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Objective Plant hormones act as chemical messengers in the regulation of plant development and metabolism. The production of ginsenosides in Panax hybrid is promoted by auxins that are transported and accumulated by PIN-FORMED (PIN) and PIN-LIKES (PILS) auxin transporters. However, genome-wide studies of PIN/PILS of ginseng are still scarce. In current study, identification and transcriptional profiling of PIN/PILS gene families, as well as their potential relationship with ginsenoside biosynthesis in Panax ginseng were investigated. Methods PIN/PILS genes in P. ginseng was identified via in silico genome-wide analysis, followed by phylogenetic relationships, gene structure, and protein profiles investigation. Moreover, previously reported RNA-sequence data from various tissues and roots after infection were utilized for PIN/PILS genes expression pattern analysis. The Pearson’s correlation analysis of specific PIN/PILS genes expression level and main ginsenoside contents were taken to reveal the potential relationship between auxin transports and ginsenoside biosynthesis in P. ginseng. Results A genome-wide search of P. ginseng genome for homologous auxin transporter genes identified a total of 17 PIN and 11 PILS genes. Sequence alignment, putative motif organization, and sub-cellular localization indicated redundant and complementary biological functions of these PIN/PILS genes. Most PIN/PILS genes were differentially expressed in a tissue-specific manner, and showed significant correlations with ginsenoside content correspondingly. Eight auxin transporter genes, including both PIN and PILS subfamily members, were positively correlated with ginsenoside content (cor > 0.60; P-value Conclusion Based on the results, we speculate that the accumulation or depletion in temporal or spatial manner of auxin by PIN/PILS transporters involved in the regulation of HMGR activity and subsequent ginsenoside biosynthesis.

Cassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-β-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease., Luo, Wu, et al. assess the ability of Cassiae Semen and its extracted components to alleviate non-alcoholic fatty liver disease (NAFLD) in mice. In addition to reducing the symptoms of NAFLD, the authors find that Cassiae Semen modifies the gut microbiome of mice, and that its effects on the symptoms of NAFLD can also be conferred by fecal microbiome transfer.

Genomic data have demonstrated considerable traction in accelerating contemporary studies in traditional medicine. However, the lack of a uniform format and dispersed storage limits the full potential of herb genomic data. In this study, we developed a Global Pharmacopoeia Genome Database (GPGD). The database contains 34,346 records for 903 herb species from eight global pharmacopoeias (Brazilian, Egyptian, European, Indian, Japanese, Korean, the Pharmacopoeia of the People’s Republic of China, and U.S. Pharmacopoeia’s Herbal Medicines Compendium). In particular, the GPGD contains 21,872 DNA barcodes from 867 species, 2,203 organelle genomes from 674 species, 55 whole genomes from 49 species, 534 genomic sequencing datasets from 366 species, and 9,682 transcriptome datasets from 350 species. Among the organelle genomes, 534 genomes from 366 species were newly generated in this study. Whole genomes, organelle genomes, genomic fragments, transcriptomes, and DNA barcodes were uniformly formatted and arranged by species. The GPGD is publicly accessible at http://www.gpgenome.com and serves as an essential resource for species identification, decomposition of biosynthetic pathways, and molecular-assisted breeding analysis. Thus, the database is an invaluable resource for future studies on herbal medicine safety, drug discovery, and the protection and rational use of herbal resources. Supporting Information The supporting information is available online at 10.1007/s11427-021-1968-7. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Background: Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo. Methods: Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing. Results: The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella, which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P

Polygonum is a generalized genus of the Polygonaceae family that includes various herbaceous plants. In order to provide aid in understanding the evolutionary and phylogenetic relationship in Polygonum at the chloroplast (cp) genome-scale level, we sequenced and annotated the complete chloroplast genomes of four Polygonum species using next-generation sequencing technology and CpGAVAS. Then, repeat sequences, IR contractions, and expansion and transformation sites of chloroplast genomes of four Polygonum species were studied, and a phylogenetic tree was built using the chloroplast genomes of Polygonum. The results indicated that the chloroplast genome construction of Polygonum also displayed characteristic four types of results, comparable to the published chloroplast genome of recorded angiosperms. The chloroplast genomes of the four Polygonum plants are highly consistent in genome size (159,015 bp–163,461 bp), number of genes (112 genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes), gene types, gene order, codon usage, and repeat sequence distribution, which identifies the high preservation among the Polygonum chloroplast genomes. The Polygonum phylogenetic tree was recreated by a full sequence of the chloroplast genome, which illustrates that the P. bistorta, P. orientale, and P. perfoliatum are divided into the same branch, and P. aviculare belongs to Fallopia. The precise system site of lots base parts requires further verification, but the study would provide a basis for developing the available genetic resources and evolutionary relationships of Polygonum.

