Weak Acidic pH Research Articles

Preparation and Evaluation of Immune Boosting Syrup using Wheat Grass & Pumpkin Seeds Extract

A research work on Preparation and Evaluation of Immune Boosting Syrup using Wheat grass & Pumpkin seeds extract. Human immune system is a complex network of cells, tissues, organs and proteins. When bacteria, virus, toxins, chemicals invade the body, immune system recognizes an antigen and help the body fight infections and other diseases by producing antibodies. Antibodies are proteins that work to attack the antigen and also weaken, destroy antigens. In this research work wheat grass and pumpkin seeds used as immune boosting agents. Wheat grass and pumpkin seeds contain variety of nutrients, minerals, vitamins, ant-bacterial, anti-microbial, anti-oxidizing agents that boost the immune system. Extracts of natural immune boosters added to the sucrose syrup one by one. Add orange syrup as flavoring agent to the syrup. A lemon yellow color, moderate viscous, orange flavored syrup, weak acidic pH, good theology of syrup was prepared. Stability analysis studies of syrup at different temperatures gives good results.

5-N-Carboxyimino-6-aminopyrimidine-2,4(3H)-dione, a novel indicator for hypochlorite formation.

Uric acid is an adequate and endogenous probe for identifying reactive oxygen or nitrogen species generated in vivo because its oxidation products are specific to reacted reactive oxygen or nitrogen species. Recently, we identified 5-N-carboxyimino-6-N-chloroaminopyrimidine-2,4(3H)-dione as a hypochlorite-specific oxidation product. 5-N-carboxyimino-6-N-chloroaminopyrimidine-2,4(3H)-dione was anticipated to be a biomarker for hypochlorite production in vivo. However, while it was stable in aqueous solution at weak acidic and alkaline pH (6.0-8.0), it was unstable in human plasma. In this study, we found that 5-N-carboxyimino-6-N-chloroaminopyrimidine-2,4(3H)-dione rapidly reacted with thiol compounds such as cysteine and glutathione to yield 5-N-carboxyimino-6-aminopyrimidine-2,4(3H)-dione, which was stable in human plasma unlike 5-N-carboxyimino-6-N-chloroaminopyrimidine-2,4(3H)-dione. 5-N-carboxyimino-6-aminopyrimidine-2,4(3H)-dione was produced upon uric acid degradation during myeloperoxidase-induced uric acid oxidation and lipopolysaccharide-induced pseudo-inflammation in collected 2,4(3H)-dione has potential as a marker for hypochlorite production in vivo.

Study on semi-dynamic leaching and microstructure characteristics of MSWI fly ash solidified sediment

municipal solid waste incineration (MSWI) fly ash partially replaces cement to solidify sediment, and then can be used as intermediate cover materials in landfill as one of the resources utilization ways of MSWI fly ash and sediment. The strength and the semi-dynamic leaching characteristics of MSWI fly ash solidified sediment under hydrochloric acid attack at different pH were studied by means of unconfined compressive strength (UCS), semi-dynamic leaching, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA). Results revealed that the UCS strength increased as the curing age and cement content increased. When the curing content is 50% and the replacement ratio of MSWI fly ash is 75% and 80%, the UCS of 7 d can be greater than 50 kPa. The primary contribution to the strength development was from silicic acid gels such as calcium silicate hydrate (C–S–H) and carbonates. Notably, the leaching behavior of Zn and Cu within the solidified sediment underwent substantial alterations. The leaching amount of heavy metals in a strong acidic environment (pH = 2) is significantly greater than that in a weak acidic (pH = 4) and neutral (pH = 7) environment. Conversely, minimal disparities were observed in the leaching characteristics of Zn and Cu between the weakly acidic and neutral environments. Ca(OH)2, C–S–H and carbonate exhibits a remarkable acid-resistant buffering capacity in the solidified sediment. The obvious diffusion coefficient (Dobs) was less than 10−9 m2/s in semi-dynamic leaching tests. Moreover, the mobility of Zn and Cu surpassing 12.5, coupled with a leaching index exceeding 8, further attests to the favorable S/S outcome achieved. Based on these findings, the solidified material is confidently recommended to be used as suitable landfill middle soil cover material.

