Identification of therapeutic targets and prognostic biomarkers of the ephrin receptor subfamily in pancreatic adenocarcinoma.

OBJECTIVES: We aimed to examine the significance of ephrin receptor A2 (EphA2) expression in pancreatic adenocarcinoma (PAAD) and its associated mechanism. METHODS: EphA2 mRNA expression patterns were compared in pancreatic cancer and normal tissues using GEPIA. Kaplan-Meier analysis was used to examine the correlation between EphA2 expression and PAAD patient prognosis. EphA2 gene methylation and associations with tumor immune cell infiltration were analyzed with UALCAN and TIMER, respectively. EphA2-interacting proteins were investigated with GeneMANIA, while STRING helped predict potentially relevant signaling pathways. EphA2 protein expression was examined with immunohistochemistry (IHC) in PAAD patient tissues. RESULTS: EphA2 was highly expressed in pancreatic cancer tissues and associated with pathological stage. PAAD patients with high EphA2 expression had shorter overall survival and disease-free survival times. EphA2 expression levels were significantly and positively associated with CD4+ T cell infiltration. EphA2 can interact with ENFNA1, ACP1, and CDC42. High EphA2 mRNA expression was enriched for regulation of cell size and cell proliferation. IHC assays suggested that pancreatic cancer tissues had higher EphA2 protein levels than normal pancreatic tissues. CONCLUSIONS: EphA2 is highly expressed in PAAD and closely related to poor patient prognosis, and is therefore a potential biomarker and target for PAAD diagnosis and treatment.

Oral Lycopene Administration Attenuates Inflammation and Oxidative Stress by Regulating Plasma Lipids in Rats with Lipopolysaccharide-Induced Epididymitis.

Purpose: Epididymitis histological alterations and related long-term reproductive issues cannot be cured by antibiotics alone. Few studies have been done on the effect of lycopene on epididymitis, despite the fact that it is an efficient antioxidant. The objective of this study was to assess the impact of lycopene on Lipopolysaccharide (LPS)-induced epididymis and lipid metabolism. Methods: Thirty-one 260-290g rats were separated into the blank control group (n=10), the oil-control group (n=10), the single intraperitoneal injection of 5 mg/kg LPS (n=5), and the continuous intragastric of 5 mg/kg lycopene (n=6). The animals were euthanized after four weeks, and blood and the epididymis were removed for analysis. Results: Lycopene significantly decreased IL-1α, IL-1ß, TNF-α, MCP-1, IL-6 and lipid peroxidation product Malondialdehyde in serum and epididymis. It significantly increased the epididymis's antioxidant enzyme and total antioxidant capacity. According to LC-MS plasma lipidomics, lycopene increased phosphatidylcholine, lysophosphatidylcholine, decreased phosphatidylethanolamine, triacylglycerol, and diacylglycerol levels, changed the composition of lipids, altered metabolic pathways, and these changes were related to the mechanism of anti-inflammatory and oxidative stress. 20 lipids, including PC (20:5e) and LPC (14:0), were identified through additional Spearman correlation analysis as being related to cytokines and oxidation indices. They served as possible lipid markers that may be utilized to gauge the severity of inflammation. Conclusion: Lycopene has anti-inflammatory and antioxidant properties that improve histopathological and functional damage in LPS-induced epididymitis and is an alternate supplement for treating epididymitis. Lipidomics provide new perspectives on the possible mechanism of lycopene in protecting against LPS-induced epididymitis by integrating lipid metabolism and inflammation.

Identification of Therapeutic Targets and Prognostic Biomarkers among Genes from the Mediator Complex Family in the Hepatocellular Carcinoma Tumour-Immune Microenvironment.

