The added value of [68Ga]Ga-DOTA-FAPI-04 PET/CT in pancreatic cancer: a comparison to [18F]F-FDG.

OBJECTIVES: We aimed to compare the diagnostic and prognostic performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in pancreatic cancer. METHODS: This single-center retrospective study enrolled 51 patients who underwent [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT. The final diagnosis on PET/CT images was verified by histopathology or 1-year follow-up. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were calculated to compare the diagnostic efficacy. Progression-free survival (PFS) was the endpoint for the survival analysis. Twenty-six patients were eligible for the Kaplan-Meier survival analysis using a log-rank test. And multivariate analysis including age, sex, stage, CA199 level, and SUVmax of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 was also performed. Two-tailed p < 0.05 was considered statistically significant. RESULTS: [68Ga]Ga-DOTA-FAPI-04 showed a higher sensitivity than [18F]FDG for detecting primary tumor (100% vs. 95.0%), metastatic lymph nodes (96.2% vs. 61.5%), and distant metastases (100% vs. 84.0%) (p < 0.0001, respectively). For [68Ga]Ga-DOTA-FAPI-04, the tumor-to-liver background ratio (TLBR) of liver metastases was higher (5.7 ± 3.2 vs. 3.2 ± 1.3, p < 0.0001). Furthermore, SUVmax > 14.9 on [68Ga]Ga-DOTA-FAPI-04 was significantly associated with PFS rates (chi-square = 12.05, p = 0.001). The Cox regression analysis showed that SUVmax of [68Ga]Ga-DOTA-FAPI-04 was an independent prognostic factor for PFS (p = 0.001; hazard ratio, 8.877). CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a higher sensitivity and accuracy than [18F]FDG PET/CT in diagnosing pancreatic cancer and might have an independent prognostic value for pancreatic cancer patients. KEY POINTS: • [68Ga]Ga-DOTA-FAPI-04 PET/CT had a higher sensitivity and accuracy in detecting primary tumors, metastatic lymph nodes, and distant metastases than [18F]FDG PET/CT. • SUVmax > 14.9 on [68Ga]Ga-DOTA-FAPI-04 PET/CT before chemotherapy was significantly associated with progress-free status rates (chi-square = 12.05, p = 0.001) in pancreatic cancer patients.

PIK3R3 Missense and NOTCH2 Synonymous Single Nucleotide Polymorphisms Are Associated with Liver Cancer.

BACKGROUND: Single nucleotide polymorphism (SNP) of candidate genes also affects the occurrence and prognosis of liver cancer. We mainly explored the effects of PIK3R3 and NOTCH2 polymorphisms on liver cancer risk among Chinese people. METHODS: Four SNPs (rs785468, rs785467, rs3795666, and rs17024525 in PIK3R3 and NOTCH2) from 709 liver cancer patients and 700 healthy controls were genotyped using the Agena MassARRAY system. The correlation between SNPs and liver cancer risk was evaluated using logistic regression analysis. The SNP-SNP interactions were conducted by the multifactor dimensionality reduction method. RESULTS: The results revealed that PIK3R3-rs785467 reduced the likelihood of liver cancer among Chinese Han people (p < 0.05). In addition, PIK3R3-rs785467 decreased the susceptibility to liver cancer in different populations (females, non-smokers, and age >55 years, p < 0.05). NOTCH2-rs3795666 reduced the susceptibility to liver cancer among males, drinkers, and patients aged >55 years (p < 0.05). CONCLUSIONS: Our results demonstrate that PIK3R3-rs785476 and NOTCH2-rs3795666 polymorphisms are responsible for decreasing the susceptibility of liver cancer development in the Chinese Han population.

Annotating BCMA Expression in Multiple Myelomas.

