Eudragit S100 coated nanodiamond-based nanoparticles as an oral chemo-photothermal delivery system for local treatment of colon cancer.

Oral colonic nano-drug delivery system has received more and more attention in the treatment of colon cancer due to local precision treatment and reduction of drug system distribution. However, the complex and harsh gastrointestinal environment and the retention of nanoparticles in the colon limit its development. To this end, we designed Eudragit S100 (ES) coated nanoparticles (ES@PND-PEG-TPP/DOX). Polydopamine coated nanodiamond (PND) was modified with amino-functionalized polyethylene glycol (NH2-PEG-NH2) and triphenylphosphine (TPP) successively. Due to the high specific surface area of PND, it can efficiently load the model drug doxorubicin hydrochloride (DOX). In addition, PND also has high photothermal conversion efficiency, generating heat to kill cancer cells under near infrared (NIR) laser, realizing the combination of chemotherapy and photothermal therapy (CT-PTT). TPP modification enhanced nanoparticle uptake by colon cancer cells and prolonged preparations retention time at the colon. ES shell protected the drug from being destroyed and prevented the nanoparticles from sticking to the small intestine. Ex vitro fluorescence imaging showed that TPP modification can enhance the residence time of nanoparticles in the colon. In vivo pharmacodynamics demonstrated that CT-PTT group has the greatest inhibitory effect on tumor growth, which means that the nanocarrier has potential clinical value in the in-situ treatment of colon cancer.

Effect of yoga on cancer-related fatigue in patients with breast cancer: A systematic review and meta-analysis.

BACKGROUND: Breast cancer is a common malignant tumor in women and most patients with breast cancer experience fatigue. Numerous studies have investigated the relationship between yoga and cancer-related fatigue (CRF) in patients with breast cancer. However, these studies drew their conclusions from small sample sizes and lacked sufficient evidence to demonstrate that yoga can effectively alleviate CRF. Therefore, this meta-analysis aims to systematically examine the effects of yoga on cancer fatigue in patients with breast cancer and establish a scientific basis for enhancing their quality of life. OBJECTIVE: To assess the effect of yoga on CRF in patients with breast cancer. METHODS: Computer searches were conducted on PubMed, Embase, Web of Science, CKNI, and Wanfang databases to retrieve articles related to yoga and CRF in patients with breast cancer from the hospital establishment date to July 2023. The literature was independently screened, and the information was extracted by the researchers. A meta-analysis was conducted using Review Manager Software (version 5.3). RESULTS: The findings from the meta-analysis of 18 studies indicate that yoga can effectively enhance CFR (standardized mean difference (SMD) = -0.51, 95% confidence interval [CI] = -0.92 to -0.10), improve sleep quality (MD = -3.86, 95%CI = -4.03 to -3.70) in patients with breast cancer, alleviate anxiety and depression (SMD = -0.93, 95%CI = -1.68, -0.18, SMD = -1.23, 95%CI = -2.02 to -0.44), and enhance quality of life (MD = -11.20, 95%CI = -14.16 to -8.24). CONCLUSION: Our study offers evidence for the subsequent reduction of CFR in patients with breast cancer. Yoga can alleviate fatigue, improve sleep quality and negative emotions, and improve the quality of life of patients with breast cancer.

Comparison of prediction models for soy protein isolate hydrolysates bitterness built using sensory, spectrofluorometric and chromatographic data from varying enzymes and degree of hydrolysis.

The bitterness of soy protein isolate hydrolysates prepared using five proteases at varying degree of hydrolysis (DH) and its relation to physicochemical properties, i.e., surface hydrophobicity (H0), relative hydrophobicity (RH), and molecular weight (MW), were studied and developed for predictive modelling using machine learning. Bitter scores were collected from sensory analysis and assigned as the target, while the physicochemical properties were assigned as the features. The modelling involved data pre-processing with local outlier factor; model development with support vector machine, linear regression, adaptive boosting, and K-nearest neighbors algorithms; and performance evaluation by 10-fold stratified cross-validation. The results indicated that alcalase hydrolysates were the most bitter, followed by protamex, flavorzyme, papain, and bromelain. Distinctive correlation results were found among the physicochemical properties, influenced by the disparity of each protease. Among the features, the combination of RH-MW fitted various classification models and resulted in the best prediction performance.

Guided self-help mindfulness-based intervention for increasing psychological resilience and reducing job burnout in psychiatric nurses: A randomized controlled trial.

