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1.
Ren Fail ; 46(2): 2365408, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38874119

RESUMEN

Podocyte loss in glomeruli is a fundamental event in the pathogenesis of chronic kidney diseases. Currently, mitotic catastrophe (MC) has emerged as the main cause of podocyte loss. However, the regulation of MC in podocytes has yet to be elucidated. The current work aimed to study the role and mechanism of p53 in regulating the MC of podocytes using adriamycin (ADR)-induced nephropathy. In vitro podocyte stimulation with ADR triggered the occurrence of MC, which was accompanied by hyperactivation of p53 and cyclin-dependent kinase (CDK1)/cyclin B1. The inhibition of p53 reversed ADR-evoked MC in podocytes and protected against podocyte injury and loss. Further investigation showed that p53 mediated the activation of CDK1/cyclin B1 by regulating the expression of Wee1. Restraining Wee1 abolished the regulatory effect of p53 inhibition on CDK1/cyclin B1 and rebooted MC in ADR-stimulated podocytes via p53 inhibition. In a mouse model of ADR nephropathy, the inhibition of p53 ameliorated proteinuria and podocyte injury. Moreover, the inhibition of p53 blocked the progression of MC in podocytes in ADR nephropathy mice through the regulation of the Wee1/CDK1/cyclin B1 axis. Our findings confirm that p53 contributes to MC in podocytes through regulation of the Wee1/CDK1/Cyclin B1 axis, which may represent a novel mechanism underlying podocyte injury and loss during the progression of chronic kidney disorder.


Asunto(s)
Proteína Quinasa CDC2 , Proteínas de Ciclo Celular , Ciclina B1 , Doxorrubicina , Mitosis , Podocitos , Proteínas Tirosina Quinasas , Proteína p53 Supresora de Tumor , Podocitos/metabolismo , Podocitos/patología , Animales , Proteína Quinasa CDC2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ratones , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Doxorrubicina/farmacología , Ciclina B1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino
2.
Br J Neurosurg ; 37(5): 1375-1378, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33491507

RESUMEN

OBJECTIVE: To evaluate the effectiveness and safety of microvascular decompression (MVD) using a fully transcranial neuroendoscopic approach. METHODS: Thirty-one patients who underwent MVD using a fully transcranial neuroendoscopic approach in our department between May 2016 and September 2019 were retrospectively reviewed. RESULTS: All patients successfully underwent MVD, and immediate pain relief was achieved in all 17 cases of trigeminal neuralgia (TGH) and 3 cases of glossopharyngeal neuralgia (GPN). Hemifacial spasm (HFS) was completely resolved in all 11 patients. No mortality or permanent complication was seen. CONCLUSIONS: The endoscope is a useful tool for confirming vascular conflict identified by the microscope and is helpful in detecting the vessel responsible for neuralgia without retracting the brain and nerves. MVD using a fully transcranial neuroendoscopic approach is an effective and safe alternative to endoscopic-assisted MVD and traditional MVD.


Asunto(s)
Enfermedades del Nervio Glosofaríngeo , Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Neuroendoscopía , Neuralgia del Trigémino , Humanos , Estudios Retrospectivos , Espasmo Hemifacial/cirugía , Neuralgia del Trigémino/cirugía , Resultado del Tratamiento
3.
BMC Neurol ; 22(1): 400, 2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-36324078

