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Laurencia undulata, as one of the most biologically active species in the genus Laurencia, is an edible folk herb red algae. Among them, d-isofloridoside (DIF, 940.68 Da) is isolated from Laurencia undulata, which has antioxidant and matrix metalloproteinases (MMP) inhibitory activities. However, its mechanism of action on tumor angiogenesis has not yet been reported. In this study, we have studied the mechanism of DIF on tumor metastasis and angiogenesis in HT1080 cell and human vascular endothelial cell (HUVEC). The results show that DIF can reduce the activity of MMP-2/9, and can inhibit the expression of hypoxia-inducible factor-1α (HIF-1α) by regulating the downstream PI3K/AKT and mitogen-activated protein kinases (MAPK) pathways, thereby down-regulating the production of vascular endothelial growth factor (VEGF) in CoCl2-induced HT1080 cell. In addition, DIF can inhibit the activation of VEGF receptor (VEGFR-2), regulate downstream PI3K/AKT, MAPK, nuclear factor-kappa B (NF-κB) signal pathways, activate apoptosis, and thus down-regulate the production of platelet-derived growth factor (PDGF) in VEGF-induced HUVEC. In conclusion, our research shows that DIF has the potential to develop into a tumor-preventing functional food and tumor angiogenesis inhibitor, and it can provide theoretical guidance for the high-value comprehensive utilization of edible red algae Laurencia undulata.

Objective: The expression and function of platinum transporters affect drug tissue concentration and therapeutic effects. We had previously characterized functional variant of platinum intake transporter SLC31A1 gene. We aimed to investigate the association of platinum efflux transporter gene ABCG2 polymorphism and combined ABCG2 and SLC31A1 polymorphisms with clinical outcomes of NSCLC patients receiving platinum-based chemotherapy. Methods: We genotyped thirteen tagging and functional SNPs of ABCG2 in 1004 patients, and assessed their association with response, toxicity and survival using unconditional logistic regression and Cox proportional hazards regression analyses respectively. Results: Nonsynonymous rs2231142 (odds ratio [OR] 2.07; 95 % confidence interval [CI] 1.26-3.63), rs1871744 (OR 0.60; 95 % CI 0.42-0.87) and their haplotype and diplotype were associated with objective response. Rs4148157 was associated with shorter overall survival (Log-rank P = 0.002; hazard ratio [HR] 1.22; 95 % CI 1.05-1.42). Furthermore, the combined SLC31A1 rs2233914 and ABCG2 rs1871744 genotype was significantly associated with poor response (OR 0.31; 95 % CI 0.17-0.56; P interaction = 0.003). And the combined genotypes of the functional rs10759637 of SLC31A1 and the nonsynonymous rs2231142 (Log-rank P = 5.20×10-5; HR 1.47; 95 % CI 1.19-1.81; P interaction = 0.007) or linked rs4148157 of ABCG2 were significantly associated with poor survival. Conclusion: This study reveals divergent association of ABCG2 polymorphism with response and survival of NSCLC patients receiving platinum-based chemotherapy, demonstrates the combined effects of functional variants of ABCG2 and SLC31A1 on clinical outcomes, and highlights pharmacogenetic relevance of platinum transporter genes interaction.

Microalgae are primary producers with multiple nutrients in aquatic environments and mostly have applications in biological feed and fuel industry. There are few studies assessing the angiotensin-I-converting enzyme (ACE) inhibition potential of Isochrysis zhanjiangensis, other than its antioxidant potential. In this study, we evaluated a peptide from I. zhanjiangensis (PIZ, FEIHCC) and its vascular endothelial factors and mechanism in human umbilical vein endothelial cells (HUVEC). The results reveal that PIZ (IC50 = 61.38 μM) acts against ACE in a non-competitive binding mode. In addition, PIZ inhibits angiotensin II (Ang II)-induced vascular factor secretion and expression by blocking inflammation and apoptosis through nuclear factor κB (NF-κB), nuclear erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), and the serine/threonine kinase (Akt) signal pathways. This study reveals that PIZ has potential to be developed as a therapeutic agent for hypertension and provides a new method of high-value utilization of I. zhanjiangensis.

Background In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. Results This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50 = 2.577 μmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. Conclusion LSGYGP, with an IC50 value of 2.577 μmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.

Introduction A previous study has shown that Ala-Thr-Pro-Gly-Asp-Glu-Gly (ATPGDEG) peptide identified from boiled abalone by-products has high antioxidant activities and antihypertensive effect. Objective In this study, we further investigated its antiphotoaging activities by ultraviolet B (UVB)-induced HaCaT cells. Result UVB irradiation significantly increased the content of intercellular reactive oxygen species (ROS) and the production of matrix metalloproteinases (MMPs) in HaCaT cells and decreased its content of collagen. First, the generation of intercellular ROS was reduced by abalone peptide in UVB-induced HaCaT cells. And activities of MMP-1 and MMP-9 were reduced by abalone peptide in a dose-dependent manner. Furthermore, western blot analysis demonstrated that abalone peptide downregulated the expression of p38, c-Jun N-terminal kinases, and extracellular signal-regulated kinases via mitogen-activated protein kinases (MAPKs) and NF-κB signaling to protect type I pro collagen and DNA damage. Molecular docking simulation confirms that abalone peptide inhibited activities of MMP-1 and MMP-9 by docking their active site, among them N-terminal Ala, C-terminal Gly, and Pro at the third position of N-terminal made a great contribution. Conclusion and recommendation Abalone peptide could protect type I procollagen synthesis in UVB-irradiated HaCaT cells, and it is a potential peptide for the treatment of skin photoaging in the future.

