[Preparation and characterization of co-loaded indocyanine green and elemene nano-emulsion in situ gel and its effect on proliferation of breast cancer MCF-7 cells].

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.

Conservation and Divergence of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) Gene Family between Wheat and Rice.

The SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) gene family affects plant architecture, panicle structure, and grain development, representing key genes for crop improvements. The objective of the present study is to utilize the well characterized SPLs' functions in rice to facilitate the functional genomics of TaSPL genes. To achieve these goals, we combined several approaches, including genome-wide analysis of TaSPLs, comparative genomic analysis, expression profiling, and functional study of TaSPL3 in rice. We established the orthologous relationships of 56 TaSPL genes with the corresponding OsSPLs, laying a foundation for the comparison of known SPL functions between wheat and rice. Some TaSPLs exhibited different spatial-temporal expression patterns when compared to their rice orthologs, thus implicating functional divergence. TaSPL2/6/8/10 were identified to respond to different abiotic stresses through the combination of RNA-seq and qPCR expression analysis. Additionally, ectopic expression of TaSPL3 in rice promotes heading dates, affects leaf and stem development, and leads to smaller panicles and decreased yields per panicle. In conclusion, our work provides useful information toward cataloging of the functions of TaSPLs, emphasized the conservation and divergence between TaSPLs and OsSPLs, and identified the important SPL genes for wheat improvement.

Purity Assessment of Aryltetralin Lactone Lignans by Quantitative 1H Nuclear Magnetic Resonance.

In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized, including relaxation delay (D1), scan numbers (NS), and pulse angle. 1,4-Dinitrobenzene was used as internal standard (IS), and deuterated dimethyl sulfoxide (DMSO-d6) as the NMR solvent. The purities were calculated by the area ratios of H-2,6 from target analytes vs. aromatic protons from IS. Six aryltetralin lactone lignans (deoxypodophyllotoxin, podophyllotoxin, 4-demethylpodophyllotoxin, podophyllotoxin-7'-O-ß-d-glucopyranoside, 4-demethylpodophyllotoxin-7'-O-ß-d-glucopyranoside, and 6''-acetyl-podophyllotoxin-7'-O-ß -d-glucopyranoside) were analyzed. The analytic results of qHNMR were further validated by high performance liquid chromatography (HPLC). Therefore, the qHNMR method was a rapid, accurate, reliable tool for monitoring the purity of aryltetralin lactone lignans.

A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug.

SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S351, S470-471and S493-494 as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.

[Study on preparation and optimization of saikoside liposomes].

OBJECTIVE: To optimize the prescription and technique for preparing saikoside (SS) liposomes and evaluate its quality. METHODS: The preparation methods of liposomes included film dispersion, ether injection, reverse phase evaporation and pH gradients were explored. The encapsulation ratio was determined by macroreticular resin method. The main factors affecting encapsulation ratio were studied by single factor analysis and central composite design. RESULTS: The appearance of SS liposomes prepared by optimized method was satisfactory. The encapsulation ratio was more than 60% and the verage particle size of SS liposomes was 110 nm. CONCLUSION: The formulation and preparation process is practical and simple for the preparation of SS liposomes. It is valuable to be further studied.

Thermo-sensitive injectable hydrogel loading with elemene-loaded liposomes for enhanced anti-tumor effect.

Due to the heterogeneity and the complexity of the tumor microenvironment, combination therapy, especially the combination of chemotherapy and photothermal therapy (PTT), had received increasing attention. However, the co-delivery of small molecule drugs for chemotherapy and photothermal agents was a key issue. Herein, we prepared a novel thermo-sensitive hydrogel loading with elemene (ELE)-loaded and nano graphene oxide (NGO)-based liposomes for enhanced combined therapy. ELE was applied as the model drug for chemotherapy because it was a natural sesquiterpene drug with broad-spectrum and efficient antitumor activity. NGO was applied as drug carrier and photothermal agent simultaneously due to its two-dimensional structure and high photo-thermal conversion efficacy. NGO was further modified with glycyrrhetinic acid (GA) to improve its water dispersion, biocompatibility and tumor-targeting ability. ELE was loaded by GA-modified NGO (GA/NGO) to prepare the liposomes designated as ELE-GA/NGO-Lip, which was further mixed with chitosan (CS) solution and ß-glycerin sodium phosphate (ß-GP) solution to prepare the thermo-sensitive hydrogel designated as ELE-GA/NGO-Lip-gel. The obtained ELE-GA/NGO-Lip-gel had the gelling temperature of 37°C, temperature and pH-response gel dissolution and high photo-thermal conversion effect. More importantly, ELE-GA/NGO-Lip-gel upon 808 nm laser irradiation had relative high anti-tumor efficiency against SMMC-7721 cells in vitro. This research might provide a potent platform for the application of thermos-sensitive injectable hydrogel in combined tumor therapy.

