Laminarin ameliorates iodoacetamide-induced functional dyspepsia via modulation of 5-HT3 receptors and the gut microbiota.

Visceral and somatic hypersensitivity is a common cause of functional dyspepsia. Marine bioactive components have been revealed to possess numerous valuable abilities. However, as a kind of polysaccharide extracted from brown algae, the study focused on the biological properties of laminarin is still limited, especially in gastrointestinal disorders. In our study, indicators associated with visceral sensational function and gastrointestinal microecology were determined to investigate the modulatory effects of laminarin on functional dyspepsia induced by iodoacetamide. Mice with visceral hypersensitivity were orally administrated with laminarin (50 and 100 mg per kg bw) for fourteen days. The results indicated that laminarin partly alleviated the dysfunction by regulating corticosterone secretion, the expression of 5HT3 receptors at both protein and mRNA levels, and mechanical transduction through the PIEZO2-EPAC1 axis. Furthermore, laminarin administration moderated the imbalanced gut microbial profile, including modulating the abundance of Bacteroidetes and Firmicutes. Our findings revealed that laminarin may restore the overexpression of 5HT3 receptors, the abnormal mechanical transduction, and impaired gut microecology. In conclusion, we provide evidence to support the utilization of laminarin as the ingredient of complementary and alternative medicine of regulating visceral and somatic hypersensitivity.

XQZ3, a Chlorella pyrenoidosa polysaccharide suppresses cancer progression by restraining mitochondrial bioenergetics via HSP90/AKT signaling pathway.

The mitochondria are known to exert significant influence on various aspects of cancer cell physiology. The suppression of mitochondrial function represents a novel avenue for the advancement of anti-cancer pharmaceuticals. The heat shock protein HSP90 functions as a versatile regulator of mitochondrial metabolism in cancer cells, rendering as a promising target for anticancer interventions. In this work, a novel acid polysaccharide named as XQZ3 was extracted from Chlorella pyrenoidosa and purified by DEAE-cellulose and gel-filtration chromatography. The structural characteristic of XQZ3 was evaluated by monosaccharides composition, methylation analysis, TEM, FT-IR, and 2D-NMR. It was found that XQZ3 with a molecular weight of 29.13 kDa was a complex branched polysaccharide with a backbone mainly composed of galactose and mannose. It exhibited good antitumor activity in vitro and in vivo by patient-derived 3D organoid models and patient-derived xenografts models. The mechanistic investigations revealed that XQZ3 specifically interacted with HSP90, impeding the activation of the HSP90/AKT/mTOR signaling cascade. This, in turn, led to the induction of mitochondrial dysfunction, autophagy, and apoptosis, ultimately resulting in the demise of cancer cells due to nutrient deprivation. This study offers a comprehensive theoretical foundation for the advancement of XQZ3, a novel polysaccharide inhibitor targeting HSP90, with potential as an effective therapeutic agent against cancer.

Comprehensive investigation of milk oligosaccharides in different mammalian species and the effect of breed and lactation period on sheep milk oligosaccharides.

Milk oligosaccharides (MOs) have unique health benefits for newborns, and MOs are important components in mammalian milk. The present study was conducted to provide a comprehensive analysis of MOs in important domestic animals, including goats, cows, camels and sheep. The comparison with human MOs was conducted simultaneously. Furthermore, analysis of the relative abundance of sheep MOs among different breeds (Hu sheep, East Friesen sheep, East Friesen-Hu crossbred sheep) and lactation periods (colostrum, mature milk) was performed. In general, 35, 24 19, 26, and 16 MOs were identified in human, goat, bovine, camel and sheep milk, respectively. The type of sheep MOs was not greatly influenced by the breeds and lactation period. Hu sheep colostrum had the highest abundance of MOs among six sheep milks, followed by East Friesen sheep colostrum, while East Friesen-Hu crossbred sheep mature milk had the lowest abundance of MOs. These findings provide evidence for the potential value of MOs from domestic animal milk for the commercial applications.