AIMS: The present study aimed to explore the effects of a guided self-help mindfulness intervention on psychological resilience and job burnout among psychiatric nurses. BACKGROUND: Psychiatric nurses work in challenging and potentially high stress settings. Mindfulness interventions can improve psychological resilience and reduce job burnout of nurses. However, face-to-face delivery of mindfulness interventions may be inconvenient for individuals. Guided self-help interventions may be more accessible. METHODS: This randomized controlled trial was conducted from January to August 2022. One hundred and eighteen psychiatric nurses were randomized into the intervention and control groups. The individuals in the intervention group received an 8-week guided self-help mindfulness intervention, while the individuals in the control group received a psycho-educational brochure. The Five Facet Mindfulness Questionnaire, the Connor-Davidson Resilience Scale and the Maslach Burnout Inventory-Human Services Survey were used to evaluate the levels of mindfulness, psychological resilience and job burnout, respectively. RESULTS: After an 8-week intervention, compared with the control group, the levels of mindfulness and psychological resilience were higher, while the level of job burnout was lower in the intervention group. CONCLUSIONS: The guided self-help mindfulness intervention can improve psychological resilience and reduce job burnout among psychiatric nurses.

Chemoproteomics reveals Sofalcone inhibits the inflammatory response of Caco-2 cells by covalently targeting HMGB1.

Sofalcone (Sof), a synthetic analog of sophoradin, is a type of natural phenol derived from the traditional medicinal herb Sophora subprostrata, with potent anti-inflammatory activity. However, the mechanisms of action of Sof for treating intestinal-associated inflammation are not well known. In this work, we identified high mobility group box 1 (HMGB1) as the key covalent target of Sof for the anti-inflammatory activity in the human colonic epithelial cells through quantitative chemoproteomics profiling.

Using a Multi-isotope Approach and Isotope Mixing Models to Trace and Quantify Phosphorus Sources in the Tuojiang River, Southwest China.

Identifying phosphorus (P) sources is critical for solving eutrophication and controlling P in aquatic environments. Phosphate oxygen isotopes (δ18Op) have been used to trace P sources. However, the application of this method has been greatly restricted due to δ18OP values from the potential source having wide and overlapping ranges. In this research, P sources were traced by combining δ18Op with multiple stable isotopes of nitrogen (δ15N), hydrogen (δD), and dissolved inorganic carbon (δ13C). Then, a Bayesian-based Stable Isotope Analysis in R (SIAR) model and IsoSource model were used to estimate the proportional contributions of the potential sources in the Tuojiang River. δ18Op was not in equilibrium with ambient water, and statistically significant differences in the δ18Op values were found between the potential sources, indicating that δ18Op can be used to trace the P sources. δ15N, δD, and δ13C could assist δ18Op in identifying the main sources of P. The SIAR and IsoSource models suggested that industrial and domestic sewage was the largest contributor, followed by phosphate rock and phosphogypsum and agricultural sewage. The uncertainty of the calculation results of the SIAR model was lower than that of the IsoSource model. These findings provide new insights into tracing P sources using multiple stable isotopes in watersheds.

Tea intake and risk of kidney stones: A mendelian randomization study.

OBJECTIVES: Observational studies indicate that tea intake is associated with a decreased risk of kidney stones. Here we performed a mendelian randomization (MR) analysis to evaluate whether this association is causal. METHODS: Forty-four independent genetic variants strongly associated with tea intake were identified from a large genome-wide association study, including 448 060 individuals of the UK Biobank. We additionally obtained genome-wide association study summary statistics for kidney stones from the FinnGen consortium (5985 cases and 253 943 controls) and UK Biobank (6536 cases and 388 508 controls). Random-effect inverse variance weighted regression was used to evaluate causal estimates. The random-effect inverse variance weighted estimates based on the FinnGen consortium and UK Biobank were meta-analyzed using fixed-effects meta-analysis. Other MR methods, including MR-Egger, weighted median, weighted mode, and MR-Pleiotropy RESidual Sum and Outlier, were also performed to test the robustness of our results. RESULTS: In a combined sample of 12 521 cases and 642 451 controls, the inverse variance weighted analysis indicated that genetically predicted tea intake was causally associated with a decreased risk of kidney stones (odds ratio = 0.47; 95% CI, 0.34-0.66; P < 0.001). This association was consistent in other MR methods. CONCLUSIONS: This study suggests that tea intake may be causally associated with a decreased risk of kidney stones.

Juglone promotes antitumor activity against prostate cancer via suppressing glycolysis and oxidative phosphorylation.