BACKGROUND: Hepatocellular carcinoma (HCC) is predominant among all types of primary liver cancers characterised by high morbidity and mortality. Genes in the mediator complex (MED) family are engaged in the tumour-immune microenvironment and function as regulatory hubs mediating carcinogenesis and progression across diverse cancer types. Whereas research studies have been conducted to examine the mechanisms in several cancers, studies that systematically focused on the therapeutic and prognostic values of MED in patients with HCC are limited. METHODS: The online databases ONCOMINE, GEPIA, UALCAN, GeneMANIA, cBioPortal, OmicStudio, STING, Metascape, and TIMER were used in this study. RESULTS: The transcriptional levels of all members of the MED family in HCC presented an aberrant high expression pattern. Significant correlations were found between the MED1, MED6, MED8, MED10, MED12, MED15, MED17, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, and MED27 expression levels and the pathological stage in the patients with HCC. The patients with high expression levels of MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 were significantly associated with poor prognosis. Functional enrichment analysis revealed that the members of the MED family were mainly enriched in the nucleobase-containing compound catabolic process, regulation of chromosome organisation, and transcriptional regulation by TP53. Significant correlations were found between the MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 expression levels and all types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). B cells and MED8 were independent predictors of overall survival. We found significant correlations between the somatic copy number alterations of the MED6, MED8, MED10, MED20, MED21, MED22, MED24, and MED25 molecules and the abundance of immune infiltrates. CONCLUSIONS: Our study delineated a thorough landscape to investigate the therapeutic and prognostic potentials of the MED family for HCC cases, which yielded promising results for the development of immunotherapeutic drugs and construction of a prognostic stratification model.

[Correlation of seminal plasma elastase with sperm reactive oxygen species and semen parameters in infertile men].

OBJECTIVE: To investigate the relationship of seminal plasma elastase (SPE) with sperm reactive oxygen species (ROS) and semen parameters in infertile men. METHODS: Between July 2021 and December 2021, a total of 145 subjects aged 20-51 years with male infertility were enrolled. SPE, seminal leukocytes, sperm ROS, DNA fragmentation index (DFI) and other semen parameters were detected. We divided patients into an inflammation group (SPE ≥ 290 ng/ml, n = 48) and a non-inflammation group (SPE < 290 ng/ml, n = 97), analyzed the relationship of SPE with seminal leukocytes, sperm ROS, semen volume, sperm concentration, total sperm motility, the percentages of progressively motile sperm (PMS) , morphologically normal sperm (MNS), and DFI. RESULTS: The concentration of seminal leukocytes, sperm ROS level and DFI were significantly higher in inflammation group than in non-inflammation group (P < 0.05). No statistically significant differences were observed in semen volume, sperm concentration, total sperm motility, PMS, MNS or sperm deformity index (SDI) between two groups of patients (P > 0.05). Spearman correlation analysis showed that the SPE level was correlated positively with the concentration of seminal leukocytes (r = 0.658, P < 0.01), sperm ROS level (r = 0.229, P = 0.006) and DFI (r = 0.192, P = 0.021), but not correlated with semen volume, sperm concentration, total sperm motility, PMS, MNS or SDI (P > 0.05). CONCLUSION: The level of seminal plasma elastase is related with the concentration of seminal leukocytes, sperm ROS level and DFI, and has some reference value in the diagnosis of male infertility.

miR-221-3p regulates hepatocellular carcinoma cell proliferation, migration and invasion via targeting LIFR.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the world. This study aims to investigate the mechanism by which miR-221-3p regulates HCC cell proliferation, migration and invasion, so as to provide a new idea for targeted therapy towards HCC. MATERIALS AND METHODS: Expression quantification data including mature miRNA and mRNA were accessed from TCGA-LIHC dataset, and matched clinical information was obtained as well, which helped identify the miRNA of interest. Thereafter, effect of the miRNA on HCC cell biological functions was assessed with a series of in vitro experiments, such as qRT-PCR, MTT, wound healing assay and Transwell. To gain more insight into the mechanism of the miRNA in HCC, bioinformatics method was conducted to predict downstream target gene. The potential targeting relationship between the miRNA and the predicted mRNA was validated by dual-luciferase reporter assay. Western blot was performed to test protein expression. RESULTS: MiR-221-3p identified by differential expression analysis was found to be significantly elevated in HCC tissue. Overexpressing miR-221-3p noticeably enhanced HCC cell proliferative, migratory and invasive abilities. Leukemia inhibitory factor receptor (LIFR), confirmed as a downstream target of miR-221-3p in HCC by dual-luciferase reporter assay, was poorly expressed in HCC tissue and cells. Additionally, the expression of LIFR was decreased following the targeted binding between miR-221-3p and LIFR 3'-UTR, while increasing the expression of LIFR attenuated the promoting effect of miR-221-3p on HCC cells. CONCLUSION: MiR-221-3p is an oncogene in HCC cells, and it exerts its role in HCC cell viability and motility via targeting LIFR.

