A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery.

Purpose: Post-mastectomy pain syndrome is a common yet debilitating neuropathic complication after breast cancer procedures, resulting in significantly reduced quality of life. Recently, emerging evidence has supported the therapeutic effect of magnesium administration in chronic pain. However, the role of magnesium supplementation in development of chronic pain after breast cancer surgery remains less known. The aim of this study was to evaluate therapeutic effect of magnesium supplementation on persistent pain after breast cancer procedure. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. A total of 109 patients who underwent breast cancer procedure received magnesium-L-threonate (n = 48) or placebo (n = 61) for 12 weeks. Chronic pain incidence, short form of the McGill Pain Questionnaire (SF-MPQ), Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Telephone Interview for Cognitive Status (TICS) were evaluated at 3- and 6-month follow-up. Results: About 31% (15 out of 48) of patients reported chronic pain after magnesium supplementation, and 26% (16 out of 61) of the control group at 6-month follow-up respectively. Total scores of SF-MPQ were significantly increased in the control group 6 months after surgical intervention (mean difference, 1.475; 95% CI, -2.730 to -0.2211), but NOT in the magnesium treated group (mean difference, 1.250; 95% CI, -2.775 to 0.2748). No significant differences were found between two cohorts on SF-MPQ, GAD-7, PHQ-9, PSQI, or TICS at each timepoint. Conclusion: Oral supplementation of magnesium-L-threonate did not effectively prevent the development of persistent pain in breast cancer survivors, nor provide sufficient pain relief over placebo. We did not observe improvement of pain, mood, sleep disorder, or cognitive function after 12-week magnesium supplementation. Future study may focus on magnesium combined with other effective anti-neuropathic pain treatment.

Oral Liushen pill for patients with COVID-19: A prospective randomized controlled trial.

We examined the efficacy and safety of Liushen pill combined with basic treatment for patients with COVID-19. In total, 181 patients hospitalized with COVID-19, classified as asymptomatic mild type, were randomly divided into the experimental (n = 91) and control (n = 90) groups and were administered placebo (Maizao decoction) and Maizao decoction and Liushen pill, in addition to standard care, respectively. The negative conversion rate of nucleic acid (Day 7), hospital discharge rate (Days 8, 10, and 14), symptom disappearance rate (Days 3, 5, and 7), inflammatory cytokine levels, and adverse events were compared between the groups. The negative viral conversion rate was significantly higher in the experimental than in the control group (48.35 vs. 31.11%, p < 0.05). Subgroup analysis showed a similar significant trend when the Ct value was ≤30 at baseline. After 10 days, the hospital discharge rate was significantly higher in the experimental than in the control group (69.23 vs. 53.33%, p < 0.05). After 3-day medication, the headache symptoms significantly disappeared in the experimental (88.57%) compared to the control group (63.33%) (p < 0.05). After 5 days, the symptom disappearance rates of headache and cough were significantly higher in the experimental (97.14%) than in the control group (97.14 vs. 80.00, p < 0.05; 82.65 vs. 58.93%, p < 0.01, respectively). Posttreatment, the procalcitonin level was significantly lower in the experimental than in the control group (0.09 ± 0.00 vs. 0.14 ± 0.05 ng/L; p < 0.05). There were no significant between-group differences in clinical safety test indices. Early intervention with Liushen pill improved cough and headache and increased negative viral conversion and discharge rate.

Simultaneous quantification of cellulose and pectin in tobacco using a robust solid-state NMR method.

Cellulose and pectin are the important components of tobacco (Nicotiana tabacum L.) cell wall, which affect the formation of undesirable compounds. Their contents are closely related to the harmfulness of tobacco. But the simultaneous quantitative analysis of cellulose and pectin is hard to be achieved for traditional analytical methods. A solid-state 13C cross-polarization by multiple contact periods (multiCP) NMR method was developed for the simultaneous quantification of cellulose and pectin in tobacco. The multiCP spectrum at optimal parameters agreed well with the direct polarization (DP) spectrum within one-thirtieth of the measurement time and provided satisfactory signal to noise ratio (SNR). After three simple procedures of sample preparation and spectra deconvolution, simultaneous quantification of cellulose and pectin extracted from tobacco was effectively achieved. Compared with the chemical method, this interesting method was rapid, practicable, and very promising, which provided the technical support for the simultaneous quantification of cell wall substances in biological sample.

Mechanism of taurine reducing inflammation and organ injury in sepsis mice.

