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1.
Sensors (Basel) ; 24(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39001033

ABSTRACT

Presently, the prevailing approaches to assessing hinge joint damage predominantly rely on predefined damage indicators or updating finite element models (FEMs). However, these methods possess certain limitations. The damage indicator method requires high-quality monitoring data and demonstrates variable sensitivities of distinct indicators to damage. On the other hand, the FEM approach mandates a convoluted FEM update procedure. Hinge joint damage represents a major kind of defect in prefabricated assembled multi-girder bridges (AMGBs). Therefore, effective damage detection methods are imperative to identify the damage state of hinge joints. To this end, a stiffness-based method for the performance evaluation of hinge joints of AMGBs is proposed in this paper. The proposed method estimates hinge joint stiffness by solving the characteristic equations of the multi-beam system. In addition, this study introduces a method for determining baseline joint stiffness using design data and FEM. Subsequently, a comprehensive evaluation framework for hinge joints is formulated, coupling a finite element model with the baseline stiffness, thereby introducing a damage indicator rooted in stiffness ratios. To verify the effectiveness of the proposed method, strain and displacement correlations are analyzed using actual bridge monitoring data, and articulation joint stiffness is identified. The results underscore the capability of the proposed method to accurately pinpoint the location and extent of hinge joint damage.

2.
ACS Omega ; 9(21): 23069-23085, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38826548

ABSTRACT

The design of particle size and morphology are a promising approach to investigating the properties exhibited by different types of materials. In the present study, the silver phosphate microcrystals (Ag3PO4) were first time synthesized using the hydrothermal and solvothermal method by combination of the solvents water/isopropyl alcohol (SP-IA), water/acetone (SP-AC), water/ammonium hydroxide (AP-AH), all in a ratio of 1:1 (v/v). The synthesized materials were structurally characterized by X-ray diffraction (XRD), Rietveld refinement, and Raman vibrational spectroscopy, where it was confirmed that the pure phase was achieved for all prepared samples. The study of the optical properties by UV-vis diffuse reflectance spectroscopy (UV-vis/DRS) and colorimetry revealed that the obtained materials have an optical bandgap between 2.30 and 2.32 eV. The FE-SEM images collected revealed different morphologies for the synthesized materials, with a predominance of tetraploid-shaped microcrystals for the SP-AC sample, rods for the SP-IA sample, cubes and polyhedral for the SP-WT sample and condensed polyhedral for the SP-AH sample. The photocatalytic performance against the Rhodamine B dye (RhB) was 100%, 98.2%, 94.2%, and 87.8%, using the samples SP-AC, SP-IA, SP-WT, and SP-AH as photocatalyst at time of 12 min. On the other hand, the antimicrobial performance of SP-AC sample showed superior performance, resulting in the minimum inhibitory concentration-MIC of 7.81 µg mL-1 for the strain of E. coli, 7.81 µg mL-1 for the strain of E. aureus, 15.62 µg mL-1 for the strain of P. auruginosa, and 15.62 µg mL-1 for the strains of C. albicans. In this way, was synthesized a promissory antimicrobial and photocatalyst material, through an easy and cost-effective method.

