The safety signal detection and analysis of monoclonal antibodies against SARS-CoV-2 based on real-world evidence - the suitable selectivity for different populations.

OBJECTIVE: Bebtelovimab (BEB), Tixagevimab/Cilgavimab (TIX/CIL), and Sotrovimab (SOT) are important agents against the severe acute respiratory syndrome coronavirus 2-Omicron strain. However, due to their short duration of application, little is known about their safety profiles. This research aimed to explore the safety profile of these monoclonal antibodies (mAbs) via real-world evidence databases and data mining tools. MATERIALS AND METHODS: Safety reports were retrieved from the database of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System from April 2022 to March 2023. To detect the safety signal, the disproportionality analysis was performed using the reporting odds ratio method. RESULTS: SOT had the greatest proportion of "skin and subcutaneous tissue disorders" and "disorders of investigations"; BEB showed significant associations with "gastrointestinal disorders" and "nervous system disorders"; TIX/CIL had the weakest correlation with "skin and subcutaneous tissue disorders" and "general disorders and administration site conditions". Furthermore, there were still other signals related to nervous system disorders, gastrointestinal disorders only caused by BEB. TIX/CIL has been reported solely to be associated with multiple types of cardiovascular disorders. As for SOT alone, signals were strongly related to infusion reactions and hypersensitivity. CONCLUSIONS: In summary, SOT may be unsuitable for allergic patients and may lead to abnormal test results. BEB showed the highest correlations with gastrointestinal and neuropsychiatric events. In addition, its infusion reactions should also be noted. TIX/CIL can lead to a variety of cardiovascular events.

NF-κB inhibits the differentiation of hysteromyoma cells by reducing myocardin expression.

OBJECTIVE: To investigate the effect of nuclear factor-kappaB (NF-κB) on the myocardin-mediated differentiation of hysteromyoma cells. MATERIALS AND METHODS: Expression levels of myocardin in hysteromyoma cells from patients with hysteromyoma were detected. Normal uterine smooth muscle cells were used as control group. Overexpression of myocardin in hysteromyoma cells was achieved through lentivirus infection. Changes in expression levels of uterine smooth muscle cell maker p21, p57, Cyclin D1, PCNA, SM22α, and αSMA were detected. Hysteromyoma cells with lentivirus infection were stimulated by lipopolysaccharide (LPS), and changes in expression levels of myocardin were detected. RESULTS: Compared with normal uterine smooth muscle cells, the expression level of myocardin in hysteromyoma cells was extremely low, or even undetectable, and expression levels of smooth muscle cell differentiation markers were also minimal, and cells were in the de-differentiated state. Expression of exogenous myocardin can improve the expression of smooth muscle cell differentiation markers to induce cell re-differentiation. LPS stimulation can activate NF-κB to inhibit myocardin expression, thereby inducing cell dedifferentiation. CONCLUSIONS: NF-κB can inhibit the differentiation of hysteromyoma cells by decreasing the expression level of myocardin.

Expression of miR-205 in renal cell carcinoma and its association with clinicopathological features and prognosis.

OBJECTIVE: The aim of the present study was to examine the expression of miR-205 in renal cell carcinoma (RCC) tissue and carcinoma cells; also, we aimed to determine the association of miR-205 expression with the clinicopathological features and prognosis of RCC, and to explore the mechanism of miR-205. PATIENTS AND METHODS: Carcinoma tissue and adjacent normal tissue were collected from 60 patients with RCC, and the expression of miR-205 was determined by semi-quantitative PCR, followed by correlation analysis of miR-205 with clinicopathological features and prognosis. Subsequently, the human RCC line, ACHN, was transfected with miR-205, and the effect of miR-205 overexpression on the growth of RCC was examined by MTT assay. Moreover, the effect of miR-205 on the migration of colon cancer cells was studied by transwell assay. Additionally, immunohistochemistry and Western blot were used to investigate the epithelial-mesenchymal transition in renal cancer tissue. RESULTS: The expression of miR-205 was downregulated in RCC tissue compared with adjacent non-cancerous tissue (p < 0.01). The expression of miR-205 was closely related to the infiltration and recurrence of tumors (p < 0.01), but was not correlated with a pathological grade or clinical stage (p > 0.05). We also found that overexpression of miR-205 in RCC significantly inhibited the growth of cancer cells (p < 0.01) and significantly reduced the migration ability (p < 0.01). The epithelial-mesenchymal transition occurs in RCC, and miR-205 might inhibit cell proliferation and migration by blocking the epithelial-mesenchymal transition. CONCLUSIONS: The expression of miR-205 is low in RCC, and may play an important role throughout the progression of RCC. Further study of miR-205 may promote the development of a novel therapeutic approach for the treatment of RCC.

