RESUMO
Magnetic field exposure is an accepted safe and effective modality for nerve injury. However, it is clinically used only as a supplement or salvage therapy at the later stage of treatment. Here, we used a planarian Girardia sinensis decapitated model to investigate beneficial effects of early rotary non-uniform magnetic fields (RMFs) exposure on central nervous regeneration. Our results clearly indicated that magnetic stimulation induced from early RMFs exposure significantly promoted neural regeneration of planarians. This stimulating effect is frequency and intensity dependent. Optimum effects were obtained when decapitated planarians were cultured at 20 °C, starved for 3 days before head-cutting, and treated with 6 Hz 0.02 T RMFs. At early regeneration stage, RMFs exposure eliminated edema around the wound and facilitated subsequent formation of blastema. It also accelerated cell proliferation and recovery of neuron functionality. Early RMFs exposure up-regulated expression of neural regeneration related proteins, EGR4 and Netrin 2, and mature nerve cell marker proteins, NSE and NPY. These results suggest that RMFs therapy produced early and significant benefit in central nervous regeneration, and should be clinically used at the early stage of neural regeneration, with appropriate optimal frequency and intensity.
Assuntos
Sistema Nervoso Central/fisiologia , Campos Magnéticos , Regeneração Nervosa , Planárias/fisiologia , Rotação , Animais , Biomarcadores/metabolismo , Regulação da Expressão Gênica , Temperatura , Fatores de TempoRESUMO
Objective To observe serum levels of interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) in dermatomyositis (DM) patients with different syndrome types of Chinese medicine (CM). Methods Totally 68 dermatomyositis patients were recruited and grouped by syndrome typing of CM, i.e., heat-toxin flourishing syndrome (20 cases) , damp-heat accumulation syndrome (14 cases) , cold-dampness obstruction syndrome (12 cases) , Pi-Shen deficiency syndrome (12 cases) , Gan-Shen yin deficiency syndrome (10 cases). Meanwhile, 64 healthy volunteers were recruited as healthy con- trols. The levels of IL-17 and TNF-α in serum were detected in patient groups and the healthy group. Results Compared with the healthy control group, the serum IL-17 level increased in patients with heat-toxin flourishing syndrome, damp-heat accumulation syndrome, and cold-dampness obstruction syndrome (P <0. 01) ; the serum TNF-α level increased in DM patients with each syndrome (P <0. 01 , P < 0. 05). Compared with the heat-toxin flourishing syndrome group, the serum IL-17 level decreased in patients with cold-dampness obstruction syndrome, Pi-Shen deficiency syndrome, and Gan-Shen yin deficiency syndrome (P <0. 01) ; and the serum TNF-α level decreased in patients with Pi-Shen deficiency syndrome and Gan-Shen yin deficiency syndrome (P <0. 01). Compared with the dampheat accumulation syndrome group, the serum IL-17 level decreased in patients with cold-dampness obstruction syn- drome, Pi-Shen deficiency syndrome, and Gan-Shen yin deficiency syndrome (P <0. 01) , and the serum TNF-α level decreased in patients with Pi-Shen deficiency syndrome and Gan-Shen yin deficiency syndrome (P <0. 01). Compared with the cold-dampness obstruction syndrome group, the serum levels of IL-17 and TNF-α decreased in patients with Pi-Shen deficiency syndrome and Gan-Shen yin deficiency syndrome (P <0. 01 , P <0. 05). Conclusion Serum levels of IL-17 and TNF-α are different in DM patients with different syndrome types of CM.
Assuntos
Dermatomiosite , Interleucina-17 , Medicina Tradicional Chinesa , Fator de Necrose Tumoral alfa , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Humanos , Interleucina-17/sangue , Fator de Necrose Tumoral alfa/sangue , Deficiência da Energia YinRESUMO
Cells establish the asymmetrical distribution of phospholipids and alter their distribution by phospholipid scrambling (PLS) to adapt to environmental changes. Here, we demonstrate that a protein complex, consisting of the ion channel Tmem63b and the thiamine transporter Slc19a2, induces PLS upon calcium (Ca2+) stimulation. Through revival screening using a CRISPR sgRNA library on high PLS cells, we identify Tmem63b as a PLS-inducing factor. Ca2+ stimulation-mediated PLS is suppressed by deletion of Tmem63b, while human disease-related Tmem63b mutants induce constitutive PLS. To search for a molecular link between Ca2+ stimulation and PLS, we perform revival screening on Tmem63b-overexpressing cells, and identify Slc19a2 and the Ca2+-activated K+ channel Kcnn4 as PLS-regulating factors. Deletion of either of these genes decreases PLS activity. Biochemical screening indicates that Tmem63b and Slc19a2 form a heterodimer. These results demonstrate that a Tmem63b/Slc19a2 heterodimer induces PLS upon Ca2+ stimulation, along with Kcnn4 activation.