3.
Stem Cell Res Ther ; 15(1): 168, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886849

ABSTRACT

BACKGROUND: Mechanical stimulation (MS) significantly increases the release of adenine and uracil nucleotides from bone marrow-derived mesenchymal stem cells (BM-MSCs) undergoing osteogenic differentiation. Released nucleotides acting via ionotropic P2X7 and metabotropic P2Y6 purinoceptors sensitive to ATP and UDP, respectively, control the osteogenic commitment of BM-MSCs and, thus, bone growth and remodelling. Yet, this mechanism is impaired in post-menopausal (Pm)-derived BM-MSCs, mostly because NTPDase3 overexpression decreases the extracellular accumulation of nucleotides below the levels required to activate plasma membrane-bound P2 purinoceptors. This prompted us to investigate whether in vitro MS of BM-MSCs from Pm women could rehabilitate their osteogenic commitment and whether xenotransplantation of MS purinome-primed Pm cells promote repair of critical bone defects in an in vivo animal model. METHODS: BM-MSCs were harvested from the neck of femora of Pm women (70 ± 3 years old) undergoing total hip replacement. The cells grew, for 35 days, in an osteogenic-inducing medium either submitted (SS) or not (CTR) to MS (90 r.p.m. for 30 min) twice a week. Increases in alkaline phosphatase activity and in the amount of osteogenic transcription factors, osterix and osteopontin, denoted osteogenic cells differentiation, while bone nodules formation was ascertain by the alizarin red-staining assay. The luciferin-luciferase bioluminescence assay was used to quantify extracellular ATP. The kinetics of the extracellular ATP (100 µM) and UDP (100 µM) catabolism was assessed by HPLC. The density of P2Y6 and P2X7 purinoceptors in the cells was assessed by immunofluorescence confocal microscopy. MS-stimulated BM-MSCs from Pm women were xenotransplanted into critical bone defects drilled in the great trochanter of femora of one-year female Wistar rats; bone repair was assessed by histological analysis 10 days after xenotransplantation. RESULTS: MS-stimulated Pm BM-MSCs in culture (i) release 1.6-fold higher ATP amounts, (ii) overexpress P2X7 and P2Y6 purinoceptors, (iii) exhibit higher alkaline phosphatase activity and overexpress the osteogenic transcription factors, osterix and osteopontin, and (iv) form larger bone nodules, than CTR cells. Selective blockage of P2X7 and P2Y6 purinoceptors with A438079 (3 µM) and MRS 2578 (0.1 µM), respectively, prevented the osteogenic commitment of cultured Pm BM-MSCs. Xenotransplanted MS purinome-primed Pm BM-MSCs accelerated the repair of critical bone defects in the in vivo rat model. CONCLUSIONS: Data suggest that in vitro MS restores the purinergic cell-to-cell communication fostering the osteogenic differentiation and osteointegration of BM-MSCs from Pm women, a strategy that may be used in bone regeneration and repair tactics.


Subject(s)
Cell Differentiation , Mesenchymal Stem Cells , Osteogenesis , Postmenopause , Female , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Humans , Osteogenesis/drug effects , Animals , Aged , Rats , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Mesenchymal Stem Cell Transplantation/methods , Sp7 Transcription Factor/metabolism , Sp7 Transcription Factor/genetics , Cells, Cultured , Transcription Factors/metabolism , Transcription Factors/genetics , Rats, Wistar
4.
Phys Chem Chem Phys ; 26(17): 13164-13171, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38630007

ABSTRACT

The metathesis reaction has been an important tool in both organic and inorganic synthetic chemistry. More specifically in polymer chemistry, ring opening metathesis polymerization (ROMP), via the formation of an active metal-carbene species (MCHR), has been widely used. The elucidation of the mechanism for ROMP opened the way for the development of well-defined catalysts, suited to local conditions. In the present study, we employed density functional theory (DFT) to investigate three reaction pathways for the formation of a species capable of activating ROMP. The active species is formed from the [RuCl2(PPh3)2(pip)] complex in the presence of norbornadiene (NBD) and the carbene source ethyl diazoacetate (EDA). Formation of a hexacoordinated intermediate [RuCl2(PPh3)2(pip)(NBD)] is favored in the first step, with NBD doubly coordinated to the [RuCl2(PPh3)2(pip)] moiety. Analysis of donation (X → Ru) and back-donation (Ru → X) processes in the [RuCl2(PPh3)2(pip)(NBD)] complex shows that piperidine behaves as a σ donor, while NBD behaves as a π donor and the PPh3 groups act as π acceptors. The intensity of the orbital component is predominant in relation to the steric component in the complex. Thus, we propose that the reaction occurs through the formation of a hexacoordinated complex, followed by the dissociation of a PPh3 group, thus forming a complex where NBD is doubly coordinated to the metal center. Coordination of EDA leads finally to the catalyst capable of forming the metallocyclobutane intermediate required for the ROMP reaction.

