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1.
BMC Ecol Evol ; 24(1): 95, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982371

RESUMEN

BACKGROUND: Adaptation to a stressor can lead to costs on other traits. These costs play an unavoidable role on fitness and influence the evolutionary trajectory of a population. Host defense seems highly subject to these costs, possibly because its maintenance is energetically costly but essential to the survival. When assessing the ecological risk related to pollution, it is therefore relevant to consider these costs to evaluate the evolutionary consequences of stressors on populations. However, to the best of our knowledge, the effects of evolution in irradiate environment on host defense have never been studied. Using an experimental evolution approach, we analyzed fitness across 20 transfers (about 20 generations) in Caenorhabditis elegans populations exposed to 0, 1.4, and 50.0 mGy.h- 1 of 137Cs gamma radiation. Then, populations from transfer 17 were placed in the same environmental conditions without irradiation (i.e., common garden) for about 10 generations before being exposed to the bacterial parasite Serratia marcescens and their survival was estimated to study host defense. Finally, we studied the presence of an evolutionary trade-off between fitness of irradiated populations and host defense. RESULTS: We found a lower fitness in both irradiated treatments compared to the control ones, but fitness increased over time in the 50.0 mGy.h- 1, suggesting a local adaptation of the populations. Then, the survival rate of C. elegans to S. marcescens was lower for common garden populations that had previously evolved under both irradiation treatments, indicating that evolution in gamma-irradiated environment had a cost on host defense of C. elegans. Furthermore, we showed a trade-off between standardized fitness at the end of the multigenerational experiment and survival of C. elegans to S. marcescens in the control treatment, but a positive correlation between the two traits for the two irradiated treatments. These results indicate that among irradiated populations, those most sensitive to ionizing radiation are also the most susceptible to the pathogen. On the other hand, other irradiated populations appear to have evolved cross-resistance to both stress factors. CONCLUSIONS: Our study shows that adaptation to an environmental stressor can be associated with an evolutionary cost when a new stressor appears, even several generations after the end of the first stressor. Among irradiated populations, we observed an evolution of resistance to ionizing radiation, which also appeared to provide an advantage against the pathogen. On the other hand, some of the irradiated populations seemed to accumulate sensitivities to stressors. This work provides a new argument to show the importance of considering evolutionary changes in ecotoxicology and for ecological risk assessment.


Asunto(s)
Evolución Biológica , Caenorhabditis elegans , Animales , Caenorhabditis elegans/efectos de la radiación , Caenorhabditis elegans/microbiología , Radiación Ionizante , Serratia marcescens , Rayos gamma/efectos adversos , Aptitud Genética
2.
J Invest Surg ; 37(1): 2376548, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39004421

RESUMEN

As far as we know, no report uses the Swenson transanal endorectal pull-through technique in an animal model. Our objective is to describe the use of this technique as an experimental model for training and research purposes. Ten Norfolk hybrid rabbits were randomly selected from our experimental laboratory, with a mean weight of 3539.3 (± 678.4) g. Neither colon preparation nor fast were used before the procedures. The surgical technique was based on the description performed by Levitt et al. (2013, J Pediatr Surg. 2013;48(11):2289-2295). Information related to the surgical procedures and the clinical evolution in the postoperative period were recorded and analyzed. There were no deaths or severe complications. The anesthetic and the surgical times were significantly higher for the first three animals of the experiment. Our animal model proved adequate to perform the transanal endorectal Swenson pull-through technique, allowing the training of surgical skills through a model similar to the human, with few anesthetic complications and good postoperative evolution, including postoperative follow-up. We believe that it will serve as a learning tool in many institutions that are continuously searching for improved new techniques and will support new researches in this area.


