The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Effect of Strain Rate and Temperature on the Tensile Properties of Long Glass Fiber-Reinforced Polypropylene Composites.

Strain rate and temperature are influential factors that significantly impact the mechanical properties of long glass fiber-reinforced polypropylene composites. This study aims to investigate the tensile properties of these composites, analyzing the effects of temperature, strain rate, and their interplay on variables such as tensile stress, tensile strength, fracture stress, and fracture morphology through a series of comprehensive tensile experiments. The experimental results demonstrate a notable increase in both tensile strength and tensile fracture stress when the temperature is set at 25 °C, accompanied by strain rates of 10-4, 10-3, 10-2, and 10-1 s-1. Conversely, a significant decrease is observed in the aforementioned properties when the strain rate is fixed at 10-4, while varying temperatures of -25 °C, 0 °C, 25 °C, 50 °C, and 75 °C are applied. At lower temperatures, cracks manifest on the fracture surface, while matrix softening occurs at higher temperatures. Additionally, in the context of strain rate-temperature coupling, the decreasing trend of both tensile strength and tensile fracture stress decelerates as the temperature ranges from -25 °C to 75 °C at a strain rate of 10-1, compared to 10-4 s-1. These findings highlight the significant influence of both strain rate and temperature on high fiber content long glass fiber-reinforced polypropylene composites.

Optimal clinical protocols for total-body 18F-FDG PET/CT examination under different activity administration plans.

BACKGROUND: Highly sensitive digital total-body PET/CT scanners (uEXPLORER) have great potential for clinical applications and fundamental research. Given their increasing sensitivity, low-dose scanning or snapshot imaging is now possible in clinics. However, a standardized total-body 18F-FDG PET/CT protocol is still lacking. Establishing a standard clinical protocol for total-body 18F-FDG PET/CT examination under different activity administration plans can help provide a theoretical reference for nuclear radiologists. METHODS: The NEMA image quality (IQ) phantom was used to evaluate the biases of various total-body 18F-FDG PET/CT protocols related to the administered activity, scan duration, and iterations. Several objective metrics, including contrast recovery (CR), background variability (BV), and contrast-to-noise ratio (CNR), were measured from different protocols. In line with the European Association of Nuclear Medicine Research Ltd. (EARL) guidelines, optimized protocols were suggested and evaluated for total-body 18F-FDG PET/CT imaging for three different injected activities. RESULTS: Our NEMA IQ phantom evaluation resulted in total-body PET/CT images with excellent contrast and low noise, suggesting great potential for reducing administered activity or shortening the scan duration. Different to the iteration number, prolonging the scan duration was the first choice for achieving higher image quality regardless of the activity administered. In light of image quality, tolerance of oncological patients, and the risk of ionizing radiation damage, the 3-min acquisition and 2-iteration (CNR = 7.54), 10-min acquisition and 3-iteration (CNR = 7.01), and 10-min acquisition and 2-iteration (CNR = 5.49) protocols were recommended for full-dose (3.70 MBq/kg), half-dose (1.95 MBq/kg), and quarter-dose (0.98 MBq/kg) activity injection schemes, respectively. Those protocols were applied in clinical practices, and no significant differences were observed for the SUVmax of large/small lesions or the SUVmean of different healthy organs/tissues. CONCLUSION: These findings support that digital total-body PET/CT scanners can generate PET images with a high CNR and low-noise background, even with a short acquisition time and low administered activity. The proposed protocols for different administered activities were determined to be valid for clinical examination and can maximize the value of this imaging type.

[18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04.

PURPOSE: [18F]FAPI-42 is a new fibroblast activation protein (FAP)-specific tracer used for cancer imaging. Here, we describe the optimal acquisition time and in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04. METHODS: A total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-h, and static 2-h scans. The in vivo biodistribution in normal organs and tumor uptake were semiquantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability. RESULTS: [18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 min, which stayed at a similarly high level to 2 h. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 h postinjection. For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 showed a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura, and peritoneal lesions (all P < 0.05). CONCLUSION: The present study demonstrates that the optimal image acquisition time of [18F]FAPI-42 is 1 h postinjection and that [18F]FAPI-42 exhibits comparable lesion detectability to [68Ga]Ga-FAPI-04. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100045757).

