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1.
Apoptosis ; 29(5-6): 620-634, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38281282

RESUMEN

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.


Asunto(s)
Lesión Renal Aguda , Apoptosis , Maleatos , Ratones Endogámicos C57BL , Mitocondrias , ATPasas de Translocación de Protón Mitocondriales , Animales , Humanos , Masculino , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Apoptosis/efectos de los fármacos , Línea Celular , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , ATPasas de Translocación de Protón Mitocondriales/metabolismo , ATPasas de Translocación de Protón Mitocondriales/genética , Especies Reactivas de Oxígeno/metabolismo
2.
J Med Ultrasound ; 31(3): 171-177, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025006

RESUMEN

Poststroke spasticity (PSS) is a common complication that affects function and daily self-care. Conservative PSS treatments include traditional rehabilitation, botulinum toxin injection, and extracorporeal shock wave therapy. Currently, the Modified Ashworth Scale and Modified Tardieu Scale are widely used tools to clinically evaluate spasticity, but the best tool for PSS assessment remained controversial. Ultrasound elastography (UE), including shear wave and strain image as the emerging method to evaluate soft tissue elasticity, became popular in clinical applications. Spastic biceps and gastrocnemius muscles were reported to be significantly stiffer compared to nonparetic muscles or healthy control using shear wave or strain elastography. More studies investigated the utility, reliability, and validity of UE in patients with PSS, but the contemporary consensus for the utility of UE in the measurement and therapeutic follow-up of PSS remained lacking. Therefore, this narrative review aimed to appraise the literature on the shear wave and strain elastography on PSS and summarize the roles of UE in assessing the therapeutic efficacy of different PSS interventions.

3.
J Am Acad Dermatol ; 86(4): 748-757, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34547358

RESUMEN

BACKGROUND: Among patients in the United States with psoriasis (PsO), limited data exist on the incidence and prevalence of psoriatic arthritis (PsA) based on disease severity. OBJECTIVE: To assess the incidence, prevalence, and predictors of PsA among patients with PsO stratified by PsO severity using treatment type. METHODS: Incidence of PsA per 100 PsO patient-years (PY) and prevalence were assessed using the Optum electronic health records database. Incidence was assessed from PsO diagnosis and 1 year after PsO diagnosis overall and stratified by mutually exclusive treatment classes as a severity surrogate. RESULTS: The overall incidence of PsA was 2.9 (95% CI, 2.9-3.0) events per 100 PY. The incidence (95% CI) by severity surrogate was 2.1 (2.1-2.1), 9.9 (9.5-10.4), and 17.6 (16.9-18.3) events per 100 PY for patients with mild, moderate, and severe PsO as determined by receiving nonsystemics, nonbiologic systemic therapy, and biologics, respectively. When excluding patients diagnosed with PsA 1 year after PsO diagnosis, overall incidence was lower (1.7 [95% CI, 1.6-1.7] events per 100 PY), with similar trends for treatment-severity surrogates. LIMITATIONS: Results may not be generalizable to a wider population. CONCLUSION: The risk of developing PsA increased with disease severity and was highest in patients with the most severe PsO.


Asunto(s)
Artritis Psoriásica , Psoriasis , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/epidemiología , Artritis Psoriásica/terapia , Registros Electrónicos de Salud , Humanos , Incidencia , Prevalencia , Psoriasis/diagnóstico , Psoriasis/epidemiología , Psoriasis/terapia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología
4.
Medicina (Kaunas) ; 58(3)2022 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-35334626

