Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism.

BACKGROUND: The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. PURPOSE: The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. METHODS: The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. RESULTS: Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 µM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. CONCLUSION: In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy.

Clinical updates suggest conserving metastatic sentinel lymph nodes (SLNs) of breast cancer (BC) patients during surgery; however, the immunoadjuvant potential of this strategy is unknown. Here we leverage an immune-fueling flex-patch to animate metastatic SLNs with personalized antitumor immunity. The flex-patch is implanted on the postoperative wound and spatiotemporally releases immunotherapeutic anti-PD-1 antibodies (aPD-1) and adjuvants (magnesium iron-layered double hydroxide, LDH) into the SLN. Genes associated with citric acid cycle and oxidative phosphorylation are enriched in activated CD8+ T cells (CTLs) from metastatic SLNs. Delivered aPD-1 and LDH confer CTLs with upregulated glycolytic activity, promoting CTL activation and cytotoxic killing via metal cation-mediated shaping. Ultimately, CTLs in patch-driven metastatic SLNs could long-termly maintain tumor antigen-specific memory, protecting against high-incidence BC recurrence in female mice. This study indicates a clinical value of metastatic SLN in immunoadjuvant therapy.

Soil multifunctionality of paddy field is explained by soil pH rather than microbial diversity after 8-years of repeated applications of biochar and nitrogen fertilizer.

Biochar and nitrogen (N) fertilizer application can increase soil carbon sequestration and enhance soil nutrient cycling. However, few studies have systematically explored the effects of the long-term application of biochar and N fertilizer on soil multifunctionality and characterized its driving factors. Based on an 8-year biochar paddy-field experiment in anthropogenic alluvial alkaline soil in northwest China, we measured eleven soil functions associated with soil carbon sequestration and nutrient cycling and four potential factors (soil bacterial and fungal richness, pH, and aggregates) governing soil functions to investigate the effects of three biochar rates (C0, no biochar; C1, 4.5 t ha-1 year-1; C2, 13.5 t ha-1 year-1) and two N fertilizer rates (N0, no N fertilizer; N1, 300 kg N ha-1 year-1) on individual soil ecosystem functions and soil multifunctionality. Our results showed that biochar and N fertilizer application increased soil organic carbon (SOC) by 20-58 % and total N content by 9.3-15 % and had a varied effect (but mainly positive) on the activity of enzymes associated with soil carbon, N, and phosphorus cycling. Different application rates of biochar and N fertilizer had no influence on soil DNA concentrations, but did change soil microbial diversity, soil aggregation, and pH. The carbon storage function (SOC content) of soils is an important predictor of multifunctionality. Long-term biochar and N fertilizer application indirectly explained soil multifunctionality by altering soil pH, whereas bacterial and fungal diversity and soil aggregates did not play significant roles in explaining soil multifunctionality. These findings suggest that the application of biochar and N fertilizer can enhance soil multifunctionality by directly improving the individual functions [soil carbon sequestration (SOC content)] and decreasing soil pH in alkaline paddy fields.

Soy oil and SPI based-oleogels structuring with glycerol monolaurate by emulsion-templated approach: Preparation, characterization and potential application.

In this study, soybean oil-based oleogels were prepared using soy-protein isolate (SPI) and glycerol monolaurate (GML) in an emulsion-template approach. The rheological, texture, microstructure, and oil-retention properties of the obtained oleogels were analyzed. Results showed that the soy oil-based oleogel prepared with 6 wt% GML exhibited high oil loss, low-hardness, and needle-like morphology compared to the soy-oil/SPI-based oleogel. On the other hand, soy oil-based /SPI-based oleogels structured by 3 or 6 wt% GML presented moderate thermal-stability and lowest oil loss than those prepared without GML. Furthermore, SPI-based oleogel containing 6 wt% GML showed highest free fatty acids release (62.07%) with significantly improved elastic modulus and apparent viscosity. Additionally, the obtained oleogels displayed the occurrence of van der Waals interactions and intermolecular hydrogen bonds, presenting enhanced thermal stability. These results contribute to a better understanding of oleogelation-based emulsions for formulating trans-free and low-saturated foodstuffs with desired physical and functional properties.

