Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice.

Excessive oxidative stress impairs cartilage matrix metabolism balance, significantly contributing to osteoarthritis (OA) development. Celastrol (CSL), a drug derived from Tripterygium wilfordii, has recognized applications in the treatment of cancer and immune system disorders, yet its antioxidative stress mechanisms in OA remain underexplored. This study aimed to substantiate CSL's chondroprotective effects and unravel its underlying mechanisms. We investigated CSL's impact on chondrocytes under both normal and inflammatory conditions. In vitro, CSL mitigated interleukin (IL)-1ß-induced activation of proteinases and promoted cartilage extracellular matrix (ECM) synthesis. In vivo, intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice. Mechanistically, it was found that inhibiting nuclear factor erythroid 2-related factor 2 (NRF2) abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA. This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2, offering a novel therapeutic avenue for arthritis therapy.

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of ß-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

Yishen-Qingli-Huoxue formula attenuates renal fibrosis by inhibiting indoxyl sulfate via AhR/snai1 signaling.

BACKGROUND: Chronic kidney disease (CKD) is challenging to reverse and its treatment options are limited. Yishen-Qingli-Huoxue Formula (YQHF) is an effective treatment Chinese formula for CKD, as verified by clinical randomized controlled trial. However, the correlative YQHF therapeutic mechanisms are still unknown. PURPOSE: The current study aimed to investigate the potential anti-renal fibrosis effects of YQHF as well as the underlying mechanism. METHODS: After affirming the curative effects of YQHF on adenine-induced CKD rats, Masson staining, immunohistochemistry, and ELISA were used to assess the effects of YQHF on renal fibrosis. Subsequently, metabolomics and transcriptomics analyses were conducted to clarify the potential mechanisms. Furthermore, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), molecular docking analysis and in vitro experiments were used to verify final mechanism of anti-fibrosis. RESULTS: Our results demonstrated that YQHF could improve renal morphology, decrease blood urea nitrogen (BUN), serum creatinine (Scr), and increase body weight gain of model rats. Masson staining, immunohistochemistry of collagen I, fibronectin (FN), α-smooth muscle actin (α-SMA), vimentin and E-cadherin showed that YQHF delayed CKD progression by alleviating renal fibrosis, and the expression of fibrotic factors smoc2 and cdh11 were obviously suppressed by YQHF. Metabolomic and transcriptomic measures discovered that indoxyl sulfate might be a crucial factor inducing renal fibrosis, and the antagonistic effect of YQHF on renal fibrosis may be exerted via AhR/snai1 signaling. Subsequently, western blot and immunohistochemical experiments revealed YQHF indeed inhibited AhR/snai1 signaling in adenine-induced renal fibrosis of CKD rat, which confirmed previous results. In addition, molecular docking and in vitro experiments further supported this conclusion, in which astilbin, the main compound identified YQHF, was certified to exert a significant effect on AhR. CONCLUSION: Our findings showed that YQHF can effectively treat CKD by antagonizing renal fibrosis, the potential mechanisms were relating with the regulation on AhR/snai1 signaling.

Total extract of Abelmoschus manihot L. alleviates uric acid-induced renal tubular epithelial injury via inhibition of caspase-8/caspase-3/NLRP3/GSDME signaling.

