Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

The optimal time for laparoscopic excision of ovarian endometrioma: a prospective randomized controlled trial.

OBJECTIVE: This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve. MATERIALS AND METHODS: This prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured. RESULTS: Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP, significantly higher than those in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an ovarian endometrioma cyst wall (r=-0.564, P<0.001). CONCLUSION(S): The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian endometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and safely.

Oxidative stress and antioxidant imbalance in ovulation disorder in patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that is characterized by oligo-ovulation or anovulation, hyperandrogenism, and polycystic ovaries observed using ultrasound with high clinical heterogeneity. At present, the etiology of PCOS is not clear but is thought to be related to genetic, metabolic, endocrine and environmental factors. Hyperandrogenism interacts with insulin resistance and overweight/obesity, forming a vicious cycle of mutual promotion and participating in the occurrence and progression of PCOS. Oxidative stress (OS) refers to the imbalance between the oxidation system and antioxidation system in the human body, which is associated with the occurrence and development of various diseases. Recent studies have shown that OS may be closely related to ovulation disorders in PCOS, and antioxidants can improve the oxidative stress state of PCOS. However, previous studies did not examine the effect of the interaction between OS and hyperandrogenism, insulin resistance or overweight/obesity on ovulation disorders in PCOS. This article reviews the interaction between OS and hyperandrogenism, insulin resistance and overweight/obesity; the effects of OS, hyperandrogenism, insulin resistance and overweight/obesity on ovulation disorders in PCOS; and the application of antioxidants in PCOS.

Identification of a novel autophagy signature for predicting survival in patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most commonhistological lung cancer subtype, with an overall five-year survivalrate of only 17%. In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature. METHODS: In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (n = 490) for a training and testing dataset, and GSE50081 (n = 127) as the external validation dataset.The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients. RESULTS: We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0.05 and |Fold change| > 1.5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low-risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels. CONCLUSION: Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.

Identification of alternative splicing and lncRNA genes in pathogenesis of small cell lung cancer based on their RNA sequencing.

BACKGROUND: The molecular mechanisms involved in small-cell lung cancer (SCLC) are largely unknown. Recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a critical role. OBJECTIVES: There is an urgent need for suitable molecular biomarkers for SCLC diagnosis and for assessing patient prognosis. MATERIAL AND METHODS: In this study, we used public databases to identify mRNA-like candidate lncRNAs. A multi-step computational approach was used to construct a functional SCLC lncRNAs-mediated competing with endogenous RNA (ceRNA) network (LMCN) by integrating genome-wide lncRNAs and mRNA expression profiles, miRNA-target interactions, functional analyses, and clinical survival analyses. RESULTS: The results revealed the significance of lncRNAs interactions with ceRNAs in SCLC, indicating that integration of expression profiles and alternative splicing could be used to identify biomarkers and the underlying pathological changes. The following genes: EPB41L4A-AS1, HOXA-AS2, XIST, DLEU2, FGD5-AS1, ALMS1-IT1, SNHG12, MIR17HG, MIR4720, and SCARNA10 in cluster, as well as shared alternative splicing events, were considered to be critical genes. CONCLUSIONS: Olfactory transduction and endocytosis were the top-enriched pathways in SCLC. The selected cluster, including critical genes, might also be a potential pathway of SCLC pathogenesis. As a result, this research provides the perspective information to explore the potential critical genes and its pathways in SCLC therapy.

Primary hepatoid adenocarcinoma of the lung in Yungui Plateau, China: A case report.

BACKGROUND: Hepatoid adenocarcinoma (HAC) occurs in extrahepatic organs such as the gastrointestinal tract, testes, ovaries, lungs, mediastinum and pancreas, and frequently produces α-fetoprotein (AFP). HAC of the lung (HAL) is rare, characterized by difficult treatment and poor prognosis. There are no reports of HAL in Yunnan-Guizhou Plateau, China. CASE SUMMARY: A 60-year-old male patient was clinically diagnosed with HAL pT3N0M0, stage IIB. Chest computed tomography revealed a 7.5 cm × 7.2 cm soft tissue mass located in the right lung upper lobe and the adjacent superior mediastinum. Right upper lobectomy was performed. The diagnosis of HAL was confirmed by pathological examination, and the patient received paclitaxel and carboplatin as adjuvant chemotherapy after surgery. CONCLUSION: Clinical manifestations, pathological features, imaging findings, auxiliary examination, and treatment planning of HAL are presented to help clinicians improve their diagnosis and treatment.

Adiponectin protects against uric acid­induced renal tubular epithelial inflammatory responses via the AdipoR1/AMPK signaling pathway.