B cell maturation antigen (BCMA) is a promising theranostic target for multiple myeloma (MM). BCMA-targeted therapeutics, such as antibody-drug conjugates and chimeric antigen receptor T-cell immunotherapies, are rapidly reshaping the treatment landscape of MM. Along with the progress, a critical challenge is to noninvasively visualize the dynamic change of BCMA for a better-personalized prescription of the above-mentioned therapeutics. We aim to develop immuno-positron emission tomography (immunoPET) imaging strategies to visualize BCMA expression and realize target-specific diagnosis of MM in the work. A series of BCMA-targeting nanobodies were produced and two of them were successfully labeled with gallium-68 (68Ga). MM models were established using MM.1S cell line and NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju mice. The diagnostic efficacies of the developed probes (i.e., [68Ga]Ga-NOTA-MMBC2 and [68Ga]Ga-NOTA-MMBC3) were investigated in disseminated MM models by immunoPET imaging, region of interest analysis on PET images, biodistribution study, and histopathological staining study. [68Ga]Ga-NOTA-MMBC2 and [68Ga]Ga-NOTA-MMBC3 were developed with radiochemical purities of >99%. ImmunoPET imaging with either [68Ga]Ga-NOTA-MMBC2 or [68Ga]Ga-NOTA-MMBC3 precisely visualized BCMA expression and delineated MM lesions throughout the bone marrows. Moreover, [68Ga]Ga-NOTA-MMBC3 immunoPET successfully detected remnant MM after treatment with daratumumab, a prescription medicine used to treat MM. The immunoPET imaging data correlated well with the biodistribution and immunohistochemistry staining results. The work successfully developed two state-of-the-art BCMA-targeted radiotracers for annotating BCMA expression and diagnosing MM. Translational studies interpreting the diagnostic efficacies of the immunoPET radiotracers are warranted.

Influence of CMTM8 polymorphisms on lung cancer susceptibility in the Chinese Han population.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide and CMTM8 is a potential tumor suppressor gene, which is down-regulated in lung cancer. The objective of this research was to assess the association of CMTM8 genetic polymorphisms with lung cancer risk. METHODS: To evaluate the correlation between CMTM8 polymorphisms and lung cancer risk, Agena MassArray platform was used for genotype determination among 509 lung cancer patients and 506 controls. Multiple genetic models, stratification analysis and Haploview analysis were used by calculating odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Significant associations were detected between CMTM8 rs6771238 and an increased lung cancer risk in codominant (adjusted OR = 1.57, 95% CI: 1.01-2.42, P = 0.044) and dominant (adjusted OR = 1.54, 95% CI: 1.01-2.36, P = 0.047) models. After sex stratification analysis, we observed that rs6771238 was related to an increased risk of lung squamous cell carcinoma, while rs6771238 was associated with an increased risk of lung adenocarcinoma. Rs9835916 was linked to increased risk of lymph node metastasis in lung cancer patients. CONCLUSION: Our study first reported that CMTM8 polymorphisms were a risk factor for lung cancer, which suggested the potential roles of CMTM8 in the development of lung cancer.

ImmunoPET imaging of multiple myeloma with [68Ga]Ga-NOTA-Nb1053.

PURPOSE: Multiple myeloma (MM) remains incurable and its diagnosis relies heavily on bone marrow aspiration and biopsy. CD38 is a glycoprotein highly specific for MM. Antibody therapeutics (e.g., daratumumab) targeting CD38 have shown encouraging efficacy in treating MM, either as a monotherapy agent or in combination with other regimens. However, efficient stratification of patients who might benefit from daratumumab therapy and timely monitoring of the therapeutic responses are still clinical challenges. This work aims to devise a CD38-targeted imaging strategy and assess its value in diagnosing MMs. METHODS: By labeling a CD38-specific single domain antibody (Nb1053) with 68Ga (t1/2 = 1.1 h), we developed a CD38-targeted immuno-positron emission tomography (immunoPET) imaging probe [68Ga]Ga-NOTA-Nb1053. The probe was developed with good radiochemical yield (> 50%), excellent radiochemical purity (> 99%), and immunoreactivity (> 95%). The diagnostic accuracy of the probe was thoroughly investigated in preclinical MM models. RESULTS: ImmunoPET imaging with [68Ga]Ga-NOTA-Nb1053 specifically depicted all the subcutaneous and orthotopic MM lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. More importantly, daratumumab preloading significantly reduced [68Ga]Ga-NOTA-Nb1053 uptake in the disseminated bone lesions, indicating the overlapping targeting epitopes of [68Ga]Ga-NOTA-Nb1053 with that of daratumumab. Furthermore, premedication with sodium maleate or fructose significantly decreased kidney retention of [68Ga]Ga-NOTA-Nb1053 and improved the diagnostic value of the probe in lymphoma models. CONCLUSION: This work successfully developed a novel CD38-targeted immunoPET imaging approach that enabled precise visualization of CD38 and diagnosis of MMs. Upon clinical translation, [68Ga]Ga-NOTA-Nb1053 immunoPET may serve as a valuable CD38-targeted molecular imaging toolbox, facilitating early diagnosis of MM and precise assessment of the therapeutic responses.