Purpose: The incidence of uric acid (UA)-induced kidney injury is increasing owing to the high incidence of hyperuricemia in recent years. The flower of Abelmoschus manihot (Linneus) Medik is a traditional Chinese medicinal herb widely used in the treatment of some kidney diseases. In our previous study, we reported that the total extract of A. manihot L. flower (TEA) attenuated adriamycin-induced renal tubular cell injury. In this study, we aimed to evaluate the role of TEA in UA-induced tubular cell injury. Methods: Normal rat proximal epithelial NRK-52E cells were incubated with UA to mimic hyperuricemia conditions. The role of TEA in the renal tubular cells was also assessed. The cellular morphology was observed using phase-contrast microscopy, and cell viability was analyzed using the Cell Counting kit-8. Living and dead cells were stained using a Calcein-AM/PI double stain kit. The release of lactate dehydrogenase (LDH) was analyzed by LDH cytotoxicity Assay Kit. The expression of target proteins was analyzed using western blot analysis. Results: UA triggered NRK-52E cell injury, as evidenced by morphological changes, detachment of cells from the bottom, cell swelling, large bubbles blowing from cell membrane and loss of cell viability. UA increased release of LDH. UA induced the expression of p-ERK1/2 and the subsequent activation of caspase-8, caspase-3, and NLRP3 inflammasomes. Pyroptosis was elicited by UA after gasdermin E N-terminal (GSDME-NT) was cleaved from gasdermin E (GSDME). Z-DEVD-FMK, a caspase-3 inhibitor, suppressed the expression of both NLRP3 and GSDME-NT, but not that of caspase-8. INF39, an NLRP3 inhibitor, altered the expression of GSDME-NT expression, but not that caspase-3 and caspase-8. TEA alleviated UA-induced cell injury by suppressing ERK1/2/caspase-8/caspase-3/NLRP3/GSDME signaling. Conclusion: GSDME-mediated pyroptosis was involved in UA-induced renal tubular cell injury. This is the first study to report that TEA protects renal tubular epithelial cells against UA by inhibiting the ERK/1/2/caspase-8/caspase-3/NLRP3/GSDME pathway.

Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies.

Sweet tea (Lithocarpus polystachyus Rehd.), a natural functional food highly rich in dihydrochalcones including trilobatin, phlorizin and phloretin, is reported to possess numerous biological activities especially for treating diabetes. Here, the aim of this systematical review and meta-analysis is to assess the effect of dihydrochalcones in sweet tea (DST) on diabetes and summarize their possible mechanisms. We searched in eight databases including Embase, PubMed, Cochrane, Web of Science, WanFang database, VIP database, China National Knowledge Infrastructure and China Biology Medicine from Jan 2000 to Nov 2021 and ultimately included 21 animal studies in this review. A total of 10 outcome measurements including blood lipid indexes, blood glucose, insulin resistance indicators and oxidative stress biomarkers were extracted for meta-analysis using RevMan 5.4 software. DST significantly decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), blood glucose (BG), homeostasis model assessment of insulin resistance (HOMA-IR) and malondialdehyde (MDA), and increased high-density lipoprotein cholesterol (HDL-c), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in diabetic animal models. In summary, DST could treat diabetes by regulation of blood glucose/lipid metabolism, oxidative/carbonyl stress, inflammatory response etc.

Goethite modified biochar simultaneously mitigates the arsenic and cadmium accumulation in paddy rice (Oryza sativa) L.

Cadmium (Cd) and arsenic (As) contamination of paddy soils is a serious global issue because of the opposite geochemical behavior of Cd and As in paddy soils. Rice plant (Oryza sativa L.) cultivation in Cd- and As- contaminated paddy soil is regarded as one of the main dietary cause of Cd and As entry in human beings. This study aimed to determine the impact of goethite-modified biochar (GB) on bioavailability of both Cd and As in Cd- and As- polluted paddy soil. Contrary to control and biochar (BC) amendments, the application of GB amendments significantly impeded the accumulation of both Cd and As in rice plants. The results confirmed an obvious reduction in Cd and As content of rice grains by 85% and 77%, respectively after soil supplementation with GB 2% amendment. BC 3% application minimized the Cd uptake by 59% in the rice grains as compared to the control but exhibited a little impact on As accumulation in rice grains. Sequential extraction results displayed an increase in immobile Cd and As fractions of the soil by decreasing the bioavailable fractions of both elements after GB treatments. Fe-plaque formation on the root surfaces was significantly variable (P Ë‚ 0.05) among all the amendments. GB 2% treatment significantly increased the Fe content (10 g kg-1) of root Fe-plaque by 48%, which ultimately enhanced the sequestration of Cd and As by Fe-plaque and minimized the transport of Cd and As in rice plants. Moreover, GB treatments significantly changed the relative abundance of the microbial community in the rice rhizosphere and minimized the metal(loid)s mobility in the soil. The relative abundance of Acidobacteria, Firmicutes and Verrucomicrobia increased with GB 2% treatment while those of Bacteroidetes and Choloroflexi decreased. Our findings confirmed improvement in the rice grains quality regarding enhanced amino acid contents with GB application. Overall, the results of this study demonstrated that GB amendment simultaneously alleviated the Cd and As concentrations in edible parts of rice plant and provided a new valuable method to protect the public health by effectively remediating the co-occurrence of Cd and As in paddy soils.

Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology.

Chronic kidney disease (CKD) is a chronic progressive disease that seriously threatens human health. Some patients will continue to progress into the CKD stage 3-5 (also called chronic renal failure), which is mainly manifested by a decline in renal function and multi-system damage. Perilla frutescens (L.) Britton. (Lamiaceae) is one of the most widely used traditional Chinese medicine (TCM) herbs in CKD, especially in CKD stage 3-5. But its active components and mechanisms are still unclear. In this study, we used network pharmacology to analyze the active components of P. frutescens and the main therapeutic targets for intervention in CKD stage 3-5. Then, the key components were selected for enrichment analysis and identified by high performance liquid chromatograph (HPLC). Finally, we verified the critical components through molecular docking, and in vitro experiments. The results show that 19 main active components of P. frutescens were screened, and 108 targets were intersected with CKD stage 3-5. The PPI network was constructed and found that the core nodes AKT1, TP53, IL6, TNF, and MAPK1 may be key therapeutic targets. Enrichment analysis shows that related targets may be involved in regulating various biological functions, and play a therapeutic role in CKD stage 3-5 by regulating apoptosis, T cell receptor, and PI3K-AKT signaling pathways. Molecular docking indicates that the key active components were well docked with its corresponding targets. Five active components were identified and quantified by HPLC. According to the results, luteolin was selected as the critical component for further verification. In vitro experiments have shown that luteolin can effectively alleviate adriamycin (ADR)-induced renal tubular apoptosis and suppress AKT and p53 phosphorylation. The effects of luteolin to reduce apoptosis may be mediated by inhibiting oxidative stress and downregulating the mitogen-activated protein kinase (MAPK) and p53 pathways. In general, we screened and analyzed the possible active components, therapeutic targets and pathways of P. frutescens for treating CKD. Our findings revealed that luteolin can reduce renal tubular epithelial cell apoptosis and may be the critical component of P. frutescens in the treatment of CKD. It provides references and direction for further research.

A Brief, Individualized Exercise Program at Intensities Below the Ventilatory Threshold Exerts Therapeutic Effects for Depression: A Pilot Study.

Due to the fact that existing pharmacological treatments for depression are not ideal, effort has been devoted to the development of complementary, alternative therapies such as physical exercise. The antidepressant effect of exercise is well documented. However, current recommendations and prescriptions of exercise may be too demanding for depressed patients, as some complain about the design of exercise programs and depression is associated with reduced motivation and capacity to exercise. Therefore, appropriately designed, patient-friendly exercise programs may prove critical for the long-term maintenance and therapeutic effects of exercise. In this pilot study, we developed an exercise program based on patients' individual level of ventilatory threshold (VT), a submaximal index of aerobic capacity measured by Cardiopulmonary Exercise Testing (CPX). Compared to traditional measures, CPX provides more trustable indices of aerobic capacity and more homogenous exercise prescriptions. The main episode of the program consisted of 15-25 min of cycling twice a week at an intensity that approached but never went higher than subjects' VT (considered low to moderate in intensity). We found that in patients diagnosed with major depressive disorder or persistent depressive disorder (n = 8), the program resulted in a significant reduction in depressive symptoms at week 8, which was maintained at week 16. Meanwhile, patients' social functioning, quality of life, and cognitive functions improved. Although we used a single arm, non-randomized design, our results suggest that even a brief, low to moderate intensity exercise program may exert therapeutic effects for depression and CPX may be a useful tool for exercise prescriptions.

The Mood-Improving Effect of Viewing Images of Nature and Its Neural Substrate.

