Efficient decolorization of oligosaccharides in ginseng (Panax ginseng) residue using ultrasound-assisted macroporous resin.

An efficient decolorization method for ginseng residue oligosaccharides (GROs) using ultrasound-assisted D392 macroporous resin was developed. The decolorization effects and color differences of activated carbon adsorption, hydrogen peroxide oxidation, and resin adsorption were evaluated. The optimal conditions of the three decolorization methods for static, dynamic, ultrasound-assisted resin adsorption were compared. The results showed that ultrasound-assisted decolorization had the best decolorization effect of greatly decreasing the decolorization time to 80 min. Color difference analysis revealed the process of pigment removal during GRO decolorization. The UV-visible full-wavelength scan showed that most pigments were removed after decolorization. The characterizations by the Fourier-transform infrared spectroscopy and X-ray diffraction analysis showed that the chemical structure and crystallinity of the GROs did not change upon decolorization. In addition, the molecular weight distribution did not change significantly. This research contributes to further exploration of the structures and functions of GROs.

Convenient tumor 3D spheroid arrays manufacturing via acoustic excited bubbles for in situ drug screening.

The quick and convenient fabrication of in vitro tumor spheroids models has been pursued for clinical drug discovery and personalized therapy. Here, uniform three-dimensional (3D) tumor spheroids are quickly constructed by acoustically excited bubble arrays in a microfluidic chip and performed drug response testing in situ. In detail, bubble oscillation excited by acoustic waves induces second radiation force, resulting in the cells rotating and aggregating into tumor spheroids, which obtain controllable sizes ranging from 30 to 300 µm. These spherical tumor models are located in microfluidic networks, where drug solutions with gradient concentrations are generated from 0 to 18 mg mL-1, so that the cell spheroids response to drugs can be monitored conveniently and efficiently. This one-step tumor spheroids manufacturing method significantly reduces the model construction time to less than 15 s and increases efficiency by eliminating additional transfer processes. These significant advantages of convenience and high-throughput manufacturing make the tumor models promising for use in tumor treatment and point-of-care diagnosis.

Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by suppressing leucine-related mTORC1 signaling and reducing oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng decoction (BTW) has been used for hundreds of years to treat ulcerative colitis (UC) in China and has produced remarkable clinical results. However, the knowledge in protective mechanism of BTW against UC is still unclear. AIM OF THE STUDY: The present study was designed to investigate the anti-UC effects of BTW and the underlying mechanisms involved. METHODS: 3.5% dextran sulfate sodium (DSS)-induced experimental colitis was used to simulate human UC and the mice were treated with BTW (6.83 g/kg), leucine (200 mg/kg, Leu) or rapamycin (2 mg/kg, RAPA) as a positive control for 7 days. The clinical symptoms, serum myeloperoxidase (MPO) and malondialdehyde (MDA) levels were evaluated. Biological samples were collected to detect the effects of BTW on mechanistic target of rapamycin complex 1 (mTORC1) pathway and Leu metabolism. RESULTS: In our study, BTW notably improved the clinical symptoms and histopathological tissue damage and reduced the release of proinflammatory cytokines, including IL-6, IL-1ß and TNF-α in UC mice. BTW also alleviated oxidative stress by decreasing serum MPO and MDA levels. Additionally, BTW significantly suppressed mTORC1 activity in the colon tissues of UC mice. Serum metabolomics analysis revealed that the mice receiving BTW had lower Leu levels, which was in line with the decreased expression of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in the colon tissues. Furthermore, oral administration of Leu aggravated DSS-induced acute colitis and enhanced mTORC1 activity in the colon. CONCLUSION: These data strongly demonstrated that BTW could ameliorate DSS-induced UC by regulating the Leu-related mTORC1 pathway and reducing oxidative stress.

Low-level laser therapy with different irradiation methods modulated the response of bone marrow mesenchymal stem cells in vitro.