A pH-responsive photoacoustic imaging probe for tumor pH imaging in vivo based on polyaniline-bovine serum albumin.

Precise pH detection in tumors can guide the design of pH-responsive drugs and theranostic agents to improve treatment efficacy. However, most reported pH-responsive probes are fluorescent probes, for which in vivo application is limited by low probe penetration depth. In this study, a pH-responsive polyaniline-bovine serum albumin (BSA) probe was constructed for precise pH detection in tumors using photoacoustic imaging. The probe can be used to generate high-resolution images of deep biological tissues. The photoacoustic signal of the polyaniline-BSA probe exhibits a clear linear relationship with pH in the range of 5-6.8 both in vitro and in vivo, indicating that the probe is ideal for precise pH detection in most tumors. The polyaniline-BSA probe also exhibits satisfactory biocompatibility, low toxicity, fast response, and good reversibility. This work provides a useful in vivo pH detection probe for developing pH-responsive drugs and theranostic agents.

EFFECT OF POST-SURGICAL RAI THERAPY ON PARATHYROID FUNCTION IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients. Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (99mTc)-pertechnetate thyroid scan (99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (131I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) 131I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment. Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of 99mTc thyroid scan, scores of 131I WBS, Tumor (T) stage, and Node (N) stage. Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients. Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan.

Ellagic acid-Fe nanoscale coordination polymer with higher longitudinal relaxivity for dual-modality T1-weighted magnetic resonance and photoacoustic tumor imaging.

Dual-modality contrast agents for T1-weighted magnetic resonance imaging (MRI) and photoacoustic imaging have attracted substantial attention as they combine the advantages of unlimited penetration depth and high sensitivity. However, most of the reported agents are Gd-based materials that exhibit nephrotoxicity, and few studies have focused on Fe-based materials owing to their lower relaxivity. This work describes the development of an ellagic acid (EA)-Fe nanoscale coordination polymer with high longitudinal relaxivity and strong near-infrared absorption for dual-modality T1-weighted MRI and photoacoustic imaging. The longitudinal relaxivity (r1) of the prepared EA-Fe@BSA nanoparticles was 2.54 mM-1 s-1, an increase of 185% compared with previously reported gallic acid-Fe nanoparticles. Furthermore, in vitro and in vivo experiments demonstrate that the EA-Fe@BSA NPs are an excellent T1-weighted MRI and photoacoustic dual-modality contrast agent with the advantages of convenient synthesis and low toxicity, exhibiting great potential for clinical use in tumor imaging.

IL1RN Polymorphisms Are Associated with a Decreased Risk of Esophageal Cancer Susceptibility in a Chinese Population.

BACKGROUND: Recent evidence suggested that IL1RN (interleukin-1 receptor antagonist) polymorphisms increased the susceptibility to cancers. The present study aimed to evaluate whether IL1RN was related to esophageal cancer susceptibility in a Northwest Han Chinese population. METHODS: The case-control study was conducted on 384 esophageal cancer patients and 499 healthy controls. We successfully genotyped four SNPs distributed in IL1RN. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to observe the expression of IL1RN in esophageal cancer tissues and normal tissues. RegulomeDB and HaploReg v4.1 were used to calculate possible functional effects of the polymorphisms. We also used genetic models to detect any potential association between IL1RN variants and esophageal cancer risk. RESULTS: In our study, rs3181052 was associated with a reduced risk of esophageal cancer in the codominant (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52-0.93, p = 0.040), the dominant (OR = 0.75, 95% CI 0.57-0.99, p = 0.041), and the overdominant (OR = 0.71, 95% CI 0.54-0.93, p = 0.012) model. The rs452204 was associated with a 0.76-fold (OR = 0.76, 95% CI 0.58-0.99; p = 0.043) decreased esophageal cancer risk under the overdominant model without adjustment. We also found that rs3181052 had a negative effect on esophageal cancer under the overdominant model (OR = 0.72, 95% CI 0.53-0.97, p = 0.033) adjusted for age and gender. In stratified analyses by age >55 years, rs3181052 reduced the risk of esophageal cancer in the dominant and overdominant models. In addition, rs315919 had a remarkable influence on esophageal cancer risk in females, while the association was not significant between rs3181052 and esophageal cancer risk in males. CONCLUSIONS: Our study provided the first evidence that IL1RN rs3181052, rs452204, and rs315919 are correlated with a decreased risk of esophageal cancer in a Northwest Han Chinese population. These findings may be useful for the development of early prognostics for esophageal cancer. However, further larger studies on different ethnic populations are warranted to verify these findings.

