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1.
Food Chem Toxicol ; : 114815, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876381

ABSTRACT

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

2.
Nanomedicine ; 60: 102756, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851439

ABSTRACT

The advancement of nanobiocomposites reinforced with 2D nano-materials plays a pivotal role in enhancing bone tissue engineering. In this study, we introduce a nanobiocomposite that reinforces bovine collagen with 2D nano-talc, a recently exfoliated nano-mineral. These nanobiocomposites were prepared by blending collagen with varying concentrations of 2D nano-talc, encompassing mono- and few-layers talc from soapstone nanomaterial. Extensive characterization techniques including AFM, XPS, nano-FTIR, s-SNOM nanoimaging, Force Spectroscopy, and PeakForce QNM® were employed. The incorporation of 2D nano-talc significantly enhanced the mechanical properties of the nanobiocomposites, resulting in increased stiffness compared to pristine collagen. In vitro studies supported the growth and proliferation of osteoblasts onto 2D nano-talc-reinforced nanobiocomposites, as well as showed the highest mineralization potential. These findings highlight the substantial potential of the developed nanobiocomposite as a scaffold material for bone tissue engineering applications.

3.
Nanoscale Horiz ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38808602

ABSTRACT

2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.

4.
Chemosphere ; 359: 142289, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723690

ABSTRACT

The speciation of arsenic in fish has been widely investigated, but bioaccumulation and biotransformation of inorganic As in different tissues of Nile tilapia (Oreochromis niloticus) are not fully understood. The present study aimed to investigate the bioaccumulation of As in Nile tilapia, as well as to evaluate the distribution of the main arsenic species (As(III), As(V), MMA, DMA, and AsB) in liver, stomach, gill, and muscle, after controlled exposures to As(III) and As(V) at concentrations of 5.0 and 10.0 mg L-1 during periods of 1 and 7 days. Total As was determined by inductively coupled plasma mass spectroscopy (ICP-MS). For both exposures (As(III) and As(V)), the total As levels after 7-day exposure were highest in the liver and lowest in the muscle. Overall, the Nile tilapia exposed to As(III) showed higher tissue levels of As after the treatments, compared to As(V) exposure. Speciation of arsenic present in the tissues employed liquid chromatography coupled to ICP-MS (LC-ICP-MS), revealing that the biotransformation of As included As(V) reduction to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to nontoxic arsenobetaine (AsB), which was the predominant arsenic form. Finally, the interactions and antagonistic effects of selenium in the bioaccumulation processes were tested by the combined exposure to As(III), the most toxic species of As, together with tetravalent selenium (Se(IV)). The results indicated a 4-6 times reduction of arsenic toxicity in the tilapia.


Subject(s)
Arsenic , Bioaccumulation , Biotransformation , Cichlids , Liver , Selenium , Water Pollutants, Chemical , Animals , Arsenic/metabolism , Cichlids/metabolism , Water Pollutants, Chemical/metabolism , Selenium/metabolism , Liver/metabolism , Liver/drug effects , Gills/metabolism , Muscles/metabolism
5.
J Appl Microbiol ; 135(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38710582

ABSTRACT

AIMS: This study aimed to evaluate the efficiency of two phages [VB_VaC_TDDLMA (phage TDD) and VB_VaC_SRILMA (phage SRI)] alone and in a cocktail to control Vibrio alginolyticus in brine shrimp before their administration in larviculture. METHODS AND RESULTS: Phages were isolated from seawater samples and characterized by host spectrum, growth parameters, adsorption rate, genomic analysis, and inactivation efficiency. Both phages belong to the Caudoviricetes class and lack known virulence or antibiotic-resistance genes. They exhibit specificity, infecting only their host, V. alginolyticus CECT 521. Preliminary experiments in a culture medium showed that phage TDD (reduction of 5.8 log CFU ml-1 after 10 h) outperformed phage SRI (reduction of 4.6 log CFU ml-1 after 6 h) and the cocktail TDD/SRI (reduction of 5.2 log CFU ml-1 after 8 h). In artificial marine water experiments with Artemia franciscana, both single phage suspensions and the phage cocktail, effectively inactivated V. alginolyticus in culture water (reduction of 4.3, 2.1, and 1.9 log CFU ml-1 for phages TDD, SRI, and the phage cocktail, respectively, after 12 h) and in A. franciscana (reduction of 51.6%, 87.3%, and 85.3% for phages TDD, SRI, and the phage cocktail, respectively, after 24 h). The two phages and the phage cocktail did not affect A. franciscana natural microbiota or other Vibrio species in the brine shrimp. CONCLUSIONS: The results suggest that phages can safely and effectively control V. alginolyticus in A. franciscana prior to its administration in larviculture.