Tumor acidity and near-infrared light responsive drug delivery MoS2-based nanoparticles for chemo-photothermal therapy.

The rational design of tumor microenvironment (TME)- multifunctional stimuli-responsive nanocomposites is appealing for effective cancer treatment. However, multidrug resistance remains an obstacle to construct responsive oncotherapy. Herein, a novel MoS2/PDA-TPP nanocomposite loaded with chemotherapy drug of doxorubicin (DOX) is designed for TME dual-response and synergistically enhanced anti-tumor therapy based on the tumor-specific mitochondria accumulation ability and photothermal (PTT) therapy. In detail, the designed MoS2/PDA-TPP nanoplatform can act as a pH-responsive dissociation to endow fast release of DOX under an acidic TME and simultaneously improve the efficiency of PTT. Moreover, the mechanism shows that MoS2/PDA-TPP trigger mitochondrial-dependent apoptosis by producing reactive oxygen species (ROS) and reducing mitochondrial membrane potential (MMP). Most importantly, during PTT procedure, hyperthermia up to 50 °C can effectively induce tumor cell death without causing severe inflammation to adjacent tissues. Tumor targeting double stimulation response of nanocomposites is a novel idea to overcome drug resistance, which will provide a more effective strategy for solving practical problems.

Integrated traditional Chinese and conventional medicine in the treatment of anemia due to lower-risk myelodysplastic syndrome: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Erythropoiesis and iron homeostasis are closely related; anemia due to lower-risk myelodysplastic syndromes (MDS) remains difficult to treat. In the last decade, we have been committed to improving the regulation of iron metabolism using traditional Chinese medicine (TCM). Previous studies have found that the TCM Yi Gong San (YGS) can reduce the expression of transferrin by inhibiting hepcidin overexpression caused by inflammation, promote the outward transfer of intracellular iron, and improve the symptoms of anemia. Here, our study aimed to compare the efficacy of a conventional drug with YGS with that of conventional medicine with placebo to provide a scientific basis for making clinical decisions. METHODS: A prospective, multicenter, double-blinded, randomized controlled clinical trial will be conducted to evaluate the therapeutic efficacy of conventional medicine combined with YGS with that of conventional medicine alone in the treatment of MDS. A total of 60 patients would be enrolled in this study, with each treatment group (conventional medicine + YGS and conventional medicine + placebo) comprising 30 patients. Oral medication would be administered twice daily for 3 months. All patients would be followed up throughout the 3-month period. The primary outcome was measured by assessing blood hemoglobin level. The secondary outcome was measured by assessing TCM symptom score, iron metabolism, hepcidin levels, and inflammatory factors. DISCUSSION: This trial would aim to demonstrate the effectiveness and feasibility of YGS in the treatment of lower-risk MDS anemia, as well as its impact on inflammatory factors and iron metabolism in patients with lower-risk MDS. TRIAL REGISTRATION: Chinese Clinical Trials Registry ( http://www.chictr.org.cn/ ) ChiCTR1900026774 .  Registered on October 21, 2019.

Activation of FGFR2 Signaling Suppresses BRCA1 and Drives Triple-Negative Mammary Tumorigenesis That is Sensitive to Immunotherapy.

Fibroblast growth factor receptor 2 (FGFR2) is a membrane-spanning tyrosine kinase that mediates FGF signaling. Various FGFR2 alterations are detected in breast cancer, yet it remains unclear if activation of FGFR2 signaling initiates tumor formation. In an attempt to answer this question, a mouse model berrying an activation mutation of FGFR2 (FGFR2-S252W) in the mammary gland is generated. It is found that FGF/FGFR2 signaling drives the development of triple-negative breast cancer accompanied by epithelial-mesenchymal transition that is regulated by FGFR2-STAT3 signaling. It is demonstrated that FGFR2 suppresses BRCA1 via the ERK-YY1 axis and promotes tumor progression. BRCA1 knockout in the mammary gland of the FGFR2-S252W mice significantly accelerated tumorigenesis. It is also shown that FGFR2 positively regulates PD-L1 and that a combination of FGFR2 inhibition and immune checkpoint blockade kills cancer cells. These data suggest that the mouse models mimic human breast cancers and can be used to identify actionable therapeutic targets.

