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1.
Int J Biol Sci ; 16(7): 1252-1263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174799

RESUMO

Although EHMT2 (also known as G9a) plays a critical role in several kinds of cancers and cardiac remodeling, its function in vascular smooth muscle cells (VSMCs) remains unknown. In the present study, we revealed a novel function of EHMT2 in regulating autophagic cell death (ACD) of VSMC. Inhibition of EHMT2 by BIX01294 or knockdown of EHMT2 resulted in reduced VSMC numbers which were independent of proliferation and apoptosis. Interestingly, EHMT2 protein levels were significantly decreased in VSMCs treated with autophagic inducers. Moreover, more autophagic vacuoles and accumulated LC3II were detected in VSMCs treated with BIX01294 or lenti-shEHMT2 than their counterparts. Furthermore, we found that EHMT2 inhibited the ACD of VSMCs by suppressing autophagosome formation. Mechanistically, the pro-autophagic effect elicited by EHMT2 inhibition was associated with SQSTM1 and BECN1 overexpression. Moreover, these detrimental effects were largely nullified by SQSTM1 or BECN1 knockdown. More importantly, similar results were observed in primary human aortic VSMCs. Overall, these findings suggest that EHMT2 functions as a crucial negative regulator of ACD via decreasing SQSTM1 or BECN1 expression and that EHMT2 could be a potent therapeutic target for cardiovascular diseases (e.g., aortic dissection).

2.
J Infect ; 80(4): 401-406, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112886

RESUMO

BACKGROUND: Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. METHODS: We collected patients who were transferred by Beijing Emergency Medical Service to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. FINDINGS: By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. INTERPRETATION: On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. FUNDING: Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.

3.
J Neurol Sci ; 413: 116741, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32146216

RESUMO

OBJECTIVE: Compare driving capacity of individuals with Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC) using a driving simulation program. METHODS: A prospective study was performed on individuals with ALS who reported they were still driving, and a group of HCs. Demographic data included age and gender. Assessment included cognitive assessments (Montreal cognitive assessment [MoCA] and ALS Cognitive Behavioral Scale [ALS-CBS]); gait speed (m/s); ALS Functional Rating Scale-revised total score (ALSFRS-R); and simulated driving assessment (Lane Change Task [LCT]). The LCT is a simple assessment tool which simulates the visual, cognitive, and motor demands of driving to detect at-risk drivers and uses distractions (secondary tasks) to quantify the performance loss on the primary task (lane changes). RESULTS: Twenty-eight individuals with ALS (22 males, mean age 64 years) and 20 HCs (7 males, mean age 59 years) were studied. Individuals with mild to moderate ALS (ALSFRS-R mean 36.2) were older, had mild cognitive difficulty (MoCA 24 vs 27; ALS-CBS 14.19 [SD 3.85]) and mobility decline (gait speed 1.1 vs 1.4 m/s) compared to HC. Driving assessment using the LCT found no differences in baseline scores or during motor, cognitive, or visually distracting conditions. CONCLUSIONS: Individuals with ALS with mild to moderate disease progression, with cognitive and motor weakness still demonstrate similar driving capacity to HCs using a driving simulation task. Driving assessment needs to be expanded longitudinally and perhaps with more robust measures to more precisely identify types of driving challenges that lead to cessation of driving in individuals with ALS.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32069792

RESUMO

Hospital sewage plays a key role in the dissemination of antibiotic-resistant genes (ARGs) by serving as an environmental antimicrobial resistance reservoir. In this study, we aimed to characterize the cephalosporin- and carbapenem-resistant isolates from hospital sewage and receiving rivers. The results showed that ESBL (blaCTX-M) and carbapenemase genes (blaNDM and blaKPC) were widely detected in a number of different bacterial species. These resistance genes were mainly harbored in Enterobacteriaceae, followed by Acinetobacter and Aeromonas isolates. More attention should be given to these bacteria as important vectors of ARGs in the environment. Furthermore, we showed that the multidrug resistance phenotype was highly prevalent, which was found in 85.5% Enterobacteriaceae and 75% Acinetobacter strains. Notably, the presence of carbapenemase genes in isolates from treated effluents and receiving rivers indicates that the discharges of wastewater treatment plants could be an important source for high-risk resistance genes propagation to the environment. In conclusion, this study shows a high prevalence of ESBL- and carbapenemase-producing bacteria in hospital sewage and receiving rivers in China. These findings have serious implications for human health, and also suggest the need for more efforts to control the dissemination of resistant bacteria from hospital sewage into the environment.