Background Both doctors’ and patients’ opinions are important in the process of treatment and healthcare of Chinese medicine. This study is to compare patients’ and doctors’ treatment satisfaction over the course of two visits in a Chinese medicine outpatient setting, and to explain their respective views. Methods Patients’ chief complaints were collected prior to the outpatient encounter. The doctor was then asked (through a questionnaire) to state what complaints he or she was prioritizing during the process of diagnosing disease and making a prescription for herbal medicine or acupuncture treatment. On the next visit, both the patient and the doctor completed a questionnaire assessing satisfaction with the treatment of Chinese medicine prescribed in the first visit and administered by the patient at home. A 5-point Likert scales was used to assess the patients’ and doctors’ satisfaction with treatment. The timing of the follow-up appointment was determined by the doctor. One chief specialist, one associate chief specialist and one attending practitioner in Chinese medicine, and 60 patients having a follow-up appointment with one of the doctors, participated in the study. Results For 11 patients, their most urgent complaint was different from what the doctor’s choose to focus on in his or her treatment. And only one patient refused to comply due to his or her dissatisfaction with the treatment focus of the doctor. Overall, 59 patients completed the satisfaction assessment, and 53 patients visited their doctors for a follow-up appointment. Patients’ total satisfaction was higher than their doctors’ (mean 3.55 vs. 3.45), and correlation of patients’ and doctors’ treatment satisfaction was moderate (r = 0.63, P P Conclusion Patients and doctors form their opinion about the treatment effects in different ways. When evaluating treatment satisfaction, doctor’s opinions are also an important indicator of positive or negative clinical effects and affect the subsequent decisions-making.

Gelidium crinale, the red algae belonging to Geliaceae Gelidium, is a traditional edible and industrial alga in China. A sulfated polysaccharide (GNP) is successfully separated from Gelidium crinale by acid extraction and two-step column chromatography. Chemical analysis showed that the molecular weight of GNP was 25.8 kDa and the monosaccharide composition had the highest galactose content and confirmed the presence and content (16.5%) of sulfate by Fourier transform infrared spectroscopy (FT-IR) spectrometry as well as barium chloride-gelatin methods. In addition, the effect of GNP on lipopolysaccharide (LPS)-induced oxidative stress and inflammation in macrophages was also evaluated. The research results showed that GNP had fairly strong scavenging activities on 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and had Fe2+-chelating ability in a dose-dependent manner. At the same time, it significantly inhibits the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the production of pro-inflammatory cytokines in RAW 264.7 cells induced by LPS through blocking the mitogen-activated protein kinase (MAPK)/nuclear factor kappa beta (NF-κB) signaling pathway. These results indicate that GNP may be a latent component anti-inflammation in pharmaceutical and functional food industries.

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Background: Knee osteoarthritis (KOA) refers to a chronic deteriorating disease distinguished by degeneration of joint cartilage. Many clinical studies have demonstrated that isokinetic muscle strength training can improve muscle function in patients with KOA. However, although such studies deduce an excellent effect, the results remain controversial. Therefore, the present systematic review seeks to explore the curative effects of isokinetic muscle strength training to establish if it can improve muscle function in patients experiencing KOA. Methods: This review will entail a systematic review and a comprehensive examination to establish all randomized controlled studies covering curative effects of isokinetic muscle strength training to improve muscle function in patients with KOA. We will obtain data from PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, and WanFang databases from inception to September 2021. In addition, the study will employ the criterion postulated by Cochrane to ascertain a quality evaluation and risk assessment of the studies included for analysis. Also, we will employ relative risk, mean differences, and standardized mean differences with 95% confidence intervals to estimate the effective measures. Also, we will employ Cochran Q test and I2 statics to assess heterogeneity among the 2 studies. Results: Overall, this study anticipates providing accurate results and balanced inferences on curative effects of isokinetic muscle strength training for improving muscle function in patients with KOA. Conclusion: The study's inferences will offer evidence to decide whether isokinetic muscle strength training is an effective measure for improving muscle function in patients with KOA.

The coexistence of nanoplastics (NPs) and pollutants such as arsenic (As) has become an unignorable environmental problem. However, there is still a considerable knowledge gap about the impact of NPs and pollutants on human health risks. In this study, the human gastric adenocarcinoma (AGS) cells were used as a model to investigate the toxicity of NPs with different particle sizes and As by MTT assay, western blotting, immunofluorescence and so on. The results showed that 20 nm (8 μg/mL), 50 nm (128 μg/mL), 200 nm (128 μg/mL), 500 nm (128 μg/mL), 1000 nm (128 μg/mL) polystyrene (PS) did not affect cell viability, ROS, intracellular calcium and activate apoptosis pathway in AGS cells. However, noncytotoxic concentration of NPs enhanced the cytotoxicity and intracellular accumulation of As. NPs destroys the fluidity of cell membrane and cytoskeleton, inhibits the activity of ABC transporter, and leads to the accumulation of As in cells. This work highlights that the damage caused by NPs, especially at the level of noncytotoxicity, joint with As cannot be ignored and provides a specific toxicological mechanism of NPs accompanied by exposure to As.

