The efficacy and safety of monoclonal antibody therapies for interstitial cystitis/bladder pain syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

Combined Ultrasensitive Detection of Renal Cancer Proteins and Cells Using an Optical Microfiber Functionalized with Ti3C2 MXene and Gold Nanorod-Nanosensitized Interfaces.

The ultrasensitive and quantitative detection of renal cancer protein biomarkers present at ultralow concentrations for early-stage cancer diagnosis requires a biosensing probe possessing ultrahigh detection sensitivity and remarkable biosensing selectivity. Here, we report an optical microfiber integrated with Ti3C2-supported gold nanorod hybrid nanointerfaces for implementation in ultrasensitive sensing of the carbonic anhydrase IX (CAIX) protein and renal cancer cells. Because the evanescent field of the fiber is strongly coupled with nanointerfaces in the near-infrared region, the proposed optical microfiber biosensor achieves ultrahigh-sensitivity detection of the CAIX protein biomarker with ultralow limits of detection (LODs) of 13.8 zM in pure buffer solution and 0.19 aM in 30% serum solution. In addition, the proposed sensor also successfully and specifically recognizes living renal cancer cells in cell culture media with a LOD of 180 cells/mL. This strategy may serves as a powerful biosensing platform that combines the quantification of protein biomarkers and cancer cells, resulting in a higher accuracy of early-stage renal cancer diagnosis and screenings.

Performance evaluation of plastic optical fiber communication using micro-lens coupling and computational temporal ghost imaging algorithm.

Plastic optical fiber communication (POFC) systems are particularly sensitive to signal performance and power budget. In this paper, we propose what we belive to be a novel scheme to jointly enhance the bit-error-ratio (BER) performance and coupling efficiency for multi-level pulse amplitude modulation (PAM-M) based POFC systems. The computational temporal ghost imaging (CTGI) algorithm is developed for PAM4 modulation for the first time to resist the system distortion. The simulation results reveal that enhanced BER performance and clear eye diagrams are acquired by using CTGI algorithm with an optimized modulation basis. Experimental results also investigate and show, with CTGI algorithm, the BER performance for 180 Mb/s PAM4 signals is enhanced from 2.2 × 10-2 to 8.4 × 10-4 over 10 m POF by using a 40 MHz photodetector. The POF link is equipped with micro-lenses at its end faces by using a ball-burning technique, which helps to increase the coupling efficiency from 28.64% to 70.61%. Both simulation and experimental results show that the proposed scheme is feasible to achieve a cost-effective and high-speed POFC system with short reach.

Voltage, thermal and magnetic field fiber sensors based on magnetic nanoparticles-doped photonic liquid crystal fibers.

In this article, highly sensitive voltage, thermal and magnetic field fiber sensors were obtained in magnetic nanoparticles-doped E7 liquid crystals filled into photonic crystal fibers (PLCF). The voltage and temperature sensitivity reached at 12.598 nm/V and -3.874 nm/°C, respectively. The minimum voltage response time is 48.2 ms. The phase transition temperature Tc of liquid crystal with magnetic dopant was reduced from 60 °C to 46 °C. The magnetic field sensor based on magnetic nanoparticles-doped PLCF were obtained with sensitivity of 118.2 pm/mT from 400 to 460 mT.

Laser Velocimetry for the In Situ Sensing of Deep-Sea Hydrothermal Flow Velocity.

Laser Doppler velocimetry (LDV) based on a differential laser Doppler system has been widely used in fluid mechanics to measure particle velocity. However, the two outgoing lights must intersect strictly at the measurement position. In cross-interface applications, due to interface effects, two beams of light become easily disjointed. To address the issue, we present a laser velocimeter in a coaxial arrangement consisting of the following components: a single-frequency laser (wavelength λ = 532 nm) and a Twyman-Green interferometer. In contrast to previous LDV systems, a laser velocimeter based on the Twyman-Green interferometer has the advantage of realizing cross-interface measurement. At the same time, the sensitive direction of the instrument can be changed according to the direction of the measured speed. We have developed a 4000 m level laser hydrothermal flow velocity measurement prototype suitable for deep-sea in situ measurement. The system underwent a withstand voltage test at the Qingdao Deep Sea Base, and the signal obtained was normal under a high pressure of 40 MPa. The velocity contrast measurement was carried out at the China Institute of Water Resources and Hydropower Research. The maximum relative error of the measurement was 8.82% when compared with the acoustic Doppler velocimeter at the low-speed range of 0.1-1 m/s. The maximum relative error of the measurement was 1.98% when compared with the nozzle standard velocity system at the high-speed range of 1-7 m/s. Finally, the prototype system was successfully evaluated in the shallow sea in Lingshui, Hainan, with it demonstrating great potential for the in situ measurement of fluid velocity at marine hydrothermal vents.

