Alteration of soil pH induced by submerging/drainage and application of peanut straw biochar and its impact on Cd(II) availability in an acidic soil to indica-japonica rice varieties.

The effects of soil pH variations induced by submergence/drainage and biochar application on soil cadmium (Cd) availability to different rice (Oryza sativa L.) varieties are not well understood. This study aims to investigate the possible reasons for available Cd(II) reduction in paddy soil as influenced by biochar and to determine Cd(II) absorption and translocation rates in different parts of various rice varieties. A pot experiment in a greenhouse using four japonica and four indica rice varieties was conducted in Cd(II) contaminated paddy soil with peanut straw biochar. The results indicated that the submerging led to an increase in soil pH due to the consumption of protons (H+) by the reduction reactions of iron/manganese (Fe/Mn) oxides and sulfate (SO42-) and thus the decrease in soil available Cd(II) contents. However, the drainage decreased soil pH due to the release of protons during the oxidation of Fe2+, Mn2+, and S2- and thus the increase in soil available Cd(II) contents. Application of the biochar increased soil pH during soil submerging and inhibited the decline in soil pH during soil drainage, and thus decreased soil available Cd(II) contents under both submerging and drainage conditions. The indica rice varieties absorbed more Cd(II) in their roots and accumulated higher amounts of Cd(II) in their shoots and grains than the japonica rice varieties. The Cd(II) sensitive varieties exhibited a greater absorption and translocation rate of Cd(II) compared to the tolerant varieties of both indica and japonica rice. Biochar inhibited the absorption and accumulation of Cd(II) in the rice varieties, which ultimately lowered the Cd(II) contents in rice grains below the national food safety limit (0.2 mg kg-1). Overall, planting japonica rice varieties in Cd(II) polluted paddy soils combined with the use of biochar can effectively reduce Cd(II) content in rice grains which protects human health against Cd(II) toxicity.

Diffusion-induced lithium isotopic heterogeneity in olivines from peridotites of an oceanized mantle lithosphere at the Yunzhug ophiolite (central Tibet).

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ7Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 µm. A negative correlation of δ7Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ7Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites.

Organophosphate esters in the seawater of the Bohai Sea: Environmental occurrence, sources and ecological risks.

Organophosphate esters (OPEs) are widely distributed in surface water systems, but limited information was available on the spatial occurrence and ecological risks of OPEs in the Bohai Sea. In this study, 89 water samples in the Bohai Sea and the five surrounding rivers were investigated for the determination of 15 OPEs. The concentration of ∑15OPEs ranged from 373.20 to 2931.27 ng·L-1 in the river water and 137.81 to 2641.30 ng·L-1 in the seawater, with high levels of OPEs in Liaodong Bay. Tris(2-chloroethyl) phosphate (TCEP, 10- 92 %) and triethyl phosphate (TEP, 5- 64 %) were dominant for OPEs. The correlation analysis, principal component analysis and hierarchical cluster analysis suggested the conjunction of municipal wastewater via river input and maritime shipping was the main source of OPEs in the Bohai Sea. The ecological risk assessment indicated that the individual OPEs arise low ecological risks in the Bohai Sea, while medium ecological risks of ∑15OPEs are in minority river samples.

Dissolved biochar fractions and solid biochar particles inhibit soil acidification induced by nitrification through different mechanisms.

Biochar can inhibit soil acidification by decreasing the H+ input from nitrification and improving soil pH buffering capacity (pHBC). However, biochar is a complex material and the roles of its different components in inhibiting soil acidification induced by nitrification remain unclear. To address this knowledge gap, dissolved biochar fractions (DBC) and solid biochar particles (SBC) were separated and mixed thoroughly with an amended Ultisol. Following a urea addition, the soils were subjected to an incubation study. The results showed that both the DBC and SBC inhibited soil acidification by nitrification. The DBC inhibited soil acidification by decreasing the H+ input from nitrification, while SBC enhanced the soil pHBC. The DBC from peanut straw biochar (PBC) and rice straw biochar (RBC) decreased the H+ release by 16 % and 18 % at the end of incubation. The decrease in H+ release was attributed to the inhibition of soil nitrification and net mineralization caused by the toxicity of the phenols in DBC to soil bacteria. The abundance of ammonia-oxidizing bacteria (AOB) and total bacteria decreased by >60 % in the treatments with DBC. The opposite effects were observed in the treatments with SBC. Soil pHBC increased by 7 % and 19 % after the application of solid RBC and PBC particles, respectively. The abundance of carboxyl on the surface of SBC was mainly responsible for the increase in soil pHBC. Generally, the mixed application of DBC and SBC was more effective at inhibiting soil acidification than their individual applications. The negative impacts of dissolved biochar components on soil microorganisms need to be closely monitored.