Asunto(s)
Modelos Animales , Recto , Animales , Conejos , Recto/cirugía , Canal Anal/cirugía , Cirugía Endoscópica Transanal/métodos , Humanos , Tempo Operativo
3.
Inflammation ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980500

RESUMEN

Methylprednisolone (MP) is a potent glucocorticoid that can effectively inhibit immune system inflammation and brain tissue damage in Multiple sclerosis (MS) patients. T follicular helper (Tfh) cells are a subpopulation of activated CD4 + T cells, while T follicular regulatory (Tfr) cells, a novel subset of Treg cells, possess specialized abilities to suppress the Tfh-GC response and inhibit antibody production. Dysregulation of either Tfh or Tfr cells has been implicated in the pathogenesis of MS. However, the molecular mechanism underlying the anti-inflammatory effects of MP therapy on experimental autoimmune encephalomyelitis (EAE), a representative model for MS, remains unclear. This study aimed to investigate the effects of MP treatment on EAE and elucidate the possible underlying molecular mechanisms involed. We evaluated the effects of MP on disease progression, CNS inflammatory cell infiltration and myelination, microglia and astrocyte activation, as well as Tfr/Tfh ratio and related molecules/inflammatory factors in EAE mice. Additionally, Western blotting was used to assess the expression of proteins associated with the PI3K/AKT pathway. Our findings demonstrated that MP treatment ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Furthermore, it reduced microglial and astrocytic activation. MP may increase the number of Tfr cells and the levels of cytokine TGF-ß1, while reducing the number of Tfh cells and the levels of cytokine IL-21, as well as regulate the imbalanced Tfr/Tfh ratio in EAE mice. The PI3K/AKT/FoxO1 and PI3K/AKT/mTOR pathways were found to be involved in EAE development. However, MP treatment inhibited their activation. MP reduced neuroinflammation in EAE by regulating the balance between Tfr/Tfh cells via inhibition of the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR signalling pathways.

4.
Int J Biol Macromol ; : 133519, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960235

RESUMEN

This study investigated the development of a genipin-crosslinked chitosan (CS)-based polyvinylpyrrolidone (PVP) hydrogel containing curcumin nanosuspensions (Cur-NSs) for promoting wound healing in an excisional wound model. Cur-NSs were first prepared, and a simplex centroid mixture design was employed to optimize the hydrogel for high water absorption, degree of crosslinking, and sufficient toughness. The in vivo wound healing effect was investigated on Wistar rats. The optimized hydrogel consisted of CS:PVP at a 70:30 ratio, crosslinked with a 2 % w/w genipin solution. It exhibited high swelling capability (486 %) while maintaining solidity, robustness, and durability. Incorporation of 5 % w/w Cur-NSs resulted in a more compact structure, although with reduction in swelling properties. The release kinetics of Cur from the hydrogel followed the Korsmeyer-Peppas Fickian diffusion model. In vitro biocompatibility studies demonstrated that the hydrogel was non-toxic to skin fibroblast cells. The in vivo experiment revealed a desirable wound healing rate with over 80 % recovery at day 7. Cur-NSs likely aided wound healing by reducing inflammatory response and stimulating fibroblast proliferation. Additionally, the CS-based hydrogel provided a moist wound environment with hydration and gas transfer, further accelerating wound closure. These findings suggest that the Cur-NS-embedded hydrogel shows promise as a desirable wound dressing material.

5.
Int J Biol Macromol ; : 133555, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960240

RESUMEN

Here, we report a study of the effect of the blocking agent on the properties of the lipase from Thermomyces lanuginosus (TLL) immobilized on a heterofunctional support (Purolite C18-ethylnediamina (EDA)- vinyl sulfone (VS)-TLL-blocking agent) in different reactions. The performance of the biocatalysts was compared to those immobilized on standard hydrophobic support (Purolite C18-TLL) and the commercial one (TLL-IM). The nature of the blocking agent (Cys, Gly and Asp) altered the enzyme features. TLL-IM always gave a comparatively worse performance, with its specificity for the oil being very different to the Purolite biocatalysts. Under optimized conditions, Purolite C18-TLL yielded 97 % of hydrolysis conversion after 4 h using a water/waste cooking soybean oil (WCSO) mass ratio of 4.3, biocatalyst load of 6.5 wt% and a temperature of 44.2 °C (without buffer or emulsification agent). In esterification reactions of the purified free fatty acids (FFAs) obtained from WCSO, the best TLL biocatalysts depended on the utilized alcohol: linear amyl alcohol was preferred by Purolite C18-TLL and Purolite C18-EDA-VS-TLL-Gly, while higher activity was achieved utilizing isoamyl alcohol as nucleophile by Purolite C18-EDA-VS-TLL-Cys, Purolite C18-EDA-VS-TLL-Asp and IM-TLL as catalysts. All the results indicate the influence of the blocking step on the final biocatalyst features.

