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1.
Microorganisms ; 11(12)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38138105

RESUMO

In this study, we reported the complete genome sequence of Shewanella oncorhynchi for the first time. S. oncorhynchi Z-P2 is a bacterium that produces the siderophore putrebactin. Its genome consists of a circular chromosome of 5,034,612 bp with a G + C content of 45.4%. A total of 4544 protein-coding genes, 109 tRNAs and 31 rRNAs were annotated by the RAST. Five non-ribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) gene clusters were identified by the antiSMASH analysis. The pan-genome analysis of Z-P2 and 10 Shewanella putrefaciens revealed 9228 pan-gene clusters and 2681 core gene clusters, with Z-P2 having 618 unique gene clusters. Additionally, the gene cluster involved in putrebactin biosynthesis in Z-P2 was annotated, and the mechanism of putrebactin biosynthesis was analyzed. The putrebactin produced by Z-P2 was detected using UPLC-MS analysis, with an [M + H]+ molecular ion at m/z 373.21. These findings provide valuable support for further research on the genetic engineering of putrebactin biosynthetic genes of Z-P2 and their potential applications.

2.
Proc Natl Acad Sci U S A ; 120(21): e2207185120, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37192169

RESUMO

Collecting complete network data is expensive, time-consuming, and often infeasible. Aggregated Relational Data (ARD), which ask respondents questions of the form "How many people with trait X do you know?" provide a low-cost option when collecting complete network data is not possible. Rather than asking about connections between each pair of individuals directly, ARD collect the number of contacts the respondent knows with a given trait. Despite widespread use and a growing literature on ARD methodology, there is still no systematic understanding of when and why ARD should accurately recover features of the unobserved network. This paper provides such a characterization by deriving conditions under which statistics about the unobserved network (or functions of these statistics like regression coefficients) can be consistently estimated using ARD. We first provide consistent estimates of network model parameters for three commonly used probabilistic models: the beta-model with node-specific unobserved effects, the stochastic block model with unobserved community structure, and latent geometric space models with unobserved latent locations. A key observation is that cross-group link probabilities for a collection of (possibly unobserved) groups identify the model parameters, meaning ARD are sufficient for parameter estimation. With these estimated parameters, it is possible to simulate graphs from the fitted distribution and analyze the distribution of network statistics. We can then characterize conditions under which the simulated networks based on ARD will allow for consistent estimation of the unobserved network statistics, such as eigenvector centrality, or response functions by or of the unobserved network, such as regression coefficients.

3.
Cell Res ; 33(6): 421-433, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37085732

RESUMO

The lung is the primary respiratory organ in human, in which the proximal airway and the distal alveoli are responsible for air conduction and gas exchange, respectively. However, the regulation of proximal-distal patterning at the embryonic stage of human lung development is largely unknown. Here we investigated the early lung development of human embryos at weeks 4-8 post fertilization (Carnegie stages 12-21) using single-cell RNA sequencing, and obtained a transcriptomic atlas of 169,686 cells. We observed discernible gene expression patterns of proximal and distal epithelia at week 4, upon the initiation of lung organogenesis. Moreover, we identified novel transcriptional regulators of the patterning of proximal (e.g., THRB and EGR3) and distal (e.g., ETV1 and SOX6) epithelia. Further dissection revealed various stromal cell populations, including an early-embryonic BDNF+ population, providing a proximal-distal patterning niche with spatial specificity. In addition, we elucidated the cell fate bifurcation and maturation of airway and vascular smooth muscle progenitor cells at the early stage of lung development. Together, our study expands the scope of human lung developmental biology at early embryonic stages. The discovery of intrinsic transcriptional regulators and novel niche providers deepens the understanding of epithelial proximal-distal patterning in human lung development, opening up new avenues for regenerative medicine.


