Development of flow battery technologies using the principles of sustainable chemistry.

Realizing decarbonization and sustainable energy supply by the integration of variable renewable energies has become an important direction for energy development. Flow batteries (FBs) are currently one of the most promising technologies for large-scale energy storage. This review aims to provide a comprehensive analysis of the state-of-the-art progress in FBs from the new perspectives of technological and environmental sustainability, thus guiding the future development of FB technologies. More importantly, we evaluate the current situation and future development of key materials with key aspects of green economy and decarbonization to promote sustainable development and improve the novel energy framework. Finally, we present an analysis of the current challenges and prospects on how to effectively construct low-carbon and sustainable FB materials in the future.

Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.

Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P. pastoris, and examined the impact of antioxidants on HSA-hIL-22 production. We have achieved the production of HSA-hIL-22 in the culture medium at a yield of approximately 2.25 mg/ml. Moreover, 0-40 mM ascorbic acid supplementation did not significantly affect HSA-hIL-22 production or the growth rate of the recombinant strain. However, 80 mM ascorbic acid treatment had a detrimental effect on the expression of HSA-hIL-22. In addition, 5-10 mM N-acetyl-l-cysteine (NAC) resulted in an increase of HSA-hIL-22 production, accompanied by a reduction in the growth rate of the recombinant strain. Conversely, 20-80 mM NAC supplementation inhibited the growth of the recombinant strains and reduced intact HSA-hIL-22 production. However, neither NAC nor ascorbic acid exhibited any effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, except that NAC increased GSH content. Furthermore, our findings indicate that recombinant HSA-hIL-22, which demonstrated the ability to stimulate the proliferation of HepG2 cells, possesses bioactivity. In addition, NAC did not affect HSA-hIL-22 bioactivity. In conclusion, our study demonstrates that NAC supplementation can enhance the secretion of functional HSA-hIL-22 proteins produced in P. pastoris without compromising their activity.

ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Spectasterols, Aromatic Ergosterols with 6/6/6/5/5, 6/6/6/6, and 6/6/6/5 Ring Systems from Aspergillus spectabilis.

Spectasterols A-E (1-5), aromatic ergosterols with unique ring systems, were isolated from Aspergillus spectabilis. Compounds 1 and 2 possess a 6/6/6/5/5 ring system with an additional cyclopentene, while 3 and 4 have an uncommon 6/6/6/6 ring system generated by the D-ring expansion via 1,2-alkyl shifts. Compound 3 exhibited cytotoxic activity (IC50 6.9 µM) and induced cell cycle arrest and apoptosis in HL60 cells. Compound 3 was anti-inflammatory; it decreased COX-2 levels at the transcription and protein levels and inhibited the nuclear translocation of NF-κB p65.

Surgical outcomes of laparoscopic proximal gastrectomy for upper-third gastric cancer: esophagogastrostomy, gastric tube reconstruction, and double-tract reconstruction.

BACKGROUND: There is no consensus on the optimal reconstruction technique after proximal gastrectomy. The purpose of this study was to retrospectively compare the surgical outcomes among esophagogastrostomy (EG) anastomosis, gastric tube (GT) reconstruction and double-tract (DT) reconstruction in patients who underwent laparoscopic proximal gastrectomy (LPG) to clarify the superior reconstruction method. METHODS: This study enrolled 164 patients who underwent LPG at the Northern Jiangsu People's Hospital in Jiangsu between January 2017 to January 2022 (EG: 51 patients; GT: 77 patients; DT: 36 patients). We compared the clinical and pathological characteristics, surgical features, postoperative complications, nutritional status, and quality of life (QOL) among the above three groups. RESULTS: Mean operative time was longer with the DT group than the remaining two groups (p = 0.001). With regard to postoperative complications, considerable differences in the postoperative reflux symptoms (p = 0.042) and reflux esophagitis (p = 0.040) among the three groups were found. For the nutritional status, total protein, hemoglobin and albumin reduction rates in the GT group were significantly higher than the other two groups at 12 months postoperatively. In the PGSAS-45, three assessment items were better in the DT group significantly compared with the esophageal reflux subscale (p = 0.047, Cohen's d = 0.44), dissatisfaction at the meal (p = 0.009, Cohen's d = 0.58), and dissatisfaction for daily life subscale (p = 0.012, Cohen's d = 0.56). CONCLUSIONS: DT after LPG is a valuable reconstruction technique with satisfactory surgical outcomes, especially regarding reduced reflux symptoms, improving the postoperative nutritional status and QOL.