Analgesic effect of electroacupuncture on bone cancer pain in rat model: the role of peripheral P2X3 receptor.

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 104 cells/3 µL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,ß-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,ß-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,ß-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

Effect of Erxian Decoction-containing serum on H_2O_2-induced proliferation and osteogenic differentiation of MC3T3-E1 cells via BK channels / 中国中药杂志

This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.

Application of chitosan- and alginate-modified biochars in promoting the resistance to paddy soil acidification and immobilization of soil cadmium.

To develop more green, practical and efficient biochar amendments for acidic soils, chitosan-modified biochar (CRB) and alginate-modified biochar (ARB) were prepared, and their effects on promoting soil pH buffering capacity (pHBC) and immobilizing cadmium (Cd) in the paddy soils were investigated through indoor incubation experiments. The results of Fourier transform infrared spectroscopy and Boehm titration indicated that the introduction of chitosan and sodium alginate effectively amplified the functional groups of the biochar, and improved acid buffering capacity of the biochar. Since there was a plateau region between pH 4.5 and 5.5 in acid-base titration curve of the CRB, adding this biochar to acidic paddy soils apparently improved the pHBC and enhanced the acidification resistance of the paddy soils. The addition of ARB enhanced the reduction reactions during submerging and weakened the oxidation reactions during draining, thus retarded the decline of paddy soil pH during drainage. Furthermore, the pH of the paddy soils with ARB addition was higher at the end of draining, which reduced the activity of soil Cd. Considering the environmental sustainability of chitosan and sodium alginate and convenience of preparation method, biochars modified with these two materials provided alternatives for acidic paddy soil amelioration and heavy metal immobilization. However, the additional experiments should be conducted under field conditions to confirm practical application effects in the future.

vvi-miPEP172b and vvi-miPEP3635b increase cold tolerance of grapevine by regulating the corresponding MIRNA genes.

As a kind of small molecular weight proteins, many peptides have been discovered, including peptides encoded by pri-miRNA (miPEPs). Similar as traditional phytohormone or signaling molecular, these peptides participate in numerous plant growth processes. MicroRNAs (miRNAs) play an important regulatory role in plant stress response. While the roles of miPEPs in response to abiotic stress has not been studied now. In this study, to explore whether miPEPs could contribute to low temperature (4ºC) tolerance of plants, the expression pattern of 23 different vvi-MIRs were analyzed by qRT-PCR in 'Thompson Seedless' (Vitis vinifera) plantlets under cold stress (4ºC) firstly, and vvi-MIR172b and vvi-MIR3635b which showed an elevated expression levels were selected to identify miPEPs. Through transient expression, one small open reading frame (sORF) in each of the two pri-miRNAs could increase the expression of corresponding vvi-MIR, and the amino acid sequences of sORFs were named vvi-miPEP172b and vvi-miPEP3635b, respectively. The synthetic vvi-miPEP172b and vvi-miPEP3635b were applied to the grape plantlets, and the tissue culture plantlets exhibited a higher cold tolerance compared with the control groups. These results revealed the effective roles of miPEPs in plant cold stress resistance for the first time, providing a theoretical basis for the future application of miPEPs to agricultural production.

A Comprehensive Study to Identify Major Metabolites of an Amoxicillin-Sulbactam Hybrid Molecule in Rats and Its Metabolic Pathway Using UPLC-Q-TOF-MS/MS.

Amoxicillin and sulbactam are widely used compound drugs in animal food. The amoxicillin-sulbactam hybrid molecule can achieve better curative effects through the combination of the two drugs. However, its pharmacokinetic behavior needs to be explored. In this study, a randomized crossover experiment was performed to investigate the metabolism of the novel amoxicillin-sulbactam hybrid molecule in rats after gastric administration. Ultrahigh performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was used to isolate and to identify the metabolites in rats. Amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were eventually detected in the plasma, liver, urine, and kidneys; no hybrid molecules and their metabolites were detected in feces. The in vivo metabolism results showed that the hybrid molecule was absorbed into the body in the intestine, producing amoxicillin and sulbactam, then amoxicillin was partially metabolized to amoxicilloic acid and amoxicillin diketopiperazine, which are eventually excreted in the urine by the kidneys. In this study, four major metabolites of the amoxicillin-sulbactam hybrid molecule were identified and their metabolic pathways were speculated, which provided scientific data for understanding the metabolism of the hybrid molecule and for its clinical rational use.

Critical values of soil solution Al3+ activity and pH for canola and maize cultivation in two acidic soils.

