[Screening and validation of pivotal genes in hepatitis B virus-associated hepatocellular carcinoma].

Objective: To screen the pivotal genes involved in the occurrence and development of HBV-associated HCC. Additionally, perform validation and biological function analysis to evaluate changes in the expression of pivotal genes and their prognostic value in patients with hepatocellular carcinoma. Methods: The GSE121248 gene expression profile data of HBV-HCC patients were searched and downloaded from the GEO database. The R language was used to compare the differences in gene expression between hepatocellular carcinoma and paracancerous tissues. KEGG and GO function enrichment analyses were performed on the differential genes. PPI plots and pivotal gene screening were carried out through online tools like STRING and Cytoscape software. 369 cases of hepatocellular carcinoma and 160 healthy controls in TCGA and GTEx were used as validation cohorts to verify the expression levels of the pivotal genes. A Kaplan-Meier plot was drawn to evaluate the prognostic value of the pivotal gene. Results: A total of 120 differentially expressed genes were screened, of which 89 were up-regulated and 31 were down-regulated. Differential genes were mainly enriched in the metabolic pathways related to retinol metabolism, cytochrome P450 metabolism, and the p53 signaling pathway. The top 10 differential genes were selected as pivotal genes by the Cytoscape plug-in cytoHubba. There were significant differences in the expression levels of four types of CCNB1, CDK1, RRM2, and TOP2A genes in the validation cohort. All four types of genes were up-regulated. Survival analysis showed that patients with elevated expression levels of four genes had a poorer prognosis, with statistical differences in results. Conclusion: Four types of genes, CCNB1, CDK1, RRM2, and TOP2A, have high expression levels in patients with HBV-HCC and are correlated to shorter survival times, making them a potential target for diagnosis, prognosis, and treatment.

Efficient construction of bioactive trans-5A5B6C spirolactones via bicyclo[4.3.0] α-hydroxy ketones.

An efficient, convenient short synthetic procedure for the synthesis of the intricate 5A5B6C-ring fusion topologies of tricyclic spiranoid ß-hydroxybutyrolactones through lactonization of the key intermediate trans-α-hydroxyindenones with malonates is described. All the compounds synthesized exhibited environmentally benign characteristics, moderate fungicidal, nematocidal, and anti-TMV activities.

HLA-A2-restricted cytotoxic T lymphocyte epitopes from human hepsin as novel targets for prostate cancer immunotherapy.

Hepsin is a type II transmembrane serine protease that is overexpressed in prostate cancer, and it is associated with prostate cancer cellular migration and invasion. Therefore, HPN is a biomarker for prostate cancer. CD8(+) T cells play an important role in tumour immunity. This study predicted and identified HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes in human hepsin protein. HLA-A2-restricted CTL epitopes were identified using the following four-step procedure: (1) a computer program generated predicted epitopes from the amino acid sequence of human hepsin; (2) an HLA-A2-binding assay detected the affinity of the predicted epitopes to the HLA-A2 molecule; (3) the primary T cell response against the predicted epitopes was stimulated in vitro; and (4) the induced CTLs towards different types of hepsin- or HLA-A2-expressing prostate cancer cells were detected. Five candidate peptides were identified. The effectors that were induced by human hepsin epitopes containing residues 229 to 237 (Hpn229; GLQLGVQAV), 268 to 276 (Hpn268; PLTEYIQPV) and 191 to 199 (Hpn199; SLLSGDWVL) effectively lysed LNCaP prostate cancer cells that were hepsin-positive and HLA-A2 matched. These peptide-specific CTLs did not lyse normal liver cells with low hepsin levels. Hpn229, Hpn268 and Hpn199 increased the frequency of IFN-γ-producing T cells compared with the negative peptide. These results suggest that the Hpn229, Hpn268 and Hpn199 epitopes are novel HLA-A2-restricted CTL epitopes that are capable of inducing hepsin-specific CTLs in vitro. Hpn229, Hpn268 and Hpn199 peptide-based vaccines may be useful for immunotherapy in patients with prostate cancer.

Top-cited works about exercise for knee osteoarthritis: a bibliometric analysis from 2000 to 2021.

OBJECTIVE: Previous trials demonstrated the effectiveness of exercise in improving pain and functional impairment in patients with knee osteoarthritis (KOA). However, a bibliometric analysis of top-cited papers on exercise treatment for KOA has not yet been conducted. The aim of the present study was to critically analyze the bibliometric characteristics of the most frequently cited articles on exercise treatment for KOA. MATERIALS AND METHODS: Publications about exercise treatment for KOA from 2000 to 2021 were searched from the Web of Science database. Two authors independently collected 100 top-cited articles, and a consensus was reached to form the final list. The title, journal, author, year of publication, country and institution of origin, total citations, citations in 2021, main topics, research nature, and level of evidence were extracted, and the publication trends in exercise treatment for KOA were evaluated. RESULTS: A total of 1,258 papers were retrieved from the database. According to the final list, clinical research accounted for 81% of the studies, but no statistical difference in the number of citations was found among the four types of articles (p=0.194). Seventy articles had a level of evidence of Ib, and no statistical differences in citations were found per level of evidence (p=0.767). Most of the top-cited articles were published between 2005-2014, and Dr Messier was the prominent writer in this field. CONCLUSIONS: This bibliometric study is the first to identify the most cited papers in exercise treatment for KOA research. Traditional Chinese exercise, comorbidity, and exercise adherence may be the next popular research trends that will receive more attention in the future.