Metal–Organic Framework PCN-224 Integrated with Manganese Dioxide, Platinum Nanoparticles, and Glucose Oxidase for Enhanced Cancer Chemodynamic Therapy

Chemodynamic therapy (CDT) is a highly promising tumor treatment modality that uses the Fenton reaction to convert intracellular hydrogen peroxide (H2O2) into cytotoxic hydroxyl groups (•OH). However, the therapeutic effects of CDT have been restricted by weak acidic pH values, insufficient H2O2 levels, and high glutathione (GSH) concentrations in the tumor microenvironment (TME). In this study, to construct PCN-224-Pt/GOD, porphyrin-based metal–organic framework nanoparticles (PCN-224) were used as the carrier to load Pt and glucose oxidase (GOD). The surface of PCN-224-Pt/GOD was covered with manganese dioxide (MnO2) to fabricate the multifunctional composite nanoparticles PCN-224-Pt/GOD@MnO2 (P–P/GOD@Mn). P–P/GOD@Mn was used to increase H2O2 levels and to decrease GSH levels for combined CDT and starvation therapy. As a result, we developed P–P/GOD@Mn nanoparticles (diameter, approximately 280 nm) with favorable size and biocompatibility. Under simulated TME conditions, P–P/GOD@Mn nanoparticles could catalyze H2O2 to generate cytotoxic hydroxyl radicals (•OH), consume glutathione (GSH), and decompose H2O2 to generate oxygen (O2). Cellular toxicity assay results showed that P–P/GOD@Mn killed MCF-7 cells in the TME, with a rate of 77%. The results of tumor-bearing mouse experiments proved that P–P/GOD@Mn nanoparticles could significantly suppress tumor cell growth, which shows the great potential of this entity in CDT and its possibility in bimodal cancer therapy.

PH and GSH dual-responsive drug-controlled nanomicelles for breast cancer treatment

We developed a pH/glutathione (GSH) dual-responsive smart nano-drug delivery system to achieve targeted release of a chemotherapeutic drug at breast tumor site. Doxorubicin (DOX) was linked to polyethylene glycol (PEG) through cis-aconitic anhydride (CA) and disulfide bonds (SS) to obtain the PEG-SS-CA-DOX prodrug, which spontaneously assembled into nanomicelles with a particle size of 48 ± 0.45 nm. PEG-SS-CA-DOX micelles achieved an efficient and rapid release of DOX under dual stimulation by weak acidic pH and high GSH content of tumors, with the release amount reaching 88.0% within 48 h. Cellular uptake experiments demonstrated that PEG-SS-CA-DOX micelles could efficiently transport DOX into cells and rapidly release it in the tumor microenvironment. In addition, in vivo antitumor experiments showed that PEG-SS-CA-DOX had a high inhibition rate of 70% against 4T1 breast cancer cells along with good biosafety. In conclusion, dual-responsive smart nanomicelles can achieve tumor-targeted drug delivery and specific drug release, thus improving therapeutic efficacy of drugs.

Retention potential of a drained wetland in the Lusatian lignite mining district, Briesener Niedermoor, Germany, Europe

