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Objective To observe the effects of oxaliplatin on the concentration of neurotransmitters in dorsal root ganglia in a rat model of chronic peripheral neurotoxicity. Methods A total of 24 male SD rats (SPF grade) were randomly divided into model group and normal control group (n=12 in each group). The model of chronic peripheral neurotoxicity was established by multiple cumulative doses and multiple intraperitoneal injections (cumulative dose of 48 mg/m2, simulated human dose > 1 200 mg/m2). The neurotransmitters with significant concentration changes in the dorsal root were screened out by a quantitative detection. Results At a cumulative dose of 48 mg/m2 oxaliplatin, a rat model of chronic peripheral neurotoxicity was established successfully. In the dorsal root, the neurotransmitters with obviously increase in concentration were L-glutamine (58.54±10.46 nmol/L, P < 0.05), L-glutamic acid (43.12±7.76 nmol/L, P < 0.05), dopamine (0.03±0.02 nmol/L, P < 0.01), norepinephrine (0.25±0.04 nmol/L, P < 0.05), 3、4-dihydroxyphenylacetic acid (0.41±0.01 nmol/L, P < 0.01), and vanillylmandelic acid (3.30±0.63 nmol/L, P < 0.05) when compared with the normal control group. Among them, dopamine and its metabolite 3、4-dihydroxyphenylacetic acid were the most significant. Conclusion Chronic accumulation of oxaliplatin can cause changes in the concentration of neurotransmitters in the dorsal root ganglia, which may be related to neuronal damage and chronic peripheral neurotoxicity.

Abstract Background Epstein-Barr virus (EBV) presumably plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC), but the molecular mechanism of EBV-dependent neoplastic transformation is not well understood. The combination of bioinformatics with evidences from biological experiments paved a new way to gain more insights into the molecular mechanism of cancer. Results We profiled gene expression using a meta-analysis approach. Two sets of meta-genes were obtained. Meta-A genes were identified by finding those commonly activated/deactivated upon EBV infection/reactivation. These genes could be key players for pathways de-regulated by EBV during latent infection and lytic proliferation. Meta-B genes were obtained from differential genes commonly expressed in NPC and PEL (primary effusion lymphoma). We then integrated meta-A, meta-B and associated factors into an interaction network using acquired information. Our analysis suggests that NPC transformation depends on timely regulation of DEK, CDK inhibitor(s), p53, RB and several transcriptional cascades, interconnected by E2F, AP-1, NF-κB, STAT3 among others during latent and lytic cycles. Conclusion In conclusion, our meta-analysis strategy re-analyzed EBV-related tumor data sets and identified sets of meta-genes possibly involved in maintaining latent or switching to lytic cycles of EBV in NPC. The results of this analysis may shed new lights to further our understanding of the EBV-led neoplastic transformation.

MicroRNAs (miRNAs) can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05), which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy. [ABSTRACT FROM AUTHOR]

Introduction: Resistant ovary syndrome (ROS) represents a rare reproductive endocrine disorder that is predominantly associated with infertility, characterized by heightened endogenous gonadotropin levels in the presence of a normal ovarian reserve. Patients with ROS typically exhibit a poor response to exogenous gonadotropins during controlled ovarian stimulation (COS). Due to the absence of a universally accepted effective COS protocol, this study aims to contribute to the existing body of literature by detailing 2 successful pregnancies achieved through conventional in vitro fertilization (c-IVF) in patients with ROS, and through retrospective analysis, seeks to elucidate the factors contributing to the successful ovarian stimulation in these cases, with the ultimate goal of establishing clinical guidelines for ROS management., Patient Concerns: The central challenge addressed in this study pertains to the effective induction of oocyte maturation during c-IVF COS in ROS patients., Diagnosis: The study focuses on 2 infertile women diagnosed with ROS who sought to conceive via c-IVF., Interventions: The patients were subjected to a COS protocol involving pituitary downregulation followed by ovarian stimulation using recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin (HMG), preceded by 3 cycles of hormone replacement therapy (HRT) pretreatment., Outcomes: The proposed protocol elicited a favorable ovarian response, culminating in the retrieval of numerous mature oocytes and the development of multiple viable embryos via c-IVF, ultimately leading to successful live births post-embryo transfer., Conclusions: Our study suggests that the outlined COS protocol may serve as a viable treatment option for ROS patients aspiring to conceive through c-IVF, thereby potentially expanding the therapeutic repertoire for this challenging condition., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the expression of HERC4 in human breast cancer tissues and its relationship with the clinicopathological features., Methods: RT-qPCR was used to detect mRNA expression of HERC4, and Western blotting and immunohistochemistry were employed to detect protein expression of HERC4 in 67 breast cancer tissues and adjacent breast tissues., Results: The results of RT-qPCR showed a significantly higher mRNA expression of HERC4 in breast cancer tissues than in the adjacent breast tissues (P<0.05). Western blotting demonstrated HERC4 over-expression in breast cancer tissues compared with the adjacent breast tissues (P<0.05). Immunohistochemistry revealed HERC4 expression located predominantly in the cell cytoplasm. Positive HERC4 expression was detected in 61.2% of the breast cancer tissues as compared to 19.4% in the adjacent breast tissues, and its expression level was closely correlated with TNM stage and the histological grade (P<0.05)., Conclusion: HERC4 is correlated with the tumorigenesis and progression of breast cancer and may serve as a potential biomarker for early diagnosis and also as a potential therapeutic target in breast cancer.