Adiponectin (APN) exerts anti­inflammatory effects in various cells. Uric acid (UA) induces inflammation in proximal renal tubular epithelial cells (PTECs). It remains unknown whether APN protects against UA­induced inflammation. In the present study, human PTECs were incubated with 100 µg/ml soluble (S) UA in the presence or absence of globular (g) APN, APN receptor 1 (AdipoR1)­short hairpin RNA lentivirus or compound C. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) assays were performed to assess APN mRNA expression. Immunoblotting was used to assess the protein expression of APN, AdipoR1, NACHT, leucine rich repeat and pyrin domain­containing protein 3 (NLRP3) and the activation of tumor necrosis factor (TNF) α and adenosine monophosphate­activated protein kinase (AMPK). ELISA analyses were performed to assess supernatant levels of interleukin (IL)­1ß and TNFα. It was observed that SUA significantly enhanced APN mRNA and protein expression (both P<0.05) and increased NLRP3 (P<0.001) and TNFα (P<0.05) protein levels, as well as supernatant levels of IL­1ß (P<0.01) and TNFα (P<0.001) compared with untreated cells. gAPN administration significantly limited TNFα synthesis and secretion (both P<0.001), significantly decreased IL­1ß release (P<0.01), impacted NLRP3 protein expression and augmented AdipoR1 protein (P<0.01) and AMPK phosphorylation (P<0.05) levels compared with SUA­treated cells. AdipoR1 knockdown significantly promoted the synthesis (P<0.05) and release of TNFα (P<0.001), significantly increased IL­1ß supernatant levels (P<0.01) and exhibited little influence on NLRP3 production (P>0.05) compared with the SUA­treated cells. Secreted TNFα levels were significantly increased upon the inhibition of AMPK (P<0.05) and protein levels of IL­1ß, NLRP3 and TNFα in cell lysates were not significantly affected (P>0.05). In summary, the data demonstrated that SUA promoted APN expression in PTECs and that gAPN attenuated SUA­induced inflammation through the AdipoR1/AMPK signaling pathway. AdipoR1 knockdown and AMPK inactivation increased SUA­induced inflammatory damage in PTECs. These findings may help to further understand and regulate UA­associated inflammation in proximal renal tubules.

Dysregulated Long Non-coding RNAs in Parkinson's Disease Contribute to the Apoptosis of Human Neuroblastoma Cells.

The molecular mechanism underlying Parkinson's disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human diseases. We hypothesize that lncRNAs are involved in neuronal degeneration of PD. Using microarray, we identified 122 differentially expressed (DE) lncRNAs and 48 DE mRNAs between the circulating leukocytes from PD patients and healthy controls. There were 714 significant correlations (r ≥ 0.8 or ≤-0.8, p < 0.05) among the DE lncRNAs and mRNAs. Gene function and pathway analysis of the 48 DE mRNAs revealed biological pathways related to PD pathogenesis, including immune response, inflammatory response, MAPK, and Jak-STAT pathway. In a cohort of 72 PD patients and 22 healthy controls, the upregulation of four lncRNAs (AC131056.3-001, HOTAIRM1, lnc-MOK-6:1, and RF01976.1-201) in circulating leukocytes of PD patients were further confirmed. These lncRNAs were also upregulated in THP-1 cells, a human monocytic cell line, after inflammatory stimulation. Interestingly, the conditioned culture medium of THP-1 cells or 6-OHDA significantly increased the expression of these lncRNAs in SH-SY5Y cells, a human neuroblastoma cell line expressing dopaminergic markers. Importantly, overexpression of AC131056.3-001 or HOTAIRM1 increased baseline and 6-OHDA-induced apoptosis of SH-SY5Y cells. Taken together, we identified distinct expression profiles of lncRNA and mRNA in circulating leukocytes between PD patients and healthy controls. Dysregulated lncRNAs such as HOTAIRM1 and AC131056.3-001 may contribute to PD pathogenesis by promoting the apoptosis of dopaminergic neuron.

MicroRNA-494-3p Promotes Cell Growth, Migration, and Invasion of Nasopharyngeal Carcinoma by Targeting Sox7.