5.
J Am Vet Med Assoc ; 262(7): 966-972, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38503057

ABSTRACT

OBJECTIVE: The purpose of the study reported herein was to determine the dose of oleander extract and oleandrin (the key pharmacologically active constituent) that could be safely administered PO to dogs. ANIMALS: 42 purebred Beagle dogs were used to study an extract of Nerium oleander. METHODS: 3 studies were performed in 42 purebred young adult (ages 12 months or older) Beagle dogs using a supercritical fluid extract of N oleander leaves. The first study was an 8-day initial dose-ranging study in 2 dogs, a second 7-day repeat-dosing study was performed in 4 dogs, and the final study was performed in 32 dogs where test subjects were given extract or placebo once daily for 28 consecutive days via oral (gavage) administration followed by a 14-day recovery period. RESULTS: At 2.3 µg/kg of oleandrin, there were no observable adverse effects during the duration of the study. Adverse effects were not seen until doses exceeded 6.9 µg/kg of oleandrin, at which time mild, reversible clinical signs were noted. However, a dose > 460 µg of oleandrin/kg was fatal in 1 of 2 dogs in this study. CLINICAL RELEVANCE: The studies reported here, taken in totality, suggest that doses exceeding 6.9 µg/kg of oleandrin may be associated with cardiac abnormalities. An estimated no treatment effective adverse event oral dose of oleandrin appears to be 4.6 µg of oleandrin/kg. Higher doses may be tolerable but should be used with appropriate monitoring.


Subject(s)
Cardenolides , Dose-Response Relationship, Drug , Nerium , Plant Extracts , Animals , Dogs , Cardenolides/administration & dosage , Male , Administration, Oral , Female , Plant Extracts/administration & dosage
6.
J Vet Intern Med ; 38(2): 922-930, 2024.
Article in English | MEDLINE | ID: mdl-38362960

ABSTRACT

BACKGROUND: Artificial intelligence (AI) could improve accuracy and reproducibility of echocardiographic measurements in dogs. HYPOTHESIS: A neural network can be trained to measure echocardiographic left ventricular (LV) linear dimensions in dogs. ANIMALS: Training dataset: 1398 frames from 461 canine echocardiograms from a single specialist center. VALIDATION: 50 additional echocardiograms from the same center. METHODS: Training dataset: a right parasternal 4-chamber long axis frame from each study, labeled by 1 of 18 echocardiographers, marking anterior and posterior points of the septum and free wall. VALIDATION DATASET: End-diastolic and end-systolic frames from 50 studies, annotated twice (blindly) by 13 experts, producing 26 measurements of each site from each frame. The neural network also made these measurements. We quantified its accuracy as the deviation from the expert consensus, using the individual-expert deviation from consensus as context for acceptable variation. The deviation of the AI measurement away from the expert consensus was assessed on each individual frame and compared with the root-mean-square-variation of the individual expert opinions away from that consensus. RESULTS: For the septum in end-diastole, individual expert opinions deviated by 0.12 cm from the consensus, while the AI deviated by 0.11 cm (P = .61). For LVD, the corresponding values were 0.20 cm for experts and 0.13 cm for AI (P = .65); for the free wall, experts 0.20 cm, AI 0.13 cm (P < .01). In end-systole, there were no differences between individual expert and AI performances. CONCLUSIONS AND CLINICAL IMPORTANCE: An artificial intelligence network can be trained to adequately measure linear LV dimensions, with performance indistinguishable from that of experts.


Subject(s)
Artificial Intelligence , Echocardiography , Dogs , Animals , Reproducibility of Results , Echocardiography/veterinary , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Diastole
7.
Appl Microbiol Biotechnol ; 108(1): 210, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38355912

ABSTRACT

The influence of pulp carryover on the efficiency of the xylanase (X) treatment of industrial unbleached and oxygen-delignified eucalypt kraft pulps (A1 and A2 pulps, with kappa number (KN) values of 16 and 10, respectively), collected at the same pulp mill, was studied regarding the consumption of bleaching chemicals and pulp bleachability. Another non-oxygen-delignified eucalyptus kraft pulp of KN 13 was received after the extended cooking from a different pulp mill (pulp B). The assays were performed with both lab-washed (carryover-free) and unwashed (carryover-rich) pulps. Both lab-washed and unwashed pulps with carryover were subjected to X treatment, the former being demonstrating considerably higher ClO2 savings than the pulps containing carryover. The savings of bleaching reagents were higher when the X stage was applied to the A1 pulp than to the A2 pulp. This advantage of A1 pulp, however, was not confirmed when using unwashed pulps. In contrast, the gains obtained from the X treatment of unwashed pulp A2 were practically as high as those observed for the lab-washed A2 pulp. Furthermore, a similar effect in X stage was recorded for unwashed pulps having close KN: oxygen-delignified A2 pulp and non-oxygen-delignified B pulp. The results suggest that pulp carryover and initial pH were the key factors relating to the effectiveness of X treatment. The application of X treatment to the A2 unwashed pulp (after the oxygen stage) not only saved 20% of the ClO2 and 10% of the sodium hydroxide, but also improved the brightness stability of the bleached pulp without affecting its papermaking properties. KEY POINTS: • Xylanase treatment boosts kraft pulp bleaching • Pulp carryover hinders the xylanase treatment • Nearly 20% of ClO2 and 10% NaOH savings can be reached using xylanase.


