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Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.
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ABSTRACT: Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy.
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Antiinflamatorios , Modelos Animales de Enfermedad , Lipopolisacáridos , Ratones Endogámicos C57BL , Miocitos Cardíacos , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Sepsis , Transducción de Señal , Espirostanos , Animales , Lipopolisacáridos/toxicidad , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Espirostanos/farmacología , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Piroptosis/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Línea Celular , Antiinflamatorios/farmacología , Ratones , Cardiomiopatías/prevención & control , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/inducido químicamente , Mediadores de Inflamación/metabolismoRESUMEN
CA is a plant derivative with antibacterial and antiviral pharmacological effects, however, the therapeutic effect of CA on Klebsiella pneumonia and its mechanism study is still unclear. A rat KP model was established in vitro, a pneumonia cell model was established in vivo, the histopathological changes in the lungs were observed by HE staining after CA treatment, the expression of relevant inflammatory factors was detected by ELISA, the changes in the expression of proteins related to the AhR-Src-STAT3-IL-10 signaling pathway were detected by Western blot and immunofluorescence in the lungs, and the interactions between the proteins were verified by COIP relationship. The results showed that CA was able to attenuate the injury and inflammatory response of lung tissues, and molecular docking showed that there were binding sites between CA and AhR, and COIP demonstrated that AhR interacted with both STAT3 and Ser. In addition, CA was able to up-regulate the expression levels of pathway-related proteins of AhR, IL-10, p-Src, and p-STAT3, and AhR knockdown was able to reduce LPS-induced inflammatory responses and up-regulate pathway-related proteins, whereas CA treatment of AhR-knockdown-treated A549 cells did not show any statistically significant difference compared with the AhR knockdown group, demonstrating that CA exerts its pharmacological effects. These findings elucidated the mechanism of CA in the treatment of KP and demonstrated that CA is a potential therapeutic agent for KP.
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Ácidos Cafeicos , Interleucina-10 , Neumonía , Ratas , Animales , Simulación del Acoplamiento Molecular , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Transducción de Señal , Neumonía/tratamiento farmacológico , Klebsiella/metabolismoRESUMEN
BACKGROUND: We aimed to examine prospective associations between different intensities and different types of physical activity (PA) in early pregnancy and hypertensive disorders of pregnancy (HDP) among Chinese women. METHODS: A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study. The pregnancy physical activity questionnaire (PPAQ) was used to assess PA, including household/caregiving, occupational, sports/exercise, and transportation activities in the first trimester of pregnancy. The diagnosis of HDP was collected, including gestational hypertension (GH) and preeclampsia (PE). Data were analyzed by unconditional multivariate logistic regression, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 178 (2.6%) of the 6,820 women were diagnosed with HDP, of which 126 (1.8%) were GH and 52 (0.8%) were PE. Overall, we found no association between PA in early pregnancy and PE. A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity (MVPA) (adjusted OR 0.54, 95% CI 0.31-0.96). No association was observed between PA and HDP in early pregnancy, regardless of different intensities or types of PA. CONCLUSION: MVPA in the first trimester is an influencing factor of HDP. Encouraging pregnant women to engage in MVPA in the first trimester may help to prevent GH.
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CRISPR/Cas(the clustered regularly interspaced short palindromic repeats-CRISPR associated)system exists in most bacteria and all archaea. It is an important strategy for bacteria and archaea to resist foreign nucleic acid invasion and use for self-defense. The CRISPR/Cas system is a simple, fast, and specific diagnostic tool, which is widely used in agriculture, industry, animal husbandry, and medicine. This article mainly introduces and discusses recently advantages and limitations of biosensors combining CRISPR/Cas system with fluorescence, visualization and surface enhanced raman related technologies, as well as future research directions.
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Animales , Sistemas CRISPR-Cas , Bacterias/genética , ArchaeaRESUMEN
Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.
