HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment, and the underlying mechanism has not been fully elucidated. This study aimed to clarify the role and mechanism of Human antigen R (HuR) as a therapeutic target for CRPC progression. METHODS: HuR was knocked out by Cas9 or inhibited by the HuR-specific inhibitor KH-3 in CRPC cell lines and in a mouse xenograft model. The effects of HuR inhibition on tumour cell behaviors and signal transduction were examined by proliferation, transwell, and tumour xenograft assays. Posttranscriptional regulation of BCAT1 by HuR was determined by half-life and RIP assays. RESULTS: HuR knockout attenuated the proliferation, migration, and invasion of PC3 and DU145 cells in vitro and inhibited tumour progression in vivo. Moreover, BCAT1 was a direct target gene of HuR and mediated the oncogenic effect of HuR on CRPC. Mechanistically, HuR directly interacted with BCAT1 mRNA and upregulated BCAT1 expression by increasing the stability and translation of BCAT1, which activated ERK5 signalling. Additionally, the HuR-specific inhibitor KH-3 attenuated CRPC progression by disrupting the HuR-BCAT1 interaction. CONCLUSIONS: We confirmed that the HuR/BCAT1 axis plays a crucial role in CRPC progression and suggest that inhibiting the HuR/BCAT1 axis is a promising therapeutic approach for suppressing CRPC progression.

Comparison and Evaluation of Two Combination Modes of Angiotensin for Establishing Murine Aortic Dissection Models.

Aortic dissection (AD) is a potentially fatal cardiovascular emergency caused by separation of different layers of aortic wall. However, because of limited time window available for clinical research, there is an urgent need for an ideal animal research model. In recent years, the incidence of AD complicated by atherosclerosis has increased with improvements of living standards and changes of eating habits. Accordingly, considering multiple risk factors, we successfully and efficiently established a novel AD model through a high-fat diet combined with chronic angiotensin II (AngII) infusion. Compared with traditional chemical induction model using AngII and ß-aminopropionitrile, our model is more clinically relevant for atherosclerosis-related AD. Moreover, infiltration of neutrophils and apoptosis of vascular smooth muscle cells in AD tissues were more significant. In addition to enriching the existing models, the novel model may be a long-term useful tool for more in-depth investigation of AD mechanisms and preclinical therapeutic developments.

Change and challenge: An online course in Medical Biochemistry and Molecular Biology.

The development of information technology and portable devices has sparked a revolution in the field of education, facilitating access to diverse educational resources and lifelong learning. In particular, the COVID-19 pandemic has accelerated the transition from face-to-face to distance teaching, which requires online education to be provided worldwide. Biochemistry and Molecular Biology are key basic medical courses in laboratory-based science that cover complicated theories and applications. The balance between traditional and online courses, and the effectiveness of online courses, are fundamental to the teaching quality of Biochemistry and Molecular Biology. In this study, we explored the concepts, designs, and practices of a new blended online course and identified potential challenges. We hope that our experiences will provide new ideas for online teaching and promote teaching reform and the development of Medical Biochemistry and Molecular Biology education.

Evaluation of the health risk using multi-pollutant air quality health index: case study in Tianjin, China.

Introduction: Air pollution imposes a significant burden on public health. Compared with the popular air quality index (AQI), the air quality health index (AQHI) provides a more comprehensive approach to measuring mixtures of air pollutants and is suitable for overall assessments of the short-term health effects of such mixtures. Methods: We established an AQHI and cumulative risk index (CRI)-AQHI for Tianjin using single-and multi-pollutant models, respectively, as well as environmental, meteorological, and daily mortality data of residents in Tianjin between 2018 and 2020. Results and discussion: Compared with the AQI, the AQHI and CRI-AQHI established herein correlated more closely with the exposure-response relationships of the total mortality effects on residents. For each increase in the interquartile range of the AQHI, CRI-AQHI and AQI, the total daily mortality rates increased by 2.06, 1.69 and 0.62%, respectively. The AQHI and CRI-AQHI predicted daily mortality rate of residents more effectively than the AQI, and the correlations of AQHI and CRI-AQHI with health were similar. Our AQHI of Tianjin was used to establish specific (S)-AQHIs for different disease groups. The results showed that all measured air pollutants had the greatest impact on the health of persons with chronic respiratory diseases, followed by lung cancer, and cardiovascular and cerebrovascular diseases. The AQHI of Tianjin established in this study was accurate and dependable for assessing short-term health risks of air pollution in Tianjin, and the established S-AQHI can be used to separately assess health risks among different disease groups.