BACKGROUND: Aluminum (Al) toxicity caused by soil acidification is the main constraint for crop growth in tropical and subtropical areas of southern China. The critical values of soil solution Al3+ activity and pH for crops in acidic soils can provide a useful reference for soil acidity amelioration. RESULTS: A pot experiment in a greenhouse was conducted to investigate the critical values of soil solution Al3+ activity and pH for canola and maize in an Ultisol and an Alfisol. The critical values of soil solution Al3+ activity in Ultisol and Alfisol for canola were 1.5 and 10.0 µmol L-1 , and 13.9 and 30.4 µmol L-1 for maize, respectively. The Al tolerance varied with soil type for the same variety of crop. There was more biomass of roots and shoots and higher plant height under the same Al3+ activity, and thus greater critical values of soil solution Al3+ activity for both crops in Alfisol than those in Ultisol, owing to higher Ca2+ /Al3+ , Mg2+ /Al3+ and K+ /Al3+ ratios in soil solution caused by higher cation exchange capacity and exchangeable base cations in Alfisol, when compared with those in Ultisol. The critical values of soil solution pH for canola and maize in Ultisol were 5.09 and 4.72, respectively; while those in Alfisol were 4.87 and 4.54, respectively. CONCLUSION: The critical values of Al3+ activity were higher for maize than for canola and the critical values for both crops were higher in Alfisol than in Ultisol. The critical soil pH for both crops showed opposite trends to soil Al3+ activity. © 2022 Society of Chemical Industry.

Effects of pH variations caused by redox reactions and pH buffering capacity on Cd(II) speciation in paddy soils during submerging/draining alternation.

Incubation experiments were conducted to investigate the influencing factors of pH variation in different paddy soils during submerging/draining alternation and the relationship between pH buffering capacity (pHBC) and Cd speciation in ten paddy soils developed from different parent materials (including 8 acid paddy soils and 2 alkaline paddy soils). The soil pHBC and the changes in soil pH, Eh, Fe2+, Mn2+, SO42- and Cd speciation were determined. The results showed that there was a significant positive correlation between cation exchange capacity (CEC) and pHBC of these paddy soils, indicating that soil CEC is a key factor affecting the pHBC of paddy soils. The contribution of Fe(III) oxide reduction to H+ consumption is far greater than the reduction of Mn(IV)/Mn(III) oxides and SO42- during the submerging. For example, the contribution of the reduction of manganese oxides, SO42- and iron oxides to H+ consumption in the paddy soils from Anthrosol at 15 d submerging was 1.2%, 11.6% and 87.2%, respectively. This confirms that the reduction of Fe(III) oxides plays a leading role in increasing soil pH. Importantly, we noticed that during submerging, soil pH was increased and resulted in the content of available Cd in soils being reduced. This was due to the transformation of Cd to less active forms. Also, there was a significant positive correlation between the change rate of available Cd, the percentage of acid extractable Cd and pH variation. This suggests that the variation in soil pH was responsible for the transformation of Cd speciation. In addition, the change rate of available Cd and the percentage of acid extractable Cd concentration were significantly negatively correlated with soil pHBC. The soil with higher pHBC experienced less pH change, and thus the change rate of available Cd and the percentage of acid extractable Cd concentration were less for the soil. The results of this study can provide a basis for the remediation of Cd-contaminated acidic paddy soils.

The effects of H2O2- and HNO3/H2SO4-modified biochars on the resistance of acid paddy soil to acidification.

Biochar was prepared from rice straw and modified with 15% H2O2 and 1:1 HNO3/H2SO4, respectively. The unmodified biochars and HCl treated biochars for carbonate removal were used as control. The biochars were added to the acid paddy soil collected from Langxi, Anhui Province, China at the rate of 30 g/kg. The paddy soil was flooded and then air-dried, and soil pH and Eh were measured in situ with pH electrode and platinum electrode during wet-dry alternation. Soil pH buffering capacity (pHBC) was determined by acid-base titration after the wet-dry treatment. Then, the simulated acidification experiments were carried out to study the changing trends of soil pH, base cations and exchangeable acidity. The results showed that soil pHBC was effectively increased and the resistance of the paddy soil to acidification was apparently enhanced with the incorporation of H2O2- and HNO3/H2SO4-modified biochars. Surface functional groups on biochars were mainly responsible for enhanced soil resistance to acidification. During soil acidification, the protonation of organic anions generated by dissociation of these functional groups effectively retarded the decline of soil pH. The modification of HNO3/H2SO4 led to greater increase in carboxyl functional groups on the biochars than H2O2 modification and thus HNO3/H2SO4-modified biochars showed more enhancement in soil resistance to acidification than H2O2-modified biochars. After a wet-dry cycle, the pH of the paddy soil incorporated with HNO3/H2SO4-modified biochar increased apparently. Consequently, the addition of HNO3/H2SO4-modified biochar can be regarded as a new method to alleviate soil acidification. In short, the meaning of this paper is to provide a new method for the amelioration of acid paddy soils.

