Effect of icariin on depressive behaviour in rat pups. Evidences for its mechanism of action by integrating network pharmacology, metabolomics and gut microbiota composition.

BACKGROUND: Prenatal stress (PS) can cause cognitive disorder and a range of psychological illnesses, including anxiety and depression. Icariin (ICA) has shown promising effects in improving PS-induced depressive behaviour. However, its mechanism of action remains unclear. PURPOSE: This study was performed to reveal the key targets, metabolites and gut microbiota for ICA in improving depressive behaviour in PS rat pups. METHODS: A prenatal restraint stress animal model was established for Sprague-Dawley (SD) rats in late pregnancy. Male pups were randomly divided into six groups: no stress group (NS), PS group, PS + saline group (PS_S), PS + high-dose ICA group (ICAH, 80 mg/kg*day), PS + low-dose ICA group (ICAL, 40 mg/kg*day) and PS + fluoxetine group (FLU, 10 mg/kg*day). The depressive behaviour of each group of rat pups was evaluated using open field test, forced swimming test and sucrose preference test. Different metabolites were identified using untargeted metabolomics of serum and faeces, and metabolic pathways were analyzed through MetaboAnalyst. Targets for ICA acting on depression were determined after network pharmacology was applied. An integrated network of network pharmacology and metabolomics were constructed using Cytoscape software, and molecular docking were performed to verify the interactions between ICA and key targets. Finally, gut microbiota of rat pups in each group were analyzed after 16S rDNA sequencing. RESULTS: PS could cause rat pups to exhibit depressive behaviour, and ICA could significantly improve this depressive behaviour. A total of 49 differential metabolites were found in serum and 23 differential metabolites were found in faeces, and 24 metabolites in serum and 6 metabolites in faeces could be reversed following ICA administration. Integrated analysis focused on five key targets (i.e. adenosyl homocysteinase; medium-chain specific acyl-CoA dehydrogenase, mitochondrial; thymidine phosphorylase; cGMP-specific 3',5'-cyclic phosphodiesterase and xanthine dehydrogenase/oxidase) and three metabolites (i.e. palmitoylcarnitine, methionine and hypoxanthine). Molecular docking indicated that ICA combined well with key targets. Gut microbiota analysis showed that g_Bacteroides, f_Bacteroidaceae and s_Lactobacillus reuteri were required for ICA to improve depressive behaviour. CONCLUSION: In this study, the antidepressant mechanism of ICA was clarified with a strategy of integrating metabolomics, network pharmacology and gut microbiota. ICA has a good effect on improving metabolism and increasing the abundance of probiotics in the intestine. The present research provided new insights into the anti-depressant mechanism of ICA.

Performance Evaluation and Oil Displacement Effect of Amphiphilic Polymer Heavy Oil Activator.

A heavy oil activator is an amphiphilic polymer solution that contains hydrophilic and oleophobic groups. It can enhance heavy oil recovery efficiency. This paper studied the changes in the distribution of the remaining oil after activator flooding and the performance of heavy oil's active agent. Nuclear magnetic resonance spectroscopy, laser confocal microscopy, microscopic visualization, and CT scanning techniques were used to analyze crude oil utilization, and the distribution characteristics of the remaining oil during activator flooding of heavy oil. The results showed that the heavy oil activator solution presented a dense spatial network and good viscosification ability. The activator could reduce the interfacial tension of oil and water, disassemble the heavy components of dispersed heavy oil and reduce the viscosity of heavy oil. The utilization degree of the remaining oil in small and middle pores increased significantly after activator flooding, the remaining oil associated with membranous-like and clusterlike structures was utilized to a high degree, and the decline of light/heavy fraction in heavy oil slowed down. Heavy oil activator improved the swept volume and displacement efficiency of heavy oil, playing a significant role in improving the extent of recovery of heavy oil reservoirs.

pH-responsive in situ gelling properties of thiolated citrus high-methoxyl pectin and its potential gel mechanism.