New insight into the effect of nitrogen on hydrocarbon degradation in petroleum-contaminated soil revealed through 15N tracing and flow cytometry.

Nitrogen (N) has been widely used to dissipate total petroleum hydrocarbons (TPH) in the oil-contaminated soil, but the relationships of hydrocarbon transformation, N cycling and utilization, and microbial characteristics during TPH biodegradation still remain unclear. In this study, 15N tracers (K15NO3 and 15NH4Cl) were used as stimulants for TPH degradation to compare the bioremediation potential of TPH in the historically (5 a) and freshly (7 d) petroleum-contaminated soils. During bioremediation process, TPH removal and carbon balance, N transformation and utilization, as well as microbial morphologies were investigated using 15N tracing and flow cytometry. Results showed that TPH removal rates were higher in the freshly polluted soils (61.59 % for K15NO3 amendment and 48.55 % for 15NH4Cl amendment) than in the historically polluted soils (35.84 % for K15NO3 amendment and 32.30 % for 15NH4Cl amendment), and TPH removal rate through K15NO3 amendment was higher than that of 15NH4Cl in the freshly polluted soils. This result was attributed to the higher N gross transformation rates in the freshly contaminated soils (0.0034-0.432 mmol N kg-1 d-1) when compared with that in the historically contaminated soils (0.009-0.04 mmol N kg-1 d-1), which led to more TPH transformation to residual carbon (51.84 %-53.74 %) in the freshly polluted soils than that in the historically polluted soils (24.67 %-33.47 %). Based on the fluorescence intensity displayed by the combination of stains and cellular components to indicate microbial morphology and activity, flow cytometry analysis showed that nitrogen addition was beneficial for the membrane integrity of TPH-degrading bacteria, and nitrogen also enhanced DNA synthesis and activity of TPH-degrading fungi in freshly polluted soil. Correlation and structural equation modeling analysis identified that K15NO3 was beneficial to synthesize DNA of the TPH-degrading fungi but not the bacteria, which contributed to enhance TPH bio-mineralization in the soils with K15NO3 amendment.

Load quantification and effect evaluation of urban non-point source pollution in the Licun River based on SWAT model.

With the gradual control of point source pollution, the impact of urban nonpoint source pollution on river water quality is becoming more prominent. Regarding the current problem that nonpoint source pollution loads in urban basins are difficult to quantify and the impact on water quality is difficult to analyze, the Licun River basin in Qingdao was selected as the research object. Through the field survey and surface accumulation sampling analysis of the basin, the evaluation model of urban nonpoint source pollution was constructed by revising the land type data of the basin and the urban database of the SWAT model. The results showed that concentration of nitrate in precipitation was most sensitive to the simulation of nitrogen loading; organic P in baseflow was most sensitive to the simulation of phosphorus loading. The Nash-Sutcliffe efficiency coefficient (ENS) and the coefficients of determination (R2) of the SWAT model for runoff, total phosphorus (TP), and total nitrogen (TN) in the simulation validation period meet the model requirements,indicating a good model fit. In addition, the spatial and temporal distribution characteristics of urban nonpoint source pollution of TN and TP in 2021 were analyzed. In July, rainfall-runoff from the Licun River basin was the most polluted.

Calcium supplements and structure-activity relationship of peptide-calcium chelates: a review.

In recent years, the functional properties of peptides derived from food proteins have attracted considerable interest. Among them, bioactive peptides that can effectively bind metals have application prospects in the improvement of mineral bioavailability, and compensating for the shortcomings of the generally low bioavailability of inorganic mineral supplements. Although a reasonable understanding of structure activity relationship related to the calcium binding of peptides has been gained, physiological connections of peptides as mineral carriers to gastrointestinal uptake needs further research. Hence, this article reviews (1) the development of calcium supplements; (2) inorganic calcium sources and bone calcium; (3) source and acquisition of biologically active peptides; (4) calcium peptide chelation mechanism and structure-activity relationship; and (5) Methods for evaluating calcium bioavailability.

