Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis.

Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.Communicated by Ramaswamy H. Sarma.

The biomarker N-terminal pro-brain natriuretic peptide and liver diseases.

PURPOSE: NT-proBNP has emerged as a powerful diagnostic and prognostic biomarker in heart disease. Studies showed that NT-proBNP is a sensitive biomarker for identifying patients with heart failure caused by hepatitis C virus (HCV) related myocarditis. The purpose of this study was to evaluate the correlation between the serum concentration of NT-proBNP and hepatitis virus infection/liver disease. METHODS: 223 serum samples from blood donors (aged 19~50 years old) were collected as a control group, and 644 samples were obtained from patients infected by hepatitis viruses including 493 HBV: 364 chronic hepatitis (CH), 86 hepatocellular carcinoma (HCC) and 43 liver cirrhosis (LC) and 151 HCV (85 CH, 14 HCC, 52 LC). All samples were assayed with an Elecsys immunoassay analyzer for NT-proBNP concentration. RESULTS: The mean concentration of NT-proBNP in the control group was 21.77 pg/ml and showed no significant variation with either age or gender. Both the mean value and the rate of abnormality of NT-proBNP were significantly higher for the HBV- and HCV-infected groups in comparison with the control group. The mean NT-proBNP value (380.24 pg/ml) and abnormality rate (38.41%) in the HCV group were higher than that of the HBV group. For samples from patients with HBV/HCV-related hepatic disease/pathology, the mean NT-proBNP value (517.19 pg/ml/597.18 pg/ml) were the highest in the liver cirrhosis group. CONCLUSIONS: Hepatic pathologic lesions, particularly cirrhosis, may contribute to the elevation of NT-proBNP in subjects with HBV/HCV infection.

Swine hepatitis E virus in rural southern China: genetic characterization and experimental infection in rhesus monkeys (Macaca mulatta).

BACKGROUND: In rural areas of southern China, where hepatitis E is endemic, residents generally rear pigs in pigsties near their houses. The study was conducted to assess the possibility that hepatitis E virus (HEV) infections in this region are acquired primarily through contact with swine. METHODS: One hundred twenty swine fecal samples collected from pigsties located in eight rural communities of southern China were tested for HEV RNA. The swine HEV isolates were analyzed genetically and were experimentally inoculated into rhesus monkeys to determine the potential risk of cross-species infection. RESULTS: Twenty-nine of the 120 swine fecal samples were positive for HEV RNA. The nucleotide sequences of these swine HEV strains shared 85%-99% identities with the local human genotype 4 isolates and belonged to two subgroups of genotype 4. Importantly, swine HEV strains representing both subgroups induced hepatitis in rhesus monkeys by inoculation with the virus, evidenced by elevated serum alanine transaminase (ALT), viremia, fecal viral shedding, anti-HEV seroconversion, and liver histopathological changes. CONCLUSIONS: Swine may be the principal reservoir for human HEV infection in rural southern China.

Association of TNF-alpha genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a Han Chinese population.

The single nucleotide polymorphisms (SNPs) within the tumor necrosis factor-a (TNF-a) gene promoter region have been reported to be associated with susceptibility to various types of cancers. A case-control study (126 hepatocellular carcinoma [HCC] patients and 126 normal controls) was conducted to elucidate their possible association with the risk of hepatitis B virus (HBV)-related HCC in a Han Chinese population. TNF-alpha polymorphisms -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped by polymerase chain reaction (PCR) and direct DNA sequencing. Disease associations were analyzed by the chi-square test or Fisher's exact test. When analyzed by overall groups, no significant differences in genotype and allele distributions were observed between the control and cases. However, stratified analysis according to sex showed that the frequency of the homozygous C allele of the -857 polymorphism was lower in female cases than in female controls (62.9% vs. 88.9%, p=0.026). In addition, further haplotype analysis revealed that the TCCGA (-1031/-863/-857/-308/-238) was more frequent in controls than cases (p=0.018; odds ratio = 0.266; 95% confidence interval, 0.083-0.857). These results indicated that the TNF-alpha-857C/T polymorphism may modify HBV-related HCC risk among women, and the haplotype TCCGA (-1031/-863/-857/-308/-238) may account for a decreased susceptibility to HCC development in the Han Chinese population. Additional studies in patients with different ethnic backgrounds are needed to validate these finding and to further explore the genetic pathogenesis of HBV-related HCC.

Hepatitis E virus infection among animals and humans in Xinjiang, China: possibility of swine to human transmission of sporadic hepatitis E in an endemic area.