[18F-FDG PET/CT manifestations of massive type active pulmonary tuberculosis and its differentiation from lung cancer].

OBJECTIVE: To investigate 18F-FDG PET/CT manifestations of massive type active tuberculosis and lung cancer and the differential diagnosis of the two diseases based on 18F-FDG PET/CT findings. METHODS: We retrospectively collected the data from 74 patients with active tuberculosis and 64 patients with lung cancer, whose lesions presented as solid masses on CT. The demographic and clinical data of the patients, 18F-FDG PET characteristics including SUVmax, 18F-FDG uptake (higher than mediastinal blood pool or not), radioactive defect within the lesion, and the CT findings including the lesion size, signs of cavity, vacuoles, lobulation, smooth border, and mediastinal/lung window ratio (M/L ratio) of the lesions were analyzed. Univariate and multivariate analyses were used to compare the variables between the two groups, and a logistic regression model was established for differentiation of the two diseases. The diagnostic efficiency was evaluated by area under the receiver-operating characteristic (ROC) curve analysis. RESULTS: No significant differences were found in the quantitative index (SUVmax >2.5 or not) or in the qualitative index (uptake of lesion higher than mediastinal blood pool or not) in PET between massive type active tuberculosis and lung cancer (P>0.05). Univariate analysis revealed that SUVmax, 18F-FDG uptake of the lesion, age, lesion size, signs of cavity, or M/L ratio were not significantly different (P>0.05), but gender, signs of radioactive defect, vacuoles, smooth border and lobulation were significantly different (P < 0.05) between the two diseases. Multivariate analysis showed that gender, signs of radioactive defect, smooth border and lobulation of the lesion were independent factors for discrimination of the two diseases (P < 0.05). A risk prediction model for active tuberculosis was established based on logistic regression analysis: P=1/(1+e-x), X=-0.530+1.978×gender+3.343×radioactive defect +2.846×smooth border-2.116×lobulation. For diagnosis of active tuberculosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of this model were 78.4%, 92.2%, 84.8%, 92.1%, and 78.7%, respectively. CONCLUSIONS: The combined analysis of gender, signs of radioactive defect, smooth border and lobulation of the lesions is useful for discriminating massive type active tuberculosis from lung cancer in the majority of the patients, whereas 18F-FDG uptake alone has only limited value for a differential diagnosis.

Application of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography in mantle cell lymphoma.

OBJECTIVE: The study is to investigate the application of F-fluorodeoxyglucose (F-FDG) PET/computerized tomography (CT) for the evaluation of mantle cell lymphoma (MCL). METHODS: We retrospectively analyzed 39 patients who were pathologically diagnosed with MCL and underwent F-FDG PET/CT before treatment between August 2007 and August 2018. We compared the clinical information and PET/CT imaging characteristics in different groups based on bone marrow invasion, spleen invasion or International Prognostic Index (IPI) score. We also assessed the efficacy of PET/CT evaluation basing on the follow-up PET CT findings of 21 MCL patients and their biopsies. RESULTS: Thirty-five patients were stage IV according to the Revised Ann Arbor Staging System. Lymph node involvement was observed in all 39 cases. The maximum diameter of the affected lymph nodes (4.33 ± 3.09 cm) and maximum standardized uptake value (SUVmax) (8.38 ± 4.99) was positively correlated (r = 0.486, P = 0.002). Extranodal invasion was identified in 38 patients with MCL, and the SUVmax of extranodal invasion was 7.34 ± 3.31. Extranodal invasion was most common in the spleen (25/38) and bone marrow (18/38). The group with bone marrow invasion was more prone to nasopharyngeal, lung and renal invasions (all P < 0.05). The groups with bone marrow invasion or spleen invasion were more likely to have decreased hemoglobin (Hgb) and platelets (all P < 0.01). The IPI high-risk group was more prone to lung involvement, elevated LDH and CRP, and decreased Hgb (all P < 0.05). Among the follow-up of 30 MCL patients, the 2-year progression-free survival and overall survival rates were 73.33 and 87.50%, respectively. PET/CT reexaminations of 21 MCL patients after treatment showed that the sensitivity, specificity, negative predictive value, positive predictive value and accuracy of the efficacy evaluation were 80, 90.91, 88.89, 83.33 and 85.71%, respectively. CONCLUSION: F-FDG PET/CT imaging has important application value in the diagnosis, staging, treatment efficacy assessment and prognosis monitoring of MCL, especially in the systemic assessment of advanced MCL.