[Lycopene for the treatment of chronic prostatitis / chronic pelvic pain syndrome: Effect and mechanism based on network pharmacology and molecular docking].

OBJECTIVE: To explore the action mechanisms of lycopene in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) based on network pharmacology and molecular docking. METHODS: We obtained the drug targets of lycopene from the databases TCMSP and PharmMapper, the therapeutic targets of CP/CPPS from OMIM, Disgenet and Genecards, and the common targets of lycopene and CP/CPPS with the Venny software. We constructed a protein-protein interaction (PPI) network of lycopene acting on CP/CPPS using the STRING database, screened the core targets with the Cytoscape software, followed by GO functional analysis and KEGG pathway analysis with the R software and molecular docking of lycopene and the core targets using AutoDock Tools, Vina and Pymol. RESULTS: A total of 187 drug targets, 1 557 disease targets and 46 common targets were screened out. PPI network analysis showed that ALB, IGF1, EGFR, SRC, CASP3 and ESR1 were the core targets of lycopene in the treatment of CP/CPPS. GO functional analysis showed the common targets to be involved in the reproductive structure development, extrinsic apoptotic signaling pathway, and response to reactive oxygen species. KEGG pathway analysis indicated the association of Ras, PI3K-Akt, Rap1, FoxO and MAPK signaling pathways with the mechanism of lycopene acting on CP/CPPS. Molecular docking exhibited a great affinity of lycopene to all the core targets. CONCLUSION: This study revealed the potential targets and signaling pathways of lycopene in the treatment of CP/CPPS and its action mechanisms from the perspective of network pharmacology and molecular docking, which has provided some reference for future studies.

MiR-20b-5p promotes hepatocellular carcinoma cell proliferation, migration and invasion by down-regulating CPEB3.

INTRODUCTION AND OBJECTIVES: This study aimed to explore the functional mechanism of the miRNA-20b-5p/cytoplasmic polyadenylation element binding protein 3 (miR-20b-5p/CPEB3) axis in hepatocellular carcinoma (HCC) so as to provide a new idea for targeted therapy of HCC. MATERIALS AND METHODS: Bioinformatics analysis was employed to obtain markedly differentially expressed miRNAs and mRNAs in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset, so as to find target miRNA and its target mRNA. Real-time quantitative PCR was conducted to detect miR-20b-5p and CPEB3 mRNA expression. Western blot was performed to determine CPEB3 protein expression. Dual-luciferase reporter assay was carried out to verify the targeting relationship between miR-20b-5p and CPEB3. Cell counting kit-8 assay, wound healing assay, Transwell invasion assay and flow cytometry were conducted to evaluate the proliferation, migration, invasion and apoptosis of HCC cells. RESULTS: Bioinformatics analysis suggested that miR-20b-5p and CPEB3 were markedly highly and lowly expressed, respectively, in HCC tissue in TCGA-LIHC dataset. Over-expressing miR-20b-5p facilitated the proliferation, migration and invasion, and suppressed the apoptosis of HCC cells. Dual-luciferase reporter assay validated that there was a targeting relationship between miR-20b-5p and CPEB3. The inhibitory effect of CPEB3 over-expression on HCC cell proliferation, migration and invasion was reversed by over-expressing miR-20b-5p. CONCLUSIONS: The present study proved that miR-20b-5p promotes HCC cell proliferation, migration and invasion by inhibiting CPEB3 expression, which may provide a theoretical basis for the prognosis and treatment of HCC patients.