Determination of 25 quaternary ammonium compounds in sludge by liquid chromatography-mass spectrometry.

With the pandemic of COVID-19, the application of quaternary ammonium compounds (QACs), which can be used in SARS-CoV-2 disinfection products, has increased substantially. QACs cumulated in sewer system are ultimately deposited and enriched in sludge. QACs in the environment can adversely affect human health and the environment. In this study, a liquid chromatography-mass spectrometry method was established for the simultaneous determination of 25 QACs in sludge samples. Ultrasonic extraction and filtration of the samples was performed using a 50 mM hydrochloric acid-methanol solution. The samples were separated by liquid chromatography and detected in multiple reaction monitoring mode. The matrix effects of the sludge on the 25 QACs ranged from - 25.5% to 7.2%. All substances showed good linearity in the range of 0.5-100 ng/mL, with all determination coefficients (R2) greater than 0.999. The method detection limits (MDLs) were 9.0 ng/g for alkyltrimethylammonium chloride (ATMAC), 3.0 ng/g for benzylalkyldimethylammonium chloride (BAC), and 3.0 ng/g for dialkyldimethylammonium chloride (DADMAC). The spiked recovery rates were in the range of 74-107%, while the relative standard deviations were in the range of 0.8-20.6%. Considering its sensitivity, accuracy, and easy operation, the proposed method in this study was used to determine 22 sludge samples collected from a comprehensive wastewater treatment plant. The results showed that the concentrations of ΣATMACs, ΣBACs, and ΣDADMACs were 19.684, 3.199, and 8.344 µg/g, respectively. The main components included ATMAC-C16, ATMAC-C18, ATMAC-C20, ATMAC-C22, BAC-C12, and DADMAC-C18:C18, with concentrations exceeding 1.0 µg/g. The concentration relationships of different components in the congeners showed that some components were of similar origin.

MiR-216a-3p inhibits the proliferation and invasion of fibroblast-like synoviocytes by targeting dual-specificity phosphatase 5.

Dual-specificity phosphatase 5 (DUSP5) is a novel anti-inflammatory modulator in many inflammatory diseases. However, the role of DUSP5 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) remains unknown. In this study, we aimed to explore the biological function and regulation of DUSP5 in FLS. We found that lower DUSP5 expression level was detected in collagen-induced arthritis (CIA) and synoviocyte MH7A. Overexpression of DUSP5 markedly decreased the proliferation, migration, and invasion of MH7A, which correlated with suppressing the phosphorylation of extracellular signal-regulated kinase (ERK). Moreover, DUSP5 was identified as a novel target gene of miR-216a-3p, which was upregulated in FLS. Therefore, DUSP5 expression was negatively regulated by miR-216a-3p, and the effect of DUSP5 overexpression on FLS was reversed by miR-216a-3p mimics. Overall, our study demonstrates that DUSP5 is a miR-216a-3p target gene and its anti-inflammatory function in FLS via inactivation of ERK. These results revealed that the miR-216a-3p/DUSP5 pathway may play a crucial role in the malignant behavior of FLS, which may serve as a new target for the treatment of RA.

Structural characterization and immunomodulatory activity of an arabinogalactan from Jasminum sambac (L.) Aiton tea processing waste.