The fundamental basis for the pathogenesis of sepsis is an inflammatory imbalance, which is considered to be the main target for treatment. Taurine is an intracellular free amino acid that has anti-inflammatory and antioxidant effects. To investigate the protective mechanism of taurine in sepsis, we used in vitro and in vivo experiments to explore the effects of taurine on neutrophil and monocyte immune function. Metabolomic analysis showed large amounts of taurine in neutrophils and monocytes and a dramatic decrease in taurine levels after LPS exposure. Taurine supplementation decreased the expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) in LPS-challenged neutrophils and monocytes and reduced the formation of neutrophil extracellular traps by restricting reactive oxygen species. Moreover, taurine protected septic mice from death, improved tissue injuries in the lung, liver, and kidney by reducing neutrophil infiltration and TNF-α production. Our data indicate that a supplement with taurine might be a promising therapeutic strategy for sepsis to reduce hyper inflammation and improve multi-organ dysfunctions.

Protective effect of baicalin against arsenic trioxide-induced acute hepatic injury in mice through JAK2/STAT3 signaling pathway.

Baicalin (BA) is a kind of flavonoid that is isolated from Scutellaria baicalensis Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.

A practical and fast isolation of 12 cyclolinopeptides (linusorbs) from flaxseed oil via preparative HPLC with phenyl-hexyl column.

Linusorbs, known as cyclolinopeptides, are a group of cyclic hydrophobic peptides derived from flaxseed oil with various health benefits. However, the current research efforts on both the biological activities and antioxidant capacities of linusorbs are limited because of existing issues with their purification and characterization. A practical method based on preparative HPLC for isolating 12 linusorbs simultaneously was developed and factors such as the solvent selection, gradient elution program, flow rate, loaded mass, and loading concentration, were optimized. The optimum conditions were an initial acetonitrile (ACN) to water ratio of 40%, final ACN ratio of 80%, eluting time of 21 min, a flow rate of 16 mL/min, sample load of 12.5 mg, and concentration of 80 mg/mL (in methanol). The 12 linusorbs obtained were verified using off-line MS/MS, recording purities of above 95.5%. The method could serve as a practical and fast isolation method enabling further investigation of minor linusorbs.

MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC.

BACKGROUND: The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as "self", evade the surveillance of the immune system, and accumulate to the tumor sites actively. RESULTS: Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate-an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. CONCLUSIONS: These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

Gut microbiota composition influences outcomes of skeletal muscle nutritional intervention via blended protein supplementation in posttransplant patients with hematological malignancies.

BACKGROUND: Skeletal muscle atrophy is an important and independent predictor of survival after hematopoietic stem cell transplantation (HSCT). Our previous study found that soy-whey blended protein (SWP) can improve muscle mass in acute leukemia patients. OBJECTIVE: We aimed to explore potential factors that influence muscle outcomes after nutritional intervention. METHODS: In this case-control study, 13 patients who received HSCT and failed to improve muscle function within half a year were included. After two months of SWP intervention, the subjects were divided into two groups (MSI: muscle status improved; MNI: muscle status not improved). 16S rDNA sequencing, principal coordinate analysis (PCoA) and the PICRUSt algorithm were used to analyze the composition, structure and function of the intestinal microbiota between the groups. This study was registered in the Chinese Clinical Trial Registry (ChiCTR 1800017765). RESULTS: SWP significantly improved muscle status (muscle area: from 330.4 mm2 to 384.8 mm2, p = 0.02; muscle strength: from 19.2 kg to 21.3 kg, p = 0.04). However, there were a small number of subjects whose muscle status was not effectively improved. After SWP intervention, the diversity (Shannon: from 1.7 to 3.8, p = 0.01; Simpson: from 0.6 to 0.8, p = 0.015) of the intestinal microbiota in the MSI group increased significantly, whereas that in the MNI group did not. Principal component analysis (PCA) revealed separate groupings of the microbiota of the Baseline-MSI and Endpoint-MSI time points in the MSI group. Opposite patterns of microbial abundance change were found between the MSI group (75% of changed genera were increased) and the MNI group (80% of changed genera were decreased). Three bacterial taxa (negative correlation: Streptococcus; positive correlations: Ruminococcus and Veillonella) were significantly related to muscle improvement outcomes. Both pentose phosphate (p = 0.048) and amino acid biosynthesis (p = 0.039), which are related to muscle metabolism, were found to be significantly changed in the MSI group through PICRUSt algorithm prediction. CONCLUSIONS: Our results suggest that the intestinal microbiota plays important roles in the regulation of muscle metabolism.

Comparable outcomes among unmanipulated haploidentical, matched unrelated, and matched sibling donors in BU-based myeloablative hematopoietic stem cell transplantation for intermediate and adverse risk acute myeloid leukemia in complete remission: a single-center study.