RESUMEN

A thyroid storm is an extreme manifestation of thyrotoxicosis, and is life threatening without an early diagnosis. Pregnancy or childbirth may worsen maternal hyperthyroidism or induce the development of a thyroid storm. Gestational hypertension, a disorder defined as new-onset hypertension, develops after 20 weeks of gestation and shares symptoms with a thyroid storm. The diagnosis of a thyroid storm may be challenging in patients with gestational hypertension. To highlight the significance of early thyrotoxicosis-related gastrointestinal symptoms, we report a case of a 38-year-old woman with a twin pregnancy, who was diagnosed with gestational hypertension, and then developed a thyroid storm during the peripartum period. She complained of nausea and abdominal pain, followed by tachycardia, hypertension, and a disturbance of consciousness with desaturation. After emergency caesarean section, fever, diarrhea, and high-output heart failure, with pulmonary edema, were noted during the postoperative period in the intensive care unit. The diagnosis of a thyroid storm was confirmed using the Burch-Wartofsky point scale, which was 75 points. In this patient, the uncommon gastrointestinal symptoms, as initial manifestations of thyrotoxicosis, indicated the development of a thyroid storm. The distinguished presentation of thyrotoxicosis-induced cardiomyopathy and peripartum cardiomyopathy also helped in the differential diagnosis between a thyroid storm and gestational hypertension. Aggressive treatment for thyrotoxicosis should not be delayed because of a missed diagnosis.


Asunto(s)
Cardiomiopatías , Hipertensión Inducida en el Embarazo , Crisis Tiroidea , Tirotoxicosis , Adulto , Cardiomiopatías/complicaciones , Cesárea/efectos adversos , Femenino , Humanos , Embarazo , Crisis Tiroidea/complicaciones , Crisis Tiroidea/diagnóstico , Tirotoxicosis/complicaciones
5.
Nano Lett ; 20(10): 7405-7412, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-32915579

RESUMEN

Iron oxide nanorings have great promise for biomedical applications because of their magnetic vortex state, which endows them with a low remanent magnetization while retaining a large saturation magnetization. Here we use micromagnetic simulations to predict the exact shapes that can sustain magnetic vortices, using a toroidal model geometry with variable diameter, ring thickness, and ring eccentricity. Our model phase diagram is then compared with simulations of experimental geometries obtained by electron tomography. High axial eccentricity and low ring thickness are found to be key factors for forming vortex states and avoiding net-magnetized metastable states. We also find that while defects from a perfect toroidal geometry increase the stray field associated with the vortex state, they can also make the vortex state more energetically accessible. These results constitute an important step toward optimizing the magnetic behavior of toroidal iron oxide nanoparticles.

6.
BMC Bioinformatics ; 21(Suppl 13): 389, 2020 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-32938376

RESUMEN

BACKGROUND: MicroRNAs (miRNAs) play a key role in mediating the action of insulin on cell growth and the development of diabetes. However, few studies have been conducted to provide a comprehensive overview of the miRNA-mediated signaling network in response to glucose in pancreatic beta cells. In our study, we established a computational framework integrating multi-omics profiles analyses, including RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) data analysis, inverse expression pattern analysis, public data integration, and miRNA targets prediction to illustrate the miRNA-mediated regulatory network at different glucose concentrations in INS-1 pancreatic beta cells (INS-1), which display important characteristics of the pancreatic beta cells. RESULTS: We applied our computational framework to the expression profiles of miRNA/mRNA of INS-1, at different glucose concentrations. A total of 1437 differentially expressed genes (DEGs) and 153 differentially expressed miRNAs (DEmiRs) were identified from multi-omics profiles. In particular, 121 DEmiRs putatively regulated a total of 237 DEGs involved in glucose metabolism, fatty acid oxidation, ion channels, exocytosis, homeostasis, and insulin gene regulation. Moreover, Argonaute 2 immunoprecipitation sequencing, qRT-PCR, and luciferase assay identified Crem, Fn1, and Stc1 are direct targets of miR-146b and elucidated that miR-146b acted as a potential regulator and promising target to understand the insulin signaling network. CONCLUSIONS: In this study, the integration of experimentally verified data with system biology framework extracts the miRNA network for exploring potential insulin-associated miRNA and their target genes. The findings offer a potentially significant effect on the understanding of miRNA-mediated insulin signaling network in the development and progression of pancreatic diabetes.