Exosomes function as nanoparticles to transfer miR-199a-3p to reverse chemoresistance to cisplatin in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a frequently seen malignant tumor globally. The occurrence of cisplatin (DDP) resistance is one of the main reasons for the high mortality of HCC patients. Therefore, it is of great theoretical significance and application value to explore the mechanism of chemotherapy resistance. Drug resistance can be modulated by exosomes containing mRNAs, micro RNAs (miRNAs) and other non-coding RNA (ncRNAs). Exosomal miR-199a-3p (Exo-miR-199a-3p) was subjected to extraction and verification. Whether exo-miR-199a-3p could make HCC cells sensitive to DDP in vitro was verified via flow cytometry, Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay and Transwell assay. Intravenous injection of exo-miR-199a-3p and intraperitoneal injection of DDP were carried out in vivo. Moreover, the possible targets of miR-199a-3p were screened through bioinformatics analysis, which were ascertained by Western blotting (WB). Then, miR-199a-3p levels in human normal liver epithelial cell line HL-7702 and HCC cell lines HuH7 and HuH7/DDP were elevated in a concentration-dependent manner. Exo-miR-199a-3p has abilities to adjust underlying targets and conjugate cells, to repress cells to invade, stimulate their apoptosis and abate their ability. Additionally, the caudal injection of exo-miR-199a-3p reversed the chemoresistance of tumors and slowed down their growth in the body owing to the up-regulation of miR-199a-3p and down-regulation of underlying target proteins in tumors. Finally, exo-miR-199a-3p was found to overturn the HCC's resistance to DDP, and it may function in DDP-refractory HCC therapy as an underlying option in the future.

The energy based characteristics of sperm whale clicks using the Hilbert Huang transform analysis method.

In this paper, a unique analysis method for sperm whale clicks based on Hilbert-Huang transform (HHT) is proposed. Four sperm whale click samples with durations of 10 ms (defined as click I), and four sperm whale click samples with durations of 5 ms (defined as click II) were illustrated. These click samples were recorded in the Mediterranean Sea by Centro Interdisciplinare di Bioacusticae Ricerche Ambientali, Università degli Studi di Pavia. The empirical mode decomposition method was used to decompose click I samples into seven intrinsic mode functions (IMFs) and one residue function (RF), and click II samples were decomposed into six IMFs and one RF. The average energy distributions of multiple IMFs and the single RF domain for click I and click II samples were explored using the HHT analysis method. The average energy-frequency representations were also investigated for the same click I and click II samples. The analysis results show that the energy-frequency characteristics of sperm whale clicks can be extracted and understood by applying several IMFs and one RF signal with a high-resolution analysis.

Abdominal distension and diarrhea as the main symptoms of primary amyloidosis: A case report and literature review.

Amyloidosis is a systemic disease caused by the accumulation of extracellular protein into amyloid deposits. Due to the involvement of a variety of organs and tissues, the disease has no specific clinical features and a high rate of misdiagnosis. The present study describes one case of primary amyloidosis, as confirmed by biopsies of rectal and renal tissues using Congo red staining, demonstrating that abdominal distension and diarrhea were the main symptoms of disease. The current case is also discussed within the context of a review of the associated literature.

Diagnostic accuracy of serum squamous cell carcinoma antigen and squamous cell carcinoma antigen-immunoglobulin M for hepatocellular carcinoma: A meta-analysis.

A number of individual studies have evaluated the diagnostic efficiency of serum squamous cell carcinoma antigen (SCCA) and SCCA-immunoglobulin (IgM) for diagnosing hepatocellular carcinoma (HCC), but the results have been conflicting. The aim of this study was to determine the diagnostic accuracy of serum SCCA and SCCA-IgM for HCC. A systematic review of related studies was conducted and relevant data on the accuracy of serum SCCA and SCCA-IgM in the diagnosis of HCC were pooled using random-effects models. Summary receiver operating characteristic curve (SROC) analysis was used to summarize the overall test performance. A total of 12 studies were included in our meta-analysis. The summary estimates for serum SCCA and SCCA-IgM for HCC diagnosis in the included studies were as follows: Sensitivity = 0.59 (95% CI: 0.56-0.62) vs. 0.60 (95% CI: 0.56-0.63); specificity = 0.76 (95% CI: 0.73-0.79) vs. 0.70 (95% CI: 0.67-0.73); diagnostic odds ratio (DOR) = 6.68 (95% CI: 3.71-12.03) vs. 7.32 (95% CI: 3.31-16.15); and area under the SROC curve = 0.7826 vs. 0.7955. Therefore, SCCA and SCCA-IgM exhibited moderate diagnostic accuracy for HCC. Due to the design limitations, the results of published studies should be interpreted with caution. In addition, well-designed studies including larger sample sizes should be conducted to rigorously evaluate the diagnostic value of SCCA and SCCA-IgM.