Subject(s)
Aquaculture , Artemia , Bacteriophages , Vibrio alginolyticus , Vibrio alginolyticus/virology , Animals , Artemia/microbiology , Artemia/virology , Animal Feed , Seawater/microbiology , Larva/microbiology
6.
Rev Esp Enferm Dig ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767010

ABSTRACT

Flexible esophagogastroduodenoscopy is the gold standard for removing FB of the upper gastrointestinal tract. However large sharped FB are usually challenging to remove and are the subtype that most often requires surgery. We describe a case of a patient with a dental prothesis impacted in the proximal oesophagus. After a failed conventional approach, we made a successful attempt with two regular scopes with two independent operators.

7.
J Surg Oncol ; 129(7): 1325-1331, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38583145

ABSTRACT

BACKGROUND: The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel-based and lymphangiographic approaches could lead to reduced morbidity without sacrificing oncologic safety. OBJECTIVE: To evaluate the feasibility and diagnostic value of fluorescence-guided template sentinel region dissection (FTD) using a handheld near-infrared fluorescence (NIRF) camera in open radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS-00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back-up. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Descriptive analysis of positive and negative results per template region. RESULTS AND LIMITATIONS: FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55-125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF-positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF-negative template regions. Outside the standard template, two NIRF-positive benign nodes were identified. CONCLUSION: The concept of NIRF-guided FTD proved for this group all lymph node metastases to be found in NIRF-positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity.


Subject(s)
Cystectomy , Lymph Node Excision , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/diagnostic imaging , Lymph Node Excision/methods , Lymph Node Excision/instrumentation , Cystectomy/methods , Cystectomy/instrumentation , Female , Male , Aged , Middle Aged , Indocyanine Green , Feasibility Studies , Fluorescence , Prognosis , Follow-Up Studies , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/instrumentation , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymph Nodes/diagnostic imaging , Aged, 80 and over , Coloring Agents
8.
Environ Toxicol Pharmacol ; 108: 104453, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642625

ABSTRACT

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.


Subject(s)
Benzo(a)pyrene , Carcinogens, Environmental , Diclofenac , Humans , Diclofenac/toxicity , Benzo(a)pyrene/toxicity , Hep G2 Cells , Carcinogens, Environmental/toxicity , Reactive Oxygen Species/metabolism , Cyclooxygenase 1/metabolism , Cell Survival/drug effects , Cyclooxygenase Inhibitors/pharmacology , Cyclooxygenase Inhibitors/toxicity , Cyclooxygenase 2/metabolism , DNA Damage/drug effects , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/toxicity , Histones
9.
J Nucl Med ; 65(6): 931-937, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38637142

ABSTRACT

Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce 177Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received 177Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.


Subject(s)
Kidney , Neuroendocrine Tumors , Octreotide , Humans , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/metabolism , Male , Female , Middle Aged , Aged , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Octreotide/adverse effects , Kidney/radiation effects , Kidney/metabolism , Receptors, Peptide/metabolism , Adult , Radiation Protection , Safety , Organometallic Compounds/therapeutic use , Organometallic Compounds/adverse effects
10.
Sci Rep ; 14(1): 7705, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565954