pH-responsive in situ gelling properties of thiolated citrus high-methoxyl pectin (TCHMP) were investigated in this study. The gelation capacity results revealed that the in situ gelation behavior of TCHMP only occurred when the pH value was higher than 6.25. The gel strength increased from 26.63 g to 42.77 g as the pH value increased from 7.4 to 8.9. Rheological measurements confirmed that the apparent viscosity and viscoelasticity of TCHMP were highly dependent on pH value and dialysis time. Compared with the control group, the apparent viscosity of TCHMP dialyzed in phosphate-buffered saline (PBS) of pH 8.9 for 180 min increased 695-fold. During the dialysis process of TCHMP at different pH values (7.4-8.9), the final thiol groups content decreased and the final disulfide bonds content increased with the increase in pH value. This illustrates that the mechanism of in situ gelation is mainly the oxidation of thiol-thiol groups to form disulfide bonds. These results can put forward new insights into the pH-responsive in situ gelling properties of TCHMP and provide a theoretical basis for the application of TCHMP in neutral and alkaline gel systems.

Compound treatment of thiolated citrus high-methoxyl pectin and sodium phosphate dibasic anhydrous improved gluten network structure.

The effects of pectin or thiolated pectin alone and combined with sodium phosphate dibasic anhydrous (Na2HPO4) on the performances of gluten were studied. Results showed that compared with pectin treated gluten, the thiols of thiolated pectin treated gluten increased by 8.7 times. Analysis of the extensibility and rheological properties revealed that pectin reduced gluten strength, whereas thiolated pectin improved the strength and viscoelasticity of gluten, especially with the assistance of Na2HPO4. Furthermore, thiolated pectin and Na2HPO4 compound increased enthalpy (ΔH, from 150.42 to 168.60 J/g) and decreased Imax (from 5255.33 to 2775.33) markedly, indicating gluten aggregation. The highest ß-sheet (76.47%) and the lowest α-helix/ß-sheet ratio (0.11) were found in gluten treated with thiolated pectin and Na2HPO4 and suggested gluten stability was enhanced. SEM observation confirmed that thiolated pectin and Na2HPO4 compound strengthened the gluten structure. These results are of great significance for the supplementation of pectin in wheat products.

Vasorelaxant effect of curcubisabolanin A isolated from Curcuma longa through the PI3K/Akt/eNOS signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa L. (Zingiberaceae) is a known blood-activating and stasis-removing traditional Chinese medicine and has relevant pharmacological properties. The rhizomes of C. longa have been used for the treatment of cardiovascular disease (CVD) in China. Previous studies have shown that sesquiterpenoids from C. longa have significant vasorelaxant effects, which are closely associated with the prevention and treatment of CVD. AIM OF THE STUDY: To explore the sesquiterpenoids with vasorelaxant effects from C. longa and investigate the underlying mechanisms. MATERIALS AND METHODS: The compound was isolated from C. longa by multiple chromatography technologies. Its structure was determined by extensive spectroscopic analyses, nuclear magnetic resonance (NMR) data calculations, electronic circular dichroism (ECD) data calculations, and optical rotation (OR) data calculations. The vasorelaxant effect of the isolated compound was evaluated by KCl- or phenylephrine (PHE)-inducing contraction of the rat thoracic aortic rings. Endothelial removal and L-NAME pretreatment experiments were used to verify the endothelium-dependent vasorelaxant effect of the isolated compound in rat thoracic aortic rings. NO production was monitored in human umbilical vein endothelial cells (HUVECs). Western blot was carried out in HUVECs to elucidate the potential mechanisms. RESULTS: A new bisabolane-type sesquiterpenoid, curcubisabolanin A [(+)-(1S,7S,9E)-bisabola-2(3),4(15),9(10)-trien-11-ol], was isolated from the rhizomes of C. longa. curcubisabolanin A exhibited endothelium-dependent relaxation on rat thoracic aortic rings, while pre-treatment of intact aortic rings with an eNOS inhibitor (L-NAME) attenuated the vasorelaxant response of curcubisabolanin A. In addition, curcubisabolanin A induced intracellular NO production and significantly increased the levels of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), and phosphorylated eNOS (p-eNOS) in HUVECs. LY294002 (a blocker of PI3K) and MK-2206 (a highly selective inhibitor of Akt) significantly decreased these effects of curcubisabolanin A. CONCLUSIONS: These findings demonstrated that the vasorelaxant effect of curcubisabolanin A was partially endothelium-dependent and was related to regulation of NO production in vascular endothelial cells through the PI3K/Akt/eNOS signaling pathway.