BACKGROUND: There is mounting evidence that microRNAs play an important role in nasopharyngeal carcinoma, which is widely prevalent in South China and is the most prevalent metastatic cancer among head and neck cancers. Recently, it has been shown that miR-494 is involved in the progression and prognosis of nasopharyngeal carcinoma. However, little is known about the function and mechanism of miR-494-3p in nasopharyngeal carcinoma. In the present study, we aimed to investigate the effects of miR-494-3p on the migration and invasion of nasopharyngeal carcinoma and to further explore the underlying mechanisms of these processes. METHODS: The expression levels of miR-494-3p and Sox7 in nasopharyngeal carcinoma specimens and nasopharyngeal carcinoma cell lines were measured using quantitative reverse transcription polymerase chain reaction. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, and Western blotting were used to confirm whether Sox7 was a direct target of miR-494-3p. Additionally, the roles of miR-494-3p and Sox7 on cell proliferation, migration, and invasion of nasopharyngeal carcinoma were analyzed by Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and Boyden chamber assay, respectively. RESULTS: Our study demonstrated that miR-494-3p was commonly upregulated in nasopharyngeal carcinoma specimens and nasopharyngeal carcinoma cell lines compared with nontumor nasopharyngeal epithelial tissue or nasopharyngeal cells (NP69). Moreover, miR-494-3p negatively regulated Sox7 at the posttranscriptional level by binding to a specific site in the Sox7 3'-untranslated region. In addition, synthetic miR-494-3p mimics significantly promoted proliferation, migration, and invasion of S18 and S26 nasopharyngeal carcinoma cells, while a synthetic miR-494-3p inhibitor resulted in suppressed nasopharyngeal carcinoma cell migration and invasion. CONCLUSION: miR-494-3p promotes nasopharyngeal carcinoma cell growth, migration, and invasion by directly targeting Sox7. Our results suggest that miR-494-3p might be a potential therapeutic target for nasopharyngeal carcinoma.

Impaired Na+-K+-ATPase signaling in renal proximal tubule contributes to hyperuricemia-induced renal tubular injury.

Hyperuricemia contributes to renal inflammation. We aimed to investigate the role of Na+-K+-ATPase (NKA) in hyperuricemia-induced renal tubular injury. Human primary proximal tubular epithelial cells (PTECs) were incubated with uric acid (UA) at increasing doses or for increasing lengths of time. PTECs were then stimulated by pre-incubation with an NKA α1 expression vector or small interfering RNA before UA (100 µg ml-1, 48 h) stimulation. Hyperuricemic rats were induced by gastric oxonic acid and treated with febuxostat (Feb). ATP levels, the activity of NKA and expression of its α1 subunit, Src, NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and interleukin 1ß (IL-1ß) were measured both in vitro and in vivo. Beginning at concentrations of 100 µg ml-1, UA started to dose-dependently reduce NKA activity. UA at a concentration of 100 µg ml-1 time-dependently affected the NKA activity, with the maximal increased NKA activity at 24 h, but the activity started to decrease after 48 h. This inhibitory effect of UA on NKA activity at 48 h was in addition to a decrease in NKA α1 expression in the cell membrane, but an increase in lysosomes. This process also involved the subsequent activation of Src kinase and NLRP3, promoting IL-1ß processing. In hyperuricemic rats, renal cortex NKA activity and its α1 expression were upregulated at the 7th week and both decreased at the 10th week, accompanied with increased renal cortex expression of Src, NLRP3 and IL-1ß. The UA levels were reduced and renal tubular injuries in hyperuricemic rats were alleviated in the Feb group. Our data suggested that the impairment of NKA and its consequent regulation of Src, NLRP3 and IL-1ß in the renal proximal tubule contributed to hyperuricemia-induced renal tubular injury.

Uric acid upregulates the adiponectin­adiponectin receptor 1 pathway in renal proximal tubule epithelial cells.

Adiponectin (APN) is a protein hormone that is primarily derived from adipocytes. It can also be secreted by renal cells. Hypoadiponectinemia has been documented in patients with hyperuricemia, however, whether soluble uric acid (SUA) regulates the expression of APN and APN receptor 1 (AdipoR1) in renal proximal tubule epithelial cells (PTECs) remains to be elucidated. The present study investigated the expression of APN and AdipoR1 in cultured PTECs that were exposed to SUA through immunofluorescence and western blot analysis. In addition, Sprague­Dawley rats with oxonic acid­induced hyperuricemia (HUA) with or without febuxostat treatment were employed as an animal model to measure 24 h urine protein, serum creatinine, urea nitrogen, uric acid and homeostasis model assessment of insulin resistance. Renal pathology was evaluated using hematoxylin and eosin and immunohistochemical staining. APN and AdipoR1 expression in the renal cortex were evaluated by western blotting. The results demonstrated that, in PTECs, the expression of APN and AdipoR1 was constant and increased upon SUA exposure. Similar observations were made within the proximal renal tubules of rats, and the oxonic acid­induced increases in APN and AdipoR1 were offset by febuxostat treatment. Furthermore, SUA­treated PTECs exhibited an increase in the expression of NLR family pyrin domain­containing (NLRP) 3, which was dose­dependent. NLRP3 expression was also significantly increased in the renal cortex of HUA rats compared with control and febuxostat­treated rats. In conclusion, SUA enhanced the expression of APN and AdipoR1 in PTECs, which was associated with an increase in NLRP3 expression. The APN­AdipoR1 pathway was demonstrated to have an important role in in vitro and in vivo models of renal proximal tubule inflammatory injury. Therefore, this pathway may be a potential therapy target in urate nephropathy.