An arabinogalactan named JSP-1a was isolated from Jasmine tea processing waste by DEAE Sepharose FF and Sephacryl S-200 HR chromatography. Polysaccharide JSP-1a, with an average molecular weight of 87.5 kDa, was composed of galactose (59.60 %), arabinose (33.89 %), mannose (4.81 %), and rhamnose (1.70 %). JSP-1a was found to be a type II arabinogalactan comprising the main backbone of 1, 6-linked Galp residues, and the side chain containing α-T-Araf, α-1,5-Araf, ß-T-Galp, ß-1,3-Galp, and ß-1,4-Manp residues was attached to the O-3 position of ß-1,3,6-Galp residues. Evidence from bioactivity assays indicated that JSP-1a possessed potent immunomodulatory effects on RAW264.7 macrophages: treatment with JSP-1a increased phagocytosis, activated NF-κB p65 translocation, and promoted the production of NO, reactive oxygen species (ROS), the tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Furthermore, inhibition of Toll-like receptor 4 caused the suppression of NO release and cytokines secretion, which indicated that TLR-4/NF-κB pathway might play a significant role in JSP-1a-induced macrophages' immune response. The results of this study could provide a theoretical basis of JSP-1a as a safe immunostimulatory functional foods or a treatment for immunological diseases.

Single-cell transcriptomics provides insights into the origin and microenvironment of human oesophageal high-grade intraepithelial neoplasia.

BACKGROUND: High-grade intraepithelial neoplasia (HIN) is the precursor of oesophageal squamous cell carcinoma. The molecular and functional properties of HIN are determined by intrinsic origin cells and the extrinsic microenvironment. Yet, these factors are poorly understood. METHODS: We performed single-cell RNA sequencing of cells from HINs and adjacent tissues from the human oesophagus. We analysed the heterogeneity of basal layer cells and confirmed it using immunostaining. Aneuploid cells in HIN were studied using primary cell culture combined with karyotype analysis. We reconstructed the lineage relationship between tumour and normal populations based on transcriptome similarity. Integration analysis was applied to our epithelial data and published invasive cancer data, and results were confirmed by immunostaining and 3D organoid functional experiments. We also analysed the tumour microenvironment of HIN. RESULTS: The basal layer contained two cell populations: KRT15high STMN1low and KRT15high STMN1high cells, which were located mainly in the interpapillary and papillary zones, respectively. The KRT15high STMN1low population more closely resembled stem cells and transcriptome similarity revealed that HIN probably originated from these slow-cycling KRT15high STMN1low cells. 3D Organoid experiments and RNA-sequencing showed that basal-cell features and the differentiation ability of the normal epithelium were largely retained in HIN, but may change dramatically in tumour invasion stage. Moreover, the tumour microenvironment of HIN was characterised by both inflammation and immunosuppression. CONCLUSIONS: Our study provides a comprehensive single-cell transcriptome landscape of human oesophageal HIN. Our findings on the origin cells and unique microenvironment of HIN will allow for the development of strategies to block tumour progression and even prevent cancer initiation.

Glutamate blunts cell-killing effects of neutrophils in tumor microenvironment.

Neutrophils are the first defenders of the innate system for injury and infection. They have gradually been recognized as important participants in tumor initiation and development due to their heterogeneity and plasticity. In the tumor microenvironment (TME), neutrophils can exert antitumor and protumor functions, depending on the surroundings. Tumor cells systemically alter intracellular amino acid (AA) metabolism and extracellular AA distribution to meet their proliferation need, leading to metabolic reprogramming and TME reshaping. However, the underlying mechanisms that determine how altered AAs affect neutrophils in TME are less-explored. Here, we identified that abundant glutamate releasing from tumor cells blunted neutrophils' cell-killing effects toward tumor cells in vitro and in vivo. Mass spectrometric detection, flow cytometry, and western blot experiments proved that increased levels of pSTAT3/RAB10/ARF4, mediated by glutamate, were accompanied with immunosuppressive phenotypes of neutrophils in TME. We also discovered that riluzole, an FDA-approved glutamate release inhibitor, significantly inhibited tumor growth by restoring neutrophils' cell-killing effects and decreasing glutamate secretion from tumor cells. These findings highlight the importance of tumor-released glutamate on neutrophil transformation in TME, providing new possible cancer treatments targeting altered glutamate metabolism.