Acid mine drainage (AMD) is one of the most important global causes for polluted water. It occurs in mining areas due to oxidation of sulfide minerals. Depending on hydrological conditions, wetlands are considered suitable for passive treatment of AMD. The aim of the study was to characterize the long-term retention performance of a drained wetland, Briesener Niedermoor, in an iron and sulfate contaminated catchment area. The site is located in the Lusatian lignite mining district, Germany. Hydrological and hydrochemical measurements as well as time series of groundwater and surface water were evaluated and saturation conditions of iron species were determined using Phreeqc Interactive and EH–pH diagrams for the Fe–S–K–O–H system. Progressing peat degradation due to drainage leads to a hydraulic behaviour of the wetland that is more comparable to a rain bog than a fen, and thus to more pronounced oxic conditions. Groundwater feeds the wetland with significant loads of iron and sulfate, which are temporally stored in the wetland. At low surface water discharge, iron is removed and weak acidic pH is buffered by the dominant phase of schwertmannite (Fe8O8(OH)6SO4), usually during summer months. In winter, greater water availability initializes a high source strength from the wetland, that cannot be retarded. Thus, only during summer, there is a retention potential; in winter, the retention potential is not strong enough to prevent an inflow of iron and sulfate. Only a significant rewetting of the wetland may result in a restoration of the retention potential of the wetland Briesener Niedermoor.

A phase separation process induced by pH change for purification of His-tagged protein at low salt concentration

Protein purification is critical for protein research and enzyme manufacture, and efficient purification methods with low cost have a high priority. In this study, the difference in solubility between His-tagged protein and nontagged protein led to a liquid-solid phase separation at neutral pH and low salt concentration and purified His-tagged protein to some extent. The investigation of impurity in the precipitate indicated that solvation behavior varied from several oligo-amino acid tagged proteins. Among them, proteins with oligo-Lys, oligo-Trp and oligo-Arg obviously precipitated at low salt concentration and weak acidic pH, which is similar to that for the precipitation of His-tagged protein. Further study suggested that proteins with oligo-Lys, oligo-Trp and oligo-Arg remained a precipitate state while His-tagged protein dissolved at a slightly higher pH value. Based on these finding, a method was developed for the purification of His-tagged protein via phase separation induced by pH (PSIP) at low salt concentration. Though the yield and purity of protein purified by PSIP were slightly inferior to that by immobilized metal ion affinity chromatography (IMAC), PSIP was a high-throughput and low-cost method for purification of His-tagged proteins. Beyond the purification process, the various solvation behaviors of proteins with different oligo-amino acid also provide a reference for solvation research of protein.

Photocatalytic transfer of aqueous nitrogen into ammonia using nickel-titanium-layered double hydroxide.

The development of solar-driven transfer of atmospheric nitrogen into ammonia is one of the green and sustainable strategies in industrial ammonia production. Nickel-titanium-layered double hydroxide (NiTi-LDH) was synthesised using the soft-chemical process for atmospheric nitrogen fixation application under photocatalysis in an aqueous system. NiTi-LDH was investigated using advanced characterisation techniques and confirmed the potential oxygen vacancies and/or surface defects owing to better photocatalytic activity under the solar spectrum. It also exhibited a bandgap of 2.8eV that revealed its promising visible-light catalytic activities. A maximum of 33.52µmol L-1 aqueous NH3 was obtained by continuous nitrogen (99.9% purity) supply into the photoreactor under an LED light source. Atmospheric nitrogen supply (≈78%) yielded 14.67µmol L-1 aqueous NH3 within 60min but gradually reduced to 3.6µmol L-1 at 330min. Interestingly, in weak acidic pH, 20.90µmol L-1 NH3 was produced compared to 11.51µmol L-1 NH3 in basic pH. The application of NiTi-LDH for visible-light harvesting capability and photoreduction of atmospheric N2 into NH3 thereby opens a new horizon of eco-friendly NH3 production using natural sunlight as alternative driving energy.