Peptide-drug co-assembling: A potent armament against cancer.

Cancer is still one of the major problems threatening human health and the therapeutical efficacies of available treatment choices are often rather low. Due to their favorable biocompatibility, simplicity of modification, and improved therapeutic efficacy, peptide-based self-assembled delivery systems have undergone significant evolution. Physical encapsulation and covalent conjugation are two common approaches to load drugs for peptide assembly-based delivery, which are always associated with drug leaks in the blood circulation system or changed pharmacological activities, respectively. To overcome these difficulties, a more elegant peptide-based assembly strategy is desired. Notably, peptide-mediated co-assembly with drug molecules provides a new method for constructing nanomaterials with improved versatility and structural stability. The co-assembly strategy can be used to design various nanostructures for cancer therapy, such as nanotubes, nanofibrils, hydrogels, and nanovesicles. Recently, these co-assembled nanostructures have gained tremendous attention for their unique superiorities in tumor therapy. This article describes the classification of assembled peptides, driving forces for co-assembly, and specifically, the design methodologies for various drug molecules in co-assembly. It also highlights recent research on peptide-mediated co-assembled delivery systems for cancer therapy. Finally, it summarizes the pros and cons of co-assembly in cancer therapy and offers some suggestions for conquering the challenges in this field.

The additive interactions between high-molecular-weight glutenin subunits and tannic acid improve the wheat quality.

Wheat gluten proteins, especially high-molecular-weight glutenin subunits (HMW-GS), are the main contributor to flour processing quality. Tannic acid (TA) consisting of a central glucose unit and ten gallic acid molecules is a phenolic acid that improves the processing quality. However, the underlying mechanism of TA's improvement remains largely unknown. Here, we showed that TA's improving effects on gluten aggregation, dough-mixing and bread-making properties were directly associated with the kinds of HMW-GS expressed in wheat seeds in HMW-GS near-isogenic lines (NILs). We established a biochemical framework, elucidated the additive effects of HMW-GS-TA interaction and discovered that TA cross-linked specifically with wheat glutenins but not gliadins, and reduced gluten surface hydrophobicity and SH content depending on the kinds of expressed HMW-GS in the wheat seeds. We also demonstrated that hydrogen bonds play an essential role in TA-HMW-GS interactions and improvement of wheat processing quality. Additionally, the effects of TA on the antioxidant capacity and on nutrient (protein and starch) digestibility were also investigated in the NILs of HMW-GS. TA increased antioxidant capacity but did not affect the digestion of starches and proteins. Our results revealed that TA more effectively strengthened wheat gluten in the presence of more HMW-GS kinds, highlighting TA's potential as an improver toward healthy and quality bread and demonstrating that manipulating hydrogen bonds was a previously overlooked approach to improve wheat quality.

Integrative gene duplication and genome-wide analysis as an approach to facilitate wheat reverse genetics: An example in the TaCIPK family.

INTRODUCTION: Reverse genetic studies conducted in the plant with a complex or polyploidy genome enriched with large gene families (like wheat) often meet challenges in identifying the key candidate genes related to important traits and prioritizing the genes for functional experiments. OBJECTIVE: To overcome the above-mentioned challenges of reverse genetics, this work aims to establish an efficient multi-species strategy for genome-wide gene identification and prioritization of the key candidate genes. METHODS: We established the integrative gene duplication and genome-wide analysis (iGG analysis) as a strategy for pinpointing key candidate genes deserving functional research. The iGG captures the evolution, and the expansion/contraction of large gene families across phylogeny-related species and integrates spatial-temporal expression information for gene function inference. Transgenic approaches were also employed to functional validation. RESULTS: As a proof-of-concept for the iGG analysis, we took the wheat calcineurin B-like protein-interacting protein kinases (CIPKs) family as an example. We identified CIPKs from seven monocot species, established the orthologous relationship of CIPKs between rice and wheat, and characterized Triticeae-specific CIPK duplicates (e.g., CIPK4 and CIPK17). Integrated with our analysis of CBLs and CBL-CIPK interaction, we revealed that divergent expressions of TaCBLs and TaCIPKs could play an important role in keeping the stoichiometric balance of CBL-CIPK. Furthermore, we validated the function of TaCIPK17-A2 in the regulation of drought tolerance by using transgenic approaches. Overexpression of TaCIPK17 enhanced antioxidant capacity and improved drought tolerance in wheat. CONCLUSION: The iGG analysis leverages evolutionary and comparative genomics of crops with large genomes to rapidly highlight the duplicated genes potentially associated with speciation, domestication and/or particular traits that deserve reverse-genetic functional studies. Through the identification of Triticeae-specific TaCIPK17 duplicates and functional validation, we demonstrated the effectiveness of the iGG analysis and provided a new target gene for improving drought tolerance in wheat.