6.
bioRxiv ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38948761

RESUMEN

The ecological and evolutionary success of multicellular lineages is due in no small part to their increased size relative to unicellular ancestors. However, large size also poses biophysical challenges, especially regarding the transport of nutrients to all cells; these constraints are typically overcome through multicellular innovations (e.g., a circulatory system). Here we show that an emergent biophysical mechanism - spontaneous fluid flows arising from metabolically-generated density gradients - can alleviate constraints on nutrient transport, enabling exponential growth in nascent multicellular clusters of yeast lacking any multicellular adaptations for nutrient transport or fluid flow. Surprisingly, beyond a threshold size, the metabolic activity of experimentally-evolved snowflake yeast clusters drives large-scale fluid flows that transport nutrients throughout the cluster at speeds comparable to those generated by the cilia of extant multicellular organisms. These flows support exponential growth at macroscopic sizes that theory predicts should be diffusion limited. This work demonstrates how simple physical mechanisms can act as a 'biophysical scaffold' to support the evolution of multicellularity by opening up phenotypic possibilities prior to genetically-encoded innovations. More broadly, our findings highlight how co-option of conserved physical processes is a crucial but underappreciated facet of evolutionary innovation across scales.

7.
Front Nephrol ; 4: 1406655, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006160

RESUMEN

Anticoagulant related nephropathy (ARN) is the result of glomerular hemorrhage in patients on systemic anticoagulation therapy or underlying coagulopathy. Red blood cells (RBC) that passed through the glomerular filtration barrier form RBC casts in the tubules, increase oxidative stress and result in acute tubular necrosis (ATN). The mechanisms of ARN still not completely discovered. Plasminogen activator inhibitor-1 (PAI-1) plays a significant role in the maintenance of coagulation homeostasis. We developed an animal model to study ARN in 5/6 nephrectomy (5/6NE) rats. The aim of this study was to elucidate the role of PAI-1 in the ARN pathogenesis. 5/6NE rats were treated per os with warfarin (0.75 mg/kg/day) or dabigatran (150 mg/kg/day) alone or in combination with PAI-1 antagonist TM5441 (2.5, 5.0 and 10 mg/kg/day). TM5441 in a dose dependent manner ameliorated anticoagulant-induced increase in serum creatinine in 5/6NE rats. Anticoagulant-associated increase in hematuria was no affected by TM5441. The levels of reactive oxygen species (ROS) in the kidneys were in a dose-dependent manner decreased in 5/6NE rats treated with an anticoagulant and TM5441. Our data demonstrates that PAI-1 may reduce ARN by decreasing ROS in the kidneys. Glomerular hemorrhage is not affected by anti-PAI-1 treatment. These findings indicate that while symptoms of ARN can be reduced by PAI-1 inhibition, the main pathogenesis of ARN - glomerular hemorrhage - cannot be prevented.

8.
Drug Des Devel Ther ; 18: 2847-2868, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006190

RESUMEN

Purpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro. Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model. Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2. Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology.


Asunto(s)
Berberina , Colitis Ulcerosa , Biología Computacional , Subunidad alfa del Factor 1 Inducible por Hipoxia , FN-kappa B , Receptor Toll-Like 4 , Berberina/farmacología , Berberina/química , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Animales , Ratones , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Simulación del Acoplamiento Molecular , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Masculino , Sulfato de Dextran , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Farmacología en Red
9.
Swiss J Palaeontol ; 143(1): 26, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006952