The treatments currently used for prostate cancer (PC) do not meet clinical needs, and thus, new therapies with greater effectiveness are urgently required. Metabolic reprogramming of tumor cells is emerging as an exciting field for cancer therapy. Although the Warburg effect is a common feature of glucose metabolism in many cancers, PC cells have a unique metabolic phenotype. Non-neoplastic prostate cells show reduced oxidative phosphorylation (OXPHOS) because large, accumulated zinc inhibits citrate oxidation. During transformation, there are low levels of zinc in PC cells, and the tricarboxylic acid (TCA) cycle is reactivated. However, metastatic PC exhibits the Warburg effect. Due to metabolic differences in prostate tissue, targeting metabolic alterations in PC cells is an attractive therapeutic strategy. In this study, we investigated the effect of juglone on energy metabolism in PC cells. We found that juglone inhibited cell proliferation and induced apoptosis. Mechanistically, we demonstrated that juglone suppressed OXPHOS and glycolysis due to its inhibition of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) activity. Furthermore, downregulation of PFK and PK, but not HK contributed to the inhibition of these enzyme activities. The current study indicates that further development of juglone for PC treatment would be beneficial.

Preparation and activity study of Ruoqiang jujube polysaccharide copper chelate.

Background: Polysaccharide metal chelate exhibit both immunoregulatory activity and metal element supplementation effects. Methods: In this study, Ruoqiang jujube polysaccharide copper chelate (RJP-Cu) was prepared and the preparation conditions were optimized using the response surface method. Subsequently, RJP-Cu was administered to lambs to evaluate its impact on growth performance, copper ion (Cu2+) supplementation, immune enhancement, and intestinal flora was evaluated. Results: The results indicated that optimal RJP-Cu chelation conditions included a sodium citrate content of 0.5 g, a reaction temperature of 50°C, and a solution pH of 8.0, resulting in a Cu2+ concentration of 583°mg/kg in RJP-Cu. Scanning electron microscopy (SEM) revealed significant structural changes in RJP before and after chelation. RJP-Cu displaying characteristic peaks of both polysaccharides and Cu2+ chelates. Blood routine indexes showed no significant differences among the RJP-Cu-High dose group (RJP-Cu-H), RJP-Cu-Medium dose group (RJP-Cu-M), RJP-Cu-low dose group (RJP-Cu-L) and the control group (p > 0.05). However, compared with the control group, the RJP-Cu-H, M, and L dose groups significantly enhanced lamb production performance (p < 0.05). Furthermore, RJP-Cu-H, M, and L dose groups significantly increased serum Cu2+ concentration, total antioxidant capacity (T-AOC), catalase (CAT), and total superoxide dismutase (T-SOD) contents compared with control group (p < 0.05). The RJP-Cu-H group exhibited significant increases in serum IgA and IgG antibodies, as well as the secretion of cytokines IL-2, IL-4, and TNF-α compared to the control group (p < 0.05). Furthermore, RJP-Cu-H group increased the species abundance of lamb intestinal microbiota, abundance and quantity of beneficial bacteria, and decrease the abundance and quantity of harmful bacteria. The RJP-Cu-H led to the promotion of the synthesis of various Short Chain Fatty Acids (SCFAs), improvements in atrazine degradation and clavulanic acid biosynthesis in lambs, while reducing cell apoptosis and lipopolysaccharide biosynthesis. Conclusion: Thus, these findings demonstrate that RJP-Cu, as a metal chelate, could effectively promote lamb growth performance, increase Cu2+ content, and potentially induce positive immunomodulatory effects by regulating antioxidant enzymes, antibodies, cytokines, intestinal flora, and related metabolic pathways.

Acupoint application therapy for diarrhea-predominant irritable bowel syndrome: a protocol for systematic review and network meta-analysis.