Matrine Targets Intestinal Lactobacillus acidophilus to Inhibit Porcine Circovirus Type 2 Infection in Mice.

Porcine circovirus type 2 (PCV2) has caused huge economic losses to the pig industry across the world. Matrine is a natural compound that has been shown to regulate intestinal flora and has anti-PCV2 activity in mouse models. PCV2 infection can lead to changes in intestinal flora. The intestinal flora has proved to be one of the important pharmacological targets of the active components of Traditional Chinese Medicine. This study aimed to determine whether matrine exerts anti-PCV2 effects by regulating intestinal flora. In this study, fecal microbiota transplantation (FMT) was used to evaluate the effect of matrine on the intestinal flora of PCV2-infected Kunming (KM) mice. The expression of the Cap gene in the liver and the ileum, the relative expression of IL-1ß mRNA, and the Lactobacillus acidophilus (L. acidophilus) gene in the ileum of mice were determined by real-time quantitative polymerase chain reaction (qPCR). ELISA was used to analyze the content of secretory immunoglobulin A (SIgA) in small intestinal fluid. L. acidophilus was isolated and identified from the feces of KM mice in order to study its anti-PCV2 effect in vivo. The expression of the Cap gene in the liver and the ileum and the relative expression of L. acidophilus and IL-1ß mRNA in the ileum were determined by qPCR. The results showed that matrine could reduce the relative expression of IL-1ß mRNA by regulating intestinal flora, and that its pharmacological anti-PCV2 and effect may be related to L. acidophilus. L. acidophilus was successfully isolated and identified from the feces of KM mice. The in vivo experiment revealed that administration of L. acidophilus also reduced the relative expression of IL-1ß mRNA, and that it had anti-PCV2 effects in PCV2-infected mice. It was found that matrine could regulate the abundance of L. acidophilus in the gut of mice to exert an anti-PCV2 effect and inhibit PCV2-induced inflammatory response.

Target Discovery of Matrine against PRRSV in Marc-145 Cells via Activity-Based Protein Profiling.

Porcine reproductive and respiratory syndrome (PRRS) seriously endangers the sustainable development of the pig industry. Our previous studies have shown that matrine can resist porcine reproductive and respiratory syndrome virus (PRRSV) infection. This study aimed to explore the anti-PRRSV targets of matrine in Marc-145 cells. Biotin-labeled matrine 1 and 2 were used as probes. MTT assay was used to determine the maximum non-cytotoxic concentration (MNTC) of each probe in Marc-145 cells. The anti-PRRSV activity of each probe was evaluated via MTT, qPCR and Western blot, and its anti-inflammatory activity was evaluated via qPCR and Western blot. The targets of matrine in Marc-145 cells were searched using activity-based protein profiling (ABPP), and compared with the targets predicted via network pharmacology for screening the potential targets of matrine against PRRSV. The protein-protein interaction networks (PPI) of potential targets were constructed using a network database and GO/KEGG enrichment analysis was performed. ACAT1, ALB, HMOX1, HSPA8, HSP90AB1, PARP1 and STAT1 were identified as potential targets of matrine, and their functions were related to antiviral capacity and immunity. Matrine may play an anti-PRRSV role by directly acting on ACAT1, ALB, HMOX1, HSPA8, HSP90AB1, PARP1 and STAT1.

A novel strategy for optimal component formula of anti-PRRSV from natural compounds using tandem mass tag labeled proteomic analyses.