5.
Int Immunopharmacol ; 82: 106302, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32086097

RESUMO

Toxoplasma gondii (T. gondii) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti-T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii-infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii-induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii. AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidated the effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.

6.
Acta Biomater ; 106: 360-375, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32058083

RESUMO

The poor adhesion of anodic TiO2 nanotubes (TNTs) arrays on titanium (Ti) substrates adversely affects applications in many fields especially biomedical engineering. Herein, an efficient strategy is described to improve the adhesion strength of TNTs by performing grain refinement in the underlying Ti substrate via high-pressure torsion processing, as a larger number of grain boundaries can provide more interfacial mechanical anchorage. This process also improves the biocompatibility and osseointegration of TNTs by increasing the surface elastic modulus. The TNTs in length of 0.4 µm have significantly larger adhesion strength than the 2.0 µm long ones because the shorter TNTs experience less interfacial internal stress. However, post-anodization annealing reduces the fluorine concentration in TNTs and adhesion strength due to the formation of interfacial cavities during crystallization. The interfacial structure of TNTs/Ti system and the mechanism of adhesion failures are further investigated and discussed. STATEMENT OF SIGNIFICANCE: Self-assembled TiO2 nanotubes (TNTs) prepared by electrochemical anodization have a distinct morphology and superior properties, which are commonly used in photocatalytic systems, electronic devices, solar cells, sensors, as well as biomedical implants. However, the poor adhesion between the TNTs and Ti substrate has hampered wider applications. Here in this study, we describe an efficient strategy to improve the adhesion strength of TNTs by performing grain refinement in the underlying Ti substrate via high-pressure torsion (HPT) processing. The interfacial structure of TNTs/Ti system and the mechanism of adhesion failure are systematically studied and discussed. Our findings not only develop the knowledge of TNTs/Ti system, but also provide new insights into the design of Ti-based implants for orthopedic applications.

7.
J Clin Neurosci ; 73: 245-251, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32067828

RESUMO

Fragile X syndrome (FXS) is a common mental retardation syndrome. Anxiety and abnormal social behaviors are prominent features of FXS in humans. To better understand the effects of hyperbaric oxygen therapy (HBOT) on these behaviors, we analyzed anxiety-related and social behaviors in Fmr1 knockout mice treated by HBOT. In the open field test, HBOT group mice preferred the periphery to central areas and tended to run or walk along the wall. The results suggested that thigmotaxis was significantly increased in the HBOT group compared with the control group. In the elevated plus maze test, the percentage of distance traveled was significantly increased in the open arm and significantly decreased in the closed arm for HBOT group mice compared with control group mice. These results suggested that HBOT group mice displayed enhanced motor activity in the open arm and exhibited fewer anxiety-related behaviors. In the three-chambered social approach test, the HBOT group mice made more approaches to the wire cup containing an acquaintance mouse than control group mice in the sociability test and made more approaches to the wire cup containing a stranger mouse than control group mice in the social novelty preference test. The results suggested that HBOT group mice showed increased levels of social interaction and decreased "social anxiety" than the control group to partner mice in this test. Our findings indicated that HBOT resulted in altered anxiety and social behavior in Fmr1 knockout mice and could possibly be used as a treatment for FXS.