As one of the malignant tumors with high mortality, liver cancer has the characteristics of early invasion and metastasis, and lacks effective treatment methods. Therefore, it is urgent to find new safe, efficient and low-toxic anti-liver cancer drugs. In this study, the evaluated mechanism of Ecklonia cava polyphenols (7PE, 7-phloro-eckol) as a potential active substance for inhibiting liver cancer metastasis (HepG2 cell) and angiogenesis (HUVEC cell). The results have shown that 7PE can inhibit the expression of hypoxia-inducible factors (HIF-1α) protein by regulating the PI3K/AKT/mTOR and Ras/MEK/ERK/MNK signaling pathways under hypoxic conditions in HepG2 cells, thereby blocking the secretion of vascular growth factor (VEGF) protein. At the same time, 7PE can significantly inhibit the conduction of AKT and MAPK signaling pathways in HUVEC by suppressing the activation of VEGFR-2 protein, which verifies the prediction of molecular docking. Therefore, the results of this study provide a research basis for 7PE to inhibit metastasis and angiogenesis of liver cancer cells, and provide a theoretical basis for the high-value utilization of Ecklonia cava.

In this study, we investigated the protective effects of a peptide (YGDEY, Tyr-Gly-Asp-Glu-Tyr) isolated from tilapia skin gelatin hydrolysates (TGHs), against UVB-induced photoaging in human keratinocytes (HaCaT) cells. Results showed that YGDEY significantly decreased levels of intracellular reactive oxygen species (ROS), increased antioxidant factors (Superoxide Dismutase, SOD and Glutathione, GSH) expression and maintained balance between GSH and GSSG in HaCaT cells. Comet assay shows that YGDEY can protect DNA from oxidative damage. Furthermore, it significantly inhibited MMP-1 (collagenase) and MMP-9 (gelatinase) expression and increased Type I procollagen production. In addition, the molecular docking study showed that YGDEY may form active sites with MMP-1 and MMP-9. Moreover, Western blot analysis was utilized to measure the protein levels of UVB-induced mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Therefore, these results suggested that YGDEY has a therapeutic effectiveness in prevention of UVB-induced cellular damage, and it is a candidate worthy of being developed as a potential natural antioxidant and food additive.

Matrix metalloproteinases (MMPs), the key enzymes in extracellular matrix degradation, seemed to increase in tumorigenesis, which has a relationship with metastasis and invasions. In this study, we investigated the MMP inhibitory effect of viridicatol and viridicatin, two compounds extracted from shark-gill-derived fungus Penicilliumpolonicum AP2T1, on MMP-2 and -9 in vitro and in silico. The MTT assay showed that viridicatol and viridicatin had no cytotoxicity at a concentration of 50 µM on HT1080 human fibrosarcoma cells. In addition, the studies by gelatin zymography and Western blot analysis confirmed that the two compounds effectively inhibited the protein activities and expressions of MMP-2 and -9. Moreover, molecular docking studies simulated and clarified the interaction between compounds and MMPs, respectively. Furthermore, the effect of those two compounds on mitogen activated protein kinases (MAPKs) was also assessed by Western blot analysis. Collectively, these results suggested that viridicatol and viridicatin could be potential inhibitors of MMPs and P.polonicum may be a rich source of bioactive compounds with MMP inhibitory property.

Seahorse has been used as a traditional medicine in Southeast Asian countries for a long time. A compound, 2'-Hydroxy-5'-Methoxyacetophenone (2H5M) isolated from seahorse, Hippocampus kuda, was tested for its anti-inflammatory effect in lipopolysaccharides (LPS)-stimulated BV-2 cells and RAW264.7 cells. MTT assay indicated that 2H5M has no cytotoxicity on two kinds of cells. The concentration of nitric oxide (NO) measured by Griess Reaction System showed that 2H5M could significantly inhibit the NO concentration. The ELISA results showed that 2H5M could suppress the secretion of TNF-α in a dose-dependent manner. Moreover, western blot analysis was utilized to measure the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Electrophoretic mobility shift assay (EMSA) demonstrated that 2H5M reduced NF-κB DNA binding activity. Furthermore, the molecular docking study showed that 2H5M can form active sites with NF-κB. Collectively, these results indicated that 2H5M possesses anti-inflammatory effects and may have a potential application in inflammatory disorders in the future.