Nitrogen and phosphorus trajectories (1998-2030) under regional development strategy of mainland China.

A good understanding of the nutrient cycle under a regional development strategy is crucial for nutrient management decision-making. Quantitatively assessment of nutrient flow under the regional coordinated development strategy in mainland China can provide scientific reference for achieving global high-quality coordinated economic and agricultural development. In this study, the characteristics of nitrogen (N) and phosphorus (P) flows of agricultural systems in mainland China from 1998 to 2030 were quantified using nutrient flows in food chain environment and resource (NUFER) model. The results revealed that national N and P surplus intensity were 50.3 and 18.6 kg·hm-2 in 2018, respectively, and there is still space for soil nutrient retention. The national input and output of N and P showed a continuous upward trend over the last two decades. Chemical fertilizer application and livestock rearing are the key points for nutrient management in China's agricultural systems. Under the regional development strategy, considerable geographical variation in N and P surplus intensity was observed across the country. From 1998 to 2013, the regional distribution of N and P surplus intensity was in accordance with regional economic characteristics. Areas with higher N and P surplus intensities were mainly in the eastern and central regions. From 2014 to 2018, equal emphasis on ecology and economy in the Yangtze River Economic Belt allowed development without aggravating the deterioration of the N and P surplus in the region. Over the next 10 years, our simulation predicts that future nutrient footprints tend to decrease, and coordinated governance of regional development and agricultural environment protection are the key to regional sustainable development.

[Grade evaluation of Sophorae Tonkinensis Radix et Rhizoma based on quality constant evaluation method].

The traditional Chinese medicine(TCM) quality constant herbal slices evaluation method was applied to evaluate the grade of Sophorae Tonkinensis Radix et Rhizoma based on the combination of traditional character identification and modern scientific and technological methods. The TCM quality constant evaluation method was used to determine the appearance and index content of medicinal slices, calculate the quality constant and percentile quality constant of Sophorae Tonkinensis Radix et Rhizoma from different sources, and discuss their classification. The quality constants of 15 batches of Sophorae Tonkinensis Radix et Rhizoma slices were between 0.004 and 0.063. The slices with the percentage quality constant ≥80% were classified as the first grade; those with the percentage quality constant ≥50% and <80% were classified as the second grade; and those with the percentage quality constant <50% were classified as the third grade. Then the slices with the quality constant ≥0.050 were classified as the first grade; those with the quality constant ≥0.032 and <0.050 were classified as the second grade; and those with the quality constant <0.032 were classified as the third grade. According to the results, the 15 batches of Sophorae Tonkinensis Radix et Rhizoma slices were divided into 1 batch of the first grade, 4 batches of the second grade, and 10 batches of the third grade. The quality constant evaluation method established is scientific, objective, simple and feasible. The application of the method in Sophorae Tonkinensis Radix et Rhizoma slices has reasonable results, which is helpful to promote the classification of Sophorae Tonkinensis Radix et Rhizoma and promotes the high-quality application of Sophorae Tonkinensis Radix et Rhizoma.

Pluronic-based graphene oxide-methylene blue nanocomposite for photodynamic/photothermal combined therapy of cancer cells.