Integrated Metabolomic and Transcriptomic Analysis Reveals Differential Mechanism of Flavonoid Biosynthesis in Two Cultivars of Angelica sinensis.

Angelica sinensis is a traditional Chinese medicinal plant that has been primarily used as a blood tonic. It largely relies on its bioactive metabolites, which include ferulic acid, volatile oils, polysaccharides and flavonoids. In order to improve the yield and quality of A. sinensis, the two cultivars Mingui 1 (M1), with a purple stem, and Mingui 2 (M2), with a green stem, have been selected in the field. Although a higher root yield and ferulic acid content in M1 than M2 has been observed, the differences of flavonoid biosynthesis and stem-color formation are still limited. In this study, the contents of flavonoids and anthocyanins were determined by spectrophotometer, the differences of flavonoids and transcripts in M1 and M2 were conducted by metabolomic and transcriptomic analysis, and the expression level of candidate genes was validated by qRT-PCR. The results showed that the contents of flavonoids and anthocyanins were 1.5- and 2.6-fold greater in M1 than M2, respectively. A total of 26 differentially accumulated flavonoids (DAFs) with 19 up-regulated (UR) and seven down-regulated (DR) were obtained from the 131 identified flavonoids (e.g., flavonols, flavonoid, isoflavones, and anthocyanins) in M1 vs. M2. A total 2210 differentially expressed genes (DEGs) were obtained from the 34,528 full-length isoforms in M1 vs. M2, and 29 DEGs with 24 UR and 5 DR were identified to be involved in flavonoid biosynthesis, with 25 genes (e.g., CHS1, CHI3, F3H, DFR, ANS, CYPs and UGTs) mapped on the flavonoid biosynthetic pathway and four genes (e.g., RL1, RL6, MYB90 and MYB114) belonging to transcription factors. The differential accumulation level of flavonoids is coherent with the expression level of candidate genes. Finally, the network of DAFs regulated by DEGs was proposed. These findings will provide references for flavonoid production and cultivars selection of A. sinensis.

Expression profiles of genes involved in fatty acid and lipid biosynthesis in developing seeds of Paeonia ostii.

BACKGROUND: Paeonia ostii seeds were identified as novel sources of edible plant oil with a high proportion of α-linolenic acid, a type of n-3 fatty acid with many health benefits. Due to the unreliability of seed oil content and quality, it is necessary to discover the mechanism underlying lipid biosynthesis in Paeonia ostii seeds. OBJECTIVES: This study aimed to identify the key genes involved in lipid biosynthesis in Paeonia ostii seeds by analyzing the relationship among the seed characteristics and the expression patterns of lipid genes in Paeonia ostii during seed development. METHODS: Preliminary research on Paeonia ostii seed development was carried out from 10 days after pollination until maturity, focusing on phenology, oil content and lipid profiles. In addition, we investigated the spatiotemporal expression of 36 lipid biosynthetic genes in Paeonia ostii by using quantitative real-time PCR. RESULTS: The results suggested that the development of Paeonia ostii seeds from pollination to maturity could be divided into three periods. The 36 lipid genes showed various spatiotemporal expression patterns and five gene groups with distinct temporal patterns during seed development were identified by clustering analysis of expression data. Furthermore, the relationships between gene expression and lipid/fatty acid accumulation and some candidate key lipid genes were discussed. CONCLUSIONS: This study provided the global patterns of fatty acid and lipid biosynthesis-related gene expression, which are critical to understanding the molecular basis of lipid biosynthesis and identifying the lipid accumulation rate-limiting genes during seed development.

Therapeutic effects and mechanisms study of Hanchuan Zupa Granule in a Guinea pig model of cough variant asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or "Nai-Zi-Lai" in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases. However, the pharmacological mechanisms of HCZP remain unrevealed. AIM OF THE STUDY: To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. MATERIALS AND METHODS: A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. RESULTS: Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. CONCLUSIONS: HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.

Design of a Sea Snake Antimicrobial Peptide Derivative with Therapeutic Potential against Drug-Resistant Bacterial Infection.