ABSTRACT

Negative attitudes toward Lesbian, Gay, and Bisexual (LGB) individuals leads to a perceived inability of LGB individuals to foster 'appropriate' family relationships, inciting negative attitudes specifically toward same-sex parenting. Intergroup and interpersonal relationships play a critical role in fostering attitudes toward others wherein type of contact, frequency, degree of closeness in the relationship, and the positivity/negativity of interactions are potential mediator of these relations, Moreover, the mechanism behind co-constructing positive relationships with sexual and gender minorities is comfort with contact with LGB individuals. The present study explored the effects of interpersonal contact and the mediator role of comfort with LGB people in explaining attitudes toward same-sex parenting in Spanish-speaking countries in North, Central, and South America. These countries are of particular interest given the dearth of research in the region on attitudes toward same-sex parenting as well as the varying degrees of acceptance of and protections for same-sex parented families. A non-probabilistic sample of 1955 heterosexual cisgender participants from 14 countries was asked to complete a series of sociodemographic questions, a questionnaire about their interpersonal contact/comfort experiences with LGB people, and the Attitudes Toward Gay and Lesbian Parenting Scale. Results showed that comfort was vital in fostering accepting attitudes toward Same-Sex Parenting across countries. Findings also suggested that comfort with LGB people has a particularly powerful influence in regions with less legal and cultural acceptance of LGB individuals. Policies are not enough to instill widespread change: we must encourage, facilitate, and supervise the formation of relationships with LGB people.


Subject(s)
Parenting , Sexual and Gender Minorities , Humans , Attitude , Hispanic or Latino , United States , South American People , Central American People
11.
Sensors (Basel) ; 24(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38610305

ABSTRACT

The flexibility and versatility associated with autonomous mobile robots (AMR) have facilitated their integration into different types of industries and tasks. However, as the main objective of their implementation on the factory floor is to optimize processes and, consequently, the time associated with them, it is necessary to take into account the environment and congestion to which they are subjected. Localization, on the shop floor and in real time, is an important requirement to optimize the AMRs' trajectory management, thus avoiding livelocks and deadlocks during their movements in partnership with manual forklift operators and logistic trains. Threeof the most commonly used localization techniques in indoor environments (time of flight, angle of arrival, and time difference of arrival), as well as two of the most commonly used indoor localization methods in the industry (ultra-wideband, and ultrasound), are presented and compared in this paper. Furthermore, it identifies and compares three industrial indoor localization solutions: Qorvo, Eliko Kio, and Marvelmind, implemented in an industrial mobile platform, which is the main contribution of this paper. These solutions can be applied to both AMRs and other mobile platforms, such as forklifts and logistic trains. In terms of results, the Marvelmind system, which uses an ultrasound method, was the best solution.

12.
ACS Appl Electron Mater ; 6(4): 2152-2160, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38680726

ABSTRACT

Screen printing is one of the most used techniques for developing printed electronics. It stands out for its simplicity, scalability, and effectivity. Specifically, the manufacturing of hybrid integrated circuits has promoted the development of the technique, and the photovoltaic industry has enhanced the printing process by developing high-performance metallization pastes and high-end screens. In recent years, fine lines of 50 µm or smaller are about to be adopted in mass production, and screen printing has to compete with digital printing techniques such as inkjet printing, which can reach narrower lines. In this sense, this work is focused on testing the printing resolution of a high-performance stainless-steel screen with commercial conductive inks and functional lab-made inks based on reduced graphene oxide using an interdigitated structure. We achieved electrically conductive functional patterns with a minimum printing resolution of 40 µm for all inks.

13.
Micron ; 182: 103638, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38663276

ABSTRACT

Microtextures imprinted on the surface of quartz grains provide in-depth information on the environmental conditions and sedimentary processes that affected the study sediments. Microtextural analyses are therefore widely used in the provenance studies of sediments. In order to minimize the subjectivity of microtextural recognition, we propose a new software, called DeepGrain (source codes are available at https://github.com/deepgrains/deepgrain), for the automatic identification of microtextures on the surface of quartz grains using the DeepLabV3 model with applied improving techniques. The approach provides an accuracy of 99 % of the area of the tested grains and 63 % of the mechanical features on the surfaces of the tested grains. The inference of a single SEM image of quartz grain took an average of 3.10 sec, leading to a significant reduction in the analysis time of a single grain.

