Pathology and physiology of acid-sensitive ion channels in the bladder.

Acid-sensitive ion channels (ASICs) are sodium-permeable channels activated by extracellular acidification. They can be activated and trigger the inward flow of Na+ when the extracellular environment is acidic, leading to membrane depolarization and thus inducing action potentials in neurons. There are four ASIC genes in mammals (ASIC1-4). ASIC is widely expressed in humans. It is closely associated with pain, neurological disorders, multiple sclerosis, epilepsy, migraines, and many other disorders. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a specific syndrome characterized by bladder pain. Recent studies have shown that ASICs are closely associated with the development of BPS/IC. A study revealed that ASIC levels are significantly elevated in a BPS/IC model. Additionally, researchers have reported differential changes in ASICs in the bladders of patients with neurogenic lower urinary tract dysfunction (NLUTD) caused by spinal cord injury (SCI). In this review, we summarize the structure and physiological functions of ASICs and focus on the mechanisms by which ASICs mediate bladder disease.

Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis.

Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-ß1+Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-ß1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/ß-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.

Iron decoration in binary graphene oxide and copper iron sulfide nanocomposites boosting catalytic antibacterial activity in acidic microenvironment against antimicrobial resistance.

The strong antimicrobial resistance (AMR) of multidrug-resistant (MDR) bacteria and biofilm, especially the biofilm with extracellular polymeric substance (EPS) protection and persister cells, not only renders antibiotics ineffective but also causes chronic infections and makes the infectious tissue difficult to repair. Considering the acidic properties of bacterial infection microenvironment and biofilm, herein, a binary graphene oxide and copper iron sulfide nanocomposite (GO/CuFeSx NC) is synthesized by a surfactant free strategy and utilized as an alternative smart nanozyme to fight against the MDR bacteria and biofilm. For the GO/CuFeSx NC, the iron decoration facilitates the well distribution of bimetallic CuFeSx NPs on the GO surfaces compared to monometallic CuS NPs, providing synergistically enhanced peroxidase (POD)-like activity in acidic medium (pH 4 âˆ¼ 5) and intrinsic strong near infrared (NIR) light responsive photothermal activity, while the ultrathin and sharp structure of 2D GO nanosheet allows the GO/CuFeSx NC to strongly interact with the bacteria and biofilm, facilitating the catalytic and photothermal attacks on the bacterial surfaces. In addition, the GO in GO/CuFeSx NC exhibits a "Pseudo-Photo-Fenton" effect to promote the ROS generation. Therefore, the GO/CuFeSx NC can effectively kill bacteria and biofilm both in vitro and in vivo, finally eliminating the infections and accelerating the tissue repair when treating the biofilm-infected wound. This work paves a new way to the design of novel nanozyme for smart antibacterial therapy against antimicrobial resistance.

Anti-apoptotic effect of adrenomedullin gene delivery on Leydig cells by suppressing TGF-ß1 via the Hippo signaling pathway.

This study aims to establish whether adrenomedullin (ADM) is capable to restore the steroidogenic functions of Leydig cells by suppressing transforming growth factor-ß1 (TGF-ß1) through Hippo signaling. Primary Leydig cells were treated with lipopolysaccharide (LPS), an adeno-associated virus vector that expressed ADM (Ad-ADM) or sh-RNA of TGF-ß1 (Ad-sh-TGF-ß1). The cell viability and medium concentrations of testosterone were detected. Gene expression and protein levels were determined for steroidogenic enzymes, TGF-ß1, RhoA, YAP, TAZ and TEAD1. The role of Ad-ADM in the regulation of TGF-ß1 promoter was confirmed by ChIP and Co-IP. Similar to Ad-sh-TGF-ß1, Ad-ADM mitigated the decline in the number of Leydig cells and plasma concentrations of testosterone by restoring the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD. Similar to Ad-sh-TGF-ß1, Ad-ADM not only inhibited the LPS-induced cytotoxicity and cell apoptosis but also restored the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD, along with the medium concentrations of testosterone in LPS-induced Leydig cells. Like Ad-sh-TGF-ß1, Ad-ADM improved LPS-induced TGF-ß1 expression. In addition, Ad-ADM suppressed RhoA activation, enhanced the phosphorylation of YAP and TAZ, reduced the expression of TEAD1 which interacted with HDAC5 and then bound to TGF-ß1 gene promoter in LPS-exposed Leydig cells. It is thus suspected that ADM can exert anti-apoptotic effect to restore the steroidogenic functions of Leydig cells by suppressing TGF-ß1 through Hippo signaling.