Assuntos
Pulmão , Alvéolos Pulmonares , Humanos , Pulmão/metabolismo , Diferenciação Celular/genética , Embrião de Mamíferos , Análise de Sequência de RNA
4.
Cell Biosci ; 12(1): 174, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243732

RESUMO

BACKGROUND: The kidneys require vast amounts of mitochondria to provide ample energy to reabsorb nutrients and regulate electrolyte, fluid, and blood pressure homeostasis. The lack of the human model hinders the investigation of mitochondria homeostasis related to kidney physiology and disease. RESULTS: Here, we report the generation of mitochondria-rich kidney organoids via partial reprogramming of human urine cells (hUCs) under the defined medium. First, we reprogrammed mitochondria-rich hUCs into expandable intermediate mesoderm progenitor like cells (U-iIMPLCs), which in turn generated nephron progenitors and formed kidney organoids in both 2D and 3D cultures. Cell fate transitions were confirmed at each stage by marker expressions at the RNA and protein levels, along with chromatin accessibility dynamics. Single cell RNA-seq revealed hUCs-induced kidney organoids (U-iKOs) consist of podocytes, tubules, and mesenchyme cells with 2D dominated with mesenchyme and 3D with tubule and enriched specific mitochondria function associated genes. Specific cell types, such as podocytes and proximal tubules, loop of Henle, and distal tubules, were readily identified. Consistent with these cell types, 3D organoids exhibited the functional and structural features of the kidney, as indicated by dextran uptake and transmission electron microscopy. These organoids can be further matured in the chick chorioallantoic membrane. Finally, cisplatin, gentamicin, and forskolin treatment led to anatomical abnormalities typical of kidney injury and altered mitochondria homeostasis respectively. CONCLUSIONS: Our study demonstrates that U-iKOs recapitulate the structural and functional characteristics of the kidneys, providing a promising model to study mitochondria-related kidney physiology and disease in a personalized manner.

5.
Stem Cell Rev Rep ; 18(7): 2414-2430, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35246800

RESUMO

Despite direct reprogramming of human cardiac fibroblasts into induced cardiomyocytes (iCM) holds great potential for heart regeneration, the mechanisms are poorly understood. Whether other human somatic cells could be reprogrammed into cardiomyocytes is also unknown. Here, we report human urine cells (hUCs) could be converted into CM-like cells from different donors and the related chromatin accessibility dynamics (CAD) by assay for transposase accessible chromatin(ATAC)-seq. hUCs transduced by MEF2C, TBX5, MESP1 and MYOCD but without GATA4 expressed multiple cardiac specific genes, exhibited Ca2+ oscillation potential and sarcomeric structures, and contracted synchronously in coculture with mouse CM. Additionally, we found that MYOCD is required for both closing and opening critical loci, mainly by hindering the opening of loci enriched with motifs for the TEAD and AP1 family and promoting the closing of loci enriched with ETS motifs. These changes differ partially from CAD observed during iCM induction from human fibroblasts. Collectively, our study offers one practical platform for iCM generation and insights into mechanisms for iCM fate determination.


Assuntos
Cromatina , Miócitos Cardíacos , Animais , Células Cultivadas , Cromatina/genética , Fibroblastos , Humanos , Camundongos , Transposases
6.
Front Public Health ; 9: 591614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33634064

RESUMO

Based on the Cumulative Risk Model, a single risk factor cannot play a decisive role, but the cumulative ecological risks may have complex superposition effects on adolescents' problem behaviors. However, although many studies have investigated the specific influences of single external risk factors on problem behaviors, the effect of cumulative ecological risk on problem behaviors and especially the underlying mechanisms therein have been under-investigated. Therefore, this study aimed to explore the effect of cumulative ecological risk on adolescents' problem behaviors, and the mediating effects of core self-evaluation and basic psychological needs satisfaction therein. To achieve this, 1,080 adolescents in secondary vocational schools were surveyed with the questionnaires of cumulative ecological risk, basic psychological need satisfaction, core self-evaluation, externalizing and internalizing problem behaviors. Results showed that: (a) cumulative ecological risk was positively related with both internalizing problem behavior and externalizing problem behavior; (b) core self-evaluation and basic psychological need satisfaction not only respectively but also sequentially mediated the relationship between cumulative ecological risk and two sorts of problem behaviors. These results provide some pivotal implications for the precaution and intervention of the adolescent problem behaviors.