Low-level laser therapy (LLLT) also known as photobiomodulation is a treatment to change cellular biological activity. The exact effects of LLLT remain unclear due to the different irradiation protocols. The purpose of this study was to investigate the effects of LLLT by three different irradiation methods on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. BMSCs were inoculated in 24-well plates and then irradiated or not (control) with a laser using three different irradiation methods. The irradiation methods were spot irradiation, covering irradiation, and scanning irradiation according to different spot areas (0.07 cm2 or 1.96 cm2) and irradiation areas (0.35 cm2 or 1.96 cm2), respectively. The laser was applied three times at energy densities of 4 J/cm2. The cell proliferation by CCK-8. ALP activity assay, alizarin red, and quantitative real-time polymerase chain reaction (RT-PCR) were performed to assess osteogenic differentiation and mineralization. Increases in cell proliferation was obvious following irradiation, especially for covering irradiation. The ALP activity was significantly increased in irradiated groups compared with non-irradiated control. The level of mineralization was obviously improved following irradiation, particularly for covering irradiation. RT-PCR detected significantly higher expression of ALP, OPN, OCN, and RUNX-2 in the group covering than in the others, and control is the lowest. The presented results indicate that the biostimulative effects of LLLT on BMSCs was influenced by t he irradiation method, and the covering irradiation is more favorable method to promote the proliferation and osteogenic differentiation of BMSCs.

Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2.

Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form. Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation. Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2. Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism.

Identification of the occurrence and potential mechanisms of heterotopic ossification associated with 17-beta-estradiol targeting MKX by bioinformatics analysis and cellular experiments.

BACKGROUND: Tendon heterotopic ossification (HO) is a common condition occurring secondary to tendon injury or surgical trauma that significantly affects the patient's quality of life. The treatment of tendon HO remains challenging due to a lack of clarity regarding the pathological mechanism. Mohawk (MKX) is a key factor in preventing tendon HO; however, its upstream regulatory mechanism remains to be understood. This study aimed to identify potential compounds that target and regulate MKX and explore their functional mechanisms. METHODS: Bioinformatics analysis of MKX-related compounds and proteins was performed based on data from the STITCH and OncoBinder databases. Subsequently, the SymMap database was used to study MKX-related traditional Chinese medicine drugs and symptoms. Next, the OncoBinder genomic and proteomic discovery model was applied to identify potential regulators of MKX. The analytical tool Expert Protein Analysis System for proteomics was used to predict the three-dimensional structure of MKX, and the AutoDockTools software was used to identify pockets of activity at potential sites for molecular docking. Furthermore, we evaluated the effect of different doses of 17-beta-estradiol on bone marrow-derived mesenchymal stem cells (BM-MSCs). RESULTS: By predicting the three-dimensional structure of MKX and simulating molecular docking, Pro-Tyr and 17-beta-Estradiol were found to target and bind to MKX. Analysis of the STITCH and OncoBinder databases showed that MKX had a significant regulatory correlation with suppressor interacting 3 A/histone deacetylase 1 (SIN3A/HDAC1). The GO and KEGG pathway enrichment analysis revealed that the functions of MKX and its associated proteins were mainly enriched in osteogenic-related pathways. Assessment of the proliferation of BM-MSCs revealed that 17-beta-estradiol possibly upregulated the mRNA expression of the HDAC1-SIN3A/BMP pathway-related RUNX2, thereby promoting the proliferation of BM-MSCs. CONCLUSIONS: The compounds Pro-Tyr and 17-beta-Estradiol may bind to MKX and thus affect the interaction of MKX with SIN3A/HDAC1.

RBC-derived nanosystem with enhanced ferroptosis triggered by oxygen-boosted phototherapy for synergized tumor treatment.