18F-Deoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) Monitoring of Dynamic Growth Characteristics of Walker-256 Tumor Models in 3 Different Locations in Rats.

BACKGROUND We explored the ideal method of establishing subcutaneous, breast, and liver tumor models using the same Walker-256 cells, and investigated the dynamic growth characteristics using ¹8F-deoxyglucose (¹8F-FDG) positron emission tomography/computed tomography (PET/CT), which provides basic information for choosing an experimental animal model. MATERIAL AND METHODS We established tumor models in 3 locations (subcutaneous, breast, and liver) in W256 Sprague-Dawley rats. ¹8F-FDG PET/CT imaging was performed from 6 days to 18 days after injecting the cells subcutaneously. Tumor volume of interest (VOI), maximum standard uptake value (SUVmax), and average standard uptake value (SUVavg) were obtained from the image. The difference of the growth characteristics in tumor volume and SUVs among the 3 groups were compared. Histopathology of the tumors was also analyzed. RESULTS The tumors in subcutaneous location grew fastest, followed by tumors located in the breast, and tumors in the liver grew slowest. Significant differences in tumor VOI (p=0.01) were observed. ¹8F-FDG uptake of the subcutaneous and breast tumors increased until day 10 and then decreased subsequently. ¹8F-FDG uptake of the liver tumor reached a peak at day 10, and necrosis peaked at day 12. The histopathology analysis results indicated that the necrosis was mainly located in the center of tumors while the viable tissues were located on the periphery. Similarly, CD 31 and Ki-67 were mainly expressed on the tumor periphery. CONCLUSIONS Subcutaneous, breast, and liver tumor models were easy to establish using Walker-256 cells. They showed fast growth and high uptake of ¹8F-FDG. These kinds of tumor models were optimal in evaluating anti-tumor efficacy by ¹8F-FDG PET/CT, but it may be essential to determine the best time-points at which to use it.

NR2F2 inhibits Smad7 expression and promotes TGF-ß-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21.

Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-ß induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-ß-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-ß-induced EMT in CRC. Using comparative miRNA profiling TGF-ß pre-treated CRC cells in which NR2F2 had been knocked down with that of control cells, we identified miR-21 as a commonly downregulated miRNA in HT29 cells treated with TGF-ß and NR2F2 siRNA, and its downregulation inhibiting migration and invasion of CRC cells. Moreover, we found NR2F2 could transcriptional activated miR-21 expression by binding to miR-21 promoter in HT29 by ChIP and luciferase assay. In the last, our data demonstrated that Smad7 was the direct target of miR-21 in CRC cells. Thus, NR2F2 could promote TGF-ß-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC.

Lesion based diagnostic performance of dual phase 99mTc-MIBI SPECT/CT imaging and ultrasonography in patients with secondary hyperparathyroidism.

BACKGROUND: We aimed to evaluate the diagnostic performance of 99mTc-MIBI SPECT/CT and ultrasonography in patients with secondary hyperparathyroidism (SHPT), and explored the factors that affect the diagnostic performance. METHODS: 99mTc-MIBI SPECT/CT and ultrasonography were performed in 50 patients with SHPT within 1 month before they underwent surgery. Imaging results were confirmed by the pathology. Pearson correlation analysis was used to determine the correlation of PTH level with clinical data. The optimal cutoff value for predicting positive 99mTc-MIBI results was evaluated by ROC analysis in lesions diameter. RESULTS: Forty-nine patients had a positive 99mTc-MIBI imaging results and 39 patients had positive ultrasonography results. The sensitivities of 99mTc-MIBI and ultrasonography were 98.00% and 78.00%, respectively. A total of 199 lesions were resected in 50 patients. Among them, 183 lesions were proved to be parathyroid hyperplasia. On per-lesion basis analysis, the sensitivity and specificity of 99mTc-MIBI and ultrasonography were 59.34% and 75.00% vs 46.24% and 80.00%, respectively. The Pearson correlation analysis showed that the serum AKP and PTH level had a significant linear association (r = 0.699, P < 0.001). The lesion diameter was a statistically significant predictive factor in predicting positive 99mTc-MIBI SPECT/CT. The optimal cutoff value for predicting positive 99mTc-MIBI results evaluated by ROC analysis in lesions diameter was 8.05 mm. CONCLUSION: Dual phase 99mTc-MIBI SPECT/CT imaging had a higher sensitivity in patients with SHPT than ultrasonography. Therefore, using 99mTc-MIBI positioning the lesion could be an effective method pre-surgical in patients with SHPT.