Hepatitis E is a worldwide public health problem, especially in areas with poor sanitation. This study examines the potential hepatitis E virus (HEV) animal reservoirs and the current status of HEV infection among animals and humans in an endemic area of Xinjiang, China. One thousand five hundred twenty-one serum samples from 12 different animal species and 296 sera from humans were detected for anti-HEV with an in-house enzyme immunoassay, and partial HEV RNA was amplified with a reverse transcription-nested polymerase chain reaction (RT-nPCR). All these distinct animal species, except jerboa and hoptoad, were positive for anti-HEV. However, HEV RNA was only amplified from pigs and a sporadic hepatitis E case in humans. The human HEV strain (CHN-XJ-HE29) shared 100% nucleotide identity with the swine HEV strain (CHN-XJ-SW50), both of which were collected from the same district; this indicates the possibility of HEV transmission from swine to humans in an endemic area.

[Hepatitis E virus (HEV) genotype and the prevalence of anti-HEV in 8 species of animals in the suburbs of Beijing].

OBJECTIVE: To investigate the prevalence of anti-hepatitis E virus (HEV) and genotypes of hepatitis E virus in 8 species of animals including swine, cattle, sheep, horse, donkey, dog, chicken and duck in the suburb of Beijing. METHODS: Serum samples were collected from the 8 species of animals, and fecal samples of younger swine were collected from 2 stock farms. Anti-HEV was detected by Double Antigen Sandwich Assay. HEV RNA from fecal samples was detected by a reverse transcription nested polymerase chain reaction (RT-nPCR). Parts of the PCR products were cloned and sequenced. The swine HEV sequences were analyzed genetically. RESULTS: The positive rates of anti-HEV in serum specimens of swine, cattle, horse, donkey, sheep, dog, duck and chicken were 80.43% (481/598), 15.02% (52/346), 14.29% (40/280), 0 (0/26), 9.88% (33/334), 0 (0/21), 3.03% (7/231) and 2.53% (8/316), respectively. The anti-HEV prevalence of adult swine (>/= 6 months) and younger swine ( < / = 3 months) were 87.86% (369/420) and 62.92% (112/178) respectively. 74 of 111 (66.67%) pig faces were positive for HEV RNA. Sequence analysis on these positive samples showed that there were 6 groups of HEV designated as bjsw1, bjsw2, bjsw3, bjsw4, bjsw5 and bjsw6. The 6 strains of HEV shared 94.5% - 99.6% sequence identity of partial HEV ORF2 nucleotide with each other. The identities of HEV ORF2 nucleotide sequences between the 6 strains and genotype 1, 2, 3 and 4 were 75.6% - 78.6%, 75.6% - 76.2%, 77.1% - 80.7% and 83.7% - 94.5%, respectively. The sequence identity between the 6 strains and human HEV genotype 4d was 90.0% - 94.5%. CONCLUSION: HEV infection was seen in swine, cattle, horse, sheep, duck and chicken in the suburbs of Beijing. The anti-HEV positive rate appeared the highest in swine and the lowest in dog and donkey. The six strains of HEV isolated from younger swine belonged to genotype 4d.

Zoonotic risk of hepatitis E virus (HEV): A study of HEV infection in animals and humans in suburbs of Beijing.

AIM: To investigate hepatitis E virus (HEV) infection among different animals and workers in pig farms and slaughterhouses, and analyze the genotype of HEV isolated in this study. METHODS: Serum samples were collected from adult swine, cows, sheep, younger swine (< 3 months), and workers in pig farms and slaughterhouses (professional group). Fecal samples were collected from younger swine in the south suburbs of Beijing. Anti-HEV antibody was evaluated by direct sandwich enzyme immunoassay. HEV RNA was extracted from fecal samples and amplified by nested reverse transcription polymerase chain reaction (RT-nPCR). The PCR products were sequenced, and the sequence homology and phylogenetics of the HEV strains isolated from swine were analyzed. RESULTS: The anti-HEV positivity rates in adult swine, cows, sheep, younger swine, professional group and general population were 98.23% (222/226), 29.35% (54/184), 9.80% (20/207), 60.73% (99/164), 42.51% (105/247) and 20.29% (522/2572), respectively. The HEV RNA positivity rate of fecal samples was 22.89% (19/83) and 16/19 samples were positive for HEV RNA amplified with both primers, HEV open reading frame (ORF)1 and HEV ORF2. Sequence analysis of these 16 samples showed that there were two groups, designated BJ-1 and BJ-2. The nucleotide homology of BJ-1 and BJ-2 was 99%. Phylogenetic analysis indicated that both of these groups belonged to genotype 4d. CONCLUSION: Workers in pig farms and slaughterhouses were more likely to contract HEV infection than the general population because of close contact with swine with a high prevalence of anti-HEV.