There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.

Seasonal drought events in tropical East Asia over the last 60,000 y.

The cause of seasonal hydrologic changes in tropical East Asia during interstadial/stadial oscillations of the last glaciation remains controversial. Here, we show seven seasonal drought events that occurred during the relatively warm interstadials by phytolith and pollen records. These events are significantly manifested as high percentages of bilobate phytoliths and are consistent with the large zonal sea-surface temperature (SST) gradient from the western to eastern tropical Pacific, suggesting that the reduction in seasonal precipitation could be interpreted by westward shifts of the western Pacific subtropical high triggered by changes of zonal SST gradient over the tropical Pacific and Hadley circulation in the Northern Hemisphere. Our findings highlight that both zonal and meridional ocean-atmosphere circulations, rather than solely the Intertropical Convergence Zone or El Niño-Southern Oscillation, controlled the hydrologic changes in tropical East Asia during the last glaciation.

Lipid peroxidation aggravates anti-tuberculosis drug-induced liver injury: Evidence of ferroptosis induction.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common adverse reaction of anti-tuberculosis drug treatment. Studies have shown that isoniazid (INH) and rifampicin (RFP) are mainly metabolized in the liver and a large amount of intracellular glutathione is used up during the metabolism of these drugs, resulting in lipid peroxidation and hepatocyte death. Ferroptosis is a novel form of programmed cell death caused by iron-ion-dependent lipid peroxidation. In this study, we explored lipid peroxidation and ferroptosis during ATB-DILI. Morphology of ferroptosis was discovered in ATB-DILI mouse livers by transmission electron microscopy. Flow cytometry was used to assess the molecular markers of lipid peroxidation and ferroptosis including reactive oxygen species, lipid peroxidation, and cellular iron content. Glutathione peroxidase 4 (GPX4) was depleted, while acyl-CoA synthetase long chain family member 4 (ACSL4) was overexpressed in the ATB-DILI tissues. And glutathione supplementation significantly reduced the level of lipid peroxidation and the risk of liver damage. Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate. In addition, iron supplementation enhanced the degree of lipid peroxidation and liver injury induced by INH and RFP in vivo and clinical retrospective study. Taken together, these results indicate that lipid peroxidation and evidence suggestive of ferroptosis occurs during ATB-DILI, and glutathione replenishment prevents this process while iron supplementation augmenting this effect.

Identification and Characterization of microRNAs in the Developing Seed of Linseed Flax (Linum usitatissimum L.).

Seed development plays an important role during the life cycle of plants. Linseed flax is an oil crop and the seed is a key organ for fatty acids synthesis and storage. So it is important to understand the molecular mechanism of fatty acid biosynthesis during seed development. In this study, four small RNA libraries from early seeds at 5, 10, 20 and 30 days after flowering (DAF) were constructed and used for high-throughput sequencing to identify microRNAs (miRNAs). A total of 235 miRNAs including 114 known conserved miRNAs and 121 novel miRNAs were identified. The expression patterns of these miRNAs in the four libraries were investigated by bioinformatics and quantitative real-time polymerase chain reaction (qPCR) analysis. It was found that several miRNAs, including Lus-miRNA156a was significantly correlated with seed development process. In order to confirm the actual biological function of Lus-miRNA156a, over-expression vector was constructed and transformed to Arabidopsis. The phenotypes of homozygous transgenic lines showed decreasing of oil content and most of the fatty acid content in seeds as well as late flowering time. The results provided a clue that miRNA156a participating the fatty acid biosynthesis pathway and the detailed molecular mechanism of how it regulates the pathway needs to be further investigated.

Safranal, an active constituent of saffron, ameliorates myocardial ischemia via reduction of oxidative stress and regulation of Ca2+ homeostasis.

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Ca2+ transient and L-type Ca2+ current (ICa-L) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Ca2+ transients and ICa-L in isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, ICa-L and the regulation of Ca2+ homeostasis.

6-Gingerol, an active pungent component of ginger, inhibits L-type Ca2+ current, contractility, and Ca2+ transients in isolated rat ventricular myocytes.