Panax ginseng (Panax ginseng C. A. Mey.) is a perennial herb of the genus ginseng, which is used as medicine with dried roots and rhizomes. With the deepening of research on ginseng, the chemical components and pharmacological effects of ginseng have gradually been discovered. Endophytes are beneficial to host plants. However, the composition of endophytes in different organs from ginseng is poorly elucidated. The report of ginsenoside production by endophytic microbes isolated from Panax sp., motivated us to explore the endophytic microbial diversity related to the roots, stems, and leaves. In this study, the V5-V7 variable region of endophytic bacteria 16S rRNA gene and V1 variable region of endophytic fungi ITS gene in different organs were analyzed by high-throughput sequencing. The diversity and abundance of endophytic microbes in the three organs are different and are affected by the organs. For example, the most abundant endophytic bacterial genera in roots was Mycobacterium; while, the stems and leaves were Ochrobactrum. Similarly, the fungal endophytes, Coniothyrium and Cladosporium, were also found in high abundance in stems, in comparison to roots and leaves. The Shannon index shows that the diversity of endophytic bacteria in roots is the highest (pstem (p

Coriolopsis trogii is a typical thermotolerant basidiomycete fungus, but its thermotolerance mechanisms are currently unknown. In this study, two monokaryons of C. trogii strain Ct001 were assembled: Ct001_29 had a genome assembly size of 38.85 Mb and encoded 13,113 genes, while Ct001_31 was 40.19 Mb in length and encoded 13,309 genes. Comparative intra- and interstrain genomic analysis revealed the rich genetic diversity of C. trogii, which included more than 315,194 single-nucleotide polymorphisms (SNPs), 30,387 insertion/deletions (indels), and 1,460 structural variations. Gene family analysis showed that the expanded families of C. trogii were functionally enriched in lignocellulose degradation activities. Furthermore, a total of 14 allelic pairs of heat shock protein 20 (HSP20) genes were identified in the C. trogii genome. The expression profile obtained from RNA sequencing (RNA-Seq) showed that four tandem-duplicated allelic pairs, HSP20.5 to HSP20.8, had more than 5-fold higher expression at 35°C than at 25°C. In particular, HSP20.5 and HSP20.8 were the most highly expressed HSP20 genes. Allelic expression bias was found for HSP20.5 and HSP20.8; the expression of Ct29HSP20.8 was at least 1.34-fold higher than that of Ct31HSP20.8, and that of Ct31HSP20.5 was at least 1.5-fold higher than that of Ct29HSP20.5. The unique structural and expression profiles of the HSP20 genes revealed by these haplotype-resolved genomes provide insight into the molecular mechanisms of high-temperature adaptation in C. trogii. IMPORTANCE Heat stress is one of the most frequently encountered environmental stresses for most mushroom-forming fungi. Currently available fungal genomes are mostly haploid because high heterozygosity hinders diploid genome assembly. Here, two haplotype genomes of C. trogii, a thermotolerant basidiomycete, were assembled separately. A conserved tandem cluster of four HSP20 genes showing allele-specific expression was found to be closely related to high-temperature adaptation in C. trogii. The obtained haploid genomes and their comparison offer a more thorough understanding of the genetic background of C. trogii. In addition, the responses of HSP20 genes at 35°C, which may contribute to the growth and survival of C. trogii at high temperatures, could inform the selection and breeding of elite strains in the future.