Marine microalgae have been widely applied in cosmaceuticals, nutraceuticals, and functional foods. In the present study, we first investigated the hepatoprotective effects of peptide purified from microalgae, Isochrysis zhanjiangensis on HepG2 cells alcoholic injury. I. zhanjiangensis was hydrolyzed utilizing chymotrypsin, trypsin, pepsin, and by vitro gastrointestinal digestion. Among hydrolysates, the gastrointestinal hydrolysate showed relatively high free radical scavenging ability preliminarily and was purified with following sequential chromatography methods. The amino acid sequence and molecular mass of the purified peptide from I. zhanjiangensis (PIZ) was identified as Asn-Asp-Ala-Glu-Tyr-Gly-Ile-Cys-Gly-Phe (NDAEYGICGF; MW, 1088.16 Da) via Q-TOF ESI/MS. Additionally, PIZ attenuated ethanol-induced cytotoxicity and inhibited the production of intracellular reactive oxygen species by DCFH-DA assay. Western blot results showed that superoxide dismutase (SOD) and glutathione (GSH) levels up-regulated with PIZ treatment before alcohol exposure while gamma-glutamyltransferase (GGT) protein expression down-regulated. These results provide an opportunity to discover new highly active peptide against alcohol toxicity in HepG2 cells.

Soluble sugars and starches are important metabolites of plant life and physiological markers of plant stress response. There is an urgent need to develop a non-destructive and rapid method for determining plant starch and soluble sugar contents. Electrical impedance tomography (EIT) technology has been used to determine the physiological state and cold resistance of select plant tissues. However, so far there have been no reports on the use of EIT for the rapid estimation of soluble sugar and starch contents. In this study, EIT was used to obtain reconstructed voltage values and estimate starch and soluble sugar contents in the stems of three Rosa hybrida cultivars during February to May, which were grown in the Specimen Park (38° 50′ N, 115° 26′ E) of Hebei Agricultural University, Baoding City, Hebei Province, China. Stems from two of the cultivars were used for establishing regression models for starch and soluble sugar contents as functions of reconstructed voltage values. The third cultivar was used to test the accuracy of the regression models. The quadratic regression model was best for determining soluble sugar content and the logarithmic regression model was best for determining starch content. Thus, this research provided technical support for using EIT to analyze changes in physiological parameters and to rapidly estimate physiological indexes of plants. More studies were now needed to validate the results in this paper.

Sepsis is a clinical syndrome that resulting from a dysregulated inflammatory response to infection that leads to organ dysfunction. The dysregulated inflammatory response transitions from a hyper-inflammatory phase to a hypo-inflammatory or immunosuppressive phase. Currently, no phase-specific molecular-based therapies are available for monitoring the complex immune response and treating sepsis due to individual variations in the timing and overlap of the dysregulated immune response in most patients. Glucocorticoid-induced leucine zipper (GILZ), is broadly present in multiple tissues and circumvent glucocorticoid resistance (GCR) or unwanted side effects. Recently, the characteristics of GILZ downregulation during acute hyperinflammation and GILZ upregulation during the immunosuppressive phase in various inflammatory diseases have been well documented, and the protective effects of GILZ have gained attention in the field of sepsis. However, whether GILZ could be a promising candidate biomarker for monitoring and treating septic patients remains unknown. Here, we discuss the effect of GILZ in sepsis and sepsis-induced immunosuppression.

Ultraviolet radiation B cause photoaging of the skin by enhancing the high expression of matrix metalloproteinases (MMPs) to degrade collagen and inhibit the synthesis of procollagen. Trehalose (TRE), a widely occurring natural disaccharide, has been shown to play a cytoprotective role in many pathological processes. However, few studies have evaluated whether it has anti-photoaging potential. In this study, we investigated the anti-photoaging and mechanism of action of TRE using Human immortalized keratinocytes (HaCaT) cells. The results indicated that TRE pretreatment effectively scavenges reactive oxygen species (ROS) accumulation induced by UVB and increases the content of certain endogenous antioxidant factors in HaCaT cells. TRE suppressed UVB-induced MMP expression by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1) and NF-κB signaling. TRE treatment increased procollagen I synthesis via activating transforming growth factor-β (TGF-β)/Smad pathway and demonstrated that TRE may be a potential natural disaccharide for photoaging therapy in the future.

The polyoxymethylene dimethyl ethers (PODE)/methanol reactivity controlled compression ignition (RCCI) mode was realized by direct injection of PODE as high-reactivity fuel to ignite pre-mixed methanol as low-reactivity fuel in a high-pressure common-rail diesel engine. The effects of load extension ratio (LER) on in-cylinder combustion, emission characteristics and fuel economy of RCCI engine were investigated, and the influences of PODE injection strategy on the high-load extension of PODE/methanol RCCI mode were also systematically studied, including the start of main-injection (SOImain), start of pilot-injection (SOIpilot) and pilot-injection quantity (PIQ). The results show that with the increase of LER, the peak values of in-cylinder pressure and heat release rate of RCCI mode increase, the brake thermal efficiency (BTE) and the hydrocarbons (HC), carbon monoxide (CO) and unregulated emissions also increase, but the increase of the ringing intensity (RI), the coefficient of variation of IMEP (COVIMEP) and nitrogen oxides (NOx) limit the further increase of LER. The delay of SOImain can effectively reduce RI, but it will lead to the deterioration of CO and HC emissions and fuel economy. The pilot-injection strategy can weaken the trade-off relationship between NOx and soot emissions and improve combustion stability. With the advance of SOIpilot, the RCCI combustion process evolves from two-stage heat release to single-stage heat release, and the emissions of HC, CO, NOx and soot are reduced. With the increase of PIQ, the combustion phase of PODE/methanol RCCI mode advances, and the RI, COVIMEP and IMEP increase. At 59.5 mg/cycle condition, when PIQ is increased from 2 mg to 10 mg, CO and HC emissions decrease by 19.57% and 6.97% respectively, while NOx emissions increase by 7.93%. With the appropriate LER combined with the optimized PODE injection strategy, the BTE of PODE/methanol RCCI engine reaches 48.68%, and the IMEP is extended from 0.77 MPa to 1.08 MPa.