BACKGROUND: Irritable bowel syndrome is a chronic functional gastrointestinal disease, of which diarrhea-predominant irritable bowel syndrome (IBS-D) is a common subtype. In China, acupoint application therapy is currently widely used as an effective complementary therapy for IBS-D. In the clinical management of IBS-D, acupoint application is usually combined with other therapies, including acupuncture, moxibustion, and Chinese herbal and Western medicine. However, at present, evidence regarding the most effective options for treating IBS-D is insufficient. Therefore, this protocol proposes a systematic review and network meta-analysis for evaluating the effectiveness of acupoint application and its combination therapies in treating IBS-D, and for identifying the acupoint application-related treatments with the highest probability of being the best intervention. METHODS: Six English electronic databases (PubMed, Ovid MEDLINE, Scopus, Web of Science, the Cochrane Library, and EMBASE), four Chinese electronic databases [China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), WanFang, and SinoMed), and one Japanese medical database (Citation Information by National Institute of Informatics (CiNii)] will be searched for eligible randomized controlled trials from their inception to June 1, 2022. The efficacy and safety of acupoint application therapy and its combination therapies for patients with IBS-D will be evaluated. The STATA 14.0 (StataCorp, USA) software package will be used for the meta-analysis. A Bayesian network meta-analysis (NMA) will be performed using R (version 4.0.2) and Aggregate Data Drug Information System (ADDIS, version 1.16.8) software packages. Bias risk will be assessed using the Cochrane Collaboration's risk of bias tool; specifically, publication bias will be evaluated using Egger's test and funnel plots. The rank probabilities of various outcomes for each intervention will be calculated, clustered, and ranked using the cumulative ranking curve method. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method will be employed to assess the certainty of evidence for NMA outcomes. CONCLUSIONS: This study will aim to determine the clinical efficacy of acupoint application therapy and its combined therapy in the treatment of IBS-D and provide an evidence-based foundation for identifying the best acupoint application program.

The therapeutic and preventive effects of a canine-origin VB12 -producing Lactobacillus on DSS-induced colitis in mice.

Vitamin B12 (VB12 ) plays vital roles as a cofactor in reactions related to biosynthesis and metabolic regulation. Animals with diarrhoea from intestinal inflammation are susceptible to VB12 deficiency due to dysfunctional absorption. No current medications for canine intestinal inflammation can simultaneously act as VB12 supplements. Here we have tested a strain of VB12 -producing Lactobacillus, to investigate its safety in healthy dogs and test for hypothesized therapeutic and preventive effects on murine colitis. Results from enzyme-linked immunosorbent assay, histopathological analysis, and quantitative polymerase chain reaction showed normal physical conditions of healthy dogs given Lactobacillus, and blood biochemical indices showed no significant differences in markers, indicating safety of Lactobacillus to healthy dogs. The microbiota in animals receiving VB12 -producing Lactobacillus probiotic exhibited decreased abundance of Escherichia coli and concomitant increase in Lactobacillus. The probiotic supplement also resulted in downregulation of proinflammatory cytokines in murine colon tissues, reduced myeloperoxidase activity and malondialdehyde level, and significantly increased serum VB12 level and decreased homocysteine in therapeutic and preventive experiments. Moreover, Lactobacillus supplement decreased colonic inflammation and injury, improved gut microbiota, and ameliorated VB12 deficiency as an adjunctive therapy. We conclude this product is potentially beneficial for efficient therapy and prevention of VB12 deficiency form intestinal inflammation in canine clinical practice.

Exploration of the potential mechanism of Pushen capsule in the treatment of vascular dementia based on network pharmacology and experimental verification.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Pushen capsule is a traditional Chinese medicine compound functioning as 'stimulating blood circulation to remove blood stasis', which widely used to treat hyperlipidemia. Recent clinical research showed that Pushen capsule ameliorated cognitive function in patients with vascular mild cognitive impairment. AIM OF THE STUDY: Explore the potential mechanism of Pushen capsule in vascular dementia (VaD) using network pharmacology analysis and experimental verification. MATERIALS AND METHODS: Active ingredients and their related targets of Pushen capsule, and VaD-related targets were searched in public databases. Core targets, potential functions and mechanisms of Pushen capsule on VaD were predicted by protein-protein interaction (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were conducted to demonstrate the potential mechanisms of Pushen capsule in the treatment of VaD. RESULTS: In total, 155 active ingredients, 273 related targets of Pushen capsule, and 1035 VaD-related targets were selected from the public databases. 147 common targets of Pushen capsule against VaD were obtained. The PPI network, GO and KEGG enrichment analyses revealed that some core targets and signaling pathways are related to inflammation. The experimental results showed that Pushen capsule treatment largely alleviated hippocampal glial activation, accelerated the polarization of activated microglia from the M1 to the M2 phenotype and reduced associated inflammatory factor expression to protect against VaD-induced neuronal loss, synaptic protein reduction and cognitive defects in a dose-dependent manner. Moreover, Pushen capsule reduced the mRNA expression of NF-κB p65; and STAT1. CONCLUSION: Our study demonstrates that Pushen capsule alleviates hippocampal neuroinflammation to protect against VaD-induced cognitive impairment in a dose-dependent manner. The neuroprotective effect of Pushen capsule on VaD might be regulated by the NF-κB; and JAK-STAT pathway.