PVA/Tween 20 thin-film-based fiber optic humidity sensor with enhanced sensing performance.

A fiber optic humidity sensor based on polyvinyl alcohol (PVA)/Tween 20 film has been fabricated by modulating the intensity of light transmitted in optical fiber. PVA/Tween 20 film was used as the cladding and humidity-sensitive material of optical fiber. The logarithmic of output light intensity exhibited a linear increase with the increase of humidity (22%-82%RH). With the addition of Tween 20 in the formation of film, average sensitivity increased by 13-fold. Fast equilibrium on adsorption and desorption of water molecules were also achieved on the film. The response and recovery times were determined to be 11 s and 9 s, respectively. Moreover, the sensor possesses good repeatability. The sensing mechanism was probably based on the swelling of PVA after adsorbing water molecules, which affected scattering of evanescent waves in the cladding. The output light intensity varied with the decay of evanescent waves.

Fiber optic evanescent wave humidity sensor based on SiO2/TiO2 bilayer films.

A SiO2/TiO2 bilayer thin-film-based fiber optic humidity sensor was fabricated via a modified dip coating process with enhanced sensitivity. SiO2 film was coated on the surface of the fiber core, followed by deposition of the TiO2 layer on SiO2. The relative humidity (RH) is measured by modulation in intensity of the transmitted laser at room temperature. The optical fiber humidity sensor based on SiO2/TiO2 film shows two-segmented linearity in measurement with sensitivities of 5.35 and 1.94 µW/% RH at 15%-50% RH and 50%-95% RH, respectively. The response time and recovery time are 25 s and 50 s, respectively. To our knowledge, the superior response time and recovery time of the sensor in our study were achieved over those fiber optic humidity sensors reported with modulation in intensity. Furthermore, this fiber optic humidity sensor has a good reproducibility and long-term stability. The sensing mechanism is attributed to effects of moisture on the refractive index and the light absorption coefficient of SiO2 film and modulation in the transmission characteristic of evanescent waves in the optical fiber.

CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is aggressive with limited treatment options upon recurrence. Molecular discordance between primary and metastatic TNBC has been observed, but the degree of biological heterogeneity has not been fully explored. Furthermore, genomic evolution through treatment is poorly understood. In this study, we aim to characterize the genomic changes between paired primary and metastatic TNBCs through transcriptomic and genomic profiling, and to identify genomic alterations which may contribute to chemotherapy resistance. METHODS: Genomic alterations and mRNA expression of 10 paired primary and metastatic TNBCs were determined through targeted sequencing, microarray analysis, and RNA sequencing. Commonly mutated genes, as well as differentially expressed and co-expressed genes were identified. We further explored the clinical relevance of differentially expressed genes between primary and metastatic tumors to patient survival using large public datasets. RESULTS: Through gene expression profiling, we observed a shift in TNBC subtype classifications between primary and metastatic TNBCs. A panel of eight cancer driver genes (CCNE1, TPX2, ELF3, FANCL, JAK2, GSK3B, CEP76, and SYK) were differentially expressed in recurrent TNBCs, and were also overexpressed in TCGA and METABRIC. CCNE1 and TPX2 were co-overexpressed in TNBCs. DNA mutation profiling showed that multiple mutations occurred in genes comprising a number of potentially targetable pathways including PI3K/AKT/mTOR, RAS/MAPK, cell cycle, and growth factor receptor signaling, reaffirming the wide heterogeneity of mechanisms driving TNBC. CCNE1 amplification was associated with poor overall survival in patients with metastatic TNBC. CONCLUSIONS: CCNE1 amplification may confer resistance to chemotherapy and is associated with poor overall survival in TNBC.

