Fabrication of bio-inspired carbon nanodot-corn starch nanocomposite films via extrusion process for sustainable active food packaging applications.

In this study, carbon nanodot (CD)-corn starch (CS) nanocomposite films are fabricated for active food packaging applications. First, ginkgo biloba leaves (GBL) were used as a biomass-derived carbon precursor, and a facile hydrothermal method was employed to synthesise environmentally sustainable CDs. The GBL-derived carbon nanodots (gCDs) were then characterised and incorporated into a CS matrix via an extrusion process to fabricate the CS/gCD nanocomposite film. The effects of various gCD concentrations on the physicochemical and functional properties of CS/gCD composite films were systematically investigated. The gCD exhibited non-cytotoxic effect against human colorectal adenocarcinoma cell line (Caco-2) cells when exposed up to 1000 µg/mL. The incorporation of gCDs into the CS film improved its mechanical properties, with the toughness of the CS/gCD2% nanocomposite film exhibiting 198 % superiority compared to the CS film. In addition, the oxygen barrier and UV-blocking properties were significantly improved. Furthermore, the CS/gCD nanocomposite film significantly extended the shelf life of ω-3 oils owing to the superior antioxidant activity of the gCDs, exhibiting only 9 meq/kg during the 15-day storage period. Our results suggest that the developed CS/gCD active composite film is a promising candidate for environmentally sustainable solutions to enhance food shelf life and reduce food waste.

Novel insights into regulators and functional modulators of adipogenesis.

Adipogenesis is a process that differentiates new adipocytes from precursor cells and is tightly regulated by several factors, including many transcription factors and various post-translational modifications. Recently, new roles of adipogenesis have been suggested in various diseases. However, the molecular mechanisms and functional modulation of these adipogenic genes remain poorly understood. This review summarizes the regulatory factors and modulators of adipogenesis and discusses future research directions to identify novel mechanisms regulating adipogenesis and the effects of adipogenic regulators in pathological conditions. The master adipogenic transcriptional factors PPARγ and C/EBPα were identified along with other crucial regulatory factors such as SREBP, Kroxs, STAT5, Wnt, FOXO1, SWI/SNF, KLFs, and PARPs. These transcriptional factors regulate adipogenesis through specific mechanisms, depending on the adipogenic stage. However, further studies related to the in vivo role of newly discovered adipogenic regulators and their function in various diseases are needed to develop new potent therapeutic strategies for metabolic diseases and cancer.

Bee (Apis mellifera L. 1758) wax restores adipogenesis and lipid accumulation of 3T3-L1 cells in cancer-associated cachexia condition.

Cachexia is associated with various diseases, such as heart disease, infectious disease, and cancer. In particular, cancer-associated cachexia (CAC) accounts for more than 20% of mortality in cancer patients worldwide. Adipose tissue in CAC is characterized by adipocyte atrophy, mainly due to excessively increased lipolysis and impairment of adipogenesis. CAC is well known for the loss of skeletal muscle mass and/or fat mass. CAC induces severe metabolic alterations, including protein, lipid, and carbohydrate metabolism. The objectives of this study were to evaluate the effects of bee wax (Apis mellifera L. 1758) (BW) extract on adipogenesis, lipolysis, and mitochondrial oxygen consumption through white adipocytes, 3T3-L1. To achieve this study, cancer-associated cachexia condition was established by incubation of 3T3-L1 with colon cancer cell line CT26 cultured media. BW extract recovered the reduced adipogenesis under cachectic conditions in CT26 media. Treatment of BW showed increasing lipid accumulation as well as adipogenic gene expression and its target gene during adipogenesis. The administration of BW to adipocytes could decrease lipolysis. Also, BW could significantly downregulated the mitochondrial fatty acid oxidation-related genes, oxygen consumption rate, and extracellular acidification rate. Our results suggest that BW could improve metabolic disorders such as CAC through the activation of adipogenesis and inhibition of lipolysis in adipocytes, although we need further validation in vivo CAC model to check the effects of BW extract. Therefore, BW extract supplements could be useful as an alternative medicine to reverse energy imbalances.