Genetic and Transcriptomic Analysis Reveal the Molecular Basis of Photoperiod-Regulated Flowering in Xishuangbanna Cucumber (Cucumis sativus L. var. xishuangbannesis Qi et Yuan).

Xishuangbanna (XIS) cucumber (Cucumis sativus L. var. xishuangbannesis Qi et Yuan), is a botanical variety of cucumber cultivars native to southwest China that possesses excellent agronomic traits for cucumber improvement. However, breeding utilization of XIS cucumber is limited due to the current poor understanding of its photoperiod-sensitive flowering characteristics. In this study, genetic and transcriptomic analysis were conducted to reveal the molecular basis of photoperiod-regulated flowering in XIS cucumber. A major-effect QTL locus DFF1.1 was identified that controls the days to first flowering (DFF) of XIS cucumbers with a span of 1.38 Mb. Whole-genome re-sequencing data of 9 cucumber varieties with different flowering characteristics in response to photoperiod suggested that CsaNFYA1 was the candidate gene of DFF1.1, which harbored a single non-synonymous mutation in its fifth exon. Transcriptomic analysis revealed the positive roles of auxin and ethylene in accelerating flowering under short-day (SD) light-dark cycles when compared with equal-day/night treatment. Carbohydrate storage and high expression levels of related genes were important reasons explaining early flowering of XIS cucumber under SD conditions. By combining with the RNA-Seq data, the co-expression network suggested that CsaNFYA1 integrated multiple types of genes to regulate the flowering of XIS cucumber. Our findings explain the internal regulatory mechanisms of a photoperiodic flowering pathway. These findings may guide the use of photoperiod shifts to promote flowering of photoperiod-sensitive crops.

New lignans from the fruits of Leonurus japonicus and their hepatoprotective activities.

Twelve tetrahydrofuran lignans (1-12), including six new compounds (1-6), were isolated from the 70% EtOH extract of the fruits of Leonurus japonicus. Spectroscopic analyses and ECD and OR calculations were used to determine their structures. Compounds 5 and 6 were unusual alkaloidal lignans with a butyrolactam unit. Based on the beneficial effects of the fruits of L. japonicus (Chongweizi in Chinese) on the liver in traditional Chinese medicine (TCM), the hepatocyte protective activities of the isolates were studied by MTT, Hoechst 33,342 staining, and western blotting. The MTT results revealed that compounds 1, 2, 7, and 8 significantly increased the survival rates of HL-7702 cells injured by acetaminophen, with EC50 values of 10.41 ± 0.90 µM, 19.86 ± 3.13 µM, 9.68 ± 1.93 µM, and 21.35 ± 3.58 µM, respectively. In the Hoechst 33,342 fluorescence staining, compounds 1 and 7 suppressed the apoptosis of the injured HL-7702 cells. Furthermore, the western blot analysis showed that compounds 1 and 7 increased the Bcl-2/Bax protein expression ratio and procaspase-3 protein expression, indicating that compounds 1 and 7 may exert hepatoprotective activity by regulating the mitochondrial apoptotic pathway.

Traditional Chinese medicine formulas, extracts, and compounds promote angiogenesis.

Ischemic diseases, such as ischemic heart diseases and ischemic stroke, are the leading cause of death worldwide. Angiogenic therapy is a wide-ranging approach to fighting ischemic diseases. However, compared with anti-angiogenesis therapy for tumors, less attention has been paid to therapeutic angiogenesis. Recently, Traditional Chinese medicine (TCM) has garnered increasing interest for its definite curative effect and low toxicity. A growing number of studies have reported that TCM formulas, extracts, and compounds from herbal medicines exert pro-angiogenic activity, which has been confirmed in a few clinical trials. For comprehensive analysis of relevant literature, global and local databases including PubMed, Web of Science, and China National Knowledge Infrastructure were searched using keywords such as "angiogenesis," "neovascularization," "traditional Chinese medicine," "formula," "extract," and "compound." Articles were chosen that are closely and directly related to pro-angiogenesis. This review summarizes the pro-angiogenic activity and the mechanism of TCM formulas, extracts, and compounds; it delivers an in-depth understanding of the relationship between TCM and pro-angiogenesis and will provide new ideas for clinical practice.