Comprehensive Analyses of Breads Supplemented with Tannic Acids.

Tannic acid (TA) has been recently considered as a new dough additive for improving the bread-making quality of wheat. However, the effects of TA supplementation on the sensory quality parameters (color, crumb grain structure, and sensory properties) of bread have not been studied. Further, the potential of TA supplementation in bread-making quality improvement has not been evaluated by using commercial flour. In the present study, three commercial wheat flours (namely, XL, QZG, and QZZ) with different gluten qualities were used to evaluate the effects of TA supplementation (in concentrations of 0.1% and 0.3%, respectively). TA supplementation did not change the proximate composition of the breads but increased the volumes and specific volumes of XL and QZG breads. TA supplementation enhanced antioxidant activities, with 0.3% TA significantly increasing the antioxidant capacities of bread made from all three flour samples by approximately four-fold (FRAP method)/three-fold (ABTS method). Positive effects of TA on the reduction in crumb hardness, gumminess, and chewiness were observed in the XL bread, as determined by the texture profile analysis. For the analyses on visual and sensory attributes, our results suggest that TA did not affect the crust color, but only slightly reduced the L* (lightness) and b* (yellowness) values of the crumb and increased the a* (redness) value. TA supplementation also increased the porosity, total cell area, and mean cell area. Satisfactorily, the sensory evaluation results demonstrate that TA-supplemented breads did not exhibit negative sensory attributes when compared to the non-TA-added breads; rather, the attributes were even increased. In summary, TA-supplemented breads generally had not only better baking quality attributes and enhanced antioxidant activities, but, more importantly, presented high consumer acceptance in multiple commercial flour samples. Our results support the commercial potential of TA to be used as a dough improver.

Injectable in situ intelligent thermo-responsive hydrogel with glycyrrhetinic acid-conjugated nano graphene oxide for chemo-photothermal therapy of malignant hepatocellular tumor.

Malignant tumor is one of the major diseases with high morbidity and mortality. The purpose of this study is to prepare berberine hydrochloride (BH) in situ thermo-sensitive hydrogel based on glycyrrhetinic acid (GA) modified nano graphene oxide (NGO) (GA-BH-NGO-gel). NGO was taken as the photosensitizer, GA was taken as the target molecule, and BH was taken as the model drug. The physicochemical properties and anti-tumor activity in vivo and in vitro were also studied. This subject could provide a certain theoretical basis for the chemo-photothermal therapy combined treatment of malignant tumor. The release behavior of GA-BH-NGO-gel in vitro presented sustained and temperature-dependent drug release effect. The anti-tumor activity studies in vivo and in vitro had shown that GA-BH-NGO-gel had stronger anti-tumor activity, which could be targeting distributed to the tumor tissues. Moreover, the inhibitory effect of GA-BH-NGO-gel was enhanced when combined with 808 nm of laser irradiation. In this research, the chemo-photothermal combination therapy was applied into the tumor treatment, which may provide certain research ideas for the clinical treatment of malignant tumor.

TRPM2-AS Promotes Bladder Cancer by Targeting miR-22-3p and Regulating GINS2 mRNA Expression.