It has been recently suggested that contact with nature improves mood via reducing the activity of the prefrontal cortex. However, the specific regions within the prefrontal cortex that underlie this effect remain unclear. In this study, we aimed to identify the specific regions involved in the mood-improving effect of viewing images of nature using a 52-channel functional near-infrared spectroscopy (fNIRS). Specifically, we focused on the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (dlPFC), two regions associated with affective processing and control. In a randomized controlled crossover experiment, we assigned thirty young adults to view images of nature and built environments for three minutes each in a counterbalanced order. During image viewing, participants wore a fNIRS probe cap and had their oxyhemoglobin (oxy-Hb) measured. Immediately following each image viewing, participants indicated their mood in terms of comfortableness, relaxation, and vigor. Results showed that viewing images of nature significantly increased comfortableness and relaxation but not vigor compared to viewing images of built environments, with a large effect size. Meanwhile, the concentration of oxy-Hb in only the right OFC and none of the other regions significantly decreased while viewing the images of nature compared to built environments, with a medium effect size. We speculate that viewing images of nature improves mood by reducing the activity of or calming the OFC. Since the OFC is hyperactive in patients with depression and anxiety at rest, contact with nature might have therapeutic effects for them.

Study of monoglycerides enriched with unsaturated fatty acids at sn-2 position as oleogelators for oleogel preparation.

The effect of using highly unsaturated 2-monoglycerides as oleogelators on the properties of soybean oil oleogels designed to eliminate saturated and trans fatty acids was investigated in this study. We adopted a novel two-step synthesis aiming to increase the yield of the 2-monoglycerides. The optimal synthesis conditions were a substrate weight ratio of 2:1 (w/w), 10% Lipozyme 435 (w/w total reactants), and 4 h of reaction time at room temperature. Under these conditions, the 2-monoglyceride yield (40.69%) increased by 10% compared to that of the conventional synthesis route. Additionally, soybean oil oleogels prepared using 10% 2-monoglycerides with or without rice bran wax were systematically characterized by polarized light microscopy, a texture analyzer, XRD spectroscopy, and rheometry. Comparative studies indicated that a combination of rice bran wax and 2-monoglycerides had synergistic effects on gel properties. A mixture of 4% rice bran wax and 6% 2-monoglycerides was found to provide better oleogels.

An organoid-based drug screening identified a menin-MLL inhibitor for endometrial cancer through regulating the HIF pathway.

Tumor organoids recapitulate pathological properties and would serve as an excellent ex vivo model for drug discovery. Here, we performed an unbiased drug screening on drivers-defined tumor organoids from mouse endometrial cancer, the most prevalent gynecological malignancy in human, with a small molecule library targeting epigenetic factors. Among them, menin-MLL inhibitors MI-136 and MI-463 scored. The therapeutic capacity of MI-136 was further validated in tumor organoids in vitro and an orthotopic model in vivo. CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136. Transcriptome analysis showed that the hypoxia-inducible factor (HIF) pathway was the most significantly downregulated pathway by MI-136 treatment. Consistently, Men1, Kmt2a, and Ash2l knockout also repressed the expressions of the HIF target genes. Loss of Hif1a or Hif1b partially phenocopied the inhibition of the menin-MLL complex by MI-136 or mutations in term of tumor organoid growth. Further, we found that MEN1 was upregulated in human endometrial cancers, which were tightly correlated with the expression levels of HIF1A, and associated with poor prognosis. Importantly, MI-136 also significantly inhibited the growth of endometrial cancer organoids derived from patients. Thus, our study identified MI-136 as a potential inhibitor for endometrial cancer through regulating the HIF pathway, a novel molecular mechanism distinguished from those in AML and prostate cancer.

Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial.

BACKGROUND: Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. OBJECTIVE: To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. METHODS: This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. RESULTS: Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001). CONCLUSION: Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline.