A precise self-built secondary mass database for identifying red dyes and dyeing techniques with UPLC-MS/MS.

Dyes on ancient silks have been a worth studying field through human's history, although current reports ignore the connection between natural dyes origin and relevant colour reduction methods, which poses an insurmountable obstacle for restoration of historical silks. In this paper, a series of 12 red hue silks from six natural dyes (sappanwood, Chinese madder, safflower, lac, cochineal, dragon's blood) via three different dyeing techniques were used to establish a self-built precise tandem mass spectrometry (MS/MS) database. With organic solvent extracting on those manual-dyed silks, ultraperformance liquid chromatography - electrospray ionization - quadrupole time of flight mass spectrometry (UPLC-ESI-QTOF-MS) was utilized to form preliminary MS database for screening and identifying of the potential dyes compounds without standard references. Furthermore, combining the targeted MS/MS mode and the matching threshold of 70.00, a self-built secondary MS/MS database was successfully established, which contains 33 compounds, 32 chromatograms and 32 MS/MS fragments. As for real sample application, the self-built precise MS/MS database had revealed that the dyes on two historical silks (Shanghai Museum, China) belong to Chinese madder just with different mordant dyeing ordinal. Additionally, by experimental restoration, visually indistinguishable silks (ΔEab * < 1.5 NBS) were successfully restored. This explorative methodology can further inspire the traceability of biological dyestuffs, which lays instructive foundation on protection and restoration of artefacts, connecting the archaeological science and human art.

Comparing the effect of a consult model versus an integrated palliative care and medical oncology co-rounding model on health care utilization in an acute hospital - an open-label stepped-wedge cluster-randomized trial.

BACKGROUND: The benefit of specialist palliative care for cancer inpatients is established, but the best method to deliver specialist palliative care is unknown. AIM: To compare a consult model versus a co-rounding model; both provide the same content of specialist palliative care to individual patients but differ in the level of integration between palliative care and oncology clinicians. DESIGN: An open-label, cluster-randomized trial with stepped-wedge design. The primary outcome was hospital length of stay; secondary outcomes were 30-day readmissions and access to specialist palliative care. ClinicalTrials.gov number NCT03330509. SETTING/PARTICIPANTS: Cancer patients admitted to the oncology inpatient service of an acute hospital in Singapore. RESULTS: A total of 5681 admissions from December 2017 to July 2019 were included, of which 5295 involved stage 3-4 cancer and 1221 received specialist palliative care review. Admissions in the co-rounding model had a shorter hospital length of stay than those in the consult model by 0.70 days (95%CI -0.04 to 1.45, p = 0.065) for all admissions. In the sub-group of stage 3-4 cancer patients, the length of stay was 0.85 days shorter (95%CI 0.05-1.65, p = 0.038). In the sub-group of admissions that received specialist palliative care review, the length of stay was 2.62 days shorter (95%CI 0.63-4.61, p = 0.010). Hospital readmission within 30 days (OR1.03, 95%CI 0.79-1.35, p = 0.822) and access to specialist palliative care (OR1.19, 95%CI 0.90-1.58, p = 0.215) were similar between the consult and co-rounding models. CONCLUSIONS: The co-rounding model was associated with a shorter hospital length of stay. Readmissions within 30 days and access to specialist palliative care were similar.

Decreased phosphorylation facilitates the degradation of the endogenous protective molecule c-Ski in vascular smooth muscle cells.