RESUMEN

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that involves damage to the peripheral nervous system. The course of the disease can progress for more than 8 weeks, with frequent incidences of relapse-remission courses. This article reported a rare combination of CIDP with fluctuating symptoms, recurrence-remission, and comorbidity with psoriasis. CASE PRESENTATION: A 29-year-old male patient with repeated limb weakness and numbness was admitted to the hospital several times in the past six months. He had a history of psoriasis for 6 years, and the medications (clobetasol propionate ointment and calcipotriol ointment) treated for psoriasis were discontinued 1 year ago. During the hospitalization, repeated intravenous injections of human immunoglobulin G (IVIg), immunoadsorption, and secukinumab were performed. Nerve electrophysiology tests, ganglioside autoantibody spectrum tests, and clinical MRC muscle strength scores were performed on a regular basis to confirm the diagnosis of CIDP. The patient was regularly followed up. RESULTS: After repeated rounds of human IVIg and immunoadsorption, the patient's MRC score was increased by ≥ 6 points. The first ganglioside autoantibody spectrum test showed anti-GQ1b IgG ( +) and anti-GM1 IgM ( +) antibodies, and all were negative after re-examination. Finally, the patient was treated with the IL-17A inhibitor secukinumab for psoriasis. During 7 months of follow-up, the CIDP and psoriasis symptoms are relatively stable. CONCLUSION: Combination of IVIg and immunoadsorption was highly effective in treating CIDP complicated with psoriasis. The clinical manifestations of CIDP are diverse. When relapse-remission occurs in the course of the disease, it is necessary to clarify whether it is combined with other autoimmune diseases and should control the autoimmune diseases as soon as possible.


Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Psoriasis , Masculino , Humanos , Adulto , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/complicaciones , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Inmunoglobulinas Intravenosas/uso terapéutico , Pomadas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunoglobulina G , Gangliósidos , Enfermedad Crónica , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Comorbilidad , Recurrencia
4.
Neurol Sci ; 43(7): 4547-4549, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35396637

RESUMEN

GNAL mutations (DYT25) have lately been identified as the firstly proven cause of focal adult-onset dystonia. We report here a new mutation in the GNAL gene in two siblings with dystonia. The new mutation is called NM 001,142,339:c.97C > T. Our research emphasizes the possible effects of new mutation on disease risk and the significance of genetic tests for GNAL mutations in confirming the molecular diagnosis.


Asunto(s)
Distonía , Trastornos Distónicos , Adulto , Distonía/genética , Trastornos Distónicos/genética , Subunidades alfa de la Proteína de Unión al GTP/genética , Pruebas Genéticas , Humanos , Mutación/genética
5.
Biochem Biophys Res Commun ; 544: 22-30, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33516878

RESUMEN

Hyperglycemia-induced podocyte damage contributes to the onset of diabetic nephropathy, a severe complication of diabetes. Perilipin 5 (Plin5) exerts a vital role in numerous pathological conditions via affecting cell apoptosis, oxidative stress, and inflammation. However, whether Plin5 plays a role in regulating podocyte damage of diabetic nephropathy has not been fully determined. This work aimed to explore the role of Plin5 in mediating high glucose (HG)-induced injury of podocytes in vitro. Our results demonstrated that Plin5 expression was markedly decreased in mouse podocytes challenged with HG. Plin5 overexpression markedly suppressed HG-induced apoptosis, reactive oxygen species (ROS) production, and the pro-inflammatory response in podocytes. On the contrary, Plin5 silencing produced the opposite effects. Further mechanistic analysis demonstrated that Plin5 upregulation remarkably increased the levels of phospho-Akt and phospho-glycogen synthase kinase-3ß (GSK-3ß) in HG-exposed podocytes. Moreover, Plin5 overexpression increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 signaling. Akt inhibition markedly blocked Plin5-mediated activation of Nrf2, while GSK-3ß inhibition reversed Plin5-silencing-induced suppressive effects on Nrf2 activation. Notably, Nrf2 suppression significantly blocked Plin5-mediated protective effects against HG-induced podocyte injury. In summary, our work indicates a vital role for Plin5 in protecting against HG-induced apoptosis, oxidative stress, and inflammation in podocytes via modulation of Akt/GSK-3ß/Nrf2 signaling. This study suggests that Plin5 may participate in modulating podocyte damage in diabetic nephropathy.