Ultra-smooth TiO2 thin film based optical humidity sensor with a fast response and recovery.

An ultra-smooth $\text{TiO}_2$TiO2 thin film based optical humidity sensor was fabricated via a modified dip coating process. The $\text{TiO}_2$TiO2 film possessed a root mean square roughness of ${2.6 \pm 0.3}\;\text{nm}$2.6±0.3nm. Measurement of relative humidity (RH) was performed by modulation in the intensity of laser transmitted at room temperature. The optical humidity sensor based on $\text{TiO}_2$TiO2 film exhibited two-segmented linearity in the whole RH range. The response time and recovery time were determined to be 27 s and 23 s, respectively. To our knowledge, the optical humidity sensor achieved the fastest recovery to date among those modulated in optical power. The fast response and recovery are attributed to the smooth surface of sensing film, which allows the rapid equilibrium between adsorption and desorption of water molecules on the film surface. In addition, this optical humidity sensor possessed an excellent reproducibility and long-term stability after aging. The sensing mechanism is based on the chemisorption of water molecules in the low RH range and formation of water droplets in the high RH range on the surface of ${\text{TiO}_2}$TiO2 film.

Early and multiple origins of metastatic lineages within primary tumors.

Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases.

Weipiling ameliorates gastric precancerous lesions in Atp4a-/- mice.

BACKGROUND: Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4-17, 2014; Kim and Bae, Curr Opin Hematol 25:52-59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. METHODS: Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a-/- mouse model (Spicer etal., J Biol Chem 275:21555-21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a-/-mice. RESULTS: In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a-/- mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). CONCLUSIONS: Conclusively, WPL could ameliorate GPLs in Atp4a-/- mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.

Detection of Regional Variation in Selection Intensity within Protein-Coding Genes Using DNA Sequence Polymorphism and Divergence.

Numerous approaches have been developed to infer natural selection based on the comparison of polymorphism within species and divergence between species. These methods are especially powerful for the detection of uniform selection operating across a gene. However, empirical analyses have demonstrated that regions of protein-coding genes exhibiting clusters of amino acid substitutions are subject to different levels of selection relative to other regions of the same gene. To quantify this heterogeneity of selection within coding sequences, we developed Model Averaged Site Selection via Poisson Random Field (MASS-PRF). MASS-PRF identifies an ensemble of intragenic clustering models for polymorphic and divergent sites. This ensemble of models is used within the Poisson Random Field framework to estimate selection intensity on a site-by-site basis. Using simulations, we demonstrate that MASS-PRF has high power to detect clusters of amino acid variants in small genic regions, can reliably estimate the probability of a variant occurring at each nucleotide site in sequence data and is robust to historical demographic trends and recombination. We applied MASS-PRF to human gene polymorphism derived from the 1,000 Genomes Project and divergence data from the common chimpanzee. On the basis of this analysis, we discovered striking regional variation in selection intensity, indicative of positive or negative selection, in well-defined domains of genes that have previously been associated with neurological processing, immunity, and reproduction. We suggest that amino acid-altering substitutions within these regions likely are or have been selectively advantageous in the human lineage, playing important roles in protein function.

Receptor for Advanced Glycation End-Products (RAGE) Blockade Do Damage to Neuronal Survival via Disrupting Wnt/ß-Catenin Signaling in Spinal Cord Injury.

Wnt signaling are recognized key factors in neuronal development, cell proliferation and axonal guidance. However, RAGE effect on wnt signaling after spinal cord injury (SCI) are poorly understood. Our study aims to explore RAGE blockade effect on wnt signaling after SCI. We constructed Allen SCI model and micro-injected with RAGE neutralizing antibody or IgG after injury. We determined ß-catenin, wnt3a and its receptor frizzled-5 via Western blot. We determined ß-catenin/NeuN expression at 2 weeks after SCI via immunofluorescence (IF). We found that ß-catenin, wnt3a and wnt receptor frizzled5 expression were activated after SCI at 3 days after injury. However, RAGE blockade inhibit ß-catenin, wnt3a and frizzled5 expression. We found that ß-catenin accumulation in NeuN cells were activated after SCI via IF, however, RAGE blockade reduced ß-catenin and NeuN positive cells. RAGE blockade attenuated number of survived neurons and decreased area of spared white matter around the epicenter. RAGE signaling may involved in disrupting wnt signaling to aids neuronal recovery after SCI.