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Although cisplatin drugs have achieved great success in cancer therapy, they also easily cause drug resistance and other side effects. Non-classical platinum (II) complexes with targeted therapy characteristics have become one of the hotspots in the research of new anticancer drugs. In the present work, a series of carbonic anhydrase IX (CAIX)-targeted and inhibited cyclometalated platinum (II) complexes with near-infrared (NIR) phosphorescent emission have been developed, due to the calculation of Molecular docking and the result of CAIX inhibition assay in vitro, all complexes show a high binding affinity and effective inhibition on CAIX in vitro. Moreover, Pt2 shows a significant cellar uptake efficiency, and translocation of red emission in Pt2 from the cytoplasm to nuclear in Hela cell can be recorded by confocal within 24 h, while Pt2 can selectively target and locate in the lysosome of MDA-MB-231 cell, thus resulting in significantly enhanced therapeutic effect on multiple cancer cell lines compared with cisplatin, as well as the killing selectivity towards cancer cell of CAIX-inhibited cyclometalated platinum (II) complex are 6.0-14.6 times higher than that of cisplatin. Hence, our work presents the rational design of Pt (II)-CAIX conjugates as a promising strategy in the application of constructing a new platform for cancer theragnostic agents.
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Antineoplásicos , Platino (Metal) , Humanos , Anhidrasa Carbónica IX/metabolismo , Platino (Metal)/química , Cisplatino/farmacología , Simulación del Acoplamiento Molecular , Células HeLa , Antineoplásicos/farmacología , Antígenos de Neoplasias/metabolismo , Línea Celular TumoralRESUMEN
By rational altering the structure of CN auxiliary ligand, Near-infrared (NIR) phosphorescent cyclometalated platinum (II) and iridium (III) complexes with metformin (Met) have been successfully obtained and characterized. The dissociation of Met in aqueous solution can be accelerated by addition of Glutathione (GSH) and alleviated by drop of histidine, accompanied with a significant decay change of deep red phosphorescence. Besides, Pt3 and Ir1 with moiety of btpq mainly selectively targeted and located in Mitochondrial, while Pt1 of ppy and Pt2 with thpy mainly accumulated in endoplasmic reticulum. Moreover, Pt1-3 and Ir1 with metformin moiety all exert a significant enhanced anticancer activity, among them, Pt3 displays ca.66-fold, ca.147-fold and ca.588-fold higher cytotoxicity than cisplatin, Met-free analogue Pt3a and Met. Their relative anticancer mechanism was further investigated, both Pt2 and Pt3 could form covalent interaction with bovine serum albumin (BSA) and effectively induce reactive oxygen species (ROS) generation, arrest of cell cycle, loss of Mitochondrial membrane potential (MMP), display effective anti-metastasis activity and eventually induce apoptosis of cancer cell.
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Antineoplásicos , Complejos de Coordinación , Metformina , Iridio/química , Platino (Metal)/farmacología , Metformina/farmacología , Medicina de Precisión , Antineoplásicos/química , Apoptosis , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Línea Celular TumoralRESUMEN
BACKGROUND: The high morbidity, high mortality and low survival rate of cardiac arrest (CA) cause a heavy global burden. We aimed to analyze the changes in scientific output related to CA over the past two decades. METHODS: We analyzed the scientific output related to CA from 2000 to 2020 via the Web of Science. The data were analyzed using CiteSpace software. RESULTS: In total, 28,312 articles relating to CA were identified in the Web of Science. The volume of scientific research output in the field of global CA research was mainly distributed in the Americas, Europe and Asia, covering a wide range. Of the 28,312 articles, the research content of the highly cited literature mainly focused on CA, mild hypothermia treatment, and prognosis of CA patients. CONCLUSION: Various scientific methods were applied to reveal scientific productivity, collaboration, and research hotspots in the CA research field. Cardiopulmonary resuscitation (CPR), extracorporeal membrane oxygenation (ECMO), survival and target temperature management are research hotspots. Future research on CA will continue to focus on its treatment and prognosis to improve the survival rate of CA patients.