8.
ACS Sens ; 5(2): 412-422, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32028771

RESUMO

Rapid, accurate and inexpensive monitoring of water quality parameters is indispensable for continued water safety, especially in resource-limited areas. Most conventional sensing systems either can only monitor one parameter at a time or lack user-friendly on-site monitoring capabilities. A fully integrated electrochemical sensor array is an excellent solution to this barrier. Electrochemical sensing methods involve transduction of water quality parameters where chemical interactions are converted to electrical signals. The challenge remains in designing low-cost, easy-to-use, and highly sensitive sensor array that can continuously monitor major water quality parameters such as pH, free chlorine, temperature along with emerging pharmaceutical contaminants, and heavy metal without the use of expensive laboratory-based techniques and trained personnel. Here, we overcame this challenge through realizing a fully integrated electrochemical sensing system that offers simultaneous monitoring of pH (57.5 mV/pH), free chlorine (186 nA/ppm), and temperature (16.9 mV/°C) and on-demand monitoring of acetaminophen and 17ß-estradiol (<10 nM) and heavy metal (<10 ppb), bridging the technological gap between signal transduction, processing, wireless transmission, and smartphone interfacing. This was achieved by merging nanomaterials and carbon nanotube-based sensors fabricated on microscopic glass slides controlled by a custom-designed readout circuit, a potentiostat, and an Android app. The sensing system can be easily modified and programmed to integrate other sensors, a capability that can be exploited to monitor a range of water quality parameters. We demonstrate the integrated system for monitoring tap, swimming pool, and lake water. This system opens the possibility for a wide range of low-cost and ubiquitous environmental monitoring applications.

9.
Clin Neurophysiol ; 131(3): 703-715, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991313

RESUMO

OBJECTIVE: We proposed a 40-Hz auditory steady-state response (ASSR) automatic detection method, and studied the prognosis of comatose patients by combining the 40-Hz ASSR detection results of multiple paradigms of auditory stimulation. METHODS: The 40-Hz ASSR elicitation experiments were carried out on 32 comatose patients, with the detection results used as prognosis predictors. To achieve automatic detection, the detection was modeled as a binary hypothesis test for a sinusoidal waveform with unknown amplitude and phase, based on the generalized likelihood ratio test (GLRT). The patients were followed up for 6 months, and each patient's outcome was classified as either favorable outcome (severe disability, moderate disability or good recovery) or unfavorable outcome (vegetative state/unresponsive wakefulness syndrome or death) according to the Glasgow outcome scale (GOS). The performance of the prognosis predictors was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The largest AUC in univariate analysis involving a single stimulation paradigm was 0.849, while the AUC obtained by combining multiple predictors was increased to 0.966. CONCLUSIONS: For comatose patients, the absence of 40-Hz ASSR in multiple stimulation paradigms may indicate an unfavorable prognosis. Furthermore, the combination of multiple auditory stimulation paradigms may increase the outcome prediction accuracy. SIGNIFICANCE: The combination of multi-paradigm 40-Hz ASSR automatic detection results may provide a feasible automatic outcome prediction method for comatose patients.

10.
Mol Med Rep ; 21(3): 1172-1180, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922229

RESUMO

Alzheimer's disease (AD) is the most prevalent age­related neurodegenerative disorder. It is featured by the progressive accumulation of ß­amyloid (Aß) plaques and neurofibrillary tangles. This can eventually lead to a decrease of cholinergic neurons in the basal forebrain. Stem cell transplantation is an effective treatment for neurodegenerative diseases. Previous studies have revealed that different types of stem or progenitor cells can mitigate cognition impairment in different Alzheimer's disease mouse models. However, understanding the underlying mechanisms of neural stem cell (NSC) therapies for AD requires further investigation. In the present study, the effects and the underlying mechanisms of the treatment of AD by NSCs are reported. The latter were labelled with the enhanced green fluorescent protein (EGFP) prior to implantation into the bilateral hippocampus of an amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (Tg) mouse model of AD. It was observed that the number of basal forebrain cholinergic neurons was restored and the expression of choline acetyltransferase (ChAT) protein was increased. Moreover, the levels of synaptophysin (SYP), postsynaptic density protein 95 (PSD­95) and microtubule­associated protein (MAP­2) were significantly increased in the hippocampus of NSC­treated AD mice. Notably, spatial learning and memory were both improved after transplantation of NSCs. In conclusion, the present study revealed that NSC transplantation improved learning and memory functions in an AD mouse model. This treatment allowed repairing of basal forebrain cholinergic neurons and increased the expression of the cognition­related proteins SYP, PSD­95 and MAP­2 in the hippocampus.