Coriolopsis trogii is a typical thermotolerant basidiomycete fungus, but its thermotolerance mechanisms are currently unknown. In this study, two monokaryons of C. trogii strain Ct001 were assembled: Ct001_29 had a genome assembly size of 38.85 Mb and encoded 13,113 genes, while Ct001_31 was 40.19 Mb in length and encoded 13,309 genes. Comparative intra- and interstrain genomic analysis revealed the rich genetic diversity of C. trogii, which included more than 315,194 single-nucleotide polymorphisms (SNPs), 30,387 insertion/deletions (indels), and 1,460 structural variations. Gene family analysis showed that the expanded families of C. trogii were functionally enriched in lignocellulose degradation activities. Furthermore, a total of 14 allelic pairs of heat shock protein 20 (HSP20) genes were identified in the C. trogii genome. The expression profile obtained from RNA sequencing (RNA-Seq) showed that four tandem-duplicated allelic pairs, HSP20.5 to HSP20.8, had more than 5-fold higher expression at 35°C than at 25°C. In particular, HSP20.5 and HSP20.8 were the most highly expressed HSP20 genes. Allelic expression bias was found for HSP20.5 and HSP20.8; the expression of Ct29HSP20.8 was at least 1.34-fold higher than that of Ct31HSP20.8, and that of Ct31HSP20.5 was at least 1.5-fold higher than that of Ct29HSP20.5. The unique structural and expression profiles of the HSP20 genes revealed by these haplotype-resolved genomes provide insight into the molecular mechanisms of high-temperature adaptation in C. trogii. IMPORTANCE Heat stress is one of the most frequently encountered environmental stresses for most mushroom-forming fungi. Currently available fungal genomes are mostly haploid because high heterozygosity hinders diploid genome assembly. Here, two haplotype genomes of C. trogii, a thermotolerant basidiomycete, were assembled separately. A conserved tandem cluster of four HSP20 genes showing allele-specific expression was found to be closely related to high-temperature adaptation in C. trogii. The obtained haploid genomes and their comparison offer a more thorough understanding of the genetic background of C. trogii. In addition, the responses of HSP20 genes at 35°C, which may contribute to the growth and survival of C. trogii at high temperatures, could inform the selection and breeding of elite strains in the future.

Herbgenomics is an emerging field of traditional Chinese medicine (TCM) research and development. By combining TCM research with genomics, herbgenomics can help to establish the scientific validity of TCM and bring it into wider usage within the field of medicine. Salvia Linn. (S. Linn.) is a large genus of Labiatae that includes important medicinal plants. In this herbgenomics study, the complete chloroplast (cp) genomes of two Salvia spp.—namely, S. przewalskii and S. bulleyana, which are used as a surrogate for S. miltiorrhiza—were sequenced and compared with those of two other reported Salvia spp.—namely, S. miltiorrhiza and S. japonica. The genome organization, gene number, type, and repeat sequences were compared. The annotation results showed that both Salvia plants contain 114 unique genes, including 80 protein-coding, 30 transfer RNA (tRNA), and four ribosomal RNA (rRNA) genes. Repeat sequence analysis revealed 21 forward and 22 palindromic sequences in both Salvia cp genomes, and 17 and 21 tandem repeats in S. przewalskii and S. bulleyana, respectively. A synteny comparison of the Salvia spp. cp genomes showed a high degree of sequence similarity in the coding regions and a relatively high divergence of the intergenic spacers. Pairwise alignment and single-nucleotide polymorphism (SNP) analyses found some candidate fragments to identify Salvia spp., such as the intergenic region of the trnV–ndhC, trnQ–rps16, atpI–atpH, psbA–ycf3, ycf1, rpoC2, ndhF, matK, rpoB, rpoA, and accD genes. All of the results—including the repeat sequences and SNP sites, the inverted repeat (IR) region border, and the phylogenetic analysis—showed that S. przewalskii and S. bulleyana are extremely similar from a genetic standpoint. The cp genome sequences of the two Salvia spp. reported here will pave the way for breeding, species identification, phylogenetic evolution, and cp genetic engineering studies of Salvia medicinal plants. Keywords: Salvia, Chloroplast genome, Comparative analysis

Ginseng, the root and rhizome of Panax ginseng C. A. Mey., is a famous herbal medicine, and its major ginsenosides exert beneficial effects on nonalcoholic fatty liver disease (NAFLD). Due to the multicomponent and multitarget features of ginsenosides, their detailed mechanisms remain unclear. This study aimed to explore the role of ginsenosides on NAFLD and the potential mechanisms mediated by the gut microbiota and related molecular processes. C57BL/6J mice were fed a high-fat diet (HFD) supplemented or not supplemented with ginsenoside extract (GE) for 12 weeks. A strategy that integrates bacterial gene sequencing, serum pharmacochemistry and network pharmacology was applied. The results showed that GE significantly alleviated HFD-induced NAFLD symptoms in a dose-dependent manner. Furthermore, GE treatment modulated the HFD-induced imbalance in the gut microbiota and alleviated dysbiosis-mediated gut leakage and metabolic endotoxemia. Additionally, 20 components were identified in the mouse plasma after the oral administration of GE, and they interacted with 82 NAFLD-related targets. A network analysis revealed that anti-inflammatory effects and regulation of the metabolic balance might be responsible for the effects of GE on NAFLD. A validation experiment was then conducted, and the results suggested that GE suppressed NF-κB/IκB signaling activation and decreased the release and mRNA levels of proinflammatory factors (TNF-α, IL-1β and IL-6). Additionally, GE promoted hepatic lipolytic genes (CPT-1a), inhibited lipogenic genes (SREBP-1c, FAS, ACC-1) and improved leptin resistance. These findings imply that the benefits of GE are involved in modulating the gut microbiota, enhancing the gut barrier function, restoring the energy balance, and alleviating metabolic inflammation. Moreover, GE might serve as a potential agent for the prevention of NAFLD through the integration of prebiotic, anti-inflammatory and energy-regulatory effects.