Assuntos
Comportamento do Adolescente , Comportamento Problema , Adolescente , Autoavaliação Diagnóstica , Humanos , Satisfação Pessoal , Instituições Acadêmicas
7.
PLoS Negl Trop Dis ; 14(8): e0008525, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32785225

RESUMO

Burkholderia pseudomallei is the causative agent of melioidosis, endemic in Southeast Asia and Northern Australia, and increasingly recognized in southern China, especially in Hainan Province. Mycotic aneurysm caused by B. pseudomallei is a rare but potentially severe illness with a high mortality rate. The clinical features of the mycotic aneurysm secondary to melioidosis have not been illustrated in China. Over a seven-year period (2013 to 2019), 159 patients with bacteremic melioidosis were retrospectively analyzed in Hainan province, China, of whom eight patients were confirmed to have mycotic aneurysm through the combination of imaging examination, pathologic examination and aneurysm tissue culture. We summarized these eight patients' clinical characteristics, demographical features, treatments and outcomes. The susceptibilities to five commonly-used antibiotics for these eight B. pseudomallei isolates were also determined by E-test strips. Furthermore, the mycotic aneurysm cases secondary to melioidosis retrieved from the literature were also reviewed. Of the eight cases, six had abdominal mycotic aneurysms, one had a left iliac aneurysm, and the other one had an infectious mesenteric aneurysm. They were aged from 48 to 69 years old, and had the underlying risk factors of diabetes mellitus (2 patients), long-term smoking (4 patients), hypertension (6 patients), and soil and water contact history (6 patients), respectively. The positive arterial aneurysm imaging was observed in all patients via computed tomography (CT) or angiography. Eight B. pseudomallei isolates collected from both blood and mycotic aneurysm tissues remained 100% susceptible to imipenem and ceftazidime. After surgery combined with antibiotic administration, six patients survived, with a mortality rate of 25%. In melioidosis endemic areas, the mycotic aneurysm secondary to melioidosis might be underdiagnosed, and increased awareness of predisposing risk factors and clinical features of the mycotic aneurysm is required. Following a positive B. pseudomallei blood culture, the diagnosis of mycotic aneurysm should be under consideration in those with abdominal pain and/or hypertension. Imaging by CT or angiography is indispensable for its timely diagnosis and management.


Assuntos
Aneurisma Infectado/complicações , Aneurisma Infectado/diagnóstico por imagem , Burkholderia pseudomallei/isolamento & purificação , Melioidose/complicações , Melioidose/diagnóstico por imagem , Idoso , Aneurisma Infectado/tratamento farmacológico , Aneurisma Infectado/microbiologia , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/genética , Ceftazidima , China , Feminino , Humanos , Imipenem , Masculino , Melioidose/tratamento farmacológico , Melioidose/microbiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Solo , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Genoma
8.
Exp Neurol ; 327: 113215, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31991126

RESUMO

Neurogenic differentiation 1 (NeuroD1) is mainlyexpressed in developing neurons where it plays critical roles in neuronal maturation and neurite elongation. The potential role and mechanism of NeuroD1 in adult axonal regeneration is not clear. The present study used synapsin (SYN) Cre and AAV9-Flex vectors to conditionally overexpress NeuroD1 in adult spinal neurons and found that NeuroD1 overexpression significantly accelerated axonal regeneration and functional recovery after sciatic nerve injury. Further in vitro and in vivo experiments suggested that the mechanism of NeuroD1 promotion on axonal regeneration was related to its regulation of the expression of neurotrophin BDNF and its receptor TrkB as well as a microtubule severing protein spastin.


