctions
PubMed: 38878440
DOI: 10.1016/j.jhazmat.2024.134900 -
Life Science Alliance Sep 2024Innate lymphoid cells (ILCs) are critical for intestinal adaptation to microenvironmental challenges, and the gut mucosa is characterized by low oxygen. Adaptation to...
Innate lymphoid cells (ILCs) are critical for intestinal adaptation to microenvironmental challenges, and the gut mucosa is characterized by low oxygen. Adaptation to low oxygen is mediated by hypoxia-inducible transcription factors (HIFs), and the HIF-1α subunit shapes an ILC phenotype upon acute colitis that contributes to intestinal damage. However, the impact of HIF signaling in NKp46 ILCs in the context of repetitive mucosal damage and chronic inflammation, as it typically occurs during inflammatory bowel disease, is unknown. In chronic colitis, mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in NKp46 ILC1s but a concomitant rise in neutrophils and Ly6C macrophages. Single-nucleus RNA sequencing suggests enhanced interaction of mesenchymal cells with other cell compartments in the colon of HIF-1α KO mice and a loss of mucus-producing enterocytes and intestinal stem cells. This was, furthermore, associated with increased bone morphogenetic pathway-integrin signaling, expansion of fibroblast subsets, and intestinal fibrosis. In summary, this suggests that HIF-1α-mediated ILC1 activation, although detrimental upon acute colitis, protects against excessive inflammation and fibrosis during chronic intestinal damage.
Topics: Animals; Hypoxia-Inducible Factor 1, alpha Subunit; Natural Cytotoxicity Triggering Receptor 1; Mice; Colitis; Fibrosis; Mice, Knockout; Lymphocytes; Intestinal Mucosa; Inflammation; Mice, Inbred C57BL; Chronic Disease; Immunity, Innate; Signal Transduction; Disease Models, Animal; Male; Intestines; Antigens, Ly
PubMed: 38876796
DOI: 10.26508/lsa.202402593 -
Comparative Biochemistry and... Jun 2024The swimming activity, although an essential trait in the life cycle of fish, is still poorly understood in farmed fish. The current study aimed to investigate the...
The swimming activity, although an essential trait in the life cycle of fish, is still poorly understood in farmed fish. The current study aimed to investigate the impact of short-term induced swimming on the immune and antioxidant defence systems in European eel (Anguilla anguilla). Sixteen male yellow European eels (total length: 39.9 ± 0.7 cm; body weight: 108.8 ± 6.1 g) were individually placed in swimming flumes and divided into two groups: i) no swimming (n = 8); and ii) induced-swimming (n = 8) at 0.3 body lengths (BL)·s for 7 h. Swimming resulted in a 2-fold lower cortisol concentration in plasma, whereas plasma glucose, lactate, and several immune-related parameters did not present variations between groups. Interestingly, swimming led to higher lysozyme, peroxidase, and protease activities in skin mucus, whereas bactericidal activity did not show differences among groups. Additionally, the gene expression of interleukin 1 beta showed an up-regulation in the skin of fish with induced swimming, while no differences were observed in the head-kidney or gills. Furthermore, modulation of the antioxidant status was observed in the liver and posterior skeletal muscle after induced swimming. Fish subjected to swimming showed lower lipid peroxidation and higher reduced glutathione levels, increasing the reduced/oxidized glutathione ratio. However, no variations in the antioxidant status were observed between groups in the anterior skeletal muscle. This study showed modulation of immune and oxidative stress markers in European eels upon short-term induced swimming compared to non-swimming fish.
PubMed: 38876440
DOI: 10.1016/j.cbpa.2024.111680