Plant hormones act as chemical messengers in the regulation of plant development and metabolism. The production of ginsenosides inA genome-wide search ofBased on the results, we speculate that the accumulation or depletion in temporal or spatial manner of auxin by PIN/PILS transporters involved in the regulation of HMGR activity and subsequent ginsenoside biosynthesis.

Background: Panax ginseng is a valuable herbal medicine which has been applied in eastern Asia to maintain their physical vitality for millennia. However, continuous cropping leads to the accumulation of allelochemicals, which subsequently reduces the quality and yield of P. ginseng, and arable soils for P. ginseng cultivation are getting scarce. Methods: In this study, a strain highly efficient degrading p-hydroxybenzoic acid was isolated from the rhizosphere soil of a ginseng cultivation field. Subsequently, its draft genome was sequenced, and the key genes involving the p-hydroxybenzoic acid-degrading pathway were identified by bioinformatics software. Results: Based on its biophysical/biochemical characteristics, analysis of the 16S rRNA sequence and gyrB gene authentication, strain LD6 was identified as Pseudomonas putida LD6. The initial p-hydroxybenzoic acid concentration in minimal salt medium was 100 mg•L-1, and after 8 d of bacterial culture in the laboratory, the degraded reached 97.35%. The p-hydroxybenzoic acid content was decreased by 35.21%, and the ginseng death rate was decreased by 38.46% in the rhizosphere soil of P. ginseng inoculated with strain LD6. The draft genome sequence consisted of 5,765,634 bp, and the genome comprised 5186 protein-coding genes, and the pobA, catB, pcaG, UbiA, and UbiX genes were annotated, and may play important roles in p-hydroxybenzoic acid degradation.Conclusion: Isolation and manipulation of functional bacteria is an effective strategy to alleviate ginseng continuous cropping problems and enhance the quality and yield of P. ginseng.

Ginseng (Panax ginseng C.A. Meyer) is one of the best-selling herbal medicines, with ginsenosides as its main pharmacologically active constituents. Although extensive chemical and pharmaceutical studies of these compounds have been performed, genome-wide studies of the basic helix-loop-helix (bHLH) transcription factors of ginseng are still limited. The bHLH transcription factor family is one of the largest transcription factor families found in eukaryotic organisms, and these proteins are involved in a myriad of regulatory processes. In our study, 169 bHLH transcription factor genes were identified in the genome of P. ginseng, and phylogenetic analysis indicated that these PGbHLHs could be classified into 24 subfamilies. A total of 21 RNA-seq data sets, including two sequencing libraries for jasmonate (JA)-responsive and 19 reported libraries for organ-specific expression analyses were constructed. Through a combination of gene-specific expression patterns and chemical contents, 6 PGbHLH genes from 4 subfamilies were revealed to be potentially involved in the regulation of ginsenoside biosynthesis. These 6 PGbHLHs, which had distinct target genes, were further divided into two groups depending on the absence of MYC-N structure. Our results would provide a foundation for understanding the molecular basis and regulatory mechanisms of bHLH transcription factor action in P. ginseng. KEY WORDS: Genome-wide characterization, bHLH transcription factors, Panax ginseng, Ginsenosides, Phylogenetic analysis

We sequenced and analyzed the complete chloroplast genome of Aster tataricus (family Asteraceae), a Chinese herb used medicinally to relieve coughs and reduce sputum. The A. tataricus chloroplast genome was 152,992 bp in size, and harbored a pair of inverted repeat regions (IRa and IRb, each 24,850 bp) divided into a large single-copy (LSC, 84,698 bp) and a small single-copy (SSC, 18,250 bp) region. Our annotation revealed that the A. tataricus chloroplast genome contained 115 genes, including 81 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. In addition, 70 simple sequence repeats (SSRs) were detected in the A. tataricus chloroplast genome, including mononucleotides (36), dinucleotides (1), trinucleotides (23), tetranucleotides (1), pentanucleotides (8), and hexanucleotides (1). Comparative chloroplast genome analysis of three Aster species indicated that a higher similarity was preserved in the IR regions than in the LSC and SSC regions, and that the differences in the degree of preservation were slighter between A. tataricus and A. altaicus than between A. tataricus and A. spathulifolius. Phylogenetic analysis revealed that A. tataricus was more closely related to A. altaicus than to A. spathulifolius. Our findings offer valuable information for future research on Aster species identification and selective breeding.