Current applications of nanomaterials in urinary system tumors.

The development of nanotechnology and nanomaterials has provided insights into the treatment of urinary system tumors. Nanoparticles can be used as sensitizers or carriers to transport drugs. Some nanoparticles have intrinsic therapeutic effects on tumor cells. Poor patient prognosis and highly drug-resistant malignant urinary tumors are worrisome to clinicians. The application of nanomaterials and the associated technology against urinary system tumors offers the possibility of improving treatment. At present, many achievements have been made in the application of nanomaterials against urinary system tumors. This review summarizes the latest research on nanomaterials in the diagnosis and treatment of urinary system tumors and provides novel ideas for future research on nanotechnologies in this field.

Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo.

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)-induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS-treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad-ADM, an adeno-associated virus vector that expressed ADM. Then, rat testes were collected for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor-1 (SF-1), liver receptor homologue-1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3ß-HSD, cytochrome P450 17α-hydroxylase/17, 20 lyase (CYP17) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF-1, LRH1, Nur77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.

Mussel-Inspired Clickable Antibacterial Peptide Coating on Ureteral Stents for Encrustation Prevention.

Long-term indwelling catheters or stents often cause complications like infection, encrustation, hematuria, pain, and so on. The source of these problems is bacteria, which can form biofilms on the stents to reduce antibiotic sensitivity and produce urease to form encrustation by increasing the urine pH. Urinary tract infection (UTI) can aggravate the body damage and even seriously endanger lives, and the encrustation will block the stents, which can cause hydronephrosis and renal function damage. Therefore, the prevention of UTI and encrustation represents a great challenge in clinical ureteral stent uses. In this work, a clickable mussel-inspired peptide and antimicrobial peptide (AMP) were used to functionalize the commercial stents' surfaces to inhibit long-term infection and encrustation caused by bacteria. Copper (Cu) ions were used to coordinate the mussel-inspired peptide to improve the stability. The AMP with an azido group was clicked to the mussel-inspired Cu-coordinated peptide coating through click chemistry. The bio-inspired antibacterial coating was constructed with excellent stability, bactericidal properties, and improved biological compatibility. In in vitro and in vivo experiments, it was further found that the coating showed bactericidal and encrustation reduction abilities. This study thus developed an effective, safe, and stable AMP coating on urinary stents/catheters capable of long-term antibacterial and encrustation inhibition.

Bio-inspired antibacterial coatings on urinary stents for encrustation prevention.

Urinary tract infection (UTI) represents one of the most common nosocomial infections, which is mainly related to indwelling catheters or stents. In addition to the formation of biofilms to reduce antibiotic sensitivity, the urease-producing bacteria can also increase urine pH, causing Ca2+ and Mg2+ deposition and finally catheter obstruction. The prevention of UTIs and its complication (i.e., encrustation) thus is a great challenge in design of catheters and ureteral stents. In this work, a metal-catechol-assisted mussel chemistry (i.e., dopamine self-polymerization) was employed for surface functionalization of commercially available catheters with antimicrobial peptides (AMP), for the purpose of long-term anti-infection and encrustation prevention. To improve the stability of the polydopamine coating on polymeric stents, we used Cu2+-coordinated dopamine self-polymerization. Then, a cysteine-terminated AMP was introduced on the polydopamine coating through Michael addition. We found that the Cu2+-coordinated polydopamine coating showed improved stability and antibacterial effect. The cytotoxicity test confirmed that the bioinspired antibacterial coating showed good biocompatibility and no obvious toxicity. The results confirmed that the stents with AMP could in situ inhibit bacterial growth and biofilm formation, and finally reduce the deposition of struvite and hydroxyapatite crystals both in vitro and in vivo. We anticipate that this bioinspired strategy would develop a safe, stable and effective antibacterial coating on urinary tract medical devices for long-term bacterial inhibition and encrustation prevention.

A novel prognostic cancer-related lncRNA signature in papillary renal cell carcinoma.

