In JoVE (1)
Other Publications (14)
- BMC Cancer
- Biochemical and Biophysical Research Communications
- Annals of Laboratory Medicine
- Cancer Science
- Neuroscience Bulletin
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- OncoTargets and Therapy
- Sensors (Basel, Switzerland)
- Scientific Reports
- Cell Reports
- Dalton Transactions (Cambridge, England : 2003)
- Frontiers of Medicine
- Cancer Medicine
Articles by Jingjing Cheng in JoVE
An Automated Rapid Iterative Negative Geotaxis Assay for Analyzing Adult Climbing Behavior in a Drosophila Model of Neurodegeneration Wenze Cao*1,2,3, Li Song*1,2,3, Jingjing Cheng1,2,3, Na Yi1,2,3, Luyi Cai1,2,3, Fu-de Huang4,5, Margaret Ho1,2,3 1Research Center for Translational Medicine, Tongji University School of Medicine, 2Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, 3Department of Anatomy and Neurobiology, Tongji University School of Medicine, 4Shanghai Advanced Research Institute, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 5Sino-Danish College, University of Chinese Academy of Sciences, Chinese Academy of Sciences This step-by-step protocol analyzes Drosophila negative geotaxis behavior using an automated multi-cylinder system that hosts hundreds of flies and synchronizes their action by an electric motor. Upon synchronization, fly negative geotaxis behavior is assayed, digitally recorded, and analyzed using the self-designed RflyDetection software.
Other articles by Jingjing Cheng on PubMed
Inhibition of Long Non-coding RNA NEAT1 Impairs Myeloid Differentiation in Acute Promyelocytic Leukemia Cells BMC Cancer. Sep, 2014 | Pubmed ID: 25245097 Acute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17), which fuses PML with retinoic acid receptor alpha (RARα). Although PML-RARα is crucially important for pathogenesis and responsiveness to treatment, the molecular and cellular mechanisms by which PML-RARα exerts its oncogenic potential have not been fully elucidated. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to the precise control of gene expression and are involved in human diseases. Little is known about the role of lncRNA in APL.
Endoplasmic Reticulum Stress Involved in High-fat Diet and Palmitic Acid-induced Vascular Damages and Fenofibrate Intervention Biochemical and Biophysical Research Communications. Feb, 2015 | Pubmed ID: 25592967 Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS.
Fenofibrate Treatment Attenuated Chronic Endoplasmic Reticulum Stress in the Liver of Nonalcoholic Fatty Liver Disease Mice Pharmacology. 2015 | Pubmed ID: 25896720 Fenofibrate is widely used in clinical practice, but its influence on chronic endoplasmic reticulum (ER) stress induced by feeding a high-calorie and high-cholesterol diet (HCD) has still not been studied. We thus investigated its effects on the liver of the nonalcoholic fatty liver disease (NAFLD) mouse model. Male C57BL/6 mice fed an HCD for 3 months were treated with fenofibrate (HCD + FF, 40 mg/kg, once daily) via gavage for 4 weeks. Insulin sensitivity, serum lipid and inflammatory cytokines were measured. Liver tissues were procured for histological examination as well as analysis of hepatic triglyceride levels, distribution of inflammatory cytokines and genes involved in ER stress. Our results showed that chronic feeding of an HCD successfully induced an NAFLD model accompanied by inflammatory activation, apoptosis and severe ER stress in the liver. Fenofibrate administration significantly improved symptoms of NAFLD and decreased apoptosis, expression of inflammatory cytokines and genes involved in ER stress, such as inositol-requiring enzyme 1α (IRE1α), X-box binding protein 1 (XBP1) and JNK phosphorylation. Thus, our study suggests that fenofibrate protected against inflammatory injury and apoptosis, maybe alleviating ER stress through the IRE1α-XBP1-JNK pathway in the liver of NAFLD mice.