11.
Psychooncology ; 29(1): 148-155, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520429

RESUMO

OBJECTIVE: Melanoma preventive interventions for children with familial risk are critically needed because ultraviolet radiation (UVR) exposure and sunburn occurrence early in life are the primary modifiable risk factors for melanoma. The current study examined the feasibility and acceptability of a new, family-focused telehealth intervention for children with familial risk for melanoma and their parents. The study also explored changes in child sun protection and risk behaviors, sunburn occurrence, and objectively measured UVR exposure. METHODS: This was a prospective study with a single-group design (n = 21 parent-child dyads, children ages 8-17). Dyads were asked to participate in three in-person assessments and three live video teleconference intervention sessions. RESULTS: The intervention was feasibly delivered, and the intervention content was acceptable to parents and children. The intervention was associated with improvements in child use of certain sun protection strategies over time and declines in child UVR exposure. CONCLUSIONS: A telehealth-delivered,family-focused melanoma preventive intervention was feasibly delivered and was acceptable to parent-child dyads. Future melanoma preventive interventions for this at-risk population could incorporate eHealth technologies to facilitate improvements in use of sun protection and monitoring of UVR exposure. This trial was registered with Clinicaltrials.gov, number NCT02846714.

12.
Prep Biochem Biotechnol ; 50(1): 37-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31453755

RESUMO

Casein was the major protein in the milk of mammals and it was massively lost in the discharged wastewater during dairy product manufacture. This work was aimed at recovering casein from the dairy wastewater by using foam fractionation. In order to improve the foam stability, xanthan gum was used as the foam stabilizer based on the association between protein and polysaccharide. The results of the scanning electron microscope (SEM) and fluorescence emission spectrum suggested that casein could be associated with xanthan gum primarily through electrostatic attraction, which was significantly affected by pH. Moreover, the introduction of xanthan gum had a marked impact on the surface tension, foam ability, foam stability, turbidity, zeta potential and average particle size of casein dispersion. Foam fractionation was performed under the suitable operation condition of pH 6.0, loading liquid volume 400 mL, amount ratio of casein and xanthan gum 1:2, volumetric airflow rate 100 mL/min and pore diameter of gas distributor 0.180 mm. The enrichment ratio and the recovery percentage of casein reached as high as 16.81 and 86.51%, respectively. This work is expected to provide a cost-effective method to recover the trace desired material through improving foam stability based on intermolecular forces.Research highlightsFoam fractionation has been proposed to recover casein from dairy wastewater.Xanthan gum has been used to improve the foam stability of casein.The main interaction between casein and xanthan gum was an electrostatic attraction.Xanthan gum contributed to weakening the flowability of interstitial liquid.


Assuntos
Caseínas/isolamento & purificação , Polissacarídeos Bacterianos/química , Águas Residuárias/química , Animais , Fracionamento Químico/métodos , Indústria de Laticínios/métodos , Leite/química , Tamanho da Partícula
14.
In Vivo ; 34(1): 133-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882472

RESUMO

BACKGROUND/AIM: Dermal mesenchymal stem cells (DMSCs) are pluripotent stem cells found in the skin which maintain the thickness of the dermal layer and participate in skin wound healing. MATERIALS AND METHODS: The MTT assay was performed to detect cell proliferation and cell-cycle progression and cell-surface markers were assessed by flow cytometry. The levels of proteins in related signaling pathways were detected by western blotting assay and the translocation of ß-catenin into the nucleus were detected by immunofluorescence. Red oil O staining was performed to examine the differentiational ability of DMSCs. RESULTS: Knockout of PRDX2 inhibited DMSC cell growth, and cell-cycle arrest at G0/G1 phase; p16, p21 and cyclin D1 expression levels in Prdx2 knockout DMSCs were significantly increased. Furthermore, AKT phosphorylation were significantly increased in Prdx2 knockout DMSCs, GSK3ß activity were inhibited, result in ß-Catenin accumulated in the nucleus. CONCLUSION: In conclusion, these results demonstrated that PRDX2 plays a pivotal role in regulating the proliferation of DMSCs, and this is closely related to the AKT/glycogen synthase kinase 3 beta/ß-catenin signaling pathway.