Infections caused by drug-resistant pathogens are a worldwide challenge for public health. Antimicrobial peptides (AMPs) are regarded as promising antibiotic alternatives for the treatment of drug-resistant infections. In the present study, a series of small peptides were designed based on our previously reported sea snake AMP Hc-CATH. From them, the lead peptide HC1-D2, a truncated peptide entirely substituted by d-amino acids, was selected. HC1-D2 exhibited significantly improved stability and antibiofilm and anti-inflammatory activities. Meanwhile, HC1-D2 retained potent, broad-spectrum, and rapid antimicrobial properties against bacteria and fungi, especially drug-resistant bacteria. Moreover, HC1-D2 showed low propensity to induce bacterial resistance and low cytotoxicity and hemolytic activity. Notably, HC1-D2 showed potent in vivo anti-infective ability in mouse peritonitis models infected by both standard and drug-resistant bacteria. It significantly decreased the bacterial counts in the abdominal cavity and spleen of mice and apparently increased the survival rates of the mice. Acting through the MAPKs inflammatory pathway, HC1-D2 selectively induced the production of chemokine and the subsequent immune cell recruitment to the infection site, while inhibiting the production of pro-inflammatory cytokines with undesirable toxicities. These much improved properties make HC1-D2 a promising candidate for the development of novel peptide anti-infective agents against drug-resistant infections.

Dendrobium alkaloids decrease Aß by regulating α- and ß-secretases in hippocampal neurons of SD rats.

BACKGROUND: Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The imbalance between production and clearance of amyloid ß (Aß) is a very early, often initiating factor in AD. Dendrobium nobile Lindl. alkaloids (DNLA) extracted from a Chinese medicinal herb, which have been shown to have anti-aging effects, protected against neuronal impairment in vivo and in vitro. Moreover, we confirmed that DNLA can improve learning and memory function in elderly normal mice, indicating that DNLA has potential health benefits. However, the underlying mechanism is unclear. Therefore, we further explored the effect of DNLA on neurons, which is closely related to learning and memory, based on Aß. METHODS: We exposed cultured hippocampal neurons to DNLA to investigate the effect of DNLA on Aß in vitro. Cell viability was evaluated by MTT assays. Proteins were analyzed by Western blot analysis. RESULTS: The cell viability of hippocampal neurons was not changed significantly after treatment with DNLA. But DNLA reduced the protein expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), ß-site APP cleaving enzyme 1 (BACE1) and Aß1-42 of hippocampal neurons in rats and increased the protein expression of ADAM17. CONCLUSIONS: DNLA decreases Aß by regulating α- and ß-secretase in hippocampal neurons of SD rats.

Efficacy of ivabradine for heart failure: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Previous clinical trials have reported that ivabradine can effectively treat heart failure (HF). However, no systematic review has explored its efficacy and safety for HF. This systematic review will aim to evaluate the efficacy and safety of ivabradine for the treatment of patients with HF. METHODS: We will search the literature from the following electronic databases from inception to the January 31, 2019: Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. All randomized controlled trials (RCTs) of ivabradine for HF will be fully considered for inclusion without any restrictions. Additionally, grey literature including clinical trial registries, dissertations, and reference lists of included studies, conference abstracts will also be searched. Two researchers will review these literatures, extract data, and assess risk of bias of included RCTs separately. Data will be pooled by either fixed-effects model or random-effects model, and meta-analysis will be conducted if it is appropriate. RESULTS: The primary outcome is all-cause mortality. The secondary outcomes comprise of change in body weight, urine output, change in serum sodium, and all adverse events. CONCLUSIONS: The results of this study will summary provide up-to-dated evidence for assessing the efficacy and safety of ivabradine for HF. ETHICS AND DISSEMINATION: It is not necessary to acquire ethical approval for this systematic review, because no individual patient data will be used in this study. The results of this systematic review will be published through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019120814.

Association between sn-2 fatty acid profiles of breast milk and development of the infant intestinal microbiome.