Assuntos
Axônios/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Nervo Isquiático/lesões , Nervos Espinhais/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Feminino , Camundongos , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/genética , Traumatismos dos Nervos Periféricos/fisiopatologia , Receptor trkB/metabolismo , Recuperação de Função Fisiológica/fisiologia
9.
Cells ; 9(1)2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963385

RESUMO

RhoA-GTPase (RhoA) is widely regarded as a key molecular switch to inhibit neurite outgrowth by rigidifying the actin cytoskeleton. However, during neurite outgrowth, whether and how microtubule dynamics are regulated by RhoA remains to be elucidated. Herein, CT04 and Y27632 were used to inactivate RhoA and its downstream effector Rho-associated coiled coil-forming kinase (ROCK), while the RhoAQ63L lentiviral vector was utilized to overexpress the constitutively activated RhoA in dorsal root ganglion (DRG) neurons or neuronal differentiated PC12 cells. The current data illustrate that the RhoA signaling pathway negatively modulates neurite outgrowth and elevates the expression of Glu-tubulin (a marker for a stabilized microtubule). Meanwhile, the microtubule-severing proteins spastin and p60-katanin were downregulated by the RhoA signaling pathway. When spastin and p60-katanin were knocked down, the effects of RhoA inhibition on neurite outgrowth were significantly reversed. Taken together, this study demonstrates that the RhoA pathway-mediated inhibition of neurite outgrowth is not only related to the modulation of microfilament dynamics but is also attributable to the regulation of the expression of spastin and p60-katanin and thus influences microtubule dynamics.


Assuntos
Katanina/metabolismo , Crescimento Neuronal , Espastina/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Diferenciação Celular , Gânglios Espinais/metabolismo , Técnicas de Silenciamento de Genes , Neurônios/citologia , Neurônios/metabolismo , Células PC12 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Tubulina (Proteína)/metabolismo
10.
Am Econ Rev ; 110(8): 2454-2484, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34526729

RESUMO

Social network data are often prohibitively expensive to collect, limiting empirical network research. We propose an inexpensive and feasible strategy for network elicitation using Aggregated Relational Data (ARD): responses to questions of the form "how many of your links have trait k ?" Our method uses ARD to recover parameters of a network formation model, which permits sampling from a distribution over node- or graph-level statistics. We replicate the results of two field experiments that used network data and draw similar conclusions with ARD alone.

11.
Front Cell Dev Biol ; 8: 591883, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425896

RESUMO

Spinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms. In vivo neuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion in mouse brains with injury or Alzheimer's disease by overexpressing a single neural transcription factor NeuroD1. Here we demonstrate regeneration of spinal cord neurons from reactive astrocytes after SCI through AAV NeuroD1-based gene therapy. We find that NeuroD1 converts reactive astrocytes into neurons in the dorsal horn of stab-injured spinal cord with high efficiency (~95%). Interestingly, NeuroD1-converted neurons in the dorsal horn mostly acquire glutamatergic neuronal subtype, expressing spinal cord-specific markers such as Tlx3 but not brain-specific markers such as Tbr1, suggesting that the astrocytic lineage and local microenvironment affect the cell fate after conversion. Electrophysiological recordings show that the NeuroD1-converted neurons can functionally mature and integrate into local spinal cord circuitry by displaying repetitive action potentials and spontaneous synaptic responses. We further show that NeuroD1-mediated neuronal conversion can occur in the contusive SCI model with a long delay after injury, allowing future studies to further evaluate this in vivo reprogramming technology for functional recovery after SCI. In conclusion, this study may suggest a paradigm shift from classical axonal regeneration to neuronal regeneration for spinal cord repair, using in vivo astrocyte-to-neuron conversion technology to regenerate functional new neurons in the gray matter.

