Leveraging the high resolution,sensitivity,and wide frequency coverage of the Atacama Large Millimeter/submillimeter Array(ALMA),the QUARKS survey,standing for“Querying Underlying mechanisms of massive star formation...Leveraging the high resolution,sensitivity,and wide frequency coverage of the Atacama Large Millimeter/submillimeter Array(ALMA),the QUARKS survey,standing for“Querying Underlying mechanisms of massive star formation with ALMA-Resolved gas Kinematics and Structures”,is observing 139 massive starforming clumps at ALMA Band 6(λ~1.3 mm).This paper introduces the Atacama Compact Array(ACA)7 m data of the QUARKS survey,describing the ACA observations and data reduction.Combining multiwavelength data,we provide the first edition of QUARKS atlas,offering insights into the multiscale and multiphase interstellar medium in high-mass star formation.The ACA 1.3 mm catalog includes 207 continuum sources that are called ACA sources.Their gas kinetic temperatures are estimated using three formaldehyde transitions with a non-LTE radiation transfer model,and the mass and density are derived from a dust emission model.The ACA sources are massive(16–84 percentile values of 6–160 M_(⊙)),gravity-dominated(M∝R^(1.1))fragments within massive clumps,with supersonic turbulence(M>1)and embedded star-forming protoclusters.We find a linear correlation between the masses of the fragments and the massive clumps,with a ratio of 6%between the two.When considering fragments as representative of dense gas,the ratio indicates a dense gas fraction(DGF)of 6%,although with a wide scatter ranging from 1%to 10%.If we consider the QUARKS massive clumps to be what is observed at various scales,then the size-independent DGF indicates a self-similar fragmentation or collapsing mode in protocluster formation.With the ACA data over four orders of magnitude of luminosity-to-mass ratio(L/M),we find that the DGF increases significantly with L/M,which indicates clump evolutionary stage.We observed a limited fragmentation at the subclump scale,which can be explained by a dynamic global collapse process.展开更多
Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphoc...Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphocytic leukemia. Patient and Methods: Magnetic Resonance Imaging (MRI), histological picture (H.E., Kluver-Barrera) and immunohistochemical picture (GFAP, neurofilaments, CD68, JC virus) were obtained. Results: 1) Magnetic resonance imaging: Asymmetric and progressive lesions on middle cerebellar peduncles, that were hyperintense in T2/FLAIR, extended towards the pons, had no mass effect and were unmodified after intravenous contrast. 2) Histology: Marked reactive gliosis with cytopathic changes suggesting viral infection, plus demyelination areas with axonal preservation. 3) Immunohistochemistry: Marked positivity for viral (polyoma and JC virus) markers in glial cells showing cytopathic changes. Conclusions: The importance of histological and immunohistochemical diagnosis in everyday assistance;of the collaboration between clinicians, radiologists and pathologists;and the validity of postmortem studies as a key element for research and clinical quality assessment must be stressed.展开更多
Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A...Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.展开更多
Here, we evaluated the possibility of growing grape tomatoes on three different mixtures of composted agave bagasse substrate. Tomatoes were grown in 28-L pots for 106 days under a drip irrigation system with a hydrop...Here, we evaluated the possibility of growing grape tomatoes on three different mixtures of composted agave bagasse substrate. Tomatoes were grown in 28-L pots for 106 days under a drip irrigation system with a hydroponic crop nutrient solution. The average production of grape tomatoes was 338.9, 358.9, and 325.7 g/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean of numbers of grape tomatoes were 34.6, 38.8, and 34.2/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean weight of individual grape tomatoes was about 10.4 g for all of the substrates tested. These results confirmed the notion that a composted agave bagasse substrate could replace an expensive imported substrate. The remaining challenge is to produce agave bagasse substrate commercially, because to date, agave bagasse substrates have only been produced on a pilot scale for testing. Therefore, it is necessary to implement a stabilized process for producing agave bagasse at a commercial level. This process must consider economic production costs and market value to ensure that the product is competitive with other substrates typically used in soilless crops.展开更多