Effects of Electroacupuncture on Gastrointestinal Motility Function, Pain, and Inflammation via Transient Receptor Potential Vanilloid 1 in a Rat Model after Colonic Anastomoses.

Background: Complications after colon surgery are a major obstacle to postoperative recovery. The purpose of this study was to investigate the effect of electroacupuncture (EA) at Zusanli (ST36) on gastrointestinal motility in rats after colonic anastomosis and the mechanism of transient receptor potential vanillin 1 (TRPV1) channel in regulating gastrointestinal motility, pain, and inflammation. Methods: The rats were randomly divided into six groups, including the control, model, EA, sham-EA, capsaicin, and capsaicin+EA groups, with preoperative capsaicin pretreatment and EA treatment at ST36 acupoint after surgery. Rats were treated using EA at ST36 or sham acupoints after surgery for 5 days. Capsaicin was intraperitoneally injected into rats 3 hours before surgery. Gastrointestinal motility was assessed by measuring the gastric residue, small intestinal propulsion in vivo, contractile tension, and frequency of isolated muscle strips in vitro. The mechanical withdrawal threshold (MWT) of abdominal incision skin and spontaneous nociceptive scores were observed and recorded in rats after colon anastomosis. The expressions of TRPV1, substance P (SP), neurokinin 1 (NK1) receptor, nuclear factor kappa-B (NF-κB), interleukin- (IL-) 6, L-1ß, and tumor necrosis factor- (TNF-) α were determined. Results: Compared with the model group, electroacupuncture at ST36 point could significantly reduce the residual rate of stomach in rats after operation and increase the propulsive force of the small intestine and the contraction tension of the isolated smooth muscle. Electroacupuncture also increased postoperative day 3 MWT values and decreased postoperative spontaneous nociception scores. In addition, electroacupuncture treatment downregulated the expressions of IL-6, IL-1ß, TNF-α, TRPV1, NF-κB, SP, and NK1 receptors in the colon tissue of rats after colonic anastomosis. Conclusions: Our study showed that electroacupuncture at ST36 acupoint could improve gastrointestinal motility in rats after colonic anastomosis and relieve intestinal inflammation and pain. The mechanism may be to inhibit the activation of NF-κB and SP/NK1 receptor signaling pathways by inhibiting TRPV1.

Effect of thermosonication on texture degradation of carrot tissue in relation to alterations in cell membrane and cell wall structure.

Thermosonication as an alternative to hot water blanching of carrots, the effect of thermosonication on the carrot texture and cell structure required deep investigation. This study was conducted from the aspects of cell membrane, cell water, and cell wall pectin. Results showed that thermosonication at 60 °C significantly increased carrot tissue hardness by up to 10.3% compared with fresh. Rheological curves showed that the carrot tissues remained rigid after thermosonication. Cell membrane permeability was damaged to different extents during processing, inducing bound and immobilized water to migrate to free water and bring intracellular electrolytes to outflow. Thermosonication affected cell structure by altering the characteristics of pectin, including uronic acids and neutral sugar contents, degree of linearity and branching, and degree of methoxylation. The modified pectin can seize more divalent cations such as Ca2+ retained in the thermosonicated carrot cell wall, conducive to preserving the textural property of processed fruits and vegetables.

Quantitative chemical proteomics reveals anti-cancer targets of Celastrol in HCT116 human colon cancer cells.

BACKGROUND: Celastrol (Cel) is a naturally-derived compound with anti-cancer properties and exerts beneficial effects against various diseases. Although an extensive body of research already exists for Cel, the vast majority are inductive studies with limited validation of specific pathways and functions. The cellular targets that bind to Cel remain poorly characterized, which limits attempts to uncover its mechanism of action. PURPOSE: The present study aims to comprehensively identify the protein targets of Cel in HCT116 cells in an unbiased manner, and elucidate the mechanism of the anti-cancer activity of Cel based on target information. METHODS: A comprehensive analysis of protein targets that bind to Cel was performed in HCT116 colon cancer cells using a quantitative chemical biology method. A Cel probe (Cel-P) was synthesized to allow in situ monitoring of treatment in living HCT116 cells, and specific targets were identified with a quantitative chemical biology method (isobaric tags for relative and absolute quantitation) using mass spectrometry. RESULTS: In total, 100 protein targets were identified as specific targets of Cel. Pathways associated with the targets were investigated. Multiple pathways were demonstrated to be potential effectors of Cel. These pathways included the suppression of protein synthesis, deregulation of cellular reactive oxygen species, and suppression of fatty acid metabolism, and they were validated with in vitro experiments. CONCLUSION: The extensive information on the protein targets of Cel and their functions uncovered by this study will enhance the current understanding of the mechanism of action of Cel and serve as a valuable knowledge base for future studies.