Biomarkers of Cellular Senescence and Aging: Current State-of-the-Art, Challenges and Future Perspectives.

Population aging has increased the global prevalence of aging-related diseases, including cancer, sarcopenia, neurological disease, arthritis, and heart disease. Understanding aging, a fundamental biological process, has led to breakthroughs in several fields. Cellular senescence, evinced by flattened cell bodies, vacuole formation, and cytoplasmic granules, ubiquitously plays crucial roles in tissue remodeling, embryogenesis, and wound repair as well as in cancer therapy and aging. The lack of universal biomarkers for detecting and quantifying senescent cells, in vitro and in vivo, constitutes a major limitation. The applications and limitations of major senescence biomarkers, including senescence-associated ß-galactosidase staining, telomere shortening, cell-cycle arrest, DNA methylation, and senescence-associated secreted phenotypes are discussed. Furthermore, explore senotherapeutic approaches for aging-associated diseases and cancer. In addition to the conventional biomarkers, this review highlighted the in vitro, in vivo, and disease models used for aging studies. Further, technologies from the current decade including multi-omics and computational methods used in the fields of senescence and aging are also discussed in this review. Understanding aging-associated biological processes by using cellular senescence biomarkers can enable therapeutic innovation and interventions to improve the quality of life of older adults.

Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells.

Tumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interaction, and that tumor-bystander cell fusion has contrasting effects. By trapping fusion hybrids in the heterokaryon or synkaryon state, tumor-bystander cell fusion prevents the progression of heterogeneity. However, if trapping fails, fusion hybrids will resume replication to form derivative clones with diverse genomic makeups and behavioral phenotypes. To determine the characteristics of bystander cells that influence the fate of fusion hybrids, we co-cultured prostate mesenchymal stromal cell lines and their spontaneously transformed sublines with LNCaP as well as HPE-15 prostate cancer cells. Subclones derived from cancer-stromal fusion hybrids were examined for genotypic and phenotypic diversifications. Both stromal cell lines were capable of fusing with cancer cells, but only fusion hybrids with the transformed stromal subline generated large numbers of derivative subclones. Each subclone had distinct cell morphologies and growth behaviors and was detected with complete genomic hybridization. The health conditions of the bystander cell compartment play a crucial role in the progression of tumor cell heterogeneity.

Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate.

Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors' inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC.

Anti-Inflammatory Effects of Spirodela polyrhiza (L.) SCHLEID. Extract on Contact Dermatitis in Mice-Its Active Compounds and Molecular Targets.

Spirodela polyrhiza (L.) SCHLEID. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in S. polyrhiza and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of S. polyrhiza (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (<-8 kcal/mol) and IL-6 (<-6 kcal/mol). Our in vivo studies showed that topical EESP ameliorated DNFB-induced skin lesions and histopathological abnormalities, and reduced the levels of TNF-α, interferon (IFN)-É£, IL-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues. In conclusion, our findings suggest the potential for dermatological applications of S. polyrhiza and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides.

The Anti-Inflammatory and Skin Barrier Function Recovery Effects of Schisandra chinensis in Mice with Atopic Dermatitis.

