Inducer Research Articles

A case report of secondary pulmonary tuberculosis complicated with COVID-19

To investigate the early diagnosis and treatment of secondary tuberculosis complicated with COVID-19. The clinical manifestation, auxiliary examination, diagnosis and treatment of one case of secondary tuberculosis complicated with COVID-19 admitted to Wuhan Pulmonary Hospital were analyzed retrospectively. The patient had a clear history of COVID-19 exposure. The clinical manifestations were cough, expectoration, fever and gasp. Chest CT showed multiple patch, nodule, spot, strip and cavity shadow in two lungs. COVID-19 was diagnosed as early as possible by detection of SARS-CoV-2 nucleic acid in respiratory specimens. After reasonable anti-tuberculosis combined with antiviral treatment, the detection of SARS-CoV-2 nucleic acid in respiratory specimens and acid-fast bacilli smear of sputum specimens turned negative, the symptoms were relieved and discharged. In the epidemic period of COVID-19, we should pay attention to the identification of secondary pulmonary tuberculosis with COVID-19, the formulation of drug programs for the treatment of two diseases, and avoid the use of rifampicin, a liver drug enzyme inducer, so as to avoid missed treatment due to the weakened efficacy of lopinavir / ritonavir and abidol, etc. 摘要： 探讨继发性肺结核合并新型冠状病毒肺炎(coronavirus disease 2019, COVID-19)的早期诊断和治疗。回顾 性分析武汉市肺科医院收治的1例继发性肺结核合并COVID-19患者的临床表现、辅助检查及诊治经过。患者有明确 的COVID-19的接触史,临床表现为晐嗽、晐痰,发热及气喘,胸部CT可见双肺散在多发的斑片、结节、斑点、条索及空 洞影。通过呼吸道标本新型冠状病毒核酸检测尽早确诊了 COVID-19,通过合理的抗结核联合抗病毒治疗后,呼吸道 标本新型冠状病毒核酸及痰标本结核细菌涂片转阴,症状缓解出院。在COVID-19流行时期,需注意鉴别继发性肺结 核合并COVID-19情况,以及治疗两种疾病药物方案的制定,避免使用肝药酶诱导剂利福平,其会使克力芝(洛匹那韦/利托那韦）、阿比多尔等药效减弱贻误治疗。

CURRÍCULO E CONTEXTO MULTICULTURAL: SIGNIFICAÇÕES A PARTIR DA REALIDADE VIVIDA NA FORMAÇÃO DOCENTE

Este artigo apresenta um estudo sobre currículo e suas políticas na formação docente, tendo como espaço a realidade específica do contexto multicultural do estado de Roraima. Toma como percurso metodológico a modalidade de pesquisa fenomenológica. As interpretações feitas a partir das significações expressas nos relatos de experiências com o fenômeno investigado possibilitaram conhecer como professores e gestores, que atuam na formação do Curso de Pedagogia da Universidade Estadual de Roraima, percebem e significam o currículo e a formação mediante a realidade multicultural local. Os resultados revelaram a necessidade de elaborar e inserir políticas curriculares e educacionais voltadas ao espírito próprio do lugar onde o currículo se desvela e se realiza. Apontam para a importância de uma proposta curricular dinâmica e criativa, capaz de envolver políticas culturais que reafirmem o currículo como lugar do conhecimento e da aprendizagem criativa. Como um espaço de produção simbólica, de sentidos e significações existenciais.

