RESUMEN
MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes.
Asunto(s)
Epigénesis Genética , Humanos , AnimalesRESUMEN
BACKGROUND: Modular prosthesis fracture, especially distal femoral fracture, is a rare complication of total hip arthroplasty (THA). However, it is catastrophic, and may have a serious impact on the patients. A distal femoral prosthesis fracture in a patient with developmental dysplasia of the hip (DDH) with nonunion at the subtrochanteric osteotomy site has not yet been reported in any literature. This report presents the first such case, with a purpose of analyzing the causes of modular prosthesis fractures and nonunion of the osteotomy area, so as to provide orthopedic surgeons with experience and lessons. CASE PRESENTATION: We report the case of a 52-year-old woman with the distal femoral prosthesis fracture after THA and subtrochanteric osteotomy for Crowe type IV DDH. The patient had severe pain in the left thigh and her activities were limited. Plain radiographs revealed fracture of the left distal femoral prosthesis and nonunion in the subtrochanteric osteotomy region of the left femur. After a revision of the THA, the patient's symptoms were resolved. CONCLUSIONS: A prosthesis fracture combined with nonunion at the subtrochanteric osteotomy site is a rare complication. Modular THA combined with a subtrochanteric osteotomy in the treatment of Crowe type IV DDH should reduce the damage to blood supply and avoid further nonunion of the osteotomy area, which may otherwise lead to modular prosthesis fractures. A detailed preoperative plan and suitable rehabilitation program may help minimize the occurrence of subtrochanteric osteotomy nonunion and reduce complications, including femoral prosthesis fractures, in patients with DDH.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Prótesis de Cadera , Artroplastia de Reemplazo de Cadera/efectos adversos , Femenino , Fémur/cirugía , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Prótesis de Cadera/efectos adversos , Humanos , Persona de Mediana Edad , Osteotomía , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
Insulin promotes larval growth of insects by stimulating the synthesis of the steroid hormone 20-hydroxyecdysone (20E), which induces pupation and apoptosis. However, the mechanism underlying the coordinate regulation of insect pupation and apoptosis by these two functionally opposing hormones is still unclear. Here, using the lepidopteran insect and serious agricultural pest Helicoverpa armigera (cotton bollworm) as a model, we report that phosphoinositide-dependent kinase-1 (PDK1) and forkhead box O (FoxO) play key roles in these processes. We found that the transcript levels of the PDK1 gene are increased during the larval feeding stages. Moreover, PDK1 expression was increased by insulin, but repressed by 20E. dsRNA-mediated PDK1 knockdown in the H. armigera larvae delayed pupation and resulted in small pupae and also decreased Akt/protein kinase B expression and increased FoxO expression. Furthermore, the PDK1 knockdown blocked midgut remodeling and decreased 20E levels in the larvae. Of note, injecting larvae with 20E overcame the effect of the PDK1 knockdown and restored midgut remodeling. FoxO overexpression in an H. armigera epidermal cell line (HaEpi) did not induce apoptosis, but promoted autophagy and repressed cell proliferation. These results reveal cross-talk between insulin and 20E and that both hormones oppose each other's activities in the regulation of insect pupation and apoptosis by controlling PDK1 expression and, in turn, FoxO expression. We conclude that sufficiently high 20E levels are a key factor for inducing apoptosis during insect pupation.
Asunto(s)
Proteínas Quinasas Dependientes de 3-Fosfoinosítido/metabolismo , Ecdisterona/fisiología , Proteínas de Insectos/metabolismo , Insulina/fisiología , Lepidópteros/crecimiento & desarrollo , Pupa/crecimiento & desarrollo , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/genética , Animales , Apoptosis/genética , Autofagia/genética , Proliferación Celular/genética , Factores de Transcripción Forkhead/genética , Técnicas de Silenciamiento del Gen , Larva/crecimiento & desarrollo , Fosforilación , ARN Mensajero/metabolismoRESUMEN
Although studies have shown the concomitant occurrence of autophagic and programmed cell death (PCD) in plants, the relationship between autophagy and PCD and the factors determining this relationship remain unclear. In this study, seedlings of the wheat cultivar Jimai 22 were used to examine the occurrence of autophagy and PCD during polyethylene glycol (PEG)-8000-induced drought stress. Autophagy and PCD occurred sequentially, with autophagy at a relatively early stage and PCD at a much later stage. These findings suggest that the duration of drought stress determines the occurrence of PCD following autophagy. Furthermore, the addition of 3-methyladenine (3-MA, an autophagy inhibitor) and the knockdown of autophagy-related gene 6 (ATG6) accelerated PEG-8000-induced PCD, respectively, suggesting that inhibition of autophagy also results in PCD under drought stress. Overall, these findings confirm that wheat seedlings undergo autophagic survival under mild drought stress, with subsequent PCD only under severe drought.