15.
In Vivo ; 34(1): 143-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882473

RESUMO

BACKGROUND/AIM: Numerous studies on various cancer cell lines have reported that direct exposure to non-thermal plasma treatment using plasma-activated medium (PAM) can be applied as a novel technology for cancer therapy. In this study, we investigated the inhibitory effects of PAM on Aspc1 pancreatic cancer cells and the mechanisms responsible for the cell death observed. MATERIALS AND METHODS: A colony-formation, sphere-formation, wound-healing and transwell assays, immunocytochemistry and western blot analysis were used monitor effects of PAM. RESULTS: PAM induced a greater cytotoxic effect in pancreatic cancer cells compared to that induced in NIH3T3 cells and 293T cells, and significantly inhibited colony and sphere formation, and cell migration of Aspc1 cells. Furthermore, PAM treatment increased the accumulation of reactive oxygen species (ROS) and reduced the mitochondrial membrane potential in Aspc1 cells. In addition, PAM treatment down-regulated the AKT serine/threonine kinase 1/signal transducer and activator of transcription 3 signaling pathway and induced ROS-dependent cellular autophagy. CONCLUSION: Our findings suggest that PAM can induce apoptosis of Aspc1 cells through ROS-dependent autophagy and may be a candidate for use in pancreatic cancer therapeutics.

16.
Int Immunopharmacol ; 79: 106067, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31881377

RESUMO

BACKGROUND: There is growing evidence of the ability of microRNAs (miRs) in rheumatoid arthritis (RA), thus our objective was to discuss the impact of miR-365 on the apoptosis and proliferation of synoviocytes in mice with RA by targeting IGF1 and mediating the PI3K/AKT/mTOR pathway. METHODS: RA model mice was induced by type II collagen and freund's adjuvant. The successfully modeled mice were injected with normal saline, miR-365 mimics, miR-365 inhibitors or their controls. TUNEL assay was adopted to detect apoptosis in synovial tissues, and expression of IL-1ß and IL-6 in serum and synovial tissues was measured by ELISA and RT-qPCR. Mouse synoviocytes were isolated and cultured in vitro and identified by experiments. Cells were transfected with miR-365 mimics, IGF1 siRNA, or their controls to verify the role of miR-365 and IGF1 in cell vitality, proliferation and apoptosis of synoviocytes. RESULTS: Upregulation of miR-365 increased the number of TUNEL positive cells, depressed arthritis index, X-ray imaging score, and the expression of IL-1ß and IL-6. High expression of miR-365 and low expression of IGF1 restrained the proliferation and facilitated apoptosis of synoviocytes. MiR-365 inhibited the expression of IGF1 and inhibited the activation of the PI3K/AKT/mTOR pathway. CONCLUSION: Our study presents that up-regulation of miR-365 drives on apoptosis and restrains proliferation of synoviocytes in RA through downregulation of IGF1 and the inhibition of the PI3K/AKT/mTOR pathway. Thus, miR-365 may be a potential candidate for treatment of RA.

17.
Am J Infect Control ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31812271

RESUMO

BACKGROUND: Clostridioides difficile infection (CDI) causes significant morbidity in nursing home residents. Our aim was to describe adherence to a bundled CDI prevention initiative, which had previously been deployed nationwide in Veterans Health Administration (VA) long-term care facilities (LTCFs), and to improve compliance with reinforcement. METHODS: A multicenter pre- and post-reinforcement of the VA bundle consisting of environmental management, hand hygiene, and contact precautions was conducted in 6 VA LTCFs. A campaign to reinforce VA bundle components, as well as to promote select antimicrobial stewardship recommendations and contact precautions for 30 days, was employed. Hand hygiene, antimicrobial usage, and environmental contamination, before and after bundle reinforcement, were assessed. RESULTS: All LTCFs reported following the guidelines for cleaning and contact precautions until diarrhea resolution pre-reinforcement. Environmental specimens rarely yielded C difficile pre- or post-reinforcement. Proper hand hygiene across all facilities did not change with reinforcement (pre 52.51%, post 52.18%), nor did antimicrobial use (pre 87-197 vs. post 84-245 antibiotic days per 1,000 resident-days). LTCFs found it challenging to maintain prolonged contact precautions. DISCUSSION: Variation in infection prevention and antimicrobial prescribing practices across LTCFs were identified and lessons learned. CONCLUSIONS: Introducing bundled interventions in LTCFs is challenging, given the available resources, and may be more successful with fewer components and more intensive execution with feedback.

