Climate and urbanization drive changes in the habitat suitability of Schistosoma mansoni competent snails in Brazil.

Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Schistosoma are obligate parasites of freshwater Biomphalaria and Bulinus snails, thus controlling snail populations is critical to reducing transmission risk. As snails are sensitive to environmental conditions, we expect their distribution is significantly impacted by global change. Here, we used machine learning, remote sensing, and 30 years of snail occurrence records to map the historical and current distribution of forward-transmitting Biomphalaria hosts throughout Brazil. We identified key features influencing the distribution of suitable habitat and determined how Biomphalaria habitat has changed with climate and urbanization over the last three decades. Our models show that climate change has driven broad shifts in snail host range, whereas expansion of urban and peri-urban areas has driven localized increases in habitat suitability. Elucidating change in Biomphalaria distribution-while accounting for non-linearities that are difficult to detect from local case studies-can help inform schistosomiasis control strategies.

Bladder-sparing treatment using tislelizumab combined with gemcitabine/cisplatin in selected patients with muscle-invasive bladder cancer: a real-world study.

PURPOSE: To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). METHODS: Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. RESULTS: The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12 months, 85.7% (95%CI: 74.9%, 96.5%) at 18 months, and 66.6% (95%CI: 45.2%, 88.0%) at 24 months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12 months, 65.6% (95%CI: 40.3%, 90.9%) at 18 months, and 52.5% (95%CI: 21.9%, 83.1%) at 24 months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24 months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. CONCLUSIONS: Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.

Climate and urbanization drive changes in the habitat suitability of Schistosoma mansoni competent snails in Brazil.

Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Schistosoma are obligate parasites of freshwater Biomphalaria snails, so controlling snail populations is critical to reducing transmission risk. As snails are sensitive to environmental conditions, we expect their distribution is significantly impacted by global change. Here, we leveraged machine learning, remote sensing, and 30 years of snail occurrence records to map the historical and current distribution of competent Biomphalaria throughout Brazil. We identified key features influencing the distribution of suitable habitat and determined how Biomphalaria habitat has changed with climate and urbanization over the last three decades. Our models show that climate change has driven broad shifts in snail host range, whereas expansion of urban and peri-urban areas has driven localized increases in habitat suitability. Elucidating change in Biomphalaria distribution - while accounting for non-linearities that are difficult to detect from local case studies - can help inform schistosomiasis control strategies.

Testicular orphan receptor 4 induced hepatic stellate cells activation via the regulation of TGF-ß receptor â /Smad2/3 signaling pathway.

INTRODUCTION AND OBJECTIVES: Liver fibrosis is a common pathological change in many chronic liver diseases. Activation of hepatic stellate cells (HSCs) is the core event in liver fibrosis. This study aimed to investigate the role of testicular orphan receptor 4 (TR4) in the activation of HSCs. MATERIALS AND METHODS: In vivo, bile duct ligation (BDL)-induced rat liver fibrosis model was established, and the expressions of TR4 and α-smooth muscle actin (α-SMA) in liver tissues were detected. In vitro, TR4 knockdown and overexpression in JS-1 cells using lentiviral vectors were constructed, and the expressions of TR4, α-SMA, Col-I, and TGF-ß1/smads and retinoid X receptor (RXR) pathway-related genes were detected. RESULTS: TR4 was highly expressed in BDL-induced fibrotic liver, accompanied by increased expression of α-SMA. Knockdown of TR4 significantly inhibited the expressions of α-SMA, Col-I, p-TßRI, and p-Smad2/3, and up-regulated the expression of RXRα in HSCs in vitro. In contrast, TR4 overexpression significantly increased the expressions of α-SMA, Col-I, p-TßRI, and p-Smad2/3, and inhibited the expression of RXRα. CONCLUSIONS: TR4 may promote the activation of HSCs by up-regulating TßR I/Smad2/3 signaling pathway and down-regulating RXRα signaling, thereby promoting the progression of liver fibrosis. Our findings may provide a new therapeutic target against hepatic fibrosis.

Licorice zinc suppresses melanogenesis via inhibiting the activation of P38MAPK and JNK signaling pathway in C57BL/6J mice skin.