Breast-specific gamma camera imaging with 99mTc-MIBI has better diagnostic performance than magnetic resonance imaging in breast cancer patients: A meta-analysis.

OBJECTIVE: This study aimed to evaluate the diagnostic role of breast-specific gamma camera imaging (BSGI) with technetium-99m-methoxy isobutyl isonitrile (99mTc-MIBI) and magnetic resonance imaging (MRI) in patients with breast cancer through a meta-analysis. METHODS: Three reviewers searched articles published in medical journals before June 2016 in MEDLINE, EMBASE and Springer Databases; the references listed in original articles were also retrieved. We used the quality assessment of diagnostic accuracy studies (QUADAS) tool to assess the quality of the included studies. Heterogeneity, pooled sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves were calculated by Meta-DiSc software to estimate the diagnostic performance of BSGI and MRI. Ten studies with 517 patients were included after meeting the inclusion criteria. We did a subgroup analysis of the same data type. RESULTS: The pooled sensitivities of BSGI and MRI were: 0.84 (95% CI, 0.79-0.88) and 0.89 (95% CI, 0.84-0.92) respectively, and the pooled specificities of BSGI and MRI were: 0.82 (95% CI, 0.74-0.88) and 0.39 (95% CI, 0.30-0.49) respectively. The areas under the SROC curve of BSGI and MRI were 0.93 and 0.72 respectively. CONCLUSION: The results of our meta-analysis indicated that compared with MRI, BSGI has similar sensitivity, higher specificity, better diagnostic performance, and can be widely used in clinical practice.

Cerebral blood perfusion changes in amputees with myoelectric hands after rehabilitation: a SPECT computer-aided analysis.

BACKGROUND: Rehabilitation, which is essential for amputees with myoelectric hands, can improve the quality of daily life by remodeling the neuron network. In our study, we aim to develop a cerebral blood perfusion (CBF) single-photon emission computed tomography computer-aided (SPECT-CA) detection scheme to automatically locate the brain's activated regions after rehabilitation. RESULTS: Five participants without forearms (three male, two female, mean age 51 ± 12.89 years, two missing the right side, and three missing the left side) were included in our study. In the clinical assessment, all of the participants received higher scores after training. The results of the SPM analysis indicated that CBF in the precentral gyrus, postcentral gyrus, frontal lobe, temporal lobe and cerebellum was significantly different among the five participants (P < 0.05). Moreover, SPECT-CA showed that the activated brain areas mainly included the precentral gyrus, postcentral gyrus, cerebellum and extensive cerebral cortex. CONCLUSION: Our study demonstrated that the CBF SPECT-CA method can detect the brain blood perfusion changes induced by rehabilitation with high sensitivity and accuracy. This method has great potential for locating the remodeled neuron regions of amputees with myoelectric hands after rehabilitation.

Identification of novel susceptibility markers for the risk of overall breast cancer as well as subtypes defined by hormone receptor status in the Chinese population.

Genome-wide association studies (GWAS) have identified common variants associated with breast cancer (BC) risk at multiple genetic loci. Above all, accumulated evidence suggests that inherited risk variants may vary in BC subtypes defined by estrogen receptor (ER) or progesterone receptor (PR) status. However, the underlying susceptibility of some variants for BC subtypes has not been well investigated in the Chinese population. Our objective was to explore the association among 23 GWAS-identified single-nucleotide polymorphisms (SNPs) and overall BC incidence, as well as its subtypes, in Chinese women. An extensive association analysis using the Sequenom MassARRAY® platform was conducted in a case-control study, including 551 BC patients and 577 healthy controls. Using the chi-squared (χ2) test and genetic model analysis, we found an association with BC for four SNPs (rs616488 (1p36.22/PEX14), rs6678914 (1q32.1/LGR6), rs17530068 (6q14/unknown) and rs6001930 (22q13.1/MKL1)) at a 5% level. Stratified analyses under this genetic model determined that rs616488 and rs6001930 were specific to ER positive and PR positive, rs17530068 was specific to ER positive and PR negative, rs3817198 (11p15.5/LSP1) was specific to ER negative and rs4784227 (16q12.1/CASC16) was specific to PR positive. Our study provides powerful new evidence for the relationship between SNPs and BC susceptibility.