Subject(s)
Oxygen , Paper , Oxygen/chemistry
8.
MMWR Morb Mortal Wkly Rep ; 73(3): 62-65, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38271279

ABSTRACT

Although infections resulting from cosmetic surgery performed outside the United States have been regularly reported, deaths have rarely been identified. During 2009-2022, 93 U.S. citizens died after receiving cosmetic surgery in the Dominican Republic. The number of deaths increased from a mean of 4.1 per year during 2009-2018 to a mean of 13.0 during 2019-2022 with a peak in of 17 in 2020. A subset of post-cosmetic surgery deaths occurring during peak years was investigated, and most deaths were found to be the result of embolic events (fat emboli or venous thromboembolism) for which a high proportion of the patients who died had risk factors, including obesity and having multiple procedures performed during the same operation. These risk factors might have been mitigated or prevented with improved surgical protocols and postoperative medical care, including prophylactic measures against venous thromboembolism. U.S. citizens interested in receiving elective cosmetic surgery outside the United States should consult with their health care professionals regarding their risk for adverse outcomes. Public health authorities can support provider education on the importance of preoperative patient evaluation and the potential danger of performing multiple cosmetic procedures in one operation.


Subject(s)
Surgery, Plastic , Venous Thromboembolism , United States/epidemiology , Humans , Dominican Republic/epidemiology , Risk Factors
9.
J Vet Intern Med ; 38(1): 61-70, 2024.
Article in English | MEDLINE | ID: mdl-38038190

ABSTRACT

BACKGROUND: Impairment of left ventricular (LV) longitudinal function is an early marker of systolic dysfunction in hypertrophic cardiomyopathy (HCM). Aortic annular plane systolic excursion (AAPSE) is a measure of LV longitudinal function in people that has not been evaluated in cats. HYPOTHESIS: Aortic annular plane systolic excursion is lower in cats with HCM compared to control cats, and cats in stage C have the lowest AAPSE. ANIMALS: One hundred seventy-five cats: 60 normal, 61 HCM stage B and 54 HCM stage C cats. MATERIALS: Multicenter retrospective case-control study. Electronic medical records from 4 referral hospitals were reviewed for cats diagnosed with HCM and normal cats. HCM was defined as LV wall thickness ≥6 mm and normal cats ≤5 mm. M-mode bisecting the aorta in right parasternal short-axis view was used to measure AAPSE. RESULTS: Aortic annular plane systolic excursion was lower in HCM cats compared to normal cats (3.9 ± 0.9 mm versus 4.6 ± 0.9 mm, P < .001) and was lowest in HCM stage C (2.4 ± 0.6 mm, P < .001). An AAPSE <2.9 mm gave a sensitivity of 83% (95% CI 71%-91%) and specificity of 92% (95% CI 82%-97%) to differentiate HCM stage C from stage B. AAPSE correlated with mitral annular plane systolic excursion (r = .6 [.4-.7], P < .001), and atrial fractional shortening (r = .6 [.5-.7], P < .001), but showed no correlation with LV fractional shortening. CONCLUSIONS AND CLINICAL IMPORTANCE: Aortic annular plane systolic excursion is an easily acquired echocardiographic variable and might be a new measurement of LV systolic performance in cats with HCM.