Sirt 1 activator attenuates the bleomycin-induced lung fibrosis in mice via inhibiting epithelial-to-mesenchymal transition (EMT).

OBJECTIVE: The aim of this study was to investigate the effect of resveratrol on the idiopathic bleomycin (BLM)-induced pulmonary fibrosis, which is increasingly recognized as an epithelial-to-mesenchymal transition (EMT)-associated disease. MATERIALS AND METHODS: We evaluated the effect of resveratrol on the BLM-induced fibrosis in a mouse model, via monitoring the pathological chance in mice lung, the mice body weight change and the mice death. And we also explored the regulation by BLM on (and) resveratrol on the expression and activity of Sirt 1 and on the expression of epithelial-to-mesenchymal transition (EMT)-associated markers in mice lung. RESULTS: It was demonstrated that resveratrol ameliorated the BLM-induced fibrosis-like pathological change in mice lung, inhibited BLM-induced mice body weight loss and death. Moreover, resveratrol also inhibited the BLM-induced EMT-associated molecular events, such as reduced E-cadherin and elevated Collagen I and α-SMA. We also confirmed the amelioration by resveratrol on the BLM-mediated inhibition of Sirt 1 in expression and activity in mice lung. CONCLUSIONS: Our study confirmed the inhibitory role of resveratrol in the BLM-induced pulmonary fibrosis in a mouse model. Resveratrol ameliorated the BLM-induced pathological change of fibrosis, mice body weight loss and death. And such amelioration might be associated with the activation of Sirt 1 in mice lung. The present study implied that resveratrol might be a promising agent for effective control the pulmonary fibrosis.

Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer

Background: The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis. Methods: We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC. Results: The results showed that high expression of FOXM1 staining was 85.44 % (88/103) in 103 cases of CRC and 20.39 % (21/103) in 103 cases of adjacent noncancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines. Conclusions: Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC

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The ultra early diagnosis of Parkinson's disease by the enhanced substantia nigra echo.

OBJECTIVE: Our objective is to determine the value of enhanced substantia nigra echo in the diagnosis of Parkinson's disease by analyzing the intensity and area of substantia nigra echo by transcranial Doppler sonography (TCS). PATIENTS AND METHODS: 36 patients diagnosed as ultra early stage Parkinson's disease between 2013 November and 2014 August were selected as the disease group, and 32 healthy people with the similar representation of age and gender were selected as the control group. TCS was used to detect the echo intensity and the echo intensity of the same location of bilateral hemicerebrum was used to evaluate the bilateral substantia nigra echo. The age and gender were also used for correlation analysis with the results of substantia nigra echo. RESULTS: In the control group, there were 17 patients of substantia nigra echo grade I (53.1%), 13 cases of substantia nigra echo grade II (40.6%), 2 cases of substantia nigra echo grade III (6.3%). While in the disease group, there were 4 cases of substantia nigra echo grade II (11.1%), 13 cases of substantia nigra echo grade III (36.1%), 12 cases of substantia nigra echo grade IV (33.3%) and 7 cases of substantia nigra echo grade V (19.4%). The ratio of enhanced substantia nigra echo in Parkinson's disease patients was significantly higher than the control group. The analysis of the factors related to motor symptoms in Parkinson's disease patients revealed that the area of bilateral substantia nigra echo was negatively correlated with gender, but positively correlated with age, S/M ratio and UPDRS II score. However, there was no correlation with H-Y stage. The sensitivity of substantia nigra echo in diagnosing Parkinson's disease was 32/36=88.89% and the specificity was 30/32 = 93.75%. CONCLUSIONS: Analysis of substantia nigra echo is practically useful for the diagnosis of the ultra early stage Parkinson's disease, which can potentially improve the accuracy of clinical diagnosis to significantly enhance the early clinical prevention and reduce later disability.

Randomised controlled trial: sequential vs. standard triple therapy for Helicobacter pylori infection in Chinese children-a multicentre, open-labelled study.