Increasing evidence shows that host diet and gut microbes are related. Previous studies have shown the effects of specific dietary fatty acids (FAs) on intestinal microbiota, but little is known about the effect of the stereospecifically numbered sn-2 position in triglycerides (TG) of human milk on the gut microbiome of infants. This study aimed at examining possible effects of sn-2 FAs of human milk on the gut microbial development of breastfeeding babies. Sn-2 FAs and intestinal microbiota were assessed by GC-MS and high-throughput 16S rRNA sequencing, respectively. The results showed that breast milk from mothers in China contained ten major sn-2 FAs dominated by palmitic acid (C16:0, 54.42%), oleic acid (C18:1 n-9, 14.95%), linoleic acid (LA, C18:2 n-6, 12.81%), myristic acid (C14:0, 4.50%) and C12:0 (3.17%). Total long chain unsaturated fatty acids (LCUFA) decreased from colostrum to mature milk, while total saturated fatty acids (SFA) showed no significant difference during lactation. A significant association between sn-2 FAs in milk and infant gut microbiota was found between decanoic acid (C10:0), myristic acid (C14:0), stearic acid (C18:0), C16:0, arachidonic acid (AA, C20:4 n-6), docosahexaenoic acid (DHA, C22:6 n-3) with Bacteroides, Enterobacteriaceae, Veillonella, Streptococcus, and Clostridium. These microbes were involved in short-chain fatty acid (SCFA) production and other functions, and significantly increased at 13-15 d after breastfeeding was initiated. C16:0 and DHA were relevant to most of the microbes. This study demonstrated the relatively steady profiles of sn-2 FAs in breast milk and gut microbiota of infants, together with their correlation during the breastfeeding period. The above results provided important information for designing the configuration of FAs in next-generation formulas for Chinese infants.

Automatic Thalamus Segmentation from Magnetic Resonance Images Using Multiple Atlases Level Set Framework (MALSF).

In this paper, we present an original multiple atlases level set framework (MALSF) for automatic, accurate and robust thalamus segmentation in magnetic resonance images (MRI). The contributions of the MALSF method are twofold. First, the main technical contribution is a novel label fusion strategy in the level set framework. Label fusion is achieved by seeking an optimal level set function that minimizes energy functional with three terms: label fusion term, image based term, and regularization term. This strategy integrates shape prior, image information and the regularity of the thalamus. Second, we use propagated labels from multiple registration methods with different parameters to take full advantage of the complementary information of different registration methods. Since different registration methods and different atlases can yield complementary information, multiple registration and multiple atlases can be incorporated into the level set framework to improve the segmentation performance. Experiments have shown that the MALSF method can improve the segmentation accuracy for the thalamus. Compared to ground truth segmentation, the mean Dice metrics of our method are 0.9239 and 0.9200 for left and right thalamus.

[Effects and Biological Response on Bioremediation of Petroleum Contaminated Soil].

Bioaugmentation and biostimulation were used to remediate petroleum-contaminated soil which were collected from Zichang city in North of Shaanxi. The optimal bioremediation method was obtained by determining the total petroleum hydrocarbon(TPH) using the infrared spectroscopy. During the bioremediation, number of degrading strains, TPH catabolic genes, and soil microbial community diversity were determined by Most Probable Number (MPN), polymerase chain reaction (PCR) combined agarose electrophoresis, and PCR-denaturing gradient electrophoresis (DGGE). The results in different treatments showed different biodegradation effects towards total petroleum hydrocarbon (TPH). Biostimulation by adding N and P to soils achieved the best degradation effects towards TPH, and the bioaugmentation was achieved by inoculating strain SZ-1 to soils. Further analysis indicated the positive correlation between catabolic genes and TPH removal efficiency. During the bioremediation, the number of TPH and alkanes degrading strains was higher than the number of aromatic degrading strains. The results of PCR-DGGE showed microbial inoculums could enhance microbial community functional diversity. These results contribute to understand the ecologically microbial effects during the bioremediation of petroleum-polluted soil.

[Effect of Cordyceps sinensis powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats].