Subject(s)
Cardiomyopathy, Hypertrophic , Cat Diseases , Humans , Cats , Animals , Retrospective Studies , Case-Control Studies , Echocardiography/veterinary , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/veterinary , Aorta , Cat Diseases/diagnostic imaging
10.
Surg Endosc ; 38(3): 1329-1341, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38110794

ABSTRACT

BACKGROUND: Trans-abdominal pre-peritoneal (TAPP) hernia repair is a complex procedure that presents several challenges. Even though, due to the high prevalence of inguinal hernia, TAPP technique is increasing in frequency and robotic Abdominal Wall Surgery (rAWS) is emerging as a valuable tool in this regard. Although inguinal TAPP procedure principles have been published and simulation is needed, the availability of validated models remains scarce. METHODS: A new low-cost model was developed to simulate inguinal rTAPP repair. For validity assessment, a new TAPP-specific fidelity questionnaire and assessment scale were developed to compare the performance of novices and experts in the simulated procedure. The models used were assessed at 60 min for execution and quality score. RESULTS: Twenty-five residents and specialists from all over the country participated in this study. Execution, quality, and global performance was higher in the seniors group compared to juniors (8.91 vs 6.36, p = 0.02; 8.09 vs 5.14, p < .001; and 17 vs. 11,5, p < .001, respectively). Overall fidelity was assessed as being very high [4.41 (3.5-5.0), α = .918] as well as face [4.31 (3.0-5.0), α = .867] and content validity [4.44 (3.2-5.0), α = .803]. Participants strongly agreed that the model is adequate to be used with the DaVinci® Robot [4.52 (3.5-5.0), α = .758]. CONCLUSION: This study shows face, content, and construct validity of the model for inguinal TAPP simulation, including for robotic surgery. Therefore, the model can be a valuable tool for learning, understanding, practicing, and mastering the TAPP technique prior to participating in the operating room.


Subject(s)
Hernia, Inguinal , Laparoscopy , Robotic Surgical Procedures , Robotics , Humans , Laparoscopy/methods , Robotic Surgical Procedures/methods , Hernia, Inguinal/surgery , Peritoneum/surgery , Herniorrhaphy/methods , Surgical Mesh , Treatment Outcome
11.
Anim Reprod ; 20(4): e20230071, 2023.
Article in English | MEDLINE | ID: mdl-38148927

ABSTRACT

The Brazilian Buriti oil presents low extraction costs and relevant antioxidant properties. Thus, this work aimed to analyze Buriti oil biomaterial (BB), within its physicochemical properties, biocompatibility and cellular integration, with the purpose to the use as a growth matrix for Goat Wharton's jelly mesenchymal stem cells. Biomaterials were produced from Buriti oil polymer (Mauritia flexuosa), for it's characterization were performed Infrared Region Spectroscopy (FTIR) and Thermogravimetric Analysis (TG and DTG). The biointegration was analyzed by Scanning Electron Microscopy (SEM) and histological techniques. In order to investigate biocompatibility, MTT (3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio) test and hemolytic activity tests were performed. The activation capacity of immune system cellswas measured by phagocytic capacity assay and nitric oxide synthesis . The BB presented an amorphous composition, with high thermal stability and high water expansion capacity, a surface with micro and macropores, and good adhesion of Wharton's jelly mesenchymal stem cells (MSCWJ). We verified the absence of cytotoxicity and hemolytic activity, in addition, BB did not stimulate the activation of macrophages. Proving to be a safe material for direct cultivation and also for manufacturing of compounds used for in vivo applications.

12.
iScience ; 26(7): 107196, 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37485357

ABSTRACT

The Maghreb is a key region for understanding the dynamics of cattle dispersal and admixture with local aurochs following their earliest domestication in the Fertile Crescent more than 10,000 years ago. Here, we present data on autosomal genomes and mitogenomes obtained for four archaeological specimens of Iron Age (∼2,800 cal BP-2,000 cal BP) domestic cattle from the Eastern Maghreb, i.e. Althiburos (El Kef, Tunisia). D-loop sequences were obtained for an additional eight cattle specimens from this site. Maternal lineages were assigned to the elusive R and ubiquitous African-T1 haplogroups found in two and ten Althiburos specimens, respectively. Our results can be explained by post-domestication hybridization of Althiburos cattle with local aurochs. However, we cannot rule out an independent domestication in North Africa considering the shared ancestry of Althiburos cattle with the pre-domestic Moroccan aurochs and present-day African taurine cattle.