Asunto(s)
Apoptosis , Autofagia , Sequías , Triticum/crecimiento & desarrollo , Adenina/análogos & derivados , Adenina/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Familia de las Proteínas 8 Relacionadas con la Autofagia/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Beclina-1/antagonistas & inhibidores , Beclina-1/genética , Beclina-1/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/antagonistas & inhibidores , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Polietilenglicoles/toxicidad , Interferencia de ARN , ARN Bicatenario/metabolismo , Plantones/efectos de los fármacos , Plantones/metabolismo , Triticum/metabolismoRESUMEN
OBJECTIVE: ITS2 of DNA barcoding was used to study genetic polymorphism of Platycodon grandiflorum. METHOD: Total genomic DNA was isolated from P. grandiflorum. PCR was used to amplified the region of internal transcribed spacer 2 (ITS2), and PCR products were sequenced. The sequences of ITS2 were analyzed and compared by Clustal. The intraspecies genetic distance was calculated based on Kimura 2-parameter model by using MEGA 5.05. The ITS2 sequence of Codonopsis pilosula was used as the outreach value for plants of the genus, and the phylogenic tree used constructed by Neighbor-Joining (NJ) method. RESULT: The K2-P's genetic distance of all samples were ranged from 0 to 0.930. The K2-P's genetic distance of samples at the same area were ranged from 0 to 0.178. The K2-P's genetic distance of samples at different areas were ranged from 0.735 to 0.930. The analytical result showed that the degree of genetic variation were heavy in intraspecies of P. grandiflorum and significantly correlated with geographical location. CONCLUSION: The DNA barcoding of ITS2 can applied to study the intraspecific genetic diversity, it provides a reference for further development of DNA barcoding technology applications.
Asunto(s)
ADN de Plantas/genética , ADN Espaciador Ribosómico/genética , Platycodon/clasificación , Platycodon/genética , Polimorfismo Genético , China , Código de Barras del ADN Taxonómico , Datos de Secuencia Molecular , FilogeniaRESUMEN
BACKGROUND: The Cabrol procedure has undergone various modifications and developments since its invention. However, there is a notable gap in the literature regarding meta-analyses assessing it. METHODS: A systematic review and meta-analysis was conducted to evaluate the effectiveness and long-term outcomes of the Cabrol procedure and its modifications. Pooling was conducted using random effects model. Outcome events were reported as linearized occurrence rates (percentage per patient-year) with 95% confidence intervals. RESULTS: A total of 14 studies involving 833 patients (mean age: 50.8 years; 68.0% male) were included in this meta-analysis. The pooled all-cause early mortality was 9.0% (66 patients), and the combined rate of reoperation due to bleeding was 4.9% (17 patients). During the average 4.4-year follow-up (3,727.3 patient-years), the annual occurrence rates (linearized) for complications were as follows: 3.63% (2.79-4.73) for late mortality, 0.64% (0.35-1.16) for aortic root reoperation, 0.57% (0.25-1.31) for hemorrhage events, 0.66% (0.16-2.74) for thromboembolism, 0.60% (0.29-1.26) for endocarditis, 2.32% (1.04-5.16) for major valve-related adverse events, and 0.58% (0.34-1.00) for Cabrol-related coronary graft complications. CONCLUSION: This systematic review provides evidence that the outcomes of the Cabrol procedure and its modifications are acceptable in terms of mortality, reoperation, anticoagulation, and valve-related complications, especially in Cabrol-related coronary graft complications. Notably, the majority of Cabrol procedures were performed in reoperations and complex cases. Furthermore, the design and anastomosis of the Dacron interposition graft for coronary reimplantation, considering natural anatomy and physiological hemodynamics, may promise future advancements in this field.
