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1.
J Am Vet Med Assoc ; : 1-8, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39127080

RESUMEN

OBJECTIVE: To evaluate outcomes and complication rate of utilizing a string-of-pearls (SOP) plate augmented with adjunctive fixation in the repair of canine femur fractures. METHODS: Records of canine patients with mid-diaphyseal femoral fractures repaired with the SOP plate and adjunctive fixation were reviewed. Information retrieved from medical records included signalment, patient weight, fracture configuration, repair technique, healing time, and complications based on perioperative radiographic follow-up to clinical union. Forty client-owned dogs met inclusion criteria for this study. Variables analyzed for association with major complications included body weight, fracture configuration, repair technique, and adjunctive fixation. RESULTS: Major complications requiring surgical revision occurred in 8 of 40 fractures. Five cases experienced intramedullary pin migration and were successfully treated with sedated pin removal. The remaining 3 cases involved implant failure via screw shear breakage and required surgical revision of the fixation to achieve a successful outcome. On the basis of a calculated Bonferroni correction, no statistical significance of the tested variables was found in association with major complications; however, significance was limited due to the low statistical power of this study. CONCLUSIONS: The use of adjunctive fixation with the SOP locking plate system led to radiographic union without complication in most cases, and no instances of plate breakage were reported. However, implant complications secondary to the adjunctive fixation can occur. CLINICAL RELEVANCE: Adjunctive fixation used with the SOP plate for repair of canine femur fractures has a high success rate, though pin migration as a complication persists.

2.
Cureus ; 16(7): e64118, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39119379

RESUMEN

Amalgam has made dental restorations more manageable, especially in difficult cases, due to its strength, durability, and relatively low cost. There can be pros and cons of each dental material depending on which class of cases it is applied or not applied for, depending on the patient's need, and, of course, the dentist's choice. These materials are used frequently for their hardness and durability and are ideal for extensive restoration procedures. On the other hand, composite resins are considered to be more aesthetic for the profitable areas where esthetics are more important. In contrast, glass ionomer cement is considered to be ideal for low-stress-bearing areas. The following case report of pin-retained amalgam restoration presents an example of its application in practical situations and the factors that must be considered to justify the use of this material against others. This paper explains various factors in considering pin-retained amalgam restorations and the procedure for a better and positive outcome.

3.
Materials (Basel) ; 17(15)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39124466

RESUMEN

Modern engine bearing materials encounter the challenge of functioning under conditions of mixed lubrication, low viscosity oils, downsizing, start-stop engines, potentially leading to metal-to-metal contact and, subsequently, premature bearing failure. In this work, two types of polymer overlays were applied to the bearing surface to compensate for extreme conditions, such as excessive loads and mixed lubrication. Two different polymer overlays, created through a curing process on a conventional engine bearing surface with an approximate thickness of 13 µm, were investigated for their friction and wear resistances under a 30 N load using a pin-on-disc setup. The results indicate that the newly developed polymer overlay (NDP, PAI-based coating) surface has a coefficient of friction (COF) of 0.155 and a wear volume loss of 0.010 cm3. In contrast, the currently used polymer overlay (CPO) in this field shows higher values with a COF of 0.378 and a wear volume loss of 0.024 cm3, which is significantly greater than that of the NDP. It was found that, in addition to accurately selecting the ratios of solid lubricants, polymer resins, and wear-resistant hard particle additives (metal powders, metal oxides, carbides, etc.) within the polymer coating, the effective presence of a transfer film providing low friction on the counter surface also played a crucial role.

4.
Plant J ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162107

RESUMEN

Plants synthesize hundreds of small secretory peptides, which are perceived by the receptor-like kinase (RLK) family at the cell surface. Various signaling peptide-RLK pairs ensure plant adaptation to distinct environmental conditions. Here, we report that SERINE RICH ENDOGENOUS PEPTIDE (SCOOP) immune peptides modulate root growth and development by regulating PIN-FORMED (PIN)-regulated polar auxin transport in Arabidopsis. The SCOOP4 and SCOOP12 treatments impaired root gravitropic growth, auxin redistribution in response to gravistimulation, and PIN abundance in the PM. Furthermore, genetic and cell biological analyses revealed that these physiological and cellular effects of SCOOP4 and SCOOP12 peptides are mediated by the receptor MALE DISCOVERER1-INTERACTING RECEPTOR LIKE KINASE2 (MIK2) and the downstream mitogen-activated kinase MPK6. Biochemical evidence indicates that MPK6 directly phosphorylates the cytosolic loop of PIN proteins. Our work established a link between the immune signaling peptide SCOOPs and root growth pathways, providing insights into the molecular mechanisms underlying plant root adaptive growth in the defense response.