We sequenced and analyzed the complete chloroplast genome of Aster tataricus (family Asteraceae), a Chinese herb used medicinally to relieve coughs and reduce sputum. The A. tataricus chloroplast genome was 152,992 bp in size, and harbored a pair of inverted repeat regions (IRa and IRb, each 24,850 bp) divided into a large single-copy (LSC, 84,698 bp) and a small single-copy (SSC, 18,250 bp) region. Our annotation revealed that the A. tataricus chloroplast genome contained 115 genes, including 81 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. In addition, 70 simple sequence repeats (SSRs) were detected in the A. tataricus chloroplast genome, including mononucleotides (36), dinucleotides (1), trinucleotides (23), tetranucleotides (1), pentanucleotides (8), and hexanucleotides (1). Comparative chloroplast genome analysis of three Aster species indicated that a higher similarity was preserved in the IR regions than in the LSC and SSC regions, and that the differences in the degree of preservation were slighter between A. tataricus and A. altaicus than between A. tataricus and A. spathulifolius. Phylogenetic analysis revealed that A. tataricus was more closely related to A. altaicus than to A. spathulifolius. Our findings offer valuable information for future research on Aster species identification and selective breeding.

Ginseng (Panax ginseng C.A. Meyer) is one of the best-selling herbal medicines, with ginsenosides as its main pharmacologically active constituents. Although extensive chemical and pharmaceutical studies of these compounds have been performed, genome-wide studies of the basic helix-loop-helix (bHLH) transcription factors of ginseng are still limited. The bHLH transcription factor family is one of the largest transcription factor families found in eukaryotic organisms, and these proteins are involved in a myriad of regulatory processes. In our study, 169 bHLH transcription factor genes were identified in the genome of P. ginseng, and phylogenetic analysis indicated that these PGbHLHs could be classified into 24 subfamilies. A total of 21 RNA-seq data sets, including two sequencing libraries for jasmonate (JA)-responsive and 19 reported libraries for organ-specific expression analyses were constructed. Through a combination of gene-specific expression patterns and chemical contents, 6 PGbHLH genes from 4 subfamilies were revealed to be potentially involved in the regulation of ginsenoside biosynthesis. These 6 PGbHLHs, which had distinct target genes, were further divided into two groups depending on the absence of MYC-N structure. Our results would provide a foundation for understanding the molecular basis and regulatory mechanisms of bHLH transcription factor action in P. ginseng., Graphical abstract Altogether 169 basic helix-loop-helix type transcription factor genes were identified in the genome of P. ginseng, and phylogenetic analysis indicated that these PGbHLHs could be classified into 24 subfamilies. Six PGbHLH genes from 4 subfamilies were revealed to be potentially involved in the regulation of ginsenoside biosynthesis. These 6 PGbHLHs, which had distinct target genes, were further divided into two groups depending on the absence of MYC-N structure.fx1

Pharmacological prophylaxis for early seizures following traumatic brain injury (TBI) is a recommendation in the Brain Trauma Foundation Guidelines. However, several studies have challenged the efficacy and safety of this practice, resulting in varied practice across centers around the world. The purpose of the present study was to compare the incidence of early clinical seizures following TBI, between two large centers, a US Center that practises routine seizure prophylaxis and a Chinese Center that does not use seizure prophylaxis following TBI. This was a prospective observational study including an urban level I trauma center in the USA and a large hospital in Shenzhen, China. At the US Center, all patients received seizure prophylaxis with levetiracetam. At the Chinese Center, no seizure prophylaxis was given. All patients with blunt TBI and positive computed tomography findings for epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intracerebral hemorrhage or diffuse axonal injury were included. Patients who died within 24 h of admission were excluded. The study population was monitored daily for clinical seizures for the first 7 post-injury days. Data collected included demographics, mechanism of injury, vital signs upon arrival, injury severity and emergency interventions. Primary outcome was the incidence of early seizures, defined as those occurring within 7 days of injury. A total of 522 patients were included in the analysis: 272 patients at the US Center who received seizure prophylaxis and 250 patients at the Chinese Center who did not receive prophylaxis. Overall, 3.7% of patients who received seizure prophylaxis developed early seizures, compared to 2.8% of patients who did not receive any prophylaxis (p = 0.573). Decompressive craniectomy was associated with the highest incidence of early seizure (9.2%). In this subgroup, the seizure rate was 10.4% in the prophylaxis group and 7.1% in the no-prophylaxis group (p = 0.738). Patients with admission GCS