Comprehensive profiling of Stephania tetrandra (Fangji) by stepwise DFI and NL-dependent structure annotation algorithm-based UHPLC-Q-TOF-MS and direct authentication by LMJ-HRMS.

Stephania tetrandra S. Moore, a widely used traditional antirheumatic herbal medicine (HM), is a rich source of isoquinoline alkaloids. With the exception of the two recognized isoquinolines, viz. tetrandrine and fangchinoline, the other isoquinoline alkaloids present in S. tetrandra have not been clearly clarified. In addition, due to their similar names and morphological similarities, S. tetrandra is often mistakenly substituted and adulterated with the nephrotoxic Aristolochia fangchi. In this study, ultra-high-performance liquid chromatography-triple time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was initially employed to comprehensively profile the isoquinolines from S. tetrandra. To overcome the complexities arising due to the similar mass behaviors of the isoquinolines, a stepwise diagnostic fragment ion (DFI) and neutral loss (NL)-dependent structure annotation algorithm was proposed, and this accelerated the identification of 393 isoquinolines distributed over twenty classes. Consequently, liquid microjunction surface sampling-high-resolution mass spectrometry (LMJ-HRMS) was deployed in an attempt to directly authenticate S. tetrandra by the chemical profiling of its crude slice. By matching the 393 isoquinolines, the 87 peaks detected by LMJ-HRMS were assigned to 270 isoquinolines, including the recognized tetrandrine and fangchinoline. The absence of aristolochic acid-related mass signals confirmed the authentication of S. tetrandra. In summary, LMJ-HRMS can be considered a direct, nondestructive, high-throughput, and environment-friendly analytical method for the authentication of HMs. Moreover, the stepwise DFI- and NL-dependent structure annotation algorithm-based UHPLC-Q-TOF-MS method allowed high-coverage detection and high-quality data processing of the inherent structural similarity and complexity of isoquinolines or other phytochemical compounds.

Comparative study on metabolic profiling and excretion in rat bile between combination of notoginseng total saponins and safflower total flavonoids and its individual extracts by LC-MS/MS.

The combination of notoginseng total saponins (NS) and safflower total flavonoids (SF), namely CNS, presents a synergistic protection effect on the myocardial ischemia rats. The aim of this study was to find the clues for their synergistic actions by comparing the biliary metabolism and excretion profiles after oral administration of CNS and its individual extracts. An ultra-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS/MS) platform was used to identify and quantify the CNS-derived components in bile. The neutral losses, precursor ions, and predictive multiple reaction monitoring (pMRM) scans were firstly used to detect the CNS-derived ingredients in vivo. A total of 43 components, including 38 flavonoids and 5 ginsenosides were tentatively identified according to the previously established chemical and metabolic profiles of NS and SF. Afterwards, the primary circulating and biological components, hydroxysafflor yellow A (HSYA), ginsenosides Rg1 (GRg1), Re (GRe), and Rd (GRd) were chosen to compare the bile excretion between CNS and its individual extract groups, by using a validated LC-MRM-MS/MS method. The approach was proved to be well satisfied the related requirements from the guidelines of FDA (specificity, calibration curve, sensitivity, precision, accuracy, matrix effect, recovery, and stability). Comparing with the SF and NS groups, the combination group did not affect the metabolic pathways of the CNS-related components, however, it decreased the cumulative excretion ratios of HSYA, GRg1, GRe, and GRd. In conclusion, the compatibility of SF and NS could reduce the bile excretion of the CNS-derived compounds, which may be one of the reasons for the enhancement of anti-myocardial ischemia after combination.

[Identification of metabolites in rat plasma,bile,urine and feces after oral administration of Cinnamomi Cortex aqueous extract by UPLC-Qtrap-MS].