12.
BMC Infect Dis ; 19(1): 984, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752745

RESUMO

BACKGROUND: Burkholderia pseudomallei is a gram-negative bacterium and the causative pathogen of melioidosis, which manifests a variety ranges of infection symptoms. However, deep venous thrombosis (DVT) and pulmonary embolism (PE) secondary to bacteremic melioidosis are rarely documented in the literature. Herein, we reported a fatal case of melioidosis combined with DVT and PE. CASE PRESENTATION: A 54-year-old male construction worker and farmer with a history of diabetes was febrile, painful in left thigh, swelling in left lower limb, with chest tightness and shortness of breath for 4 days. He was later diagnosed as DVT of left lower extremity and PE. The culture of his blood, sputum and bone marrow samples grew B. pseudomallei. The subject was administrated with antibiotics (levofloxacin, cefoperazone/tazobactam, and imipenem) according to antimicrobial susceptibility testing and low molecular heparin for venous thrombosis. However, even after appropriate treatment, the patient deteriorated rapidly, and died 2 weeks after admission. CONCLUSIONS: This study enhanced awareness of the risk of B. pseudomallei bloodstream infection in those with diabetes. If a patient has predisposing factors of melioidosis, when DVT is suspected, active investigation and multiple therapeutic interventions should be implemented immediately to reduce mortality rate.


Assuntos
Melioidose/complicações , Embolia Pulmonar/etiologia , Trombose Venosa/etiologia , Antibacterianos/administração & dosagem , Burkholderia pseudomallei/classificação , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/isolamento & purificação , China , Evolução Fatal , Heparina/administração & dosagem , Humanos , Masculino , Melioidose/microbiologia , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Trombose Venosa/tratamento farmacológico
13.
Front Cell Neurosci ; 13: 108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949031

RESUMO

Ascorbic acid (AA) is an essential micronutrient that has been safely used in the clinic for many years. The present study indicates that AA has an unexpected function in facilitating nerve regeneration. Using a mouse model of sciatic nerve crush injury, we found that AA can significantly accelerate axonal regrowth in the early stage [3 days post-injury (dpi)], a finding that was revealed by immunostaining and Western blotting for antibodies against GAP-43 and SCG10. On day 28 post-injury, histomorphometric assessments demonstrated that AA treatment increased the density, size, and remyelination of regenerated axons in the injured nerve and alleviated myoatrophy in the gastrocnemius. Moreover, the results from various behavioral tests and electrophysiological assays revealed that nerve injury-derived functional defects in motor and sensory behavior as well as in nerve conduction were significantly attenuated by treatment with AA. The potential mechanisms of AA in nerve regeneration were further explored by investigating the effects of AA on three types of cells involved in this process [neurons, Schwann cells (SCs) and macrophages] through a series of experiments. Overall, the data illustrated that AA treatment in cultured dorsal root ganglionic neurons resulted in increased neurite growth and lower expression of RhoA, which is an important inhibitory factor in neural regeneration. In SCs, proliferation, phagocytosis, and neurotrophin expression were all enhanced by AA. Meanwhile, AA treatment also improved proliferation, migration, phagocytosis, and anti-inflammatory polarization in macrophages. In conclusion, this study demonstrated that treatment with AA can promote the morphological and functional recovery of injured peripheral nerves and that this effect is potentially due to AA's bioeffects on neurons, SCs and macrophages, three of most important types of cells involved in nerve injury and regeneration.