BACKGROUND: Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most important porcine viral diseases which have been threatening the pig industry in China. At present, most commercial vaccines fail to provide complete protection because of highly genetic diversity of PRRSV strains. This study aimed to optimize a component formula from traditional Chinese medicine(TCM)compounds with defined chemical characteristics and clear mechanism of action against PRRSV. METHODS: A total of 13 natural compounds were screened for the anti-PRRSV activity using porcine alveolar macrophages (PAMs). Three compounds with strong anti-PRRSV activity were selected to identify their potential protein targets by proteomic analysis. The optimal compound formula was determined by orthogonal design based on the results of proteomics. MTT assay was used to determine the maximum non-cytotoxic concentration (MNTC) of each compound using PAMs. QPCR and western blot were used to investigate the PRRSV N gene and protein expression, respectively. The Tandem Mass Tag (TMT) technique of relative quantitative proteomics was used to detect the differential protein expression of PAMs treated with PRRSV, matrine (MT), glycyrrhizic acid (GA) and tea saponin (TS), respectively. The three concentrations of these compounds with anti-PRRSV activity were used for orthogonal design. Four formulas with high safety were screened by MTT assay and their anti-PRRSV effects were evaluated. RESULTS: MT, GA and TS inhibited PRRSV replication in a dose-dependent manner. CCL8, IFIT3, IFIH1 and ISG15 were the top four proteins in expression level change in cells treated with MT, GA or TS. The relative expression of IFIT3, IFIH1, ISG15 and IFN-ß mRNAs were consistent with the results of proteomics. The component formula (0.4 mg/mL MT + 0.25 mg/mL GA + 1.95 µg/mL TS) showed synergistic anti-PRRSV effect. CONCLUSIONS: The component formula possessed anti-PRRSV activity in vitro, in which the optimal dosage on PAMs was 0.4 mg/mL MT + 0.25 mg/mL GA + 1.95 µg/mL TS. Compatibility of the formula was superposition of the same target with GA and TS, while different targets of MT. IFN-ß may be one of the targets of the component formula possessed anti-PRRSV activity.

Method for controlling temperature sensitivity of the fiber intermodal sensor and its application in the torsion sensor.

Temperature crosstalk has always been a critical problem for fiber intermodal sensors. In this work, we have proposed a novel method based on the special temperature response of photosensitive fiber to control the temperature sensitivity of the fiber intermodal sensor. The control of temperature sensitivity has been realized via adjusting the proportion of photosensitive fiber to single-mode fiber in the sensing part. The temperature sensitivity as high as -192 pm/°C, and as low as -2.6 pm/°C can be obtained, satisfying the demand in both research and application. The torsion sensor is taken as an example to illustrate feasibility of this method, showing no evident interference in the measurement of torsion parameters. The proposed method outstrips the conventional one by simple structure, facile manufacture, multiple use and low cost, which brings great promise for further employment in laboratory and industry.

Optical feedback interferometry with 40 km transmission distance based on a distributed feedback fiber laser.

This Letter proposes an all-fiber self-mixing interferometric method based on laser feedback technology with long transmission distance, which has advantages of high sensitivity and compact structure. We theoretically and experimentally verify that the measurement distance of the self-mixing sensor is not limited to the coherence length of the solitary laser used. In the experiment, the velocity of a non-cooperative target was successfully measured with 40 km transmission distance. Therefore, the all-fiber self-mixing Doppler velocimeter has a great application prospect in the field of remote sensing measurement. Its unique flexibility can be applied to a variety of complex environments of non-cooperative target measurement.

UPLC-MS/MS assay for the simultaneous determination of pyrotinib and its oxidative metabolite in rat plasma: Application to a pharmacokinetic study.

Pyrotinib is an irreversible EGFR/HER2 inhibitor that has been approved for the treatment of breast cancer. The aim of this work was to establish a quantification method for the simultaneous determination of pyrotinib and its metabolite pyrotinib-lactam in rat plasma using UPLC-MS/MS. After simple protein precipitation with acetonitrile, the analytes and internal standard (neratinib) were separated on an ACQUITY BEH C18 column (2.1 × 50 mm, 1.7 µm) using a mobile phase of water containing 0.1% formic acid and acetonitrile. The detection was performed using selected reaction monitoring mode with precursor-to-product ion transitions at m/z 583.2 > 138.1 for pyrotinib, m/z 597.2 > 152.1 for pyrotinib-lactam, and m/z 557.2 > 112.1 for internal standard. The assay exhibited excellent linearity in the concentration range of 0.5-1000 ng/mL for pyrotinib and pyrotinib-lactam. The assay met the criteria of the United States Food and Drug Administration-validated bioanalytical methods and was successfully applied to a pharmacokinetic study of pyrotinib and its metabolite for the first time. Our results demonstrated that pyrotinib rapidly converted into pyrotinib-lactam, whose in vivo exposure was 21% that of pyrotinib.