The aim of this study was to detect the expression of the pp GalNac-T10 protein in gastric carcinoma and to investigate the role of pp GalNac-T10 in the occurrence and development of gastric cancer tissues. pp GalNac-T10 protein expression was immunohistochemically analyzed in 96 gastric adenocarcinoma tissue samples, and in 88 5-cm adjacent non-tumor gastric mucosa samples, used as controls. pp GalNAc-T10 expression in gastric cancer tissues was higher compared with that in the adjacent non-tumor gastric tissue. pp GalNAc-T10 protein expression had a significant positive correlation with histological type and degree of differentiation of gastric cancer (P<0.05). Expression in diffuse type gastric cancer was notably higher compared with that in intestinal type gastric cancer. Expression in poorly differentiated tumors was markedly higher compared with that in high and mid degree differentiated tumors. pp GalNAc-T10 protein expression was not significantly positively correlated with clinical stage, depth of invasion or lymph node metastasis (P>0.05). pp GalNAc-T10 expression is a useful indicator of tumor differentiation in gastric cancer.

Background and Objective: Lung adenocarcinoma (AC) is the most common type of lung cancer, however, its mechanism of oncongenesis is still unknown. The aim of this study is to screen candidate genes of lung adenocarcinoma using bioinformatics strategy and elucidate the mechanism of lung adenocarcinoma., Methods: Two published microarray data (GSE7670 and GSE10072) was obtained from Gene Expression Omnibus (GEO). Significance analysis of microarrays was performed with the software dchip, and differential expression genes from dchip analysis were defined as "test gene set". Genes correlated with lung adenocarcinoma, obtained by data mining tools genecard and Fable were regarded as "train gene set". Finally, candidate genes of lung adenocarcinoma were screened by the tool "Toppgene"., Results: Three hundred and forty-four differential genes were defined as "test gene set", and 277 genes correlated with lung adenocarcinoma were regarded as "train gene set". Thirty-six candidate genes were screened out by Toppgene, among them, 21 genes had nearly no report in cancer. In the following QRT-PCR experiment, CD36, PMAIP1 and FABP4 were down-regulated expression in A549, which coincided with the gene chip., Conclusion: It is demonstrated that Toppgene is useful in identification of the candidate genes of lung adenocacinoma, which provides the proof for the discovery of the specific disease genes.

Human Embryonic Stem Cells (hESCs) have a great therapeutic potential in regenerative medicine, but the precise molecular mechanisms by which hESCs maintain or regulate their characteristics remain largely unknown. Since protein-protein interaction is vitally important in regulating hESCs, we utilized a network-based bioinformatics analysis in order to learn what and how specific proteins interact with each other. By combining protein-protein interaction data and a collection of genes over-expressed in hESCs, we constructed a protein interaction network using a breadth-first search algorithm. This scale-free network which is significantly larger than networks generated by random samplings, illustrates how these hESC-enriched proteins might interact with each other in hESCs. Of the top 5% highly connected nodes (corresponding to 21 proteins including MYC, H2AFX, RUVBL1, DDX18, CDC2, HDAC2 and HIST1H4C) presumably critical for determining the fate of hESCs, nearly half are known to be regulated by NANOG/SOX2/MYC. This underscores importance of these transcription factors in hESCs. In addition, in silico cis-element analysis suggests that NF-Y may be an important transcription factor regulating many of these hub proteins (high connected nodes) in hESCs. To further abstract the functional significance, directly connected proteins were matched to and grouped by gene ontology (GO) terms in molecular function category. Sixty- six interacting GO-GO terms paired through protein interactions were found over-represented in hESCs. This functional enrichment may be essential for understanding molecular characteristics in hESCs. Collectively, we analyzed hESC-enriched genes based on protein-protein interaction data, from which an hESC-enriched protein interaction network was constructed and a network of molecular functional terms was also identified. The results of this analysis, on the systems level, may shed new light to further our understanding of hESCs.