Protective Role of tert-Butylhydroquinone Against Sodium Fluoride-Induced Oxidative Stress and Apoptosis in PC12 Cells.

The neurotoxicity of fluoride is associated with oxidative stress due to imbalance between production and removal of reactive oxygen species (ROS). In contrast, induction of detoxifying and antioxidant genes through activation of NF-E2-related factor 2 (Nrf2) has been implicated in preventing oxidative stress and apoptosis in neurodegenerative diseases. The present study aimed to investigate the possible neuroprotective role of tert-butylhydroquinone (tBHQ), a general Nrf2 activator, on sodium fluoride (NaF)-induced oxidation damage and apoptosis in neuron-like rat pheochromocytoma (PC12) cells. Pretreatment with tBHQ protected PC12 cells against NaF-induced cytotoxicity as measured by MTT assay and apoptosis detection, simultaneously, inhibited NaF-induced overproduction of intracellular ROS and reduction of total glutathione content. Furthermore, NaF or tBHQ induced the stabilization of Nrf2, and enhanced expression of heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) as a consequence of Nrf2 inducing. These findings indicated that tBHQ pretreatment conferred protective effect on PC12 cells against NaF-induced apoptotic cell death and oxidation-redox imbalance through stabilization of Nrf2 and elevation of downstream HO-1 and γ-GCS expressions.

Lanthanum chloride impairs spatial memory through ERK/MSK1 signaling pathway of hippocampus in rats.

Rare earth elements (REEs) are used in many fields for their diverse physical and chemical properties. Surveys have shown that REEs can impair learning and memory in children and cause neurobehavioral defects in animals. However, the mechanism underlying these impairments has not yet been completely elucidated. Lanthanum (La) is often selected to study the effects of REEs. The aim of this study was to investigate the spatial memory impairments induced by lanthanum chloride (LaCl3) and the probable underlying mechanism. Wistar rats were exposed to LaCl3 in drinking water at 0 % (control, 0 mM), 0.25 % (18 mM), 0.50 % (36 mM), and 1.00 % (72 mM) from birth to 2 months after weaning. LaCl3 considerably impaired the spatial learning and memory of rats in the Morris water maze test, damaged the synaptic ultrastructure and downregulated the expression of p-MEK1/2, p-ERK1/2, p-MSK1, p-CREB, c-FOS and BDNF in the hippocampus. These results indicate that LaCl3 exposure impairs the spatial learning and memory of rats, which may be attributed to disruption of the synaptic ultrastructure and inhibition of the ERK/MSK1 signaling pathway in the hippocampus.

Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies.

OBJECTIVE: The objective of this study is to assess the performance of noninvasive prenatal testing for trisomies 21 and 18 on the basis of massively parallel sequencing of cell-free DNA from maternal plasma in twin pregnancies. METHOD: A double-blind study was performed over 12 months. A total of 189 pregnant women carrying twins were recruited from seven hospitals. Maternal plasma DNA sequencing was performed to detect trisomies 21 and 18. The fetal karyotype was used as gold standard to estimate the sensitivity and specificity of sequencing-based noninvasive prenatal test. RESULTS: There were nine cases of trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA sequencing correctly identified nine cases of trisomy 21 and one case of trisomy 18. The discordant case of trisomy 18 was an unusual case of monozygotic twin with discordant fetal karyotype (one normal and the other trisomy 18). The sensitivity and specificity of maternal plasma DNA sequencing for fetal trisomy 21 were both 100% and for fetal trisomy 18 were 50% and 100%, respectively. CONCLUSION: Our study further supported that sequencing-based noninvasive prenatal testing of trisomy 21 in twin pregnancies could be achieved with a high accuracy, which could effectively avoid almost 95% of invasive prenatal diagnosis procedures.