Asunto(s)
Apoptosis , Glucosa/toxicidad , Inflamación/tratamiento farmacológico , Enfermedades Renales/prevención & control , Estrés Oxidativo , Perilipina-5/farmacología , Podocitos/efectos de los fármacos , Animales , Células Cultivadas , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Inflamación/metabolismo , Inflamación/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Fosforilación , Podocitos/metabolismo , Podocitos/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Edulcorantes/toxicidad
6.
Clin Exp Pharmacol Physiol ; 47(3): 495-502, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31785117

RESUMEN

Renal ischaemia/reperfusion (I/R) is a major cause of acute renal failure with increased morbidity, mortality, and prolonged hospitalizations. Clematichinenoside (AR), a triterpenoid saponin isolated from the roots of Clematis chinensis, was reported to possess a protective effect against I/R injury. However, the effect of AR on renal I/R injury has not been evaluated. This study aims to examine the effect of AR on an in vitro I/R model in human proximal tubular epithelial cells HK-2. HK-2 cells were subjected to hypoxia/reoxygenation (H/R) stimulation to mimic I/R in vitro. The results showed that AR improved cell viability of H/R-stimulated HK-2 cells. AR pretreatment resulted in decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased in superoxide dismutase (SOD) activity in H/R-stimulated HK-2 cells. In addition, AR also presented an anti-inflammatory activity, as evidenced by decreased secretion of pro-inflammatory cytokines including IL-6, IL-1ß, and TNF-α. Moreover, apoptotic rate was markedly decreased in HK-2 cells pretreated with AR. The bax expression was decreased, while bcl-2 expression was increased by AR pretreatment. Furthermore, AR enhanced the H/R-stimulated activation of the Nrf2/HO-1 signalling pathway in HK-2 cells. In conclusion, these findings indicated that AR protected HK-2 cells from H/R-induced cell injury via regulating the Nrf2/HO-1 signalling pathway.


Asunto(s)
Células Epiteliales/metabolismo , Hemo-Oxigenasa 1/metabolismo , Túbulos Renales Proximales/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Saponinas/farmacología , Transducción de Señal/fisiología , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Epiteliales/efectos de los fármacos , Humanos , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
8.
Ann Diagn Pathol ; 34: 60-65, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29661730

RESUMEN

To explore the distribution of lymphoid neoplasms in Northwest China, the clinical and pathological data of lymphoma patients from 2006 to 2014 were analyzed according to the WHO classification in Xijing Hospital. Of the 3244 cases, mature B-cell neoplasms occupied 60.7%, while mature T/NK-cell neoplasms and Hodgkin's lymphomas (HL) occupied 26.2% and 8.1%, respectively. The most common subtype of lymphoma was diffuse large B-cell lymphoma (35.0%), followed by extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (12.9%) and marginal zone B-cell lymphoma (7.8%). Mixed cellularity (34.0%) was the most common subtype of HL. The especially high proportion of ENKTCL was the most outstanding feature of our study in comparison to previous reports. The mean age of all lymphoid neoplasms cases was 51years and most subtypes showed male predominance, with an average male-female ratio of 1.6. Extranodal lymphomas took up about 60% of all cases and gastrointestinal tract was the most frequently involved site. In conclusion, the distribution of lymphoid neoplasms of Northwest China showed some features similar to previous reports of China and other countries, but some subtypes presented distinct features.


Asunto(s)
Linfoma de Células B de la Zona Marginal/clasificación , Linfoma Extranodal de Células NK-T/clasificación , Linfoma de Células B Grandes Difuso/clasificación , Linfoma/clasificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Humanos , Lactante , Linfoma/epidemiología , Linfoma/patología , Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma de Células B de la Zona Marginal/patología , Linfoma Extranodal de Células NK-T/epidemiología , Linfoma Extranodal de Células NK-T/patología , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Prevalencia , Organización Mundial de la Salud , Adulto Joven
9.
J Phys Ther Sci ; 29(4): 737-743, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28533621