Asunto(s)
Reoperación , Humanos , Reoperación/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Implantación de Prótesis de Válvulas Cardíacas/métodos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Resultado del TratamientoRESUMEN
Wheat is one of the most important food crops in the world, with development of the grains directly determining yield and quality. Understanding grain development and the underlying regulatory mechanisms is therefore essential in improving the yield and quality of wheat. In this study, the developmental characteristics of the pericarp was examined in developing wheat grains of the new variety Jimai 70. As a result, pericarp thickness was found to be thinnest in grains at the top of the spike, followed by those in the middle and thickest at the bottom. Moreover, this difference corresponded to the number of cell layers in the pericarp, which decreased as a result of programmed cell death (PCD). A number of autophagy-related genes (ATGs) are involved in the process of PCD in the pericarp, and in this study, an increase in ATG8-PE expression was observed followed by the appearance of autophagy structures. Meanwhile, following interference of the key autophagy gene ATG8, PCD was inhibited and the thickness of the pericarp increased, resulting in small premature grains. These findings suggest that autophagy and PCD coexist in the pericarp during early development of wheat grains, with both processes increasing from the bottom to the top of the spike. Moreover, PCD was also found to rely on ATG8-mediated autophagy. The results of this study therefore provide a theoretical basis for in-depth studies of the regulatory mechanisms of wheat grain development.
RESUMEN
With the rapid development of China's economy, volatile organic compounds (VOCs) as the precursor of smog and ozone are of increasing concern, especially in rapidly developing areas. This paper is a systematic analysis of VOCs emissions and distribution trends in 12 typical industrial sectors, garbage and wastewater treatment plants, comprehensive industrial parks, and residential districts in Beijing-Tianjin-Hebei, Yangtze River Delta, and Pearl River Delta Regions. The results show that pharmacy, rubber producing, as well as paint spraying are the top three industries among the 12 typical industries with the highest average VOCs emission concentrations at 541, 499, and 450 mg·m-3, respectively. By comparison, the average emission concentration of VOCs from the pharmaceutical industry in Yangtze River Delta and Beijing-Tianjin-Hebei Region was, respectively, about 112 and 1.00×103 mg·m-3. The paint spraying industry in the Pearl River Delta region has the highest emission rate with an average concentration of 1.04×103 mg·m-3. The investigation pertaining to the distribution of different VOCs categories indicates that highly toxic aromatics and halogenated hydrocarbons account for the highest emissions in paint spraying and pharmaceutical industries, reaching ratios of 55.99% and 26.57%, respectively. Additionally, among the three major economic zones, the VOCs concentration is the lowest in residential areas and comprehensive industrial parks in the Yangtze River Delta but the highest in the Beijing-Tianjin-Hebei Region, which is consistent with the distribution of industrial emissions in each region. Moreover, the research reveals that VOCs concentration in residential districts experienced a fluctuating reduction from 2002 to 2018. The significant reduction since 2016 suggests that formulated policies, laws and standards, along with the performed techniques have made significant contributions to the control of VOCs.
RESUMEN
A short and practical synthesis of oseltamivir was accomplished in 11 steps from inexpensive and abundant diethyl D-tartrate starting material. This azide-free route featured an asymmetric aza-Henry reaction and a domino nitro-Michael/Horner-Wadsworth-Emmons (HWE) reaction as the key steps to construct the relevant cyclohexene ring of the product, which provided an economical and practical alternative for the synthesis of oseltamivir.
Asunto(s)
Antivirales/síntesis química , Inhibidores Enzimáticos/síntesis química , Neuraminidasa/antagonistas & inhibidores , Oseltamivir/síntesis química , Tartratos/química , Animales , Ciclización , Ciclohexenos/química , Humanos , Subtipo H5N1 del Virus de la Influenza A/enzimología , Estructura MolecularRESUMEN
Autophagy requires the conjugation of autophagy-related protein 12 (ATG12) to autophagy-related protein 5 (ATG5) through covalent attachment. However, the signals regulating ATG12-ATG5 conjugation are unclear. The larval midgut of lepidopteran insects performs autophagy and apoptosis sequentially during the transition of larvae to pupae under regulation by the steroid hormone 20-hydroxyecdysone (20E), thus representing a model to study steroid hormone regulation of ATG12-ATG5 conjugation. In the present study, using the lepidopteran insect Helicoverpa armigera as a model, we report that 20E regulates the conjugation of ATG12-ATG5 in a concentration and time-dependent manner. The ATG12-ATG5 conjugate was abundant in the epidermis, midgut, and fat body during metamorphosis from the larvae to the pupae; however, the ATG12-ATG5 conjugate level decreased at the time of pupation. At low concentrations (2-5 µM) over a short time course (1-48 h), 20E promoted the conjugation of ATG12-ATG5; however, at 10 µM and 72 h, 20E repressed the conjugation of ATG12-ATG5. ATG12 was localized in the larval midgut during metamorphosis. Knockdown of ATG12 in larvae caused death with delayed pupation, postponed the process of midgut programmed cell death (PCD), and repressed ATG8 (also called LC3-I) transformation to LC3-II and the cleavage of caspase-3; therefore, knockdown of ATG12 in larvae blocked both autophagy and apoptosis. Knockdown of ATG12 in H. armigera epidermis cell line cells also repressed 20E-induced autophagosome formation and caspase-3 activation. The results suggested that 20E plays key role in the regulation of ATG12-ATG5 conjugation in a concentration and time-dependent manner for autophagy or apoptosis, and that ATG12 is necessary by both autophagy and apoptosis during insect midgut PCD.