Meta-Analysis of the SLCO1B1 C.521T>C Variant Reveals Slight Influence on the Lipid-Lowering Efficacy of Statins Annals of Laboratory Medicine. May, 2015 | Pubmed ID: 25932441 Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins.
XRCC3 is a Promising Target to Improve the Radiotherapy Effect of Esophageal Squamous Cell Carcinoma Cancer Science. Dec, 2015 | Pubmed ID: 26383967 Radiotherapy is widely applied for treatment of esophageal squamous cell carcinoma (ESCC). The Rad51-related protein XRCC3 plays roles in the recombinational repair of DNA double-strand breaks to maintain chromosome stability and repair DNA damage. The present study aimed to investigate the effect of XRCC3 on the radiotherapy response of ESCC and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC3 expression in ESCC cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC3 expression was positively correlated with resistance to chemoradiotherapy in ESCC and an independent predictor for short disease-specific survival of ESCC patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro and in vivo was substantially increased by knockdown of XRCC3 in ESCC cells. Ectopic overexpression of XRCC3 in both XRCC3-silenced ESCC cells dramatically enhanced ESCC cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC cell death by radiation-induced apoptosis and mitotic catastrophe. Our data suggest that XRCC3 protects ESCC cells from ionizing radiation-induced death by promoting DNA damage repair and/or enhancing telomere stability. XRCC3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC.
Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict Neuroscience Bulletin. Apr, 2016 | Pubmed ID: 26898297 Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient (TLR4(-/-)) and wild-type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4(-/-) mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4(-/-) mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approach-avoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4(-/-) mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4(-/-) mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4(-/-) mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon.
High Expression of Rad51c Predicts Poor Prognostic Outcome and Induces Cell Resistance to Cisplatin and Radiation in Non-small Cell Lung Cancer Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Oct, 2016 | Pubmed ID: 27465554 Rad51c is critical for homologous recombination repair and genomic stability and may play roles in tumorigenesis and cancer therapy. We investigated the expression level and clinical significance of Rad51c in non-small cell lung cancer (NSCLC) and determined the effect of Rad51c on NSCLC cell chemosensitivity and radiosensitivity. Rad51c expression was detected using immunohistochemistry and was higher in NSCLC patient samples than in adjacent normal tissues. Kaplan-Meier analysis revealed that high Rad51c expression was an independent predictor of short overall survival (OS) and disease-free survival (DFS) in NSCLC patients receiving chemotherapy and/or radiotherapy. Furthermore, Rad51c knockdown increased the killing effect of ionizing radiation (IR) and enhanced cisplatin-induced apoptotic cells in NSCLC cells by disrupting the repair of cisplatin- and IR-induced DNA damage. In addition, ectopic expression of Rad51c dramatically enhanced NSCLC cell resistance to cisplatin and radiotherapy. These findings suggest that increased expression of Rad51c may confer resistance to chemotherapy and/or radiotherapy of NSCLC, and also be an independent prognostic factor for patient outcome. Therefore, targeting Rad51c may represent an improved therapeutic strategy for NSCLC patients with locally advanced disease.
PinX1 Suppresses Tumorigenesis by Negatively Regulating Telomerase/telomeres in Colorectal Carcinoma Cells and is a Promising Molecular Marker for Patient Prognosis OncoTargets and Therapy. 2016 | Pubmed ID: 27536146 PinX1 plays positive and negative roles in the maintenance of telomerase and telomeres, as well as in tumorigenesis. The aim of the present study was to investigate the expression and clinical significance of PinX1 in colorectal carcinoma (CRC) and to determine the effect of PinX1 on CRC cell proliferation and apoptosis. A total of 86 CRC patients treated with radical resection and 5-fluorouracil-based adjuvant chemotherapy were enrolled in this study. The expression dynamics of PinX1 was detected by immunohistochemistry in the CRC patients and 25 normal colonic mucosa controls. PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, and the rate of PinX1 protein low/negative expression in CRC and normal tissues was 60% (52/86) and 24% (6/25), respectively (P=0.037). In addition, PinX1 downregulation was significantly associated with short overall survival (P=0.016) and disease-free survival (P=0.042) in CRC patients. Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting overall survival and disease-free survival for CRC patients. Furthermore, we demonstrated that ectopic overexpression of PinX1 in CRC cells inhibited their proliferation, promoted apoptosis, repressed telomerase activity, and induced telomere shortening. These findings suggest that PinX1 may be a prognostic biomarker for CRC patients' survival and that it inhibits cell proliferation and promotes apoptosis by repressing telomerase activity and inducing telomere shortening. Targeting PinX1 may therefore provide a novel therapeutic strategy for CRC patients.