5.
Plant Cell Environ ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136400

RESUMEN

In the investigation of heterotrimeric G protein-mediated signal transduction in planta, their roles in the transmittance of low K+ stimuli remain to be elucidated. Here, we found that the primary root growth of wild-type Arabidopsis was gradually inhibited with the decrease of external K+ concentrations, while the primary root of the mutants for G protein ß subunit AGB1 and γ subunits AGG1, AGG2 and AGG3 could still grow under low K+ conditions (LK). Exogenous NAA application attenuated primary root elongation in agb1 and agg1/2/3 but promoted the growth in wild-type seedlings under LK stress. Using ProDR5:GFP, ProPIN1:PIN1-GFP and ProPIN2:PIN2-GFP reporter lines, a diminishment in auxin concentration at the radicle apex and a reduction in PIN1and PIN2 efflux carrier abundance were observed in wild-type roots under LK, a phenomenon not recorded in the agb1 and agg1/2/3. Further proteolytic and transcriptional assessments revealed an enhanced degradation of PIN1 and a suppressed expression of PIN2 in the wild-type background under LK, contrasting with the stability observed in the agb1 and agg1/2/3 mutants. Our results indicate that the G protein ß and γ subunits play pivotal roles in suppressing of Arabidopsis root growth under LK by modulating auxin redistribution via alterations in PIN1 degradation and PIN2 biosynthesis.

6.
ACS Appl Mater Interfaces ; 16(32): 42577-42587, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39099305

RESUMEN

As a two-dimensional (2D) material, palladium diselenide (PdSe2) has attracted extensive research attention due to its unique asymmetric crystal structure and extraordinary optoelectronic properties, showing great potential in electronic, optoelectronic, and other application fields. Thinner PdSe2 exhibits semiconductor properties, while the photoresponse of the photodetectors based on this film is weaker. Although increasing the thickness of the PdSe2 film can improve the photoresponse, thicker PdSe2 exhibits metallic-like properties, which is not conducive to the formation of the heterojunction. In this work, a PdSe2 2D material with a quantum island structure is prepared by a simple thermal-assisted conversion method. A new type of photodetector with a PdSe2/n--Si/n+-Si vertical PIN-like structure is innovatively proposed. Broad spectral absorption from 532 to 2200 nm and a high rectification ratio (106) of the device are achieved. The introduced n--Si layer concentrates the electric field in the depletion region, thereby shortening the transit time and accelerating the separation and collection of the carriers, resulting in the enhancement of the responsivity and 3 dB frequency compared to the traditional device with a PN structure. A recorded highest 3 dB frequency of ∼25 kHz is achieved for the PdSe2 2D-3D PIN-like device.

7.
Heliyon ; 10(13): e33550, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39040276

RESUMEN

An experimental and numerical study on the ejector pin's mechanics during automatic multistage cold forging (AMSCF) of an automobile wheel nut is conducted. The traditional, decoupled die structural analysis method (DDSM) of analyzing die structures as one of the post-processing functions is criticized, which uses the tractions exerting on the die parts predicted from the forging simulation under the rigid die assumption. To cope with the matter of the DDSM, a multibody treatment scheme (MBTS) is proposed to simulate the AMSCF process, emphasizing the ejector pin's mechanics, using an implicit elastoplastic finite element method. The experiments qualitatively validate the finite element predictions. It is shown that the asymmetric sheared material in AMSCF greatly influences the ejector pin's mechanics, which is characterized by its lateral and longitudinal displacements because of its structural flexibility. It is emphasized that the detailed understanding of the ejector pin's mechanics may not only give a helpful connection towards smart manufacturing because of its mechanical flexibility and sensitivity to the excitations and responses, but it also reveals the reason for the die's high-cycle fatigue (HCF) fracture of the critical die corner (CDC) near at the end of the ejector pin.