Doxorubicin (DOX) is limited to use in clinical practice because of poor targeting, serious side effects and multidrug resistance (MDR). Vitamin E and its derivatives are currently considered as hydrophobic material that can reverse tumor MDR by suppressing the action of p-glycoprotein (p-gp). Therefore, reduction-sensitive amphiphilic heparosan polysaccharide-cystamine-vitamin E succinate (KSV) copolymers were designed to reverse breast cancer MDR cells. The spherical micelles (DOX/KSV) micelles which had suitable particle size presented redox-sensitive release character. Simultaneously, DOX-loaded reduction insensitive heparosan-adipic dihydrazide-vitamin E succinate (KV) micellar system was designed as a control. DOX/KSV and DOX/KV micelles had the higher capability to overcome tumor MDR than that free DOX. However, DOX/KSV had the highest amount of cellular uptake which might be caused by the synergistic intracellular drug release and inhibition of p-gp expression. The mechanism experiments revealed that DOX/KSV could be fast disassembled to release DOX after internalization into tumor cells. Moreover, DOX/KSV produced more ROS than free DOX and DOX/KV resulting in enhanced anticancer effect. In vivo tumor-bearing mice study suggested that DOX/KSV micelles could efficiently enhance antitumor effect by overcoming tumor MDR and reduce toxicity of DOX. The DOX/KSV micelles could synergistically increase the therapeutic effect of chemotherapeutic drug on tumor MDR cells.

Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of &gamma, glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase ) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods.

Cholinergic disorder, oxidative stress, and neuroinflammation play important roles in the pathology of Alzheimer's disease. To explore the healthy potential of the edible seaweed Hizikia fusiforme on this aspect, a functional oil (HFFO) was extracted from this alga and investigated on its constituents by gas chromatography-mass spectrometry (GC/MS) in this study. Its anti-Alzheimer's related bioactivities including acetylcholinesterase (AChE) inhibition, antioxidation, and anti-neuroinflammation were evaluated, traced, and simulated by in vitro and in silico methods. GC/MS analysis indicated that HFFO mainly contained arachidonic acid (ARA), 11,14,17-eicosatrienoic acid (ETrA), palmitic acid, phytol, etc. HFFO showed moderate AChE inhibition and antioxidant activity. Bioactivity tracing using commercial standards verified that AChE inhibition of HFFO mainly originated from ARA and ETrA, whereas antioxidant activity mainly from ARA. Lineweaver-Burk plots showed that both ARA and ETrA are noncompetitive AChE inhibitors. A molecular docking study demonstrated low CDOCKER interaction energy of -26.33 kcal/mol for ARA and -43.70 kcal/mol for ETrA when interacting with AChE and multiple interactions in the ARA (or ETrA)-AChE complex. In the anti-neuroinflammatory evaluation, HFFO showed no toxicity toward BV-2 cells at 20 μg/mL and effectively inhibited the production of nitroxide and reduced the level of reactive oxygen species in lipopolysaccharide-induced BV-2 cells. The results indicated that HFFO could be used in functional foods for its anti-Alzheimer's disease-related activities.

The diabetic wounds do not heal easily in part because they are susceptible to infection due to environmental influences. Wound dressing is crucial to wound healing, as it can basically protect the wound from external damages and provide a suitable microenvironment for tissue regeneration. In this study, a double-layer membrane that consists of chitosan sponge and decellularized bovine amniotic membrane (dBAM) has been developed by freeze-casting method. The results showed that the porous structure of the sponge layer improved the performances of blood coagulation and swelling. The dense dBAM can optimize the mechanical property of wound dressing. In vitro studies revealed that the bilayer membrane had favorable biocompatible, especially for human foreskin fibroblast cells (HFF-1) cell adhesion and proliferation. Moreover, the full-thickness skin defects of diabetic model mice that treated with bilayer membrane showed over 80% closure in 8 days. Our findings imply that the double-layer dressing has great potentials to be used in diabetic patients.