A nanocomposite containing methylene blue (MB), graphene oxide (GO) and Pluronic F127 (PF127) had been developed for combined photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, GO was firstly loaded with MB to form GO-MB by a self-assembly method, and then the surface was modified with PF127 to form GO-MB/PF127 nanocomposite (GO-MB/PF127) by a thin-film hydration method. The structure and properties of the nanocomposite were characterized by Ultraviolet-Visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DLS) and zeta potential. The results showed that the as-prepared nanocomposite exhibited high stability in aqueous solution, high release rate of MB from the nanocomposite under acidic conditions. In addition, when excited by 808 nm near infrared (NIR) light and 660 nm light emitting diode (LED) source, GO in GO-MB/PF127 caused photothermal ablation of cancer cells while MB produced singlet oxygen (1O2) to kill cancer cells through oxidative stress in PDT. The combined therapy had a synergistic effect and can achieve a strong killing effect on SiHa cells at a low dose of GO-MB/PF127 containing GO (10 µg mL-1) and MB (5 µg mL-1). And PF127 did not affect the photothermal heating of GO and the 1O2 generation of MB. Moreover, light-induced GO-MB/PF127 nanocomposite killed SiHa cells by apoptosis pathway. The results indicated that the nanocomposite had the potential to effectively treat cancer via noninvasive phototherapy, and could be served as a multifunctional therapeutic agent for photodynamic/photothermal cancer therapy.

Protective Effect and Mechanisms of New Gelatin on Chemotherapy-Induced Hematopoietic Injury Zebrafish Model.

The aim of the study is to explore the protective effect of new gelatin (NG, Xin'ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 µg·mL-1 and 100 µg·mL-1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.

Inhibition of Glutathione Synthesis via Decreased Glucose Metabolism in Stored RBCs.

BACKGROUND/AIMS: Although red blood cells (RBCs) transfusions can be lifesaving, they are not without risk. RBCs storage is associated with the abnormal metabolism of glutathione (GSH), which may increase the risk of the oxidative damage of RBCs after transfusion. The responsible mechanisms remain unknown. METHODS: We determined the L-cysteine efflux and influx by evaluating the changes of free -SH concentrations in stored RBCs. The glutamate cysteine ligase (GCL) activities and protein content in stored RBCs was determined by fluorescence assay and western blotting. In addition, the glucose metabolism enzyme activity of RBCs was measured by spectrophotometric assay under in vitro incubation conditions. RESULTS: We found that both L-cysteine transport and GCL activity significantly declined, thereby inducing the dysfunction of GSH synthesis during blood storage, which could be attenuated by ATP supplement and DTT treatment. In addition, the glycometabolic enzyme (G6PDH, HK, PK and LDH) activity significantly decreased after 6 weeks storage. Oxidant stress-induced dysfunction in glucose metabolism was the driving force for decreased GSH synthesis during storage. CONCLUSION: These experimental findings reflect an underlying molecular mechanism that oxidant stress induced glucose metabolism dysfunction contribute to decreased GSH synthesis in stored RBCs.

Apoptosis of Platelets Inhibited By Herba Sarcandrae Extract through the Mitochondria Pathway.

The purpose of the present study is to decode the underlying mechanism of Herba Sarcandrae that indicated antipurpuric effect and to unveil one of its primary components, flavonoids, which play an important role. An immune mediated bone marrow failure (BMF) model in mouse was established by infusion thymus suspension cells after radiation in vivo. Platelets isolated in vitro were prepared from normal mice and BMF mice, respectively. The expressions of PS, P-selectin, PAC-1, Bax, Bad, Bid, and caspase-9 were examined by flow cytometry, and alteration of morphology of platelets under different conditions was observed. Our results indicated that the number of platelets was increased by addition of total flavonoids, and some of apoptotic markers such as Bax, Bad, Bid, and Caspase-9 were downregulated. In addition, the phosphatidylserine (PS) exposure on platelets was inhibited by total flavonoids, and the expressions of PAC-1 and P-selectin were decreased. In conclusion, it is suggested that the total flavonoids of Herba Sarcandrae may inhibit the excessive platelet apoptosis through mitochondrial pathway. In addition, activation of platelets may be also involved in mediating apoptosis of platelets.

Deep eutectic solvents from hemicellulose-derived acids for the cellulosic ethanol refining of Akebia' herbal residues.