BACKGROUND: Papillary renal cell carcinoma (pRCC) ranks second in renal cell carcinoma and the prognosis of pRCC remains poor. Here, we aimed to screen and identify a novel prognostic cancer-related lncRNA signature in pRCC. METHODS: The RNA-seq profile and clinical feature of pRCC cases were downloaded from TCGA database. Significant cancer-related lncRNAs were obtained from the Immlnc database. Differentially expressed cancer-related lncRNAs (DECRLs) in pRCC were screened for further analysis. Cox regression report was implemented to identify prognostic cancer-related lncRNAs and establish a prognostic risk model, and ROC curve analysis was used to evaluate its precision. The correlation between RP11-63A11.1 and clinical characteristics was further analyzed. Finally, the expression level and role of RP11-63A11.1 were studied in vitro. RESULTS: A total of 367 DECRLs were finally screened and 26 prognostic cancer-related lncRNAs were identified. Among them, ten lncRNAs (RP11-573D15.8, LINC01317, RNF144A-AS1, TFAP2A-AS1, LINC00702, GAS6-AS1, RP11-400K9.4, LUCAT1, RP11-63A11.1, and RP11-156L14.1) were independently associated with prognosis of pRCC. These ten lncRNAs were incorporated into a prognostic risk model. In accordance with the median value of the riskscore, pRCC cases were separated into high and low risk groups. Survival analysis indicated that there was a significant difference on overall survival (OS) rate between the two groups. The area under curve (AUC) in different years indicated that the model was of high efficiency in prognosis prediction. RP11-63A11.1 was mainly expressed in renal tissues and it correlated with the tumor stage, T, M, N classifications, OS, PFS, and DSS of pRCC patients. Consistent with the expression in pRCC tissue samples, RP11-63A11.1 was also down-regulated in pRCC cells. More importantly, up-regulation of RP11-63A11.1 attenuated cell survival and induced apoptosis. CONCLUSIONS: Ten cancer-related lncRNAs were incorporated into a powerful model for prognosis evaluation. RP11-63A11.1 functioned as a cancer suppressor in pRCC and it might be a potential therapeutic target for treating pRCC.

Long non-coding RNA HCP5 in cancer.

Cancer remains a major threat to human health worldwide. Long non-coding RNA (lncRNA) comprises a group of single-stranded RNA with lengths longer than 200 bp. LncRNAs are aberrantly expressed and play a variety of roles involving multiple cellular processes in cancer. Histocompatibility leukocyte antigen complex P5 (HCP5), initially reported in 1993, is an important lncRNA located between the MICA and MICB genes in MHC I region. HCP5 is involved many autoimmune diseases as well as malignancies. Abnormal HCP5 expression occurs in many types of cancer and its dysregulation appears closely associated with tumor progression. HCP5 is also involved in anti-tumor drug resistance as well. As such, HCP5 represents a promising biomarker and therapeutic target in cancer. In this review, we summarize recent researches and provide an overview of the role and mechanism of HCP5 in human cancer.

Identification of novel prognostic biomarkers in renal cell carcinoma.

OBJECTIVE: To identify novel prognostic biomarkers in renal cell carcinoma (RCC). RESULTS: 12 coding genes and one miRNA were finally identified as prognostic biomarkers. All of them were related to a poor prognosis. Lower expression levels of the coding genes were observed in higher clinical stages. Prognostic signatures including 7 biomarkers were identified. Patients in the high-risk group had worse survival than those in the low-risk group. The areas under the curves in different years indicated that it was a valuable signature in prognosis. It was found that elevated WDR72 inhibited the survival and invasion of 786-O and 769P cells in vitro. CONCLUSIONS: Thirteen prognostic biomarkers of RCC were identified. Among them, 7 biomarkers comprised a signature to evaluate the RCC prognosis. WDR72 was a cancer suppressor and a potential therapeutic target in RCC. METHODS: Differentially expressed genes/miRNAs (DEGs/DEMs) and prognosis-related genes/miRNAs were acquired from public database. Prognostic biomarkers were identified by overlapping the significant DEGs/DEMs and prognosis-related genes/miRNAs. The associations between these biomarkers and the clinical stages were analyzed. All of these prognostic biomarkers were further investigated with multi-variable Cox regression. Finally, the inhibitory effect of WDR72 on the growth and invasion of RCC cells was studied.

GAS5­mediated regulation of cell signaling (Review).