Ensuring Safe Use of Isotretinoin

For individuals with severe acne, isotretinoin is a first-line therapy. As this agent is both a cytochrome P-450 enzyme inducer and a potent teratogen,

Volatile compound and gene expression profiles associated with the storage of two peach fruit varieties differently sensitive to chilling injuries

The patterns of volatile organic compounds (VOCs) emission and the expression of genes associated with the lipoxygenase (LOX) pathway have been studied in harvested peach fruit of two cultivars ('Flaminia', FL, and 'Red Haven', RH) during and after cold storage. Two temperature storage conditions have been applied for two weeks: 0.5 and 5.5°C, the latter recognized to be an inducer factor of chilling injury (CI) of the flesh. Fruit were also monitored during 3 days of shelf-life (SL) at room temperature after removing from the cold storage. A different behaviour between cultivars has been observed in terms of internal browning (more evident in FL after 2 weeks) and extractable juice (already reduced in RH at the end of 1 week of storage at 5.5°C). Although some common responses have been observed (e.g. a general increase of 2-hexenal and 2-hexenal-E at the end of both cold storage conditions), LOX pathway-associated volatiles (aldehydes, alcohols, esters) showed different trends in relation to the genotype and the applied stress, with apparently no specific correlations with the incidence of CI. The expression level of five LOX pathway-associated genes (PpLOX1, PpLOX4, PpHPL1, PpADH1, PpAAT1) have been analysed and the results point out that a genotype-dependent behaviour is present, but specific responses (up-regulation of PpLOX1 and PpAAT1 during SL) appear to be present in both cultivars. In addition, the expression of two C-repeat-binding factors (PpCBF1 and PpCBF6), recognized to be involved in the responses of plant tissues to low temperature stress, showed marked changes in relation to the applied temperature, suggesting that these genes might play a regulatory role in the overall metabolism of cold stored peaches.

Bacteriophage induction versus vaginal homeostasis: role of H(2)O(2) in the selection of Lactobacillus defective prophages.

Vaginal disorders associated with systemic chemotherapy arise by direct inhibition of the resident microbiota (dominated by lactobacilli) or, possibly, by induction of prophages harbored in their genomes, leading to cell lysis. In the present study, proficient Lactobacillus phages could not be isolated from vaginal exudates. However, lysogeny appeared to be widespread, although about half of the strains harbored prophage sequences that were not responsive to SOS activation. In other cases, prophage induction was achieved, but viable phages were not generated, despite the fact that the induced supernatants of some strains were bactericidal. In one case, this activity was accompanied by the production of a bacteriophage subsequently identified as a member of the family Siphoviridae (isometric capsid and long non-contractile tail). Most of the lactobacilli tested generated hydrogen peroxide, which acted as an inducer of the SOS response, suggesting that H2O2 selects for strains that harbor SOS-insensitive, defective prophages, which are thus unable to promote vaginal lactobacilli phage-induced lysis.

The role of adenosine deaminase acting on RNA in the remission of aggression behavior in socially isolated mice and the mechanism of 5-serotonin-2C receptor

Objective To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice. Methods Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×104 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group (t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group (t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice (t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group (t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group (t=3.02, 4.401; P<0.05). Conclusion ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice. Key words: Social isolation; Aggressive behavior; Adenosine deaminase acting on RNA 1; 5-serotonin-2C receptor; Mice

Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder. Neuroinflammation is a critical cause of brain injury following SAH in both acute and chronic phases. While accumulating evidence has shown that therapies targeting neuroinflammation exerted beneficial effects in experimental SAH, there is little clinical evidence. One of the factors making neuroinflammation complicated is that inflammatory signaling pathways and mediators act as protective or detrimental responses at different phases. In addition, biomarkers to detect neuroinflammation are little known in clinical settings. In this review, first, we discuss how the inflammatory signaling pathways contribute to brain injury and other secondary pathophysiological changes in SAH. Damage-associated molecular patterns arising from mechanical stress, transient global cerebral ischemia, red blood cell breakdown and delayed cerebral ischemia following SAH trigger to activate pattern recognition receptors (PRRs) such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and receptors for advanced glycation end products. Most of PRRs activate common downstream signaling transcriptional factor nuclear factor-κΒ and mitogen-activated protein kinases, releasing pro-inflammatory mediators and cytokines. Next, we focus on how pro-inflammatory substances play a role during the course of SAH. Finally, we highlight an important inducer of neuroinflammation, matricellular protein (MCP). MCPs are a component of extracellular matrix and exert beneficial and harmful effects through binding to receptors, other matrix proteins, growth factors, and cytokines. Treatment targeting MCPs is being proved efficacious in pre-clinical models for preventing brain injury including neuroinflammation in SAH. In addition, MCPs may be a candidate of biomarkers predicting brain injury following SAH in clinical settings.