Role of caveolin-1 in chronic postsurgical pain in rats.

Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanisms remain elusive. Previous studies have indicated that caveolin-1 (Cav-1) plays a notable role in pain modulation. To study the role of Cav-1 in CPSP in the present study, a rat model of skin/muscle incision and retraction (SMIR) was established. Under anesthesia, skin and superficial muscle of the medial thigh were incised and a small pair of retractors inserted. It was revealed that SMIR increased the expression of Cav-1 in the dorsal root ganglion (DRG) and the injured tissue around the incision. Furthermore, the infiltration of endothelial cells and macrophages in the injured tissue around the incision increased constantly, and the vascular permeability increased due to the destruction of the vascular endothelial barrier function around the injured tissue. Cav-1 was mainly expressed by CD68-positive macrophages and CD34-positive endothelial cells in the injured tissues around the incision, while it was also primarily localized in the medium and large neurofilament 200-positive neurons and a small number of calcitonin gene-related peptide- and isolectin B4-positive small and medium-sized neurons in the DRG. The results demonstrated that the sustained high expression levels of Cav-1 in the injured tissue around the incision could lead to the dysfunction of the vascular endothelial barrier and, thus, could induce the inflammatory response through the lipoprotein transport of endothelial cells, thereby resulting in peripheral sensitization. In addition, the sustained high expression levels of Cav-1 in the DRG could sensitize large-sized neurons and change the transmission mode of noxious stimuli. The findings of the present study indicated that a Cav-1-mediated process could participate in neuronal transmission pathways associated with pain modulation.

Neutrophil-to-Lymphocyte Ratio and Treatment Failure in Peritoneal Dialysis-Associated Peritonitis.

Objective: We sought to explore if there is an association between neutrophil-to-lymphocyte ratio (NLR) and treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP). Methods: Our cohort involved 337 episodes of PDAP experienced by 202 patients who were undergoing continuous ambulatory peritoneal dialysis at a single center from 1 July 2013 to 30 June 2018. The exposures were log-transformed NLR and a categorical variable grouped by the tertiles of NLR levels (T1, <3.75; T2, 3.75-6.53; and T3, >6.53) at baseline. Generalized estimating equation (GEE) and restricted cubic spline (RCS) analyses were done to determine the association between NLR and treatment failure, defined as catheter removal or all-cause mortality during therapy. Results: After adjusting for other potential predictors, the log-transformed NLR exhibited an incremental relationship with the risk of treatment failure (odds ratio, 1.82; 95% confidence interval, 1.05-3.15). RCS analyses showed that the relationship was positively and linearly correlated (P for nonlinearity = 0.104). As a three-level categorical variable, in reference to T1, the T3 of NLR showed a 3.41-fold increased venture of treatment failure in fully adjusted model. Subgroup analyses suggested that the prognostic relevance of NLR in PDAP was particularly significant in gram-negative peritonitis. Conclusions: A greater level of NLR at baseline was remarkably associated with a higher incidence of treatment failure among PDAP episodes regardless of other potential risk factors.

Prevalence and risk factors of relapse in patients with ANCA-associated vasculitis receiving cyclophosphamide induction: a systematic review and meta-analysis of large observational studies.

BACKGROUND: Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse. METHODS: We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed. RESULTS: Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10-0.14), 0.33 (0.29-0.38), and 0.47 (0.42-0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine). CONCLUSIONS: Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

Gut-Brain-Skin Axis in Psoriasis: A Review.

INTRODUCTION: Psoriasis is a common skin disease, with chronic inflammation and a complex etiology. It has long been recognized that chronic skin conditions and mental health disorders are often co-morbid. Thus, the concept of the gut-brain-skin axis emphasized in mental health disorders may also regulate the health of skin. RESULTS: The gut microbiota has been found to be the bridge between the immune system and nervous system. By leveraging clinical cases and animal models of psoriasis, an important communication pathway has been identified along the gut-brain-skin axis that is associated with the modulation of neurotransmitters from the microbiota. Furthermore, mammalian neurotransmitters, including dopamine, serotonin, or γ-aminobutyric acid (GABA), can be produced and/or consumed by several types of bacteria. Other studies suggest that manipulating these neurotransmitters by bacteria may have an effect on host physiology, and the levels of neurotransmitter can be altered by microbiota-based interventions. CONCLUSIONS: Nonetheless, it is unknown whether or not the manipulation of neurotransmitter levels by bacteria can affect the occurrence and development of psoriasis. Notably, preliminary experiments found that oral consumption of probiotics improves the clinical symptoms in patients with psoriasis, perhaps correlated with the gut microbiome-mediated crosstalk between the immune system and the nervous system by secreting neurotransmitters in psoriasis. In this review, the communication along the gut-brain-skin axis is discussed.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Effect of Erxian Decoction on proteomics and PI3K signaling pathway of osteoblasts stimulated by H2O2 / 中国中药杂志