Asunto(s)
Regulación de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Insulina/metabolismo , MicroARNs/genética , Humanos , Transducción de Señal
7.
Int J Mol Sci ; 21(8)2020 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-32326191

RESUMEN

BACKGROUND: Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the economy in our society. Current treatments, such as the use of thrombolytic agents, are often limited by a narrow therapeutic time window. However, the regeneration of the brain after damage is still active days, even weeks, after stroke occurs, which might provide a second window for treatment. Emodin, a traditional Chinese medicinal herb widely used to treat acute hepatitis, has been reported to possess antioxidative capabilities and protective effects against myocardial ischemia/reperfusion injury. However, the underlying mechanisms and neuroprotective functions of Emodin in a rat middle cerebral artery occlusion (MCAO) model of ischemic stroke remain unknown. This study investigates neuroprotective effects of Emodin in ischemia both in vitro and in vivo. METHODS: PC12 cells were exposed to oxygen-glucose deprivation to simulate hypoxic injury, and the involved signaling pathways and results of Emodin treatment were evaluated. The therapeutic effects of Emodin in ischemia animals were further investigated. RESULTS: Emodin reduced infarct volume and cell death following focal cerebral ischemia injury. Emodin treatment restored PC12 cell viability and reduced reactive oxygen species (ROS) production and glutamate release under conditions of ischemia/hypoxia. Emodin increased Bcl-2 and glutamate transporter-1 (GLT-l) expression but suppressed activated-caspase 3 levels through activating the extracellular signal-regulated kinase (ERK)-1/2 signaling pathway. CONCLUSION: Emodin induced Bcl-2 and GLT-1 expression to inhibit neuronal apoptosis and ROS generation while reducing glutamate toxicity via the ERK-1/2 signaling pathway. Furthermore, Emodin alleviated nerve cell injury following ischemia/reperfusion in a rat MCAO model. Emodin has neuroprotective effects against ischemia/reperfusion injury both in vitro and in vivo, which may be through activating the ERK-1/2 signaling pathway.


Asunto(s)
Emodina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Animales , Biomarcadores , Supervivencia Celular , Susceptibilidad a Enfermedades , Hipoxia/metabolismo , Inmunohistoquímica , Células PC12 , Ratas , Daño por Reperfusión/tratamiento farmacológico
8.
Int J Mol Sci ; 20(20)2019 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-31600973

RESUMEN

Anemia is a severe complication in patients with chronic kidney disease (CKD). Treatment with exogenous erythropoietin (EPO) can correct anemia in many with CKD. We produced 5/6-nephrectomized rats that became uremic and anemic at 25 days post surgery. Injection of the anemic 5/6-nephrectomized rats with 2.8 mg zinc/kg body weight raised their red blood cell (RBC) levels from approximately 85% of the control to 95% in one day and continued for 4 days. We compared the effect of ZnSO4 and recombinant human erythropoietin (rHuEPO) injections on relieving anemia in 5/6-nephrectomized rats. After three consecutive injections, both the ZnSO4 and rHuEPO groups had significantly higher RBC levels (98 ± 6% and 102 ± 6% of the control) than the saline group (90 ± 3% of the control). In vivo, zinc relieved anemia in 5/6-nephrectomized rats similar to rHuEPO. In vitro, we cultured rat bone marrow cells supplemented with ZnCl2, rHuEPO, or saline. In a 4-day suspension culture, we found that zinc induced erythropoiesis similar to rHuEPO. When rat bone marrow cells were supplement-cultured with zinc, we found that zinc stimulated the production of EPO in the culture medium and that the level of EPO produced was dependent on the concentration of zinc supplemented. The production of EPO via zinc supplementation was involved in the process of erythropoiesis.