Photodynamic and ferroptosis therapies for cancer treatment are restricted by the scarcity of oxygen and Fe in cancer cells, and the complicated structure of delivery systems. Herein, a red blood cell-derived vehicle (RDV) inherently enriched with hemoglobin co-delivers a photosensitizer, Ce6, and a ferroptosis promoter, sorafenib (SRF) into cancer cells for boosting oxygen and providing iron, which leads to enhanced PDT and stronger ferroptosis therapy. Damage to the RDV membrane under local irradation leads to SRF release at the tumor site for tumor-targeted therapy. The lipid membrane of the RDV could also improve the drug delivery efficiency in vitro and in vivo. The novel nanosystem exhibited enhanced tumor killing efficacy and improved safety compared with traditional PDT and ferroptosis therapy.

Traditional herbal medicine and nanomedicine: Converging disciplines to improve therapeutic efficacy and human health.

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.

Genetic and Functional Evaluation of the Role of FOXO1 in Antituberculosis Drug-Induced Hepatotoxicity.

BACKGROUND: The accumulation of the hepatotoxic substance protoporphyrin IX (PPIX) induced by aminolevulinate synthase 1 (ALAS1) activation is one of the important mechanisms of antituberculosis drug-induced hepatotoxicity (ATDH). Forkhead box protein O1 (FOXO1) may activate ALAS1 transcription. However, little is known about their roles in ATDH; we performed a study to determine the association between polymorphisms in the two genes and ATDH susceptibility. Then, we verified this possible association by cellular functional experiments. MATERIALS AND METHODS: Tag single-nucleotide polymorphisms (TagSNPs) in the two genes were genotyped in 746 tuberculosis patients. The frequencies of the alleles, genotypes, genetic models, and haplotype distribution of the variants were compared between the case and control groups. L-02 cells and HepG2 cells were incubated with the indicated concentration of isoniazid (INH) and rifampicin (RIF) for the desired times, and then the expression levels of ALAS1 and FOXO1 mRNAs and proteins were detected. HepG2 cells were transiently transfected with FOXO1 siRNA to observe the effect of changes in the FOXO1 expression on the cell survival rate and ALAS1 expression. RESULTS: The C allele at rs2755237 and the T allele at rs4435111 in the FOXO1 gene were associated with a decreased risk of ATDH. The expression of ALAS1 in both L-02 cells and HepG2 cells was increased by the coadministration of INH/RIF (600/200 µM) for 24 h. Although FOXO1 expression was reduced slightly by the same treatment, its content in the nucleus was significantly increased. However, the cell survival rate and ALAS1 expression level were not significantly altered by the downregulation of FOXO1 in HepG2 cells. CONCLUSIONS: Variants of the rs4435111 and rs2755237 loci in the FOXO1 gene were associated with susceptibility to ATDH. Coadministration of INH/RIF promoted the transfer of FOXO1 from the cytoplasm to the nucleus, but the functional significance of its nuclear translocation requires further verification.

Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is a valuable medicinal herb used in China for the prevention and treatment of cancer, diabetes, cardiovascular diseases and other diseases. As the main active ingredient of ginseng, ginsenoside has a wide range of pharmacological effects. Ginsenoside Rh2, a protopanaxadiol saponin from ginseng, exhibits anti-inflammatory and anticancer effects. AIM OF THE STUDY: The potential biological mechanism of Rh2 in the treatment of ulcerative colitis (UC) has not been clarified clearly. In our research, we aimed to explore the therapeutic effects of Rh2 on dextran sodium sulfate (DSS)-induced colitis and elucidate the mechanism of Rh2 in treating UC. METHODS: DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, Rh2 (50 mg/kg) group and sulfasalazine (SASP, 200 mg/kg) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with Rh2 and SASP for 10 days. At the end of the experiment, colon samples were collected, and phenotypic and pathological analyses were performed in UC mice. Then, Western blot, immunohistochemistry and quantitative real-time PCR analyses were performed to determine the expression of signaling pathway-related factors. RESULTS: Rh2 markedly alleviated DSS-induced body weight loss, intestinal damage, colon length shortening and disease activity index (DAI) scores. Furthermore, proinflammatory cytokines, such as TNF-α, IL-6 and IL-1ß, were reduced by Rh2. Additionally, STAT3/miR-214 activation was also suppressed by Rh2 administration. In vitro, we demonstrated that Rh2 effectively inhibited IL-6-induced STAT3 phosphorylation and miR-214 expression in cultured normal colonic epithelial cells. CONCLUSION: Our results suggested that Rh2 exhibits potential application value in the treatment of UC, and its mechanism is related to the downregulation of STAT3/miR-214 levels, which is expected to be applicable in the treatment of clinical UC.