There is a growing concern adout the genetic riskproduced by contamination of coastal lagoons alongthe Gulf of Mexico,it was found recently that oys-ters(Crassostrea virginica)collected from an es-tuary located near t...There is a growing concern adout the genetic riskproduced by contamination of coastal lagoons alongthe Gulf of Mexico,it was found recently that oys-ters(Crassostrea virginica)collected from an es-tuary located near the Refinery of Cd.Madero,Tam-ps.,had high amounts of both,hydrocarbons and hea-vy metals.展开更多
Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the sci...Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.展开更多
Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the pho...Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.展开更多
Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of ...Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.展开更多
Endohepatology describes the emerging field where diagnostic and therapeutic endoscopic ultrasound(EUS)are used for the diagnosis and management of liver disease and its sequelae.In this editorial we comment on the ar...Endohepatology describes the emerging field where diagnostic and therapeutic endoscopic ultrasound(EUS)are used for the diagnosis and management of liver disease and its sequelae.In this editorial we comment on the article by Gadour et al.The spectrum of EUS-guided procedures includes liver parenchymal and lesional biopsy,abscess drainage,treatment of focal liver lesions,diagnosis of portal hypertension and management of gastric varices.The data suggest that the application of EUS to hepatology is technically feasible and safe,heralding the arrival at a new frontier for EUS.More data,specifically randomised trials comparing EUS to interventional radiology techniques,and continued partnership between endoscopy and hepatology are required to see this field establish itself outside expert tertiary centres.展开更多
Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinester...Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.展开更多
Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is sti...Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.展开更多
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the und...Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.展开更多
The sandstones of the Late miocene–Pliocene Dibdibba Formation in the Najaf–Karbala Plateau and Basra were examined to determine their source rocks and origin. The rare earth elements(REE) and trace elements(Sc, Co,...The sandstones of the Late miocene–Pliocene Dibdibba Formation in the Najaf–Karbala Plateau and Basra were examined to determine their source rocks and origin. The rare earth elements(REE) and trace elements(Sc, Co, V, and Th) concentrations in these sandstones revealed that they likely derived from a single source. The steep light rare earth elements(LREE) and flat, heavy rare earth element(HREE) patterns, negative Eu anomaly, and high ΣREE contents in sandstones suggest its derivation from a suggests that a passive continental margin environment and originated from felsic source rocks. The average concentration of ΣREE is 93.5 ppm, which is lower than that of the average crustal compositions like Upper Continental Crust and Post Archean Australian Shale. The higher proportion of LREE compared to HREE implies that these sandstones were recycled and derived from a distal source. The Th/Co, Th/Sc, La/Sc, La/Co, Eu/Eu*and(La/Lu)cn elemental ratios indicated that these Late Miocene–Pliocene sandstones were derived from felsic rocks located in the marginal region of the Arabian Shield.展开更多
Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have un...Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.展开更多
AIM:To investigate the prevalence of visual impairment(VI)and provide an estimation of uncorrected refractive errors in school-aged children,conducted by optometry students as a community service.METHODS:The study was...AIM:To investigate the prevalence of visual impairment(VI)and provide an estimation of uncorrected refractive errors in school-aged children,conducted by optometry students as a community service.METHODS:The study was cross-sectional.Totally 3343 participants were included in the study.The initial examination involved assessing the uncorrected distance visual acuity(UDVA)and visual acuity(VA)while using a+2.00 D lens.The inclusion criteria for a subsequent comprehensive cycloplegic eye examination,performed by an optometrist,were as follows:a UDVA<0.6 decimal(0.20 logMAR)and/or a VA with+2.00 D≥0.8 decimal(0.96 logMAR).RESULTS:The sample had a mean age of 10.92±2.13y(range 4 to 17y),and 51.3%of the children were female(n=1715).The majority of the children(89.7%)fell within the age range of 8 to 14y.Among the ethnic groups,the highest representation was from the Luhya group(60.6%)followed by Luo(20.4%).Mean