RESUMEN

Fossilization, or the transition of an organism from the biosphere to the geosphere, is a complex mechanism involving numerous biological and geological variables. Bacteria are one of the most significant biotic players to decompose organic matter in natural environments, early on during fossilization. However, bacterial processes are difficult to characterize as many different abiotic conditions can influence bacterial efficiency in degrading tissues. One potentially important variable is the composition and nature of the sediment on which a carcass is deposited after death. We experimentally examined this by decaying the marine shrimp Palaemon varians underwater on three different clay sediments. Samples were then analyzed using 16S ribosomal RNA sequencing to identify the bacterial communities associated with each clay system. Results show that samples decaying on the surface of kaolinite have a lower bacterial diversity than those decaying on the surface of bentonite and montmorillonite, which could explain the limited decay of carcasses deposited on this clay. However, this is not the only role played by kaolinite, as a greater proportion of gram-negative over gram-positive bacteria is observed in this system. Gram-positive bacteria are generally thought to be more efficient at recycling complex polysaccharides such as those forming the body walls of arthropods. This is the first experimental evidence of sediments shaping an entire bacterial community. Such interaction between sediments and bacteria might have contributed to arthropods' exquisite preservation and prevalence in kaolinite-rich Lagerstätten of the Cambrian Explosion. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-024-00324-7.

10.
Pol Merkur Lekarski ; 52(3): 261-267, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39007463

RESUMEN

OBJECTIVE: Aim: The aim of the work was to study the ef f ect of photobiomodulation therapy on the regulation of disorders in the healing of chronic wounds at the remodeling stage using indicators of platelet aggregation activity, reactive oxygen species, platelet-derived growth factor, and interleukin-1ß. PATIENTS AND METHODS: Materials and Methods: The study included 3 groups of Wistar rats: intact animals and animals of the control and experimental groups, for which chronic wounds were simulated. Rats in the experimental group received photobiomodulation therapy once a day for 5 days. Wound defects of animals in the control group were fictitiously irradiated. The levels of reactive oxygen species, platelet-derived growth factor, and interleukin-1ß in the blood serum of animals were studied by enzyme immunoassay. The functional activity of platelets was measured on a computerized platelet aggregation analyzer using the turbidimetric method. Histological studies were carried out. RESULTS: Results: Changes in the expression of the studied indicators were found in the blood serum of animals with chronic wounds when using photobiomodulation therapy: an increase in platelet-derived growth factor concentrations, the levels of reactive oxygen species and interleukin-1ß did not have statistically signif i cant differences compared to the corresponding indicators of animals in the control group. There were no significant differences in the indicators of platelet aggregation activity in the control and experimental groups of animals. CONCLUSION: Conclusions: The findings suggest that photobiomodulation therapy may promote wound healing by increasing platelet-derived growth factor levels. Histological studies have shown that using photobiomodulation therapy helps reduce inflammation and better organization of collagen fibers in animals of the experimental group.


Asunto(s)
Interleucina-1beta , Terapia por Luz de Baja Intensidad , Ratas Wistar , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de la radiación , Terapia por Luz de Baja Intensidad/métodos , Ratas , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Especies Reactivas de Oxígeno/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Masculino , Enfermedad Crónica , Agregación Plaquetaria/efectos de la radiación
11.
Bioinspir Biomim ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38991522

RESUMEN

This work examines the acoustically actuated motions of artificial flagellated micro-swimmers (AFMSs) and compares the motility of these micro-swimmers with the predictions based on the corrected resistive force theory (CRFT) and the bar-joint model proposed in our previous work. The key ingredient in the theory is the introduction of a correction factorKin drag coefficients to correct the conventional resistive force theory so that the dynamics of an acoustically actuated AFMS with rectangular cross-sections can be accurately modeled. Experimentally, such AFMSs can be easily manufactured based on digital light processing (DLP) of UV-curable resins. We first determined the viscoelastic properties of a UV-cured resin through dynamic mechanical analysis (DMA). In particular, the high-frequency storage moduli and loss factors were obtained based on the assumption of time-temperature superposition (TTS), which were then applied in theoretical calculations. Though the extrapolation based on the TTS implied the uncertainty of high-frequency material response and there is limited accuracy in determining head oscillation amplitude, the differences between the measured terminal velocities of the AFMSs and the predicted ones are less than 50%, which, to us, is well acceptable. These results indicate that the motions of acoustic AFMS can be predicted, and thus, designed, which pave the way for their long-awaited applications in targeted therapy.