The convergence of in silico approach and nanomedicine for efficient cancer treatment; in vitro investigations on curcumin loaded multifunctional graphene oxide nanocomposite structure

The development of multifunctional nano-carriers with the ability of stimuli responsive controlled drug release can address many of the challenges of current cancer therapies. Graphene oxide (GO)-based nanomaterials with great specific surface area and oxygen-rich functional groups show desirable advantages for drug delivery systems. Therefore, in this research, GO sheets were functionalized by grafting hyperbranched polyglycerol- (HPG) through anionic ring-opening multi-branching polymerization (Anionic-ROMBP) of glycidol monomer. Then, magnetic nanoparticles (MNPs) were fabricated between the branches and on the surface of GO using the co-precipitation method (GO-HPG-MNPs). An anti-cancer model drug, curcumin (CUR), was loaded inside the nano-carrier via hydrophobic and π-π stacking interactions. After determining drug release pattern at weak acidic and physiological pH, the cytotoxicity of nano-carrier was investigated by MTT assay. FITC Annexin V/PI apoptosis detection kit was also applied to determine the method of cancer cells death. In addition to the in vitro studies, iATC-mISF bioinformatics server was used to predict the therapeutic and anatomical properties of CUR and its 75 derivatives. According to the results, GO-HPG-MNPs-(CUR) with negative surface charge (−49.4 mV) represented about 198% drug loading capacity and pH-responsive drug release. Results of MTT assay and flow cytometry confirmed cytotoxicity and apoptotic ability of GO-HPG-MNPs-(CUR) in cancer cells, while GO-HPG-MNPs (without drug) was biocompatible with no tangible toxicity. Moreover, for the first time, the conformity of MTT assay data and bioinformatics predictions exhibited the specific therapeutic/anatomical potential of CUR and about 51% of its derivatives on the nervous system. Thus, GO-HPG-MNPs-(CUR) can be suggested as a new type of functional nano-carrier in anti-cancer drug delivery and targeted cancer therapy.

Weakly Acidic pH and Reduction Dual Stimuli-Responsive Gel Particles

This paper reports the facile preparation of dual stimuli-responsive gel particles that simultaneously respond to weakly acidic and reducing stimuli and the application of these gel particles as a drug delivery carrier. The dual stimuli-responsive gel particles composed of a pH-responsive polymer network cross-linked with reduction stimuli-responsive disulfide cross-links, and biocompatible poly(ethylene glycol) cross-links were prepared by soap-free emulsion polymerization. The resulting gel particles were colloidally stable at physiological ionic strength and had a diameter of approximately 200 nm with a narrow size distribution. The resulting gel particles slightly swelled in an acidic environment. On the other hand, the gel particles drastically swelled under simultaneous weakly acidic and reducing conditions because of the ionization of tertiary amino groups in the gel network and a decrease in the cross-linking density resulting from cleavage of the disulfide cross-links. When cells were treated with the gel particles, they were taken up by cells via the endocytosis pathway and distributed in the cytosol after endosomal escape by the proton sponge effect. In addition, a hydrophobic drug, doxorubicin (Dox), was loaded into the gel particles through hydrophobic interactions. Dox was released from the gel particles under weakly acidic and reducing conditions, while the Dox release was inhibited at neutral pH. The weakly acidic pH- and reduction stimuli-responsive release of Dox from gel particles was attributed to the drastic swelling of these particles. The fascinating properties of the dual stimuli-responsive gel particles suggest that they can provide a useful platform for designing intracellular drug delivery carriers.

The adsorption of As(V) on poorly crystalline Fe oxyhydroxides, revisited: Effect of the reaction media and the drying treatment

Arsenic (As) adsorbed on Fe oxyhydroxides (adsorbent) is widely occurring in many environmental settings such as in acid mine drainage systems or in the hydrometallurgical operations to form Fe-As coprecipitates. However, the influence of the reaction media and the drying treatment on the microstructure of the directly formed adsorbents at various pHs was still not fully understood. In this work, As adsorption behaviors on various forms of Fe oxyhydroxides were systematically investigated by using XRD, FTIR, Raman, XANES, and HRTEM. The results revealed that at weak acidic pH, more As could adsorbed on the suspension adsorbent formed in sulfate and chloride media than that in nitrate media, possibly due to the microstructure alteration of the adsorbent in the presence of sulfate and chloride. Besides, the increasing crystallinity of the Fe oxyhydroxides and the aggregation effect after drying were the major reasons why less As could be hold by the dried adsorbents than that of the corresponding suspension adsorbents. These findings could shed more light on the nature of the Fe oxyhydroxides which may be helpful for more precisely predicting the fate of some toxic metal(loid)s in the environment.

Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes.

IntroductionHyperoside (HYP), a flavonol glycoside compound, has been shown to significantly inhibit the proliferation of malignant tumors. Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy.ObjectiveWe report a novel dual-functional liposome system possessing both extracellular charge reversal and mitochondrial targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of cancer cells.MethodsL-lysine was used as a linker to connect 2,3-dimethylmaleic anhydride (DMA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a new compound, DSPE-Lys-DMA (DLD). Then, DLD was mixed with other commercially available lipids to form charge reversed and mitochondria-targeted liposomes (DLD-Lip). The size, morphology, zeta potential, serum stability, and protein adsorption of the HYP loaded DLD-Lip (HYP/DLD-Lip) were measured. The release profile, cellular uptake, in vitro and in vivo toxicity, and anticancer activity of HYP/DLD-Lip were investigated.ResultsThe results showed that the mean diameter of the liposomes was less than 200 nm. The zeta potential of the liposomes was negative at pH 7.4. However, the zeta potential was positive at weak acidic pH values with the cleavage of the DMA amide. The charge reversion of HYP/DLD-Lip facilitated the cellular internalization and mitochondrial accumulation for enhanced antitumor effect. The strongest tumor growth inhibition (TGI 88.79%) without systemic toxicity was observed in DLD/HYP-Lips-treated CBRH-7919 tumor xenograft BALB/C mice.ConclusionThe charge reversed and mitochondria-targeted liposomes represented a promising anticancer drug delivery system for enhanced anticancer therapeutic efficacy.

Development of paclitaxel-loaded poly(lactic acid)/hydroxyapatite core-shell nanoparticles as a stimuli-responsive drug delivery system.

Biodegradable nanoparticles have been well studied as biocompatible delivery systems. Nanoparticles of less than 200 nm in size can facilitate the passive targeting of drugs to tumour tissues and their accumulation therein via the enhanced permeability and retention (EPR) effect. Recent studies have focused on stimuli-responsive drug delivery systems (DDS) for improving the effectiveness of chemotherapy; for example, pH-sensitive DDS depend on the weakly acidic and neutral extracellular pH of tumour and normal tissues, respectively. In our previous work, core–shell nanoparticles composed of the biodegradable polymer poly(lactic acid) (PLA) and the widely used inorganic biomaterial hydroxyapatite (HAp, which exhibits pH sensitivity) were prepared using a surfactant-free method. These PLA/HAp core–shell nanoparticles could load 750 wt% of a hydrophobic model drug. In this work, the properties of the PLA/HAp core–shell nanoparticles loaded with the anti-cancer drug paclitaxel (PTX) were thoroughly investigated in vitro. Because the PTX-containing nanoparticles were approximately 80 nm in size, they can be expected to facilitate efficient drug delivery via the EPR effect. The core–shell nanoparticles were cytotoxic towards cancer cells (4T1). This was due to the pH sensitivity of the HAp shell, which is stable in neutral conditions and dissolves in acidic conditions. The cytotoxic activity of the PTX-loaded nanoparticles was sustained for up to 48 h, which was suitable for tumour growth inhibition. These results suggest that the core–shell nanoparticles can be suitable drug carriers for various water-insoluble drugs.