logMAR UDVA choosing the best eye for each student was 0.29±0.17(range 1.70 to 0.22).Out of the total,246 participants(7.4%)had a full eye examination.The estimated prevalence of myopia(defined as spherical equivalent≤-0.5 D)was found to be 1.45%of the total sample.While around 0.18%of the total sample had hyperopia value exceeding+1.75 D.Refractive astigmatism(cil<-0.75 D)was found in 0.21%(7/3343)of the children.The VI prevalence was 1.26%of the total sample.Among our cases of VI,76.2%could be attributed to uncorrected refractive error.Amblyopia was detected in 0.66%(22/3343)of the screened children.There was no statistically significant correlation observed between age or gender and refractive values.CONCLUSION:The primary cause of VI is determined to be uncorrected refractive errors,with myopia being the most prevalent refractive error observed.These findings underscore the significance of early identification and correction of refractive errors in school-aged children as a means to alleviate the impact of VI.展开更多
Constructed wetlands(CwW)are well known nature-based systems for water treatment.This study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jar...Constructed wetlands(CwW)are well known nature-based systems for water treatment.This study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jarabacoa,the Dominican Republic.The results showed that the CWs were efficient in reducing the degree of contamination of wastewater to levels below the Dominican wastewater discharge standards for parameters such as the 5-day biochemical oxygen demand(BOD5)and chemical oxygen demand,but not for the removal of phosphorus and fecal coliforms.In addition,a horizontal flow subsurface wetland in the peri-urban area El Dorado was evaluated in terms of the performance of wastewater treatment in tropical climatic conditions.The concentrations of heavy metals,such as zinc,copper,chromium,and iron,were found to decrease in the effluent of the wetland,and the concentrations for nickel and manganese tended to increase.The levels of heavy metals in the effluent were lower than the limit values of the Dominican wastewater discharge standards.The construction cost of these facilities was around 200 USD per population equivalent,similar to the cost in other countries in the same region.This study suggested some solutions to the improved performance of CWs:selection of a microbial flora that guarantees the reduction of nitrates and nitrites to molecular nitrogen,use of endemic plants that bioaccumulate heavy metals,combination of constructed wetlands with filtration on activated carbon,and inclusion of water purification processes that allow to evaluate the reuse of treated water.展开更多
Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic rats.Methods:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+gedunin.Biochemical parameters for liver fu...Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic rats.Methods:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+gedunin.Biochemical parameters for liver function and liver histology were studied.The molecular interaction of gedunin with the liver glucose transporters GLUT2 and SGLT1 was examined using AutoDock Vina.Results:Gedunin attenuated STZ-induced increase in the levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,lactate dehydrogenase and gamma-glutamyl transferase in the serum and liver tissue,reduced lipid peroxidation,and enhanced antioxidant activity.Histopathological studies showed considerable restoration of liver architecture in gedunin-treated diabetic rats.In silico studies revealed stable binding of gedunin with GLUT2 and SGLT1.Conclusions:Gedunin exerts hepatoprotective effects in STZ-induced diabetic rats by reducing liver enzymatic activities and oxidative stress.Further studies are warranted to verify the mechanism of its hepatoprotective action.展开更多
Wildfires are complex natural phenomena that exert significant impacts on landscapes,societies,and economies.Understanding the concept of resilience is crucial in mitigating its possible negative impacts,as it involve...Wildfires are complex natural phenomena that exert significant impacts on landscapes,societies,and economies.Understanding the concept of resilience is crucial in mitigating its possible negative impacts,as it involves preparing for,responding to,and recovering from wildfires.This research aims to demonstrate the utility of in situ soil profile description in assessing land use resilience using an Analytic Hierarchy Process(AHP)through an expert panel survey.The study examines a catchment located in the Balearic Islands,considering two fire occurrences(once and twice),comparing abandoned agricultural terraces and natural hillslopes.The results demonstrated that the