Background Excessive exposure to Ultraviolet (UV) rays can cause premature skin aging. Ishigoside (IGS) is a new glyceroglycolipid compound isolated from brown algal Ishige okamurae, However, whether it can protect the skin from (Ultraviolet-B) UVB damage has not been illuminated. Methods The in vitro anti-photoaging effect of IGS was conducted in UVB-induced HaCaT. The HaCaT cells were divided into the following five groups: (1) cells didn't suffer from UVB irradiation or IGS treatment. (2–5) Cells were treated with various concentrations of IGS (0, 10, 50, and 100 μM) and irradiated by 40 mJ/cm2 UVB. The Matrix metalloproteinase (MMP) of photoaging process was determined by ELISA kits and the latent interaction between IGS and MMP was further performed by molecular docking. The crucial signaling pathway proteins involved in the collagen synthesis and degradation were subsequently evaluated by Western blotting, immunofluorescence and EMSA. Results IGS effectively suppresses the high expressions and secretions of matrix metalloproteinases (MMPs) and photo-inflammation by blocking MAPKs, AP-1 and NF-κB. Meanwhile, increasing antioxidant enzyme expression. Molecular docking results suggest that inhibition of IGS on MMPs may be attributed to its hydrogen supply and hydrophobic capacity. In addition, IGS enhanced procollagen production by upregulating the TGF-β/Smad pathways. Conclusions IGS exhibited anti-photoaging activity in UVB-damage HaCaT. These effects might be a contribution by its suppression of MMPs expression via MAPKs, AP-1 and NF-κB pathway and have anti-oxidative and anti-inflammatory effects. Therefore, IGS has the great potential to become skin-care products or functional foods for preventing skin photoaging.

According to the dispersion principle of solid particles in the liquid and polar phase solubility principle, nano-CeO2 catalytic fuels were prepared with 50 and 100 mg/L mass fractions of CeO2. The in-cylinder soot distribution was investigated on a common-rail engine using the visualization technology. The combustion characteristics and smoke emissions were also analyzed. The effects of heating rates and nano-CeO2 concentration on particle oxidation characteristics were studied using thermogravimetric analysis method. The results show that the combustion starting point of the engine with catalytic diesel advances, while the peak values of in-cylinder pressure and heat release rate increase. The location of soot flame occurrence advances, and its vanishing moment comes earlier with the addition of nano-CeO2. Compared with diesel fuel, soot concentration, soot area occupation ratio and smoke emissions are smaller with catalytic diesel. As the heating rate increases, the oxidation process of particles moves to high temperature region, however, its peak weight loss rate decreases. At a certain heating rate, the particle activation energy and initial temperature decrease with the increment of nano-CeO2 concentration. It is found that the catalytic diesel could decrease particle sizes, promote the oxidation of particles, and reduce the ignition combustion temperature of particles.

Abalone is a marine gastropod that is an important fishery and food industrial resource, massively maricultured in Asia, Africa, Australia, and America. Marine by-products from boiled abalone, norm...

The microstructure of hydroxyapatite is known to influence cellular behavior, can be used as a substrate for osteoblast growth, and exploited as a drug-release platform. However, easy delamination and self-decomposition of hydroxyapatite caused by poor adhesion with substrates are the main problems currently. In this paper, we successfully fabricated titanium dioxide/strontium-doped hydroxyapatite (TiO2/SrHA) composite scaffolds by self-generated strontium-substituted hydroxyapatite microspheres in TiO2 nanotubes. Moreover, the active compound 1-(5-bromo-2-hydroxy-methoxyphenyl)-ethanone (BHM) from Seahorse (Hippocampus kuda Bleeler) was loaded in this scaffold, and the controlled release kinetics of BHM was studied. It was found that in the first 5 h, the release concentration and time of BHM had a good linear relationship, and the correlation coefficient reached 0.98. TiO2/SrHA/BHM composites exhibited favorable cytocompatibility at a given concentration of BHM (20 μmol/L). Compared to pure SrHA, TiO2 n...

SLC31A1 is the major transporter for platinum drug intake, its expression correlates with drug disposition and response. In 1004 Chinese NSCLC patients with platinum-based chemotherapy, we investigated the association between SLC31A1 polymorphisms and clinical outcomes. Heterozygotes of rs10759637 at 3'UTR was associated with severe thrombocytopenia (odds ratio [OR]: 2.69; P = 0.012) and shorter overall survival (hazard ratio [HR]: 1.24; P = 0.005). Variant homozygote of rs2233914 was correlated with longer overall survival (hazard ratio [HR]: 0.73; P = 0.008). Haplotype and diplotype of these linked SNPs were associated with hematologic toxicities. In stratification analyses, rs10759637 and rs2233914 consistently correlated with overall survival in specific subgroups such as men, smoker, patients older than 58 years, or with ECOG PS 0-1, or with squamous cell carcinoma. rs10759637 could change the local structure of 3'UTR harboring putative binding sites for hsa-miR-29, whose transfection into 16HBE cells resulted in remarkable suppression of gene expression. The rs10759637 variant significantly correlated with lowered luciferase activity in reporter assays and decreased expression of SLC31A1 transcript in tumorous tissues. The study thereby identified functional polymorphism of SLC31A1 that modulates miRNA-3'UTR interaction and gene expression as potential pharmacogenetic biomarker for clinical outcomes of platinum-based chemotherapy in NSCLC patients.