The dysfunction of vascular smooth muscle cells (VSMCs) is critical for atherosclerosis (AS) progression. Autophagy is indispensable during phenotypic switching and proliferation of VSMCs, contribute to AS development. Cellular Sloan-Kettering Institute (c-Ski), the repressor of TGF-ß signaling, is involved in diverse physiological and pathological processes. We previously defined c-Ski also as an endogenous protective molecule against AS via inhibiting abnormal proliferation and autophagy of VSMCs. However, the endogenous level of c-Ski in VSMCs is markedly decreased during the progression of AS, so that the protective effect is drastically weakened. Elucidating the molecular mechanisms is key to the understanding of AS development and treatment. We determined that oxidized low-density lipoprotein (ox-LDL) and platelet-derived growth factor (PDGF) directly induced the degradation of c-Ski protein, closely associated with reducing its phosphorylation. Serine383 (S383) was identified as the crucial phosphorylation site for stabilizing protein expression and nuclear location of c-Ski, which was responsible for its transcriptional suppression of autophagy-related genes. Decreased S383 phosphorylation facilitated nuclear export and degradation of c-Ski, thereby lessened its inhibitory effect on induction of autophagy genes. These findings provide a novel view of c-Ski modification and function modulation under some vascular injury factors, which point to a new potential therapeutic strategy by targeting c-Ski.

Multiple-fingerprint analysis of Poria cocos polysaccharide by HPLC combined with chemometrics methods.

In this study, the multiple fingerprints, which were integrated with HPGFC-ELSD (high performance gel filtration chromatography - evaporative light scattering detector) fingerprint, PMP-HPLC-DAD (1-phenyl-3-methyl-5-pyrazolone-high performance liquid chromatography - diode array detector) fingerprint of complete acid hydrolysates and HILIC-HPLC-ELSD (hydrophilic interaction - high performance liquid chromatography - evaporative light scattering detector) fingerprint of enzyme hydrolysates, were established to evaluate the quality of polysaccharides from Poria cocos (PCPs). The similarity evaluation showed that 16 batches of PCPs from different origins had high similarity in structural characteristics based on the multiple fingerprints. The chromatographic data of multiple fingerprints of PCPs were fused, processed and analyzed by chemometric methods including HCA (hierarchical cluster analysis), PCA (principal component analysis) and PLS-DA (partial least squares discriminant analysis). The 16 batches of PCPs were divided into 3 categories in PCA, indicating a certain relationship between the structural characteristics and the origins. PLS-DA analysis indicated that Man, Glc, Gal, Fuc, the components with m/z of 2.22 × 104∼1.53 × 104 Da and 3.46 × 103∼2.69 × 103 Da, oligosaccharides with DPs of 6 and 7, respectively, could be regarded as potential chemical markers for the classification of PCPs from different origins. According to the multiple fingerprints and chemometric analysis, the two commercial samples were proved to be adulterants.

Structure characteristics, hypoglycemic and immunomodulatory activities of pectic polysaccharides from Rosa setate x Rosa rugosa waste.

In this study, two polysaccharide components named WSRP-2a and WSRP-2b, were purified from Rosa setate x Rosa rugosa waste via anion exchange and gel filtration chromatography. Monosaccharide composition, Congo red assay, FT-IR and NMR spectra analysis confirmed that both of these fractions were mainly composed of galacturonic acid, arabinose, galactose and rhamnose, which were pectin-type polysaccharides with non-triple-helix structure. WSRP-2a and WSRP-2b, however, differed in molecular weight of 56.8 kD and 23.9 kD. The followed bioassay presented their impressive hypoglycemic and immunomodulatory activities. WSRP-2a promoted more proliferation, NO release, and the secretion of cytokines in RAW264.7 macrophages, while WSRP-2b presented higher α-amylase and α-glucosidase inhibitory activities. Collectively, these results suggested that the Rosa Setate x Rosa Rugosa waste biomass could be used as a promising source of bioactive pectic polysaccharides.

LncRNA-H19 silencing suppresses synoviocytes proliferation and attenuates collagen-induced arthritis progression by modulating miR-124a.