RESUMEN

[Purpose] To clarify the features associated with decrements in compound muscle action potentials (CMAP) during slow-rate repetitive nerve stimulation (RNS) of muscles involved in amyotrophic lateral sclerosis (ALS) in mainland China. [Subjects and Methods] A retrospective study of decremental responses to slow-rate RNS was performed to compare patients with ALS to those with myasthenia gravis (MG). [Results] A significant decrement (>5%) was observed in at least one muscle in 54% of ALS patients. The trapezius muscle was the most commonly affected (67%). In the ALS group, the CMAP amplitude evoked by the first stimulus was negatively correlated with the CMAP decrement in ulnar but not accessory nerves. Additionally, a positive decrement was associated with disease progression but not gender, age at onset, disease duration, region of onset, ALSFRS-R scores, or ALS diagnostic subgroup in ALS. Furthermore, the incidence of positive decrements and the decremental percentages were significantly higher in myasthenia gravis (MG) than in ALS. [Conclusions] The lower CMAP amplitude by the first RNS stimulus was more likely to induce a positive decrement in the ulnar nerve in ALS patients. The positive decremental responses to RNS observed in ALS indicate the faster progress of the disease, which is helpful for evaluating prognoses.

10.
J Phys Ther Sci ; 28(8): 2274-8, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27630413

RESUMEN

[Purpose] To prospectively assess the effectiveness of neutral wrist nocturnal splinting in patients with carpal tunnel syndrome (CTS) by using clinical scores and nerve conduction studies (NCS). [Subjects and Methods] Forty-one patients enrolled in the study were clinically evaluated by a symptom severity scale (SSS) and functional status scale (FSS), and were electrophysiologically evaluated by conventional NCS; distal motor latency (DML), sensory conduction velocity (SCV), and difference in sensory latency between the median and ulnar nerves (ΔDSL) were measured. Subjects were treated with wrist splinting. Patients who showed no improvement in symptoms were treated with other conservative treatments, the remaining patients continued to wear splints. SSS, FSS, and NCS were evaluated after splinting as well. [Results] The follow-up was completed in 20 patients (31 wrists) with splinting. SSS and FSS decreased, the DML shortened and ΔDSL decreased significantly after splinting for 3.03 ± 1.16 months. There were significant correlations between SSS and DML, SCV of wrist digit 2, and SCV of wrist digit 4. No correlations were found between SSS and ΔDSL, and FSS and the parameters of NCS. [Conclusion] Neutral wrist nocturnal splinting is effective in at least short term for CTS patients. There is a weak correlation between clinical scores and NCS, which suggests that both approaches should be used to effectively assess the therapeutic effect of CTS treatment.

11.
Mol Cell Probes ; 28(2-3): 91-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24177199

RESUMEN

Traditionally characterization of microbial proteins is performed by a complex sequence of steps with the final step to be either Edman sequencing or mass spectrometry, which generally takes several weeks or months to be complete. In this work, we proposed a strategy for the characterization of tryptic peptides derived from Giberella zeae (anamorph: Fusarium graminearum) proteins in parallel to intact cell mass spectrometry (ICMS) in which no complicated and time-consuming steps were needed. Experimentally, after a simple washing treatment of the spores, the aliquots of the intact G. zeae macro conidia spores solution, were deposited two times onto one MALDI (matrix-assisted laser desorption ionization) mass spectrometry (MS) target (two spots). One spot was used for ICMS and the second spot was subject to a brief on-target digestion with bead-immobilized or non-immobilized trypsin. Subsequently, one spot was analyzed immediately by MALDI MS in the linear mode (ICMS) whereas the second spot containing the digested material was investigated by MALDI MS in the reflectron mode ("peptide mass fingerprint") followed by protonated peptide selection for MS/MS (post source decay (PSD) fragment ion) analysis. Based on the formed fragment ions of selected tryptic peptides a complete or partial amino acid sequence was generated by manual de novo sequencing. These sequence data were used for homology search for protein identification. Finally four different peptides of varying abundances have been identified successfully allowing the verification that our desorbed/ionized surface compounds were indeed derived from proteins. The presence of three different proteins could be found unambiguously. Interestingly, one of these proteins is belonging to the ribosomal superfamily which indicates that not only surface-associated proteins were digested. This strategy minimized the amount of time and labor required for obtaining deeper information on spore preparations within the nowadays widely used ICMS approach.