RESUMEN
OBJECTIVE: This study aimed to evaluate the difference and consistency between single-photon emission computed tomography-computed tomography (SPECT-CT) and MRI in diagnosing osteoporotic vertebral compression fractures (OVCFs) and identifying active lesions. PATIENTS AND METHODS: All 46 patients underwent SPECT-CT and MRI examinations. The pain vertebral body and pain sites were determined using both MRI and SPECT-CT during percutaneous kyphoplasty (PKP). The differences before and after treatment were assessed using visual analog scale scores and evaluated using a paired t-test. Furthermore, the difference and conformity of SPECT-CT and MRI in diagnosing OVCFs were determined using the McNemar test and the κ-statistic, and by calculating the accuracy index of SPECT-CT diagnosis. RESULTS: Among all 46 patients, MRI showed 79 segments that fulfilled the diagnostic criteria for fresh OVCFs, whereas SPECT-CT showed 83 segments, and a total of 77 affected vertebral bodies were treated with PKP. Paired t-test evaluation showed that PKP was effective, suggesting that the affected sites were determined accurately (P<0.05). Furthermore, the κ-statistics indicated that these two methods were highly consistent (P<0.05) and the McNemar test indicated that the efficacy of these two diagnostic methods was closely correlated (P>0.05). In different stages of fractures, especially the acute phase, the consistency of SPECT-CT and MRI in the diagnosis of fresh OVCFs was high. CONCLUSION: SPECT-CT is the preferred method for imaging diagnosis when patients with suspected OVCFs have contraindications to MRI, particularly for patients with acute fractures.
Asunto(s)
Fracturas por Compresión/diagnóstico por imagen , Imagen por Resonancia Magnética , Fracturas Osteoporóticas/diagnóstico por imagen , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Fracturas de la Columna Vertebral/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on respiratory rhythm. The experiments were carried out on the medullary slices of newborn Sprague-Dawley rats. The rhythmic discharge frequency (DF) of hypoglossal rootlets was taken as an index of rhythmic respiratory activity. The slices of medulla oblongata were superfused with ZnPP-9 (inhibitor of heme oxygenase), CO and hemin (substrate of heme oxygenase), respectively, to observe their effects on respiratory rhythm. The preparations were divided into 5 groups: control group of artificial cerebrospinal fluid (ACSF), group of ZnPP-9, group of exogenous CO, group of hemin and group of ZnPP-9 + hemin. The results obtained were as follows. In ZnPP-9 group, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05); while in exogenous CO group, it was decreased (P<0.05). In the groups of hemin and ZnPP-9 + hemin, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05). It is suggested that endogenous CO may play an important role in the regulation of respiratory rhythm.