OBJECTIVES: Long non-coding RNA H19 (lncRNA-H19) is highly expressed in fibroblast-like synoviocytes (FLS) from patients with RA. The present study aimed to clarify the pathological significance and regulatory mechanisms of lncRNA-H19 in FLS. METHODS: Mice with CIA were locally injected with LV-shH19. The progression of CIA was explored by measuring arthritic index (AI), paw thickness (PT) and histologic analysis. The growth and cell cycle of human synoviocyte MH7A were assessed by CCK-8 and flow cytometric analysis. The putative binding sites between lncRNA-H19 and miR-124a were predicted online, and the binding was identified by luciferase assay. RT-qPCR, Western blot and luciferase assay were performed to explore the molecular mechanisms between liver X receptor (LXR), lncRNA-H19, miR-124a and its target genes. RESULTS: The expression of lncRNA-H19 was closely associated with the proliferation of synoviocytes and knockdown of lncRNA-H19 significantly ameliorated the progression of CIA, reflected by decreased AI, PT and cartilage destruction. Notably, lncRNA-H19 competitively bound to miR-124a, which directly targets CDK2 and MCP-1. It was confirmed that lncRNA-H19 regulates the proliferation of synoviocytes by acting as a sponge of miR-124a to modulate CDK2 and MCP-1 expression. Furthermore, the agonists of LXR inhibited lncRNA-H19-mediated miR-124a-CDK2/MCP-1 signalling pathway in synoviocytes. The 'lncRNA-H19-miR-124a-CDK2/MCP-1' axis plays an important role in LXR anti-arthritis. CONCLUSION: Regulation of the miR-124a-CDK2/MCP-1 pathway by lncRNA-H19 plays a crucial role in the proliferation of FLS. Targeting this axis has therapeutic potential in the treatment of RA and may represent a novel strategy for RA treatment.

Enhanced thermotolerance of Arabidopsis by chitooligosaccharides-induced CERK1n-ERc fusion gene.

Heat stress is a major growth-limiting factor for most crops over the world. Chitin elicitor receptor kinase 1 (CERK1) is a chitin/chitooligosaccharides receptor, and ERECTA (ER) plays a crucial role in plant resistance to heat stress. In the present study, a chitooligosaccharides-induced CERK1n-ERc fusion gene was designed and synthesized, in which the extracellular domain and transmembrane domain of CERK1 gene is connected with the response region of ER gene. We successfully constructed the CERK1n-ERc fusion gene by Overlap PCR and introduced it into Arabidopsis by Agrobacterium-medicated infection. Genetically modified (GM) plants had a greater germination rate and germination index, as well as a shorter mean germination time, indicating that they had a better thermotolerance compared with the wild-type (WT) lines under heat stress. Moreover, the GM lines showed a lower level of hydrogen peroxide (H2O2) and relative electrolyte leakage (REL), suggesting that they were in better state compared with the WT plants when exposed to high temperature. UPLC-MS/MS was employed to assess the phytohormone level, suggesting that the GM lines acquired a better thermotolerance via jasmonic acid (JA) signaling pathways. In general, we constructed a COS-induced fusion gene to enhance the thermotolerance of Arabidopsis during seed germination and postgermination growth.

Liver X receptor inhibits the growth of hepatocellular carcinoma cells via regulating HULC/miR-134-5p/FOXM1 axis.

Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high rate of mortality. Highly upregulated in liver cancer (HULC), the specifically overexpressed long non-coding RNA in human HCC, plays important roles in promoting the growth and metastasis of HCC cells. So downregulating HULC will be benefit to HCC treatment. The nuclear receptor LXR (liver X receptor), consist of α and ß isoforms, exerts significant anti-HCC effects, but the corresponding mechanisms are not well known, especially, it's unclear whether LXR is involved in the regulation of HULC. In this study, we found that LXR inhibited HCC cell growth by downregulating HULC, and LXRα (but not LXRß) caused HULC downregulation. Luciferase reporter assays showed that LXR suppressed transcriptional activity of HULC gene promoter, and chromatin immunoprecipitation assays revealed that LXRα (but not LXRß) bound to HULC promoter region. Furthermore, LXR increased miR-134-5p while decreased FOXM1 by reducing HULC. Additionally, HULC upregulated FOXM1 via sequestrating miR-134-5p, and miR-134-5p downregulated FOXM1 by targeting 3'-UTR of its mRNA. The in vivo experiments showed that LXR repressed the growth of HCC xenografts, and decreased HULC and FOXM1 while increased miR-134-5p in the xenografts. In summary, these findings for the first time demonstrate that LXR inhibits HCC cell growth by modulating HULC/miR-134-5p/FOXM1 axis, suggesting that the pathway LXR/HULC/miR-134-5p/FOXM1 may serve as a novel target for HCC treatment.