Background and Objectives: The fruit of Schisandra chinensis (Turcz.) Baill. is widely used medicinally to treat coughs, asthma, exhaustion, eczema, and pruritus in Northeast Asian countries, including Korea, China, and Japan. This study was designed to investigate the effects of S. chinensis on dermatitis in mice with calcipotriol (MC-903)-induced atopic dermatitis (AD), and its effects on skin barrier dysfunction was also investigated. Materials and Methods: The inhibitory effects of an ethanolic extract of S. chinensis (EESC) on skin lesions, water content, water-holding capacity (WHC), histopathological abnormalities, and inflammatory cytokine and chemokine levels were evaluated in mice with AD induced by MC903. Results: Topical EESC ameliorated skin lesions, reduced skin water content, and increased MC903-induced WHC. EESC also prevented MC-903-induced histopathological abnormalities such as epidermal disruption, hyperkeratosis, spongiotic changes, and immune cell infiltration in inflamed tissue. Moreover, topical EESC reduced MC-903-induced levels of pro-inflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-4, IL-6, IL-8, monocyte chemotactic protein (MCP)-1, and thymic stromal lymphopoietin (TSLP). Furthermore, unlike dexamethasone, EESC did not reduce the spleen/body weight ratio. Conclusions: These results suggest that S. chinensis can be used as an alternative to external corticosteroids and that its anti-inflammatory and skin barrier dysfunction-restoring effects are related to the downregulation of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-4, IL-6, IL-8, and TSLP.

Understanding the relationship between cancer associated cachexia and hypoxia-inducible factor-1.

Cancer-associated cachexia (CAC) is a multifactorial disorder characterized by an unrestricted loss of body weight as a result of muscle and adipose tissue atrophy. Cachexia is influenced by several factors, including decreased metabolic activity and food intake, an imbalance between energy uptake and expenditure, excessive catabolism, and inflammation. Cachexia is highly associated with all types of cancers responsible for more than half of cancer-related mortalities worldwide. In healthy individuals, adipose tissue significantly regulates energy balance and glucose homeostasis. However, in metastatic cancer patients, CAC occurs mainly because of an imbalance between muscle protein synthesis and degradation which are organized by certain extracellular ligands and associated signaling pathways. Under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1α) accumulated and translocated to the nucleus and activate numerous genes involved in cell survival, invasion, angiogenesis, metastasis, metabolic reprogramming, and cancer stemness. On the other hand, the ubiquitination proteasome pathway is inhibited during low O2 levels which promote muscle wasting in cancer patients. Therefore, understanding the mechanism of the HIF-1 pathway and its metabolic adaptation to biomolecules is important for developing a novel therapeutic method for cancer and cachexia therapy. Even though many HIF inhibitors are already in a clinical trial, their mechanism of action remains unknown. With this background, this review summarizes the basic concepts of cachexia, the role of inflammatory cytokines, pathways connected with cachexia with special reference to the HIF-1 pathway and its regulation, metabolic changes, and inhibitors of HIFs.

The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of Fraxinus rhynchophylla Hance Bark on Contact Dermatitis in Mice.

Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in F. rhynchophylla, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of F. rhynchophylla (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in F. rhynchophylla, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<-6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of F. rhynchophylla has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

A Novel Urine Exosomal lncRNA Assay to Improve the Detection of Prostate Cancer at Initial Biopsy: A Retrospective Multicenter Diagnostic Feasibility Study.

PURPOSE: This study aimed at developing and validating a novel noninvasive urinary exosome-based post-DRE (digital rectal examination) lncRNA assay to diagnose PCa (prostate cancer) and clinically significant PCa (Gleason score ≥ 7) from the initial prostate biopsy. METHODS: A total of 602 urine samples from eligible participants were collected. The expression levels of urinary exosomal PCA3 (prostate cancer antigen 3) and MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) were detected by qPCR (quantitative real-time PCR). Receiver operating characteristic (ROC) analysis was applied to evaluate the diagnostic performance of PCA3, MALAT1 and the lncRNA assay. A decision curve analysis (DCA) and waterfall plots were used to assess the clinical value of the lncRNA assay. RESULTS: Urinary exosomal PCA3 and MALAT1 were overexpressed in PCa and clinically significant PCa (p < 0.001). The lncRNA assay combining PCA3 and MALAT1 had a better diagnostic performance (AUC 0.828) than the current clinical parameters in detecting PCa. More importantly, the lncRNA assay yielded an AUC of 0.831 to detect clinically significant PCa, which is much higher than that of the current clinical parameters. The lncRNA assay was superior to PSA, f/tPSA and the base model for detecting PCa and clinically significant PCa, with a higher net benefit for almost all threshold probabilities. At the cutoff value of 95% sensitivity, the lncRNA assay could avoid 24.2% unnecessary biopsies while only missing 1.2% of the cases of clinically significant PCa. CONCLUSION: We developed and validated a novel noninvasive post-DRE urine-based lncRNA assay that presented good diagnostic power and clinical utility for the early diagnosis of PCa and high-grade PCa.