BACKGROUND: Studies have showed that 10-day sequential treatment regimen achieved higher Helicobacter pylori eradication rate than standard triple therapies. AIM: To compare a 10-day sequential therapy and standard triple therapy in Chinese children with H. pylori infection. METHODS: A prospective, multicentre, open-label, randomised controlled trial was conducted in four tertiary medical centres in China. Children with H. pylori gastritis were randomly assigned to a 10-day sequential therapy consisting of omeprazole and amoxicillin for 5 days followed by omeprazole, clarithromycin and metronidazole for the remaining 5 days, or 7-day or 10-day standard triple therapy comprising of omeprazole, amoxicillin and clarithromycin. H. pylori eradication was assessed by H. pylori stool antigen test. RESULTS: A total of 360 patients were included. The eradication rate achieved with the 10-day sequential therapy was significantly higher than either the 7-day or 10-day standard triple treatment, either by the intention-to-treat analysis (81.4% vs. 61.9% or 67.7%, P < 0.05) or per-protocol analysis (89.7% vs. 70.8% or 77.8%, P < 0.05). CONCLUSIONS: The 10-day sequential regimen was significantly more effective than standard 7-day or 10-day triple regimens in eradicating H. pylori infection in Chinese children.

Six placenta permeability-related genes: molecular characterization and expression analysis in pigs.

The nutrient transportation ability of placenta depends on placental size, vascular density and permeability. Regulation of angiogenesis in the placenta is critical for successful gestation. Placenta vascularity exhibits disparity in different gestation stages and different pig breeds. To investigate the expression of genes related to permeability in the porcine placenta of different gestation stages and breeds, molecular cloning and gene expression analysis of six porcine genes, vascular endothelial growth factor (VEGF), VEGF-R1, VEGF-R2, endothelial nitric oxide synthase (eNOS), vascular endothelial cadherin (CDH5) and ß-arrestin2 (Arrb2), were performed in this study. The results demonstrated that from gestation day 33 to day 90, Landrace exhibited significant increase (P < 0.05) in placental VEGF and Arrb2 mRNA expression. Moreover, expression levels of VEGF, VEGF-R1, VEGF-R2 and eNOS mRNA were higher (P < 0.01) in the placenta of Erhualian than those in Landrace on day 90 of gestation. In contrast, CDH5 placental mRNA expression level exhibited significant decrease (P < 0.05) from day 33 to day 90 gestation in Landrace. Erhualian placental CDH5 and Arrb2 expression levels were significantly lower (P < 0.01) than those in Landrace conceptuses on day 90 of gestation. Our study offered new data on the expression of genes in VEGF signal transduction pathway in porcine placenta.

Association between tumour necrosis factor gene polymorphisms and the clinical types of patients with chronic hepatitis B virus infection.

A PCR restriction fragment length polymorphism assay was used to analyse single-nucleotide polymorphisms in the tumour necrosis factor (TNF)-alpha and TNF-beta genes of 56 patients with chronic severe hepatitis B virus (HBV) infection, 71 patients who either had chronic mild HBV infection or who were asymptomatic carriers, and 90 healthy controls. The serum TNF-alpha concentrations in patients with chronic severe HBV infection were compared to those of 30 healthy controls by radioimmunoassay. The frequencies of the TNF1/2 genotype and the TNF2 allele were greater in patients with chronic severe HBV infection than in healthy controls (25% vs. 11.1%, p 0.015; 12.5% vs. 5.6%, p 0.036, respectively) and patients with chronic mild HBV infection and asymptomatic carriers (25% vs. 8.8%, p 0.011; 12.5% vs. 4.2%, p 0.015, respectively). Heterozygotes carrying the TNF2 allele had higher levels of serum TNF-alpha than homozygotes for the wild-type allele among all patients with chronic severe HBV infection (p <0.01). The genotype distribution and allele frequency of TNF-beta were similar for patients with chronic severe HBV infection and healthy controls, but the frequency of the TNF-beta*2/2 genotype in patients with chronic mild HBV infection and asymptomatic controls was lower than for healthy controls (9.9% vs. 22.4%, p 0.043) or patients with chronic severe HBV infection (9.9% vs. 26.8%, p 0.043), although this was not significant after correction for multiple testing. It was concluded that TNF-alpha gene polymorphisms may play an important role as a host factor in the progression of HBV infection.

Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.

The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.