Emerging evidence suggests that gut microbiota contribute to the treatment of post-inflammatory irritable bowel syndrome (PI-IBS). Our previous studies have demonstrated that a Chinese formula, Wuji Wan, has the ability to mitigate abdominal pain and diarrhea in PI-IBS rats. However, little is known about the underlying mechanism and whether the gut microbiota mediate the effect of Wuji Wan on PI-IBS. Thus, the aim of this study was to determine whether Wuji Wan mitigated PI-IBS by modifying the gut microbiota. PI-IBS was induced in Sprague-Dawley rats by enema using 4% acetic acid and restraint stress. Rats were fed water, Wuji Wan extract (630 mg/kg) or pinaverium bromide (13.5 mg/kg). Our data showed that Wuji Wan effectively ameliorated abdominal pain, colonic motility abnormality and visceral hypersensitivity. Analysis of the fecal microbiota showed that Wuji Wan could reverse the reduction in richness of the gut microbiota and significantly increase the relative abundances of Akkermansia, Bacteroides, and Parasutterella; however, Lactobacillus and Prevotella were markedly decreased in the PI-IBS rats. Moreover, Wuji Wan promoted goblet cell proliferation in the colonic mucosa by increasing the release of mucin, up-regulating the distribution of tight junction proteins Occludin and ZO-1 and down-regulating the expression of MLCK in colonic epithelial cells. These findings suggest that Wuji Wan may remit IBS by modulating the gut microbiota and stabilizing the gut mucosal barrier, indicating that the use of a classical formula of Traditional Chinese Medicine (TCM) that exhibits a prebiotic effect may be a promising strategy for PI-IBS treatment.

Ginseng, which contains ginsenosides as bioactive compounds, has been regarded as an important traditional medicine for several millennia. However, the genetic background of ginseng remains poorly understood, partly because of the plant's large and complex genome composition. We report the entire genome sequence of Panax ginseng using next-generation sequencing. The 3.5-Gb nucleotide sequence contains more than 60% repeats and encodes 42 006 predicted genes. Twenty-two transcriptome datasets and mass spectrometry images of ginseng roots were adopted to precisely quantify the functional genes. Thirty-one genes were identified to be involved in the mevalonic acid pathway. Eight of these genes were annotated as 3-hydroxy-3-methylglutaryl-CoA reductases, which displayed diverse structures and expression characteristics. A total of 225 UDP-glycosyltransferases (UGTs) were identified, and these UGTs accounted for one of the largest gene families of ginseng. Tandem repeats contributed to the duplication and divergence of UGTs. Molecular modeling of UGTs in the 71st, 74th, and 94th families revealed a regiospecific conserved motif located at the N-terminus. Molecular docking predicted that this motif captures ginsenoside precursors. The ginseng genome represents a valuable resource for understanding and improving the breeding, cultivation, and synthesis biology of this key herb.

The complete chloroplast genome of Artemisia annua (Asteraceae), the primary source of artemisinin, was sequenced and analyzed. The A. annua cp genome is 150,995 bp, and harbors a pair of inverted repeat regions (IRa and IRb), of 24,850 bp each that separate large (LSC, 82,988 bp) and small (SSC, 18,267 bp) single-copy regions. Our annotation revealed that the A. annua cp genome contains 113 genes and 18 duplicated genes. The gene order in the SSC region of A. annua is inverted; this fact is consistent with the sequences of chloroplast genomes from three other Artemisia species. Fifteen (15) forward and seventeen (17) inverted repeats were detected in the genome. The existence of rich SSR loci in the genome suggests opportunities for future population genetics work on this anti-malarial medicinal plant. In A. annua cpDNA, the rps19 gene was found in the LSC region rather than the IR region, and the rps19 pseudogene was absent in the IR region. Sequence divergence analysis of five Asteraceae species indicated that the most highly divergent regions were found in the intergenic spacers, and that the differences between A. annua and A. fukudo were very slight. A phylogenetic analysis revealed a sister relationship between A. annua and A. fukudo. This study identified the unique characteristics of the A. annua cp genome. These results offer valuable information for future research on Artemisia species identification and for the selective breeding of A. annua with high pharmaceutical efficacy.