The application of virtual reality training for anastomosis during robot-assisted radical prostatectomy.

OBJECTIVE: To investigate the application of virtual reality training in vesicourethral anastomosis during robot-assisted radical prostatectomy (RARP). METHODS: Three certified robotic urologists who underwent virtual reality training were enrolled in the study group. The other three without training were enrolled in the control group. Parameters were recorded before and after the training. Then a total of 18 patients undergoing RARP were enrolled and randomized assigned to receive anastomosis procedures with certified urologists who either obtained or did not obtain training. The quality of the anastomosis was evaluated. RESULTS: For the virtual training evaluation, the overall score was significantly improved from 65.0±10.8 to 92.7±3.5 (p=0.014); the time of anastomosis was shortened; the economy of motion improved; instrument collisions decreased after training (p<0.05). Besides, the effectiveness of the virtual training was evaluated in the 18 real anastomosis procedures which were completed either by three urologists with training or three urologists without training. Most intriguingly, the average time of anastomosis was shortened from 40.0±12.4 min to 25.1±7.1 min (p=0.015). The parameters including time of operation, creatinine level of drainage, postoperative hospital stay and duration of catheter drainage were comparable before and after training. Two leakages, which were observed in procedures by doctors without training, needed salvage sutures by a senior doctor. CONCLUSIONS: Virtual reality training enabled surgeons to become quickly familiar with robotic system manipulation, improved their skills for vesicourethral anastomosis and shortened the learning curve, thus helping them operate with high efficacy and quality.

Circulating exosomal mRNA profiling identifies novel signatures for the detection of prostate cancer.

The landscape and characteristics of circulating exosomal messenger RNAs (emRNAs) are poorly understood, which hampered the accurate detection of circulating emRNAs. Through comparing RNA sequencing data of circulating exosomes with the corresponding data in tissues, we illustrated the different characteristics of emRNAs compared to tissue mRNAs. We then developed an improved strategy for emRNA detection based on the features of circulating emRNAs. Using the optimized detection strategy, we further validated prostate cancer (PCa) associated emRNAs discovered by emRNA-seq in a large cohort of patients and identified emRNA signatures for PCa screening and diagnosis using logistic regression analysis. The receiver operating characteristic curve (ROC) analysis showed that the circulating emRNA-based screening signature yielded an area under the ROC curve (AUC) of 0.948 in distinguishing PCa patients from healthy controls. The circulating emRNA-based diagnostic signature also showed a great performance in predicting prostate biopsy results (AUC: 0.851). In conclusion, our study developed an optimized emRNA detection strategy and identified novel emRNA signatures for the detection of PCa.

Cancer-stromal cell fusion as revealed by fluorescence protein tracking.

PURPOSE: We previously determined that cancer-stromal interaction was a direct route to tumor cell heterogeneity progression, since cancer-stromal cell fusion in coculture resulted in the creation of heterogeneous clones of fusion hybrid progeny. In this report, we modified the cancer-stromal coculture system to establish optimal experimental conditions for investigating cell fusion machinery and the mechanism of heterogeneity progression. EXPERIMENTAL DESIGN: Red fluorescence protein-tagged LNCaP cells were cocultured with green fluorescence protein-labeled prostate stromal cells for cancer-stromal cell fusion, which was tracked as dual fluorescent cells by fluorescence microscopy. RESULTS: We identified the most efficient strategy to isolate clones of fusion hybrid progenies. From the coculture, mixed cells including fusion hybrids were subjected to low-density replating for colony formation by fusion hybrid progeny. These colonies could propagate into derivative cell populations. Compared to the parental LNCaP cells, clones of the fusion hybrid progeny displayed divergent behaviors and exhibited permanent genomic hybridization. CONCLUSIONS: Cancer-stromal cell fusion leads to cancer cell heterogeneity. The cancer-stromal coculture system characterized in this study can be used as a model for molecular characterization of cancer cell fusion as the mechanism behind the progression of heterogeneity observed in clinical prostate cancers.