Nicotinic Agonist Inhibits Cardiomyocyte Apoptosis in CVB3-Induced Myocarditis via α3ß4-nAChR/PI3K/Akt-Dependent Survivin Upregulation.

BACKGROUND: Cardiomyocyte apoptosis is critical for the development of coxsackievirus B3- (CVB3-) induced myocarditis, which is a common cardiac disease that may result in heart failure or even sudden death. Previous studies have associated CVB3-induced apoptosis with the downregulation of antiapoptotic proteins. Here, attempts were made to examine whether nicotinic acetylcholine receptors (nAChRs), especially α3ß4-nAChRs, were a novel therapeutic antiapoptotic target via the activation of survivin, a strong antiapoptotic protein, in viral myocarditis (VMC). METHODS AND RESULTS: In the present study, we demonstrated that nAChRs, α3ß4-nAChR subunits in particular, were present and upregulated in CVB3-infected neonatal rat cardiomyocytes (NRC) and H9c2 cells by RT-qPCR. The function of α3ß4-nAChRs was next examined using its specific blocker α-CTX AuIB in vitro. The results of the TUNEL assay and western blot experiments showed that the block of α3ß4-nAChRs abrogated nicotine-mediated protection of NRC from CVB3-induced apoptosis, and this effect displayed a substantial correlation with the protein expressions of pAkt, survivin, and Cleaved Caspase-3. Hence, the involvement of the PI3K/Akt pathway was further verified by LY294002, a selective inhibitor of PI3K. As a result, nicotine-mediated induction of pAkt and survivin was abolished by LY294002; meanwhile, apoptotic NRC were increased accompanied by an increase of Cleaved Caspase-3 expression. Regarding CVB3-infected BALB/c mice, the α-CTX AuIB- and LY294002-treated groups had a lower survival rate, deteriorative ventricular systolic function, and more severe inflammation than the nicotine-treated group and the modulation of pAkt, survivin, and Cleaved Caspase-3 protein expressions was similar to that in CVB3-infected NRC. In addition, we found that a nicotinic agonist reduced CVB3 replication in a dose-dependent manner in vitro, which indicates that nAChR activation may serve as a possible protection mechanism of CVB3-induced myocarditis. CONCLUSIONS: Our study demonstrated that α3ß4-nAChR subunits are essential in the nicotine-mediated antiapoptotic effect of protecting cardiomyocytes from CVB3-induced apoptosis in vivo and in vitro. This protection correlated with the PI3K/Akt pathway and the inducement of the antiapoptotic protein survivin. A combination of these mechanisms serves as a novel protective response to treat viral myocarditis.

Combination of HSV1-TK/shTERT by retrovirus vector inhibits hepatocellular carcinoma cell growth in vitro and in vivo.

Hepatocellular carcinoma (HCC) is a common malignant carcinoma worldwide and the third leading cause of cancer mortality. However, current treatment strategies are not potent enough to combat this disease. Therefore, identification of novel and more effective treatments is crucial. Of the current methods, gene therapy, which targets cancer­specific expression and limits toxicity, is a new strategy for treating cancers. In this study, we developed a retroviral vector containing herpes simplex virus type-1-thymidine kinase (HSV1­TK) and a short hairpin RNA for the human telomerase reverse transcriptase (hTERT) gene and investigated the antitumor effects in an in vitro and in vivo mouse model of liver cancer, monitored by PET image. In vitro experiments on HCC cells in the TK-shTERT treatment group showed significant accumulation of 18F-FHBG, which preferentially inhibits HCC cell growth with extremely limited toxicity in normal cells. In vivo studies showed a significant reduction of growth in the TK-shTERT treatment group. In conclusion, these findings showed that combination HSV1-TK/hTERT gene therapy effectively and safely inhibits HCC cell growth in vitro and in vivo and is worthy of development in clinical trials for the treatment of HCC.