Asunto(s)
Anemia/etiología , Suplementos Dietéticos , Eritropoyetina/farmacología , Proteínas Recombinantes/farmacología , Insuficiencia Renal Crónica/complicaciones , Zinc/administración & dosificación , Anemia/sangre , Anemia/tratamiento farmacológico , Animales , Biomarcadores , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Índices de Eritrocitos/efectos de los fármacos , Eritropoyesis/efectos de los fármacos , Humanos , Ratas , Sulfato de Zinc/administración & dosificación
9.
J Immunol ; 196(4): 1449-54, 2016 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-26792802

RESUMEN

Type 1 innate lymphocytes comprise two developmentally divergent lineages, type 1 helper innate lymphoid cells (hILC1s) and conventional NK cells (cNKs). All type 1 innate lymphocytes (ILCs) express the transcription factor T-bet, but cNKs additionally express Eomesodermin (Eomes). We show that deletion of Eomes alleles at the onset of type 1 ILC maturation using NKp46-Cre imposes a substantial block in cNK development. Formation of the entire lymphoid and nonlymphoid type 1 ILC compartment appears to require the semiredundant action of both T-bet and Eomes. To determine if Eomes is sufficient to redirect hILC1 development to a cNK fate, we generated transgenic mice that express Eomes when and where T-bet is expressed using Tbx21 locus control to drive expression of Eomes codons. Ectopic Eomes induces cNK-like properties across the lymphoid and nonlymphoid type 1 ILC compartments. Subsequent to their divergent lineage specification, hILC1s and cNKs thus possess substantial developmental plasticity.


Asunto(s)
Células Asesinas Naturales/inmunología , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Animales , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular , Linaje de la Célula , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Ratones Transgénicos , Células TH1/inmunología
10.
J Nanosci Nanotechnol ; 18(5): 3606-3612, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29442873

RESUMEN

The differences between the macroscopic and microscopic magnetic properties of granular, rod, and tubular nano-maghemites were studied. The macroscopic magnetic properties of the different nano-maghemites were all ferrimagnetic by using a superconducting quantum interference device (SQUID). However, the coercive magnetic field and magnetization per unit volume were both in the orders of grain > tube > rod, which indicated that the crystal shape influenced macroscopic magnetic properties. A magnetic force microscope (MFM) was used to observe the microscopic magnetic structures; the samples were all magnetic in multiple domains, but the form and distribution of these domains were different. However, the domain information of nano-maghemites calculated from SQUID results suggested that all specimens were pseudo-single domains. The MFM results suggested that the crystal morphology had a significant effect on magnetic properties of these nano-maghemites owing to their different magnetic domain structures. Therefore, MFM can be used to detect minute magnetic-properties that are imperceptible to macroscopic measurements. Thus, it is a tool with potential development in earth science.

11.
Int J Mol Sci ; 19(9)2018 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-30231592

RESUMEN

In rats, mice, and humans, it is known that zinc deficiency may be related to anemia, and zinc supplementation influences hemoglobin production. Our previous studies indicate that in fish, zinc supplementation stimulates red blood cell (RBC) formation (erythropoiesis). However, it is not clear whether the mechanism of zinc-induced erythropoiesis stimulation in fish also occurs in rats. We induced anemia in rats using phenylhydrazine (PHZ) and injected either saline or ZnSO4 solution. We found that an appropriate amount of zinc stimulated erythropoiesis in the PHZ-induced anemic rats. The effects of ZnSO4 injection were dose-dependent. When the concentration of ZnSO4 was higher than 2.8 mg zinc/kg body weight, the RBC level of the anemic rats increased from 60 ± 7% to 88 ± 10% that of the normal rats in two days. Rat bone marrow cells with or without ZnCl2 supplementation were cultured in suspension in vitro. In the cell culture when the zinc concentration was at 0.3 mM, a 1.6-fold proliferation of nascent immature reticulocytes (new RBCs) was observed after one day. In the rat blood, zinc was combined with serum transferrin to induce erythropoiesis. The stimulation of RBC formation by zinc appears to be common among different animals.


Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyesis/efectos de los fármacos , Sulfato de Zinc/uso terapéutico , Zinc/uso terapéutico , Anemia/sangre , Anemia/inducido químicamente , Animales , Células Cultivadas , Cloruros/administración & dosificación , Cloruros/uso terapéutico , Eritrocitos/efectos de los fármacos , Masculino , Fenilhidrazinas , Ratas , Ratas Sprague-Dawley , Reticulocitos/efectos de los fármacos , Bazo , Zinc/administración & dosificación , Compuestos de Zinc/administración & dosificación , Compuestos de Zinc/uso terapéutico , Sulfato de Zinc/administración & dosificación
12.
Int J Mol Sci ; 19(8)2018 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-30096859

RESUMEN

Feed-forward loops (FFLs) represent an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs, such as araBAD and araFGH operons and adapts to fluctuating environmental nutrients, thereby enhancing the survivability of E. coli. Although computational simulations have been conducted to explore the potential functionality of FFLs, a comprehensive study on the functions of all structural types on the basis of in vivo data is lacking. Moreover, the regulatory role of CRP-mediated FFLs (CRP-FFLs) remains obscure. We identified 393 CRP-FFLs in E. coli using EcoCyc and RegulonDB. Dose⁻response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, which were further divided into five functional groups. The microarray and reported regulatory relationships identified 202 CRP-FFLs that were directly regulated by CRP in these eight types of FFLs. Interestingly, 34% (147/432) of genes were directly regulated by CRP and CRP-regulated TFs, which indicates that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs.


Asunto(s)
Proteína Receptora de AMP Cíclico/genética , AMP Cíclico/genética , Transcripción Genética , Proteína Receptora de AMP Cíclico/metabolismo , Escherichia coli/genética , Dosificación de Gen/genética , Regulación Bacteriana de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes/genética , Genoma Bacteriano/genética , MicroARNs/genética , Anotación de Secuencia Molecular , Análisis por Matrices de Proteínas
13.
Int J Mol Sci ; 19(10)2018 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-30347766

RESUMEN

Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer's disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.


Asunto(s)
Antioxidantes/farmacología , Apoptosis , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Talidomida/análogos & derivados , Animales , Células Cultivadas , Corteza Cerebral/citología , Peróxido de Hidrógeno/toxicidad , Neuronas/metabolismo , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Talidomida/farmacología
14.
Int J Mol Sci ; 19(4)2018 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-29641447

RESUMEN

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development.


Asunto(s)
Antiparkinsonianos/uso terapéutico , Incretinas/uso terapéutico , Trastornos Parkinsonianos/tratamiento farmacológico , Animales , Antiparkinsonianos/administración & dosificación , Incretinas/administración & dosificación , Locomoción , Masculino , Oxidopamina/toxicidad , Trastornos Parkinsonianos/etiología , Ratas , Ratas Sprague-Dawley
15.
Int J Mol Sci ; 18(1)2017 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-28085070

RESUMEN

The common carp can tolerate extremely low oxygen levels. These fish store zinc in a specific zinc-binding protein presented in digestive tract tissues, and under low oxygen, the stored zinc is released and used as a signal to stimulate erythropoiesis (red blood cell formation). To determine whether the environmental supply of zinc to other fish species can serve as a signal to induce erythropoiesis as in the common carp, head kidney cells of four different fish species were cultured with supplemental ZnCl2. Zinc stimulated approximately a three-fold increase in immature red blood cells (RBCs) in one day. The stimulation of erythropoiesis by zinc was dose-dependent. ZnSO4 solution was injected into an experimental blood loss tilapia model. Blood analysis and microscopic observation of the blood cells indicated that, in vivo, the presence of additional zinc induced erythropoiesis in the bled tilapia. In the fish species studied, zinc could be used as a signal to stimulate erythropoiesis both in vitro and in vivo. The present report suggests a possible approach for the induction of red blood cell formation in animals through the supply of a certain level of zinc through either diet or injection.