An ultra-performance liquid chromatography hybrid triple quadrupole-linear ion trap mass spectrometry(UPLC-QtrapMS) method was established to identify the metabolites in rat plasma,bile,urine and feces after oral administration of Cinnamomi Cortex(CC) aqueous extract. Several survey experiments,such as enhanced mass spectrum scan(EMS),precursor ion scan(PI),neutral loss scan(NL) and multiple ions monitoring(MIM) were applied to search target components,and two separate enhanced product ion(EPI) scans were triggered via information-dependent acquisition(IDA) method to generate the MS/MS spectra. According to the mass spectrometric data collected from reference standards and reported literature,the structures of metabolites were deduced. A total of76 metabolites and 5 original compounds were tentatively identified in rats after oral administration of CC aqueous extract. Deglycosylation,methylation,sulfonation,and glucuronidation were observed as the primary metabolic pathways for the chemical constituents of CC. These data are able to benefit the clarification of the therapeutic material basis,the clinical usage and further R&D of CC.

Terpene Glycosides from Sanguisorba officinalis and Their Anti-Inflammatory Effects.

Two new terpene glycosides (1-2) along with two known analogs (3-4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Pharmacokinetics study of 16 representative components from Baoyuan Decoction in rat plasma by LC-MS/MS with a large-volume direct injection method.

BACKGROUND: Baoyuan decoction (BYD), a well-known traditional Chinese medicine (TCM) formula, is clinically used for the treatment of aplastic anemia, chronic renal failure, coronary heart disease, etc. PURPOSE: The purpose of this study was to develop a large-volume direct injection liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of 16 representative flavonoids and saponins in rat plasma after oral administration of BYD. METHODS: The rat plasma sample was injected directly into a pre-column, which was eluted firstly by 0.05% formic acid in water. Then, the accumulated components were eluted from the pre-column and transferred into a Waters BEH C18 column with acetonitrile and water system (contain 0.05% formic acid) as the mobile phase at a rate of 0.3 ml/min. The detection was accomplished in a negative mode using the schedule multiple-reaction monitoring (sMRM). RESULTS: The correlation coefficients for calibration curves were all higher than 0.9920 for formononetin, ononin, calycosin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1 and astragaloside. The intra- and inter-day precisions (RSD) and accuracy (RE) for the investigated components were in the range of -10.9 to 13.7%. The average recoveries were in the range of 75.7-108.6%. This method was successfully applied to investigate the pharmacokinetics of 16 compounds of BYD in rats. The absorption and elimination rates of the representative saponins were significantly slower than most of the targeted-flavonoids after oral administration of BYD in rats. CONCLUSION: The results demonstrated that the large-volume direct injection LC-MS method provided a rapid and efficient approach for multi-components pharmacokinetics of TCM.

Extract of Fructus Schisandrae chinensis Inhibits Neuroinflammation Mediator Production from Microglia via NF-κ B and MAPK Pathways.

OBJECTIVE: To investigate the anti-neuroinflammation effect of extract of Fructus Schisandrae chinensis (EFSC) on lipopolysaccharide (LPS)-induced BV-2 cells and the possible involved mechanisms. METHODS: Primary cortical neurons were isolated from embryonic (E17-18) cortices of Institute of Cancer Research (ICR) mouse fetuses. Primary microglia and astroglia were isolated from the frontal cortices of newborn ICR mouse. Different cells were cultured in specific culture medium. Cells were divided into 5 groups: control group, LPS group (treated with 1 µg/mL LPS only) and EFSC groups (treated with 1 µg/mL LPS and 100, 200 or 400 mg/mL EFSC, respectively). The effect of EFSC on cells viability was tested by methylthiazolyldiphenyltetrazolium bromide (MTT) colorimetric assay. EFSC-mediated inhibition of LPS-induced production of pro-inflammatory mediators, such as nitrite oxide (NO) and interleukin-6 (IL-6) were quantified and neuron-protection effect against microglia-mediated inflammation injury was tested by hoechst 33258 apoptosis assay and crystal violet staining assay. The expression of pro-inflammatory marker proteins was evaluated by Western blot analysis or immunofluorescence. RESULTS: EFSC (200 and 400 mg/mL) reduced NO, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression in LPS-induced BV-2 cells (P<0.01 or P<0.05). EFSC (200 and 400 mg/mL) reduced the expression of NO in LPS-induced primary microglia and astroglia (P<0.01). In addition, EFSC alleviated cell apoptosis and inflammation injury in neurons exposed to microglia-conditioned medium (P<0.01). The mechanistic studies indicated EFSC could suppress nuclear factor (NF)-?B phosphorylation and its nuclear translocation (P<0.01). The anti-inflammatory effect of EFSC occurred through suppressed activation of mitogen-activated protein kinase (MAPK) pathway (P<0.01 or P<0.05). CONCLUSION: EFSC acted as an anti-inflammatory agent in LPS-induced glia cells. These effects might be realized through blocking of NF-κB activity and inhibition of MAPK signaling pathways.