priority ranking of variables to assess soil profile resilience against wildfires,determined by a panel of 10 experts,identified horizon depth(25.1%),slope inclination(21.5%),and hydrological connectivity(16.6%)as the most crucial factors.Other variables,such as number and size of roots,structure of pedal soil material,size class structure,and rock fragments,also contributed to resilience but to a lesser extent,with scores ranging from 5.7%to 9.6%.Analyzing the priorities established by the experts using AHP,the results showed that the least resilient soil horizon was H1 of the control hillslope,especially under high and low connectivity processes,which aligned with the loss of superficial soil horizons after one and two wildfires.Hillslopes showed greater changes in resilience after occurring wildfires compared to terraces,with the most significant alterations occurring after the second wildfire event.This study addresses a significant knowledge gap in the field by highlighting the interconnectedness of wildfires,resilience,and land use,providing insights into land management strategies for wildfire-prone regions.展开更多
The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lyso...The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely known.In this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons.Then we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.展开更多
Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,...Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.展开更多
基金upported by the National Natural Science Foundation of China(NSFC,Grant No.12033005)the National Key R&D Program of China(No.2022YFA1603102)+2 种基金the China Manned Space Project(CMS-CSST-2021-A09,CMS-CSST-2021-B06)the China-Chile Joint Research Fund(CCJRF No.2211)support from the Tianchi Talent Program of Xinjiang Uygur Autonomous Region。
文摘Leveraging the high resolution,sensitivity,and wide frequency coverage of the Atacama Large Millimeter/submillimeter Array(ALMA),the QUARKS survey,standing for“Querying Underlying mechanisms of massive star formation with ALMA-Resolved gas Kinematics and Structures”,is observing 139 massive starforming clumps at ALMA Band 6(λ~1.3 mm).This paper introduces the Atacama Compact Array(ACA)7 m data of the QUARKS survey,describing the ACA observations and data reduction.Combining multiwavelength data,we provide the first edition of QUARKS atlas,offering insights into the multiscale and multiphase interstellar medium in high-mass star formation.The ACA 1.3 mm catalog includes 207 continuum sources that are called ACA sources.Their gas kinetic temperatures are estimated using three formaldehyde transitions with a non-LTE radiation transfer model,and the mass and density are derived from a dust emission model.The ACA sources are massive(16–84 percentile values of 6–160 M_(⊙)),gravity-dominated(M∝R^(1.1))fragments within massive clumps,with supersonic turbulence(M>1)and embedded star-forming protoclusters.We find a linear correlation between the masses of the fragments and the massive clumps,with a ratio of 6%between the two.When considering fragments as representative of dense gas,the ratio indicates a dense gas fraction(DGF)of 6%,although with a wide scatter ranging from 1%to 10%.If we consider the QUARKS massive clumps to be what is observed at various scales,then the size-independent DGF indicates a self-similar fragmentation or collapsing mode in protocluster formation.With the ACA data over four orders of magnitude of luminosity-to-mass ratio(L/M),we find that the DGF increases significantly with L/M,which indicates clump evolutionary stage.We observed a limited fragmentation at the subclump scale,which can be explained by a dynamic global collapse process.
文摘Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphocytic leukemia. Patient and Methods: Magnetic Resonance Imaging (MRI), histological picture (H.E., Kluver-Barrera) and immunohistochemical picture (GFAP, neurofilaments, CD68, JC virus) were obtained. Results: 1) Magnetic resonance imaging: Asymmetric and progressive lesions on middle cerebellar peduncles, that were hyperintense in T2/FLAIR, extended towards the pons, had no mass effect and were unmodified after intravenous contrast. 2) Histology: Marked reactive gliosis with cytopathic changes suggesting viral infection, plus demyelination areas with axonal preservation. 3) Immunohistochemistry: Marked positivity for viral (polyoma and JC virus) markers in glial cells showing cytopathic changes. Conclusions: The importance of histological and immunohistochemical diagnosis in everyday assistance;of the collaboration between clinicians, radiologists and pathologists;and the validity of postmortem studies as a key element for research and clinical quality assessment must be stressed.