G protein regulated inducer of neurite outgrowth 1 is a potential marker for lung cancer prognosis.

Lung cancer mortality remains high, and only approximately 15% of patients with non-small cell lung cancer survive for more than five years. The purpose of this research was to investigate the prognostic value and biological functions of G protein regulated inducer of neuritis outgrowth 1(GPRIN1) in lung cancer. We used the Kaplan-Meier method to analyze the correlation between GPRIN1 and overall survival, and performed Cox regression to determine whether GPRIN1 might be an independent predictive factor for lung adenocarcinoma prognosis. qRT-PCR and Western blot assays were conducted to detect GPRIN1 expression in lung cancer cells and normal control cells. To detect the functional effects of knockdown/overexpression of GPRIN1 on lung cancer cells, we performed CCK-8, colony formation and Transwell assays. Through the Kaplan-Meier method, we found that GPRIN1 expression correlated with overall survival and adverse prognosis, and Cox regression indicated that GPRIN1 is as an independent predictive factor for lung adenocarcinoma. Furthermore, the mRNA and protein expression levels of GPRIN1 in lung cancer cells were markedly higher than those in normal cells. Downregulation of GPRIN1significantly decreased cell viability, colony formation, the number of invasive and migrating cells, and levels of epithelial-mesenchymal transition-related proteins in A549 cells. Overexpression of GPRIN1showed the opposite effect in Calu-1 cells. Together, these results indicated that GPRIN1 facilitates lung cancer proliferation and migration, possibly by affecting the epithelial-mesenchymal transition of lung cancer cells, suggesting that GPRIN1may be used as an effective target for the treatment of lung cancer.

The role of Erastin in ferroptosis

Ferroptosis is a newly discovered form of cell death in recent years. Its essence is the cell peroxidation death caused by the accumulation of intracellular lipid reactive oxygen species (L-ROS) in a iron-dependent manner. As a highly efficient ferroptosis inducer, Erastin mediates ferroptosis through multiple molecules, such as cystine-glutamate transport receptor, voltage-dependent anion channel and p53. More importantly, Erastin can enhance the sensitivity of cancer cells to chemotherapy and radiotherapy, so it can be used as a new type of anticancer drug. This article reviews the discovery of Erastin, the pathways of ferroptosis, the pathways of Erastin-induced ferroptosis, the anti-tumor characteristics of Erastin, and the latest domestic and international research results. Key words: Cell death; Antineoplastic combined chemotherapy protocols; Erastin; Ferroptosis

Mechanisms of ferroptosis and its applications in cancers

As a regulated cell death, ferroptosis is different from apoptosis, necrosis and autophagy. Its particularity is lipid peroxide accumulation and mitochondrial size reduction. There are many inducers and inhibitors to regulate the ferroptosis process by regulating the production of reactive oxygen species and the reduction of glutathione-dependent peroxidase 4, which play important roles in ferroptosis. In normal tissues, ferroptosis is characterized by aging and degenerative changes, while in cancer tissues, ferroptosis can be inhibited in many ways, thus promoting the growth of tumors. At present, several drugs have been used to promote ferroptosis in cancer cells, and the combination of traditional therapies is expected to become a new treatment mode. Key words: Ferroptosis; Inhibitor; Inducer; Caner therapy

Research progress in the role of nuclear factor-kappa B in neuropathic pain

Chronic pain is a worldwide public health problem in which neuropathic pain (NP) caused by nerve damage is the most common chronic pain. At present, NP lacks effective treatment for any reason. In recent years, increasing studies have shown that neuroimmunity and neuroinflammation play a key role in mediating NP, and nuclear factor-kappa B (NF-κB) plays the most important role in the expression of pain inducers and effectors in the immune and inflammatory systems. NF-κB promotes transcriptional up-regulation by a promoter that links to a variety of inflammatory factors. Therefore, this paper reviews the research status of the role of NF-κB in NP. Key words: NF-κappa B; Neuralgia; Neuroimmunomodulation; Review