Pollen morphology of different species of Iris barbata and its systematic significance with scanning electron microscopy methods.

Forty-eight cultivars of Iris barbata were used as research materials, and observations of their pollen morphologies were made using scanning electron microscopy (SEM). The pollen of I. barbata consisted of a single grain, which was subspheroidal or subprolate and boat-shaped in equatorial view and oval or nearly round in polar view. The pollen was symmetrical or radially symmetrical on both sides, and there were five types of germination furrows: monocolpate, dicolpate, monocolpate-colpoidal, 2-syncolpate, and parasyncolpate. The exine ornamentation was mostly crass-reticulate and occasionally verrucate or pilate. Variation in the equatorial axis length of I. barbata pollen was the lowest, and variation in pollen morphology was stable. Q-type cluster analysis was conducted using seven indexes: polar axis length (P), equatorial axis length (E), P/E, mesh diameter (D), net ridge width (W), D/W, and germination furrow width (WG). The 48 cultivars were divided into three groups. Three dwarf cultivars were clustered in one group, and the degree of evolution of this group was higher than that of the other two groups. This paper systematically describes the characteristics of I. barbata for the first time, and thus provides important palynological insights into the classification and cross-breeding of I. barbata.

Remodeling the homeostasis of pro- and anti-angiogenic factors by Shenmai injection to normalize tumor vasculature for enhanced cancer chemotherapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Normalization of the tumor vasculature can enhance tumor perfusion and the microenvironment, leading to chemotherapy potentiation. Shenmai injection (SMI) is a widely used traditional Chinese herbal medicine for the combination treatment of cancer in China. AIM OF THIS STUDY: This study aimed to investigate whether SMI can regulate tumor vasculature to improve chemotherapy efficacy and identify the underlying mechanism. MATERIALS AND METHODS: The antitumor effect of SMI combined with 5-florouracil (5-FU) was investigated in xenograft tumor mice. Two-photon microscopy, laser speckle contrast imaging and immunofluorescence staining were used to investigate the effects of SMI on tumor vasculature in vivo. The mRNA and protein expression of pro- and anti-angiogenic factors were measured by Q-PCR and ELISA. Histone acetylation and transcriptional regulation were detected by Western blot and ChIP assay. RESULTS: SMI promoted normalization of tumor microvessels within a certain time window, which was accompanied by enhanced blood perfusion and 5-FU distribution in tumors. SMI significantly increased the expression of antiangiogenic factor angiostatin and decreased the pro-angiogenic factors VEGF, FGF and PAI-1 by day 10. SMI combined with neoadjuvant chemotherapy in colorectal cancer patients also showed a significant increase in angiostatin and decrease in VEGF and FGF in surgically resected tumors when compared to the neoadjuvant chemotherapy group. Further in vitro and in vivo studies revealed that SMI downregulated VEGF, FGF and PAI-1 mRNA expression by inhibiting histone H3 acetylation at the promoter regions. The enhanced production of angiostatin was attributed to the regulation of the plasminogen proteolysis system via SMI-induced PAI-1 inhibition. CONCLUSION: SMI can remodel the homeostasis of pro- and anti-angiogenic factors to promote tumor vessel normalization, and thus enhance drug delivery and anti-tumor effect. This study provides additional insights into the pharmacological mechanisms of SMI on tumors from the perspective of vascular regulation.

Metabolic Alterations Induced by Kudingcha Lead to Cancer Cell Apoptosis and Metastasis Inhibition.

Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.

A hepatoprotection study of Radix Bupleuri on acetaminophen-induced liver injury based on CYP450 inhibition.

We investigated the potential hepatoprotective effect of Radix Bupleuri (RB) by inducing acute liver injury (ALI) in an animal model using acetaminophen (APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serumaspartate transaminase (AST) and alanine transaminase (ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine (APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione (GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2E1 and CYP3A activity. Further investigation revealed the increasing of CYP2E1 and CYP3A protein was significantly inhibited in pretreatment group, while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury.

BACKGROUND: TGFBRAP1 and TGFBR2 play important roles in the TGF-ß/smad signalling pathway and may disturb liver homeostasis by regulating liver injury and renewal. However, little is known about the association between their genetic polymorphisms and antituberculosis drug-induced liver injury (ATDILI), so we explored the association between their variants and the susceptibility to ATDILI. MATERIALS AND METHODS: A total of 746 tuberculosis patients were prospectively enrolled, and fifteen selected SNPs were genotyped. The allele, genotype, and genetic model frequencies of the variants were compared between patients with or without ATDILI, as well as the joint effect analysis of SNP-SNP interactions. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated. RESULTS: The A variant at rs17687727 was significantly associated with an increased risk for ATDILI (OR 1.55; 95% CI: 1.08-2.22; p = 0.016), which is consistent with the results in the additive and dominant models. Other allele, genotype, and genetic model frequencies were similar in the two groups for the other fourteen SNPs (all p > 0.05). CONCLUSION: Our study first implied that the A variant of rs17687727 in TGFBRAP1 influenced the susceptibility to ATDILI in first-line antituberculosis combination treatment in the Han Chinese population in a dependent manner.

Understanding the cellular uptake and biodistribution of a dual-targeting carrier based on redox-sensitive hyaluronic acid-ss-curcumin micelles for treating brain glioma.

The gliomas treatment is challenging due to the limits imposed by blood-brain barrier to the distribution of the drugs in the brain. Therefore, we designed a brain glioma targeting redox-sensitive hyaluronic acid (HA)-ss-curcumin (CUR) micelles. HA was conjugated to CUR through a disulfide bond, which could form micelles independently in aqueous solution. And we further increased the drug loading by loading free CUR. Brain penetration was achieved with Tween 80, whereas glioma-targeting was inclined by CD44-mediated endocytosis. Compared to the disulfide-free group, the redox-sensitive micelles exhibited rapid in vitro drug release under high glutathione conditions, significantly enhanced cell apoptosis and cellular uptake in G422 glioma cells. Redox-sensitive micelles displayed about 4.70-fold higher area under the curve in rats after intravenous injection in comparison to the free CUR and effectively accumulated in the brain. These findings suggest that redox-sensitive micelles could be a promising candidate to achieve brain targeted CUR delivery.

A Promising Microtubule Inhibitor Deoxypodophyllotoxin Exhibits Better Efficacy to Multidrug-Resistant Breast Cancer than Paclitaxel via Avoiding Efflux Transport.

Multidrug resistance (MDR) is a common limitation for the clinical use of microtubule-targeting chemotherapeutic agents, and it is the main factor for poor prognoses in cancer therapy. Here, we report on deoxypodophyllotoxin (DPT), a promising microtubule inhibitor in phase 1, as a promising candidate to circumvent this obstacle. DPT remarkably suppressed tumor growth in xenograft mice bearing either paclitaxel (PTX)-sensitive MCF-7/S or acquired resistance MCF-7/Adr (MCF-7/A) cells. Also, DPT exhibited similar accumulation in both tumors, whereas PTX displayed much a lower accumulation in the resistant tumors. In vitro, DPT exhibited a much lower resistance index (0.552) than those of PTX (754.5) or etoposide (38.94) in both MCF-7/S and MCF-7/A cells. Flow cytometry analysis revealed that DPT (5 and 10 nM) caused arrest of the G2/M phase in the two cell lines, whereas PTX (up to 10 nM) had no effect on cell-cycle progression of the MCF-7/A cells. Microtubule dynamics assays revealed that DPT destabilized microtubule assembly in a different mode. Cellular pharmacokinetic assays indicated comparable intracellular and subcellular accumulations of DPT in the two cell lines but a much lower retention of PTX in the MCF-7/A cells. Additionally, transport assays revealed that DPT was not the substrate of P-glycoprotein, breast cancer resistance protein, or MDR-associated protein 2, indicating a lower occurrence rate of MDR. DPT might be a promising microtubule inhibitor for breast cancer therapy, especially for treatment of drug-resistant tumors.