Asunto(s)
Monóxido de Carbono/fisiología , Respiración , Animales , Animales Recién Nacidos , Femenino , Hemina/farmacología , Nervio Hipogloso/efectos de los fármacos , Nervio Hipogloso/fisiología , Masculino , Protoporfirinas/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Animal steroid hormones stimulate extracellular Ca2+ influx into cells; however, the mechanism remains unclear. In this study, we determined that the Ca2+ influx induced by steroid hormone 20-hydroxyecdysone (20E) is mediated by the calcium release-activated calcium channel modulator 1 (CRACM1/Orai1). The Orai1 mRNA is highly expressed during midgut programmed cell death in the lepidopteran insect Helicoverpa armigera. 20E upregulated the expression of Orai1 in H. armigera larvae and in an epidermal cell line (HaEpi). Knockdown of Orai1 in HaEpi cells blocked 20E-induced Ca2+ influx, and the inhibitor of inositol 1, 4, 5-trisphosphate receptor (IP3R) Xestospongin (XeC) blocked 20E-induced Ca2+ influx, suggesting that 20E, via Orai1, induces stored-operated Ca2+ influx. Orai1 interacts with stromal interaction molecule 1(Stim1) to exert its function in 20E-induced Ca2+ influx. 20E promotes Orai1 aggregation through G-protein-coupled receptors, phospholipase C gamma 1, and Stim1. Knockdown of Orai1 in the HaEpi cell line repressed apoptosis and maintained autophagy under 20E regulation. Knockdown of Orai1 in larvae delayed pupation, repressed midgut apoptosis, maintained the midgut in an autophagic state, and repressed 20E-pathway gene expression. These results revealed that steroid hormone 20E, via Orai1, induces Ca2+ influx to promote the transition of midgut from autophagy to apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Calcio/metabolismo , Sistema Digestivo/citología , Ecdisterona/farmacología , Mariposas Nocturnas/citología , Proteína ORAI1/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Modelos Biológicos , Muda/efectos de los fármacos , Proteína ORAI1/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Autophagy regulates cell survival (or cell death in several cases), whereas apoptosis regulates cell death. However, the relationship between autophagy and apoptosis and the regulative mechanism is unclear. We report that steroid hormone 20-hydroxyecdysone (20E) promotes switching from autophagy to apoptosis by increasing intracellular calcium levels in the midgut of the lepidopteran insect Helicoverpa armigera. Autophagy and apoptosis sequentially occurred during midgut programmed cell death under 20E regulation, in which lower concentrations of 20E induced microtubule-associated protein 1 light chain 3-phosphatidylethanolamine (LC3-II, also known as autophagy-related gene 8, ATG8) expression and autophagy. High concentrations of 20E induced cleavage of ATG5 to NtATG5 and pro-caspase-3 to active caspase-3, which led to a switch from autophagy to apoptosis. Blocking autophagy by knockdown of ATG5, ATG7, or ATG12, or with the autophagy inhibitor 3-methyladenine, inhibited 20E-induced autophagy and apoptosis. Blocking apoptosis by using the apoptosis inhibitor Ac-DEVD-CHO did not prevent 20E-induced autophagy, suggesting that apoptosis relies on autophagy. ATG5 knockdown resulted in abnormal pupation and delayed pupation time. High concentrations of 20E induced high levels of intracellular Ca2+, NtATG5, and active caspase-3, which mediated the switch from autophagy to apoptosis. Blocking 20E-mediated increase of cellular Ca2+ caused a decrease of NtATG5 and active caspase-3 and repressed the transformation from autophagy to apoptosis, thereby promoting cell survival. 20E induces an increase in the concentration of intracellular Ca2+, thereby switching autophagic cell survival to apoptotic cell death.
Asunto(s)
Apoptosis , Autofagia , Calcio/metabolismo , Ecdisterona/metabolismo , Mariposas Nocturnas/fisiología , Animales , Tracto Gastrointestinal/fisiología , Espacio Intracelular/metabolismo , Larva/crecimiento & desarrollo , Larva/fisiología , Mariposas Nocturnas/crecimiento & desarrolloRESUMEN
The steroid hormone 20-hydroxyecdysone (20E) plays a critical role in insect development, particularly in larval molting and larval-pupal transition. Studies have indicated that 20E transmits its signal via a G protein-coupled receptor (GPCR)-mediated non-genomic pathway before a genomic pathway is initiated. However, the mechanism by which a 20E signal is desensitized remains unclear. We proposed that ß-arrestin1 interacts with ecdysone-responsible GPCR (ErGPCR1) to desensitize a 20E signal in the lepidopteran insect Helicoverpa armigera. Results showed that ß-arrestin1 was highly expressed in various tissues during metamorphosis. ß-Arrestin1 knockdown by RNA interference in larvae caused advanced pupation and a larval-pupal chimera. The mRNA levels of 20E-response genes were increased after ß-arrestin1 was knocked down but were decreased after ß-arrestin1 was overexpressed. 20E induced the migration of ß-arrestin1 from the cytosol to the cytoplasmic membrane to interact with ErGPCR1. The inhibitors suramin and chelerythrine chloride repressed 20E-induced ß-arrestin1 phosphorylation and membrane migration. With ErGPCR1, 20E regulated ß-arrestin1 phosphorylation on serines at positions 170 and 234. The double mutation of the amino acids Ser170 and Ser234 to asparagine inhibited phosphorylation and membrane migration of ß-arrestin1 in 20E induction. Therefore, 20E via ErGPCR1 and PKC signaling induces ß-arrestin1 phosphorylation; phosphorylated ß-arrestin1 migrates to the cytoplasmic membrane to interact with ErGPCR1 to block 20E signaling via a feedback mechanism.