Selection of Pluronic F-127 hydrogel’s optimum concentration and tests of its biocompatibility

Objective To determine the physical and chemical properties of Pluronic F-127 hydrogel and select its optimum concentration. At the same time, its biocompatibility was detected as the carrier of bone marrow mesenchymal stem cells (BMSCs). Methods 10%, 20%, 30% (m/v) Pluronic F-127 hydrogel were prepared, test its gelling properties and swelling kinetics. The structures of hydrogel with different concentrations were observed under scanning electron microscopy (SEM). Different concentrations of hydrogels were grouped and co-cultured for 7 days after containing BMSCs and transforming growth factor-β1 (TGF-β1). The proliferation and growth status of BMSCs in each group were detected by Cell counting kit-8 (CCK-8) method. After these above research, the most appropriate concentration of Pluronic F-127 hydrogel was chosen. Then, the inducer or growth factor was added to induce multi-directional differentiation of BMSCs. The Oil Red-O Staining and Alizarin red-S staining were conducted respectively. The above results were used to comprehensively evaluate the induced differentiation of cells in the vector. Results The gelation time of Pluronic F-127 hydrogel is inversely proportional to its concentration. With a higher the concentration, the lower the initial gelation temperature and the easier gelation. The higher concentration of Pluronic F-127 hydrogel, its microstructure became denser and the corresponding swelling rate was lower. CCK-8 results confirmed that compared with 20% Concentration, 30% hydrogel had a more obvious effect on the inhibition of proliferation of BMSCs. On day 5, opitical density (A) of 20% group (0.302±0.045) was significantly lower than 10% group (0.571±0.081). (t=5.120, P<0.05), while after adding the TGF-β1 to the gel carrier, it promoted the proliferation of cells. Most obviously, 20% group (using TGF-β1) (0.454±0.034) enhanced cell proliferation significantly better than 20% group (0.302±0.045) on day 5 (t=6.088, P<0.05). After adipogenic and osteogenic induction, the lipid droplets and calcification components were stained under the microscope. Conclusion 20% Concentration of Pluronic F-127 can be used as a suitable carrier to support the proliferation and differentiation of BMSCs, and the addition of growth factors or inducing fluids is more conducive to further cell growth or differentiation. Pluronic F-127 hydrogel is promising to have great value in tracheal transplantation experiments as a new type of cell carrier. Key words: Pluronic F-127 hydrogel; Bone marrow stem cells; Tracheal tissue engineering; Biocompatibility

Histological and toxicological evaluation, in rat, of a P-glycoprotein inducer and activator: 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5).

P-glycoprotein (P-gp) is an ATP-binding cassette transporter involved in the efflux of numerous compounds that influences the pharmacokinetics of xenobiotics. It reduces intestinal absorption and exposure of target cells to toxicity. Thioxanthones are compounds able to induce and/or activate P-gp in vitro. Particularly, 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) behaves as a P-gp inducer and activator in vitro. The aims of this study were: i) to perform a histological characterization, by testing a single high dose of TX5 [30 mg/kg, body weight (b.w.), gavage], administered to Wistar Han rats, 24 hours after administration; and ii) to perform both a complete histological characterization and a preliminary safety evaluation, in distinct target organs, 24 hours after administration of a single lower dose of TX5 (10 mg/kg, b.w., gavage) to Wistar Han rats. The results showed a relevant histological toxicity for the higher dose of TX5 administered (30 mg/kg, b.w.), manifested by extensive hepatic necrosis and splenic toxicity (parenchyma with hyperemia, increased volume of both white and red pulp, increased follicles marginal zone). Moreover, in the kidneys, a slight hyperemia and tubular edema were observed in TX5-treated animals, as well as an inflammation of the small intestine. On the contrary, for the lower tested dose (10 mg/kg, b.w.), we did not observe any relevant histological toxicity in the evaluated organs. Additionally, no significant differences were found in the ATP levels between TX5-exposed and control animals in any of the evaluated organs, with the exception of the intestine, where ATP levels were significantly higher in TX5-treated rats. Similarly, TX5 caused a significant increase in the ratio GSH/GSSG only in the lungs. TX5 (10 mg/kg, b.w.) did not induce any change in any of the hematological and biochemical circulating evaluated parameters. However, TX5 was able to significantly reduce the activated partial thromboplastin time, without affecting the prothrombin time. The urine biochemical analysis revealed a TX5-mediated increase in both creatinine and sodium. Taken together, our results show that TX5, at a dose of 10 mg/kg, does not induce considerable toxicity in the biological matrices studied. Given this adequate safety profile, TX5 becomes a particularly interesting compound for ex vivo and in vivo studies, regarding the potential for induction and activation of P-gp at the intestinal barrier.

Mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein in Chlamydia trachomatis via high-mobility group box 1 protein: a preliminary study

Objective To explore the molecular mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein of Chlamydia trachomatis, so as to provide an experimental basis for further clarifying the pathogenesis of Chlamydia trachomatis. Methods HeLa cells were divided into two groups: carbonyl cyanide m-chlorophenyl hydrazone (CCCP, an apoptosis inducer) group was stimulated by CCCP for 30 minutes, and pORF5 + CCCP group was pretreated with pORF5 plasmid protein for 18 hours followed by CCCP for 30 minutes. Then, Western blot analysis was performed to determine the expression of apoptosis-related proteins Bcl-2, Bax and caspase-3, JC-1 fluorescent probe was used to detect changes in the mitochondrial membrane potential in HeLa cells, and cytochrome c release from mitochondria was analyzed by indirect immunofluorescence assay. To analyze whether high-mobility group box 1 (HMGB1) protein participated in the anti-apoptotic role of pORF5 plasmid protein, HMGB1 shRNA and control RNA were separately transfected into the HeLa cells, which were then stimulated by pORF5 plasmid protein and CCCP. Then, the protein expression of Bcl-2, Bax, activated caspase-3 was determined, and cytochrome c release was analyzed. Data were compared between two groups by using paired t test. Results pORF5 plasmid protein could antagonize the CCCP-induced decrease of mitochondrial membrane potential, and the red/green fluorescence intensity ratio was significantly lower in the CCCP group (0.4 ± 0.1) than in the pORF5 + CCCP group (1.7 ± 0.3; t = 6.95, P < 0.01) . The protein expression of Bcl-2 in the HeLa cells in the pORF5 + CCCP group was 5.3 ± 0.6 times more than that in the CCCP group (t = 8.62, P < 0.01) , while the protein expression of Bax and activated caspase-3 in the pORF5 + CCCP group significantly decreased by 79% ± 10% (t = 9.23, P < 0.01) and 75% ± 8% (t = 4.26, P < 0.05) respectively compared with the CCCP group. Compared with the control RNA transfection group, the HMGB1 shRNA transfection group showed significantly decreased mitochondrial membrane potential in the HeLa cells (t = 11.23, P < 0.01) , increased cytochrome c release, decreased Bcl-2 expresson (t = 7.19, P < 0.05) and increased Bax expression (t = 13.06, P < 0.01) after stimulation with pORF5 and CCCP. Conclusion Chlamydia trachomatis plasmid protein pORF5 plays an anti-apoptosis role by blocking the mitochondrial apoptotic pathway through HMGB1 protein. Key words: Chlamydia trachomatis; Apoptosis; Proto-oncogene proteins c-bcl-2; Bcl-2-associated X protein; Caspase-3; High mobility group box protein 1; pORF5 plasmid protein

Fibroblast growth factor-10 and epithelial-mesenchymal transition in colorectal cancer.