Ornithine Decarboxylation System of Shewanella baltica Regulates Putrescine Production and Acid Resistance

Shewanella baltica, one of the dominant spoilers of seafoods, can synthesize putrescine from ornithine under acidic conditions, which could result in food spoilage and health problems. We identified three regulatory enzymes (SpeC, SpeF, and PotE) in the ornithine decarboxylation (ODC) pathway of S. baltica by searching the NCBI database and exploring their functional roles through gene knock-out technology. The ornithine decarboxylase SpeC is an auxiliary adjustor of the ODC system, whereas the ornithine-putrescine transporter SpeE and ornithine decarboxylase SpeF participate in the production of extracellular putrescine. Exogenous addition of ornithine and putrescine promotes the extracellular secretion of putrescine by upregulating the expression of speF and potE. The putrescine biosynthesis and alkalization of cytoplasm is enhanced at weak acidic pH compared with neutral pH, especially at pH 6.0. The maximum upregulation of ODC genes and the optimum decarboxylation activity of SpeF are achieved in a weak acidic environment (pH 6.0), suggesting that the ODC pathway plays an important role in putrescine production and the cytoplasmic acid counteraction of S. baltica. This study contributes to a wider understanding of spoilage mechanisms in food systems and provides theoretical support for developing novel seafood preservation methods.

Enhanced chemodynamic therapy at weak acidic pH based on g-C3N4-supported hemin/Au nanoplatform and cell apoptosis monitoring during treatment

Chemodynamic therapy (CDT), inducing tumor cell apoptosis through Fenton reaction to produce hydroxyl radical (·OH), is an emerging cancer treatment technology. Highly efficient Fenton catalytic reactions usually take place at a low pH environment. Utilizing graphitic carbon nitride supported hemin and Au nanoparticles (g-C3N4/hemin/Au) as a novel biomimetic nanocatalyst, we achieve an enhanced CDT for inducing tumor cell apoptosis in the presence of excess H2O2, and reveal the molecular events during the CDT-induced apoptosis. The prepared g-C3N4/hemin/Au nanohybrids exhibit excellent Fenton catalytic activity for the generation of highly toxic ·OH at weak acidic and neutral condition, which breaks through the limitation of traditional acidity-dependent response. The Fenton catalytic mechanism was also studied. The Fenton efficiency is primarily enhanced by the high affinity between nanohybrids and H2O2, and the transformation of Fe(III) to Fe(IV)=O without the formation of iron hydrate precipitation. Moreover, the intracellular molecular events during the CDT process were monitored. Phenylalanine metabolism was perturbed with protein degradation and DNA structures were damaged, which eventually lead to cell apoptosis. This study provides a significant guidance for the further development of more effective CDT platforms.

Molecular Dynamics Simulation of Cetyl Phosphate Adsorption in Flotation of Magnesite and Pertinent Chemical Aspects

Magnesite ores are important resources in the production of value-added magnesium materials. Generally, low selectivity of conventional collectors and the requirement of a large amount of depressant has been a motivation for researchers to identify alternate collectors. In this work, the role of potassium cetyl phosphate (PCP) as a new collector in magnesite flotation is investigated using molecular dynamics (MD) simulations and chemical equilibria, electrokinetics and wettability. The results indicate that PCP exhibits a strong collecting ability for magnesite particles even with low concentrations. The presence of PCP leads to significant alterations in the electric double layer and contact angle behavior of magnesite, which results in rapid adsorption of PCP on magnesite surface. The results from chemical computations show that the monoanionic forms of PCP are the dominant species in the weakly acidic pH range, where monohydroxy magnesium species and the ion concentration of magnesite in suspension can be controlled by adjusting pH. The adsorption models indicate that the stable adsorption of PCP on magnesite surfaces occurs spontaneously, supporting the potentiality for selective magnesite flotation in its separation from other carbonate minerals.

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone.

Ascorbic acid (AscH2) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in medical practice especially for increasing iron absorption and as an adjuvant therapeutic in iron chelation therapy, but its mode of action and implications in iron metabolism and toxicity are not yet clear. In this study, we used UV–Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe3+ to Fe2+, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe3+ ↔ Fe2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron–ascorbate complex compared to the FeL13 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL13 chelate complex resulting in the formation of mixed L12AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4–5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid, iron, and L1.