文摘Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.
文摘Here, we evaluated the possibility of growing grape tomatoes on three different mixtures of composted agave bagasse substrate. Tomatoes were grown in 28-L pots for 106 days under a drip irrigation system with a hydroponic crop nutrient solution. The average production of grape tomatoes was 338.9, 358.9, and 325.7 g/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean of numbers of grape tomatoes were 34.6, 38.8, and 34.2/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean weight of individual grape tomatoes was about 10.4 g for all of the substrates tested. These results confirmed the notion that a composted agave bagasse substrate could replace an expensive imported substrate. The remaining challenge is to produce agave bagasse substrate commercially, because to date, agave bagasse substrates have only been produced on a pilot scale for testing. Therefore, it is necessary to implement a stabilized process for producing agave bagasse at a commercial level. This process must consider economic production costs and market value to ensure that the product is competitive with other substrates typically used in soilless crops.
文摘There is a growing concern adout the genetic riskproduced by contamination of coastal lagoons alongthe Gulf of Mexico,it was found recently that oys-ters(Crassostrea virginica)collected from an es-tuary located near the Refinery of Cd.Madero,Tam-ps.,had high amounts of both,hydrocarbons and hea-vy metals.
基金This work is supported by the United Arab Emirates University UPAR(Grant No.G3458).
文摘Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.
基金supported by the European Regional Development Funds-European Union(ERDF-EU),FATZHEIMER project(EU-LAC HEALTH 2020,16/T010131 to FRdF),“Una manera de hacer Europa”Ministerio de Economía,Industria y Competitividad,Gobierno de Espa?a,Programa Estatal de Investigación,Desarrollo e Innovación Orientada a los Retos de la Sociedad(RTC2019-007329-1 to FRdF)+2 种基金Consejería de Economía,Conocimiento y Universidad,Junta de Andalucía,Plan Andaluz de Investigación,Desarrollo e Innovación(P18TP-5194 to FRdF)Instituto de Salud CarlosⅢ(DTS22/00021 to FRdF)DMV(FI20/00227)holds a“PFIS’’predoctoral contract from the National System of Health,EU-ERDF-Instituto de Salud CarlosⅢ。
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.
文摘Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.
文摘Endohepatology describes the emerging field where diagnostic and therapeutic endoscopic ultrasound(EUS)are used for the diagnosis and management of liver disease and its sequelae.In this editorial we comment on the article by Gadour et al.The spectrum of EUS-guided procedures includes liver parenchymal and lesional biopsy,abscess drainage,treatment of focal liver lesions,diagnosis of portal hypertension and management of gastric varices.The data suggest that the application of EUS to hepatology is technically feasible and safe,heralding the arrival at a new frontier for EUS.More data,specifically randomised trials comparing EUS to interventional radiology techniques,and continued partnership between endoscopy and hepatology are required to see this field establish itself outside expert tertiary centres.
文摘Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.
基金Supported by PIP-CONICET 2021-2023 grant,No.11220200100875COPICT-2020-Serie,No.A-00788and“Florencio Fiorini Foundation”grants.
文摘Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.
基金funded by the Spanish Ministry of Economy and Competitiveness,No.PID(2019)-106498GB-100 (to MVS)by the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional"Una manera de hacer Europa",No.PI19/00071 (to MAB)+2 种基金the RETICS subprograms of Spanish Networks OftoRed,Nos.RD16/0008/0026 (to DGB) and RD16/0008/0016 (to DGB)RICORS Terav,No.RD16/0011/0001 (to DGB)from Instituto de Salud CarlosⅢby the Fundacion Seneca,Agencia de Cienciay Tecnologia Región de Murcia,No.19881/GERM/15 (all to MVS)
文摘Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.