Assessing genome assembly quality using the LTR Assembly Index (LAI).

Assembling a plant genome is challenging due to the abundance of repetitive sequences, yet no standard is available to evaluate the assembly of repeat space. LTR retrotransposons (LTR-RTs) are the predominant interspersed repeat that is poorly assembled in draft genomes. Here, we propose a reference-free genome metric called LTR Assembly Index (LAI) that evaluates assembly continuity using LTR-RTs. After correcting for LTR-RT amplification dynamics, we show that LAI is independent of genome size, genomic LTR-RT content, and gene space evaluation metrics (i.e., BUSCO and CEGMA). By comparing genomic sequences produced by various sequencing techniques, we reveal the significant gain of assembly continuity by using long-read-based techniques over short-read-based methods. Moreover, LAI can facilitate iterative assembly improvement with assembler selection and identify low-quality genomic regions. To apply LAI, intact LTR-RTs and total LTR-RTs should contribute at least 0.1% and 5% to the genome size, respectively. The LAI program is freely available on GitHub: https://github.com/oushujun/LTR_retriever.

Uncovering potential anti-neuroinflammatory components of Modified Wuziyanzong Prescription through a target-directed molecular docking fingerprint strategy.

Neuroinflammation is a main factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease. Our previous studies indicated that the modified Wuziyanzong Prescription (MWP) can suppress neuroinflammatory responses via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. However, the anti-neuroinflammatory components of MWP remain unclear. Herein, a target-directed molecular docking fingerprint (TMDF) strategy, via integrating the chemical profiling and molecular docking approaches, was developed to identify the potential anti-neuroinflammatory components of MWP. First, as many as 120 possible structures, including 49 flavonoids, 28 phenylpropionic acids, 18 amides, 10 carotenoids, eight phenylethanoid glycosides, four lignans, two iridoids, and one triterpenoid were deduced by the source attribution and structural classification-assisted strategy. Then, their geometries were docked against five major targets of the NF-κB and MAPKs signaling cascades, including p38-α, IKKß, ERK1, ERK2, and TRAF6. The docking results revealed diverse contributions of different components towards the protein targets. Collectively, prenylated flavonoids showed intensive or moderate anti-neuroinflammatory activities, while phenylpropanoids, amides, phenylethanoid glycosides, lignans, and triterpenoids exhibited moderate or weak anti-neuroinflammatory effects. The anti-neuroinflammatory activities of four retrieved prenylated flavonoids were tested by Western blotting assay, and the results mostly agreed with those predicted by the docking method. These gained information demonstrates that the established TMDF strategy could be a rapid and feasible methodology to investigate the potential active components in herbal compound prescriptions.

Comparison Between Oblique Pulling Spinal Manipulation and Other Treatments for Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this review was to compare oblique pulling spinal manipulation with other treatments for lumbar disc herniation. METHODS: Randomized controlled trials of oblique pulling manipulation versus other treatment for lumbar disc herniation were identified using the following databases: China National Knowledge Infrastructure, Wanfang Data, Chinese Science and Technology Periodical Database, PubMed, the Cochrane Library, Embase, Chinese Biological Medicine, and Web of Science. Data extraction was carried out based on inclusion and exclusion criteria, and meta-analysis were performed using RevMan 5.3 software. RESULTS: Nine relevant randomized controlled trials with a total of 887 patients were included. Meta-analysis revealed that oblique pulling manipulation was superior in effective rate to lumbar traction (risk ratio = 1.12; 95% confidence interval [CI]: 1.06-1.19; P < .01) and acupuncture (risk ratio = 1.22; 95% CI: 1.06-1.39; P < .01) and more effective in Visual Analog Scale score (mean difference = - 1.03, 95% CI: -1.32 to -0.74; P < .01) when compared to lumbar traction. It also demonstrated a favorable effect of modified oblique pulling manipulation in Japanese Orthopedic Association scores when compared with lumbar traction (mean difference = 1.66, 95% CI: 0.89 to 2.43; P < .01). CONCLUSION: In the treatment of lumbar disc herniation, oblique pulling spinal manipulation presented with a higher effective rate than acupuncture and lumbar traction. Manipulation had a favorable effect in alleviating pain, and modified oblique pulling manipulation had significant superiority in improving lumbar function when compared with lumbar traction. However, considering the low methodological quality of included studies, more rigorously designed trials should be performed in the future.