PURPOSE: The active melanocytes in the skin were affected by hormones and ultraviolet (UV) irradiation. Licorice zinc has a whitening effect, which may have a prominent potential in the treatment of pigmented skin disease. METHODS: Modeling chloasma C57BL/6J mice by daily progesterone injection (15 mg/kg) and ultraviolet B (UVB) irradiation (λ = 312 nm, 2 h/day) for 30 days. Then, mice were given 0.65, 1.3, and 2.6 (g/kg) of licorice zinc and tranexamic acid 250 mg daily by oral administration for 14 days, respectively. Hematoxylin and eosin and Fontana-Masson staining, and Western blotting (WB) were performed to test the inhibitory of melanogenesis and activation of c-Jun-N-terminal (JNK)/p38 mitogen-activated protein kinases (MAPK) for licorice zinc. Melanogenesis was induced by α-melanocyte-stimulating hormone in vitro. Cell counting kit-8, melanin content determination, and WB were performed to verify the inhibitory effect of licorice zinc on melanogenesis. RESULTS: The present study showed that licorice zinc decreased melanin formation, cutaneous tissue injury, and the phosphorylation of JNK and P38MAPK, which was caused by UVB irradiation in vivo. In vitro, licorice zinc showed opposite effects from JNK/p38 activator. Meanwhile, tyrosinase-related protein-1, tyrosinase, and microphthalmia-associated transcription factor were decreased too. CONCLUSIONS: Licorice zinc induced a decrease in melanin synthesis by inhibiting the JNK and the P38MAPK signaling pathway, suggesting licorice zinc is a potential agent of anti-chloasma.

Neuropathologic damage induced by radiofrequency ablation at different temperatures.

OBJECTIVE: To explore the molecular mechanism of neuropathologic damage induced by radiofrequency ablation at different temperatures. METHODS: This is basic research, and 36 SD rats were used to construct the neuropathological injury model. The rats were subjected to radiofrequency stimulation at different temperatures and were divided into 6 groups according to the temperature injury: 42°, 47°, 52°, 57°, 62°, and 67°C groups. Conduction time, conduction distance, and nerve conduction velocity were recorded after temperature injury. HE-staining was used to observe the histopathological morphology of the sciatic nerve. The expression of SCN9A, SCN3B, and NFASC protein in sciatic nerve tissue were detected by western blot. RESULTS: With the increase in temperature, nerve conduction velocity gradually decreased, and neurons were damaged when the temperature was 67°C. HE-staining showed that the degrees of degeneration of neurons in rats at 47°, 52°, 57°, 62°, and 67°C were gradually increased. The expression of SCN9A, SCN3B protein in 57°, 62°, 67°C groups were much higher than that of NC, 42°, 47°, 52°C groups. However, the expression of NFASC protein in 57°, 62°, 67°C groups was much lower than that of the NC, 42°, 47°, 52°C groups. CONCLUSION: There was a positive correlation between temperature caused by the radiofrequency stimulation to neuropathological damage. The mechanism is closely related to the expression of SCN9A, SCN3B, and NFASC protein in nerve tissue caused by heat transfer injury.

Licorice zinc suppresses melanogenesis via inhibiting the activation of P38MAPK and JNK signaling pathway in Balb/c mice skin

Purpose: The active melanocytes in the skin were affected by hormones and ultraviolet (UV) irradiation. Licorice zinc has a whitening effect, which may have a prominent potential in the treatment of pigmented skin disease. Methods: Modeling chloasma C57BL/6J mice by daily progesterone injection (15 mg/kg) and ultraviolet B (UVB) irradiation (λ = 312 nm, 2 h/day) for 30 days. Then, mice were given 0.65, 1.3, and 2.6 (g/kg) of licorice zinc and tranexamic acid 250 mg daily by oral administration for 14 days, respectively. Hematoxylin and eosin and Fontana-Masson staining, and Western blotting (WB) were performed to test the inhibitory of melanogenesis and activation of c-Jun-N-terminal (JNK)/p38 mitogen-activated protein kinases (MAPK) for licorice zinc. Melanogenesis was induced by α-melanocyte-stimulating hormone in vitro. Cell counting kit-8, melanin content determination, and WB were performed to verify the inhibitory effect of licorice zinc on melanogenesis. Results: The present study showed that licorice zinc decreased melanin formation, cutaneous tissue injury, and the phosphorylation of JNK and P38MAPK, which was caused by UVB irradiation in vivo. In vitro, licorice zinc showed opposite effects from JNK/p38 activator. Meanwhile, tyrosinase-related protein-1, tyrosinase, and microphthalmia-associated transcription factor were decreased too. Conclusions: Licorice zinc induced a decrease in melanin synthesis by inhibiting the JNK and the P38MAPK signaling pathway, suggesting licorice zinc is a potential agent of anti-chloasma.