Here, the potential use of herbal residues of Akebia as feedstock for ethanol production is evaluated. Additionally, five deep eutectic solvents from hemicellulose-derived acids were prepared to overcome biomass recalcitrance. Reaction temperatures had more significant influences on solid loss and chemical composition than the molar ratios of choline chloride (ChCl) to derived acids. Glycolic acid resulted in the maximum levels of lignin, xylan and glucan removal, which were 60.0%, 100% and 71.5%, respectively, at 120°C with a 1:6M ratio of ChCl-glycolic acid. In contrast, ChCl-formic acid resulted in the greatest level of glucan retention, at 97.8%, with a lignin removal rate of 40.7% under the same pretreatment conditions. Moreover, ChCl loading could significantly enhance the selectivity of carboxylic acid for lignin dissolution. A 98.0% level of subsequent enzymatic saccharification and a 100% ethanol yield were achieved after ChCl-formic acid pretreatments of Akebia' herbal residues.

Phosphorous fertilization alleviates drought effects on Alnus cremastogyne by regulating its antioxidant and osmotic potential.

Alnus cremastogyne, a broad-leaved tree endemic to south-western China, has both commercial and restoration importance. However, little is known of its morphological, physiological and biochemical responses to drought and phosphorous (P) application. A randomized experimental design was used to investigate how drought affected A. cremastogyne seedlings, and the role that P applications play in these responses. Drought had significant negative effects on A. cremastogyne growth and metabolism, as revealed by reduced biomass (leaf, shoot and root), leaf area, stem diameter, plant height, photosynthetic rate, leaf relative water content, and photosynthetic pigments, and a weakened antioxidative defence mechanism and high lipid peroxidation level. However, the reduced leaf area and enhanced osmolyte (proline and soluble sugars) accumulation suggests drought avoidance and tolerance strategies in this tree. Applying P significantly improved the leaf relative water content and photosynthetic rate of drought-stressed seedlings, which may reflect increased anti-oxidative enzyme (superoxide dismutase, catalase and peroxidase) activities, osmolyte accumulation, soluble proteins, and decreased lipid peroxidation levels. However, P had only a slight or negligible effect on the well-watered plants. A. cremastogyne is sensitive to drought stress, but P facilitates and improves its metabolism primarily via biochemical and physiological rather than morphological adjustments, regardless of water availability.

Effectiveness of Xielikang capsules in treating HIV-related diarrhea by increasing the plasma concentration of interleukin-17.

OBJECTIVE: To evaluate the efficacy of Xielikang capsules (XLKC) in the treatment of HIV-related diarrhea (HRD) and its effect on the plasma concentration of interleukin-17 (IL-17). METHODS: This was a randomized, open-label, positively-controlled clinical trial. Sixty-seven HRD patients were randomly assigned to two groups: one group was treated with XLKC (n = 35), the other with diosmectite (Smecta®, n = 32). All patients were treated for 4 weeks. The HRD symptom scores were evaluated in each patient based on the frequency of diarrhea, and the quality and shape of the stool according to the Chinese Medicine Clinical Treatment of AIDS Program. The plasma concentration of IL-17 before and after treatment was measured with ELISA. RESULTS: Compared with the Smecta® group, the XLKC group had a significantly reduced frequency of diarrhea and HRD symptom score regarding the quality and shape of stools (P < 0.05). The IL-17 concentration in the peripheral blood of the XLKC group was significantly increased after treatment, while the IL-17 concentration in the Smecta® group significantly decreased after treatment. CONCLUSION: XLKC improves the symptoms of patients with HRD, and increases the plasma concentration of IL-17.

Flavone from Zhongjiefeng (Herba Sarcandrae Glabrae) inhibits platelet apoptosis in immune-induced bone marrow failure through mitochondrial pathway.