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OBJECTIVE: This study aims to establish an optimization procedure to define the cut-offs of quantitative assays for acetylcholine receptor antibody (AChRAb), evaluate their diagnostic performance in myasthenia gravis (MG), and explore the association with clinical features. METHODS: Samples from a representative cohort of 77 MG patients, 80 healthy controls (HC) and 80 other autoimmune diseases (OAD) patients were tested using competitive inhibition ELISA and RIA. Raw values (OD and cpm) and processed values (inhibition rate, binding rate and concentration) were used to define the cut-offs with statistical methods, a rough method, and receiver operating characteristic (ROC) curve. Optimal cut-offs were selected by comparing false positive rates in HC and OAD individuals. The diagnostic performance was evaluated in whole MG cohort and subgroups. Agreement between ELISA and RIA for AChRAb positivity were examined with Kappa test and McNemar test. Clinical association with AChRAb was explored by comparison among subgroups and with Spearman rank correlation. RESULTS: The optimal cut-offs for AChRAb positivity were determined as ODâ¯≤â¯1.79 for ELISA and cpmâ¯≥â¯1234.12 for RIA, which derived from statistical method and performed better than those derived from ROC curves. The sensitivity and specificity were 74.03%, 100% for ELISA, and 74.03%, 99.37% for RIA. There was good agreement between ELISA and RIA for AChRAb positivity in whole cohort and subgroups (weighted к ≥ 0.71, pâ¯<â¯0.01; McNemar test, pâ¯>â¯0.05). Levels of AChRAb were different in MG subgroups (pâ¯<â¯0.01). Correlation between Quantitative Myasthenia Gravis scores and AChRAb levels was moderate for ELISA and RIA (rsâ¯=â¯-0.60 and 0.57, pâ¯<â¯0.01). CONCLUSION: The raw testing values of ELISA and RIA were found as optimal quantitative measures of AChRAb levels. There are good agreements on diagnostic performance between two assays. Quantitative values are more informative than positivity in association with clinical features.
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Miastenia Gravis , Receptores Colinérgicos , Autoanticuerpos , Ensayo de Inmunoadsorción Enzimática , Humanos , Pruebas Inmunológicas , Miastenia Gravis/diagnóstico , Receptores Colinérgicos/inmunologíaRESUMEN
BACKGROUND: GNE myopathy is the most common distal myopathy in China. We summarized the clinical, genetic, and pathological characteristics of 125 Chinese patients with GNE myopathy. METHODS: We collected clinical data of 21 patients diagnosed at our hospital and 104 patients from previous reports. Clinical, genetic, and pathological characteristics were summarized. According to the location of mutations, patients were classified into groups to analyze genotype-phenotype correlation. We reviewed the pathological features and studied the expressions of neural cell adhesion molecule. RESULTS: The severity of involvement of lower limb muscles was in the following order: tibialis anterior > biceps femoris > gastrocnemius > iliopsoas > quadriceps femoris. Mutation p.D207V was the most common variant in China. Patients carrying p.D207V tended to show later disease onset. In the epimerase/epimerase group, men had earlier disease onset than women (p < 0.05). In other groups, age at disease onset in females was earlier than that in males. Protein analysis showed decreased sialylation of NCAM and upregulation of LC3 in patients with different mutations. CONCLUSIONS: Mutation p.D207V is the most common GNE variant in China. Involvement of flexor muscles in lower limbs was more obvious than extensor muscles. NCAM expression in patients with various mutations may be a useful diagnostic biomarker in GNE myopathy.
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Miopatías Distales , Moléculas de Adhesión de Célula Nerviosa , Antígeno CD56 , Miopatías Distales/diagnóstico , Miopatías Distales/genética , Miopatías Distales/patología , Femenino , Humanos , Masculino , Complejos Multienzimáticos/genética , Músculo Esquelético/patología , Mutación , Moléculas de Adhesión de Célula Nerviosa/genética , Racemasas y Epimerasas/genéticaRESUMEN
BACKGROUND: Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized with calcium deposition in multiple brain regions. Mutations in PDGFB have been discovered in sporadic and familial PFBC cases. While several known variants displayed loss-of function, no complete deletion of platelet-derived growth factor B (PDGFB) has been reported. METHODS: For the diagnostic purpose, brain computerized tomography or magnetic resonance imaging scanning and whole-genome sequencing were performed on the proband and family members in the pedigree. RESULTS: We identified a heterozygous PDGFB complete deletion in a Chinese pedigree. The proband presented with paroxysmal kinesigenic dyskinesia (PKD), a rare symptom in PFBC. The proband's mother carrying the same mutation was asymptomatic. CONCLUSIONS: For the first time, we reported a PFBC with a heterozygous deletion of PDGFB, and provided evidence of haploinsufficiency in the pathogenesis of PFBC.