8.
J Alzheimers Dis ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39031370

RESUMEN

Activation of cell-cycle machinery in Alzheimer's disease (AD) brain was reported by Mark Smith and colleagues and by other researchers. Among other biochemical processes underlying this activation, the notion that AD brain, under the onslaught of oxidative and nitrosative damage leading to neuronal loss, neurons would attempt to replenish their numbers by entering the cell cycle. However, being post-mitotic, neurons entering the cell cycle would become trapped therein, ultimately leading to death of these neurons. Yang and co-workers and the Butterfield laboratory first reported that similar activation of the cell cycle was present in the brains of individuals with amnestic mild cognitive impairment (MCI), arguably the earliest clinical stage of AD, but who demonstrate normal activities of daily living and no dementia. Activation of the cell cycle in MCI brain is consonant with the concept that this process is an early aspect in the progression of AD. This brief review article discusses these findings and recognizes the contribution of Dr. Mark Smith to the investigation of cell-cycle activation in AD brain and other aspects of AD neuropathology.

9.
FASEB J ; 38(14): e23839, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39037418

RESUMEN

During early pregnancy in mice, the establishment of uterine receptivity and endometrial decidualization require the extensive proliferation and differentiation of endometrial epithelial cells or stromal cells. Pin1 has been suggested to act as a molecular 'timer' of the cell cycle and is involved in the regulation of cellular proliferation and differentiation by binding many cell-cycle regulatory proteins. However, its physiological role during early pregnancy is still not fully understood. Here, we employed immunohistochemistry to determine the spatiotemporal pattern of Pin1 expression during early pregnancy. We found that Pin1 was mainly localized in subluminal stromal cells on day 4, in the decidual zone on days 5 to 8 of pregnancy and in artificial decidualization. Using a uterine stromal cell culture system, we found that progesterone, but not estrogen, induced the expression of Pin1 in a progesterone receptor-dependent manner. Inhibition of Pin1 in the uterus leads to impaired embryo implantation and decidualization in mice. Notably, a decrease in Pin1 activation affected the functional execution of several implantation- or decidualization-related factors. These findings provide new evidence for a previously unknown function of Pin1 in mediating embryo implantation and decidualization during successful pregnancy establishment and maintenance.


Asunto(s)
Decidua , Implantación del Embrión , Peptidilprolil Isomerasa de Interacción con NIMA , Útero , Animales , Femenino , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Implantación del Embrión/fisiología , Ratones , Embarazo , Decidua/metabolismo , Decidua/citología , Útero/metabolismo , Útero/citología , Progesterona/metabolismo , Células del Estroma/metabolismo , Receptores de Progesterona/metabolismo , Células Cultivadas , Endometrio/metabolismo , Endometrio/citología
10.
Neurobiol Aging ; 141: 160-170, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38964013

RESUMEN

Women have a higher incidence of Alzheimer's disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.


Asunto(s)
Enfermedad de Alzheimer , Cognición , Disfunción Cognitiva , Peptidilprolil Isomerasa de Interacción con NIMA , Neocórtex , Ovillos Neurofibrilares , Caracteres Sexuales , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/metabolismo , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Humanos , Femenino , Neocórtex/patología , Neocórtex/metabolismo , Masculino , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Disfunción Cognitiva/metabolismo , Anciano , Anciano de 80 o más Años , Ovillos Neurofibrilares/patología , Ovillos Neurofibrilares/metabolismo , Fenotipo , Sistema Límbico/patología , Sistema Límbico/metabolismo , Expresión Génica , Envejecimiento/patología , Envejecimiento/genética , Envejecimiento/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Fosforilación
11.
Micromachines (Basel) ; 15(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39064428

RESUMEN

Piezoelectric composites, which consist of piezoelectric materials and polymers, are widely employed in various applications such as underwater sonar transducers and medical diagnostic ultrasonic transducers. Acoustic transducers based on piezoelectric composites can have high sensitivity with broad bandwidth. In recent studies, it is demonstrated that 2-2 composites based on single crystals provide further increased sensitivity and wide bandwidth. In order to utilize a 2-2 composite in acoustic sensors, it is required to demonstrate the full material coefficients of the 2-2 composite. In this study, we investigated an analytic solution for determining equivalent material coefficients of a 2-2 composite. Impedance spectrums of the single-phase resonators with equivalent material coefficients and 2-2 composite resonators were compared by the finite element method in order to verify the analytic solutions. Furthermore, the equivalent material coefficients derived from the analytic solution were also verified by comparing the measured and the simulated impedance spectrums. The difference in resonance and anti-resonance frequencies between the measured and simulated impedance spectrums was around 0.5% and 1.2%. By utilizing the analytic solutions in this study, it is possible to accurately derive full equivalent material coefficients of a 2-2 composite, which are essential for the development of acoustic sensors.