In this study we isolate a heptameric peptide from the marine microalga Pavlova lutheri and examine its inhibitory effect and mechanism of action on the matrix metalloproteinase-9 (MMP-9) protein in human fibrosarcoma HT1080 cells. Through consecutive rounds of purification we isolated a potent MMP-9 inhibitory peptide composed of seven amino acids: Leu-Leu-Ala-Pro-Pro-Glu-Arg (796.4 Da). We show that the mRNA and protein expression levels of MMP-9 are reduced in the presence of this purified peptide. Furthermore, we show that this peptide inhibits PMA-induced translocation of nuclear factor-κB (NF-κB) by suppressing IκB-α phosphorylation and that it suppresses the phosphorylation of the c-Jun N-terminal (JNK) and p38 mitogen-activated protein kinases (MAPKs). Our results indicate that this peptide, purified from P. lutheri, has the potential to be a valuable natural preventive agent against MMP-related diseases.

Abalone viscera (AV) is one of the byproducts of the seafood processing industry. The low molecular weight (&lt, 5 kDa) peptides (LMW-AV) obtained from gastrointestinal digestion of AV could suppress allergenic responses on activated HMC-1 human mast cells in our previous study. Regarding the allergenic response of LMW-AV, in the present study, we further investigated the potential of oral administration of LMW-AV against atopic dermatitis (AD) in a dermatitis-induced model stimulated with Dermatophagoides farinae. The results demonstrated that the LMW-AV reduced a number of clinical symptoms, such as the severity of the dermatitis and serum immunoglobulin E levels. Moreover, LMW-AV could inhibit the expression of chemokines and cytokines. The histological analysis indicated that the LMW-AV has suppressed the eosinophil count and the mast cell infiltration into the upper dermis. The results suggest that LMW-AV can be considered as a promising candidate for AD treatment.

Background There are no generally accepted standards for evaluation of treatment outcomes in traditional Chinese medicine (TCM). Pattern differentiation and individual treatments are recognized as the most distinguishing features of TCM. Therefore, how practitioners determine curative effects is an issue worthy of research, though little has been done in this area up to this point. This study examines perceptions of the effectiveness of TCM treatments and the means of evaluating clinical outcomes from the practitioners’ perspective. Methods Qualitative analysis of semi-structured interviews. Results A total of nine TCM practitioners from three university-affiliated hospitals and two scientific institutions participated in the interviews in August 2013. Participants reported evaluation of periodical treatment as an important part of the process of individual treatment based on pattern differentiation. Themes included (1) ways of evaluating treatment outcomes; (2) relationships between treatment outcomes and pathological transformation; and (3) distinguishing manifestations of the healing process from true adverse reactions. These considerations helped determine the optional treatment principles for further follow-up. An additional theme emerged related to the characteristics of diagnosis and treatment in TCM. Conclusions Health professionals considered all of the following as important ways of evaluating TCM treatment outcomes: patients’ input and subjective experience, physicians’ intake and examination, laboratory tests and medical device measurements. Pathological conditions were determined based on all the above factors, and no single factor determined the effectiveness from the practitioners’ perspectives. If the patients felt no significant beneficial effects, then it was necessary to judge the effectiveness from adverse effect. The follow-up measures were usually based on the previous treatment, and physicians’ satisfaction with each phase of TCM treatment was a significant factor in the process of making further decisions.

The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14 rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR] = 1.39; 95% confidence interval [CI] = 1.16–1.66; P = .0003) and OS (adjusted HR = 1.41; 95% CI = 1.11-1.80; P = .005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14 rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR = 0.86; 95% CI = 0.56-1.33; P = .505). The present study provides evidence that the MAPK14 rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings.

Seahorse is been used as a traditional Chinese medicine and invigorant for many years. Among, the seahorse is considered to have anti-fatigue effects. However, few researches have demonstrated such an effect. This study, the anti-fatigue effect of a novel peptide purified (SH200) from the seahorse (Hippocampus abdominalis) was investigated in C57BL/6 mice. The effect of SH200 on exercise performance was assessed using a Rotarod test and clinical biochemical parameters. In addition, the expression levels of muscular-associated proteins were examined by western blot and immunohistochemical analysis. The results revealed that SH200 prolonged the running time of mice, reduced the expression of creatine, CK, LDH, l -lactate, Citrate, and increased the production serum glucose and FFA, hepatic glycogen, ATP, and SDH. Addition, SH200 also improved mitochondrial function and protected muscle fibers via AMMPK/PGC-1α signal pathway. Thus, the SH200 is a potential candidate natural agent that could be used to reduce physical fatigue.

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-&kappa, B) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-&kappa, B may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone (Haliotis discus hannai) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-&kappa, B pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1&alpha, and the results showed that AATP was combined with an active site of HIF-1&alpha, by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.

Porous hydroxyapatite as a drug carrier is very popular and has many clinical applications. However, traditional hydroxyapatite materials have limited osteogenic capacity. Therefore, the development of a new hydroxyapatite drug delivery system is essential for bone tissue engineering. In this study, the metal element Sr was used to replace Ca, and the SrHA microspheres were successfully prepared by hydrothermal reaction. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to characterize SrHA (strontium-doped hydroxyapatite) microspheres obtained from hydrothermal reaction conditions. In addition, the drug utility was enhanced by loading the marine active compound 1-(5-bromo-2-hydroxy-4-methoxyphenyl)-ethanone (HKB). Furthermore, after co-culture with preosteoblasts, experiments indicated that HKB/SrHA composite microspheres had a more significant effect on the proliferation and differentiation of cells compared to pure SrHA. These HKB/SrHA composite microspheres may be applied to the drug delivery system of bone tissue repair.