Structural Basis for the Robust Substrate Phosphorylation by MAPK p38α Under the Stress-Associated ATP-Decreased, Weakly Acidic pH Condition Elucidated By Solution NMR

p38α, which is a protein kinases, is activated under various kinds of stress stimuli to make cellular responses via the p38α signaling pathway. Although p38α uses ATP for its kinase activity, the ATP concentration severely decreases in stressed cells. Thus, the kinase activity of p38α can be impaired under stress conditions. In addition, stress stimuli induce cytosolic pH from the normal condition of 7.2-7.4 to the stressed condition around 6.7. Such a weak acidification could compromise the structural integrity of proteins. Nevertheless, p38α phosphorylates its substrates under the stress conditions, thereby transducing its responsive signals. However, structural bases for the robust and efficient stress signaling are yet to be elucidated. In this research, we hypothesized that the stress-associated environmental changes, ATP decrease and weak acidification, are mutually associated to optimize the kinase activity of p38α. To verify this hypothesis, we investigated the effect of the weak acidification on the kinase activity of p38α in an ATP concentration-dependent manner. As a result, we found that p38α efficiently used dilute ATP under the weakly acidic pH conditions for phosphorylating a substrate. This was achieved by the acidification-dependent enhancement of the affinity of p38α for ATP. Solution NMR analyses revealed that there was the functional equilibrium of p38α between the ATP high- and low-affinity states, which was shifted toward the high-affinity state upon the weak acidification. Mutational analyses identified two pH sensor histidine residues with protonation equilibrium constants of approx. 7.0, which were most sensitive to the stress-associated weak acidification. It was concluded that p38α utilizes the dynamic, pH-responsive structural mechanism to robustly retain the kinase activity within ATP-decreased environments that are caused by stress stimuli.

FORMULATION AND INVESTIGATION OF ANTIOXIDANT POTENTIAL OF O/W LOTIONS CONTAINING Tamarindus indica L. FRUIT PULP EXTRACT

The fruit pulp extracts of Tamarindus indica have been reported to possess several biological activities, especially antioxidant property which is suitable for cosmetic application. Therefore, the aims of this study were to formulate the tamarind fruit pulp extract loaded lotions (o/w emulsions), and to assess the antioxidant activity of tamarind fruit pulp extract loaded lotions. Initially, tamarind fruit pulp extracts were prepared by a solvent extraction method. The solvents used were water or a mixture of water and ethanol (water: ethanol= 1:1). Afterwards, the obtained tamarind fruit pulp extracts were subjected to lyophilization process. The tamarind fruit pulp extracts were tested for antioxidant activity by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay to determine suitable concentrations of the extracts to be incorporated into the lotions, which were 2 and 4%w/w in the current study. Apart from the basic ingredients of the oil phase and water phase, ViscOptima SE (2%w/w) was selected as an emulsifier and a thickener of the formulations. The tamarind fruit pulp extract loaded lotions were characterized for physicochemical property and antioxidant potential. The freshly prepared tamarind fruit pulp extract loaded lotions were light brown with homogeneity and no phase separation was observed after centrifugation at 3,000 rpm for 30 min. They had weak acidic pH (4.4-5.1), considered acceptable for skin application. The loaded formulations (F1, 2%w/w) and F2, 4%w/w)) exhibited significantly higher conductivity values than that of the unloaded formulation (F0) (p<0.05). The formulations behaved as pseudoplastic flows with low viscosity. The DPPH measurement revealed that the formulations F1 and F2 had potential antioxidant activity. In conclusion, topical o/w lotions containing tamarind fruit pulp extract were successfully prepared. They had substantial antioxidant activities. As a result, tamarind fruit pulp extract loaded lotions displayed a potential use in cosmetic formulations, especially antiaging products.

Dopamine Delivery via pH-Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs.

Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor-localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic-ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half-life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH-responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.