Neuropathologic damage induced by radiofrequency ablation at different temperatures

Abstract Objective To explore the molecular mechanism of neuropathologic damage induced by radiofrequency ablation at different temperatures. Methods This is basic research, and 36 SD rats were used to construct the neuropathological injury model. The rats were subjected to radiofrequency stimulation at different temperatures and were divided into 6 groups according to the temperature injury: 42°, 47°, 52°, 57°, 62°, and 67°C groups. Conduction time, conduction distance, and nerve conduction velocity were recorded after temperature injury. HE-staining was used to observe the histopathological morphology of the sciatic nerve. The expression of SCN9A, SCN3B, and NFASC protein in sciatic nerve tissue were detected by western blot. Results With the increase in temperature, nerve conduction velocity gradually decreased, and neurons were damaged when the temperature was 67°C. HE-staining showed that the degrees of degeneration of neurons in rats at 47°, 52°, 57°, 62°, and 67°C were gradually increased. The expression of SCN9A, SCN3B protein in 57°, 62°, 67°C groups were much higher than that of NC, 42°, 47°, 52°C groups. However, the expression of NFASC protein in 57°, 62°, 67°C groups was much lower than that of the NC, 42°, 47°, 52°C groups. Conclusion There was a positive correlation between temperature caused by the radiofrequency stimulation to neuropathological damage. The mechanism is closely related to the expression of SCN9A, SCN3B, and NFASC protein in nerve tissue caused by heat transfer injury.

miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2.

MicroRNAs (miRNAs) dysregulation is tightly related to diseases including tumor, neuro disease and cardiovascular disease. In this study, we investigated the potential biological effects of miR-34a and its target CXCR3 in phenotypic modulation of vascular smooth muscle cells (VSMCs) of intracranial aneurysms (IAs). MiR-34a was found to be down-regulated in IAs patients tested by Real-time PCR and decreased in GEO data. Meanwhile, our study also showed miR-34a inhibited matrix metalloproteinases (MMPs) and migration of VSMCs. Besides, CXCR3 is a direct target of miR-34a identified via luciferase assay. CXCR3 showed inhibitory effect on SM-MHC, SM22 while promoted MMPs expression, cell proliferation and migration in VSMCs. MiR-34a reversed the effect of CXCR3 in VSMCs. In addition, MMP-2 is a competitive endogenous RNA (ceRNA) of CXCR3 sharing common miR-34a target. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sponging endogenous miR-34a. In conclusion, miR-34a is down-regulated in IAs while CXCR3 is the direct target of miR-34a that regulates phenotypic modulation of VSMCs. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sharing common miR-34a targets.

Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results: Incidence and Characterization in a Large, Contemporary United States Cohort.

Early studies estimate that 5% to 10% of oropharyngeal squamous cell carcinomas overexpress p16 but are unassociated with transcriptionally-active high-risk human papillomavirus (HPV). Patients with discordant HPV testing may experience clinical outcomes that differ from traditional expectations. To document the rate of p16 and HPV mRNA positivity, characterize patients with discordant testing, and identify features that may warrant selective use of HPV-specific testing after p16 IHC, a multi-institutional, retrospective review of oropharyngeal squamous cell carcinoma patients with p16 IHC and HPV mRNA testing by reverse transcriptase polymerase chain reaction was performed. Of the 467 patients, most had T1 or T2 tumors (71%), 82% were p16 positive, and 84% were HPV mRNA positive. Overall, most tumors were nonkeratinizing (378, 81%), which was strongly associated with p16 and HPV positivity (93% and 95%, respectively). Overall, 81% of patients were double positive, 14% double negative, and 4.9% discordant (3.4% p16 negative/HPV mRNA positive and 1.5% p16 positive/HPV mRNA negative). The survival rates of these discordant patient groups fell squarely between the 2 concordant groups, although in multivariate analysis for both disease-free survival and overall survival, discordant patients were not found to have statistically significantly different outcomes. Reclassifying patients by applying HPV mRNA testing when p16 results and morphology do not match, or when p16 results are equivocal, improved prognostication slightly over p16 or HPV mRNA testing alone. Patients with discordant testing demonstrate a borderline significant trend toward survival differences from those with concordant tests. When evaluated independently, patients who were p16 negative but HPV mRNA positive had a prognosis somewhat closer to double-positive patients, while those who were p16 positive, but HPV mRNA negative had a prognosis closer to that of double-negative patients. We suggest an algorithm whereby confirmatory HPV mRNA testing is performed in patients where p16 status is not consistent with tumor morphology. This captures a majority of discordant patients and improves, albeit modestly, the prognostication.