Ginger has been widely used as a flavor, food, and traditional medicine for centuries. 6-Gingerol (6-Gin) is the active components of ginger and offers some beneficial effects on cardiovascular diseases. Here, the effects of 6-Gin on L-type Ca2+ current (ICa-L), contractility, and the Ca2+ transients of rat cardiomyocytes, were investigated via patch-clamp technique and the Ion Optix system. The 6-Gin decreased the ICa-L of normal and ischemic ventricular myocytes by 58.17 ± 1.05% and 55.22 ± 1.34%, respectively. 6-Gin decreased ICa-L in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of 31.25 µmol/L. At 300 µmol/L, 6-Gin reduced the cell shortening by 48.87 ± 5.44% and the transients by 42.5 ± 9.79%. The results indicate that the molecular mechanisms underlying the cardio-protective effects of 6-Gin may because of a decreasing of intracellular Ca2+ via the inhibition of ICa-L and contractility in rat cardiomyocytes.

Potential mechanisms underlying the protective effects of salvianic acid A against atherosclerosis in vivo and vitro.

Salvianic acid A (SAA) is an active water-soluble constituent derived from Salvia miltiorrhiza Bge that is used extensively in the treatment of angiocardiopathy in China. However, few reports have investigated the therapeutic effect and the underlying mechanisms of SAA on atherosclerosis (AS). This study examines the protective mechanisms of SAA on AS in vivo and in vitro. SAA treatment (3 and 10 mg/kg/d) prevented the progression of atherosclerotic lesions and decreased 58.2% and 72.8% of the lipid deposition in the aorta of high fat-diet-induced AS rat. Notably, SAA treatment ameliorated serum lipid abnormalities by decreasing 20.4% and 33.8% of triglyceride, 26.1% and 32.7% of total cholesterol, 36.0% and 57.3% of low-density lipoprotein-cholesterol levels and increasing 183.4% and 337.5% of high-density lipoprotein-cholesterol level in the serum of AS rat (all P < 0.05). SAA treatment lowered pro-inflammatory mediators including interleukin-1ß, interleukin-6, tumor necrosis factor-α, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (all P < 0.05) by inhibiting the toll-like receptor 4/nuclear factor kappa B pathway. In addition, SAA treatment significantly decreased oxidative stress by increasing antioxidant enzymes activity, upregulating nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway and downregulated expression of p47phox and p22phox (all P < 0.05) in vivo. Furthermore, SAA (10-5 and 3 × 10-5 M) suppressed oxidized low-density lipoprotein-induced expression of lectin-like oxidized low-density lipoprotein receptor-1, the phosphorylation of nuclear factor kappa B (p65), ICAM-1 and VCAM-1 (all P < 0.05) and inhibited NADPH oxidase subunit 4-mediated reactive oxygen species generation in human umbilical vein endothelial cells. The experimental data verify the protective role of SAA in AS and the underlying mechanisms are strongly associated with the inhibition of oxidative stress, inflammation, and amelioration of endothelial dysfunction.

Naturally occurring nanotube with surface modification as biocompatible, target-specific nanocarrier for cancer phototherapy.

Phototherapy has drawn increasing attention including the use of nanocarriers with high drug loading capacity and delivery efficacy for target-specific therapy. We have made use of naturally-occurring halloysite nanotubes (HNTs) to build a biomimetic nanocarrier platform for target-specific delivery of phototherapeutic agents. The HNTs were decorated with poly(sodium-p-styrenesulfonate) (PSS) to enhance the biocompatibility, and were further functionalized by lumen loading the type-II photosensitizer indocyanine green (ICG). The HNT-PSS-ICG nanocarrier, without further tethering targeting groups, was shown to associate with the membrane of giant unilamellar vesicles (GUVs) via Pickering effects. Application of HNT-PSS-ICG nanocarrier to human breast cancer cells gave rise to a cell mortality as high as 95%. The HNT-PSS-ICG nanocarrier was further coated with MDA-MB-436 cell membranes to endow it with targeting therapy performance against breast cancer, which was confirmed by in vivo experiments using breast cancer tumors in mice. The membrane-coated and biocompatible nanocarrier preferentially concentrated in the tumor tissue, and efficiently decreased the tumor volume by a combination of photodynamic and photothermal effects upon near-infrared light exposure. Our results demonstrate that the HNT-based nanocarrier by virtue of facial preparation and high loading capacity can be a promising candidate for membrane-targeting nanocarriers.

Expression Profiles of Selenium-Related Genes in Human Chondrocytes Exposed to T-2 Toxin and Deoxynivalenol.