14.
Biomacromolecules ; 25(5): 2863-2874, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38564884

ABSTRACT

With the rapid increase of the number of patients with gastrointestinal diseases in modern society, the need for the development of physiologically relevant in vitro intestinal models is key to improve the understanding of intestinal dysfunctions. This involves the development of a scaffold material exhibiting physiological stiffness and anatomical mimicry of the intestinal architecture. The current work focuses on evaluating the scaffold micromorphology of gelatin-methacryloyl-aminoethyl-methacrylate-based nonporous and porous intestinal 3D, intestine-like constructs, fabricated via digital light processing, on the cellular response. To this end, Caco-2 intestinal cells were utilized in combination with the constructs. Both porous and nonporous constructs promoted cell growth and differentiation toward enterocyte-like cells (VIL1, ALPI, SI, and OCLD expression showed via qPCR, ZO-1 via immunostaining). The porous constructs outperformed the nonporous ones regarding cell seeding efficiency and growth rate, confirmed by MTS assay, live/dead staining, and TEER measurements, due to the presence of surface roughness.


Subject(s)
Hydrogels , Tissue Scaffolds , Humans , Porosity , Hydrogels/chemistry , Caco-2 Cells , Tissue Scaffolds/chemistry , Cell Proliferation , Gelatin/chemistry , Intestines/cytology , Methacrylates/chemistry , Tissue Engineering/methods , Cell Differentiation
15.
Animals (Basel) ; 14(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38540078

ABSTRACT

The current study investigates the venom-delivery system of green and red morphotypes of the sea anemone Actinia equina to disclose its potential as a source of bioactive compounds. We compared the two morphotypes using electron and optical microscopy, proteomics, and toxicity assessment on zebrafish embryos. Specialized venom-injecting cells (nematocysts) are equally distributed and found in the tentacles of both varieties. Proteomics revealed proteins of interest in both red and green Actinia, yielding the three most abundant Gene Ontology (GO) terms related to the biological processes "proteolysis", "hemolysis in another organism" and "lipid catabolic process". Neurotoxins and cytolytic toxins similar to known cnidarian toxins like PsTX-60A and AvTX-60A, for instance, were identified in both types. Extracts from green and red anemones were toxic to zebrafish embryos, with green anemone venom appearing to be more potent. The findings highlight the presence of proteinaceous toxins in A. equina and the potential for different varieties to possess distinct bioactive compounds. Notably, pore-forming toxins are suggested for molecular probes and immunotoxins, making them valuable assets for potential biotechnological and biomedical purposes.

16.
Polymers (Basel) ; 16(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38543461

ABSTRACT

Next-generation high-performance polymers require consideration as sustainable solutions. Here, to satisfy these criteria, we propose to combine high-performance styrenic block copolymers, a class of thermoplastic elastomer, with cellulose derivatives as a reinforcing agent with the aim of maintaining and/or improving structural and surface properties. A great advantage of the proposed blends is, besides their biocompatibility, a decrease in environmental impact due to blending with a natural polymer. Particularly, we focus on identifying the effect of different blending compounds and blend ratios on the morphological, structural, thermal, mechanical, electrical and cytotoxic characteristics of materials. This research provides, together with novel material formulations, practical guidelines for the design and fabrication of next-generation sustainable high-performance polymers.

17.
Int J Nanomedicine ; 19: 2655-2673, 2024.
Article in English | MEDLINE | ID: mdl-38500680

ABSTRACT

Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice. Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.