[Intestinal dysfunction of spinal cord injury treated with tongdu tiaoshen moxibustion: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect on intestinal dysfunction of spinal cord injury (SCI) between the comprehensive therapy of tongdu tiaoshen moxibustion (moxibustion for opening the governor vessel and regulating the spirit) and rehabilitation training and the simple treatment with rehabilitation training. METHODS: A total of 60 patients with intestinal dysfunction of SCI were randomized into a comprehensive therapy group and a rehabilitation group, 30 cases in each one (3 cases were dropped out in each group). On the base of the routine western medicine treatment and rehabilitation training, the bowel training and rectal function training were provided, once a day in the rehabilitation group. In the comprehensive therapy group, on the base of the treatment as the rehabilitation group, the tongdu tiaoshen moxibustion was exerted at Yaoyangguan (GV 3), Mingmen (GV 4), Zhiyang (GV 9), Dazhui (GV 14) and Baihui (GV 20), etc, once a day, 30 min each time. In both groups, the treatment for 4 weeks was as one course and 3 courses of treatment were required. Separately, before treatment, after 4, 8 and 12 weeks of treatment, the scores of neurogenic bowel dysfunction (NBD) and World Health Organization quality of life scale (WHOQOL-BREF) were observed and the clinical effect was evaluated after 12 weeks of treatment. RESULTS: After treatment, the total effective rate was 88.9% (24/27) in the comprehensive therapy group, which was higher than 74.1% (20/27) in the rehabilitation group (P<0.05). After 4, 8 and 12 weeks of treatment, NBD scores were all reduced obviously as compared with those before treatment in the two groups (all P<0.01). After 8 and 12 weeks of treatment, NBD scores in the comprehensive therapy group were lower than the rehabilitation group (both P<0.05). After 4, 8 and 12 weeks of treatment, the scores of all of the domains (psychology, physiology, social relations and environment) in WHOQOL-BREF were higher than those before treatment in the two groups (all P<0.01). After 4 weeks of treatment, the scores in the psychology and physiology domains in the comprehensive therapy group were higher than the rehabilitation group (all P<0.05). After 8 and 12 weeks of treatment, the scores of all of the domains in the comprehensive therapy group were higher than the rehabilitation group (all P<0.05). CONCLUSION: The comprehensive treatment of tongdu tiaoshen moxibustion and rehabilitation training achieves the better effect on intestinal dysfunction of SCI than the simple rehabilitation training and greatly improves the quality of life in SCI patients.

Goethite-modified biochar restricts the mobility and transfer of cadmium in soil-rice system.

Cadmium (Cd) contamination of paddy soils has raised serious concerns for food safety and security. Remediation and management of Cd contaminated soil with biochar (BC) and modified biochar is a cost-effective method and has gained due attention in recent years. Goethite-modified biochar (GB) can combine the beneficial effects of BC and iron (Fe) for remediation of Cd contaminated soil. We probed the impact of different BC and GB amendments on Cd mobility and transfer in the soil-rice system. Both BC and GB effectively reduced Cd mobility and availability in the rhizosphere and improved the key growth attributes of rice. Although BC supply to rice plants enhanced their performance in contaminated soil but application of 1.5% GB to the soil resulted in prominent improvements in physiological and biochemical attributes of rice plants grown in Cd contaminated soil. Sequential extraction results depicted that BC and GB differentially enhanced the conversion of exchangeable Cd fractions to non-exchangeable Cd fractions thus restricted the Cd mobility and transfer in soil. Furthermore, supplementing the soil with 1.5% GB incremented the formation of iron plaque (Fe plaque) and boosted the Cd sequestration by Fe plaque. Increase in shoot and root biomass of rice plants after GB treatments positively correlates with incremented chlorophyll contents and gas exchange attributes. Additionally, the oxidative stress damage in rice plants was comparatively reduced under GB application. These findings demonstrate that amending the soil with 1.5% GB can be a potential remediation method to minimize Cd accumulation in paddy rice and thereby can protect human beings from Cd exposure.

Neuroprotective effect of omega-3 fatty acids on spinal cord injury induced rats.

INTRODUCTION: In this study, the effects of omega-3 fatty acids were examined in a rat model of spinal cord injury. METHODS: The rats were classified into sham, control, spinal cord injury plus 50 mg/kg Omega-3 fatty acids and spinal cord injury plus 100 mg/kg Omega-3 fatty acids. The levels of oxidative, apoptotic, and inflammatory markers were examined in each of these groups. RESULTS: Altered lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and catalase were normalized. Omega-3 fatty acid supplementation decreased tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels by >50%. TNF-α and IL-6 mRNA expression were reduced. Caspase-3, p53, bax, and pro-NGF mRNA expression levels were increased by 1.3-, 1.4-, 1.2-, and 0.9-fold, respectively, whereas bcl-2 mRNA expression was decreased by 0.77-fold in control rats. Omega-3 fatty acid supplementation decreased p53, caspase-3, bax, and pro-NGF mRNA expression by >40%, while the level of bcl-2 mRNA expression was increased by 286.9%. Omega-3 fatty acid supplementation decreased caspase-3 and p53 protein expression by >30%. CONCLUSION: Taken together, our results suggested that omega-3 fatty acid supplementation reduced oxidative stress, apoptosis, and the levels of inflammatory markers in ischemia-reperfusion-induced rats.