In the face of the global epidemic of metabolic syndrome (MetS) and its strong association with the increasing rate of cardiovascular morbidity and mortality, it is critical to detect MetS at an early stage in the clinical setting to implement preventive intervention long before the complications arise. Lipopolysaccharide, the cell wall component of Gram-negative bacteria produced from diet-disrupted gut microbiota, has been shown to induce metabolic endotoxemia, chronic low-grade inflammation, and ultimately insulin resistance. Therefore, ameliorating the inflammation and insulin resistance underlying MetS by gut microbiota-targeted, dietary intervention has gained increasing attention. In this review, we propose using dynamic monitoring of a set of translational biomarkers related with the etiological role of gut microbiota, including lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR), for early detection and prevention of MetS via nutritional modulation. LBP initiates the recognition and monomerization of lipopolysaccharide and amplifies host immune responses, linking the gut-derived antigen load and inflammation indicated by the plasma levels of CRP. Fasting plasma insulin and HOMA-IR are measured to evaluate insulin sensitivity that is damaged by pro-inflammatory cytokines. The dynamic monitoring of these biomarkers in high-risk populations may provide translational methods for the quantitative and dynamic evaluation of dysbiosis-induced insulin resistance and the effectiveness of dietary treatment for MetS.

Aim: Tumor metastasis is one of the leading causes of insufficient chemotherapy during cancer treatment. In this study, a poly(β-amino ester) derivate was developed to fabricate paclitaxel (PTX) entrapped pH-responsive copolymer micelles for inhibition of breast cancer metastasis. Materials & methods: PTX-loaded micelles were fabricated by thin film hydration method. The inhibition efficacy of the as-prepared micelles was evaluated on MDA-MB-231 cells and tumor bearing mice. Results: PTX-loaded micelles were successfully prepared. Such micelles could promote drug uptake and MDA-MB-231 cell deaths, and suppress tumor metastasis. Conclusion: The pH-responsive PTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor microenvironments with improved inhibitory effects on tumor metastasis.

Gene is the base of in vivo metabolism and effectiveness for traditional Chinese medicines (TCM), and the gene expression, regulation and modification are used as the research directions to perform the TCM multi-component, multi-link and multi-target in vivo metabolism studies, which will improve the research on TCM metabolic proecess, effect target and molecular mechanism. Humans are superorganisms with 1% genes inherited from parents and 99% genes from various parts of the human body, mainly coming from the microorganisms in intestinal flora. These indicate that genetically inherited human genome and "second genome" could affect the TCM in vivo metabolism from inheritance and "environmental" aspects respectively. In the present paper, typical case study was used to discuss related TCM in vivo metabolic genomics research, mainly including TCM genomics research and gut metagenomics research, as well as the personalized medicine evoked from the individual difference of above genomics (metagenomics).

Summary Background: As standard triple therapies of achieve unsatisfactory eradication of Helicobacter pylori, several alternative regimens have been proposed. Objectives: To systematically evaluate whether sequential treatment eradicates H. pylori infection better than standard triple therapies and compare the risk of adverse events with these two regimens. Methods: We searched electronic databases up to February 2008 for studies evaluating the efficacy of the 10-day sequential therapy vs. standard triple regimens for eradication of H. pylori. The pooled risk ratios (RR) and 95% confidence intervals (95% CI) were calculated. Results: We identified 11 randomized trials, including eight full-text manuscripts and three abstracts. Pooled analysis demonstrated clear superiority of the sequential therapy over 7-day triple regimen with an RR of 1·23 (95% CI 1·19–1·27), and over 10-day triple regimen with a RR of 1·16 (95% CI 1·10–1·23). Adverse event rates were similar. For sequential therapy vs. 7-day triple therapies, RR = 0·96, 95% CI 0·70–1·31. Conclusions: Sequential therapy was associated with a higher eradication rate of H. pylori compared with both 7-day triple regimen and 10-day triple regimen.

Acidithiobacillus ferrooxidans ATCC 23270 is an important model organism for bioleaching and bioremediation studies owing to its diverse metabolic capabilities, whereas lix984n is a widely used extractant. Little is known about the response of cbb genes in A. ferrooxidans to lix984n shock. Thus, to elucidate the response of the CO2 fixation genes in A. ferrooxidans ATCC 23270 to the addition of lix984n, the gene expression of cbb genes was examined using a real-time PCR. Although a natural increase or decrease in the expression of most cbb genes was observed after 5 min of shock with 3% (v/v) lix984n, sdhC and cbbR exhibited quick responses to the shock. Ten min of shock had a greater effect on the cbb gene expression, yet 15 min of shock had a significant effect on the Calvin cycle in A. ferrooxidans ATCC 23270, as the expression of all the cbb genes reached a very high level. Therefore, after a short lix984n shock, a solution of A. ferrooxidans can be re-used for bioleaching.