Clinical significance and correlation of microRNA-21 expression and the neutrophil-lymphocyte ratio in patients with acute myocardial infarction.

OBJECTIVES: To explore the clinical significance and correlation of microRNA-21 (miR-21) and the neutrophil-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). METHODS: The observation group contained 184 patients, while the control group contained 150 patients. The expression of miR-21 in the serum of each group was detected by qRT-PCR. RESULTS: A total of 184 patients and their family members were followed-up for 30 days, among which 35 patients died and 149 patients survived, resulting in a survival rate of 80.97%. According to univariate analysis, there were significant differences in age, cardiac troponin (cTn), heart rate, Killip grade, percutaneous coronary intervention (PCI) operation rate, miR-21 and NLR. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values of miR-21 and NLR for the diagnosis of AMI were 0.909 and 0.868, respectively, and the area under the combined detection curve was 0.960. In the Kaplan-Meier survival analysis, the survival of patients with high miR-21 expression and NLR was significantly higher than that of patients with low miR-21 expression and NLR (p=0.027; p=0.001). The correlation showed that miR-21 expression in serum was positively correlated with the NLR in the observation group (r=0.528, p<0.05). cTn, heart rate, Killip classification, PCI operation rate, miR-21, NLR are independent risk factors for AMI. CONCLUSION: miR-21 and NLR play a role in the diagnosis of AMI and can be used as predictors for the survival of AMI.

Short-term effects of byproduct amendments and lime on physicochemical and microbiological properties of acidic soil from Jiaodong Peninsula of China / Efeitos de alterações de subprodutos e cal em solo ácido da Península de Jiaodong da China

The influences of byproduct amendments, containing silicon, calcium, magnesium and potassium, on acidic soil quality in Jiaodong Peninsula of China had been studied and compared with that of lime through monitoring physicochemical properties and enzyme activities of acidic soil over a 120-day period. Byproduct amendments (1125, 2250, 4500 and 9000 kg ha-¹) and lime 2250 kg ha-¹ was applied in the acidic soil. Results showed that both byproduct amendments and lime significantly increased the pH, EC and enzyme activities of soil. The by-product amendments inhibited microbial biomass carbon and soil respiration. Nevertheless, the lime-treated soil had a much more higher level of CO2 emission than the by-product amendments-treated soil. Compared to the by-product amendments-treated soil, the lime-treated soil had the higher pH, peroxidase activity, phenol oxidase activity and invertase activity. Therefore, lime might be a better choice over by-product amendments to improve chemical and biological properties of the acidic soil in Jiaodong Peninsula of China. For soils lacking available calcium and magnesium, the mixture of 4500 kg ha-¹ amendments and 2250 kg ha-¹ lime was recommend to treat the soil.(AU)

As influências do emprego de subprodutos que contêm silício, cálcio, magnésio e potássio, sobre a qualidade do solo ácido na Península de Jiaodong da China, foram estudadas e comparadas com a da cal através do monitoramento das propriedades físico-químicas e atividades enzimáticas do solo ácido ao longo de um 120- período do dia. Os resultados mostraram que as alterações dos subprodutos e a cal aumentaram significativamente as atividades de pH, CE e enzimas do solo. As alterações dos subprodutos obviamente inibiram o carbono da biomassa microbiana e a respiração do solo, mas o solo tratado com cal apresentou um maior nível de emissão de CO2. Em comparação com as modificações do subproduto, o solo tratado tinha o maior pH, a atividade da peroxidase, a atividade da fenol oxidase e a atividade da invertease. Portanto, o cal pode ser uma escolha melhor em relação às alterações dos subprodutos para melhorar as propriedades químicas e biológicas do solo ácido na Península de Jiaodong da China.(AU)

Clinical significance and correlation of microRNA-21 expression and the neutrophil-lymphocyte ratio in patients with acute myocardial infarction