12.
J Plant Res ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992325

RESUMEN

Mechanical forces play a crucial role in plant development, including floral development. We previously reported that the phyllotactic variation in the staminate flowers of Ceratophyllum demersum may be caused by mechanical forces on the adaxial side of floral primordia, which may be a common mechanism in angiosperms. On the basis of this result, we developed a novel experimental system for analysis of the effects of mechanical forces on the floral meristem of Arabidopsis thaliana, aiming to induce morphological changes in flowers. In this experimental system, a micromanipulator equipped with a micro device, which is shaped to conform with the contour of the abaxial side of the young floral primordium, is used to exert contact pressure on a floral primordium. In the present study, we conducted contact experiments using this system and successfully induced diverse morphological changes during floral primordial development. In several primordia, the tip of the abaxial sepal primordium was incised with two or three lobes. A different floral primordium developed an additional sepal on the abaxial side (i.e., two abaxial sepals). Additionally, we observed the fusion of sepals in some floral primordia. These results suggest that mechanical forces have multiple effects on floral development, and changes in the tensile stress pattern in the cells of floral primordia are induced by the mechanical forces exerted with the micro device. These effects, in turn, lead to morphological changes in the floral primordia.

13.
Heliyon ; 10(12): e32919, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38994047

RESUMEN

This study provides a detailed analysis of the aerodynamic performance of various airfoil configurations, focusing on lift coefficient, stall characteristics, and maximum lift-to-drag ratio. The investigation includes the NACA23012C profile and configurations with different step geometries, ranging from one-step to five-step designs. Experimental measurements were conducted using a well-equipped aerodynamic laboratory, Institute of Aviation Engineering and Technology (IAET), Giza, Egypt. The lab features a wind tunnel, propeller test rig, and data acquisition system. The experiments were conducted meticulously to ensure accuracy and reproducibility, with a standardized method employed for uncertainty analysis. The results reveal distinct aerodynamic behaviors among the different configurations, highlighting the significant impact of design variations on aerodynamic performance. Notably, the three-step configuration consistently exhibited high performance, with a competitive or superior lift coefficient across a range of Reynolds numbers, showing an improvement of up to 35.1 %. Similarly, the four-step configuration demonstrated substantial increases in lift-to-drag ratios, reaching up to 53.2 %, while the five-step configuration exhibited varying trends with a minimum drag coefficient. The study also investigated stall characteristics and sensitivity to Reynolds numbers, revealing the complex trade-offs inherent in airfoil design. The findings provide valuable insights into optimizing airfoil performance under different operational conditions. Additionally, the adoption of two and three stepped airfoils resulted in significant reductions in blade material and associated costs for turbine blades.

14.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39000105

RESUMEN

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Esclerosis Múltiple , Animales , Encefalomielitis Autoinmune Experimental/terapia , Encefalomielitis Autoinmune Experimental/patología , Ratas , Esclerosis Múltiple/terapia , Esclerosis Múltiple/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Humanos , Femenino , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células-Madre Neurales , Modelos Animales de Enfermedad , Gelatina de Wharton/citología
15.
iScience ; 27(6): 110014, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38947512

RESUMEN

The NAD+-dependent deacetylase SIRT7 is a pivotal regulator of DNA damage response (DDR) and a promising drug target for developing cancer therapeutics. However, limited progress has been made in SIRT7 modulator discovery. Here, we applied peptide-based deacetylase platforms for SIRT7 enzymatic evaluation and successfully identified a potent SIRT7 inhibitor YZL-51N. We initially isolated bioactive YZL-51N from cockroach (Periplaneta americana) extracts and then developed the de novo synthesis of this compound. Further investigation revealed that YZL-51N impaired SIRT7 enzymatic activities through occupation of the NAD+ binding pocket. YZL-51N attenuated DNA damage repair induced by ionizing radiation (IR) in colorectal cancer cells and exhibited a synergistic anticancer effect when used in combination with etoposide. Overall, our study not only identified YZL-51N as a selective SIRT7 inhibitor from insect resources, but also confirmed its potential use in combined chemo-radiotherapy by interfering in the DNA damage repair process.