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Encefalopatías/genética , Encéfalo/patología , Distonía/genética , Eliminación de Gen , Proteínas Proto-Oncogénicas c-sis/genética , Adolescente , Encefalopatías/patología , Calcinosis/genética , Distonía/patología , Heterocigoto , Humanos , Masculino , Mutación , LinajeRESUMEN
Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.
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Antraquinonas/farmacología , Antídotos/farmacología , Antioxidantes/farmacología , Mitocondrias/efectos de los fármacos , Estrés Oxidativo , Paraquat/envenenamiento , Intoxicación/prevención & control , Células A549 , Animales , Supervivencia Celular , Herbicidas/envenenamiento , Humanos , Masculino , Mitocondrias/patología , Intoxicación/etiología , Intoxicación/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Linear aggregation is present in some animals, such as the coordinated movement of ants and the migration of caterpillars and spinylobsters, but none has been reported on rotifers. The rotifers were collected and clone cultured in the laboratory at 25 ± 1°C, under natural light (light intensity ~130 lx, L:D = 14:10). The culture medium(pH = 7.3) was formulated as described by Suga et al., and rotifers were fed on the micro algae Scenedesmus obliquus grown in HB-4 medium to the exponential growth stage. When density was high (150 individuals ml-1), the behavior of rotifers was observed using a stereo microscope (Motic ES-18TZLED). In this paper, linear aggregation in Brachionus calyciflorus was found for the first time, and experiments were carried out to verify the correlation between linear aggregation and culture density of B. calyciflorus. With the increase of density, the number of aggregations increase, the number of individuals in the aggregation increased, and the maintenance time of the aggregation was also increased. Therefore, we speculate that the formation of aggregates is related to density and may be a behavioral signal of density increase, which may transmit information between density increase and formation of dormant eggs.
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Rotíferos , Animales , Agua Dulce , ScenedesmusRESUMEN
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal disease model of multiple sclerosis (MS) that involves the immune system and central nervous system (CNS). However, it is unclear how genetic predispositions promote neuroinflammation in MS and EAE. Here, we investigated how partial loss-of-function of suppressor of MEK1 (SMEK1), a regulatory subunit of protein phosphatase 4, facilitates the onset of MS and EAE. METHODS: C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish the EAE model. Clinical signs were recorded and pathogenesis was investigated after immunization. CNS tissues were analyzed by immunostaining, quantitative polymerase chain reaction (qPCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Single-cell analysis was carried out in the cortices and hippocampus. Splenic and lymph node cells were evaluated with flow cytometry, qPCR, and western blot analysis. RESULTS: Here, we showed that partial Smek1 deficiency caused more severe symptoms in the EAE model than in controls by activating myeloid cells and that Smek1 was required for maintaining immunosuppressive function by modulating the indoleamine 2,3-dioxygenase (IDO1)-aryl hydrocarbon receptor (AhR) pathway. Single-cell sequencing and an in vitro study showed that Smek1-deficient microglia and macrophages were preactivated at steady state. After MOG35-55 immunization, microglia and macrophages underwent hyperactivation and produced increased IL-1ß in Smek1-/+ mice at the peak stage. Moreover, dysfunction of the IDO1-AhR pathway resulted from the reduction of interferon γ (IFN-γ), enhanced antigen presentation ability, and inhibition of anti-inflammatory processes in Smek1-/+ EAE mice. CONCLUSIONS: The present study suggests a protective role of Smek1 in autoimmune demyelination pathogenesis via immune suppression and inflammation regulation in both the immune system and the central nervous system. Our findings provide an instructive basis for the roles of Smek1 in EAE and broaden the understanding of the genetic factors involved in the pathogenesis of autoimmune demyelination.
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Sistema Nervioso Central/patología , Encefalomielitis Autoinmune Experimental , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Interferón gamma/metabolismo , Microglía/inmunología , Fosfoproteínas Fosfatasas/inmunología , Receptores de Hidrocarburo de Aril/metabolismo , Animales , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/fisiopatología , Citocinas , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Técnicas de Inactivación de Genes , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Esclerosis Múltiple/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Células Mieloides/inmunología , Células Mieloides/metabolismo , Fragmentos de Péptidos/inmunología , Fosfoproteínas Fosfatasas/metabolismo , Transducción de Señal , Bazo/patologíaRESUMEN
Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI). Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation. Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients. Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.
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BACKGROUND AND OBJECTIVES: The worldwide exclusive breastfeeding rate is suboptimal and this study aims to evaluate effects on infant immune development of formula feeding. METHODS AND STUDY DESIGN: A prospective study including 221 infants fed with breast milk or formula was conducted. At 3-month and 9-month, the concentrations of total immunoglobulin (Ig)G, IgM, IgA, IgG1, IgG2, interleukin (IL)-4, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were measured by using enzyme-linked immunosorbent assay (ELISA). Natural killer (NK) cell activity and lymphocyte transformation testing were conducted. Furthermore, the occurrence of infantile diarrhea, respiratory infections and allergic diseases were questioned. RESULTS: The levels of total IgG (Z=-3.21, p=0.001), IgG1 (Z=-2.12, p=0.034), IFN-γ (t=-2.09, p=0.039) and NK cell activity (t=-2.14, p=0.034) were significant higher in formula-fed infants compared to breast-fed after 3 months. At 9-month, the levels of total IgG (Z=-4.34, p<0.001), IgA (Z=-2.05, p=0.041) and TNF-α (t=-2.10, p=0.037) of formula-fed infants were higher, but the lymphocyte stimulation index (t=2.76, p=0.007) was lower than breast-fed infants. While, no significant differences were found in the incidences of diarrhea and respiratory tract infection (p>0.05). CONCLUSIONS: This investigation suggested that formula- and breast-feeding have different contributions to infant immune development, but the formula feeding would not cause significantly increase of diarrhea and respiratory infections.
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Hipersensibilidad , Leche Humana , Lactancia Materna , Femenino , Humanos , Lactante , Alimentos Infantiles , Fórmulas Infantiles , Estudios ProspectivosRESUMEN
Objective: Motor asymmetry is characteristic in Parkinson disease (PD). This phenomenon is originated from uneven degeneration of bilateral substantia nigra. However, this asymmetry may not restrict to substantia nigra or striatum. We aimed to determine the effect of asymmetry on spontaneous brain activity across the whole brain. Methods: We consecutively recruited 71 patients with PD, as well as 35 healthy controls, and collected relevant demographic, clinical, and neuropsychological information. The PD patients were divided into two groups according to the side of motor symptom onset. All the participants underwent resting-state functional magnetic resonance imaging, and spontaneous brain activity was assessed using amplitude of low-frequency fluctuation (ALFF). The associations between areas showing significant group differences and various clinical and neuropsychological measures were analyzed. Results: Finally, the data of 30 PD patients with left-onset (LPD), 27 PD patients with right-onset (RPD), and 32 healthy controls were obtained. The three groups had similar age and gender ratios. Our results demonstrated that LPD patients had increased ALFF in the left inferior temporal gyrus and decreased ALFF in bilateral thalamus and cerebellum anterior lobes than the control group. The value of ALFF of the left inferior temporal gyrus was correlated with motor function, and ALFF value of the thalamus was associated with cognition. Comparisons between LPD and RPD patients and between RPD patients and the controls did not yield significant difference. Conclusions: The present study provides new insights into the distinct characteristics of spontaneous brain activity in LPD, which may be associated with motor and cognitive function.
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An amendment to this paper has been published and can be accessed via the original article.