Asunto(s)
Proteínas Fúngicas/metabolismo , Gibberella/metabolismo , Fragmentos de Péptidos/análisis , Esporas Fúngicas/metabolismo , Bases de Datos Genéticas , Proteínas Fúngicas/química , Gibberella/química , Gibberella/clasificación , Fragmentos de Péptidos/genética , Análisis de Secuencia de Proteína , Homología de Secuencia de Aminoácido , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Esporas Fúngicas/química , Tripsina
12.
Electrophoresis ; 34(13): 1957-64, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23595693

RESUMEN

Organelle-specific cell-permeable fluorescent dyes are invaluable tools in cell biology as they reveal intracellular dynamics in living cells. Mitrotracker is a family of dyes that strongly label the mitochondrion, a key organelle associated with many crucial cellular functions. Despite the popularity of these dyes, little is known about the molecular mechanism behind their staining specificity. Here, we aimed to identify the protein targets of one member of this dye family, mitotracker red (MTR), by 2DE and MS. MTR bound to cellular proteins covalently, and its fluorescence persisted even after cell lysis, protein solubilization, denaturation, and electrophoresis. This enabled us to display MTR-labeled proteins by 2DE. The MTR-specific fluorescent signals on the gel revealed the spots that contained MTR-conjugated proteins. These spots were analyzed by MS, resulting into the identification of ten proteins. We discovered that one major target is the mitochondrial protein HSP60 and that MTR staining could induce production of HSP60, predisposing cells to heat shock-like responses. The identification of the molecular targets of biological dyes, or "stainomics," can help correlate their intracellular staining properties with biochemical affinities. We believe this approach can be applied to a wide range of fluorescent probes.


Asunto(s)
Colorantes Fluorescentes/química , Proteínas Mitocondriales/análisis , Proteómica/métodos , Coloración y Etiquetado/métodos , Chaperonina 60/análisis , Chaperonina 60/química , Chaperonina 60/metabolismo , Electroforesis en Gel Bidimensional , Colorantes Fluorescentes/metabolismo , Células HeLa , Humanos , Microscopía Fluorescente , Proteínas Mitocondriales/química , Proteínas Mitocondriales/metabolismo
13.
Sci Total Environ ; 882: 163624, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37087000

RESUMEN

Water exchange unevenness (WEU) is defined as the coefficient of variation in water exchange intensity over time. Although its influence on aquatic plant characteristics has been recently investigated, there is limited understanding regarding the effects of this hydrodynamic change on submerged vegetation. This study investigated the impacts of WEU on the species dominance and community composition of submerged macrophytes in three bays with different WEU conditions in Erhai Lake, China. Subsequently, a laboratory experiment was conducted to elucidate the mechanisms underlying these effects. The field investigation showed that the dominance values of submerged macrophytes were influenced by WEU. As WEU decreased, the average dominance value decreased for Vallisneria natans (by 34.54 %), Myriophyllum spicatum (16.82 %), and Hydrilla verticillata (12.84 %); showed no significant change for Potamogeton lucens; and increased for Potamogeton maackianus (14.22 %) and Ceratophyllum demersum (17.52 %). The laboratory experiment showed that lower WEU markedly inhibited the growth of V. natans, slightly inhibited that of M. spicatum, and stimulated that of P. maackianus, consistent with the field observations. The inhibitory effect was attributed to a reduced concentration of carbon dioxide in the water; adaptive strategies, i.e., plant height, biomass allocation, and root traits, were more effective for M. spicatum than for V. natans. The stimulated growth of P. maackianus was attributed to increased dissolved oxygen concentration, which promoted root growth and nutrient uptake. Our results indicate that WEU has significant effects on the growth and community characteristics of submerged macrophytes.