As an inducer of epithelial-mesenchymal transition (EMT), fibroblast growth factor-10 (FGF-10) has a role in cell proliferation and differentiation in the embryo in addition to invasion and metastasis during carcinogenesis. In this study, we aimed to investigate the FGF-10 gene expression in tumor tissues based on the pathological feature of tumor related to EMT and metastasis. 62 tumors were obtained from 62 colorectal cancer patients during surgery. The pathological characteristics of the patients were carefully collected and classified by Iran National Tumor Bank. To quantify FGF-10 gene expression, RNA extraction, reverse transcription-PCR and real-time PCR were respectively performed. In addition, three colorectal cancer cell lines including LS174T, SW-948 and SW-480 were collected and cultured for further molecular analysis. Consequently, FGF-10 gene expression showed increased expression level in LS174T and SW-948 while it displayed decreased level in SW-480. Considering the tumor samples, we found an upregulation of FGF-10 gene expression in 52.1 % of all tumors in stage III and only in 9.09 % of all tumors in stage I. Also, there were an upregulation of FGF-10 gene expression in 50 % of all positive lymph invasion patients. Besides, FGF-10 gene upregulation was observed in 50 % of all tumors with a size larger than 5 cm (P value < 0.05) and 69 % of all tumors located in the colon (P value < 0.05). To our knowledge, this is the first time that FGF-10 expression is reported based on pathological features of colorectal cancer.

The Study on Possible Gene Therapy on Diabetics Type I Using Insulin Gene under Control of Heat Shock Promoter in Laboratory Animals

Background: Gene therapy is one of the treatment method for diabetes mellitus. An insulin gene, under control of heat shock inducer promoter was used in the study.Materials and Methods: Six mice used in this study. Streptozotocin (STZ) induced diabetes mellitus in BALB/C mice and rats. Recombinant plasmid was injected to each animal. Animal’s blood sugar (BS) was measured. Warming was done at injection site with a hair dryer to induced gene expression.Results: Immediately after warming blood sugar was increased in mouse 1 and decreased after one hour. However, blood sugar increased again in mice 2 and 4. Blood sugar increased for two hours after warming in mouse 3. Blood sugar increased to 150 mg/dl after STZ injection and immediately after warming reached to 160 mg/dl, after one hour BS dropped to 116 mg/dl and on the second hour was 126 mg/dl, in mouse 5 BS had an increasing trend, BS in mouse 6 had a similar pattern to mouse 2.Conclusion: With fixing the defects of the project will be used in gene therapy in future.

Efeito modulador da Ritalina® (metilfenidato) sobre a ação carcinogênica da doxorrubicina em Drosophila melanogaster

Introdução: A Ritalina® (metilfenidato) é um estimulante do sistema nervoso central, derivado da anfetamina. Ficou conhecida por seu uso em crianças e adultos diagnosticados com transtornos de déficit de atenção e hiperatividade, e alternativamente para tratamento de narcolepsia, obesidade e como estimulante para estudantes. Objetivo: Avaliar o efeito carcinogênico e/ou anticarcinogênico da Ritalina®. Método: Para tanto, larvas wts+/+mwh foram tratadas com o indutor tumoral doxorrubicina (0,4 mM) e com três diferentes concentrações de Ritalina® (100; 200 e 400 μM). Resultados: Mostraram que a Ritalina® apresentou atividade anticarcinogênica, visto que houve diferença estatisticamente significativa (p&lt;0,05) nas frequências de tumores identificados com a presença da referida substância, quando comparadas à frequência de tumores no controle positivo isolado. Conclusão: Sendo assim, é possível inferir que, nas presentes condições experimentais, a Ritalina® apresentou efeito modulador sobre danos induzidos pela doxorrubicina, reduzindo a frequência de tumores em todas as concentrações testadas em células somáticas de Drosophila melanogaster.