OBJECTIVE: To investigate the effect of Flavone from Zhongjiefeng (Herba Sarcandrae Glabrae) on the platelet number in immune-induced bone marrow failure (BMF) and its mechanism of mitochondrial apoptotic pathway. METHODS: Immune-induced BMF model, established in mice, was randomly divided into four groups: normal control group without BMF, BMF control group, cyclosporine (CSA) group and flavone group (n=10 in each group). Mice were given 0.027 g/kg cyclosporine or 0.2 g/kg flavone lavage daily in either the cyclosporine or flavone group respectively. Platelet count, mitochondrial transmembrane potential, cytochrome C , phosphatidylserine (PS), changes of calcium ion (Ca2+), and protein expression of mitochondrial apoptotic pathway including B-cell lymphoma-2 (bcl-2) Homologous Antagonist-Killer Protein (Bak), bcl-2-associated X protein (Bax), caspase-3, caspase-8, and caspase-9 were examined and compared. RESULTS: Compared with the normal control group, the BMF group had significantly lower levels of platelet count, and expressions of caspase family proteins as well as higher levels of Cyt C, PS, Ca2+, and expressions of Bak and Bax (all P < 0.05). Compared with the BMF group, the CSA and flavone groups had significantly higher and expressions of caspase family proteins (all P<0.05) whereas the levels of Cyt C, PS, Ca2+, and expressions of Bak and Bax were reduced (all P<0.05). More importantly, the flavone group had higher levels of Cyt C, Ca2+ and expressions of Bak and Bax compared with the CSA group (all P<0.05), while the levels of PS and caspase family proteins were reduced (all P<0.05). CONCLUSION: Flavone from Zhongjiefeng (Herba Sarcandrae Glabrae) significantly increases the platelet number and prevents its apoptosis through mitochondrial pathway.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Isolation and characterization of lignins from Eucalyptus tereticornis (12ABL).

A three-step sequential extraction-precipitation method was used to isolate lignin from Eucalyptus tereticornis. The ball-milled eucalyptus was extracted with 96% dioxane, 50% dioxane, and 80% dioxane containing 1% NaOH at boiling temperature, consecutively resulting in solubilization of lignin and hemicelluloses. By precipitating such solutions into 70% aqueous ethanol, the hemicelluloses were removed substantially although there were still some carbohydrates left over, especially for lignin fraction extracted by 50% dioxane. Lignins dissolved in the 70% ethanol solutions were recovered via concentration and precipitation into acidified water. About 37% of the original lignin was released following such procedure whereas only 13.5% can be isolated by traditional milled wood lignin (MWL) method. The obtained lignin fractions were analyzed by high performance anion exchange chromatography (HPAEC) following acid hydrolysis for sugar composition of the contaminating carbohydrates and characterized by quantitative (31)P NMR as well as two-dimensional heteronuclear single-quantum coherence ((13)C-(1)H) NMR. The results showed that 96% aqueous dioxane extraction of ball-milled wood under conditions used in this study resulted in lignin preparation with very similar structures and sugar composition as traditional MWL. Therefore extracting ball-milled wood with 96% aqueous dioxane produced lignin in 33.6% yield, which makes it very attractive as an alternative to the traditional MWL method. However further extraction with 50% aqueous dioxane or 80% aqueous dioxane containing 1% NaOH gave just a little more lignins with different carbohydrate compositions from those in MWL. The eucalyptus lignins obtained were syringyl and guaiacyl type units. Lignin fraction obtained from 96% dioxane extraction was found to have more phenolic hydroxyl and less aliphatic hydroxyl than the other two preparations.

[Effects of Kang Gang Qian Granule (KGQG) on clinical and pathological features in chronic hepatitis B patients].

OBJECTIVE: To explore the efficacy of KGQG and its therapeutic mechanisms in chronic hepatitis B patients with liver fibrosis. METHODS: 57 chronic hepatitis B patients with liver fibrosis were randomly divided into two groups: 45 cases in KGQG group were treated by KGQG and routine medications; 12 cases in control group were treated by routine medications only. Serum liver function test results, PCIII, CIV, HA and liver biopsy results of these 57 patients were simultaneously collected and analyzed before and after this intervention. RESULTS: KGQG group showed better efficacy over control group in liver function recovery, decrease of serum PCIII, CIV, HA levels and liver pathologic grades (P 0.05 or 0.01). CONCLUSION: The KGQG could effectively ameliorate liver function and facilitate the inhibition and degradation of liver fibrosis in chronic hepatitis B patients, which may be developed as a novel therapeusis to treat this hard-to-cure disease.