文摘The sandstones of the Late miocene–Pliocene Dibdibba Formation in the Najaf–Karbala Plateau and Basra were examined to determine their source rocks and origin. The rare earth elements(REE) and trace elements(Sc, Co, V, and Th) concentrations in these sandstones revealed that they likely derived from a single source. The steep light rare earth elements(LREE) and flat, heavy rare earth element(HREE) patterns, negative Eu anomaly, and high ΣREE contents in sandstones suggest its derivation from a suggests that a passive continental margin environment and originated from felsic source rocks. The average concentration of ΣREE is 93.5 ppm, which is lower than that of the average crustal compositions like Upper Continental Crust and Post Archean Australian Shale. The higher proportion of LREE compared to HREE implies that these sandstones were recycled and derived from a distal source. The Th/Co, Th/Sc, La/Sc, La/Co, Eu/Eu*and(La/Lu)cn elemental ratios indicated that these Late Miocene–Pliocene sandstones were derived from felsic rocks located in the marginal region of the Arabian Shield.
基金supported by National Council of Science and Technology(CONACYT)(grants FC 2016/2672 and FOSISS 272757),INMEGEN(09/2017/I)the Ministry of Education,Science,Technology and Innovation of Mexico City(SECTEI)(grant 228/2021).
文摘Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.
文摘AIM:To investigate the prevalence of visual impairment(VI)and provide an estimation of uncorrected refractive errors in school-aged children,conducted by optometry students as a community service.METHODS:The study was cross-sectional.Totally 3343 participants were included in the study.The initial examination involved assessing the uncorrected distance visual acuity(UDVA)and visual acuity(VA)while using a+2.00 D lens.The inclusion criteria for a subsequent comprehensive cycloplegic eye examination,performed by an optometrist,were as follows:a UDVA<0.6 decimal(0.20 logMAR)and/or a VA with+2.00 D≥0.8 decimal(0.96 logMAR).RESULTS:The sample had a mean age of 10.92±2.13y(range 4 to 17y),and 51.3%of the children were female(n=1715).The majority of the children(89.7%)fell within the age range of 8 to 14y.Among the ethnic groups,the highest representation was from the Luhya group(60.6%)followed by Luo(20.4%).Mean logMAR UDVA choosing the best eye for each student was 0.29±0.17(range 1.70 to 0.22).Out of the total,246 participants(7.4%)had a full eye examination.The estimated prevalence of myopia(defined as spherical equivalent≤-0.5 D)was found to be 1.45%of the total sample.While around 0.18%of the total sample had hyperopia value exceeding+1.75 D.Refractive astigmatism(cil<-0.75 D)was found in 0.21%(7/3343)of the children.The VI prevalence was 1.26%of the total sample.Among our cases of VI,76.2%could be attributed to uncorrected refractive error.Amblyopia was detected in 0.66%(22/3343)of the screened children.There was no statistically significant correlation observed between age or gender and refractive values.CONCLUSION:The primary cause of VI is determined to be uncorrected refractive errors,with myopia being the most prevalent refractive error observed.These findings underscore the significance of early identification and correction of refractive errors in school-aged children as a means to alleviate the impact of VI.
基金support of the Yaque del Norte Water Fund(FAYN),INTEC(Grant No.CBA-330810-2020-P-1)Fondo Dominicano de Ciencia y Tecnologia(FONDOCYT)(Grant No.2022-2B2-161)。
文摘Constructed wetlands(CwW)are well known nature-based systems for water treatment.This study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jarabacoa,the Dominican Republic.The results showed that the CWs were efficient in reducing the degree of contamination of wastewater to levels below the Dominican wastewater discharge standards for parameters such as the 5-day biochemical oxygen demand(BOD5)and chemical oxygen demand,but not for the removal of phosphorus and fecal coliforms.In addition,a horizontal flow subsurface wetland in the peri-urban area El Dorado was evaluated in terms of the performance of wastewater treatment in tropical climatic conditions.The concentrations of heavy metals,such as zinc,copper,chromium,and iron,were found to decrease in the effluent of the wetland,and the concentrations for nickel and manganese tended to increase.The levels of heavy metals in the effluent were lower than the limit values of the Dominican wastewater discharge standards.The construction cost of these facilities was around 200 USD per population equivalent,similar to the cost in other countries in the same region.This study suggested some solutions to the improved performance of CWs:selection of a microbial flora that guarantees the reduction of nitrates and nitrites to molecular nitrogen,use of endemic plants that bioaccumulate heavy metals,combination of constructed wetlands with filtration on activated carbon,and inclusion of water purification processes that allow to evaluate the reuse of treated water.