12.
J Integr Plant Biol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990128

RESUMEN

Light and gravity coordinately regulate the directional growth of plants. Arabidopsis Gravitropic in the Light 1 (GIL1) inhibits the negative gravitropism of hypocotyls in red and far-red light, but the underlying molecular mechanisms remain elusive. Our study found that GIL1 is a plasma membrane-localized protein. In endodermal cells of the upper part of hypocotyls, GIL1 controls the negative gravitropism of hypocotyls. GIL1 directly interacts with PIN3 and inhibits the auxin transport activity of PIN3. Mutation of PIN3 suppresses the abnormal gravitropic response of gil1 mutant. The GIL1 protein is unstable in darkness but it is stabilized by red and far-red light. Together, our data suggest that light-stabilized GIL1 inhibits the negative gravitropism of hypocotyls by suppressing the activity of the auxin transporter PIN3, thereby enhancing the emergence of young seedlings from the soil.

13.
Sensors (Basel) ; 24(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39000915

RESUMEN

This paper presents a low-profile reconfigurable antenna array capable of five radiation-pattern modes for vehicular communication applications. The antenna array consists of four antenna elements, each containing four square patches. Exciting one of the square patches generates a broadside radiation. A square parasitic patch is added at the rear of the excited patch, and two square parasitic patches are placed at the front. By optimizing the design of these parasitic patches, including the treatment of center slotting and addition of shorting pins, the antenna element achieves an end-fire beam with a certain tilt angle. On this basis, a reconfigurable feeding network is designed with 1:1 and 1:4 output modes. By connecting the reconfigurable feeding network to the four antenna elements and altering the on/off states of the PIN diodes in the feeding network, a reconfigurable antenna with four end-fire beams and one omnidirectional beam in its radiation pattern is realized. Measurement results demonstrate an excellent impedance bandwidth, radiation pattern, and gain performance in all modes. The four end-fire and one omnidirectional radiation characteristics make it highly suitable for vehicular communication applications.

14.
Curr Opin Struct Biol ; 88: 102880, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38996623

RESUMEN

Co-fractionation mass spectrometry (CF-MS) uses biochemical fractionation to isolate and characterize macromolecular complexes from cellular lysates without the need for affinity tagging or capture. In recent years, this has emerged as a powerful technique for elucidating global protein-protein interaction networks in a wide variety of biospecimens. This review highlights the latest advancements in CF-MS experimental workflows including machine learning-guided analyses, for uncovering dynamic and high-resolution protein interaction landscapes with enhanced sensitivity, accuracy and throughput, enabling better biophysical characterization of endogenous protein complexes. By addressing challenges and emergent opportunities in the field, this review underscores the transformative potential of CF-MS in advancing our understanding of functional protein interaction networks in health and disease.

15.
Clin Case Rep ; 12(7): e9210, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39035125

RESUMEN

Regarding head immobilization practices in neurosurgery, secondary fixation fractures are rare, underscoring the importance of precise pin positioning and an adequate force in the three-point clamp to achieve adequate fixation. Attention should be given to factors such as changes in bone metabolism.