A Digital Lock-In Amplifier for Use at Temperatures of Up to 200 °C Sensors (Basel, Switzerland). Nov, 2016 | Pubmed ID: 27845710 Weak voltage signals cannot be reliably measured using currently available logging tools when these tools are subject to high-temperature (up to 200 °C) environments for prolonged periods. In this paper, we present a digital lock-in amplifier (DLIA) capable of operating at temperatures of up to 200 °C. The DLIA contains a low-noise instrument amplifier and signal acquisition and the corresponding signal processing electronics. The high-temperature stability of the DLIA is achieved by designing system-in-package (SiP) and multi-chip module (MCM) components with low thermal resistances. An effective look-up-table (LUT) method was developed for the lock-in amplifier algorithm, to decrease the complexity of the calculations and generate less heat than the traditional way. The performance of the design was tested by determining the linearity, gain, Q value, and frequency characteristic of the DLIA between 25 and 200 °C. The maximal nonlinear error in the linearity of the DLIA working at 200 °C was about 1.736% when the equivalent input was a sine wave signal with an amplitude of between 94.8 and 1896.0 nV and a frequency of 800 kHz. The tests showed that the DLIA proposed could work effectively in high-temperature environments up to 200 °C.
The Hypoparathyroidism-associated Mutation in Drosophila Gcm Compromises Protein Stability and Glial Cell Formation Scientific Reports. Jan, 2017 | Pubmed ID: 28051179 Differentiated neurons and glia are acquired from immature precursors via transcriptional controls exerted by factors such as proteins in the family of Glial Cells Missing (Gcm). Mammalian Gcm proteins mediate neural stem cell induction, placenta and parathyroid development, whereas Drosophila Gcm proteins act as a key switch to determine neuronal and glial cell fates and regulate hemocyte development. The present study reports a hypoparathyroidism-associated mutation R59L that alters Drosophila Gcm (Gcm) protein stability, rendering it unstable, and hyperubiquitinated via the ubiquitin-proteasome system (UPS). Gcm(R59L) interacts with the Slimb-based SCF complex and Protein Kinase C (PKC), which possibly plays a role in its phosphorylation, hence altering ubiquitination. Additionally, R59L causes reduced Gcm protein levels in a manner independent of the PEST domain signaling protein turnover. Gcm(R59L) proteins bind DNA, functionally activate transcription, and induce glial cells, yet at a less efficient level. Finally, overexpression of either wild-type human Gcmb (hGcmb) or hGcmb carrying the conserved hypoparathyroidism mutation only slightly affects gliogenesis, indicating differential regulatory mechanisms in human and flies. Taken together, these findings demonstrate the significance of this disease-associated mutation in controlling Gcm protein stability via UPS, hence advance our understanding on how glial formation is regulated.