Analysis of spike waves in epilepsy using Hilbert-Huang transform.

In this paper, we used the Hilbert-Huang transform (HHT) analysis method to examine the time-frequency characteristics of spike waves for detecting epilepsy symptoms. We obtained a sample of spike waves and nonspike waves for HHT decomposition by using numerous intrinsic mode functions (IMFs) of the Hilbert transform (HT) to determine the instantaneous, marginal, and Hilbert energy spectra. The Pearson correlation coefficients of the IMFs, and energy-IMF distributions for the electroencephalogram (EEG) signal without spike waves, Spike I, Spike II and Spike III sample waves were determined. The analysis results showed that the ratios of the referred wave and Spike III wave to the referred total energy for IMF1, IMF2, and the residual function exceeded 10%. Furthermore, the energy ratios for IMF1, IMF2, IMF3 and the residual function of Spike I, Spike II to their total energy exceeded 10%. The Pearson correlation coefficients of the IMF3 of the EEG signal without spike waves and Spike I wave, EEG signal without spike waves and Spike II wave, EEG signal without spike waves and Spike III wave, Spike I and II waves, Spike I and III waves, and Spike II and III waves were 0.002, 0.06, 0.01, 0.17, 0.03, and 0.3, respectively. The energy ratios of IMF3 in the δ band to its referred total energy for the EEG signal without spike waves, and of the Spike I, II, and III waves were 4.72, 6.75, 5.41, and 5.55%, respectively. The weighted average frequency of the IMF1, IMF2, and IMF3 of the EEG signal without spike waves was lower than that of the IMF1, IMF2, and IMF3 of the spike waves, respectively. The weighted average magnitude of the IMF3, IMF4, and IMF5 of the EEG signal without spike waves was lower than that of the IMF1, IMF2, and IMF3 of spike waves, respectively.

Chaos based encryption system for encrypting electroencephalogram signals.

In the paper, we use the Microsoft Visual Studio Development Kit and C# programming language to implement a chaos-based electroencephalogram (EEG) encryption system involving three encryption levels. A chaos logic map, initial value, and bifurcation parameter for the map were used to generate Level I chaos-based EEG encryption bit streams. Two encryption-level parameters were added to these elements to generate Level II chaos-based EEG encryption bit streams. An additional chaotic map and chaotic address index assignment process was used to implement the Level III chaos-based EEG encryption system. Eight 16-channel EEG Vue signals were tested using the encryption system. The encryption was the most rapid and robust in the Level III system. The test yielded superior encryption results, and when the correct deciphering parameter was applied, the EEG signals were completely recovered. However, an input parameter error (e.g., a 0.00001 % initial point error) causes chaotic encryption bit streams, preventing the recovery of 16-channel EEG Vue signals.

Hilbert-Huang transformation-based time-frequency analysis methods in biomedical signal applications.

Hilbert-Huang transformation, wavelet transformation, and Fourier transformation are the principal time-frequency analysis methods. These transformations can be used to discuss the frequency characteristics of linear and stationary signals, the time-frequency features of linear and non-stationary signals, the time-frequency features of non-linear and non-stationary signals, respectively. The Hilbert-Huang transformation is a combination of empirical mode decomposition and Hilbert spectral analysis. The empirical mode decomposition uses the characteristics of signals to adaptively decompose them to several intrinsic mode functions. Hilbert transforms are then used to transform the intrinsic mode functions into instantaneous frequencies, to obtain the signal's time-frequency-energy distributions and features. Hilbert-Huang transformation-based time-frequency analysis can be applied to natural physical signals such as earthquake waves, winds, ocean acoustic signals, mechanical diagnosis signals, and biomedical signals. In previous studies, we examined Hilbert-Huang transformation-based time-frequency analysis of the electroencephalogram FPI signals of clinical alcoholics, and 'sharp I' wave-based Hilbert-Huang transformation time-frequency features. In this paper, we discuss the application of Hilbert-Huang transformation-based time-frequency analysis to biomedical signals, such as electroencephalogram, electrocardiogram signals, electrogastrogram recordings, and speech signals.