Asunto(s)
Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritropoyesis/efectos de los fármacos , Peces , Zinc/farmacología , Animales , Carpas , Células Cultivadas , Cloruros/farmacología , Eritrocitos/metabolismo , Compuestos de Zinc/farmacología
16.
Mol Microbiol ; 92(5): 1072-91, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24720807

RESUMEN

The CRISPR/Cas system is an important aspect in bacterial immunology. The anti-phage activity of the CRISPR system has been established using synthetic CRISPR spacers, but in vivo studies of endogenous CRISPR spacers are relatively scarce. Here, we showed that bacteriophage P1 titre in Escherichia coli decreased in the glucose-containing medium compared with that in the absence of glucose. This glucose effect of E. coli against phage P1 infection disappeared in cse3 deletion mutants. The effect on the susceptibility to phage P1 was associated with cAMP receptor protein (CRP)-mediated repression of cas genes transcription and crRNA maturation. Analysis of the regulatory element in the cse1 promoter region revealed a novel CRP binding site, which overlapped with a LeuO binding site. Furthermore, the limited sequence identity between endogenous spacers and the phage P1 genome was necessary and sufficient for CRISPR-mediated repression of phage P1 replication. Trans-expression of the third and seventh spacers in the CRISPR I region or third and sixth spacers in the CRISPR II region effectively reduced phage P1 titres in the CRISPR deletion mutants. These results demonstrate a novel regulatory mechanism for cas repression by CRP and provide evidence that endogenous spacers can repress phage P1 replication in E. coli.


Asunto(s)
Bacteriófago P1/fisiología , Sistemas CRISPR-Cas/fisiología , Proteína Receptora de AMP Cíclico/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Sistemas CRISPR-Cas/genética , Proteína Receptora de AMP Cíclico/genética , Escherichia coli/virología , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/genética , Regulación Bacteriana de la Expresión Génica/fisiología , Replicación Viral
17.
J Manipulative Physiol Ther ; 38(8): 581-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26391236

RESUMEN

OBJECTIVE: The purposes of this study were (1) to establish the intrarater sliding and change in thickness of the transversus abdominis (TrA) measurement at the posterior muscle-fascia junction and (2) to examine the relationship between the muscle thickness and sliding of the TrA at the anterior and posterior sites. METHODS: Asymptomatic participants (n = 20) were placed into the hook-lying position to perform the abdominal drawing-in maneuver viewed in B-mode with a 5- to 12-MHz linear ultrasound transducer. The outcome variables included the resting thickness, the thickness during contraction, the change of thickness, and the change of sliding length. Both intraclass correlation coefficient and Pearson correlation were used for analysis. RESULTS: Measuring the thickness and sliding of the TrA at the posterior muscle-fascia junction showed good reliability (intraclass correlation coefficient (3,3), 0.89-0.98). The correlations between the sliding measurements of the TrA at the anterior and posterior sites were moderate to good (r = 0.41-0.74). CONCLUSION: This study found that measuring the musculofascial corset from the posterior site using ultrasonography is reliable, allowing for ultrasound measurements at both the anterior and posterior sites of the TrA to provide a comprehensive evaluation of the TrA fascia.


Asunto(s)
Músculos Abdominales/anatomía & histología , Músculos Abdominales/diagnóstico por imagen , Adulto , Fascia/anatomía & histología , Fascia/diagnóstico por imagen , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Ultrasonografía
18.
Artículo en Inglés | MEDLINE | ID: mdl-23665074

RESUMEN

The common carp is one of the few fish able to tolerate extremely low oxygen levels. These fish store zinc in their digestive tract tissue and head kidney at concentrations of 300-500µg/g of fresh tissue, which is 5-10 times higher than in other fish. Previous studies have indicated a link between the high zinc levels in the common carp and stress erythropoiesis. In this report, using suspension-cultured common carp head kidney cells with or without ZnCl2 supplementation, we found that zinc stimulated the proliferation of immature red blood cells; however, this effect was only observed when the culture was supplemented with carp serum. We identified the active component of carp serum to be transferrin. The zinc-transferrin complex interacts with the transferrin receptor and stimulates the proliferation of immature red blood cells. In addition, the growth rate of the immature red blood cells was regulated by the supplied ZnCl2 concentration. Under stress, the zinc in the common carp digestive tract tissue was released and used as a signal to induce red blood cell formation in the head kidney. This cell culture system might provide a means for exploring the regulatory role of zinc in hematopoietic cell growth.