Primary hepatic neuroendocrine carcinoma: report of two cases and literature review.

BACKGROUND: Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare. The diagnosis of PHNEC remains challenging-partly due to its rarity, and partly due to its lack of unique clinical features. Available treatment options for PHNEC include surgical resection of the liver tumor(s), radiotherapy, liver transplant, transcatheter arterial chemoembolization (TACE), and administration of somatostatin analogues. CASE PRESENTATION: We report two male PHNEC cases and discuss the diagnosis and treatment options. Both cases presented with abdominal pain; case two also presented with symptoms of jaundice. The initial diagnosis for both cases was poorly differentiated grade 3 small-cell neuroendocrine carcinoma, based on imaging characteristics and the pathology of liver biopsies. Final diagnoses of PHNEC were arrived at by ruling out non-hepatic origins. Case one presented with a large tumor in the right liver lobe, and the patient was treated with TACE. Case two presented with tumors in both liver lobes, invasions into the left branch of hepatic portal vein, and metastasis in the hepatic hilar lymph node. This patient was ineligible for TACE and was allergic to the somatostatin analogue octreotide. This limited treatment options to supportive therapies such as albumin supplementation for liver protection. Patient one and two died at 61 and 109 days, respectively, following initial hospital admission. CONCLUSIONS: We diagnosed both cases with poorly differentiated grade 3 small-cell PHNEC through imaging characteristics, immunohistochemical staining of liver biopsies, and examinations to eliminate non-hepatic origins. Neither TACE nor liver protection appeared to significantly extend survival time of the two patients, suggesting these treatments may be inadequate to improve survival of patients with poorly differentiated grade 3 small-cell PHNEC. The prognosis of poorly differentiated grade 3 small-cell PHNEC is poor due to limited and ineffective treatment options.

Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions.

BACKGROUND: Angiogenesis is a pathobiological hallmark of gastric cancer. However, rare studies focus on angiogenesis in gastric precancerous lesions (GPL). Weipixiao (WPX), a Chinese herbal preparation, is proved clinically effective in treating GPL. Here, we evaluated WPX's anti-angiogenic potential for GPL, and also investigated the possibility of its anti-angiogenic mechanisms. METHODS: HPLC analysis was applied to screen the major chemical components of WPX. After modeling N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL in male Sprague-Dawley rats, different doses of WPX were administrated orally for 10 weeks. Next, we performed histopathological examination using routine H&E staining and HID-AB-PAS staining. In parallel, we assessed angiogenesis revealed by microvessel density (MVD) using CD34 immunostaining, and subsequently observe microvessel ultrastructure in gastric mucosa under Transmission Electron Microscope. Finally, we detect expression of angiogenesis-associated markers VEGF and HIF-1α using immunohistochemistry. Moreover, mRNA expressions of ERK1, ERK2, Cylin D1 as well as HIF-1α in gastric mucosa were determined by quantitative real-time reverse transcription- polymerase chain reaction. RESULTS: We observed the appearance of active angiogenesis in GPL rats, and demonstrated that WPX could reduce microvascular abnormalities and attenuate early angiogenesis in most of GPL specimens with a concomitant regression of most intestinal metaplasia (IM) and a portion of gastric epithelial dysplasia (GED). In parallel, WPX could suppress HIF-1α mRNA expression (P < 0.01) as well as protein expression (although without statistical significance), and could markedly inhibit VEGF protein expression in GPL rats. Mechanistically, WPX intervention, especially at low dose, caused a significant decrease in the ERK1 and Cylin D1 mRNA levels. However, WPX might probably have no regulatory effect on ERK2 amplification. CONCLUSIONS: WPX could attenuate early angiogenesis and temper microvascular abnormalities in GPL rats. This might be partly achieved by inhibiting on the angiogenesis-associated markers HIF-1α and VEGF, and on the ERK1/Cylin D1 aberrant activation.

Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA-34a/LDHA pathway.

This study was designed to investigate the precancerous lesions of gastric carcinoma (PLGC)-reversing mechanisms of astragaloside IV (ASIV) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced PLGC rats. All rats were sacrificed after 10-week treatment. Gastric tissue was analyzed by using histopathology and electron microscope. To be fully evidenced, LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a were detected by Western blotting and Real-time Quantitative polymerase chain reaction (RT-qPCR). As histopathology and electron microscope showed, it can be clearly observed that the area of dysplasia was reduced in ASIV groups, indicating that MNNG-induced PLGC was markedly reversed by ASIV. Moreover, compared with model group, a significant decrease in gene expressions of LDHA, MCT1, MCT4, HIF-1α, CD147, and TIGAR was observed whereas miRNA-34a level was increased in ASIV groups. A significant up-regulation induced by MNNG in protein levels of LDHA, MCT1, MCT4, HIF-1α, and CD147 was attenuated in rats treated with ASIV. In contrast, the decreased expression of TIGAR was restored by ASIV. Interestingly, up-regulation of p53 expression induced by MNNG was further increased in ASIV groups. In brief, these results implied that abnormal glycolysis was relieved by ASIV via regulation of the expressions of LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a.

Edge-Based Efficient Search over Encrypted Data Mobile Cloud Storage.

Smart sensor-equipped mobile devices sense, collect, and process data generated by the edge network to achieve intelligent control, but such mobile devices usually have limited storage and computing resources. Mobile cloud storage provides a promising solution owing to its rich storage resources, great accessibility, and low cost. But it also brings a risk of information leakage. The encryption of sensitive data is the basic step to resist the risk. However, deploying a high complexity encryption and decryption algorithm on mobile devices will greatly increase the burden of terminal operation and the difficulty to implement the necessary privacy protection algorithm. In this paper, we propose ENSURE (EfficieNt and SecURE), an efficient and secure encrypted search architecture over mobile cloud storage. ENSURE is inspired by edge computing. It allows mobile devices to offload the computation intensive task onto the edge server to achieve a high efficiency. Besides, to protect data security, it reduces the information acquisition of untrusted cloud by hiding the relevance between query keyword and search results from the cloud. Experiments on a real data set show that ENSURE reduces the computation time by 15% to 49% and saves the energy consumption by 38% to 69% per query.

Receptor for advanced glycation end product blockade enhances the chemotherapeutic effect of cisplatin in tongue squamous cell carcinoma by reducing autophagy and modulating the Wnt pathway.

Tongue squamous cell carcinoma (TSCC) is one of the most severe types of cancer with poor outcomes. Cisplatin is used widely to treat cancer cells, but many patients develop acquired drug resistance. The receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced chemotherapy resistance. However, the effect of RAGE and cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and cisplatin effect on Tca-8113 cells' viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment; cisplatin alone; or RAGE blockade alone by flow cytometry. We observed the expressions of autophagy-related proteins beclin1, LC3II, p62; Wnt signaling-related proteins ß-catenin, GSK3ß, WNT5A, ROR-2; and apoptosis-related protein cleaved caspase-3, bcl-2-associated X proteins using western blot. We determined WNT5A and beclin1 expression on Tca-8113 cells by immunofluorescence. We further observed autophagy vacuoles by monodansylcadaverine staining. We found that RAGE blockade and cisplatin significantly decreased cell viability and increased the cell apoptosis rate compared with cisplatin alone. Furthermore, RAGE blockade suppressed the canonical Wnt pathway proteins ß-catenin and GSK-3ß, but upregulated noncanonical WNT5A and receptor ROR-2. We show that RAGE blockade suppressed the levels of autophagy-related protein LC3II/I, beclin1, accelerated degradation of autophagy for the increasing p62 expression, and increased cell apoptosis for the increasing expressions of cleaved caspase-3 and bcl-2-associated X proteins. We observed the location of WNT5A and beclin1 expressions on cells by immunofluorescence and their trends were consistent with western blotting. Taken together, our findings suggested that RAGE blockade+cisplatin improved chemotherapeutic effects by reducing autophagy and regulating Wnt/ß-catenin to suppress the progression of TSCC.

Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat.

Curcumin (CUR) is known to exert numerous health-promoting effects in pharmacological studies, but its low bioavailability hinders the development of curcumin as a feasible therapeutic agent. Piperine (PIP) has been reported to enhance the bioavailability of curcumin, but the underlying mechanism remains poorly understood. In an attempt to find the mechanism by which piperine enhances the bioavailability of curcumin, the dosage ratio (CUR: PIP) and pre-treatment with piperine were hypothesized as key factors for improving the bioavailability in this combination. Therefore, combining curcumin with piperine at various dose ratios (1:1 to 100:1) and pre-dosing with piperine (0.5-8 h prior to curcumin) were designed to investigate their contributions to the pharmacokinetic parameters of curcumin in rats and their effects on the expression of UGT and SULT isoforms. It was shown that the Cmax and AUC0-t of curcumin were slightly increased by 1.29 and 1.67 fold at a ratio of 20:1, while curcumin exposure was enhanced significantly in all the piperine pre-treated rats (0.5-8 h), peaking at 6 h (a 6.09-fold and 5.97-fold increase in Cmax and AUC0-t , p < 0.01), regardless of the unchanged t1/2 and Tmax . Also observed was a time-dependent inhibition of the hepatic expression of UGT1A6, 1A8, SULT1A1, 1A3, and the colonic expression of UGT1A6 that occurred within 6 h of piperine pre-treatment but was reversed at 8 h, which correlated with the changes in curcumin exposure. Similarly, the inhibitory effect of piperine on most of the UGTs and SULTs are time-dependent in Caco-2 and HepG2 cells. It is concluded that piperine pre-treatment time-dependently improves the bioavailability of curcumin through the reversible and selective inhibition of UGTs and SULTs. Copyright © 2016 John Wiley & Sons, Ltd.

Mineralising and antibacterial effects of modified calcium phosphate treatment on human root cementum.

BACKGROUND: Aging population will lead to the increase of incidence of root caries globally. The clinical management of root caries is challenging due to the difficulty in moisture isolation. The root caries is caused by the release of organic acids from cariogenic bacteria which results in the dissolution of cementum and dentin of the root. The purpose of this study is to study the efficacy of modified saturated calcium phosphate solution (CaP) supplement with zinc (Zn(2+)) and/or fluoride (F(-)) in providing root cementum surfaces less susceptible to acid dissolution and bacterial colonization. METHODS: Human root cementum sections from extracted premolars were treated with three modified calcium phosphate solutions (M/A-CaPs) respectively: (A) CaP-F/Zn, supplemented with F(-) and Zn(2+); (B) CaP-F, supplemented with F(-) only; (C) CaP-Zn, supplemented with Zn(2+) only. The surface characteristics of treated cementum sections were investigated using scanning electron microscopy (SEM) and fourier transform infrared spectroscopy (FT-IR). Following the acid attack and Streptococcus mutans challenge, M/A-CaPs treated cementum surfaces were analysed using inductive coupled plasma (ICP) and SEM respectively. RESULTS: Compared with the control group, M/A-CaPs treated cementum presented significant improvements in resistance to acid dissolution and bacterial colonization. Among M/A-CaPs, the CaP-F/Zn treated cementum surfaces released the lowest amount of Ca(2+) ions (2.11 ± 0.51 ppm) upon acid challenge (n = 3, p < 0.01) and also presented the most significant inhibiting effect against the colonization of S. mutans (n = 180, p < 0.05). CONCLUSIONS: Saturated calcium phosphate solution CaP supplemented with both F(-) and Zn(2+) could be applied as an effective coating material providing acid resistance and antibacterial property on cementum surfaces. The modified calcium phosphate-based solution could be a new treatment strategy to prevent the development of root caries and arrest the further progression of root caries.