Graphene oxide-facilitated uranium transport and release in saturated medium: Effect of ionic strength and medium structure.

Natural subsurface environment is a complex heterogeneous system. To investigate the effect of ionic strength (IS) and heterogeneity on the transport and remobilization of graphene oxide (GO)-facilitated uranium (U(VI)) in saturated porous media, column experiments were performed by the injection of U(VI) alone and U(VI)+GO mixtures into homogeneous and heterogeneous porous media under low and high ionic strength (1 and 50 mM) conditions, and then the columns were successively flushed with background solution and DI water. Results showed that when U(VI) only was introduced into the columns, IS had little effect on the migration of U(VI) alone in both media and the presence of preferential flow in heterogeneous media slightly enhanced the mobility of U(VI). As U(VI)+GO mixtures were injected into the columns, GO showed strong mobility at low IS and high released peak at high IS. The appearance of GO significantly enhanced U(VI) transport in both media. Under low IS condition, the mobility of U(VI) was significantly enhanced at the injection phase, and the medium heterogeneity further promoted the amount of GO-sorbed U(VI) transport. At high IS, less GO-sorbed U(VI) was observed during injection phase, and a large amount of retained GO-sorbed U(VI) were released with GO remobilization during water flushing phase, and the release showed the longer-tailing phenomenon and the release amount was more pronounced in heterogeneous media. The findings in this study showed that the coupled effect of solution chemistry and media heterogeneity played important roles on GO-facilitated U(VI) transport and release in soil and groundwater system.

Systematically identifying the hepatoprotective ingredients of schisandra lignan extract from pharmacokinetic and pharmacodynamic perspectives.

BACKGROUND: Herbal medicines (HMs) have been proven to be productive sources of leads for the development of drugs. To date approximately 150 lignans have been identified from Schisandra sphenanthera. Hepatoprotective activity is a well-known characteristic of schisandra lignans, yet the authentic types of active lignans are still not well known. PURPOSE: The present study aimed to develop a reliable and efficient strategy for identifying the hepatoprotective ingredients of schisandra lignan extract (SLE). METHODS: SLEs were prepared by extracting Schisandra sphenanthera powder using 10%, 50% and 90% ethanol (w/w 1:10) combining 5-fold volume of ethyl acetate. The schisandra lignans in SLEs were qualitatively analyzed based on liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LCMS-IT-TOF). Preparative liquid chromatography (PLC) was used to collect ingredient fractions. The hepatoprotective activity of schisandra lignans was systematically investigated on in vivo and in vitro models. RESULTS: The SLE extracted by 50% ethanol and 5-fold volume of ethyl acetate (50%SLE) had the highest lignan content and exhibited significantly stronger hepatoprotective activity than other SLEs (P <  0.01). The hepatoprotective effect of 50%SLE mainly attributed to the SLE segment which collected from 12 to 22 min by PLC. Schisantherin A (Sth A) was confirmed as the most promising hepatoprotective drug in Schisandra sphenanthera due to high content in crude materials, high exposure level in vivo and high efficiency on APAP-induced hepatotoxicity. CONCLUSION: The hepatoprotective ingredients of SLEs were systematically investigated based on the presently developed approach, and Sth A was identified as the optimum hepatoprotective candidate in Schisandra sphenanthera.

Association of Gene Mutations with Response to Arsenic-Containing Compound Qinghuang Powder () in Patients with Myelodysplastic Syndromes.

OBJECTIVES: To investigate the relationship between gene mutations and response to Compound Qinghuang Powder (, CQHP) in patients with myelodysplastic syndrome (MDS). METHODS: Forty-three MDS patients were genotyped by ultra-deep targeted sequencing and the clinical data of patients were collected and the relationship between them was analyzed. RESULTS: Up to 41.86% of patients harbored genet mutations, in most cases with more than one mutation. The most common mutations were in SF3B1, U2AF1, ASXL1, and DNMT3A. After treatment with CQHP, about 88.00% of patients no longer required blood transfusion, or needed half of prior transfusions. CONCLUSIONS: CQHP is an effective treatment for patients with MDS, especially those with gene mutations in SF3B1, DNMT3A, U2AF1, and/or ASXL1.