Asunto(s)
Carpas/metabolismo , Eritrocitos/metabolismo , Riñón Cefálico/metabolismo , Transferrina/metabolismo , Zinc/metabolismo , Animales , Carpas/sangre , Proliferación Celular/efectos de los fármacos , Separación Celular , Células Cultivadas , Cloruros/farmacología , Compuestos Férricos/farmacología , Técnica del Anticuerpo Fluorescente , Riñón Cefálico/citología , Riñón Cefálico/efectos de los fármacos , Receptores de Transferrina/metabolismo , Coloración y Etiquetado , Suspensiones , Compuestos de Zinc/farmacología
19.
PLoS One ; 18(10): e0292537, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37815994

RESUMEN

In cut flowers, xylem occlusion or blockage by bacteria negatively affects water balance and postharvest quality. Many studies have used culture-based methods to examine bacterial populations in vase water and their effects on flower longevity. It is still unclear if and how bacterial communities at the 16S rRNA gene (16S) level change during the vase period and how such change might correlate with postharvest longevity. This study compared the sequences of 16S amplicons from 4 different types of flowers and their vase water over the course of 7 days (Rosa spp., Gerbera jamesonii, and two Lilium varieties). The relative abundance of plant chloroplast and mitochondria 16S decreased significantly over the course 7 days in all 4 flowers as bacterial diversity increased. Richness and evenness of the bacterial communities increased over time, as did the number of rare taxa and phylogenetic diversity. Bacterial communities varied with time, as well as by flower source, types, and sample location (water, stem surface, whole stem). Some taxa, such as Enterobacteriacea and Bradyhizobiaceae decreased significantly over time while others such as Pseudomonas spp. increased. For example, Pseudomonas veronii, implicated in soft rot of calla lily, increased in both whole stem samples and water samples from Gerbera jamesonii. Erwinia spp., which includes plant pathogenic species, also increased in water samples. This work highlights the dynamic and complex nature of bacterial succession in the flower vase ecosystem. More work is needed to understand if and how bacterial community structure can be managed to improve cut flower vase life.


Asunto(s)
Asteraceae , Agua , ARN Ribosómico 16S/genética , Filogenia , Ecosistema , Flores , Bacterias/genética
20.
Nutrients ; 15(21)2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37960326

RESUMEN

This study investigates the impact of various zinc supplementation methods on anemia in rats induced by phenylhydrazine (PHZ) and in 5/6-nephrectomized anemic rats. We compare oral zinc sulfate (ZnSO4) supplementation, oyster Crassostrea gigas supplementation, and hard clam Meretrix lusoria supplementation on red blood cell (RBC) levels. Oral zinc-rich oyster supplementation (2.70 mg Zn (30 g oyster)/day/rat) effectively corrects anemia in both experimental groups. Rats orally fed oysters for four days exhibit similar effectiveness as those receiving a single ZnSO4 injection (0.95 mg Zn (4.18 mg ZnSO4⋅7H2O)/rat). In contrast, oral ZnSO4 supplementation (2.70 mg Zn (11.88 mg ZnSO4⋅7H2O)/day/rat) does not significantly increase RBC levels, suggesting better zinc absorption from oysters. A placebo group of anemic rats supplemented with hard clams, similar in composition to oysters but much lower in zinc, did not change RBC counts. This supports oysters' high zinc content as the key to correcting anemia. Oysters also contain high iron levels, offering a potential solution for iron-deficiency anemia while supporting bone marrow erythropoiesis. In summary, oral oyster supplementation emerges as an effective strategy to correct anemia in rats with added zinc and iron support for erythropoiesis.


Asunto(s)
Anemia , Crassostrea , Ratas , Animales , Zinc , Anemia/tratamiento farmacológico , Suplementos Dietéticos , Hierro/uso terapéutico
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