Is Chinese herbal formula (nourishing Yin therapy) effective and well tolerated as an adjunct medication to hydroxychloroquine in the treatment of primary Sjögren's syndrome? A meta-analysis of randomised controlled trials.

BACKGROUND: Previously, data mining methodology was used to identify 71 patented prescriptions in Chinese patent databases, indicating that Yin-nourishing therapy (YNT) may be an adjunct medication to hydroxychloroquine in the treatment of primary Sjögren's syndrome (pSS). The purpose of this study was to investigate effects of the addition of YNT, which includes tonifying liver and kidney therapy (TLKT) and replenishing Qi and nourishing Yin therapy (RQNYT), in the treatment of pSS. METHODS: Fourteen databases (including Chinese, English, Japanese, Korean and Latin databases) were searched to identify randomised controlled trials (RCTs) of YNT plus hydroxychloroquine (YNTPH) versus hydroxychloroquine alone in patients with pSS. Relevant publications up to June 2021 were selected. A meta-analysis and trial sequential analysis (TSA) were performed using Review Manager 5.3, Stata 14.0 and TSA 0.9 software. The quality of identified studies was assessed based on the Cochrane risk of bias tool and GRADE (grading of recommendations, assessment, development and evaluation) criteria. RESULTS: We included five RCTs with a total of 345 participants. Pooled results indicated significant differences in short-term outcomes, which were assessed via European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), tear production, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) results when YNTPH was compared with hydroxychloroquine use alone (p < 0.05). No significant difference in salivary flow rate was reported. The most common side effect reported for both groups was gastrointestinal reaction. Sensitivity analyses suggested that heterogeneity might be ascribed to clinical methodology. Subgroup analyses revealed heterogeneities regarding salivary flow rate were eliminated. TLKT appeared to be better than RQNYT for improving salivary flow rate. TSA only supported changes in ESSPRI, ESSDAI and ESR values. For all studies, the quality of evidence was low. CONCLUSION: YNTPH may be an effective complementary therapy. Current evidence, however, is insufficient for determining whether YNTPH is more effective than hydroxychloroquine alone. Well-designed RCTs are needed to determine the role of YNT in pSS treatment.

Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer.

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.

A Simple and Rapid Light-Initiated Chemiluminescence Assay for Quantitation of Artemisia-Specific Immunoglobulin E.

BACKGROUND: Light-initiated chemiluminescence assay (LICA) is a homogeneous assay that has been successfully used for the quantitation of food allergen-specific immunoglobulin E (sIgE), but not inhaled allergen-sIgE. Simultaneously, current assays used to detect allergen-sIgE are serum consuming and/or time consuming. Hence, we established a method for the quantitation of Artemisia-sIgE based on LICA and verified its performance according to the clinical guideline documents, laying a foundation for the quantitation of inhaled and food allergen-sIgE in parallel on LICA. METHODS: The assay was established after optimizing the first incubation time and the dilutions of Artemisia-coated chemibeads, biotinylated goat anti-human IgE, and serum. In order to quantitate Artemisia-sIgE, the calibration curve was established with a high positive serum of known concentration. The assay performance was confirmed per the clinical guideline documents. In addition, the correlation between the results of LICA and capture enzyme-linked immunosorbent assay was evaluated. RESULTS: The developed LICA's coefficients of variation of repeatability and intermediate precision were 3.20%, 2.14%, and 3.85% and 4.30%, 4.00%, and 4.40%, respectively. The limit of detection was 0.10 kUA/L, and the limit of quantitation was 0.11 kUA/L. The range of linearity was from 0.27 kUA/L to 97.53 kUA/L (r = 0.9968). The correlation coefficient (r) for the correlation analysis between results of LICA and capture ELISA was 0.9087. This assay was successfully applied in 64 human serum samples, showing good sensitivity (82.20%) and specificity (100%). CONCLUSION: An Artemisia-sIgE quantitation assay based on LICA was successfully established. Its performance satisfied the clinical requirements and could be widely used in clinical laboratories.

Evaluation of Origanum vulgare Essential Oil and Its Active Ingredients as Potential Drugs for the Treatment of Toxoplasmosis.

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 µg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 µg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.