Assuntos
Cálcio , Proteínas de Transferência de Fosfolipídeos , Fosfolipídeos , Humanos , Cálcio/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo , Proteínas de Transferência de Fosfolipídeos/genética , Fosfolipídeos/metabolismo , Células HEK293 , Canais Iônicos/metabolismo , Canais Iônicos/genética , Animais , Sistemas CRISPR-CasRESUMO
In the aftermath of the COVID-19 pandemic, the intricate relationship between health and the environment has emerged with unparalleled significance. This investigation examines the effect of leisure-time physical activity (LTPA) on health and environmental consciousness and its influence on attitudes towards green/sustainable products among 533 individuals. Utilizing linear structural modeling and regression analysis, the findings reveal that participation in sports and leisure activities significantly mediates the connection between individual well-being and eco-responsible consumer behaviors. Highlighting LTPA's crucial role in enhancing environmental awareness, this study offers invaluable perspectives for the green product sector. It advocates for the development of strategies that align with consumers' environmental values, underscoring the essential function of sports and leisure in fostering sustainable consumer practices. Crucially, this underscores the intertwined nature of environmental sustainability and individual health, highlighting their mutual dependence.
Assuntos
COVID-19 , Exercício Físico , Atividades de Lazer , Humanos , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Comportamento do Consumidor/estatística & dados numéricos , Conservação dos Recursos Naturais , Adulto Jovem , SARS-CoV-2RESUMO
The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.
Assuntos
Fezes , Microbioma Gastrointestinal , Humanos , Fezes/microbiologia , Clostridiales/genética , Clostridiales/metabolismo , Clostridiales/isolamento & purificação , Clostridiales/classificação , Probióticos/metabolismo , Metabolômica , Genômica , Masculino , Filogenia , Feminino , Genoma BacterianoRESUMO
Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture-independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA-originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium- and high-abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota. The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL-10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS-treated and not DSS-treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL-10 and increased IL-17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices.
RESUMO
Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
RESUMO
The authors made a theoretical analysis and experiment research on the relation of time-resolved coherent anti-Stokes Raman scattering (T-CARS) intensity and the sample concentrations in this paper. It was proved experimentally that the T-CARS intensity is quadratic at the concentration higher than 35%, but is linear with the sample concentration at the concentration lower than 20%, which fits with theoretical analysis. And the research results correct inaccurate previous perceptions, which is conducive to better interpretation and application of the CARS process. The linear relation between the intensity of the CARS with the sample concentration at low concentrations indicates that the CARS is allowed for direct and precise concentration measurements, therefore it will be of great importance in biology and biochemistry.
Assuntos
Análise Espectral Raman/métodos , Bioquímica/métodos , Biologia/métodos , Modelos TeóricosRESUMO
Local development enhances the economic capacity and quality of life of the residents and, in particular, attracts tourism to the area. The co-creative value of the residents and the tourists can improve the consensus of the residents on the sustainable development of the place. This study focuses on the factors influencing the co-creation of value between residents and visitors in the Tamsui area near Taipei. The research hypothesis is based on the components of local attachment, economic benefits brought by tourists, environmental costs, social and cultural welfare of the place, life satisfaction of the residents, and the value of co-creation between residents and tourists. A total of 430 questionnaires were collected through a questionnaire survey and statistical data were analyzed using a structural equation model, including descriptive statistical analysis, measurement reliability and validity verification, model fit, and structural model analysis to validate the research hypotheses. The study found that place attachment positively and significantly affects the economic benefits, environmental costs, and socio-cultural welfare of residents about tourists. Resident satisfaction is positively and significantly affected by the environmental costs from visitors and by socio-cultural welfare, but there is no significant impact from economic benefits. Finally, based on the findings of the study, practical recommendations were made for enhancing co-creation value between Tamsui residents and visitors, including enhancing residents' feelings of place attachment and construction of local social culture and welfare. For the residents of Tamsui, unlike the local government and enterprises, need to be able to create value with tourists in order to have a friendly relationship with them and develop regional tourism in a sustainable manner.