Asunto(s)
Hydrocharitaceae , Potamogetonaceae , Lagos , Agua , Biomasa , Plantas , China
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 960-966, 2023.
Artículo en Zh | MEDLINE | ID: mdl-37551462

RESUMEN

AbstractObjective: To investigate the efficacy and safety of venetoclax-based induction chemotherapy in newly diagnosed (ND) patients ineligible for intensive therapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 51 newly diagnosed patients ineligible for intensive therapy and patients with R/R AML treated in the Department of Hematology of Xijing Hospital from February 1, 2021 to April 30, 2022 were retrospectively analyzed. The incidence of complete remission (CR)/CR with incomplete hematological recovery (CRi), objective remission rate (ORR), minimal residual disease (MRD) status, advense events (AE), overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: Among 51 patients, 32 patients were newly diagnosed patients unfit for intensive therapy, with a median age of 60 (29-88) years, and 19 patients were R/R patients, with a median age of 49 (22-92) years. The median cycles of VEN-based treatment in the two groups were both 2. The CR/CRi rates in the ND-AML and R/R-AML group after one course of induction treatment were 65.6% and 36.9%, respectively, and the ORR were 81.3% and 42.1%, respectively. The cumulative CR/CRi rates after 1-3 courses of VEN-based treatment were 71.9% and 47.4%, respectively. The MRD negativity rates of patients achieving CR/CRi were 69.6% and 33.3%, respectively. In the ND-AML and R/R-AML group, the median PFS were 8(5-11) and 3(1-5) months, and the median OS were 13 (6-20) and 5 (3-7) months, respectively. The median OS of patients achieving CR/CRi in both groups was significantly better than that of patients not achieving CR/CRi (13 months vs 4 months; OS not reached vs 4 months). During the first induction cycle, the incidence of grade 3 or higher granulocytopenia, anemia and thrombocytopenia was 96%, 90.2% and 84.3%, respectively. 30 patients (58.8%) had granulocytopenia with fever. The most common non-hematological AE was infection (12/51, 23.5%), followed by gastrointestinal symptoms (6/51, 11.8%). CONCLUSION: The VEN-based strategy has good treatment response and tolerance in newly diagnosed patients unfit for intensive therapy and R/R AML. The most common AEs are hematological toxicities and infection.

15.
Chembiochem ; 13(18): 2729-37, 2012 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-23148033

RESUMEN

We report the cellular properties of a luminescent cyclometalated iridium(III) complex, [Ir(pq)(2)(phen-ITC)](PF(6)) (Ir-ITC; Hpq=2-phenylquinoline, phen-ITC=5-isothiocyanate-1,10-phenanthroline), that efficiently and specifically labels mitochondria in living mammalian cells. Ir-ITC can be covalently conjugated to its protein targets, and its luminescence survived cell lysis, protein extraction, and gel electrophoresis under denaturing conditions. The conjugation of Ir-ITC with live-cell proteins is rapid and highly selective; the process requires active cellular metabolism, as the conjugation is abolished at nonphysiological temperature or in the presence of sodium azide. Based on measurements of the luminescence intensity, we have devised a biochemical fractionation procedure that allows the enrichment of the conjugated proteins, and their subsequent separation by two-dimensional gel electrophoresis (2DGE). Luminescent protein spots were picked from the gel and analyzed by mass spectrometry; this resulted in the identification of 46 proteins. Many of the strongly luminescently labeled proteins are mitochondrial proteins. One of the targets is VDAC1 (voltage-dependent anion channel 1). Consistent with known phenotypes of VDAC1 deregulation, prolonged exposure of cells to Ir-ITC led to significant mitochondrial shortening and fragmentation. As far as we know, this is the first report on the molecular characterization of the interactions of a luminescent dye with its biological targets. As many biological dyes exhibit specific intracellular staining patterns, the identification of their molecular targets can help elucidate the mechanisms behind their staining specificities and cytotoxicity. We believe our biochemical approach can be applied to identify the targets of a wide range of fluorescent and luminescent probes.