14.
Aust N Z J Psychiatry ; 53(1): 68-79, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30453750

RESUMO

OBJECTIVE: The brain functional alterations at regional and network levels in post-traumatic stress disorder patients are still unclear. This study explored brain functional alterations at regional and network levels in post-traumatic stress disorder patients with resting-state functional magnetic resonance imaging and evaluated the relationship between brain function and clinical indices in post-traumatic stress disorder. METHODS: Amplitude of low-frequency fluctuation and seed-based functional connectivity analyses were conducted among typhoon survivors with ( n = 27) and without post-traumatic stress disorder ( n = 33) and healthy controls ( n = 30) to assess the spontaneous brain activity and network-level brain function. Pearson correlation analyses were performed to examine the association of brain function with clinical symptom and social support. RESULTS: Both the post-traumatic stress disorder group and the trauma-exposed control group showed decreased amplitude of low-frequency fluctuation in the dorsal anterior cingulate cortex relative to the healthy control group. The post-traumatic stress disorder group showed increased dorsal anterior cingulate cortex functional connectivity with the right paracentral lobule and bilateral precentral gyrus/postcentral gyrus relative to both control groups. Both traumatized groups exhibited decreased dorsal anterior cingulate cortex functional connectivity with the right hippocampus and left cerebellum relative to the healthy control group. More decreased dorsal anterior cingulate cortex functional connectivity with the right hippocampus was found in the post-traumatic stress disorder group. The Checklist-Civilian Version score positively correlated with functional connectivity between the dorsal anterior cingulate cortex and the right paracentral lobule as well as between the dorsal anterior cingulate cortex and the right precentral gyrus/postcentral gyrus. The social support was associated with functional connectivity between the dorsal anterior cingulate cortex and the bilateral precentral gyrus/postcentral gyrus as well as the dorsal anterior cingulate cortex and the left middle frontal gyrus. CONCLUSION: Trauma exposure may result in aberrant local and network-level functional connectivity in individuals with or without post-traumatic stress disorder. Altered amplitude of low-frequency fluctuation in the dorsal anterior cingulate cortex may be a predisposing risk factor for post-traumatic stress disorder development following trauma exposure. More prominent decreased dorsal anterior cingulate cortex functional connectivity with the right hippocampus might be specific in the post-traumatic stress disorder group. Improvement of social support might possibly be significant for post-traumatic stress disorder patients.


Assuntos
Conectoma , Giro do Cíngulo/fisiopatologia , Rede Nervosa/fisiopatologia , Trauma Psicológico/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Tempestades Ciclônicas , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Trauma Psicológico/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Sobreviventes
15.
Front Cell Neurosci ; 12: 437, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30515082

RESUMO

Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway.

16.
Exp Neurol ; 308: 26-34, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29940159

RESUMO

RhoA is a small GTPase that regulates many functions of mammalian cells via actin reorganization. Lots of studies uncovered that its activation acts as a major negative regulator of neurite extension, and inhibition of RhoA activity or reduction of its expression can promote neuron survival and axonal regeneration. However, little is known about whether RhoA also exerts important functions on Schwann cells (SCs) which are the glial cells of the peripheral nervous system (PNS). Recently, we reported that RhoA plays important roles in the proliferation, migration and myelination of SCs. In the present study, using RNA interference to knockdown RhoA expression and CT04 (a cell-permeable C3 Transferase) to inhibit RhoA activation we found that blocking RhoA can slack SC differentiation. Unexpectedly, inhibiting ROCK, the mostly well-known downstream effector of RhoA, has no influence on SC differentiation. Instead, the inhibition of RhoA in differentiating SCs results in the activation of JNK and p38 MAPK. And the inhibitor of JNK but not p38 MAPK can promote SC differentiation in the presence of RhoA inhibition. Overall results indicate that RhoA plays a vital role in SC differentiation via JNK pathway rather than ROCK pathway.


Assuntos
Diferenciação Celular/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Células de Schwann/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Neurogênese/fisiologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Neural Plast ; 2018: 8561704, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849572

RESUMO

Accumulating evidences suggest that peripheral nerve injury (PNI) may initiate astrocytic responses in the central nervous system (CNS). However, the response of astrocytes in the spinal ventral horn and its potential role in nerve regeneration after PNI remain unclear. Herein, we firstly illustrated that astrocytes in the spinal ventral horn were dramatically activated in the early stage following sciatic nerve injury, and these profiles were eliminated in the chronic stage. Additionally, we found that the expression of neurotrophins, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3), also accompanied with astrocyte activation. In comparison with the irreversible transected subjects, astrocyte activation and the neurotrophic upregulation in the early stage were more drastic in case the transected nerve was rebridged immediately after injury. Furthermore, administering fluorocitrate to inhibit astrocyte activation resulted in decreased neurotrophin expression in the spinal ventral horn and delayed axonal regeneration in the nerve as well as motor function recovery. Overall, the present study indicates that peripheral nerve injury can initiate astrocyte activation accompanied with neurotrophin upregulation in the spinal ventral horn. The above responses mainly occur in the early stage of PNI and may contribute to nerve regeneration and motor function recovery.