13.
Vet Clin North Am Small Anim Pract ; 53(6): 1277-1292, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37500329

ABSTRACT

Echocardiography is the gold standard imaging modality to diagnose hypertrophic cardiomyopathy (HCM) in cats. Echocardiographic features can predict both cats at an increased risk of developing HCM and cats with HCM at an increased risk of developing cardiovascular events or experiencing cardiac death. Left atrial dysfunction seems to be an important feature of HCM, as it is an early phenotypic abnormality and is also associated with worse outcome.

14.
Biochem Pharmacol ; 214: 115646, 2023 08.
Article in English | MEDLINE | ID: mdl-37321413

ABSTRACT

The osteochondral unit comprises the articular cartilage (90%), subchondral bone (5%) and calcified cartilage (5%). All cells present at the osteochondral unit that is ultimately responsible for matrix production and osteochondral homeostasis, such as chondrocytes, osteoblasts, osteoclasts and osteocytes, can release adenine and/or uracil nucleotides to the local microenvironment. Nucleotides are released by these cells either constitutively or upon plasma membrane damage, mechanical stress or hypoxia conditions. Once in the extracellular space, endogenously released nucleotides can activate membrane-bound purinoceptors. Activation of these receptors is fine-tuning regulated by nucleotides' breakdown by enzymes of the ecto-nucleotidase cascade. Depending on the pathophysiological conditions, both the avascular cartilage and the subchondral bone subsist to significant changes in oxygen tension, which has a tremendous impact on tissue homeostasis. Cell stress due to hypoxic conditions directly influences the expression and activity of several purinergic signalling players, namely nucleotide release channels (e.g. Cx43), NTPDase enzymes and purinoceptors. This review gathers experimental evidence concerning the interplay between hypoxia and the purinergic signalling cascade contributing to osteochondral unit homeostasis. Reporting deviations to this relationship resulting from pathological alterations of articular joints may ultimately unravel novel therapeutic targets for osteochondral rehabilitation. At this point, one can only hypothesize how hypoxia mimetic conditions can be beneficial to the ex vivo expansion and differentiation of osteo- and chondro-progenitors for auto-transplantation and tissue regenerative purposes.


Subject(s)
Cartilage, Articular , Nucleotides , Nucleotides/metabolism , Chondrocytes/metabolism , Receptors, Purinergic/metabolism , Cartilage, Articular/metabolism , Cell Membrane/metabolism
15.
Molecules ; 28(12)2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37375354

ABSTRACT

The Nerium oleander extract PBI 05204 (PBI) and its cardiac glycoside constituent oleandrin have direct anti-viral properties. Their effect on the immune system, however, is largely unknown. We used an in vitro model of human peripheral blood mononuclear cells to document effects under three different culture conditions: normal, challenged with the viral mimetic polyinosinic:polycytidylic acid Poly I:C, and inflamed by lipopolysaccharide (LPS). Cells were evaluated for immune activation marks CD69, CD25, and CD107a, and culture supernatants were tested for cytokines. Both PBI and oleandrin directly activated Natural Killer (NK) cells and monocytes and triggered increased production of cytokines. Under viral mimetic challenge, PBI and oleandrin enhanced the Poly I:C-mediated immune activation of monocytes and NK cells and enhanced production of IFN-γ. Under inflammatory conditions, many cytokines were controlled at similar levels as in cultures treated with PBI and oleandrin without inflammation. PBI triggered higher levels of some cytokines than oleandrin. Both products increased T cell cytotoxic attack on malignant target cells, strongest by PBI. The results show that PBI and oleandrin directly activate innate immune cells, enhance anti-viral immune responses through NK cell activation and IFN-γ levels, and modulate immune responses under inflamed conditions. The potential clinical impact of these activities is discussed.


Subject(s)
Cytokines , Leukocytes, Mononuclear , Humans , Immunity , Poly I
16.
Stem Cell Res Ther ; 14(1): 97, 2023 04 19.
Article in English | MEDLINE | ID: mdl-37076930