文摘Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic rats.Methods:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+gedunin.Biochemical parameters for liver function and liver histology were studied.The molecular interaction of gedunin with the liver glucose transporters GLUT2 and SGLT1 was examined using AutoDock Vina.Results:Gedunin attenuated STZ-induced increase in the levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,lactate dehydrogenase and gamma-glutamyl transferase in the serum and liver tissue,reduced lipid peroxidation,and enhanced antioxidant activity.Histopathological studies showed considerable restoration of liver architecture in gedunin-treated diabetic rats.In silico studies revealed stable binding of gedunin with GLUT2 and SGLT1.Conclusions:Gedunin exerts hepatoprotective effects in STZ-induced diabetic rats by reducing liver enzymatic activities and oxidative stress.Further studies are warranted to verify the mechanism of its hepatoprotective action.
基金supported by the research project CGL2017-88200-R,titled"Functional Hydrological and Sediment Connectivity in Mediterranean Catchments:Global Change Scenarios–MEDhyCON_2,"funded by the Spanish Ministry of Science,Innovation,and Universities,the Spanish Agency of Research (AEI)the European Regional Development Funds (ERDF)funded by COST Action (grant no. CA18135),supported by COST (European Cooperation in Science and Technology),during a Short-Term Scientific Mission (STSM) conducted by Jesús Rodrigo-Comino
文摘Wildfires are complex natural phenomena that exert significant impacts on landscapes,societies,and economies.Understanding the concept of resilience is crucial in mitigating its possible negative impacts,as it involves preparing for,responding to,and recovering from wildfires.This research aims to demonstrate the utility of in situ soil profile description in assessing land use resilience using an Analytic Hierarchy Process(AHP)through an expert panel survey.The study examines a catchment located in the Balearic Islands,considering two fire occurrences(once and twice),comparing abandoned agricultural terraces and natural hillslopes.The results demonstrated that the priority ranking of variables to assess soil profile resilience against wildfires,determined by a panel of 10 experts,identified horizon depth(25.1%),slope inclination(21.5%),and hydrological connectivity(16.6%)as the most crucial factors.Other variables,such as number and size of roots,structure of pedal soil material,size class structure,and rock fragments,also contributed to resilience but to a lesser extent,with scores ranging from 5.7%to 9.6%.Analyzing the priorities established by the experts using AHP,the results showed that the least resilient soil horizon was H1 of the control hillslope,especially under high and low connectivity processes,which aligned with the loss of superficial soil horizons after one and two wildfires.Hillslopes showed greater changes in resilience after occurring wildfires compared to terraces,with the most significant alterations occurring after the second wildfire event.This study addresses a significant knowledge gap in the field by highlighting the interconnectedness of wildfires,resilience,and land use,providing insights into land management strategies for wildfire-prone regions.
基金funded by grants from Fondo Nacional de Desarrollo Científico y Tecnológico,FONDECYT 1200499 to EM,11200592 to MJY,1211329 to ACby the ANID PIA ACT172066 to EM and AC+3 种基金by the ANID postdoctoral fellowship 3210630 to MPHCby the ANID doctoral fellowship 21230122 to DPNby the ANID doctoral fellowship 21211189 to PRby the ANID doctoral fellowship by the ANID doctoral fellowship 21210611 to FDC。
文摘The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely known.In this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons.Then we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.
文摘Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.