Interplay of pioneer transcription factor forkhead box A1 (FOXA1) and estrogen receptor has been implicated in sexual dimorphism in hepatocellular carcinoma (HCC), but etiological relevance of its polymorphism was unknown. In the case control study (1152 patients versus1242 controls), we observed significant increase in HCC susceptibility in hepatitis B virus carriers associated with a non-synonymous Thr83Ala variant of FOXA1 (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.11−1.48, for Ala83-containing genotype, after validation in an independent population with 933 patients versus 1030 controls), a tightly linked (CGC)5/6or7 repeat polymorphism at its promoter (OR 1.32; 95% CI 1.10–1.60, for (CGC)6or7-repeat-containing genotype), and their combined haplotype (OR 1.50; 95% CI 1.24–1.81, for (CGC)6or7−Ala83 haplotype). The susceptible FOXA1-Ala83 impairs its interaction with ERα, attenuates transactivation toward some of their dual target genes, such as type 1 iodothyronine deiodinase, UDP glucuronosyltransferase 2 family, polypeptide B17 and sodium/taurocholate cotransporting polypeptide, but correlates with strengthened cellular expression of α-fetoprotein (AFP) and elevated AFP serum concentration in HCC patients (n = 1096). The susceptible FOXA1 cis-variant with (CGC)6or7 repeat strengthens the binding to transcription factor early growth response 1 and enhances promoter activity and gene expression. Evolutionary population genetics analyses with public datasets reveal significant population differentiation and unique haplotype structure of the derived protective FOXA1-Thr83 and suggest that it may have undergone positive natural selection in Chinese population. These findings epidemiologically highlight the functional significance of FOXA1-ERα transcriptional program and regulatory network in liver cancer development.

Objective. The aim of this study was to evaluate the effectiveness of traditional Chinese medicine- (TCM-) guided dietary interventions in improving yang-qi deficiency and yin-blood deficiency TCM syndromes according to the principles of TCM syndrome differentiation theory in male youths undergoing drug detoxification during the rehabilitation period who stayed in a compulsory isolation detoxification center. Methods. Male youths undergoing drug detoxification who met the criteria to be included in the study were randomly divided into the intervention group (n = 62) and the control group (n = 61) according to a random number table in a 1 : 1 ratio. The intervention group received a TCM-guided diet, and the control group received routine food support. Over an intervention period of 3 months, we observed changes in the TCM syndrome element scores in the two groups before and after intervention. Results. After 3 months, the qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndrome in the intervention group improved significantly (P values 0.009, 0.000, 0.005, and 0.001, respectively). In the control group, yang deficiency, qi deficiency, and yang-qi deficiency syndromes worsened significantly (P values 0.003, 0.032, and 0.009, respectively). The differences (post-pre) in yang deficiency, qi deficiency, yang-qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndromes between the two groups were statistically significant (P values 0.003, 0.003, 0.003, 0.001, 0.005, and 0.002, respectively). Conclusion. A TCM-guided diet can delay the worsening of yang-qi deficiency syndrome symptoms and improve yin-blood deficiency syndrome and the prognosis of male youth undergoing drug detoxification during the rehabilitation period.

In order to reduce soot emission and assist diesel particulate filter regeneration, iron-based fuel borne catalyst (Fe-FBC) was added into diesel fuel with Fe element mass fractions of 0, 200 and 400 mg/kg in the preparation of FBC fuels (marked as Diesel, Fe200 and Fe400). The in-cylinder soot distribution, pollutant emissions and particle physicochemical properties of FBC fuels were investigated on a visualization modified common-rail engine. The results show that the combustion starting point is advanced with Fe-FBC addition, while the maximum combustion pressure and heat release rate increase. The addition of Fe-FBC in diesel fuel will shorten ignition delay period, accelerate combustion process and lead to the increase of in-cylinder flame temperature, while the in-cylinder soot concentration and soot area occupation ratio are reduced significantly. HC, CO and soot emissions along with the unconventional emissions such as HCHO, CH3CHO and polycyclic aromatic hydrocarbons (PAHs) decrease at each load as the increase of Fe-FBC addition ratio. Compared with Diesel, the peak soot area occupation ratio and soot emissions of Fe400 decrease by 41.6% and 20.4% respectively at full load. It is also found that Fe-FBC addition decreases particle box-counting dimension, which indicates that the polymerization degree between the particles becomes weaker and their arrangement becomes more sparse and loose, so the oxidation characteristic temperature and the activation energy of soot particles decrease significantly. Fe-FBC addition can effectively reduce the type and content of PAHs and the high carbon atom number compounds in soluble organic fraction from exhaust particles.

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people’s health, and the incidence of ALD is increasing, therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.