DLX6-AS1 accelerates cell proliferation through regulating miR-497-5p/SNCG pathway in prostate cancer.

Prostate cancer (PCa) has become the second leading cause of cancer-related mortality in males worldwide. Although the long noncoding RNA DLX6-AS1 has been recognized to be an oncogene in multiple cancers, the biological function and regulatory mechanism of DLX6-AS1 in prostate cancer are still obscure. In the present study, we observed that DLX6-AS1 was significantly upregulated in PCa tissues and cells. Knockdown of DLX6-AS1 inhibited PCa progression by suppressing cell proliferation and accelerating cell apoptosis. Molecular mechanism exploration indicated that DLX6-AS1 acted as a sponge for miR-497-5p and synuclein gamma (SNCG) was a downstream target gene of miR-497-5p. In addition, there was a negative correlation between DLX6-AS1 and miR-497-5p in PCa tissues. Rescue assays showed that SNCG overexpression could partially recover DLX6-AS1 knockdown-mediated inhibition of progression in PCa. Furthermore, xenograft tumor model was established to determine the role of DLX6-AS1 in PCa tumor growth and the results suggested that DLX6-AS1 could facilitate tumor growth by regulating SNCG in vivo. In conclusion, our study investigated the biological function and underlying mechanism of DLX6-AS1 in PCa and validated that DLX6-AS1 functioned as an oncogene through miR-497-5p/SNCG axis.

Multifactor Prognostic Evaluation of Postoperative Craniopharyngiomas.

PURPOSE: To evaluate various factors that could be associated with the postoperative prognosis of patients with craniopharyngiomas and provide evidence for the proper surgical course and optimal outcome assessments of craniopharyngiomas. METHODS: We performed a retrospective study and reviewed 68 patients with craniopharyngiomas who received surgery from May 2013 to October 2018. The relationships between the disease prognosis and age, gender, onset symptoms, size of tumor, degree of calcification, consistency, QST classification, adhesion strength, and pathological types were analyzed. RESULTS: There were no significant associations between the prognosis and age, gender, number of onset symptoms, and pathological types (P > 0.05). The severity of onset symptoms, tumor diameter, and degree of calcification was significantly associated with the prognosis (P < 0.05). There were significant different prognoses between patients with cystic and solid, mixed tumors (P < 0.05). The prognosis of patients with T type tumors was different from that of patients with either Q or S type tumors (P < 0.05). The prognoses of patients with either loose or tight type tumors were significantly different from those of patients with either invasive or fusion type tumors (P < 0.05). CONCLUSION: Clinical and pathological variables, such as onset symptoms, size of tumor, degree of calcification, consistency, QST classification, and the degree of adhesion strength, were important factors in evaluating the prognosis of patients with craniopharyngiomas.

Viral Nonstructural Protein 1 Induces Mitochondrion-Mediated Apoptosis in Mink Enteritis Virus Infection.

Mink enteritis virus (MEV), an autonomous parvovirus, causes acute hemorrhagic enteritis in minks. The molecular pathogenesis of MEV infection has not been fully understood. In this study, we observed significantly increased apoptosis in the esophagus, small intestine, mesenteric lymph nodes, and kidney in minks experimentally infected with strain MEVB. In vitro infection of feline F81 cells with MEVB decreased cell viability and induced cell cycle arrest at G1 phase and apoptosis. By screening MEV nonstructural proteins (NS1 and NS2) and structural proteins (VP1 and VP2), we demonstrated that the MEV NS1 induced apoptosis in both F81 and human embryonic kidney 293T (HEK293T) cells, similar to that induced during MEV infection in minks. We found that the NS1 protein-induced apoptosis in HEK293T cells was mediated not by the death receptor but by the mitochondrial pathway, as demonstrated by mitochondrial depolarization, opening of mitochondrial transition pore, release of cytochrome c, and activation of caspase-9 and -3. Moreover, in NS1-transfected cells, we observed an increase of Bax expression and its translocation to the mitochondria, as well as an increased ratio of the Bax/Bcl-2, reactive oxygen species (ROS) production, and activated p38 mitogen-activated protein kinase (MAPK) and p53. Taken together, our results demonstrated that MEV induces apoptosis through activation of p38 MAPK and the p53-mediated mitochondrial apoptotic pathway induced by NS1 protein, which sheds light on the molecular pathogenesis of MEV infection.IMPORTANCE MEV causes fatal hemorrhagic enteritis in minks. Apoptosis is a cellular mechanism that effectively sacrifices virus-infected cells to maintain homeostasis between the virus and host. In this study, we demonstrated that MEV induces apoptosis both in vivo and in vitro Mechanistically, the viral large nonstructural protein NS1 activates p38 MAPK, which leads p53 phosphorylation to mediate the mitochondrial apoptotic pathway but not the death receptor-mediated apoptotic pathway. This is the first report to uncover the mechanism underlying MEV-induced apoptosis.