[Value of dual-phase (18)F-FDG PET/CT in preoperative staging of bladder cancer].

OBJECTIVE: To investigate the clinical value of dual-phase (18)F-FDG PET/CT with oral diuretics in preoperative staging of bladder cancer. METHODS: The imaging data were analyzed of 73 patients with bladder cancer undergoing preoperative dual-phase (18)F-FDG PET/CT with oral diuretic between May, 2003 and May, 2012. All the patients underwent whole-body PET/CT scan 60 min after intravenous injection of 270-350 MBq of (18)F-FDG. Additional delayed pelvic PET/CT images were acquired after forced diuresis using oral furosemide (40 mg). All the patients underwent subsequent radical cystectomy, and (18)F-FDG PET/CT findings were compared with the histopathologic results to evaluate the value of dual-phase (18)F-FDG PET/CT in preoperative staging. RESULTS: The concordance rate of dual-phase FDG PET/CT-based bladder cancer staging with the histopathologic results was 63.0% in the 73 patients, and was 100% (7/7) for pT4 bladder cancers. With dual-phase FDG PET/CT, the detection rate was 75.0% (6/8) for lymph node metastases, 100% (4/4) for distant metastases, and 100% (4/4) for other concurrent primary malignancies. CONCLUSION: Though with limited accuracy in T-staging of pTa, pT1, pT2, and pT3 bladder cancer, dual-phase FDG PET/CT has important clinical value in staging of pT4 bladder cancer and in N-staging, M-staging and detection of other concurrent primary malignancies.

[Tumor targeting efficacy of a novel PET radiotracer (1)8F-AlF-NOTA-PRGD2 in mice].

OBJECTIVE: To investigate the tumor targeting efficacy of (18)F-AlF-NOTA-PRGD2, a novel radiotracer of Arginine-glycine-aspartic acid (RGD) peptides. METHODS: (18)F-AlF-NOTA-PRGD2 was synthesized in one-step by conjugating NOTA-PRGD2 with (18)F-AlF at 100 degrees celsius;. The tumor targeting efficacy and in vivo biodistribution profile of (18)F-AlF-NOTA-PRGD2, following intravenous injection via the tail vein, were evaluated in a nude mouse model bearing subcutaneous U87MG glioblastoma xenograft by radioactivity biodistribution assessment, PET/CT and microPET/CT. RESULTS: NOTA-PRGD2 was (18)F-fluorinated successfully in one-step with a yield of 17%-25% within 15-20 min. Radioactivity biodistribution study confirmed the tumor-targeting ability of (18)F-AlF-NOTA-PRGD2 in the tumor-bearing mice. At 1 and 2 h following injection, (18)F-AlF-NOTA-PRGD2 uptake in the tumor reached 4.14∓1.44 and 2.80∓1.18 % ID/g (t=1.910, P=0.070) with tumor/brain ratios of 2.95∓0.61 and 5.21∓2.62, respectively (t=-1.686, P=0.167). Both PET/CT and microPET/CT were capable of showing the radioactivity biodistribution of (18)F-AlF-NOTA-PRGD2 in the mouse model and clearly displayed the tumor, but microPET/CT showed a much better image quality. CONCLUSION: (18)F-AlF-NOTA-PRGD2 prepared by one-step radiosynthesis can selectively target to the tumor, demonstrating its potential as a good radiotracer for tumor imaging.

F-18 FDG in conjunction with 11C-choline PET/CT in the diagnosis of hepatocellular carcinoma.