The combination of excess mycotoxin exposure and selenium deficiency has been widely considered as a cause of Kashin-Beck disease (KBD). The present study aimed to investigate the expression profiles of selenium-related genes in human chondrocytes after exposure to T-2 toxin and deoxynivalenol (DON) and to preliminarily identify the potential biological functions of the identified genes. Gene expression profiling was performed on human chondrocytes treated with 0.01 µg/ml T-2 toxin and 1.0 µg/ml DON by using Affymetrix Human Gene Arrays. The 1660 selenium-related genes were derived from the Comparative Toxicogenomics Database. Gene-term enrichment analysis was conducted by the DAVID gene annotation tool. Our results showed that 69 and 191 selenium-related genes were differentially expressed after T-2 toxin and DON treatment, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these identified genes were involved in various biological functions, such as the GO terms in response to oxidative stress, cell cycle arrest, and apoptotic process and the KEGG metabolic, FoxO signaling, and p53 signaling pathways. Our results may help explain the mechanisms of interaction between mycotoxins and selenium following human chondrocyte damage and reveal the potential roles of environmental risk factors in cartilage lesions during KBD development.

Effects of Polygonum cuspidatum on AMPK-FOXO3α Signaling Pathway in Rat Model of Uric Acid-Induced Renal Damage.

BACKGROUND: To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism. METHODS: A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups (n=12 per group). A normal group (n=6) was used as the control. Rats in the normal and model groups were administered distilled water (10 mL•kg-1) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol (23.33 mg•kg-1), and 7.46, 3.73, or 1.87 g•kg-1•d-1 PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 mRNA and protein levels in renal tissue or serum. RESULTS: Compared with the normal group, the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P<0.01 or P<0.05). The mRNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated (P<0.01 or P<0.05). Compared with the model group, at the 6th week, the mRNA transcription levels of AMPK in the high- and medium-dose groups, and protein expression levels of AMPKα1, pAMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and pAMPKα1 in the mediumdose PC group, and pAMPKα1 in the low-dose PC group were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium- and low-dose PC groups were down-regulated (P<0.01 or P<0.05). At the 8th week, the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, pAMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription levels of TLR4 in the medium- and low-dose PC groups, NLRP3 in the high- and low-dose PC groups and MCP-1 in the medium- and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P<0.01 or P<0.05). CONCLUSION: PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflflammatory metabolic renal damage.

A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: Results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone.

Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15-40 years with recent onset schizophrenia-spectrum (n = 46) or bipolar (n = 4) disorders and current psychotic symptoms were treated for 16 weeks with risperidone and randomly-assigned omega-3 (EPA 740 mg and DHA 400 mg daily) or matching placebo. The primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Mean lifetime antipsychotic exposure was 18.1 days. Length of time in treatment, risperidone dose and number of omega-3/placebo capsules taken did not differ between conditions. Longitudinal analysis of the total BPRS score revealed a trend level (p = 0.0826) treatment effect favoring omega-3 treatment. Lorazepam was an allowed concomitant medication. Among the subgroup (N = 23) who did not receive lorazepam, the treatment effect on BPRS total scores favoring omega-3 was significant (p = 0.0406) and factor scores analyses revealed a substantial decrease in depression-anxiety with omega-3 but no change with placebo (treatment-by-time interaction, p = 0.0184). Motor side effects did not differ between conditions. Analysis of Systematic Assessment for Treatment Emergent Events assessments revealed fewer adverse events overall with omega-3 compared with placebo with the largest differences between conditions (all favoring omega-3) on confusion, anxiety, depression, irritability, and tiredness/fatigue. These results suggest that omega-3 adjuvant treatment is a potential option for depression and anxiety symptoms of people with recent onset psychosis. Further research is needed to confirm this potential. Clinical trial registration: NCT01786239.

The Hsp70 Gene Family in Solanum tuberosum: Genome-Wide Identification, Phylogeny, and Expression Patterns.

Heat shock protein 70 (Hsp70) family members play important roles in protecting plants against abiotic stresses, including salt, drought, heat, and cold. In this study, 20 putative StHsp70 genes were identified in potato (Solanum tuberosum L.) through the integration of the gene structures, chromosome locations, phylogenetic relationships, and expression profiles. These StHsp70 genes were classified into five sub-families based on phylogenetic analysis. Chromosome mapping revealed that they were unevenly and unequally distributed on 10 of the 12 chromosomes. Furthermore, segmental and tandem duplication events contributed to the expansion of the StHsp70 genes. Phylogenetic tree of the HSP70 genes from potato and other plant species revealed multiple sub-families. These findings indicated a common ancestor which had generated diverse sub-families prior to a mono-dicot split. In addition, expression analysis using RNA-seq revealed that the majority of these genes were expressed in at least one of the tested tissue, and were induced by Phytophthora infestans. Then, based on qRT-PCR analysis, the results showed that the transcript levels of some of the StHsp70 genes could be remarkably induced by such abiotic and hormone stresses, which indicated their potential roles in mediating the responses of potato plants to both abiotic and biotic stress conditions.