RESUMO
In the present paper, the authors used the time-resolved coherent anti-Stokes Raman scattering (CARS) spectroscopy based on supercontinuum developed by ourselves to acquire simultaneously the molecular vibration spectrum and vibrational dephasing time of the molecular various vibrational modes. Using benzonitrile as the sample, the authors measured its vibrational relaxation processes at its five typical vibrational modes and obtained their vibrational dephasing time respectively. In the experiment, the authors also found the phenomenon that oscillations appear in the vibrational dephasing of plane bending vibration mode of benzene ring in benzonitrile, which was caused by superposition of the two adjacent normal vibrational modes excited simultaneously. After mixing benzonitrile with anhydrous ethanol, the authors also measured their vibrational dephasing time. This method is capable of monitoring the changes of the molecular characteristics and its micro-environment, therefore it will find widespread applications in biology, chemistry and materials science.
RESUMO
Water-soluble CdTe/ZnTe core-shell quantum dots (QDs) coated with L-cysteine were synthesized in low-temperature aqueous-phase one-pot approach. The authors measured the spectral characteristics of QDs at different pH in various buffer solutions and under different excitation laser powers. The primary results show that the absorption spectra of QDs approximately overlap and the fluorescence spectra peaks have no shift in different pH solution. The fluorescence intensity increased linearly with increasing pH. With the incubation time in borate buffer solution, the fluorescence intensity decreased a little. Under strong power laser, the QDs were photobleached rapidly. However, QDs are strongly anti-photobleaching under appropriate laser power (< 100 microW). Thus, such QDs have good biological stability and optical stability. By conjugating the QDs with transferrin protein and constructing the targeted fluorescent nanoparticles, the authors labelled the HeLa cell successfully. Photobleaching experiments in vivo show that microenvironment inside cells affect the stability and accelerate the photobleaching of QDs.
Assuntos
Materiais Biocompatíveis , Pontos Quânticos , Telúrio , Compostos de Cádmio , Cisteína , Células HeLa , Humanos , Nanopartículas , Espectrometria de Fluorescência , ÁguaRESUMO
Alzheimer's disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of ß-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only alleviate the symptoms without curing the disease, which is a serious issue and influences the quality of life of the patients and their caregivers. In recent years, stem cell technology has provided new insights into the treatment of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Currently, the main sources of stem cells include neural stem cells, embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells. In this review, we discuss the pathophysiology and general treatment of Alzheimer's disease, and the current state of stem cell transplantation in the treatment of Alzheimer's disease. We also assess future challenges in the clinical application and drug development of stem cell transplantation as a treatment for Alzheimer's disease.
RESUMO
Presenilin-associated protein (PSAP) was originally identified as a mitochondrial proapoptotic protein. To further explore the apoptotic pathway that involves PSAP, our yeast two-hybrid screen revealed that PSAP interacts with a death receptor, DR6. DR6 is a relatively less common member of the death receptor family and has been shown to mediate the neurotoxicity of amyloid-ß, mutant SOD1, and prion proteins and has also been implicated in the regulation of immune cell proliferation and differentiation. Our previous study showed that DR6 induces apoptosis via a unique mitochondria-dependent pathway different from the conventional death receptor-mediated extrinsic apoptotic pathways. Thus, the interaction of DR6 with PSAP established a direct molecular link between DR6 and mitochondrial apoptotic pathway. We investigated the possible role of PSAP in DR6-induced apoptosis. Interestingly, it was discovered that knockdown of PSAP strongly inhibited DR6-induced apoptosis. To further elucidate the mechanism by which PSAP mediates DR6-induced mitochondria-dependent apoptosis, our data demonstrated that knockdown of PSAP blocked DR6-induced Bax translocation and cytochrome c release from the mitochondria. Moreover, it was found that both PSAP and DR6 form complexes with Bax, but at different subcellular locations. The DR6-Bax complex was detected in the cytosolic fraction while the PSAP-Bax complex was detected in the mitochondrial fraction. The observation that knockdown of DR6 significantly reduced the amount of PSAP-Bax complex detected in mitochondria suggests a possibility that DR6-bound Bax is transferred to PSAP upon interaction with PSAP at the mitochondria, leading to cytochrome c release and eventually apoptosis.
Assuntos
Apoptose , Proteínas de Membrana/fisiologia , Proteínas Mitocondriais/fisiologia , Receptores do Fator de Necrose Tumoral/fisiologia , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Mitocôndrias/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Proteína X Associada a bcl-2/metabolismoRESUMO
The interrelationships of three issues relevant to adolescents are the focus of this study, namely, work experience, idolatry, and impulsive buying. Many young people work at some time during their years at high school, which is part of the process of socialization in terms of both thinking and behavior. Idolatry is a common phenomenon among adolescents, and is the way adolescents develop their own values and ideals. Marketers have long recognized the significance of impulse buying, but most studies focus on adult consumers. The purpose of this study was to examine the part-time job effect on idolatry and impulsive buying tendencies of 13- to 20-year-old Taiwanese adolescents. A survey of 337 high school and college students was conducted and results indicate that it has a moderating effect.