Relationship between pathomechanism of neuropathic pain-induced depression and autophagy in cortex of frontal lobe in rats

Objective To evaluate the relationship between the pathomechanism of neuropathic pain(NP)-inducced depression and autophagy in the cortex of the frontal lobe in rats. Methods Forty healthy male Sprague-Dawley rats in which IT catheters were successfully placed, aged 8-10 weeks, weighing 200-220 g, were divided into 4 groups(n=10 each) using a random number table method: sham operation group(group S), group NP, NP plus dimethyl sulfoxide group(group ND) and NP plus autophagy inducer rapamycin group(group NR). The neuropathic pain model was established by ligation of the left fifth spinal nerve of anesthetized rats in NP, ND and NR groups. Rapamycin 0.1 μg was intrathecally injected via the intrathecal catheter immediately after ligation of the spinal nerve and every day after ligation once a day for 21 consecutive days in group NR. The equal volume of dimethyl sulfoxide was intrathecally injected instead of rapamycin in group ND. The mechanical paw withdrawal threshold(MWT) was measured before ligation and at 1, 3, 7, 10, 14 and 21 days after ligation. The forced swimming test was performed at 3 days before ligation and 14 and 21 days after ligation. The rats were sacrificed after the last measurement of the behaviour testing, and the prefrontal cortex was removed for determination of the expression of microtubule-associated protein light chain 3 Ⅰ(LC3Ⅰ) and LC3Ⅱ, Beclin-1 and p62(by Western blot). The ratio of LC3Ⅱ/LC3Ⅰ was calculated. Results Compared with group S, the MWT was significantly decreased after ligation, the time of immobility was prolonged, the expression of LC3Ⅰ was down-regulated, the expression of LC3Ⅱ, Beclin-1 and p62 was up-regulated, and the LC3Ⅱ/LC3Ⅰ ratio was increased in NP and ND groups(P<0.05). Compared with group NP, the MWT was significantly increased after ligation, the time of immobility was shortened, the expression of LC3Ⅰ and p62 was down-regulated, the expression of LC3Ⅱ and Beclin-1 was up-regulated, and the LC3Ⅱ/LC3Ⅰ ratio was increased in group NR(P<0.05). Conclusion Enhanced autophagy in the cortex of the frontal lobe is involved in the endogenous antidepressant mechanism in rats with NP. Key words: Neuralgia; Autophagy; Frontal lobe; Depression

Influence of Rotating Speed of Inducer on the Occurrence of Super-synchronous Rotating Cavitation

Influence of Rotating Speed of Inducer on the Occurrence of Super-synchronous Rotating Cavitation

Analysis of MiRNA-17 and MiRNA-146 Expression During Differentiation of Spermatogonial Stem Like Cells Derived from Mouse Bone Marrow Mesenchymal Stem Cells.

In vitro derivation of germ cells from different stem cell sources has been challenging in the treatment of male infertility. MicroRNAs (miRNAs) have an essential role in gene expression at post-transcriptional level. The aim of this research was to find more about miRNA-17 and miRNA-146 expression during differentiation of spermatogonial stem cell like cells (SSC like cells) from mouse bone marrow mesenchymal stem cells (BMSCs) through bone morphogenic protein 4 (BMP4) and retinoic acid (RA) induction. BMSCs were treated with BMP4 to produce primordial germ cell like cells (PGC like cells). The cells were differentiated into SSC like cells by an inducer cocktail including RA, leukemia inhibitory factor (LIF) and basic fibroblast growth factor (bFGF). The PGC like cells and SSC like cells were evaluated for pluripotency (Nanog, Oct-4) and germ cell specific gene (Piwil2, Plzf, Dazl, and Stra8) expression, protein expression (Plzf, Stra8), and miRNA-17 and miRNA-146 mRNA expression. Our results showed that BMP4 leads to Dazl upregulation and Nanog downregulation expression in PGC like cells. RA upregulated Stra8 and Piwil2, and downregulated Nanog and Oct-4. MiRNA-17 and miRNA-146 expression decreased significantly in SSC like cells after RA treatment. This research indicated the aberrant miRNA-17 and miRNA-146 expression in SSC like cells in comparison with SSCs. Downregulation of the two miRNAs using RA in the stimulated undifferentiated state could probably be one of the key factors of SSC like cell arrest.