Longitudinal health utilities, symptoms and toxicities in patients with ALK-rearranged lung cancer treated with tyrosine kinase inhibitors: a prospective real-world assessment.

Background: Tyrosine kinase inhibitors (tkis) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (nsclc). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple tki therapies in the population with ALK+ nsclc. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of tkis, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (hus). Results: In 499 longitudinal encounters of 76 patients with ALK+ nsclc, each tki had stable longitudinal hus when disease was controlled, even after months to years: the mean overall hus for each tki ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation tkis of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean hus decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from -0.094 to -0.557. Fewer symptoms and toxicities were associated with the second- and third-generation tkis compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved hus. Conclusions: There was no significant decrease in hus when patients with ALK+ disease were treated longitudinally with each tki, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean hus longitudinally in the real-world setting.

Low birth weight contributes to the excess prevalence of end-stage renal disease in African Americans.

The risk of hypertension and related target organ damage is much greater in African Americans than in Caucasians. The risk of hypertensive end-stage renal disease is approximately five-fold higher in African Americans. Many studies have shown that low birth weight is strongly associated with increased risk of hypertension, stroke, and myocardial infarction. However, until recently the relationship between birth weight and hypertension-related diseases was not clearly established in African Americans. Moreover, it was also unclear if low birth weight in humans heightened the risk for end-stage renal disease. This is a critical gap in the literature, since low birth weight occurs at twice the rate in African Americans as among Caucasians. We identified a significant relationship between end-stage renal disease and low birth weight in both African Americans and Caucasians. Given the higher rates of low birth weight in African Americans, differences in fetal development may, therefore, contribute to the racial disparity in end-stage renal disease. Continued study of the biological factors linking early development with later risk of hypertension-related diseases is important and may shed light on racial disparities in health outcomes. (c)2001 by Le Jacq Communications, Inc.

[Cultivation and ultrastructural investigation of human iris pigment epithelial cells].

UNLABELLED: The iris pigment epithelial cells of 10 human eyes were cultivated in vitro. RESULTS: The iris pigment epithelial cells obtained directly by scraping were easier to grow and to be passaged than those obtained by enzyme digestion. Under the inverted light microscope, primary cells appeared multigonal and arranged in monolayer, there were abundant pigment granules in the cytoplasm, and the nuclei each of which contained 1 or 2 nuclei were relatively transparent. Pigment granules diminished in succeeding generations. Under the transmission electron microscope, pigment granules were rich in the cytoplasm and there were plenty of microvilli at the cell membrane. There were maculae occludentes and desmosomes present in the intercellular space. The cultivated cells showed positive reaction of keratin antigen in an immunohistochemical assay. The characteristics mentioned above are consistent with the criteria of iris pigment epithelial cells.

New genotype of avian influenza H5N1 viruses isolated from tree sparrows in China.

The 2004 outbreaks of highly pathogenic avian influenza H5N1 disease in China led to a great poultry loss and society attention. A survey of avian influenza viruses was conducted on tree sparrows (Passer montanus) collected in China in 2004. Four viruses were isolated from free-living tree sparrows. The results of the whole-genome analysis indicated that an H5N1 virus with a new genotype is circulating among tree sparrows. The hemagglutinin and neuraminidase genes of the new genotype were derived from Gs/Gd/96-like viruses and the nuclear protein gene descended from the 2001 genotype A H5N1 viruses, while the other inner genes originated from an unknown influenza virus. In experimental infection, all four viruses were highly pathogenic to chickens but not pathogenic to ducks or mice. The four tree sparrow viruses were different from the 2003 tree sparrow strain (genotype Z) in Hong Kong. The results suggested that H5N1 viruses might be distributed widely in tree sparrows.

Inhibition of fibroblast proliferation by human iris pigment epithelial cells in vitro: preliminary results.

BACKGROUND: The interaction between different cells plays an important role in many physiological and pathological processes. Since the proliferation of fibroblasts is very much involved in the pathogenesis of eye diseases such as proliferative vitreoretinopathy, the failure of filtration in glaucoma surgery, etc., we attempted to ascertain whether iris pigment epithelial cells (IPE) have some modulating effect on fibroblast proliferation. METHODS: Human IPE were explanted and the third-passage culture was transferred into serum-free RPMI-1640 medium. After 48 h of further incubation, the medium was collected and submitted to centrifugation; the supernatant was used as the conditioned medium of IPE (IPE-CM). Cultured fibroblasts from Tenon's capsule were seeded in a 96-well plate and incubated with IPE-CM in different concentrations. The proliferation of fibroblasts was estimated by thymidine incorporation and cell counting. RESULTS: The incorporation of tritiated thymidine by fibroblasts was reduced to 56.68% of baseline with 1:16 diluted IPE-CM and to 13.63% and 8.20%, respectively, with 1:8 and 1:2 diluted IPE-CM. These findings were in good accordance with the results of cell counting, performed in parallel. SDS-PAGE of IPE-CM revealed two specific bands with molecular weight 65 kDa and 40 kDa. CONCLUSION: IPE-CM showed an obvious dose-dependent inhibitory effect on fibroblast proliferation and was presumed to contain some active factors contributing to this effect.