The response of Acidithiobacillus ferrooxidans ATCC 23270 to variations in extracellular pH was investigated based on some gene expression profiling. Real-time PCR analysis revealed that cells elicited both general and specific transcriptional responses when challenged with environmental acid (pH 1.3) or base (pH 2.3) conditions over a 6-h period. These responses included the differential expression of genes functionally linked to cell membrane structure, transcriptional regulation and signal transduction. Response to acid stress included the elevated expression of genes encoding the two component response regulator OmpR, the global regulator Fur, and the RNA polymerase sigma-38 factor (rpoS) and so on. Collectively, these results suggest that Acidithiobacillus ferrooxidans modulates multiple cell envelope components, transcription regulators and as part of its response to changing external pH conditions.

Summary Background The use of heparin for the treatment of ulcerative colitis has been evaluated in several open and controlled trials, with varying outcomes. Aim To evaluate the efficacy and safety of heparin as supplemental therapy compared with conventional therapy in patients with ulcerative colitis. Methods All randomized trials comparing heparin supplementation to conventional therapy were included from electronic databases. Statistical analysis was performed with review manager 4.2.8 (The Cochrane Collaboration, Oxford, UK). Sub-analysis and sensitivity analysis were also performed. Results Eight randomized-controlled trials, investigating a total of 454 participants, met the inclusion criteria. The odds ratio (OR) for the efficacy of heparin supplementation vs. conventional therapy was 0.78 (95% CI = 0.50–1.21). Few serious adverse events were observed. The OR for the efficacy of unfractionated heparin and low-molecular-weight heparin vs. conventional therapy was 0.26 (95% CI = 0.07–0.93) and 0.92 (95% CI = 0.57–1.47), respectively. The OR for the efficacy of heparin vs. conventional therapy with placebo was 0.87 (95% CI = 0.53–1.44). Conclusions Our meta-analysis suggests that administration of heparin in patients with ulcerative colitis is safe, but no additive benefit over conventional therapy is indicated.

Summary Background Recent evidence found probiotics could inhibit Helicobacter pylori colonization from both in vitro and in vivo studies. Aim To systematically evaluate whether adding probiotics to anti-H. pylori regimens could improve eradication rates and reduce side effects during anti-H. pylori treatment. Methods Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing probiotics supplementation to placebo or no treatment during anti-H. pylori regimens. Statistical analysis was performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also performed. Results We identified 14 randomized trials (n = 1671). Pooled H. pylori eradication rates were 83.6% (95% CI = 80.5–86.7%) and 74.8% (95% CI = 71.1–78.5%) for patients with or without probiotics by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34–2.54); the occurrence of total side effects were 24.7% (95% CI = 20.0–29.4%) and 38.5% (95% CI = 33.0–44.1%) for groups with or without probiotics, especially for diarrhoea, the summary OR was 0.44 (95% CI = 0.30–0.66). Conclusions Our review suggests that supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy-related side effects.

Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However, based on mass spectrometry imaging analyses, the ginsenosides varied among different tissues. In this work, ginseng root was separated into three tissues—periderm, cortex and stele—each for five duplicates. The chemical analysis and transcriptome analysis were conducted simultaneously. Gene-encoding enzymes involved in ginsenosides biosynthesis and modification were studied based on gene and molecule data. Eight widely-used ginsenosides were distributed unevenly in ginseng roots. A total of 182,881 unigenes were assembled with an N50 contig size of 1374 bp. About 21,000 of these unigenes were positively correlated with the content of ginsenosides. Additionally, we identified 192 transcripts encoding enzymes involved in two triterpenoid biosynthesis pathways and 290 transcripts encoding UDP-glycosyltransferases (UGTs). Of these UGTs, 195 UGTs (67.2%) were more highly expressed in the periderm, and that seven UGTs and one UGT were specifically expressed in the periderm and stele, respectively. This genetic resource will help to improve the interpretation on complex mechanisms of ginsenosides biosynthesis, accumulation, and transportation.

In this paper, the existence and uniqueness, the exponential stability, and the almost sure exponential stability of mild solution for impulsive stochastic partial functional differential equations with finite delay are considered. Some sufficient conditions are established for our concerned problems, and some existing results are generalized and improved. Finally, an illustrative example is provided to show the feasibility and effectiveness of the obtained results.

Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes.

In this paper, we study a class of stochastic neutral Volterra-Levin equations which are equipped with Lévy noise and variable delay and we obtain p th moment exponential stability. Some well-known results are improved and generalized.