Molecular epidemiology of Aleutian mink disease virus from fecal swab of mink in northeast China.

BACKGROUND: Aleutian mink disease parvovirus (AMDV) causes Aleutian mink disease (AMD), which is a serious infectious disease of mink. The aim of this study was to get a better understanding of the molecular epidemiology of AMDV in northeast China to control and prevent AMD from further spreading. This study for the first time isolated AMDV from fecal swab samples of mink in China. RESULTS: A total of 157/291 (54.0%) of the fecal swab samples were positive for AMDV. Of these, 23 AMDV positive samples were randomly selected for sequence alignment and phylogenetic analysis based on the acquired partial fragments of VP2 gene with the hypervariable region. Comparative DNA sequence analysis of 23 AMDV isolates with a reference nonpathogenic (AMDV-G) strain revealed 8.3% difference in partial VP2 nucleotide sequences. Amino acid alignment indicated the presence of several genetic variants, as well as one single amino acid residue deletion. The most concentrated area of variation was located in the hypervariable region of VP2 protein. According to phylogenetic analysis, the Chinese AMDV strains and the other reference AMDV strains from different countries clustered into three groups (clades A, B and C). Most of the newly sequenced strains were found to form a Chinese-specific group, which solely consisted of Chinese AMDV strains. CONCLUSION: These findings indicated that a high genetic diversity was found in Chinese AMDV strains and the virus distribution were not dependent on geographical origin. Both local and imported AMDV positive species were prevalent in the Chinese mink farming population. The genetic evidence of AMDV variety and epidemic isolates have importance in mink farming practice.

Satellite Estimation of Dissolved Carbon Dioxide Concentrations in China's Lake Taihu.

Lakes play an important role in the global carbon cycle; however, there are still large uncertainties in the estimation of global lake carbon emission due to the limitations in conducting field surveys at large geographic scales. Using long-term Moderate-Resolution Imaging Spectroradiometer (MODIS) imagery and field observation data in eutrophic Lake Taihu, we developed a novel approach to estimate the concentration of dissolved carbon dioxide (cCO2) in lakes. Based on the MODIS-derived chlorophyll-a concentration, lake surface temperature, diffuse attenuation coefficient of photosynthetically active radiation, and photosynthetically active radiation, a spatially explicit cCO2 model was developed using multivariate quadratic polynomial regression (coefficient of determination (R2) = 0.84, root-mean-square error (RMSE) = 11.81 µmol L-1, unbiased percent difference (UPD) = 22.46%). Monte Carlo simulations indicated that the model is stable with relatively small deviations in cCO2 estimates caused by input variables (UPD = 26.14%). MODIS data from 2003 to 2018 showed a significant declining trend (0.42 µmol L-1 yr-1, p < 0.05) in the annual mean cCO2. This was associated with a complex balance between the increasing algae biomass and decreasing external inputs of inorganic carbon, nutrients, and organic matter. The high spatiotemporal variabilities in cCO2 were attributed to river inputs and seasonal changes in temperature and algae biomass. The study shows that satellite remote sensing can play an important role in the field of inland water carbon cycling, providing timely much-needed insights into the drivers of the spatial and temporal changes in dissolved CO2 concentrations in inland waters.

Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation.

BACKGROUND: Traumatic brain injury (TBI) is considered a major burden across the globe affecting both individuals and their families. Therefore, the present study was conducted to determine the protective effect of diphenhydramine (DPM) against TBI in experimental rats. METHODS: The effect of DPM was evaluated on the cerebral edema (CE) and neuronal degeneration after the induction of experimental brain injury in rats. The effect of DPM was also investigated on the inflammatory cytokines, for example, tumor necrosis factor-α and interleukin 1ß and oxidative stress markers, such as malondialdehyde, superoxide dismutase, and glutathione peroxidase. Western blot analysis was used to investigate the effect of DPM on B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3. RESULTS: Results of the study suggest that DPM causes reduction in CE and prevents neuronal degeneration. It also causes reduction in inflammation and oxidative stress in a dose-dependent manner. The level of Bax was found to be elevated, together with reduction in the Bcl-2 level in the DPM-treated group. CONCLUSION: DPM exerts a neuroprotective effect after TBI via the attenuation of oxidative stress, inflammation, and mitochondrial apoptosis pathways.