Subject(s)
Colonic Neoplasms , Liposomes , Nanoparticles , Tumor Microenvironment , Animals , Mice , Ligands , Apoptosis , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Tumor Necrosis Factor-alpha , TNF-Related Apoptosis-Inducing Ligand/metabolism
18.
Animals (Basel) ; 14(4)2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38396603

ABSTRACT

Proteinaceous toxins are peptides or proteins that hold great biotechnological value, evidenced by their ecological role, whether as defense or predation mechanisms. Bioprospecting using bioinformatics and omics may render screening for novel bioactives more expeditious, especially considering the immense diversity of toxin-secreting marine organisms. Eulalia sp. (Annelida: Phyllodocidae), a toxin bearing marine annelid, was recently shown to secrete cysteine-rich protein (Crisp) toxins (hitherto referred to as 'phyllotoxins') that can immobilize its prey. By analyzing and validating transcriptomic data, we narrowed the list of isolated full coding sequences of transcripts of the most abundant toxins or accompanying bioactives secreted by the species (the phyllotoxin Crisp, hyaluronidase, serine protease, and peptidases M12A, M13, and M12B). Through homology matching with human proteins, the biotechnological potential of the marine annelid's toxins and related proteins was tentatively associated with coagulative and anti-inflammatory responses for the peptidases PepM12A, SePr, PepM12B, and PepM13, and with the neurotoxic activity of Crisp, and finally, hyaluronidase was inferred to bear properties of an permeabilizing agent. The in silico analysis succeeded by validation by PCR and Sanger sequencing enabled us to retrieve cDNAs can may be used for the heterologous expression of these toxins.

19.
Antibiotics (Basel) ; 13(2)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38391581

ABSTRACT

Urinary tract infections (UTIs) caused by resistant Klebsiella pneumoniae can lead to severe clinical complications and even death. An alternative treatment option for infected patients is using bacteriophages. In the present study, we isolated phage VB_KPM_KP1LMA (KP1LMA) from sewage water using a K. pneumoniae strain as a host. Whole-genome analysis indicated that the genome was a double-stranded linear 176,096-bp long DNA molecule with 41.8% GC content and did not contain virulence or antibiotic resistance genes. The inactivation potential of phage KP1LMA was assessed in broth at an MOI of 1 and 10, and a maximum inactivation of 4.9 and 5.4 log CFU/mL, respectively, was observed after 9 h. The efficacy at an MOI of 10 was also assessed in urine to evaluate the phage's performance in an acidic environment. A maximum inactivation of 3.8 log CFU/mL was observed after 9 h. The results suggest that phage KP1LMA could potentially control a UTI caused by this strain of K. pneumoniae, indicating that the same procedure can be used to control UTIs caused by other strains if new specific phages are isolated. Although phage KP1LMA has a narrow host range, in the future, efforts can be made to expand its spectrum of activity and also to combine this phage with others, potentially enabling its use against other K. pneumoniae strains involved in UTIs.

20.
J Bras Pneumol ; 50(1): e20230116, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-38422336

ABSTRACT

OBJECTIVE: To analyze the clinical characteristics and outcomes of patients with COVID-19-related acute respiratory failure on the basis of their vaccination status at the time of ICU admission. METHODS: We conducted a retrospective observational study using a prospective database of patients admitted to the ICU of a university hospital in the city of Murcia, in Spain, between January 1, 2021 and September 1, 2022. Clinical, analytical, and sociodemographic data were collected and analyzed on the basis of patient vaccination status. We adjusted for confounding variables using propensity score matching and calculated adjusted ORs and 95% CIs. RESULTS: A total of 276 patients were included in the study. Of those, 8.3% were fully vaccinated, 12% were partially vaccinated, and 79.7% were unvaccinated. Although fully vaccinated patients had more comorbidities, partially vaccinated patients had higher disease severity. The proportion of patients with severe acute respiratory failure was higher in the unvaccinated group, followed by the partially vaccinated group. No significant differences were found among the different groups regarding complications, duration of ventilatory support, or length of ICU/hospital stay. In the sample selected by propensity score matching, the number of patients with severe complications and the in-hospital mortality rate were higher in unvaccinated patients, but the differences were not significant. CONCLUSIONS: This study failed to show a significant improvement in outcomes in critically ill COVID-19 patients vaccinated against SARS-CoV-2. However, the CIs were wide and the mortality point estimates favored patients who received at least one dose of COVID-19 vaccine.


Subject(s)
COVID-19 , Respiratory Insufficiency , Humans , COVID-19 Vaccines , Hospital Mortality , Respiratory Insufficiency/therapy , SARS-CoV-2 , Retrospective Studies
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