Structural elucidation and immunomodulatory activity of a neutral polysaccharide from the Kushui Rose (Rosa setate x Rosa rugosa) waste.

In this present study, the structure and immunomodulatory activity of a novel polysaccharide (WSRP-1b) from Kushui rose (Rosa setate x Rosa rugosa) waste were investigated. Structure characterization demonstrated that WSRP-1b had a weight-average molecular weight of 1.11 × 104 Da and consisted of glucose (42.6 %), mannose (21.4 %), arabinose (9.9 %), xylose (2.2 %), and galactose (23.9 %). Its backbone was composed of 1, 4-linked α-Glcp, 1, 4-linked ß-Glcp, and 1, 4-linked ß-Manp, with branches of 1, 4-linked α-Glcp and 1, 4-linked ß-Manp substituted at C-6 by 1, 6-linked ß-Galp. The branches mainly contained 1, 5-linked Araf, terminal arabinose and terminal glucose. Bioactivity assays showed that WSRP-1b had immunomodulatory activity by enhancing phagocytosis of macrophages, increasing production of ROS, NO, cytokines (IL-6, TNF-α), and activating NF-κB signaling pathway. These results suggested that it could be developed as a potential and safe immunomodulatory agent in fields of pharmacological or functional foods.

Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells.

Aim: Liver cancer is one of the most common malignancies and has a high recurrence rate. However, current treatment strategies do not achieve satisfactory outcomes in the clinic. To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer, we investigated whether dichloroacetate (DCA) could enhance the sensitivity of liver cancer cells to pirarubicin (THP). Methods: Liver cancer cells were treated with DCA alone, THP alone, or DCA and THP combined. Cell viability was determined by the CCK-8 assay. Cell apoptosis was analyzed by flow cytometer. Reactive oxygen species (ROS) were detected using a CM-H2DCFDA fluorescence probe. Protein levels were identified by immunoblotting. Results: The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells. Changes in morphology and adherence ability were observed, as well as decreased cell viability. The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells. Moreover, compared with THP alone, combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells. The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation, cell viability and apoptosis. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was significantly increased in the DCA and THP combination group. The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125. Conclusion: The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway.

Sampling and analysis of airborne ammonia in workplaces of China.

OBJECTIVES: With the increasing demand for the detection of occupational hazard factors in workplaces, the national standard determination method for ammonia (sampling with absorbing solution-analysis with Nessler reagent spectrophotometry) in the air of workplace presents many drawbacks during application in China. This review summarized the improvement and the alternate methods of the current sampling and analysis procedures for ammonia, aiming to provide reference to establish an appropriate method for the determination of ammonia in workplace air. METHODS: Scientific publications in English and Chinese and the standard methods of the Deutsche Forschungsgemeinschaft (DFG) in Germany, the National Institute for Occupational Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) in the United States, and Ministry of Health in China for airborne ammonia collection and analysis in the workplace were reviewed. RESULTS: The measures to improve the current sampling and analysis procedures for ammonia in China were firstly summarized. For sampling, the decrease of absorbing solution concentration and the methanesulfonic acid solution as the alternate sampling solution were suggested. For analysis, the anti-interference measures and the optimum reaction condition between ammonia and Nessler reagent were discussed. The alternate methods including sampling conducted using solid sorbent tubes and analysis performed by ion chromatography were then considered for the determination of ammonia. CONCLUSIONS: The methods-sampling with acid-treated solid sorbent tubes and analysis with ion chromatography-were more suitable for the determination of ammonia in workplace air. However, some details about ammonia sampling and analysis still need further investigation.