Autonomic nerve regulation for prostate cancer: study based on the tissue transcriptional analysis.

BACKGROUND: The whole-body energy metabolism is regulated by autonomic nerves which also play important roles in the regulation of the generation and development of different kinds of cancers. This study is to analyze the expression of autonomic nerve receptors and their relationship with the development of prostate cancer (PCa) and to further understand the central regulation of the prostate. METHODS: RNA sequencing data concerning autonomic nerve receptors from paired tumor and adjacent benign tissues from 65 patients were collected. The mRNA expression and patient data were analyzed. The Cancer Genome Atlas (TCGA) data confirmed the results, and Pearson analysis, Pearson heat maps, gene heat maps, multivariate logistic regression models, receiver operating characteristic (ROC) curves and Gene Set Enrichment Analysis (GSEA) and Pearson's analysis were analyzed for correlation analysis in this study. RESULTS: Reads with eight receptors associated with PCa generation were finally retained in this report. Favorable relationships were found among the different autonomic nerve regulators for the prostate. In univariate logistic regression analysis, adrenoceptor alpha 1A (ADRA1A) was the most positively correlated [OR (95% CI): 1.707 (1.209, 2.410)]; the area under the curve (AUC) in the ROC for ADRA1A was 0.866 (P<0.001). In multivariate logistic regression analysis, a predicted formulation for PCa diagnosis was evident. The GSEA results also showed the effect of autonomic nerves on cancer generation and some of the key cancer-related pathways, as well as Notch, Wnt and steroid biosynthesis pathways. Finally, five articles were reviewed to elucidate the center-autonomic nerve system-periphery circuit in the prostate. CONCLUSIONS: Central regulation plays an important role in the development of PCa, presenting the opportunity to treat the disease, and additional studies are warranted.

Heterogeneity of PTEN and PPAR-γ in cancer and their prognostic application to bladder cancer.

The aim of the present study was to determine the prognostic value of peroxisome proliferator-activated receptor-γ (PPAR-γ) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) for bladder cancer. Data were collected from The Cancer Genome Atlas (TCGA), a public database, and were analyzed to assess PTEN and PPAR-γ heterogeneity as well as distinct trends in bladder cancers. Furthermore, PPAR-γ and PTEN expression levels and their association with one another were evaluated. Finally, the prognostic significance of PPAR-γ and PTEN for bladder cancer was validated in vivo using clinical samples. Based on the TCGA database, PTEN levels were significantly increased in bladder cancers (P<0.001); whereas PPAR-γ expression was downregulated in the same samples (P<0.05). Furthermore, linear correlation analysis indicated that in bladder cancers, PPAR-γ and PTEN are inversely correlated (P<0.001). The assessment and analysis of clinical samples revealed that PPAR-γ was significantly elevated in tumor tissues (P<0.001); however, PTEN was downregulated in cancer tissues (P<0.001). Furthermore, PPAR-γ expression determined by immunohistochemistry grey level (P=0.002) was also elevated in high-grade and invasive bladder cancers compared with low-grade and superficial tumors, whereas PTEN levels exhibited the opposite in this analysis (P=0.001). In individuals with lymphoid metastasis, PPAR-γ was significantly increased (P<0.001), and PTEN was significantly decreased (P<0.001). Pearson analysis revealed a significant negative correlation between PPAR-γ and PTEN expression (r=-0.604, P<0.05). In conclusion, tissue heterogeneity was observed with respect to PPAR-γ and PTEN expression in bladder cancer. PTEN and PPAR-γ expression are negatively correlated and may be excellent indicators of bladder cancer tumorigenesis and progression.