BACKGROUND: Bladder cancer (BLCA) refers to the malignancy growth that spreads from the bladder linings to the bladder muscles. However, the impact of miR-22-3p and lncRNA TRPM2-AS on this tumor has generated divergent views in the literature. This research aimed to study the effects of lncRNA TRPM2-AS on BLCA and its interaction with miR-22-3p and GINS2 mRNA. METHODS: qRT-PCR was employed to measure the expression of TRPM2-AS, miR-22-3p and GINS2 mRNA in bladder tissues and cells. The subcellular localization of TRPM2-AS in T24 and 5637 cell lines was identified using a cell fractionation system. Luciferase assay, RIP assay and RNA pull-down assay were later performed to validate the direct binding relationship between TRPM2-AS, miR-22-3p and GINS2 mRNA. Several experiments were conducted to determine the viability, proliferation, colony formation and apoptosis of the cell lines. RESULTS: Findings indicated that TRPM2-AS was significantly upregulated in BLCA tissues and cell lines. Apart from that, it was observed that TRPM2-AS knockdown significantly inhibited the viability, proliferation and colony formation of BCLA cells, but it promoted the apoptosis of the BCLA cells. A significant downstream target of TRPM2-AS, miR-22-3p was found to show a lower expression level in BLCA tissues and cell lines. However, the inhibition of miR-22-3p considerably enhanced BLCA cell phenotypes. As well as discovering that GINS2 mRNA was a downstream target of miR-22-3p and was significantly upregulated in BLCA, experimental results also indicated that the knockdown of GINS2 suppressed BLCA cell phenotypes. CONCLUSION: This research confirmed that TRPM2-AS could promote BCLA by binding to miR-22-3p to increase GINS2 expression. This novel interactome in BLCA cell lines might provide more insights into BLCA therapy.

Inhibitive effect of cremophor RH40 or tween 80-based self-microemulsiflying drug delivery system on cytochrome P450 3A enzymes in murine hepatocytes.

This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate. The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium. In vitro release was detected by a dialysis method in reverse. The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes. The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique. The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting. Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500. The MDZ was completely released in 10 h. A significant decrease in the formation of 1'-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed. A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250. This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.

MiR-582-5p Inhibits Bladder Cancer-Genesis by Suppressing TTK Expression.

BACKGROUND: Bladder cancer (BC) refers to the malignant growth found in the cells and tissues of the urinary bladder. While many studies have researched the progression of BC, scientists are yet to fully understand the mechanism of BC. This research aimed to explore the role of miR-582-5p and its target gene TTK in BC pathogenesis. METHODS: The evaluation of miR-582-5p and TTK mRNA expression in BC tissues or cells was performed using qRT-PCR. TargetScan was then used to predict the binding site of miR-582-5p on TTK mRNA. Subsequently, dual-luciferase reporter and RNA pull-down assays were employed to validate the binding relationship between miR-582-5p and TTK mRNA. CCK-8, BrdU, flow cytometry, and caspase-3 activity assays were later conducted to evaluate the viability, proliferation, cell cycle, and apoptosis of BC cells. RESULTS: Investigations revealed that miR-582-5p was downregulated in BC tissues and cells. Meanwhile, miR-582-5p inhibited the viability and proliferation of BC cells while stimulating the apoptosis and cycle arrest of the cells. TTK, the target gene of miR-582-5p, was later found to be over-expressed in BC tissues and cells. TTK, however, was observed to exhibit an opposite effect on miR-582-5p. Simply put, it stimulated BC cell malignant phenotypes, and this stimulation could be directly reversed by miR-582-5p. CONCLUSION: This research confirmed that miR-582-5p could restrain bladder carcinogenesis by inhibiting TTK expression.

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances.

Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as Dioscorea rhizome, Dioscorea villosa, Trigonella foenum-graecum, Smilax China, and Rhizoma polgonati. DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson's disease, Alzheimer's disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.

TaSPL13 regulates inflorescence architecture and development in transgenic wheat (Triticum aestivum L.).

The SQUAMOSA promoter-binding protein-like (SPL) proteins play vital roles in plant growth and development in rice (Oryza sative L.) and Arabidopsis thaliana (L.) Heynh. However, few studies regarding the SPL proteins have been reported in wheat. In this study, 56 TaSPLs were clustered into eight groups according to an OsSPL phylogenetic comparison analysis. The expression patterns of TaSPLs in different tissues were analysed by RNA-seq data, and partial results were confirmed by qRT-PCR. Based on the above results, genes such as TaSPL13 and TaSPL15 may be involved in spike or seed development in wheat. Multiple genes that regulate the inflorescence architecture of rice have been identified. Additionally, studies on the genes associated with spikelet development in wheat have been reported relatively rarely. Here, TaSPL13-2B was transferred into wheat cv. Bobwhite. Compared with the wild type, the transgenic lines showed significant increases in the number of florets and grains per spike, indicating that TaSPL13-2B could influence the floret development of wheat. TaSPL13-2B was transferred into rice cv. Nipponbare, which demonstrated that TaSPL13-2B can modify panicle architecture in transgenic rice, with significant increases in panicle length, the number and length of primary branches, and the number of secondary branches.

Effects of an Additional Cysteine Residue of Avenin-like b Protein by Site-Directed Mutagenesis on Dough Properties in Wheat (Triticum aestivum L.).