ABSTRACT

BACKGROUND: Endogenously released adenine and uracil nucleotides favour the osteogenic commitment of bone marrow-derived mesenchymal stromal cells (BM-MSCs) through the activation of ATP-sensitive P2X7 and UDP-sensitive P2Y6 receptors. Yet, these nucleotides have their osteogenic potential compromised in post-menopausal (Pm) women due to overexpression of nucleotide metabolizing enzymes, namely NTPDase3. This prompted us to investigate whether NTPDase3 gene silencing or inhibition of its enzymatic activity could rehabilitate the osteogenic potential of Pm BM-MSCs. METHODS: MSCs were harvested from the bone marrow of Pm women (69 ± 2 years old) and younger female controls (22 ± 4 years old). The cells were allowed to grow for 35 days in an osteogenic-inducing medium in either the absence or the presence of NTPDase3 inhibitors (PSB 06126 and hN3-B3s antibody); pre-treatment with a lentiviral short hairpin RNA (Lenti-shRNA) was used to silence the NTPDase3 gene expression. Immunofluorescence confocal microscopy was used to monitor protein cell densities. The osteogenic commitment of BM-MSCs was assessed by increases in the alkaline phosphatase (ALP) activity. The amount of the osteogenic transcription factor Osterix and the alizarin red-stained bone nodule formation. ATP was measured with the luciferin-luciferase bioluminescence assay. The kinetics of the extracellular ATP (100 µM) and UDP (100 µM) catabolism was assessed by HPLC RESULTS: The extracellular catabolism of ATP and UDP was faster in BM-MSCs from Pm women compared to younger females. The immunoreactivity against NTPDase3 increased 5.6-fold in BM-MSCs from Pm women vs. younger females. Selective inhibition or transient NTPDase3 gene silencing increased the extracellular accumulation of adenine and uracil nucleotides in cultured Pm BM-MSCs. Downregulation of NTPDase3 expression or activity rehabilitated the osteogenic commitment of Pm BM-MSCs measured as increases in ALP activity, Osterix protein cellular content and bone nodule formation; blockage of P2X7 and P2Y6 purinoceptors prevented this effect. CONCLUSIONS: Data suggest that NTPDase3 overexpression in BM-MSCs may be a clinical surrogate of the osteogenic differentiation impairment in Pm women. Thus, besides P2X7 and P2Y6 receptors activation, targeting NTPDase3 may represent a novel therapeutic strategy to increase bone mass and reduce the osteoporotic risk of fractures in Pm women.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Humans , Female , Aged , Adolescent , Young Adult , Adult , Postmenopause , Mesenchymal Stem Cells/metabolism , Cell Differentiation , Uracil Nucleotides/metabolism , Uracil Nucleotides/pharmacology , Uridine Diphosphate/metabolism , Uridine Diphosphate/pharmacology , Adenosine Triphosphate/metabolism , Bone Marrow Cells , Cells, Cultured
18.
Mol Neurobiol ; 60(7): 4084-4104, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37016047

ABSTRACT

The vertebrate neuromuscular junction (NMJ) is a specialised chemical synapse involved in the transmission of bioelectric signals between a motor neuron and a skeletal muscle fiber, leading to muscle contraction. Typically, the NMJ is a tripartite synapse comprising (a) a presynaptic region represented by the motor nerve ending, (b) a postsynaptic skeletal motor endplate area, and (c) perisynaptic Schwann cells (PSCs) that shield the motor nerve terminal. Increasing evidence points towards the role of PSCs in the maintenance and control of neuromuscular integrity, transmission, and plasticity. Acetylcholine (ACh) is the main neurotransmitter at the vertebrate skeletal NMJ, and its role is fine-tuned by co-released purinergic neuromodulators, like adenosine 5'-triphosphate (ATP) and its metabolite adenosine (ADO). Adenine nucleotides modulate transmitter release and expression of postsynaptic ACh receptors at motor synapses via the activation of P2Y and P2X receptors. Endogenously generated ADO modulates ACh release by acting via co-localised inhibitory A1 and facilitatory A2A receptors on motor nerve terminals, whose tonic activation depends on the neuronal firing pattern and their interplay with cholinergic receptors and neuropeptides. Thus, the concerted action of adenine nucleotides, ADO, and ACh/neuropeptide co-transmitters is paramount to adapting the neuromuscular transmission to the working load under pathological conditions, like Myasthenia gravis. Unravelling these functional complexities prompted us to review our knowledge about the way purines orchestrate neuromuscular transmission and plasticity in light of the tripartite synapse concept, emphasising the often-forgotten role of PSCs in this context.