Phytochemistry, pharmacology, and clinical use of Panax notoginseng flowers buds.

Panax notoginseng is a well-known traditional Chinese medicine, and dried flower buds of P. notoginseng (FBP) have also been used as a medicine or tea for a long time. The pharmacological effects of FBP include antihypertensive, anticancer, hepatoprotective, and cardiovascular protective effects. The compounds in FBP include saponins, flavonoids, volatile oils, and polysaccharides. The total saponins are the principal bioactive components. In modern applications, FBP is used to treat hypertension and tinnitus. There have been many studies on FBP and its effects in recent years, and it has attracted much attention in the medical field. This review summarizes the chemical components, pharmacological action, and clinical uses of FBP comprehensively to provide the references of deeper studies.

[Observation on therapeutic effect of combined acupuncture for stress gastric mucosal injury after traumatic brain injury].

OBJECTIVE: To observe the therapeutic effect of combined acupuncture combined with omeprazole on patients with craniocerebral trauma complicated with stress gastric mucosal injury. METHODS: Patients with stress gastric mucosal injury after cerebral trauma admitted to neurology of Brain Hospital, Affiliated Hospital of Logistics University from June 2016 to July 2017 were enrolled, with the inclusion criteria within 24 hours after injury at admission, and Glasgow coma scale (GCS) less than 12. Patients were divided into omeprazole group, acupuncture group and acupuncture plus omeprazole combined treatment group according to random number table method. All patients in the three groups were given symptomatic treatment in time after admission. After diagnosis, omeprazole group was injected intravenously omeprazole, 40 mg each time, one dose in 12 hours for 7 days; acupuncture group was acupunctured at bilateral Zusanli point and Zhongwan point, 20 minutes for needle retention, once a day for 7 days; combined treatment group was given acupuncture and omeprazole at the same time. The GCS score and the occult stool test were performed at admission and treatment of 7 days; the pH of gastric juice, the levels of serum neurotensin (NT) and endothelin-1 (ET-1) were measured at admission and treatment 1, 3, 5, 7 days. At the same time, 10 healthy persons were selected as the control. RESULTS: Finally, 90 patients were selected, 30 in each group. GCS score at 7 days after treatment in omeprazole group, acupuncture group and combined treatment group were significantly higher than those at admission, but there was no statistical difference among the groups (9.46±2.81, 10.26±2.24, 10.52±2.50, F = 2.010, P = 0.141). For treatment of 7 days, the incidence of occult stool in the combined treatment group was significantly lower than that in the omeprazole group and acupuncture group (13.3% vs. 36.7%, 40.0%, both P < 0.05). The pH value of gastric excretion was increased gradually after treatment in the three groups. The pH value of gastric excretion in the combined treatment group was significantly higher than that in the omeprazole group and acupuncture group at 5 days of treatment (4.58±0.53 vs. 4.20±0.52, 4.28±0.43, both P < 0.05). The levels of serum NT in the three groups were both bi-directional: the level of NT at admission was significantly higher than that in the healthy control group, then decreased significantly, and the treatment of 3 days was significantly lower than that in the healthy control group and then rise gradually. The level of NT at treatment 5 days in the combined treatment group was significantly higher than that of the omeprazole group and the acupuncture group (ng/L: 45.88±8.03 vs. 36.15±11.54, 37.32±7.79, both P < 0.05), and had returned to normal level on the 7th day after treatment (ng/L: 56.88 ±12.54). The level of serum ET-1 in the three groups showed a bimodal change: the level of ET-1 at admission was significantly higher than that of the healthy control group. The treatment of 1 day to the normal range was gradually increased, and the peak of 5 days appeared again and then decreased slowly. The level of ET-1 at treatment of 7 days in the combined treatment group was significantly lower than that of the omeprazole group and acupuncture group (ng/L: 53.25±7.60 vs. 63.74±9.05, 65.50±12.73, both P < 0.05), and had been restored to normal. CONCLUSIONS: Combined acupuncture at points of Zusanli and Zhongwan for the treatment of stress gastric mucosal injury after traumatic brain injury, can reduce gastric acid secretion, promote the level of NT in serum, reduce the secretion of ET-1 level, help to repair the gastric mucosa, and the effect of combined with omeprazole is more significant.