Assuntos
Astrócitos/metabolismo , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos da Medula Espinal/metabolismo , Corno Ventral da Medula Espinal/metabolismo , Animais , Feminino , Fatores de Crescimento Neural/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Traumatismos da Medula Espinal/complicações , Corno Ventral da Medula Espinal/fisiopatologia
18.
Appl Ergon ; 67: 1-8, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29122180

RESUMO

BACKGROUND: We sought to evaluate potential mediators of the relationship between heat exposure and traumatic injuries in outdoor agricultural workers. METHODS: Linear mixed models were used to estimate associations between maximum work-shift Wet Bulb Globe Temperature (WBGTmax) and post-shift vigilance (reaction time) and postural sway (total path length) in a cross-sectional sample of 46 Washington State tree fruit harvesters in August-September 2015. RESULTS: The mean (SD) WBGTmax was 27.4 (3.2)°C in August and 21.2 (2.0)°C in September. The mean pre-work-shift participant urine specific gravity indicated minimal dehydration. Twenty-four percent of participants exhibited possible excessive sleepiness. There was no association between WBGTmax and post-shift reaction time or total path length. CONCLUSIONS: Heat exposure was not associated with impaired vigilance or balance in this study, in which the overall mean (SD) WBGTmax was 25.9 (4.2)°C. However, the study identified opportunities to ensure adequate pre-work-shift hydration and to optimize sleep and work-shift timing in order to reduce occupational injury and heat-related illness risk.


Assuntos
Agricultura/métodos , Transtornos de Estresse por Calor/etiologia , Temperatura Alta/efeitos adversos , Exposição Ocupacional/efeitos adversos , Traumatismos Ocupacionais/etiologia , Adulto , Estudos Transversais , Desidratação , Feminino , Frutas , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Tempo de Reação , Estações do Ano , Sono , Árvores , Washington , Tolerância ao Trabalho Programado/fisiologia
19.
Exp Neurol ; 292: 92-101, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28283336

RESUMO

Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering.


Assuntos
Células-Tronco Mesenquimais/citologia , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Recuperação de Função Fisiológica/efeitos dos fármacos , Células de Schwann/citologia , Animais , Axônios/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Bainha de Mielina/metabolismo , Recuperação de Função Fisiológica/fisiologia , Células de Schwann/fisiologia , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Cicatrização
20.
Arch Environ Occup Health ; 72(6): 313-316, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-28139172

RESUMO

Recent studies suggest that heat exposure degrades work productivity, but such studies have not considered individual- and workplace-level factors. Forty-six tree-fruit harvesters (98% Latino/a) from 6 orchards participated in a cross-sectional study in central/eastern Washington in 2015. The association between maximum measured work-shift wet-bulb globe temperature (WBGTmax) and productivity (total weight of fruit bins collected per time worked) was estimated using linear mixed-effects models, adjusting for relevant confounders. The mean (standard deviation) WBGTmax was 27.9°C (3.6°C) in August and 21.2°C (2.0°C) in September. There was a trend of decreasing productivity with increasing WBGTmax, but this association was not statistically significant. When individual- and workplace-level factors were included in the model, the association approached the null. Not considering individual, work, and economic factors that affect rest and recovery in projections of the effects of climate change could result in overestimates of reductions in future productivity and underestimate risk of heat illness.


Assuntos
Mudança Climática , Eficiência , Fazendeiros , Temperatura Alta/efeitos adversos , Exposição Ocupacional , Adolescente , Adulto , Estudos Transversais , Fazendeiros/psicologia , Feminino , Humanos , Umidade , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional/estatística & dados numéricos , Saúde Ocupacional/tendências , Washington , Adulto Jovem
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