16.
ACS Appl Mater Interfaces ; 16(31): 41244-41256, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39041930

RESUMEN

In pursuing high stability and power conversion efficiency for organic photovoltaics (OPVs), a sequential deposition (SD) approach to fabricate active layers with p-i-n structures (where p, i, and n represent the electron donor, mixed donor:acceptor, and electron acceptor regions, respectively, distinctively different from the bulk heterojunction (BHJ) structure) has emerged. Here, we present a novel approach that by incorporating two polymer donors, PBDBT-DTBT and PTQ-2F, and one small-molecule acceptor, BTP-3-EH-4Cl, into the active layer with sequential deposition, we formed a device with nanometer-scale twin p-i-n structured active layer. The twin p-i-n PBDBT-DTBT:PTQ-2F/BTP-3-EH-4Cl device involved first depositing a PBDBT-DTBT:PTQ-2F blend under layer and then a BTP-3-EH-4Cl top layer and exhibited an improved power conversion efficiency (PCE) value of 18.6%, as compared to the 16.4% for the control BHJ PBDBT-DTBT:PTQ-2F:BTP-3-EH-4Cl device or 16.6% for the single p-i-n PBDBT-DTBT/BTP-3-EH-4Cl device. The PCE enhancement resulted mainly from the twin p-i-n active layer's multiple nanoscale charge carrier pathways that contributed to an improved fill factor and faster photocurrent generation based on transient absorption studies. The PBDBT-DTBT:PTQ-2F/BTP-3-EH-4Cl film possessed a vertical twin p-i-n morphology that was revealed through secondary ion mass spectrometry and synchrotron grazing-incidence small-angle X-ray scattering analyses. The thermal stability (T80) at 85 °C of the twin p-i-n PBDBT-DTBT:PTQ-2F/BTP-3-EH-4Cl device surpassed that of the single p-i-n PBDBT-DTBT/BTP-3-EH-4Cl devices (906 vs 196 h). This approach of providing a twin p-i-n structure in the active layer can lead to substantial enhancements in both the PCE and stability of organic photovoltaics, laying a solid foundation for future commercialization of the organic photovoltaics technology.

17.
Biomolecules ; 14(7)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39062525

RESUMEN

Peptide-based drug development is a promising direction due to its excellent biological activity, minimal immunogenicity, high in vivo stability, and efficient tissue penetrability. GV1001, an amphiphilic peptide, has proven effective as an anti-cancer vaccine, but its effect on osteoblast differentiation is unknown. To identify proteins interacting with GV1001, biotin-conjugated GV1001 was constructed and confirmed by mass spectrometry. Proteomic analyses were performed to determine GV1001's interaction with osteogenic proteins. GV1001 was highly associated with peptidyl-prolyl isomerase A and co-immunoprecipitation assays revealed that GV1001 bound to peptidyl-prolyl cis-trans isomerase 1 (Pin1). GV1001 significantly increased alkaline phosphatase (ALP) activity, bone nodule formation, and the expression of osteogenic gene markers. GV1001-induced osteogenic activity was enhanced by Pin1 overexpression and abolished by Pin1 knockdown. GV1001 increased the protein stability and transcriptional activity of Runx2 and Osterix. Importantly, GV1001 administration enhanced bone mass density in the OVX mouse model, as verified by µCT analysis. GV1001 demonstrated protective effects against bone loss in OVX mice by upregulating osteogenic differentiation via the Pin1-mediated protein stabilization of Runx2 and Osterix. GV1001 could be a potential candidate with anabolic effects for the prevention and treatment of osteoporosis.


Asunto(s)
Péptidos de Penetración Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Peptidilprolil Isomerasa de Interacción con NIMA , Osteogénesis , Factor de Transcripción Sp7 , Animales , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Osteogénesis/efectos de los fármacos , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Ratones , Péptidos de Penetración Celular/farmacología , Péptidos de Penetración Celular/química , Factor de Transcripción Sp7/metabolismo , Factor de Transcripción Sp7/genética , Humanos , Femenino , Estabilidad Proteica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/citología
18.
Plant Physiol Biochem ; 213: 108827, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38875779

RESUMEN

Salvia miltiorrhiza is a widely utilized medicinal herb in China. Its roots serve as crucial raw materials for multiple drugs. The root morphology is essential for the quality of this herb, but little is known about the molecular mechanism underlying the root development in S. miltiorrhiza. Previous study reveals that the polar auxin transport is critical for lateral root development in S. miltiorrhiza. Whether the auxin efflux carriers PIN-FORMEDs (PINs) are involved in this process is worthy investigation. In this study, we identified nine SmPIN genes in S. miltiorrhiza, and their chromosome localization, physico-chemical properties, and phylogenetic relationship were analyzed. SmPINs were unevenly distributed across four chromosomes, and a variety of hormone responsive elements were detected in their promoter regions. The SmPIN proteins were divided into three branches according to the phylogenetic relationship. SmPINs with close evolutionary distance showed similar conserved motif features. The nine SmPINs showed distinct tissue-specific expression patterns and most of them were auxin-inducible genes. We generated SmPIN3 overexpression S. miltiorrhiza seedlings to investigate the function of SmPIN3 in the root development in this species. The results demonstrated that SmPIN3 regulated the root morphogenesis of S. miltiorrhiza by simultaneously affecting the lateral root development and the root anatomical structure. The root morphology, patterns of root xylem and phloem as well as the expressions of genes in the auxin signaling pathway all altered in the SmPIN3 overexpression lines. Our findings provide new insights for elucidating the regulatory roles of SmPINs in the auxin-mediated root development in S. miltiorrhiza.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas , Raíces de Plantas , Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Salvia miltiorrhiza/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/anatomía & histología , Raíces de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Genes de Plantas
19.
Int Immunopharmacol ; 137: 112425, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38851160