OBJECTIVES: To explore the clinical significance and correlation of microRNA-21 (miR-21) and the neutrophil-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). METHODS: The observation group contained 184 patients, while the control group contained 150 patients. The expression of miR-21 in the serum of each group was detected by qRT-PCR. RESULTS: A total of 184 patients and their family members were followed-up for 30 days, among which 35 patients died and 149 patients survived, resulting in a survival rate of 80.97%. According to univariate analysis, there were significant differences in age, cardiac troponin (cTn), heart rate, Killip grade, percutaneous coronary intervention (PCI) operation rate, miR-21 and NLR. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values of miR-21 and NLR for the diagnosis of AMI were 0.909 and 0.868, respectively, and the area under the combined detection curve was 0.960. In the Kaplan-Meier survival analysis, the survival of patients with high miR-21 expression and NLR was significantly higher than that of patients with low miR-21 expression and NLR (p=0.027; p=0.001). The correlation showed that miR-21 expression in serum was positively correlated with the NLR in the observation group (r=0.528, p<0.05). cTn, heart rate, Killip classification, PCI operation rate, miR-21, NLR are independent risk factors for AMI. CONCLUSION: miR-21 and NLR play a role in the diagnosis of AMI and can be used as predictors for the survival of AMI.

Short-term effects of byproduct amendments and lime on physicochemical and microbiological properties of acidic soil from Jiaodong Peninsula of China / Efeitos de alterações de subprodutos e cal em solo ácido da Península de Jiaodong da China

ABSTRACT: The influences of byproduct amendments, containing silicon, calcium, magnesium and potassium, on acidic soil quality in Jiaodong Peninsula of China had been studied and compared with that of lime through monitoring physicochemical properties and enzyme activities of acidic soil over a 120-day period. Byproduct amendments (1125, 2250, 4500 and 9000 kg ha-1) and lime 2250 kg ha-1 was applied in the acidic soil. Results showed that both byproduct amendments and lime significantly increased the pH, EC and enzyme activities of soil. The by-product amendments inhibited microbial biomass carbon and soil respiration. Nevertheless, the lime-treated soil had a much more higher level of CO2 emission than the by-product amendments-treated soil. Compared to the by-product amendments-treated soil, the lime-treated soil had the higher pH, peroxidase activity, phenol oxidase activity and invertase activity. Therefore, lime might be a better choice over by-product amendments to improve chemical and biological properties of the acidic soil in Jiaodong Peninsula of China. For soils lacking available calcium and magnesium, the mixture of 4500 kg ha-1 amendments and 2250 kg ha-1 lime was recommend to treat the soil.

RESUMO: As influências do emprego de subprodutos que contêm silício, cálcio, magnésio e potássio, sobre a qualidade do solo ácido na Península de Jiaodong da China, foram estudadas e comparadas com a da cal através do monitoramento das propriedades físico-químicas e atividades enzimáticas do solo ácido ao longo de um 120- período do dia. Os resultados mostraram que as alterações dos subprodutos e a cal aumentaram significativamente as atividades de pH, CE e enzimas do solo. As alterações dos subprodutos obviamente inibiram o carbono da biomassa microbiana e a respiração do solo, mas o solo tratado com cal apresentou um maior nível de emissão de CO2. Em comparação com as modificações do subproduto, o solo tratado tinha o maior pH, a atividade da peroxidase, a atividade da fenol oxidase e a atividade da invertease. Portanto, o cal pode ser uma escolha melhor em relação às alterações dos subprodutos para melhorar as propriedades químicas e biológicas do solo ácido na Península de Jiaodong da China.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer.

OBJECTIVES: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). METHODS: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. CONCLUSION: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer / Blefaroespasmo com título elevado de anticorpos antirreceptores de acetilcolina

ABSTRACT Objective: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). Methods: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. Results: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. Conclusion: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

RESUMO Objetivo: Determinar se os níveis séricos do anticorpo antirreceptor de acetilcolina (anti-AChR-Abs) estão relacionados aos parâmetros clínicos do blefaroespasmo (BSP). Métodos: Fora recrutados 83 adultos com BSP, 60 pacientes ambulatoriais com espasmo hemifacial (HFS) e 58 controles. Foi aplicado um questionário para registrar história pessoal, fatores demográficos, resposta à toxina botulínica tipo A (BoNT-A) e outras condições neurológicas. Os níveis de anti-AChR-Abs foram quantificados usando um ensaio imunoenzimático. Resultados: O nível de anti-AChR-Abs foi de 0,237 ± 0,022 unidades de densidade óptica (OD) no grupo BSP, significativamente diferente em comparação com o grupo HFS (0,160 ± 0,064) e o grupo controle (0,126 ± 0,038). O nível de anti-AChR-Abs se correlacionou com a idade e a duração da resposta à injeção de BoNT-A. Conclusão: Pacientes com BSP apresentaram títulos elevados de anti-AChR-Abs, o que sugere que a desimunidade desempenha um papel no surgimento de BSP. O aumento do título de anti-AChR-Abs pode ser um preditor de resposta insuficiente à BoNT-A em BSP.