Dual therapy with lopinavir/ritonavir plus lamivudine could be a viable alternative for antiretroviral-therapy-naive adults with HIV-1 infection regardless of HIV viral load or subgenotype in resource-limited settings: A randomised, open-label and non-inferiority study from China.

BACKGROUNDS: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-naïve HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). METHODS: 198 were randomised to DT (n = 100) or TT (n = 98). RESULTS: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. CONCLUSION: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.

Antineuroinflammatory Effects of Modified Wu-Zi-Yan-Zong Prescription in ß-Amyloid-Stimulated BV2 Microglia via the NF-κB and ERK/p38 MAPK Signaling Pathways.

Modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese medicinal decoction, has possessed the neuroprotective and anti-inflammatory properties. The mechanisms associated with these properties, however, are not completely understood. We designed the experiments to elucidate the antineuroinflammatory property of MWP in BV2 microglia activated by ß-amyloid (Aß), which is a characteristic feature of Alzheimer's disease (AD). The composition of MWP was studied using HPLC. BV2 microglia cells were then treated with Aß in the presence or absence of MWP. The effects of MWP treatment on Aß-activated neuroinflammation were determined using PCR, western blotting, and immunofluorescence staining. MWP significantly inhibited the mRNA expression of inflammatory mediators such as IL-1ß, IL-6, TNF-α, and MCP-1, as well as the expression of inducible nitric oxide synthase (iNOS) in Aß-activated BV2 microglia. MWP also inhibited the nuclear translocation and signaling pathway of nuclear factor kappa B (NF-κB) by suppressing inhibitor of nuclear factor-κB (IκB) degradation and downregulating IκB kinase ß (IKKß) phosphorylation. Moreover, MWP decreased extracellular regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) phosphorylation, which is an important signaling pathway for proinflammatory gene expression. We concluded that MWP could suppress neuroinflammatory responses in Aß-activated BV2 microglia via the NF-κB and ERK/p38 MAPK signaling cascades and could prove an effective therapeutic agent for the prevention and treatment of neuroinflammatory diseases such as AD.

Identification of all homoeologous chromosomes of newly synthetic allotetraploid Cucumis × hytivus and its wild parent reveals stable subgenome structure.

Allopolyploidy and homoeologous recombination are two important processes in reshaping genomes and generating evolutionary novelties. Newly formed allopolyploids usually display chromosomal perturbations as a result of pairing errors at meiosis. To understand mechanisms of stabilization of allopolyploid species derived from distant chromosome bases, we investigated mitotic stability of a synthetic Cucumis allotetraploid species in relation to meiosis chromosome behavior. The Cucumis × hytivus is an allotetraploid synthesized from interspecific hybridization between cucumber (Cucumis sativus, 2n = 14) and its wild relative Cucumis hystrix (2n = 24) followed by spontaneous chromosome doubling. In the present study, we analyzed the wild parent C. hystrix and the latest generation of C. hytivus using GISH (genomic in situ hybridization) and cross-species FISH (fluorescence in situ hybridization). The karyotype of C. hystrix was constructed with two methods using cucumber fosmid clones and repetitive sequences. Using repeat-element probe mix in two successive hybridizations allowed for routine identification of all 19 homoeologous chromosomes of allotetraploid C. hytivus. No aneuploids were identified in any C. hytivus individuals that were characterized, and no large-scale chromosomal rearrangements were identified in this synthetic allotetraploid. Meiotic irregularities, such as homoeologous pairing, were frequently observed, resulting in univalent and intergenomic multivalent formation. The relatively stable chromosome structure of the synthetic Cucumis allotetraploid may be explained by more deleterious chromosomal viable gametes compared with other allopolyploids. The knowledge of genetic and genomic information of Cucumis allotetraploid species could provide novel insights into the establishment of allopolyploids with different chromosome bases.