18.
Appl Microbiol Biotechnol ; 103(23-24): 9583-9592, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707443

RESUMO

The microsporidian Nosema bombycis is an obligate intracellular parasitic fungus that causes devastating disease in sericulture. To date, no efficient biotechnological method to inhibit the proliferation of microspores has been established. Here, we developed a powerful genetic engineering technique involving microsporidia-inducible genome editing in transgenic silkworm that confers resistance to N. bombycis. This system includes an HSP70 promoter-induced expression of the Cas9 protein line and a target BmATAD3A gene line. The double-positive HSP70-Cas9(+)×sgATAD3A(+) lines were obtained by hybridization and activation of the CRISPR/Cas9 system under the condition of microsporidia infection, although it is silenced in uninfected individuals. Genome editing analysis showed that the system could efficiently edit the BmATAD3A gene and induce large deletions. It is notable that the HSP70-induced system could effectively improve the survival rate of transgenic silkworm after microsporidia infection and inhibit the expression of key microsporidia genes. Moreover, no significant developmental differences between the transgenic silkworms infected with microsporidia and normal individuals were observed. In this study, we effectively inhibited microsporidia proliferation in transgenic individuals through disruptive techniques, thereby providing a method for microsporidia treatment and prevention, paving the way for economically advantageous insect breeding.

19.
Anticancer Res ; 39(11): 6115-6123, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704839

RESUMO

BACKGROUND/AIM: Colon cancer is the second most common deadliest malignancy in the world and better understanding of its underlying mechanisms is needed to improve clinical management. Natural plant extracts are gaining attention in the development of new therapeutic strategies against various cancer types. Shikonin is a naturally extracted naphthoquinone pigment with effects against cancer, including colon cancer. MATERIALS AND METHODS: In this study, we conducted a series of in vitro experiments to show the effects of Shikonin on colon cancer cell apoptosis. A colon cancer cell line with overexpression of peroxiredoxin V (PrxV) was constructed and the relationship of PrxV expression with Shikonin-induced cell apoptosis was investigated. RESULTS: Shikonin induced colon cancer cell apoptosis via regulation of mammalian target of rapamycin signaling. Shikonin-induced cell apoptosis was abrogated by overexpression of PrxV. CONCLUSION: According to the results obtained in this study, targeting PrxV may provide new insight for the successful management of colon cancer by inducing cell apoptosis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Naftoquinonas/farmacologia , Peroxirredoxinas/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Humanos , Células Tumorais Cultivadas
20.
Elife ; 82019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674911

RESUMO

Efficient searching for resources such as food by animals is key to their survival. It has been proposed that diverse animals from insects to sharks and humans adopt searching patterns that resemble a simple Lévy random walk, which is theoretically optimal for 'blind foragers' to locate sparse, patchy resources. To test if such patterns are generated intrinsically, or arise via environmental interactions, we tracked free-moving Drosophila larvae with (and without) blocked synaptic activity in the brain, suboesophageal ganglion (SOG) and sensory neurons. In brain-blocked larvae, we found that extended substrate exploration emerges as multi-scale movement paths similar to truncated Lévy walks. Strikingly, power-law exponents of brain/SOG/sensory-blocked larvae averaged 1.96, close to a theoretical optimum (µ ≅ 2.0) for locating sparse resources. Thus, efficient spatial exploration can emerge from autonomous patterns in neural activity. Our results provide the strongest evidence so far for the intrinsic generation of Lévy-like movement patterns.

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