The present study aimed to explore the effect of Erxian Decoction on proteomics of osteoblasts stimulated by hydrogen peroxide(H_2O_2) and its protective mechanism with the H_2O_2-induced cell model of oxidative stress. The primary osteoblasts were cultured from the skulls of newborn rats(within 24 hours) and divided into a control group, a model group, a Fosamax group, and an Erxian Decoction group. Blank serum was added in the control group and model group, and the drug-containing serum was added correspondingly to the remaining two groups. After 45 hours, H_2O_(2 )stimulation was conducted for three hours except for the control group, followed by protein extraction. Nano-LC-LTQ-Orbitrap system was used for protein detection, Protein Discovery for protein identification, and SIEVE for quantitative and qualitative analysis. Furthermore, following the blocking of PI3 K signaling pathway by LY294002(10 μmol·L~(-1)), a control group, a model group, an LY294002 group, an Erxian Decoction group, and an Erxian Decoction + LY294002 group were set up to observe the effect of Erxian Decoction on cell proliferation, alkaline phosphatase(ALP) activity, and the relative expression of BMP-2, OPG, p-Akt, p-FoxO1 of osteoblasts stimulated by H_2O_2 under LY294002 intervention. The results revealed that 78 differential proteins were discovered between the Erxian Decoction group and model group, which were involved in the regulation of PI3 K/Akt, glucagon, estrogen, insulin, and other signaling pathways. LY294002 blunted the promoting effect of Erxian Decoction on osteoblast proliferation and significantly down-regulated the expression of OPG and p-FoxO1, whereas its down-regulation on the expression of BMP-2 and p-Akt was not significant. Both LY294002 and Erxian Decoction increased the ALP activity of osteoblasts, which may be related to the cell state and the cell differentiation. The above results suggest that Erxian Decoction can protect osteoblasts stimulated by H_2O_2, with the PI3 K/Akt signaling pathway as one of the internal mechanisms.

Paeonol exerts anti­tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/ß­catenin signaling pathway.

Paeonol is a simple phenolic compound isolated from herbal root bark, which has been reported to possess numerous biological and pharmacological characteristics, including a desirable anti­tumor effect. To date, the effect of paeonol against colorectal cancer (CRC) cells is yet to be fully elucidated. Therefore, the present study aimed to identify the underlying mechanism via which paeonol exerts its anti­tumor activity on HCT116 cells. After incubation with various concentrations of paeonol (7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml), the inhibitory effect of paeonol on cell viability was assessed using a Cell Counting Kit­8 assay. Cell apoptosis and cell cycle distribution were measured using flow cytometry. Moreover, caspase activity was measured using a colorimetric caspase assay. Luciferase assay was also used to determine the ß­catenin­mediated transcriptional activity of T­cell specific transcription factor/lymphoid­enhancer binding factor (TCF/LEF), and western blotting analysis was performed to measure the related expression of proteins. The results indicated that paeonol exhibited a notable effect against HCT116 cells by inducing G0/G1­phase arrest, as demonstrated by downregulation of the cell cycle regulators cyclin­dependent kinase 4 and cyclin D1 and upregulation of p21Cip1 in a dose­dependent manner. Furthermore, paeonol dose­dependently induced cell apoptosis, accompanied by an increase in the Bax/Bcl­2 ratio, release of cytochrome c and further activation of caspases. Paeonol also dose­dependently blocked the activation of the Wnt/ß­catenin signaling pathway by suppressing the expression of ß­catenin, resulting in a decrease in ß­catenin­mediated activity of TCF/LEF and downregulation of downstream target genes, including cyclin D1, survivin and c­Myc. Therefore, the present results suggested that paeonol exerted its anti­tumor effects on CRC cells, including the inhibition of cell proliferation, induction of cell cycle arrest and initiation of apoptosis, at least partly by suppressing the Wnt/ß­catenin pathway, which may offer a promising therapeutic strategy for CRC.