Assuntos
Economia , Emprego/psicologia , Comportamento Imitativo , Comportamento Impulsivo/psicologia , Psicologia do Adolescente , Identificação Social , Adolescente , Feminino , Humanos , Masculino , Inquéritos e Questionários , Taiwan , Adulto JovemRESUMO
TNFα/CHX-induced apoptosis is dependent on caspase-8 activation and regulated by Bcl-2. However, the specific participants and precise mechanisms underlying this apoptotic pathway are poorly understood. The proapoptotic proteins Bak and Bax-members of the Bcl-2 family-are essential for the functioning of the mitochondrial apoptotic pathway. In this study, we used the CRISPR/Cas9 system to knockout Bak in the human SH-SY5Y cell line and determined the effects of this knockout on TNFα/CHX-induced apoptosis. Our data showed that overexpression of Bcl-2 dramatically prevented TNFα/CHX-induced apoptosis, and then pro-apoptotic protein Bak was downregulated and became more resistant to TNFα/CHX-induced apoptosis, because both TNFα/CHX-induced PARP cleavage and caspase activation were blocked in BAK-/- cells or using specific siRNA, whereas Bax was dispensable in TNFα/CHX-induced apoptosis, as evidenced using specific siRNA. Bax translocated from the cytosol into the mitochondria in response to TNFα/CHX, and CRISPR/Cas9 knockout of Bak significantly decreased this translocation. These results indicate that TNFα/CHX-induced apoptosis does not occur in Bak-/- cells, suggesting that TNFα/CHX-induced apoptosis is Bak-dependent but Bax-independent.
Assuntos
Apoptose/genética , Caspases/genética , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína X Associada a bcl-2/genética , Apoptose/efeitos dos fármacos , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Cicloeximida/farmacologia , Citosol/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
The morphologies of pure buffer solution and DNA-containing solution in an open fluidic channel with rectangle cross section (1 microm in width and 150 nm in depth) have been explored using non-contact AFM. A remarkable feature is that a uniform nano-scale trench (approximately 15 nm deep and 14 microm long) on the surface of the DNA solution has been observed. The presence of two neighboring stretched DNA molecules near the solution surface may be responsible for the configuration of the nanotrench. This new phenomenon of partially stretched DNA molecules is likely to be useful for the future designing of fluidic devices, and for the manipulation and study of single DNA molecules.
Assuntos
DNA/ultraestrutura , Microfluídica , Microscopia de Força Atômica/métodos , DNA/química , SoluçõesRESUMO
The present authors have previously reported a novel approach to genetically engineer Salmonella typhimurium for the medically important therapeutic strategy of using bacterial agents to target malignant tumors in a breast cancer tumor-bearing nude mouse model. However, studying an immunocompromised mouse model for cancer therapy is insufficient, as certain crucial information about the influence of the immune system may be missing. In the present study, inoculation of the Salmonella strain, YB1, into a colon cancer tumor-bearing immunocompetent mouse model was investigated. The present study determined the tumor targeting efficiency, antitumor potential, the effects of multiple treatments and the systemic toxicity. Intravenous inoculation of YB1 in BALB/c mice exhibited high antitumor effects and also greatly increased the tumor targeting ability and safety compared with the previously-reported nude mouse model. In addition, repeated administration of YB1 further enhanced this effect. Furthermore, no marked toxicity was observed with YB1 treatment, while the VNP20009 and SL7207 strains demonstrated certain adverse effects. The findings of the present study indicate that the YB1 strain is effective and safe in targeting a colon cancer tumor in an immunocompetent mouse model.
RESUMO
The purpose of the study was to investigate whether the small fiber-evoked dorsal root reflex (DRR) can be obtained by electrical stimulation of the peripheral nerve in rats. Fifty-one DRRs were recorded from different kinds of fiber filaments in the proximal ends of the cut L(5) dorsal root following electrical stimulation of the sural nerve. According to the kind of afferent fibers in the sural nerve associated with the DRRs from dorsal root, these DRRs were divided into five different types: A(alphabeta) fiber-evoked A(alphabeta).DRR (A(alphabeta)- A(alphabeta).DRR), A(betadelta) - A(delta ).DRR, A(betadelta)-C.DRR, A(alphabetadelta)-C.DRR and C-C.DRR. The results obtained show that the DRR can be obtained from either A-fibers (including A(delta )-fibers) or C-fibers of dorsal root filaments by stimulation of the sural nerve. It is therefore suggested that either A(delta ).DRR or C.DRR can be used as a validity index of presynaptic inhibition of the thin primary afferent terminals for investigation of the modulation mechanisms of peripheral effectors.