Auxilin Underlies Progressive Locomotor Deficits and Dopaminergic Neuron Loss in a Drosophila Model of Parkinson's Disease Cell Reports. Jan, 2017 | Pubmed ID: 28147270 Parkinson's disease (PD) is a common neurodegenerative disorder that exhibits motor and non-motor symptoms, as well as pathological hallmarks, including dopaminergic (DA) neuron death and formation of α-synuclein (α-Syn) Lewy bodies. Cyclin-G-associated kinase (GAK), a PD susceptibility gene identified through genome-wide association studies (GWAS), is a ubiquitous serine/threonine kinase involved in clathrin uncoating, though its PD-related function remains elusive. Here, we implicate the Drosophila GAK homolog, auxilin (aux), in a broad spectrum of parkinsonian-like symptoms. Downregulating aux expression leads to progressive loss of climbing ability, decreased lifespan, and age-dependent DA neuron death similar to α-Syn overexpression. Reduced aux expression further enhances and accelerates α-Syn-mediated DA neuron loss. Flies with reduced aux expression are more sensitive to the toxin paraquat, suggesting that genetic and environmental factors intertwine. Taken together, these findings decipher a pivotal role for GAK/aux and suggest mechanisms underlying PD.
A Facile Hydrothermal Synthesis of Carbon Dots Modified G-C3N4 for Enhanced Photocatalytic H2-evolution Performance Dalton Transactions (Cambridge, England : 2003). May, 2017 | Pubmed ID: 28470324 Carbon dots (CDs)/g-C3N4 is a promising photocatalyst to split water for H2 production; however, the synthesis of CDs/g-C3N4 is usually rigorous and involves multiple steps, which limits its practical application. In this study, a facile hydrothermal approach was developed to prepare CDs/g-C3N4 photocatalysts using l-ascorbic acid and g-C3N4 as the precursors. Upon in situ thermal polymerization of l-ascorbic acid on the g-C3N4 surface, the carbon dots were homogeneously and solidly modified on the g-C3N4 surface. The CDs/g-C3N4 photocatalysts showed higher photocatalytic performance for H2 production than g-C3N4 under UV light irradiation using lactic acid as the sacrificial agent. The improved photocatalytic performance of CDs/g-C3N4 was mainly attributed to rapid interfacial charge transfer. After a Pt co-catalyst was loaded, the Pt-CDs/g-C3N4 catalyst formed exhibited a further improved photocatalytic performance for H2 production and could even split pure water to produce H2. Considering our present economic and facile synthetic approach for the modification of carbon dots on the surface of g-C3N4 photocatalysts, the as-prepared CDs/g-C3N4 photocatalysts will be promising for practical use in water splitting.
Postnatal Feeding with High-fat Diet Induces Obesity and Precocious Puberty in C57BL/6J Mouse Pups: a Novel Model of Obesity and Puberty Frontiers of Medicine. Jun, 2017 | Pubmed ID: 28500430 Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet (HFD) to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight (BW) of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet-induced postnatal childhood obesity and puberty.
High Expression of FUNDC1 Predicts Poor Prognostic Outcomes and is a Promising Target to Improve Chemoradiotherapy Effects in Patients with Cervical Cancer Cancer Medicine. Aug, 2017 | Pubmed ID: 28719148 FUN14 domain containing 1 (FUNDC1) is an important molecule in receptor-dependent mitophagy. However, the roles of FUNDC1 in human cancer biology remain unknown. The aim of this study was to explore the expression and roles of FUNDC1 in cervical cancer. Immunohistochemistry and Western blotting were applied to detect the expression of FUNDC1, and small-hairpin RNA was applied to inhibit the expression of endogenous FUNDC1 in cervical cancer cells. MTT assays and Flow cytometric analysis were applied to examine cell proliferation and apoptosis. Immunofluorescence was used to detect the formation of γH2AX foci and evaluate the extent of DNA damage. Compared with corresponding adjacent noncancerous cervical tissues, the expression of FUNDC1 in cervical cancer cells was significantly increased. High expression of FUNDC1 and the prognosis of patients with cervical cancer were correlated negatively, which could be used as an independent prognostic factor for overall survival and disease-free survival. Depletion of FUNDC1 significantly inhibited the proliferation of tumor cells, induced apoptosis, and enhanced cell sensitivity to cisplatin and ionizing radiation (IR). Our data suggested that FUNDC1 can be used as a prognostic biomarker in patients with cervical cancer, and may be a new therapeutic target to improve the antitumor effects of chemoradiotherapy.