The effect of downregulation of Stathmin gene on biological behaviors of U373 and U87-MG glioblastoma cells.

BACKGROUND: Stathmin as a critical protein involved in microtubule polymerization, is necessary for survival of cancer cells. However, extremely little is known about Stathmin in glioblastoma. So, this study was designed to elucidate the function of Stathmin gene in the tumorigenesis and progression of glioblastoma cells. METHOD: The lentiviral interference vector pLV3-si-Stathmin targeting Stathmin gene and the control vector pLV3-NC were established for the co-transfection of 293T cells together with the helper plasmids. Viral titer was determined via limiting dilution assay. Then pLV3-si-Stathmin and pLV3-NC were stably co-transfected into U373 and U87-MG glioblastoma cells. Expression levels of Stathmin protein in each group were determined by using Western Blot, and the proliferation and migration ability of the cells with downregulated Stathmin were evaluated through CCK8 assay and transwell invasion assay, respectively. Cell cycles and cell apoptosis were detected with flow cytometry. Finally, the effect of Stathmin in tumor formation was determined in nude mice. RESULT: DNA sequencing and viral titer assay indicated that the lentiviral interference vector was successfully established with a viral titer of 4 × 108 TU/ml. According to the results from Western Blotting, Stathmin protein expression level decreased significantly in the U373 and U87-MG cells after transfected with pLV3-si-Stathmin, respectively, compared with those transfected with pLV3-NC. In glioblastoma cells, the cell proliferation and migration were greatly inhibited after the downregulation of Stathmin protein. Flow cytometry showed that much more cells were arrested in G2/M phasein Stathmin downregulated group, compared with the non-transfection group and NC group. But Stathmin downregulation did not induce significant cell apoptosis. Tumor formation assay in nude mice showed that tumor formation was delayed after Stathmin downregulation, with a reduction in both tumor formation rate and tumor growth velocity. CONCLUSION: Stathmin downregulation affected the biological behaviors of U373 and U87-MG glioblastoma cells, inhibiting the proliferation and migration of tumor cells. Stathmin gene may serve as a potential target in gene therapy for glioblastoma.

The effect of downregulation of Stathmin gene on biological behaviors of U373 and U87-MG glioblastoma cells

BACKGROUND: Stathmin as a critical protein involved in microtubule polymerization, is necessary for survival of cancer cells. However, extremely little is known about Stathmin in glioblastoma. So, this study was designed to elucidate the function of Stathmin gene in the tumorigenesis and progression of glioblastoma cells. METHOD: The lentiviral interference vector pLV3-si-Stathmin targeting Stathmin gene and the control vector pLV3-NC were established for the co-transfection of 293T cells together with the helper plasmids. Viral titer was determined via limiting dilution assay. Then pLV3-si-Stathmin and pLV3-NC were stably co-transfected into U373 and U87-MG glioblastoma cells. Expression levels of Stathmin protein in each group were determined by using Western Blot, and the proliferation and migration ability of the cells with downregulated Stathmin were evaluated through CCK8 assay and transwell invasion assay, respectively. Cell cycles and cell apoptosis were detected with flow cytometry. Finally, the effect of Stathmin in tumor formation was determined in nude mice. RESULT: DNA sequencing and viral titer assay indicated that the lentiviral interference vector was successfully established with a viral titer of 4 × 108 TU/ml. According to the results from Western Blotting, Stathmin protein expression level decreased significantly in the U373 and U87-MG cells after transfected with pLV3-si-Stathmin, respectively, compared with those transfected with pLV3-NC. In glioblastoma cells, the cell proliferation and migration were greatly inhibited after the downregulation of Stathmin protein. Flow cytometry showed that much more cells were arrested in G2/M phasein Stathmin downregulated group, compared with the non-transfection group and NC group. But Stathmin downregulation did not induce significant cell apoptosis. Tumor formation assay in nude mice showed that tumor formation was delayed after Stathmin downregulation, with a reduction in both tumor formation rate and tumor growth velocity. CONCLUSION: Stathmin downregulation affected the biological behaviors of U373 and U87-MG glioblastoma cells, inhibiting the proliferation and migration of tumor cells. Stathmin gene may serve as a potential target in gene therapy for glioblastoma.