OBJECTIVE: To observe the effect of Cordyceps sinensis (CS) powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats, and to primarily explore its possible mechanisms. METHODS: Totally 30 male Sprague-Dawley rats were divided into the sham-operation group, the model group, and the treatment group by random digit table, 10 in each group. A chronic kidney disease (CKD) rat model was prepared by one step 5/6 nephrectomy. Rats in the treatment group were intragastrically administered with CS powder solution at the daily dose of 2 g/kg, once per day. Equal volume of double distilled water was intragastrically administered to rats in the sham-operation group and the model group. All medication lasted for 12 weeks. The general condition of rats, their body weight, blood pressure, 24 h proteinuria, urinary N-acetyl-ß-D-glucosaminidase (NAG), serum creatinine (SCr) , and blood urea nitrogen (BUN) were assessed before surgery, at week 2, 4, 6, 8, 10, and 10 after surgery. Pathological changes of renal tissues were observed under light microscope. Morphological changes of mitochondria in renal tubular epithelial cells were observed under transmission electron microscope. Activities of antioxidant enzymes including reduced glutathione (GSH), manganese superoxide dismutase (MnSOD), and malondialdehyde (MDA) in fresh renal tissue homogenate were detected. Mitochondria of renal tissues were extracted to detect levels of mitochondrial membrane potential and changes of reactive oxygen species (ROS). And expressions of cytochrome-C (Cyto-C) and prohibitin in both mitochondria and cytoplasm of the renal cortex were also measured by Western blot. RESULTS: (1) Compared with the sham-operation group, body weight was significantly decreased at week 2 (P <0. 01), but blood pressure increased at week 4 (P <0. 05) in the model group. Compared with the model group, body weight was significantly increased at week 12 (P <0. 01), but blood pressure decreased at week 8 (P < 0. 01) in the treatment group. (2) Compared with the sham-operation group, 24 h proteinuria, urinary NAG, blood SCr and BUN significantly increased in the model group (all P <0. 01). Compared with the model group, blood and urinary biochemical indices all significantly decreased in the treatment group (all P <0. 01). (3) Results of pathological renal scoring: Glomerular sclerosis index, scoring for tubulointerstitial fibrosis, degree of tubulointerstitial inflammatory infiltration were all obviously higher in the model group than in the sham-operation group (all P <0. 01). All the aforesaid indices were more obviously improved in the treatment group than in the model group (all P <0. 01). (4) Compared with the sham-operation group, activities of MnSOD and GSH-Px were significantly reduced, but MDA contents obviously increased in the renal cortex of the model group (all P <0. 01). Compared with the model group, activities of MnSOD and GSH-Px obviously increased (P <0. 05, P <0. 01), but MDA contents obviously decreased in the renal cortex of the treatment group (P <0. 01). (5) Compared with the sham-operation group, the mitochondrial membrane potential significantly decreased, but ROS levels significantly increased in the model group (all P <0.01). Compared with the model group, mitochondrial transmembrane potential increased in the treatment group, thereby inhibiting the tendency of increased production of ROS (both P < 0. 01). (6) Results of Western blot showed that, compared with the sham-operation group, expression levels of mitochondrial Cyto-C and Prohibitin were significantly reduced in the renal cortex (P <0. 01), but significantly elevated in the cytoplasm of the model group (P <0. 01). Compared with the model group, each index was obviously improved in the treatment group with statistical difference (P <0. 05, P <0. 01). CONCLUSION: CS powder had renal protection, and its mechanism might partially depend on in- hibition of oxidative stress and protection for mitochondria.

Chronic intake of high fish oil diet induces myeloid-derived suppressor cells to promote tumor growth.