IL-17F facilitates prostate cancer cell malignant phenotypes via activation of the PI3K/AKT signalling pathway.

Prostate cancer (PCa) is known as one of the most common cancers in men all over the world. Previous studies have identified that the pro-inflammatory mediator interleukin-17F (IL-17F) aggravates the progression of several diseases. However, whether IL-17F plays a role in PCa is still lack of enough exploration. In this study, IL-17F expression was strikingly upregulated in PCa tissues. Treatment of IL-17F promoted cell viability at a dose-dependent manner. Further, functional assays were implemented by treatment of 100 ng/ml of IL-17F. Cell viability, proliferation, migration, invasion and stemness were promoted by 100 ng/ml of IL-17F. IL-17F increased the expression of p-PI3K and p-AKT in PCa cells, indicating that IL-17F might activate the PI3K/AKT signalling pathway in PCa cells. LY294002 (the inhibitor of the PI3K/AKT signalling pathway) could reverse the facilitating effects of IL-17F treatment on PCa cell viability, proliferation, migration, invasion and stemness. Taken together, current study revealed that IL-17F facilitated PCa cell malignant phenotypes via activation of the PI3K/AKT signalling pathway, offering a potential therapeutic target for PCa.

Exosome-derived miR-27a produced by PSC-27 cells contributes to prostate cancer chemoresistance through p53.

Prostate cancer (PCa) is a major malignancy in men. Hitherto that date, surgical or chemical castration is the standard treatment to PCa. Nevertheless, there are still many patients with initial treatment progress to metastatic castration-resistant prostate cancer (mCRPC). There are many effective chemotherapeutic drugs for mCRPC, but the tumors will be resistant to these chemotherapeutic drugs, which is an urgent problem to be solved. Specifically, tumor therapy resistance driven by the pathologically active host stroma has gradually becoming the spotlight of oncotherapy in recent years. The exosome-derived miR-27a plays an important role in PCa cell chemoresistance. However, the functions of miR-27a on PCa developing chemoresistance remain unknown. In the present study, we aimed to construct potential regulatory networks of exosomal miR-27a in PCa chemoresistance. The expression of miR-27a was significantly increased by treatment with cisplatin, doxorubicin (DOX) and docetaxel in PCa tissues. We next co-cultured PCa cells (PC3 cells) with primary prostate fibroblasts (PSC27 cells) to explore the mechanisms of tumor therapy resistance. Further studies delineate that exosome-derived miR-27a produced by PSC-27 cells improved chemoresistance by restraining the expression of P53 gene. Our studies provide a new direction for exploring the effects of PCa tumor microenvironment of chemoresistance.

High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer.

BACKGROUND: Enhanced glycolysis in tumors, known as the Warburg effect, provides the metabolic basis of enhanced cancer cell proliferation and metastasis. The Warburg pathway enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a newly identified key kinase that regulates transcriptional reprogramming and cell proliferation. Here we show the prognostic value of PFKFB4 expression in patients with operable breast cancer. METHODS: PFKFB4 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from 200 patients with histologically proven invasive ductal breast cancer. Kaplan-Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PFKFB4 expression. RESULTS: Kaplan-Meier survival analysis revealed that breast cancer patients with high PFKFB4 expression demonstrated unfavorable disease-free survival (p = 0.008) and overall survival (p = 0.002). PFKFB4 had an hazard ratio (HR) of 7.38 (95% CI 1.69-32.3; p = 0.008) in univariate Cox analysis and retained prognostic power (HR 7.44, 95% CI 1.67-33.2; p = 0.009) when adjusted by tumor size, lymph node status, grade, estrogen receptor status, human epidermal growth factor receptor 2 status and subtype, which indicated PFKFB4 was an independent prognostic factor in breast cancer. CONCLUSIONS: Together, our findings establish the prognostic value of metabolic enzyme PFKFB4 in patients with operable breast cancer.