16.
J Plant Dis Prot (2006) ; 131(4): 1257-1264, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947557

RESUMEN

Plant pathogens are highly adaptable, and have evolved to overcome control measures including multiple classes of fungicides. More effective management requires a thorough understanding of the evolutionary drivers leading to resistance. Experimental evolution can be used to investigate evolutionary processes over a compressed timescale. For fungicide resistance, applications include predicting resistance ahead of its emergence in the field, testing potential outcomes under multiple different fungicide usage scenarios or comparing resistance management strategies. This review considers different experimental approaches to in vitro selection, and their suitability for addressing different questions relating to fungicide resistance. When aiming to predict the evolution of new variants, mutational supply is especially important. When assessing the relative fitness of different variants under fungicide selection, growth conditions such as temperature may affect the results as well as fungicide choice and dose. Other considerations include population size, transfer interval, competition between genotypes and pathogen reproductive mode. However, resistance evolution in field populations has proven to be less repeatable for some fungicide classes than others. Therefore, even with optimal experimental design, in some cases the most accurate prediction from experimental evolution may be that the exact evolutionary trajectory of resistance will be unpredictable.

17.
MethodsX ; 12: 102772, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38948243

RESUMEN

Lead (Pb) is a neurotoxin, and children are vulnerable due to their evolving physiology and high-risk behaviours. Soil remediation interventions have proven effective in reducing Pb exposure. The primary objective is to measure the effectiveness of soil remediation at abandoned used lead acid battery (ULAB) recycling sites, nearby household cleaning, and community awareness in reducing blood lead levels (BLLs) in children. Additionally, this study aims to examine associations of Pb exposure with hematological, cardiovascular, renal, immunological, and endocrinological parameters in children aged 0-12 years. This study employs a quasi-experimental design, with abandoned ULAB sites as intervention sites and two control sites in Bangladesh. The intervention includes soil remediation coupled with community education. Data will be collected prior to the intervention and at a 12-month follow-up, including a comprehensive Pb exposure survey and collect environmental, turmeric samples, and blood from the child. Pb concentrations in environmental samples and turmeric samples will be determined using XRF analyser. Child BLL will be measured using Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) and proposed biochemical parameters will be analysed using routine laboratory methods. This study could provide valuable insights for designing targeted interventions in similar settings and mitigating exposure to Pb.

18.
World J Exp Med ; 14(2): 94135, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38948424

RESUMEN

BACKGROUND: Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM: To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS: This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS: From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION: Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

19.
Microbiol Immunol ; 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38946035

RESUMEN

Classical swine fever (CSF) re-emerged in Japan in 2018 for the first time in 26 years. The disease has been known to be caused by a moderately pathogenic virus, rather than the highly pathogenic virus that had occurred in the past. However, the underlying pathophysiology remains unknown. This study conducted an experimental challenge on specific pathogen-free (SPF) pigs in a naïve state for 2, 4, and 6 weeks and confirmed the disease state during each period by clinical observation, virus detection, and pathological necropsy. We revealed the pathological changes and distribution of pathogens and virus-specific antibodies at each period after virus challenge. These results were comprehensively analyzed and approximately 70% of the pigs recovered, especially at 4- and 6-week post-virus challenge. This study provides useful information for future countermeasures against CSF by clarifying the pathogenicity outcomes in unvaccinated pigs with moderately pathogenic genotype 2.1 virus.

20.
Nano Lett ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949570

RESUMEN

N2O is a dominant atmosphere pollutant, causing ozone depletion and global warming. Currently, electrochemical reduction of N2O has gained increasing attention to remove N2O, but its product is worthless N2. Here, we propose a direct eight-electron (8e) pathway to electrochemically convert N2O into NH3. As a proof of concept, using density functional theory calculation, an Fe2 double-atom catalyst (DAC) anchored by N-doped porous graphene (Fe2@NG) was screened out to be the most active and selective catalyst for N2O electroreduction toward NH3 via the novel 8e pathway, which benefits from the unique bent N2O adsorption configuration. Guided by theoretical prediction, Fe2@NG DAC was fabricated experimentally, and it can achieve a high N2O-to-NH3 Faradaic efficiency of 77.8% with a large NH3 yield rate of 2.9 mg h-1 cm-2 at -0.6 V vs RHE in a neutral electrolyte. Our study offers a feasible strategy to synthesize NH3 from pollutant N2O with simultaneous N2O removal.

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