Omega-3 polyunsaturated fatty acids enriched fish oil exerts beneficial anti-inflammatory effects in animal models with acute and chronic inflammatory diseases. Myeloid-derived suppressor cells (MDSCs), comprised of myeloid progenitors and precursors of myeloid cells, play vital roles in cancer. How fish oil affects the generation of MDSCs and the tumor development remains largely unexplored. Here, we show that dietary intake of high fish oil diet suppresses CD8(+) T cells activation and proliferation in vivo via elevated levels of MDSCs. Mechanistically, high fish oil diet induces the expression of immunosuppressive cytokine IL-10 and promotes myelopoiesis in the spleen as well as other peripheral tissues. The immature myeloid cells in the spleen exhibit morphological and functional characteristics of MDSCs with the capability to downregulate CD8(+) T cells activation. Depletion of MDSCs using anti-Gr-1 antibody decreases the growth of subcutaneously transferred B16 melanoma in mice on high fish oil diet. Interestingly, diet-induced production of MDSCs is not solely dependent of the spleen, as splenectomy has no effect on the tumor progress. Our data show that the liver functions as an alternative extramedullary hematopoiesis organ to support MDSCs differentiation and maintain tumor growth. Taken together, our study provides a novel insight into the physiological effects of fish oil and points to MDSCs as a possible mediator linking dietary fish oil intake and immunosuppression in cancer immunosurveillance.

Nanofluidic diode based on branched alumina nanochannels with tunable ionic rectification.

In this work, the synthetic alumina nanochannels with bi-, tri-, and tetra-branched geometry structures exhibited ionic current rectifications with nonlinear I-V curves. Such diode performance of the branched alumina nanochannel is mainly dependent on the cooperative asymmetry of the branched structure and the surface-charge distribution on inner walls. By regulating the geometry, electrolyte pH, and solution concentration, the tunable ionic rectification properties are effectively obtained including both the rectification ratios and the rectifying direction that were deduced from the converted ion selectivity. This nanofluidic diode may open up a new opportunity for the application of the complex nanofluidic devices in contrast to previously reported channels to provide molecular analysis, controlled mass transport, drug release, and various logic gate operations.

Inhibition of TGF-ß1/Smad signal pathway is involved in the effect of Cordyceps sinensis against renal fibrosis in 5/6 nephrectomy rats.

UNLABELLED: The present study aimed to investigate the effects of Cordyceps sinensis on renal fibrosis and its possible mechanisms. Sprague-Dawley rats were randomly divided into three groups: sham operation (SHAM) group, 5/6 subtotal nephrectomy (SNx) untreated group, and 5/6 subtotal nephrectomy treated with C. sinensis (2.0 g/kg d) (CS) group. Rats were studied 12 weeks after the surgery, and the CS group presented with significantly lower proteinuria, and better renal function compared with the SNx group (p<0.05). Pathological study showed that the glomerulosclerosis tubulointerstitial injury score was significantly reduced in the CS group compared with the SNx group. Furthermore, the mRNA expression of TGF-ß1, Smad2 and Smad3 and the protein expression of TGF-ß1, TßRI, TßRII and p-Smad2/3 were attenuated by the C. sinensis treatment. In constrast, the mRNA and protein expression of Smad7 was upregulated. Furthermore, the expression of α-SMA and FSP1 was also significantly attenuated, accompanied by the increasing expression of E-cadherin, suggesting the inhibition of the epithelial-mesenchymal transition (EMT). IN CONCLUSION: C. sinensis exerted its antifibrotic effect on the SNx rats through the inhibition of the TGF-ß1/Smad pathway.

[Fingerprint research on immunosuppressive fraction of Rehmanniae Radix by HPLC].

OBJECTIVE: To study the HPLC fingerprint of immunosuppressive fraction of Rehmanniae Radix, the genuine medicinal materials in Henan province. METHODS: By HPLC method,Dikma Platisil-C18 column (250 mm x 4.6 mm, 5 microm) was used with acetonitrile-0.1% phosphoric acid as mobile phase by gradient elution. The detection wavelength was 210 nm, flow rate was 1.0 mL/min and column temperature was set at 30 degrees C. RESULTS: Compared the 10 batches sample of the fingerprint similarity, 18 common peaks were marked and five peaks were identified. The similarities were more than 0.9. CONCLUSION: HPLC fingerprint of immunosuppressive fraction of Rehmanniae Radix is established, which lays the foundation for further pharmacodynamics research on Rehmanniae Radix.