Subject(s)
Neuromuscular Junction , Synapses , Synapses/metabolism , Neuromuscular Junction/metabolism , Adenosine/metabolism , Adenosine Triphosphate/metabolism , Motor Neurons/metabolism , Acetylcholine/metabolism
19.
Cogitare Enferm. (Online) ; 28: e86953, Mar. 2023. tab, graf
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-1514043

ABSTRACT

RESUMO Objetivo: analisar os indicadores de gestão em saúde relacionados ao serviço de atendimento móvel de urgências do Ceará. Método: trata-se de um estudo documental, retrospectivo, de abordagem quantitativa, realizado no sítio eletrônico IntegraSUS do governo do estado do Ceará - Brasil, no período de julho de 2021, para análise dos indicadores "total de chamadas" e "tempo médio de resposta". Resultados: verificou-se um perfil de chamadas prevalentes para homens (52,66%), com idade avançada >70 anos (22,06%), ocorrências de atendimento Covid-19 para a Central Juazeiro (7,62%) e acidentes por motocicleta para a Central Eusébio (7,94%). O serviço obteve chamados para 177 municípios cearenses (96,19%) com tempo médio de resposta maior para Covid-19. Conclusão: a análise sinaliza a necessidade de ajuste das estratégias para melhorar o desempenho do tempo-resposta do serviço, com revisão do sistema organizacional, inclusive, da publicização dos dados pela plataforma digital.


ABSTRACT Objective: To analyze the health management indicators related to the mobile emergency care service in Ceará. Method: This is a documentary, retrospective, quantitative study, carried out on the IntegraSUS website of the Ceará state government - Brazil, during the period July 2021, to analyze the indicators "total calls" and "average response time". Results: It was verified a profile of prevalent calls for men (52.66%), with advanced age >70 years (22.06%), Covid-19 service occurrences for the Juazeiro central station (7.62%) and motorcycle accidents for the Eusébio central station (7.94%). The service got calls for 177 cities in Ceará (96.19%) with a longer average response time for Covid-19. Conclusion: The analysis signals the need to adjust strategies to improve the performance of the service response time, with a review of the organizational system, including the publication of data by the digital platform.


RESUMEN Objetivo: analizar los indicadores de gestión de salud relacionados con el servicio móvil de atención de urgencias en el Estado de Ceará. Método: se trata de un estudio documental, retrospectivo, de abordaje cuantitativo, realizado en el sitio IntegraSUS del gobierno del estado de Ceará - Brasil, en el período de julio de 2021, para el análisis de los indicadores "total de llamadas" y "tiempo medio de respuesta". Resultados: se verificó un perfil de prevalencia de llamadas para hombres (52,66%), con edad avanzada >70 años (22,06%), ocurrencias de asistencia del Covid-19 para la Central Juazeiro (7,62%) y accidentes de motocicleta para la Central Eusébio (7,94%). El servicio obtuvo llamadas para 177 municipios de Ceará (96,19%) con un tiempo medio de respuesta mayor para Covid-19. Conclusión: el análisis señala la necesidad de ajustar las estrategias para mejorar el rendimiento del tiempo de respuesta del servicio, con una revisión del sistema organizativo, incluida la publicación de datos por la plataforma digital.

20.
Plants (Basel) ; 12(4)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36840194

ABSTRACT

Cowpea (Vigna unguiculata (L.) Walp.) is currently a legume crop of minor importance in Europe but a highly relevant staple crop in Africa and the second most cultivated legume in Mozambique. In Portugal and Mozambique, cowpea's phenotypic and genetic variation has been maintained locally by farmers in some areas. We used the molecular markers SSR, SilicoDArT and SNP to analyze the genetic diversity and population structure of 97 cowpea accessions, mainly from Portugal (Southern Europe) and Mozambique (Southern Africa). As far as we know, this is the first time that the genetic variation and the relationship between cowpea landraces collected in Portugal with those originated in Mozambique is reported. Despite the shared historical past, the Portuguese landraces did not share a common genetic background with those from Mozambique, and two different gene pools were revealed. Knowledge of the genetic structure of cowpea landraces offers an opportunity for individual selection within landraces adapted to particular eco-physiological conditions and suggests the existence of a valuable gene pool for exploitation in future Portugal-PALOP (Portuguese-speaking African countries) cowpea breeding programs.

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