Quantitative assessment of iron deposition in Parkinson's disease using enhanced T2 star-weighted angiography.

BACKGROUND: It has been reported that R2* is a sensitive marker for iron deposition. The aim of this study was to quantitatively assess iron deposition in Parkinson's disease (PD) using changes of R2* in enhanced T2 star-weighted angiography (ESWAN) and to discuss the value of ESWAN for PD. METHODS: Fifty-four primary PD patients and twenty-eight healthy individuals were examined by ESWAN in the 3·0 T magnetic resonance imaging system. The R2* values were measured from the deep gray nuclei (including the substantia nigra [SN], red nuclei, globus pallidus, putamina, caudate nuclei, and thalami). The unified PD rating scale (UPDRS) III assessment, the nonmotor symptoms scale (NMSS), and the mini mental state examination (MMSE) were used to rate all the patients. RESULTS: The comparison of the R* values between the deep gray nuclei on the same side of the PD patients and the control group revealed significant differences in the SN and red nuclei (P < 0.05). There was a significant difference between Hoehn and Yahr (HY) 1 and HY2-4 patients in terms of the values of the SN. There was a slight correlation between the R* values of the SN of the PD patients (HY >1) and the UPDRS III ratings. No correlation between the R* signal values in the PD patients and the NMSS and MMSE scales was found. CONCLUSION: Iron concentrations in the regions of interest may represent the severity of the PD motor symptoms, and whether they are related to the nonmotor symptoms remains a question for further investigation. ESWAN offers special advantages in determining iron depositions in the brain and in enabling a sensitive diagnosis of PD, although further study is necessary.

Clinical significance of microRNA-155 expression in hepatocellular carcinoma.

The present study aimed to evaluate the expression of microRNA-155 (miR-155) in hepatocellular carcinoma (HCC) and adjacent normal tissues, and assess its correlation with clinicopathological characteristics of this tumor type. miR-155 expression was detected in 40 HCC tissue samples and 40 samples of adjacent tumor-free tissue using fluorescent reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The association between miR-155 expression, clinicopathological features and 1-year relapse-free survival (RFS) in HCC and adjacent normal tissue samples was analyzed. RT-qPCR results revealed that, in 25 cases (62.5%), miR-155 expression levels were significantly increased in HCC tissues compared with the expression levels observed in pericarcinomatous tissues (P<0.05). miR-155 expression was observed to be significantly correlated with vessel invasion, Edmonson classification and clinical stage (P<0.05). However, miR-155 expression was not significantly correlated with gender, age, tumor size, tumor number, hepatitis B virus DNA copy number, cirrhosis or concentration of α-fetoprotein (P>0.05). A positive correlation was observed between late TNM classification of malignant tumor stage and 1-year RFS (P<0.05). Patients exhibiting high miR-155 expression levels were observed to exhibit a lower 1-year RFS than that of patients with reduced expression of miR-155 (48 vs. 73.3%), however this difference was not statistically significant (P=0.105). Additionally, correlations were observed between miR-155 expression and reduced differentiation, increased invasiveness and late stages of HCC. The current results demonstrated that miR-155 may be involved in the tumorigenesis of HCC and may be associated with clinical characteristics of HCC patients. Additional studies are required to clarify the mechanism of miR-155.

microRNA-342-5p and miR-608 inhibit colon cancer tumorigenesis by targeting NAA10.

miRNAs have been shown to play pivotal roles in the establishment and progression of colon cancer, but their underlying mechanisms are not fully understood. N-acetyltransferase NAA10 participates in many cellular processes, including tumorigenesis. Here we showed that miR-342-5p and miR-608 suppressed the tumorigenesis of colon cancer cells in vitro and in vivo by targeting NAA10 mRNA for degradation. Overexpression of miR-342-5p or miR-608 decreased NAA10 mRNA and protein levels and thereby suppressed cell proliferation, migration, and cell-cycle progression, as well as promoted apoptosis in SW480 and SW620 cells. More importantly, miR-342-5p and miR-608 significantly decreased the tumorigenic capacity of SW480 and SW620 cells in a mouse xenograft model. We also observed an inverse correlation between the expression of NAA10 and that of both miRNAs. Our results implicate miR-342-5p and miR-608 in colon cancer development and unveil the underlying mechanism of this phenomenon, which involves NAA10.