PURPOSE: F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) alone has limited sensitivity for the diagnosis of hepatocellular carcinoma (HCC). We hoped to improve the diagnostic sensitivity by combining F-18 FDG and C-choline PET/CT. MATERIALS AND METHODS: A total of 76 consecutive patients with HCC were prospectively enrolled. Whole-body F-18 FDG PET/CT scan was performed for all patients. In those patients with negative F-18 FDG scans, a regional C-choline PET/CT scan was also performed. RESULTS: Positive F-18 FDG scans were noted in 61.1% (48/76) patients with HCC. Increased F-18 FDG uptake correlated with decreased tumor differentiation (P = 0.042). In 28 HCC patients with negative F-18 FDG scans, C-choline scan was positive in 71.4% patients. C-choline scan did not detect any significant difference between well- and moderately differentiated HCC (P = 0.585). Compared with F-18 FDG scan, C-choline scan showed a trend toward an improved detection of well-differentiated HCC (66.7% vs. 35.7%, NS). For detection of moderately differentiated HCC, the sensitivity of C-choline and F-18 FDG PET/CT was similar (85.7% vs. 72.0%, P = 0.648). The dual-tracer modality improved the diagnostic sensitivity of F-18 FDG PET/CT alone from 63.1% to 89.5% (P < 0.001). CONCLUSIONS: F-18 FDG in conjunction with C-choline increases the sensitivity of PET/CT in detecting HCC.

Utility of 18F-FDG PET/CT for staging NK/T-cell lymphomas.

PURPOSE: Extranodal natural killer (NK)/T-cell lymphoma is a rare neoplasm and limited data has reported regarding the utilization of fluorine-18, fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in this disease. The aim of this study was to assess the role of F-FDG PET/CT in the staging of NK/T-cell lymphomas. PATIENTS AND METHODS: Thirteen newly diagnosed and two recurrent patients with NK/T-cell lymphoma who received F-FDG PET/CT were studied. The lesion with intense F-FDG uptake was suggested as the positive and was measured using maximal standardized uptake values. The results of PET/CT were compared with the conventional staging examinations. RESULTS: F-FDG PET/CT detected nasal or extranasal lymphoma lesions in at least one site in all of the 15 patients. There was no significant difference of F-FDG uptake in lesions between patients with stage I-II disease and those with stage III-IV disease (maximal standardized uptake values 8.44+/-5.56 vs. 10.32+/-7.80; t=0.757, P>0.05). In two patients with an indeterminate diagnosis, the diagnosis of NK/T-cell lymphomas was established by biopsy guided by PET/CT and the status of stage IV was correctly identified. In 13 patients with definite diagnosis, the stage of disease was changed in six patients on the basis of F-FDG PET/CT. Two patients were down staged, and four patients upstaged. CONCLUSION: The lesions of the NK/T-cell lymphoma are F-FDG avid and PET/CT seems to be useful in the staging of this disease.

[Construction of a retroviral vector for RNA interference targeting human telomerase reverse transcriptase].

OBJECTIVE: To construct a recombinant retroviral vector for RNA interference targeting human telomerase reverse transcriptase (hTERT). METHODS: The sequences coding for enhanced fluorescence protein (EGFP), U6 promoter and a small interfering RNA (siRNA) targeting hTERT were amplified by PCR, respectively, and sub-cloned sequentially into the retroviral shuttle plasmid pLXSN to construct the plasmid pLXSN-EGFP-U6-siTERT. The recombinant expression plasmid was identified by restriction enzyme digestion and sequencing. Fluorescence microscopy and flow cytometry were employed to analyze EGFP expression in NIH3T3 transfected with the recombinant plasmid, and MMT assay was performed to evaluate the growth inhibition of Hela cells resulting from RNA interference mediated by the plasmid. RESULTS: Sequence analysis and restriction enzyme digestion showed that the recombinant expression plasmid pLXSN-EGFP-U6-siTERT was constructed successfully. Twenty-four hours after transfection of NIH3T3 cells with the recombinant plasmid, the expression rate of EGFP reached 24.1% as shown by flow cytometry. MTT assay demonstrated a cell death rate of 53.2% 72 h after transfection of Hela cells with the plasmid. CONCLUSION: The successful construction of the recombinant retroviral plasmid mediating potent cell growth inhibition suggests the great potential of RNA interference technique in suppressing hTERT expression in mammalian tumor cells.