Asunto(s)
Complejos de Coordinación/metabolismo , Complejos de Coordinación/farmacología , Iridio/química , Sustancias Luminiscentes/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Compuestos Organometálicos/metabolismo , Compuestos Organometálicos/farmacología , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Células 3T3 , Animales , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/toxicidad , Ratones , Compuestos Organometálicos/química , Compuestos Organometálicos/toxicidad , Unión Proteica , Proteómica , Especificidad por Sustrato
16.
Int J Mol Sci ; 13(9): 11063-11070, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23109838

RESUMEN

Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.


Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergillus fumigatus/aislamiento & purificación , Equinocandinas/uso terapéutico , Hígado/microbiología , Anemia Aplásica/complicaciones , Aspergilosis/complicaciones , Aspergilosis/diagnóstico , Caspofungina , Femenino , Humanos , Lipopéptidos , Hígado/diagnóstico por imagen , Persona de Mediana Edad , Radiografía
17.
J Mov Disord ; 15(3): 197-205, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35880382

RESUMEN

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington's Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

18.
Front Oncol ; 12: 938550, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36185185

RESUMEN

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

19.
Analyst ; 136(24): 5181-9, 2011 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-22059228

RESUMEN

Detection of cell death has extensive applications and is of great commercial value. However, most current high-throughput cell viability assays cannot distinguish the two major forms of cell death: apoptosis and necrosis. Many apoptosis-specific detection methods exist but they are time consuming and labour intensive. In this work, we proposed a novel approach based on Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) for the specific detection of apoptosis in cultured mammalian cells. Buffer washed cells were directly mixed with a matrix solution and subsequently deposited onto the stainless steel target for MALDI analysis. The resulting mass spectrometric profiles were highly reproducible and can be used to reflect cell viability. Remarkably, the mass spectrometric profiles generated from apoptotic cells were distinct from those from either normal or necrotic cells. The apoptosis-specific features of the mass spectra were proportional to the percentage of apoptotic cells in the culture, but are independent of the drugs used to stimulate apoptosis. This is the first report on the utilization of intact cell MALDI mass spectrometry in detecting mammalian cell apoptosis, and can be used as a basis for the development of a reliable, fast, label-free and high-throughput method for detecting apoptotic cell death.


Asunto(s)
Apoptosis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Animales , Camptotecina/toxicidad , Línea Celular , Diterpenos/toxicidad , Perros , Etopósido/toxicidad , Humanos , Ratones , Propidio/química
20.
Neuropsychiatr Dis Treat ; 17: 2707-2711, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34429606

RESUMEN

OBJECTIVE: To evaluate the improvement of motor, anxiety, and depression in patients with blepharospasm with the use of botulinum toxin type A (BTX-A) and repetitive transcranial magnetic stimulation (rTMS). METHODS: A total of 63 BEB patients accompanied by anxiety/depression were enrolled, among which 28 patients were treated with the injection of botulinum toxin type A (BTX-A) alone, while 35 patients were treated with BTX-A injection combined with rTMS. All patients were followed up for 6 months, and the overall efficacy was evaluated. RESULTS: BTX-A alone treatment and combined rTMS treatment could both significantly improve the symptoms of patients, and the effective rate was 92.86% and 94.29%, respectively. The duration of efficacy was significantly longer in the combined rTMS treatment group (16.89±3.39 weeks) than in BTX-A treatment group (13.04±3.48 weeks). After treatment, SDS score of BTX-A treatment group and combined rTMS treatment group was 49.69±7.90 and 49.46±6.73, respectively, and there was no significant difference between the two treatment groups; SAS score of BTX-A treatment group and combined rTMS treatment group was 53.88±7.34 and 48.79±6.62, respectively, and there was significant difference between the two treatment groups. CONCLUSION: Compared to BTX-A alone treatment, BTX-A combined with rTMS can effectively improve the effect of BTX-A, prolong the duration of blepharospasm relief, and significantly reduce depression and anxiety in patients with BEB.

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