Discovery and Validation of Serum MicroRNAs as Early Diagnostic Biomarkers for Prostate Cancer in Chinese Population.

Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.

Prostatic Acid Phosphatase (PAP) Predicts Prostate Cancer Progress in a Population-Based Study: The Renewal of PAP?

OBJECTIVE: To characterize the disease progression and median survival of patients with prostate cancer (PCa) according to the prostatic-specific acid phosphatase (PAP) analysis in a population-based study from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Prostate cancer patients with completed PAP results were identified using the SEER database of the National Cancer Institute. The Mann-Whitney Sum test was utilized to compare the statistical significance for measurement data and ranked data. Data were stratified by ages, races, TNM Classification of Malignant Tumors (TNM), pathological grades, number of tumors, PAP, and survival duration. Multivariable logistic analysis was performed to identify predictors of the presence of invasion and metastases. Cox regression was analyzed for the factors associated with all-cause mortality and prostate cancer-specific mortality. Moreover, survival curve was used to detect the survival months. The unknown data were excluded from these tests. RESULTS: In total, there are 5184 PAP+ patients and 3161 PAP- patients involved. The Mann-Whitney Sum test showed that slightly greater tumor size (P = 0.03), elevated lymphatic (P = 0.005) and distant (P < 0.001) metastasis rate, higher pathological grade (P < 0.001), localized tumor number (P < 0.001), and shortened survival months (P < 0.001) were observed in the PAP+ group compared with the PAP- group. In the multivariable logistic regression, invasion and metastasis Hazard Ratio (HR) were elevated significantly (P < 0.001) in the PAP+ individuals. In the survival analysis, PAP- patients experienced the prolonged median survival. In the postsurgical patients, the survival months were still longer in PAP+ patients compared with the negative ones (P < 0.001), though surgery prolonged the survival months of both groups. Survival months stratified by localized, invasion, and metastasis situations were analyzed. In the three stratified subgroups, the survival duration is significantly decreased in the PAP+ individuals in the localized PCa group (P < 0.001) and the metastasis group (P = 0.013). CONCLUSIONS: The findings of this study provide population-based estimates of the PCa progress and prognosis for patients with different PAP results, which may suggest a renewed period for the PAP.

Navigation of Intelligent/Interactive Qualitative and Quantitative Analysis Three-Dimensional Reconstruction Technique in Laparoscopic or Robotic Assisted Partial Nephrectomy for Renal Hilar Tumors.

Purpose: To evaluate the feasibility and effectiveness of the navigation of intelligent/interactive qualitative and quantitative analysis (IQQA) three-dimensional (3D) reconstruction technique in laparoscopic or robotic assisted partial nephrectomy (LPN or RAPN) for renal hilar tumors. Patients and Methods: The study retrospectively reviewed 26 patients with hilar tumors from February 2016 to February 2018. IQQA 3D reconstruction technique was applied for the purpose of navigation and resection of the tumors. Relevant clinical parameters and surgical outcomes were recorded. Results: All 26 LPN or RAPN were effectively completed without conversion to a hand-assisted or an open approach. Under the navigation of IQQA, all tumors were found precisely at the first time during surgeries. The mean operative time was 142 minutes (142 ± 35), with a mean warm ischemia time of 24.3 minutes (24.3 ± 9.5). The estimated blood loss was 156 mL (156 ± 112). No intraoperative complications occurred. Two patients suffered from postoperative complications. All patients had negative margins on the final pathological examination. At a mean follow-up period of 3 months, the mean glomerular filtration rate is 22.5 mL/min (22.5 ± 7.1) without tumor recurrence. Conclusions: With peculiar features, such as accurate location, complete resection, and fewer perioperative complications, the navigation of IQQA 3D reconstruction technique in partial nephrectomy represents a safe and effective procedure for hilar tumors.