Avenin-like b protein is rich in cysteine residues, providing the possibility to form intermolecular disulfide bonds and then participate in glutenin polymerization. Site-directed mutagenesis was adopted to produce mutant avenin-like b gene encoding mutant avenin-like b protein, in which one tyrosine codon at the C-terminal is substituted by a cysteine codon. Compared with the control lines, both transgenic lines with wild-type and mutant avenin-like b genes demonstrated superior dough properties. While compared within the transgenic lines, the mutant lines showed relative weaker dough strength and decreased sodium-dodecyl-sulfate sedimentation volumes (from 69.7 mL in line WT alb-1 to 41.0 mL in line Mut alb-4). These inferior dough properties were accompanied by the lower contents of large-sized glutenin polymers, the decreased particle diameters of glutenin macropolymer (GMP), due to the lower content of intermolecular ß-sheets (from 39.48% for line WT alb-2 to 30.21% for line Mut alb-3) and the varied contents of disulfide bonds (from 137.37 µmol/g for line WT alb-1 to 105.49 µmol/g for line Mut alb-4) in wheat dough. The extra cysteine might alter the original disulfide bond structure, allowing cysteine residue usually involved in an intermolecular disulfide bond to become available for an intrachain disulfide bond. Avenin-like b proteins were detected in glutenin macropolymers, providing further evidence for this protein to participate in the polymerization of glutenin. This is the first time to investigate the effect of a specific cysteine residue in the avenin-like b protein on flour quality.

Therapeutic effects of curcumin nanoemulsions on prostate cancer.

The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.

Survey and Risk Factors for Lower Urinary Tract Storage Symptoms in Middle-Aged and Older Stroke Patients in Urban China.

OBJECTIVES: To evaluate the prevalence and associated risk factors of lower urinary tract symptoms (LUTS) in people with stroke. This was the first study that systematically surveyed the risk factors for LUTS in people with various lengths of stroke history in urban Chinese communities. METHODS: A community-based, cross-sectional study was performed on 1404 residents aged over 40 years, randomly selected in the urban area of Zhengzhou, China. A questionnaire including the subjects' general health information, sociodemographic background, medical history, and the overactive bladder symptom score (OABSS) was filled by the subjects on site. RESULTS: Data from 706 (63.8.9 ± 8.9 years old) stroke subjects and 698 non-stroke subjects were analyzed. The prevalence of LUTS in stroke subjects was 62.6%, significantly higher than non-stroke subjects. The prevalence in men was higher than women (P < 0.01). The stroke subjects with diabetes mellitus had higher odds for LUTS than those without diabetes (P < 0.05). The prevalence of LUTS was also significantly correlated with increasing age, high educational level, living alone, snoring, hypertension and coronary heart diseases (P < 0.01). CONCLUSIONS: Our study identified not only putative risk factors for LUTS in middle-aged and elderly stroke patients, but genuine factors including snoring, living environment and educational background that increased the odds of storage symptoms as well. We identified that regular exercise and living with their children were protective factors for storage symptoms in stroke patients.

Chloride intracellular channel 1 regulates prostate cancer cell proliferation and migration through the MAPK/ERK pathway.

UNLABELLED: Abstract Aims: To investigate the effect of chloride intracellular channel 1 (CLIC1) on the proliferation, migration, and apoptosis of prostate cancer cell lines PC-3 and DU145 and the possible molecular mechanisms. MATERIALS AND METHODS: Using the technique of RNA interference, the expression of CLIC1 was downregulated in the PC-3 and DU145 cell lines. MTT assay, Transwell chamber, and flow cytometry were used to determine the effect of CLIC1 on the proliferation, migration, and apoptosis ability of PC-3 and DU145 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, matrix metalloproteinase (MMP)-2, and MMP-9 were examined by western blotting. RESULTS: The results showed that the knockdown of CLIC1 exerts inhibitory effects on the proliferation and migration of PC-3 and DU145 cells. At the same time, the authors found that the knockdown of CLIC1 has no effect on the apoptosis in PC-3 and DU145 cells. Meanwhile, the levels of p-ERK1/2, MMP-2, and MMP-9 were decreased in the CLIC1 small interfering RNA (siRNA) group compared with the control and vector groups. CONCLUSION: These results indicate that CLIC1 could regulate prostate cancer cell proliferation and migration by regulating the mitogen-activated protein kinase (MAPK)/ERK pathway and offers a candidate molecular target for prostate cancer prevention and therapy.