In recent years, an increasing number of long non­coding RNAs (lncRNAs) have been discovered using microarrays and nucleic acid sequencing technology. LncRNAs exert crucial biological functions by regulating signaling pathways. In particular, the lncRNA growth arrest­specific transcript 5 (GAS5) has been documented to serve a crucial role in numerous signaling pathways. This article discusses the latest developments in the association between GAS5 and microRNA (miRNA), p53, mTOR, glucocorticoid response element (GRE) and AKT in order to investigate the roles served by GAS5. miRNAs can activate related signaling pathways and GAS5 can combine with miRNA to regulate related signaling pathways. GAS5 may regulate p53 expression via derivation of snoRNA, but the underlying mechanism requires further investigation. GAS5 overxpresion reduces the expression level of mTOR, which is induced by inhibiting miR­106a­5p expression. GAS5 is a sponge of GR, and serves a role in controlling and maintaining glucocorticoid sensitivity and drug resistance via competitive combination with GR. GAS5 can interact with miRNAs, such as miR­21 and miR­532­5p, to regulate the expression of AKT signaling pathway, affecting cell survival and apoptosis. Collectively, the data indicate that GAS5 serves a key role in the miRNA, p53, mTOR, GRE, and AKT signaling pathways. GAS5 regulates complex intracellular signaling pathways primarily through three modes of action, all of which are interrelated: Signal, decoy and guide. In the present article, latest developments in the association between GAS5 and a number of cellular signaling pathways are discussed to examine the tumor suppressive role of GAS5.

Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer.

Prostate cancer is the most prevalent malignancy in men, and the identification of novel oncogenes is clinically valuable for early screening, prevention and treatment. Recently, the studies have revealed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers including prostate cancer. The present study aims to identify a novel lncRNA that correlated with the survival time of prostate cancer patients and try to explore its biological functions in prostate cancer cells. After analysing the prostate carcinoma dataset of the Cancer Genome Atlas (TCGA), the lncRNA FAM66C was screened with its expression highly correlated with patient survival time, tumour stage and Gleason pattern. Real-time PCR showed that FAM66C highly expressed in prostate cancer cells, and knockdown FAM66C by siRNAs resulted in significant inhibition of cell growth. Furthermore, the results indicated that FAM66C promoted cell growth due to increasing cell proliferation but not decreasing cell apoptosis. In addition, FAM66C activated the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation. The result of Western Blotting and lysosomal acidity detection showed that knockdown FAM66C increased the protein ubiquitination and the lysosomal acidity. Moreover, inhibition of proteasome pathway could increase the activation of EGFR-ERK signalling and cell proliferation. Taken together, these results suggested that lncRNA FAM66C activate EGFR-ERK signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA FAM66C was associated with clinical progression. In addition, highly expressed lncRNA FAM66C in prostate cancer cell lines promoted cell proliferation. Moreover, lncRNA FAM66C activate the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. This study might provide lncRNA FAM66C as a potential therapeutic target gene of prostate cancer.

Systematic re-analysis strategy of serum indices identifies alkaline phosphatase as a potential predictive factor for cervical cancer.

The aim of the present study was to identify predictive factors for cervical cancer (CC) progression using a multistage approach. The present study obtained data from 390 healthy women and 259 patients with cervical cancer between June 2012 and June 2017, and used a multiple stage re-analysis strategy for clinical detection of CC. A total of seven types of serum indices were used in the present study, including sugar chain antigen 125 (CA-125), sugar chain antigen 199 (CA-199), α fetoprotein (AFP), carcino- embryonic antigen, alkaline phosphatase (ALP), cholesterol and triglyceride (TG). The expression levels of CA-125, CA-199, AFP, ALP, cholesterol and TG were significantly different between healthy women and patients with cervical squamous cell carcinoma (SCC). Furthermore, ALP, cholesterol and TG expression levels were significantly different in healthy women compared with patients with cervical adenocarcinoma (AC). Further comparisons based on age and pathological staging demonstrated that the variability in the ALP level was not significant between the <40 years old age group and the 40-50 years old age group within healthy individuals (P>0.05); however, was significant in patients with SCC (P<0.05). Staging analysis identified significant differences in ALP between healthy women and patients with SCC (Stage I-IV), and significant differences between healthy women and patients with Stage I AC. The results of the present study indicated that the expression of ALP was significantly increased in patients with CC compared with healthy women. Therefore, ALP may be a potential predictive factor for the development of CC.

Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS-AMPK-mTOR axis.

Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells exposed to lipopolysaccharide (LPS) by promoting autophagy. Primary rat Leydig cells were treated with various concentrations of LPS and ADM, together with or without N-acetyl-L-cysteine (NAC) or 3-methyladenine (3-MA). Cell proliferation was detected through CCK-8 and BrdU incorporation assays, and ROS level was measured with the DCFDA assay. Real-time PCR, western blot, immunofluorescence, transmission electron microscopy, TUNEL and flow cytometry were performed to examine ADM's effect on the pyroptosis, autophagy and steroidogenic enzymes of Leydig cells and AMPK/mTOR signalling. Like NAC, ADM dose-dependently reduced LPS-induced cytotoxicity and ROS overproduction. ADM also dose-dependently ameliorated LPS-induced pyroptosis by reversing the increased expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18, GSDMD, caspase-3, caspase-7, TUNEL-positive and PI and active caspase-1 double-stained positive rate, DNA fragmentation and LDH concentration, which could be rescued via co-incubation with 3-MA. ADM dose-dependently increased autophagy in LPS-induced Leydig cells, as confirmed by the increased expression of LC3-I/II, Beclin-1 and ATG-5; decreased expression of p62 and autophagosomes formation; and increased LC3-II/LC3-I ratio. However, co-treatment with 3-MA evidently decreased autophagy. Furthermore, ADM dose-dependently rescued the expression of steroidogenic enzymes, including StAR, P450scc, 3ß-HSD and CYP17, and testosterone production in LPS-induced Leydig cells. Like rapamycin, ADM dose-dependently enhanced AMPK phosphorylation but reduced mTOR phosphorylation in LPS-induced Leydig cells, which could be rescued via co-incubation with 3-MA. In addition, pyroptosis was further decreased, and autophagy was further promoted in LPS-induced Leydig cells upon co-treatment with ADM and rapamycin. ADM may protect the steroidogenic functions of Leydig cells against pyroptosis by activating autophagy via the ROS-AMPK-mTOR axis.

ATP synthase is required for male fertility and germ cell maturation in Drosophila testes.

Germ cell maturation is essential for spermatogenesis and testis homeostasis. ATP synthase serves significant roles in energy storage in germ cell survival and is catalyzed by alterations in the mitochondrial membrane proton concentration. The intrinsic cellular mechanisms governing stem cell maturation remain largely unknown. In the present study, in vivo RNA interference (RNAi) screening of major ATP synthase subunits was performed, and the function of ATP synthase for male fertility and spermatogenesis in Drosophila was explored. A Upstream Activation Sequence/Gal4 transcription factor system was used to knock down gene expression in specific cell types, and immunofluorescence staining was conducted to assess the roles of ATP synthase subunits in Drosophila testes. It was identified that knockdown of ATP synthase resulted in male infertility and abnormal spermatogenesis in Drosophila testes. In addition, knockdown of the ATP synthase ß subunit in germ cells resulted in defects in male infertility and germ cell maturation, while the hub and cyst cell populations were maintained. Other major ATP synthase subunits were also examined and similar phenotypes in Drosophila testes were identified. Taken together, the data from the present study revealed that ATP synthase serves important roles for male fertility during spermatogenesis by regulating germ cell maturation in Drosophila testes.

Biochemical clinical factors associated with missed abortion independent of maternal age: A retrospective study of 795 cases with missed abortion and 694 cases with normal pregnancy.

The incidence of fertile women with missed abortion dramatically increased in recent years, while very few serum indices have been identified for the diagnosis of missed abortion. The aim of this study was to identify related factors for missed abortion through a retrospective study of serum indices.A total of 795 cases of women with missed abortion and 694 cases of women with normal pregnancy between March 2014 and March 2017 were included in the present study. The diagnosis of missed abortion was based on clinical history, clinical examination, and transvaginal ultrasound findings. The final diagnosis of missed abortion was based on assessment of pregnancy structures (i.e., a gestational sac without fetal heart rate) via transvaginal ultrasound. We evaluated the clinical values of 4 serum indices and their relationship to missed abortion: gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), adenosine deaminase (ADA), and fibrinogen (FIB).The serum levels of GGT, ADA, and FIB showed statistically significant differences comparing women who experienced missed abortion with women who had normal pregnancies (controls). Among women with missed abortion, the levels of GGT and ADA were dramatically increased (GGT: P < .0001; ADA: P = .0459), while FIB levels were slightly lower (P = .0084) compared to controls. The LDH levels exhibited a non-significant trend toward lower levels in the missed abortion group (P = .3951). Interestingly, the observed significant increase in serum GTT levels among women with missed abortion was not affected by maternal age.This study found that GTT may be a useful marker which was associated with missed abortion, indicating its potential clinical roles in missed abortion.