Sexual behavior among employed male rural migrants in Shanghai, China.

A study of sexual behavior in migrant men was conducted in construction sites, markets, and factories in Shanghai, the largest city in China. An anonymous, self-administered questionnaire was completed by the migrants. Among 986 sexually active men, 14% had had more than one sexual partner in their lifetime, 31% premarital sex, 3.3% oral sex, and 11.5% commercial sex. Seventy-eight percent never used condoms. Risk-taking was similar in different working venues but increased with decreasing age. Younger men initiated sexual intercourse earlier and had more premarital sex and sexual partners as well as more frequent sexual encounters. Risk-factors that correlate with having multiple sex partners included having seen pornography, early age at initiating sexual intercourse, premarital sex, and a desire for legalization of commercial sex. Sexually transmitted diseases and HIV are likely to increase among migrants, particularly those who are young. Intervention strategies should target younger migrants, and must accommodate a low literacy level.

Enhanced efficiency and specificity of ovarian cancer gene therapy in rats with a novel nonviral gene delivery system (GE7) via intraovarian artery perfusion approach.

Transfer of the herpes simplex virus type I-thymidine kinase gene, followed by the administration of ganciclovir (HSV1-tk/GCV) into ovarian cancer-derived cell line either in vitro or transplanted into nude mice has been shown to provide a potential strategy for the gene therapy of ovarian cancer. We investigated the antitumor effects of HSV1-tk/GCV strategy with a chemically induced rat ovarian cancer model and a tumor-selective gene delivery by a novel nonviral gene delivery system (GE7) through the ovarian artery and tail vein. We demonstrated the expression of a reporter gene, beta-gal gene, as well as HSV1-tk gene in tumors and other organs, evaluated the overall antitumor effects after the GCV treatment and analyzed the tumor cell cycle phase distribution. Via the ovarian artery route, the expressions of beta-gal and HSV1-tk in tumors were significantly stronger than those expressed in such organs as the hearts, livers, spleens, lungs and kidneys. However, no beta-gal and HSV1-tk were detected in the tumor tissues when administrated via the tail vein, and little was found in other organs. The cell cycle analysis showed that the total S-phase of tumor cells in the test intra-arterial treatment group was considerably higher than that of the controls. The weight of the tumor tissues in the group treated by the intra-arterial route (4.06+/-2.12 g) was much less than the group treated intravenously (18.25+/-8.34 g) (P<.01). These findings indicated that the administration of GE7/HSV1-tk complex via the ovarian artery route could be a promising avenue of future human ovarian cancer treatment.

Characteristics and sexually transmitted diseases of male rural migrants in a metropolitan area of Eastern China.

GOAL: The goal of this study was to identify the correlates and determine the prevalence of sexually transmitted diseases (STDs) among male rural migrants in Shanghai, China. STUDY: The authors conducted a community-based cross-sectional study with an anonymous questionnaire interview and collection of blood and first-void urine samples for STD screening. RESULTS: One thousand eighty-six (85.3%) of 1273 male rural migrants approached were interviewed. Among the 986 sexually active migrants, the prevalence of chlamydia, gonorrhea, and syphilis was 3.5%, 0.5%, and 1.0%, respectively. None were infected with HIV. The prevalence of STDs was 3.2% for construction workers, 5.6% for market vendors, and 5.6% for factory workers. Risk factors for STDs were longer duration in Shanghai, frequent hometown visits, having multiple sex partners, and the desire to have multiple sex partners. CONCLUSIONS: The prevalence of STDs among male rural migrants is relatively low. Maintaining the current low prevalence can reduce the risk of an HIV epidemic among Shanghai migrants, but prevention messages need to be tailored to the low level of literacy in many migrants.