RESUMEN

The production of superoxide anions and other reactive oxygen species (ROS) by neutrophils is necessary for host defense against microbes. However, excessive ROS production can induce cell damage that participates in the inflammatory response. Superoxide anions are produced by the phagocyte NADPH oxidase, a multicomponent enzyme system consisting of two transmembrane proteins (gp91phox/NOX2 and p22phox) and four soluble cytosolic proteins (p40phox, p47phox, p67phox and the small G proteins Rac1/2). Stimulation of neutrophils by various agonists, such as the bacterial peptide formyl-Met-Leu-Phe (fMLF), induces NADPH oxidase activation and superoxide production, a process that is enhanced by the pro-inflammatory cytokines such as GM-CSF. The pathways involved in this GM-CSF-induced up-regulation or priming are not fully understood. Here we show that GM-CSF induces the activation of the prolyl cis/trans isomerase Pin1 in human neutrophils. Juglone and PiB, two selective Pin1 inhibitors, were able to block GM-CSF-induced priming of ROS production by human neutrophils. Interestingly, GM-CSF induced Pin1 binding to phosphorylated p47phox at Ser345. Neutrophils isolated from synovial fluid of patients with rheumatoid arthritis are known to be primed. Here we show that Pin1 activity was also increased in these neutrophils and that Pin1 inhibitors effectively inhibited ROS hyperproduction by the same cells. These results suggest that the prolyl cis/trans isomerase Pin1 may control GM-CSF-induced priming of ROS production by neutrophils and priming of neutrophils in synovial fluid of rheumatoid arthritis patients. Pharmacological targeting of Pin1 may be a valuable approach to the treatment of inflammation.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos , NADPH Oxidasas , Peptidilprolil Isomerasa de Interacción con NIMA , Neutrófilos , Humanos , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Naftoquinonas/farmacología , Inflamación/inmunología , Células Cultivadas , Artritis Reumatoide/inmunología , Artritis Reumatoide/tratamiento farmacológico
20.
Alzheimers Dement ; 20(7): 4677-4691, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38829680

RESUMEN

INTRODUCTION: Individuals referred to as Non-Demented with Alzheimer's Neuropathology (NDAN) exhibit cognitive resilience despite presenting Alzheimer's disease (AD) histopathological signs. Investigating the mechanisms behind this resilience may unveil crucial insights into AD resistance. METHODS: DiI labeling technique was used to analyze dendritic spine morphology in control (CTRL), AD, and NDAN post mortem frontal cortex, particularly focusing on spine types near and far from amyloid beta (Aß) plaques. RESULTS: NDAN subjects displayed a higher spine density in regions distant from Aß plaques versus AD patients. In distal areas from the plaques, NDAN individuals exhibited more immature spines, while AD patients had a prevalence of mature spines. Additionally, our examination of levels of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), a protein associated with synaptic plasticity and AD, showed significantly lower expression in AD versus NDAN and CTRL. DISCUSSION: These results suggest that NDAN individuals undergo synaptic remodeling, potentially facilitated by Pin1, serving as a compensatory mechanism to preserve cognitive function despite AD pathology. HIGHLIGHTS: Spine density is reduced near Aß plaques compared to the distal area in CTRL, AD, and NDAN dendrites. NDAN shows higher spine density than AD in areas far from Aß plaques. Far from Aß plaques, NDAN has a higher density of immature spines, AD a higher density of mature spines. AD individuals show significantly lower levels of Pin1 compared to NDAN and CTRL.


Asunto(s)
Enfermedad de Alzheimer , Espinas Dendríticas , Humanos , Espinas Dendríticas/patología , Enfermedad de Alzheimer/patología , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Placa Amiloide/patología , Plasticidad Neuronal/fisiología , Cognición/fisiología , Lóbulo Frontal/patología
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