New insights into long noncoding RNAs and pseudogenes in prognosis of renal cell carcinoma.

BACKGROUND: Increasing evidence suggests a critical role for long noncoding RNAs (LncRNAs) and pseudogenes in cancer. Renal cell carcinoma (RCC), the most common primary renal neoplasm, is highly aggressive and difficult to treat because of its resistance to chemotherapy and radiotherapy. Despite many identified LncRNAs and pseudogenes, few have been clearly elucidated. METHODS: This study provides new insights into LncRNAs and pseudogenes in the prognosis of RCC. We searched an online database to interrogate alterations and clinical data on cBioPortal. We analysed LncRNA and pseudogene signatures to predict the prognosis of RCC based on a Cox model. We also found potential serum biomarkers of RCC and validated them in 32 RCC patients, as well as healthy controls. RESULTS: Alterations were found in 2553 LncRNAs and 8901 pseudogenes and occurred in up to 23% of all cases. Among these, 27 LncRNAs and 45 pseudogenes were closely related to prognosis. We also identified signatures of LncRNAs and pseudogenes that can predict overall survival and recurrence of RCC. We then validated the relative levels of these LncRNAs and pseudogenes in the serum of 32 patients. Six of these, including LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P, could be non-invasive biomarkers of RCC. Finally, we selected PIK3CD-AS1 to determine its role in RCC and found that upregulation of PIK3CD-AS1 was closely associated with higher tumour stage and metastasis. CONCLUSIONS: These signatures of LncRNAs and pseudogenes can predict overall survival and recurrence of RCC. LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P could be non-invasive biomarkers of RCC. These data suggest the important roles of LncRNAs and pseudogenes in RCC, and therefore provides us new insights into the prognosis of RCC.

Novel insights into biomarkers associated with renal cell carcinoma.

Renal cell carcinoma (RCC) is a common form of cancer of the urinary tract. The present study aimed to identify driver genes in RCC using a bioinformatics approach. GSE53757 and GSE40435 microarray data were analyzed, and differentially expressed genes were filtered prior to gene ontology (GO) and pathway analysis. A protein-protein interaction (PPI) network was established. Overall survival and recurrence were investigated and based on data presented in cBioPortal. The COPS7B gene within the PPI network was selected for further study in vitro. The present study identified 174 and 149 genes possessing a significant signal to noise ratio in GSE53757 and GSE40435, respectively. In total, 53 of these genes were selected based upon inclusion in both datasets. GO analysis indicated that PRKCDBP, EHD2, KCNJ10, ATP1A1, KCNJ1 and EHD2 may be involved in various biological processes. Furthermore, ALDH6A1, LDHA, SUCLG1 and ABAT may be involved in the propanoate metabolism pathway. A network consisting of 106 genes, and one typical cluster were constructed. In addition, COPS7B was selected, as it was associated with decreased overall survival and increased recurrence rates, in order to elucidate its function in RCC. Furthermore, upregulation of COPS7B was demonstrated to be predictive of advanced stage disease and metastasis of RCC. Finally, COPS7B-knockdown inhibited RCC cell proliferation and invasion ability. Collectively, these results provided novel insights into COPS7B function, indicating that COPS7B may serve as a prognostic marker and therapeutic target in RCC.

Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells.

Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms. Cd induced intracellular Ca2+ elevation through phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38 mitogen-activated protein kinases (MAPK) activation and suppressing extracellular signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell death and inhibit cell proliferation. Cd induced p38 activation also contribute to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467 reinstated Cd-induced elevation of intracellular Ca2+ and apoptosis, and it also increased cell proliferation and restored autophagic flux by switching p38 to ERK pathway. The identification of the activation of CaSR-mediated protective pathway in renal cells sheds light on a possible cellular protective mechanism against Cd-induced kidney injury.