Serum ω-3 Polyunsaturated Fatty Acids and Potential Influence Factors in Elderly Patients with Multiple Cardiovascular Risk Factors.

Recent clinical trials failed to demonstrate that ω-3 polyunsaturated fatty acid (PUFA) supplement reduced cardiovascular events, which contradicted previous evidence. However, serum ω-3 PUFA concentrations of participants remained unclear in those studies. We aimed to investigate the definite relationship between serum concentrations of ω-3 PUFAs and coronary artery disease (CAD), and to explore the potential influence factors of ω-3 PUFAs. We selected Chinese in-patients (n = 460) with multiple cardiovascular risk factors or an established diagnosis of CAD. Serum ω-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were measured by liquid chromatography mass spectrometry. Serum concentrations of ω-3 PUFAs in CAD patients were lower than that in patients with cardiovascular risk factors. Furthermore, high serum DHA concentration was an independent protective factor of CAD after adjustment for confounding factors (OR: 0.52, p = 0.014). Alcohol intake (p = 0.036) and proton pump inhibitor (PPI) usage (p = 0.027) were associated with a decreased serum ω-3 PUFA concentration. We conclude that serum concentrations of ω-3 PUFAs may associate with a decreased CAD proportion, and DHA may serve as a protective factor of CAD. Serum ω-3 PUFA concentrations may be reduced by alcohol intake and certain drugs like PPIs.

The clinical utility of QSM: disease diagnosis, medical management, and surgical planning.

Quantitative susceptibility mapping (QSM) is an MR technique that depicts and quantifies magnetic susceptibility sources. Mapping iron, the dominant susceptibility source in the brain, has many important clinical applications. Herein, we review QSM applications in the diagnosis, medical management, and surgical treatment of disease. To assist in early disease diagnosis, QSM can identify elevated iron levels in the motor cortex of amyotrophic lateral sclerosis patients, in the substantia nigra of Parkinson's disease (PD) patients, in the globus pallidus, putamen, and caudate of Huntington's disease patients, and in the basal ganglia of Wilson's disease patients. Additionally, QSM can distinguish between hemorrhage and calcification, which could prove useful in tumor subclassification, and can measure microbleeds in traumatic brain injury patients. In guiding medical management, QSM can be used to monitor iron chelation therapy in PD patients, to monitor smoldering inflammation of multiple sclerosis (MS) lesions after the blood-brain barrier (BBB) seals, to monitor active inflammation of MS lesions before the BBB seals without using gadolinium, and to monitor hematoma volume in intracerebral hemorrhage. QSM can also guide neurosurgical treatment. Neurosurgeons require accurate depiction of the subthalamic nucleus, a tiny deep gray matter nucleus, prior to inserting deep brain stimulation electrodes into the brains of PD patients. QSM is arguably the best imaging tool for depiction of the subthalamic nucleus. Finally, we discuss future directions, including bone QSM, cardiac QSM, and using QSM to map cerebral metabolic rate of oxygen. Copyright © 2016 John Wiley & Sons, Ltd.

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution.

Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg-1·3d-1) or PTX (7.5 mg·kg-1·3d-1) with or without SMI (0.01 mL·g-1·d-1) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 µL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r2=+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX.