Search

Key message: We demonstrated a short-cycle B. napus line, Sef1, with a highly efficient and fast transformation system, which has great potential in large-scale functional gene analysis in a controlled environment. Rapeseed (Brassica napus L.) is an essential oil crop that accounts for a considerable share of global vegetable oil production. Nonetheless, studies on functional genes of B. napus are lagging behind due to the complicated genome and long growth cycle, this is largely due to the limited availability of gene analysis and modern genome editing-based molecular breeding. In this study, we demonstrated a short-cycle semi-winter-type Brassica napus ‘Sef1’ with very early-flowering and dwarf phenotype, which has great potential in large-scale indoor planting. Through the construction of an F2 population of Sef1 and Zhongshuang11, bulked segregant analysis (BSA) combined with the rape Bnapus50K SNP chip assay method was used to identify the early-flowering genes in Sef1, and a mutation in BnaFT.A02 was identified as a major locus significantly affecting the flowering time in Sef1. To further investigate the mechanism of early flowering in Sef1 and discover its potential in gene function analysis, an efficient Agrobacterium-mediated transformation system was established. The average transformation efficiency with explants of hypocotyls and cotyledons was 20.37% and 12.8%, respectively, and the entire transformation process took approximately 3 months from explant preparation to seed harvest of transformed plants. This study demonstrates the great potential of Sef1 for large-scale functional gene analysis. [ABSTRACT FROM AUTHOR]

Microglia-mediated neuroinflammation contributes to major depressive disorder (MDD). Targeting microglia is a promising strategy for treating MDD. Patchouli alcohol (PA), an active component of Pogostemon cablin , has anti-inflammatory and neuroprotective effects. In this study, we investigate the microglia-mediated neurogenesis pathway in which PA ameliorates depressive-like behaviors in stress-induced animal model of depression. C57BL/6J male mice were exposed to chronic mild stress (CMS) for 4 weeks, then administered PA intraperitoneally at 10, 20 or 40 mg/kg once per day for 3 weeks. The antidepressant effects of PA were evaluated in the sucrose preference test, forced swimming test, and tail suspension test. Microglial phenotypes and activation of the NLRP3 inflammation were analyzed using RT-PCR, western blotting and immunofluorescence staining. Effects of PA on neurogenesis were analyzed in vitro and in vivo using immunofluorescence staining. Behavioral assessments showed that PA alleviated depressive-like behaviors in CMS-exposed mice. CMS induced microglial activation and pro-inflammatory profiles, which were blocked by PA treatment. PA attenuated the activation of NLRP3 inflammasome, leading to decreases in the levels of caspase-1, ASC, IL-1β, and IL-18 in the hippocampus of CMS-exposed mice. In primary microglia cultures, PA inhibited LPS-induced NLRP3 inflammasome activation. PA rescued inflammation-inhibited neurogenesis in vivo and in vitro. Our results suggest that PA inhibits the NLRP3 inflammasome and ameliorates microglia-mediated neurogenesis impairment, contributing to antidepressant effects. Thus, PA may be a novel treatment for inflammation-driven mental disorders. Patchouli alcohol inhibits NLRP3 inflammasome-mediated microglial activation, ameliorates neurogenesis impairment in the hippocampus, contributing to alleviate depressive-like behavior in CMS-exposed mice. [Display omitted] • Patchouli alcohol ameliorates depressive-like behaviors in mice exposed to chronic mild stress. • Patchouli alcohol attenuates stress-induced activation of the NLRP3 inflammasome in microglia. • Patchouli alcohol restores hippocampal neurogenesis in a mouse model of depression. [ABSTRACT FROM AUTHOR]

Gliomas are tumors of the primary central nervous system associated with poor prognosis and high mortality. The 5-year survival rate of patients with gliomas received surgery combined with chemotherapy or radiotherapy does not exceed 5%. Although temozolomide is commonly used in the treatment of gliomas, the development of resistance limits its use. MicroRNAs are non-coding RNAs involved in numerous processes of glioma cells, such as proliferation, migration and apoptosis. MicroRNAs regulate cell cycle, PI3K/AKT signal pathway, and target apoptosis-related genes (e.g., BCL6), angiogenesis-related genes (e.g., VEGF) and other related genes to suppress gliomas. Evidence illustrates that microRNAs can regulate the sensitivity of gliomas to temozolomide, cisplatin, and carmustine, thereby enhancing the efficacy of these agents. Moreover, traditional Chinese medicine (e.g., tanshinone IIA, xanthohumol, and curcumin) exert antiglioma effects by regulating the expression of microRNAs, and then microRNAs inhibit gliomas through influencing the process of tumors by targeting certain genes. In this paper, the mechanisms through which microRNAs regulate the sensitivity of gliomas to therapeutic drugs are described, and traditional Chinese medicine that can suppress gliomas through microRNAs are discussed. This review aims to provide new insights into the traditional Chinese medicine treatment of gliomas. [ABSTRACT FROM AUTHOR]

Gliomas are tumors of the primary central nervous system associated with poor prognosis and high mortality. The 5-year survival rate of patients with gliomas received surgery combined with chemotherapy or radiotherapy does not exceed 5%. Although temozolomide is commonly used in the treatment of gliomas, the development of resistance limits its use. MicroRNAs are non-coding RNAs involved in numerous processes of glioma cells, such as proliferation, migration and apoptosis. MicroRNAs regulate cell cycle, PI3K/AKT signal pathway, and target apoptosis-related genes (e.g., BCL6), angiogenesis-related genes (e.g., VEGF) and other related genes to suppress gliomas. Evidence illustrates that microRNAs can regulate the sensitivity of gliomas to temozolomide, cisplatin, and carmustine, thereby enhancing the efficacy of these agents. Moreover, traditional Chinese medicine (e.g., tanshinone IIA, xanthohumol, and curcumin) exert antiglioma effects by regulating the expression of microRNAs, and then microRNAs inhibit gliomas through influencing the process of tumors by targeting certain genes. In this paper, the mechanisms through which microRNAs regulate the sensitivity of gliomas to therapeutic drugs are described, and traditional Chinese medicine that can suppress gliomas through microRNAs are discussed. This review aims to provide new insights into the traditional Chinese medicine treatment of gliomas. [ABSTRACT FROM AUTHOR]

d‐Allulose, a low‐calorie rare sugar with various physiological functions, is mainly produced through the isomerization of d‐fructose by ketose 3‐epimerases (KEases), which exhibit various substrate specificities. A novel KEase from a Clostridia bacterium (CDAE) was identified to be a d‐allulose 3‐epimerase and was further characterized as thermostable and metal‐dependent. In order to explore its structure–function relationship, the crystal structure of CDAE was determined using X‐ray diffraction at 2.10 Å resolution, revealing a homodimeric d‐allulose 3‐epimerase structure with extensive interactions formed at the dimeric interface that contribute to structure stability. Structural analysis identified the structural features of CDAE, which displays a common (β/α)8‐TIM barrel and an ordered Mn2+‐binding architecture at the active center, which may explain the positive effects of Mn2+ on the activity and stability of CDAE. Furthermore, comparison of CDAE and other KEase structures revealed several structural differences, highlighting the remarkable differences in enzyme–substrate binding at the O4, O5 and O6 sites of the bound substrate, which are mainly induced by distinct hydrophobic pockets in the active center. The shape and hydrophobicity of this pocket appear to produce the differences in specificity and affinity for substrates among KEase family enzymes. Exploration of the crystal structure of CDAE provides a better understanding of its structure–function relationship, which might provide a basis for molecular modification of CDAE and further provides a reference for other KEases. [ABSTRACT FROM AUTHOR]

Microglia-mediated inflammatory process is recognized as a target in the treatment of depression. Ginsenoside Rg1 (GRg1), the active ingredient of traditional ginseng, regulates microglial phenotypes to resist stress-induced inflammatory responses. Here we used a mouse model of stress-induced depression to investigate the involvement of microglial Nod-like receptor protein 3 (NLRP3) in the antidepressant effects of GRg1. Male C57BL/6J mice were exposed to chronic mild stress (CMS) for three weeks, followed by intraperitoneal injection of GRg1 (20 mg/kg) or the antidepressant imipramine (20 mg/kg) for another three weeks. Depressive-like behaviors were assessed by sucrose preference test, forced swimming test, and tail suspension test. Microglial phenotypes were assessed in terms of morphological features and cytokine profiles; inflammasome activity, in terms of levels of complexes containing NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1; and neurogenesis, in terms of numbers of proliferating, differentiating, and mature neurons identified by immunostaining. GRg1 reduced abnormal animal behaviors caused by CMS, such as anhedonia and desperate behaviors, without affecting locomotor behaviors. GRg1 also reduced the number of ASC-specks, implying inhibition of inflammasome activation, which was associated with weaker activation of pro-inflammatory microglia. At the same time, GRg1 rescued impairment of hippocampal neurogenesis in vivo and in vitro , which correlated with modulation of microglial phenotypes. GRg1 exert antidepressant effects by preventing stress from activating the NLRP3 inflammasome in microglia, promoting a proneurogenic phenotype and allowing adult hippocampal neurogenesis. [Display omitted] • GRg1 inhibits microglial activation to alleviate depressive-like behaviors in mice exposed to chronic mild stress. • NLRP3 inflammasome is involved in GRg1-induced modulation of microglial phenotypes. • The pro-neurogenesis effect of GRg1 is associated with the inhibition of microglial proinflammatory profiles. [ABSTRACT FROM AUTHOR]

Bacterial leaf streak (BLS) is a destructive bacterial disease in rice (Oryza sativa L.). To date, at least 13 quantitative trait loci (QTL) conferring resistance to BLS have been identified in rice, while only one QTL, qBlsr5a, has been fine mapped and cloned. The present study focuses on fine mapping of qBlsr3d, a minor QTL conferring resistance to BLS. To fine map this QTL, 24 overlapping chromosome segment substitution lines (CSSLs) were developed from the F2 population derived from H359 × H359‐BLSR3D. Combining genotyping of molecular markers with resistant performance, qBlsr3d was delimited to an 81‐kb interval on chromosome 3, which included 12 annotated genes. Sequence alignment indicated that one of the candidate genes, LOC_Os03g03570, has three nucleotide substitutions in the CDS region between H359 and H359‐BLSR3D. In particular, LOC_Os03g03570 encodes a leucine‐rich repeat transmembrane protein, which has been reported to be associated with disease resistance, suggesting that LOC_Os03g03570 may be the target gene. Our research also suggests that CSSLs are suitable for mapping of minor QTL confering disease resistance. Furthermore, our finding has potential value in breeding rice varieties with resistance to BLS in rice. [ABSTRACT FROM AUTHOR]

The maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04 (Bst-MFA) randomly cleaves the α-1,4 glycosidic linkages of starch to produce predominantly maltopentaose and maltohexaose. The three-dimensional co-crystal structure of Bst-MFA with acarbose highlighted the stacking interactions between Trp139 and the substrate in subsites − 5 and − 6. Interactions like this are thought to play a critical role in maltopentaose/maltohexaose production. A site-directed mutagenesis approach was used to test this hypothesis. Replacement of Trp139 by alanine, leucine, or tyrosine dramatically increased maltopentaose production and reduced maltohexaose production. Oligosaccharide degradation indicated that these mutants also enhance productive binding of the substrate aglycone, leading to a high maltopentaose yield. Therefore, the aromatic stacking between Trp139 and substrate is suggested to control product specificity and the oligosaccharide cleavage pattern. [ABSTRACT FROM AUTHOR]

MicroRNAs, small non-coding RNA molecules, have gained a reputation of the most substantial regulators in gene network with the ability to down-regulate their targets. Accumulating evidence shifted insight toward microRNAs regulation as the key element of cancer initiation, development, and aggression. Recent studies have attached the importance of traditional Chinese medicine (TCM) to the treatment of various cancers, and the functional natural compounds have been considered as novel anticancer agents to directly inhibit tumor progression. In more recent decades, a wide range of biologically active components of TCM has gained increasing attention to their applications in the modulation of microRNAs. This review is on the purpose of demonstrating the significance of TCM bioactive ingredients in microRNAs regulation for cancer treatment according to the reports mainly in the recent six years, providing the evidence of efficient Chinese herbal medicine-based therapy and effective pro-diagnosis focusing on microRNAs expression of cancer patients. [ABSTRACT FROM AUTHOR]

To better understand structure-function relationships, an X-ray crystal structure of the maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04 (Bst-MFA) with bound acarbose has been determined at 2.2 Å. The structure revealed a classical three-domain fold stabilized by four calcium ions, in which CaI–CaIII form an unprecedented linear metal triad in the interior of domain B. Catalytic residues are deduced to be two aspartic acids and one glutamic acid (Asp234, Glu264, Asp331), and the acarbose is bound to surrounding amino acid residues, mainly through extensive hydrogen bonds. Furthermore, analysis of the structure indicates the existence of at least 8 subsites in Bst-MFA, six glycone sites (−6, −5, −4, −3, −2, −1) and two aglycone sites (+1, +2). Subsite +3 remains to be further explored. Sugar-binding subsites contribute to further presentation of the oligosaccharide-binding mode, which explains the product specificity of Bst-MFA to some extent. In addition, we propose a mechanism by which maltooligosaccharide-forming amylases produce particular maltooligosaccharide products, a result different from that seen with typical α-amylases. Finally, the three-dimensional structure of Bst-MFA complexed with acarbose provides the basis for further studies, designed to increase product specificity. Unlabelled Image • The structure suggests the presence of at least 8 subsites in Bst-MFA. • The oligosaccharide-binding mode explains the product specificity of Bst-MFA. • The reaction mechanism of MFAses is distinct from that of more typical α-amylases. [ABSTRACT FROM AUTHOR]

MYB genes play crucial roles in plant response to abiotic stress. However, the function of MYB genes in cotton during abiotic stress is less well elucidated. Here, we found an R2R3-type MYB gene, GhMYB44 , was induced by simulated drought (PEG6000) and ABA in three cotton varieties. After drought stress, the GhMYB44 -silenced plants showed substantial changes at the physiological level, including significantly increased malondialdehyde content and decreased SOD activity. Silencing the GhMYB44 gene increased stomatal aperture and water loss rate, reduced plant drought tolerance. Transgenic Arabidopsis thaliana over-expressed GhMYB44 (GhMYB44 -OE) enhanced resistance to mannitol-simulated osmotic stress. The stomatal aperture of the GhMYB44 -OE Arabidopsis was significantly smaller than those of the wild type (WT), and the GhMYB44 -OE Arabidopsis increased tolerance to drought stress. Transgenic Arabidopsis had higher germination rate under ABA treatment compared to WT, and the transcript levels of AtABI1 , AtPP2CA and AtHAB1 were suppressed in GhMYB44 -OE plants, indicating a potential role of GhMYB44 in the ABA signal pathway. These results showed that GhMYB44 acts as a positive regulator in plant response to drought stress, potentially useful for engineering drought-tolerant cotton. • GhMYB44 plays as a positive regulator in cotton response to drought stress. • GhMYB44 regulates stomatal aperture under drought treatment, thus enhancing the drought tolerance of cotton. • GhMYB44 regulates drought tolerance by mediating the activity of SOD and the transcription levels of PP2C genes. [ABSTRACT FROM AUTHOR]

Increased cultivar tolerance to nitrogen (N) deficiency may increase productivity and reduce environmental impact of potato crops. In this study we screened 20 cultivars for the tolerance to N-deficient (0.05 mM nitrate) in comparison with N-abundant (7.5 mM nitrate) nitrate supply using plantlets grown for 15 days in a recirculating hydroponic system. Nitrogen deficiency increased the root-to-shoot ratio in 18 cultivars. Plant total dry weight (TDW) was reduced by an average of 61% under N-deficient nitrate supply. Tolerance to N deficiency was assessed as the TDW ratio (TDWR), calculated as the ratio of TDW under N-deficient to N-abundant nitrate supply. The cultivars Norland, Raritan, Nipigon and Langlade were significantly more tolerant to nitrogen deficiency (greater TDWR) than Eramosa, Carleton, and Epicure. The results indicate that the hydroponic system has capacity to rapidly screen a large number of cultivars for tolerance to N deficiency. [ABSTRACT FROM AUTHOR]

Although accumulating evidence suggests that activated microglia are associated with deficits in neurogenesis and contribute to the physiopathology of major depressive disorder, the role of microglia in treating depression remains poorly understood. Our previous study showed that salvianolic acid (SalB) has the regulation of neuroinflammatory responses and antidepressant-like effects. Here, we hypothesized that SalB’s therapeutic effects occur because it modulates microglial phenotypes that are associated with neurogenesis. To test this hypothesis, we treated CMS-exposed C57BL/6 mice with SalB (20 mg/kg, intraperitoneally, once daily) for 3 weeks and investigated microglial phenotypic profiles and hippocampal neurogenesis. The results showed that the SalB treatment skewed M1 microglial polarization toward M2 activation in the hippocampus and cortex and remedied CMS-induced deficits in hippocampal neurogenesis. SalB (40 µM) inhibited LPS-stimulated microglial M1 activation as well as induced M2 activation in vitro , and the cultured microglia with the SalB treatment showed enhanced neural precursor cell proliferation, differentiation, and survival. SalB treatment also ameliorated the depressive-like behaviors of the CMS-treated mice in sucrose preference, forced swimming, and tail suspension tests. These findings suggest a possible antidepressive mechanism for anti-inflammatory agents that is correlated with microglial polarization and hippocampal neurogenesis and which may provide a new microglia-targeted strategy for depression therapy. [ABSTRACT FROM AUTHOR]

Bacterial antimicrobial resistance has been associated with the up regulation of genes encoding efflux pumps and the down regulation of genes encoding outer membrane proteins (OMPs). Gene expression in bacteria is primarily initiated by sigma factors (σ factors) such as RpoE, which plays an important role in responding to many environmental stresses. Here, we report the first observation that RpoE serves as an antibiotic resistance regulator in Salmonella enteric serovar Typhi ( S. Typhi). In this study, we found that the rpoE mutant (Δ rpoE) of S. Typhi GIFU10007 has elevated resistance to several antimicrobial agents, including β-lactams, quinolones, and aminoglycosides. Genomic DNA microarray analysis was used to investigate the differential gene expression profiles between a wild type and rpoE mutant in response to ampicillin. The results showed that a total of 57 genes displayed differential expression (two-fold increase or decrease) in Δ rpoE versus the wild-type strain. The expressions of two outer membrane protein genes, ompF and ompC, were significantly down-regulated in Δ rpoE (six and seven-fold lower in comparison to wild-type strain) and RamA, a member of the efflux pump AraC/XylS family, was up-regulated about four-fold in the Δ rpoE. Our results suggest RpoE is a potential antimicrobial regulator in S. Typhi, controlling both the down regulation of the OMP genes and up-regulating the efflux system. [ABSTRACT FROM AUTHOR]

Bacterial leaf steak (BLS) is one of the most destructive diseases in rice. Studies have shown that BLS resistance in rice is quantitatively inherited, controlled by multiple quantitative trait loci (QTLs). A QTL with relatively large effect, qBlsr5a, was previously mapped in a region of ∼380 kb on chromosome 5. To fine map qBlsr5a further, a set of overlapping sub-chromosome segment substitution lines (sub-CSSLs) were developed from a large secondary F2 population (containing more than 7000 plants), in which only the chromosomal region harboring qBlsr5a was segregated. By genotyping the sub-CSSLs with molecular markers covering the target region and phenotyping the sub-CSSLs with artificial inoculation, qBlsr5a was delimited to a 30.0-kb interval, in which only three genes were predicted. qRT-PCR analysis indicated that the three putative genes did not show significant response to the infection of BLS pathogen in both resistant and susceptible parental lines. However, two nucleotide substitutions were found in the coding sequence of gene LOC_Os05g01710, which encodes the gamma chain of transcription initiation factor IIA (TFIIAγ). The nucleotide substitutions resulted in a change of the 39th amino acid from valine (in the susceptible parent) to glutamic acid (in the resistant parent). Interestingly, the resistant parent allele of LOC_Os05g01710 is identical to xa5, a major gene resistant to bacterial leaf blight (another bacterial disease of rice). These results suggest that LOC_Os05g01710 is very possibly the candidate gene of qBlsr5a. [ABSTRACT FROM AUTHOR]

Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2. [Display omitted] [ABSTRACT FROM AUTHOR]

• The thermostable α-amylases can be obtained by building salt bridges. • The distribution, configuration and location of salt bridges vary in different amylases. • Appropriate salt bridges play crucial roles in both amylase stability and enzymatic function. The α-amylases are the most widely used industrial enzymes, and are particularly useful as liquifying enzymes in industrial processes based upon starch. Since starch liquefication is carried out at evaluated temperatures, typically above 60 °C, there is substantial demand for thermostable α -amylases. Most naturally occurring α -amylases exhibit moderate thermostability, so substantial effort has been invested in attempts to increase their thermostability. One structural feature that has the potential to increase protein thermostability is the introduction of salt bridges. However, not every salt bridge contributes to protein thermostability. The salt bridges in amylases have their characteristics in terms of distribution, configuration and location. The summary of these features helps to introduce new salt bridges based on the characteristics. This review focuses on salt bridges of α-amylases, both naturally present and introduced using mutagenesis. Its aim is to provide a bird's eye view of distribution, configuration, location of desirable salt bridges. [ABSTRACT FROM AUTHOR]

• Continuous AAC induces left ventricular remodeling by affecting multiple pathways, leading to chronic heart failure. • AWA alleviates left ventricular remodeling, including inhibition of myocardial hypertrophy, fibrosis, and cardiomyocyte apoptosis. • AWA alleviates chronic heart failure by promoting calcium ion balance in myocardial cells by decreasing the expression of RyR2 and SERCA2a. Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics. Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure. AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and β-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a. AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a. [ABSTRACT FROM AUTHOR]

Bacterial leaf steak (BLS) caused by Xanthomonas oryzae pv. oryzicola (Xoc) is a devastating disease in rice production. The resistance to BLS in rice is a quantitatively inherited trait, of which the molecular mechanism is still unclear. It has been proved that xa5, a recessive bacterial blast resistance gene, is the most possible candidate gene of the QTL qBlsr5a for BLS resistance. To study the molecular mechanism of xa5 function in BLS resistance, we created transgenic lines with RNAi of Xa5 (LOC_Os05g01710) and used RNA-seq to analyze the transcriptomes of a Xa5-RNAi line and the wild-type line at 9 h after inoculation with Xoc, with the mock inoculation as control. We found that Xa5-RNAi could (1) increase the resistance to BLS as expected from xa5; (2) alter (mainly up-regulate) the expression of hundreds of genes, most of which were related to disease resistance; and (3) greatly enhance the response of thousands of genes to Xoc infection, especially of the genes involved in cell death pathways. The results suggest that xa5 is the cause of BLS-resistance of QTL qBlsr5a and it displays BLS resistance effect probably mainly because of the enhanced response of the cell death-related genes to Xoc infection. [ABSTRACT FROM AUTHOR]

Objectives: Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. Methods: Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. Key findings: In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1β, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. Conclusions: FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis. [ABSTRACT FROM AUTHOR]

Background: Anti-inflammatory approaches are emerging as a new strategy for the treatment of depressive disorders. Ginsenoside Rb1 (GRb1), a major component of Panax ginseng, can inhibit inflammatory cascade and alleviate depressive-like behaviors. Microglia can promote or inhibit adult hippocampal neurogenesis according to their functional phenotypes. Here, we examine whether GRb1 may exert antidepressant effects by promoting a pro-neurogenic phenotype of microglia and thereby increasing neurogenesis.Methods: The antidepressant effects of GRb1 or the licensed antidepressant imipramine (IMI) were assessed in chronic mild stress (CMS)-exposed male mice. The depressive-like behaviors of mice were evaluated by sucrose preference test, forced swimming test (FST), and tail suspension test (TST). The microglial phenotypes were identified by pro- and anti-inflammatory cytokine expression and morphological properties, analyzed by RT-qPCR, western blotting, and immunofluorescence staining. The effect of GRb1-treated microglia on adult hippocampal neurogenesis in vivo and in vitro was detected using immunofluorescence staining.Results: Behavioral assessment indicated that GRb1 or IMI treatment alleviated depressive-like behaviors in CMS-exposed mice. Immunofluorescence examination demonstrated that GRb1 induced a pro-neurogenic phenotype of microglia via activating PPARγ in vivo and in vitro, which were effectively reversed by the PPARγ inhibitor GW9662. In addition, GRb1-treated microglia increased the proliferation and differentiation of neural precursor cells.Conclusions: These findings demonstrated that GRb1 alleviated depressive-like behaviors of CMS-exposed male mice mainly through PPARγ-mediated microglial activation and improvement of adult hippocampus neurogenesis. [ABSTRACT FROM AUTHOR]

The organ shortage crisis affects most of the world today. In Asia, rates of deceased organ donation are extremely low due to sociocultural factors. In this context, implementing new organ donation policies is not enough; xenotransplantation remains the most promising way to solve the organ crisis. Most of the early research on xenotransplantation was conducted in the US and Europe. Today, however, Asia has caught up on its Western counterparts partly due to the increasing demand for organ transplants. Given the growing influence of countries such as China, South Korea, and Japan in xenotransplantation, this article provides the reader with an essential global understanding of the scientific and ethical issues currently at stake. Furthermore, it sheds light on the beliefs and values that shape the response of the Asian public to both organ donation and xenotransplantation. [ABSTRACT FROM AUTHOR]

Background: Alcohol dehydrogenases (ADHs) are the crucial enzymes that can convert ethanol into acetaldehyde. In tobacco, members of ADH gene family are involved in various stresses tolerance reactions, lipid metabolism and pathways related to plant development. It will be of great application significance to analyze the ADH gene family and expression profile under various stresses in tobacco. Results: A total of 53 ADH genes were identified in tobacco (Nicotiana tabacum L.) genome and were grouped into 6 subfamilies based on phylogenetic analysis. Gene structure (exon/intron) and protein motifs were highly conserved among the NtADH genes, especially the members within the same subfamily. A total of 5 gene pairs of tandem duplication, and 3 gene pairs of segmental duplication were identified based on the analysis of gene duplication events. Cis-regulatory elements of the NtADH promoters participated in cell development, plant hormones, environmental stress, and light responsiveness. The analysis of expression profile showed that NtADH genes were widely expressed in topping stress and leaf senescence. However, the expression patterns of different members appeared to be diverse. The qRT-PCR analysis of 13 NtADH genes displayed their differential expression pattern in response to the bacterial pathogen Ralstonia solanacearum L. infection. Metabolomics analysis revealed that NtADH genes were primarily associated with carbohydrate metabolism, and moreover, four NtADH genes (NtADH20/24/48/51) were notably involved in the pathway of alpha-linolenic acid metabolism which related to the up-regulation of 9-hydroxy-12-oxo-10(E), 15(Z)-octadecadienoic acid and 9-hydroxy-12-oxo-15(Z)-octadecenoic acid. Conclusion: The genome-wide identification, evolutionary analysis, expression profiling, and exploration of related metabolites and metabolic pathways associated with NtADH genes have yielded valuable insights into the roles of these genes in response to various stresses. Our results could provide a basis for functional analysis of NtADH gene family under stressful conditions. [ABSTRACT FROM AUTHOR]

Objectives: Safflower is a traditional Chinese medicine for the treatment of gynecological diseases and its flavonoids have potential anti-inflammatory effects. The purpose is to explore the possible effects of safflower total flavonoids (STF) on lipopolysaccharide (LPS)-induced inflammatory damage of Ishikawa cells. Method: In this study, LPS-induced endometrial carcinoma Ishikawa cells were used to establish an inflammatory injury model. The effective concentration of STF was screened by CCK-8 and enzyme-linked immunosorbent assay. The apoptosis of damaged Ishikawa cells was detected by flow cytometry. The contents of caspase11 and caspase 3 in Ishikawa cells were observed by fluorescence imaging. Western blot and RT-qPCR were used to detect the expression of related proteins and mRNA in damaged Ishikawa cells, and the possible mechanism of safflower flavonoids against LPS-induced endometrial carcinoma Ishikawa cells was analyzed by cell transcriptomics. Key findings: The STF-reduced tumor necrosis factor α, interleukin-1β, and interleukin-6 expression level; the expression level of the proteins ASK1, Caspase3, and Caspase11 was also significantly decreased, and the proteins ERα, p-PI3K, and p-AKT were significantly increased. The transcriptome results showed that the PI3K-Akt signal pathway may be the main signal pathway for the STF. Conclusion: The STF could regulate the PI3K/AKT signal pathway to treat the inflammatory injury of Ishikawa cells. [ABSTRACT FROM AUTHOR]

• Two non-reducing-end loop structures concern substrate orientation. • The loops accompanied MFA ps substrate-binding mode and product specificity. • Structural and action-mode differences among α-amylases support this proposal. The maltooligosaccharide-forming amylases (MFAses) degrade starch into maltooligosaccharides which potentially benefit human diet and grow popular in food processing, but little has been studied about their product specificity and structures. We focused on this topic and provide evidence through an X-ray crystal structure of the maltotetraose (G4)-forming amylase from Pseudomonas saccharophila STB07 (MFA ps), as well as co-crystal structures of MFA ps with G4 and with pseudo-maltoheptaose (pseudo-G7) determined at up to 1.1 Å resolution. G4 and pseudo-G7 occupy active cleft subsites −4 to −1 and −4 to +3 respectively. Binding induces conformational changes in the active sites except Asp193, working as the base catalyst. Comparison of the MFA ps structure with those of other α-amylases revealed obvious differences in the loop structures providing dominant interactions between protein and substrate in the non-reducing side of the active sites cleft. These structures at the non-reducing end may govern the G4 specificity of MFA ps and also be relevant to its exo -type action pattern. [ABSTRACT FROM AUTHOR]

Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields. We found that PA maybe was a low toxic drug that was acquired numerously through vegetable oil isolation and chemical synthesis and its stability and low water dissolution were improved in pharmaceutics. It also possessed specific pharmacokinetic characteristics, such as two-compartment open model, first-order kinetic elimination, and certain biometabolism and biotransformation process, and was shown to have multiple biological activities, that is, immunomodulatory, anti-inflammatory, antioxidative, antitumor, antimicrobial, insecticidal, antiatherogenic, antiemetic, whitening, and sedative activity. However, the systematic evaluations of preparation, pharmaceutics, toxicology, pharmacokinetics, and bioactivities underlying molecular mechanisms of action also required further investigation prior to practices of PA in clinic. [ABSTRACT FROM AUTHOR]

High-density genetic maps can significantly improve the resolution of QTL mapping. We constructed a high-density recombination bin-based genetic map of eggplant based on 200 F2 plants from an interspecific cross (Solanum melongena × S. incanum) using the whole genome resequencing strategy. The map was 2022.8 cM long, covering near 99% of the eggplant genome. The map contained 3776 bins, with 3644 (96.5%) being effective (position non-redundant) ones, giving a nominal average distance of 0.54 cM and an effective average distance of 0.56 cM between adjacent bins, respectively. Using this map and 172 F2:3 lines, a major QTL with pleiotropic effects on two anthocyanin pigmentation-related traits, leaf vein color (LVC) and fruit pericarp color (FPC), was steadily detected in a bin interval of 2.28 cM (or 1.68 Mb) on chromosome E10 in two cropping seasons, explaining ~65% and 55% of the phenotypic variation in LVC and FPC, respectively. Genome-wide association analysis in this population validated the QTL and demonstrated the correctness of mapping two bins of chromosome E02 onto E10. Bioinformatics analysis suggested that a WDR protein gene inside the bin interval with reliable effective variation between the two parents could be a possible candidate gene of the QTL. [ABSTRACT FROM AUTHOR]

Background. Safflower is an annual herb used in traditional Chinese herbal medicine. It consists of the dried flowers of the Compositae plant safflower. It is found in the central inland areas of Asia and is widely cultivated throughout the country. Its resistance to cold weather and droughts and its tolerance and adaptability to salts and alkalis are strong. Safflower has the effect of activating blood circulation, dispersing blood stasis, and relieving pain. A natural pigment named safflower yellow (SY) can be extracted from safflower petals. Chemically, SY is a water-soluble flavonoid and the main active ingredient of safflower. The main chemical constituents, pharmacological properties, and clinical applications of SY are reviewed in this paper, thereby providing a reference for the use of safflower in preventing and treating human diseases. Methods. The literature published in recent years was reviewed, and the main chemical components of SY were identified based on chemical formula and structure. The pharmacological properties of hydroxysafflor yellow A (HSYA), SYA, SYB, and anhydrosafflor yellow B (AHSYB) were reviewed. Results. The main chemical constituents of SY included HSYA, SYA, SYB, and AHSYB. These ingredients have a wide range of pharmacological activities. SY has protective effects on the heart, kidneys, liver, nerves, lungs, and brain. Moreover, its effects include, but are not limited to, improving cardiovascular and cerebrovascular diseases, abirritation, regulating lipids, and treating cancer and diabetic complications. HSYA is widely recognised as an effective ingredient to treat cardiovascular and cerebrovascular diseases. Conclusion. SY has a wide range of pharmacological activities, among which improving cardiovascular and cerebrovascular diseases are the most significant. [ABSTRACT FROM AUTHOR]

Background: The R2R3-MYB transcription factor is one of the largest gene families in plants and involved in the regulation of plant development, hormone signal transduction, biotic and abiotic stresses. Tobacco is one of the most important model plants. Therefore, it will be of great significance to investigate the R2R3-MYB gene family and their expression patterns under abiotic stress and senescence in tobacco. Results: A total of 174 R2R3-MYB genes were identified from tobacco (Nicotiana tabacum L.) genome and were divided into 24 subgroups based on phylogenetic analysis. Gene structure (exon/intron) and protein motifs were especially conserved among the NtR2R3-MYB genes, especially members within the same subgroup. The NtR2R3-MYB genes were distributed on 24 tobacco chromosomes. Analysis of gene duplication events obtained 3 pairs of tandem duplication genes and 62 pairs of segmental duplication genes, suggesting that segmental duplications is the major pattern for R2R3-MYB gene family expansion in tobacco. Cis-regulatory elements of the NtR2R3-MYB promoters were involved in cellular development, phytohormones, environmental stress and photoresponsive. Expression profile analysis showed that NtR2R3-MYB genes were widely expressed in different maturity tobacco leaves, and however, the expression patterns of different members appeared to be diverse. The qRT-PCR analysis of 15 NtR2R3-MYBs confirmed their differential expression under different abiotic stresses (cold, salt and drought), and notably, NtMYB46 was significantly up-regulated under three treatments. Conclusions: In summary, a genome-wide identification, evolutionary and expression analysis of R2R3-MYB gene family in tobacco were conducted. Our results provided a solid foundation for further biological functional study of NtR2R3-MYB genes in tobacco. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The leaf of Malus toringoides (Rehd.) Hughes is a traditional folk medicine in Tibet, China, which is called “E Se” in Tibetan language. This original plant grows on snow mountains at an attitude of 3000 to 3700m. It is primarily used to treat hypertension, hyperlipidemia, hyperglycemia, indigestion and other diseases. This study aimed to evaluate the antidiabetic effect of flavonoids extracted from E Se (ESF) and to explore the potential mechanism in streptozotocin (STZ) or alloxan (ALX) induced diabetic mice and STZ-induced diabetic rats. Materials and methods: 72h after the establishment of a diabetic model, STZ or ALX induced diabetic mice and STZ-induced diabetic rats were treated daily with ESF at doses of 45, 90, 180mg/kg and 37.5, 75, 150mg/kg, respectively. Both mice and rats were fasted for 5h before administration and the blood glucose (BG) levels were tested 1h after treatment. Body weight was determined every other day. For STZ-induced rats, glycosylated hemoglobin (Hb1Ac), serum insulin and c-peptide, hepatic glycogen, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in liver were assessed on the fourth day after BG level detection. Results: Compared with the model group, the general behavior of mice treated with ESF (90, 180mg/kg) and rats treated with ESF (75, 150mg/kg) became better and BG levels were significantly reduced (P<0.05). Significant decrease (P<0.05) in Hb1Ac level was observed in ESF-treated rats compared with diabetic rats. Significant increase (P<0.05 ) in serum insulin and c-peptide were detected in ESF-treated rats. The treatment also significantly (P<0.05) elevated SOD activity and reduced MDA level in the liver of diabetic rats. Besides, ESF 150mg/kg had a trend of rising hepatic glycogen content of diabetic rats. Conclusions: The findings of this study suggest that flavonoids from the Malus toringoides (Rehd.) Hughes leaves may possess an antidiabetic activity in animals with established diabetes. [Copyright &y& Elsevier]

Tea is a worldwide popular drink with high nutritional and medicinal values as it is rich in nutrients, such as polyphenols, amino acids, vitamins, glycosides, and so on. Among them, tea polyphenols (TPs) are the current research hotspot. TPs are known to have multiple biological activities such as anti‐oxidation, anti‐tumor, anti‐inflammation, anti‐bacteria, lowering lipid, and liver protection. By reviewing a large number of literatures, we explained the mechanism of TPs exerting biological activity and a wide range of applications. We also discussed the deficiencies and development potential of TPs, in order to provide theoretical reference and scientific basis for the subsequent development and utilization of TPs. Practical applications: We summarized the bioactivity mechanisms of TPs in anti‐tumor, anti‐oxidation, antibacterial, anti‐inflammatory, lipid‐lowering, and liver protection, focused on its application fields in food and medicine, and discussed the deficiency and development potential of current research on TPs, so as to provide a certain convenient way for scholars studying TPs. It is expected to contribute to the subsequent discovery of biological activity and the broadening of the field of TPs. [ABSTRACT FROM AUTHOR]

The efficiency of enzymatic cyclodextrin production using cyclodextrin glycosyltransferases (CGTases) is limited by product inhibition. In this study, maltose binding site 2 (MBS2) of the β-CGTase from Bacillus circulans STB01 was modified to decrease product inhibition. First, two point mutants were prepared at position 599 (A599V and A599N). Then, two double mutants incorporating alanine at position 633 (A599N/Y633A and A599V/Y633A) were prepared. Finally, the entire MBS2 region was replaced by that of the α-CGTase from Paenibacillus macerans JFB05-01 to form multipoint mutant MBS2 β → α. All five mutants exhibited mixed-type product inhibition, although both the competitive and uncompetitive components of this inhibition were decreased. The total cyclization activities of A599N, A599V and A599V/Y633A were 15.6%, 76.8% and 70.9% lower than that of the wild-type, respectively, while that of A599N/Y633A was 22.4% higher. Among the mutants, only MBS2 β → α showed catalytic efficiency (k cat / K m) comparable with that of the wild-type. Moreover, A599N, A599N/Y633A and MBS2 β → α produced cyclodextrin yields 13.1%, 15.8% and 19.7% greater than that of the wild-type, respectively. These results suggest that A599N, A599N/Y633A and MBS2 β → α may be more suitable than the wild-type for cyclodextrin production. [ABSTRACT FROM AUTHOR]

(D,E) Percentages of the number of cells located on the lower side of chambers and Matrigel-coated chambers in the presence of ISL with miR-374a interference. (B) Chamber migration and invasion assay analysis of the effect of miR-374a transfection on breast cancer motile ability with ISL interference. [Extracted from the article]

• Maternal sleep deprivation (MSD) in late gestation impairs learning and memory in rat pups. • MSD down-regulates PPARγ in hippocampus of rat pups. • PPARγ activation by pioglitazone mitigates MSD-induced cognitive deficits. • Pioglitazone switches hippocampal microglia to an M2 phenotype and stimulates neurogenesis. Maternal sleep disturbance in pregnancy causes cognitive impairments and emotional disorders in offspring. Microglia-mediated inflammatory processes contribute to prenatal stress-induced neurodevelopmental deficits. Peroxisome proliferator-activated receptor gamma (PPARγ) activation underlies the switching of microglial activation phenotypes, which has emerged as a pharmacological target for regulating neuroinflammatory responses in the treatment of neuropsychiatric disorders. Here we investigated the effects of PPARγ-dependent microglial activation on neurogenesis and cognitive behavioral outcomes in male rat offspring exposed to maternal sleep deprivation (MSD) for 72 h from days 18–21 of pregnancy. In the Morris water maze test, male MSD rat offspring needed more time than control offspring to escape to the hidden platform and spent less time in the target quadrant when the hidden platform was removed. In MSD rat offspring, microglial density as determined by immunofluorescence was higher, microglia showed fewer and shorter processes, and neurogenesis in the hippocampus was significantly reduced. Levels of mRNA encoding pro-inflammatory markers IL-6, TNFα, and IL-1β were higher in male MSD offspring, whereas levels of anti-inflammatory markers Arg1, IL-4, and IL-10 were lower, as was PPARγ expression in the hippocampus. PPARγ activation by pioglitazone (30 mg/kg/day, i.p., 7 d) mitigated these negative effects of MSD, rescuing hippocampal neurogenesis and improving cognitive function. The PPARγ inhibitor GW9662 (1 mg/kg/day, i.p., 7 d) eliminated the effects of pioglitazone. Conditioned medium from pioglitazone-treated microglia promoted proliferation and differentiation of neural progenitor cells. These results suggest that MSD-induced deficits in spatial learning and memory can be ameliorated through PPARγ-dependent modulation of microglial phenotypes. [ABSTRACT FROM AUTHOR]

• The risk ingredients in TCM-induced liver injury are classified. • The hepatotoxic mechanisms of the risk components in TCM-induced liver damage are summarized. • The potential targets for the risk components in TCM-induced hepatotoxicity are generalized. Traditional Chinese medicine (TCM) has become a crucial cause of drug-induced liver injury (DILI). Differ from chemical medicines, TCM feature more complex and mostly indefinite components. This review aimed to clarify the classification, underlying mechanisms and targets of the risk components in TCM-induced liver injury to further guide the secure application of TCM. Relevant studies or articles published on the PubMed database from January 2008 to December 2019 were searched. Based on the different chemical structures of the risk ingredients in TCM, they are divided into alkaloids, glycosides, toxic proteins, terpenoids and lactones, anthraquinones, and heavy metals. According to whether drug metabolism is activated or hepatocytes are directly attacked during TCM-induced liver injury, the high-risk substances can be classified into metabolic activation, non-metabolic activation, and mixed types. Mechanisms of the hepatotoxic ingredients in TCM-induced hepatotoxicity, including cytochrome P450 (CYP450) induction, mitochondrial dysfunction, oxidative damage, apoptosis, and idiosyncratic reaction, were also summarized. The targets involved in the risk ingredient-induced hepatocellular injury mainly include metabolic enzymes, nuclear receptors, transporters, and signaling pathways. Our periodic review and summary on the risk signals of TCM-induced liver injury must be beneficial to the integrated analysis on the multi-component, multi-target, and multi-effect characteristics of TCM-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Safflower is a traditional Chinese medicine used for treating gynaecological diseases. However, its material basis and mechanism of action in the treatment of endometritis induced by incomplete abortion are still unclear. This study aimed to reveal the material basis and mechanism of action of safflower in the treatment of endometritis induced by incomplete abortion through comprehensive methods, including network pharmacology and 16S rDNA sequencing. Network pharmacology and molecular docking methods were used to screen the main active components and potential mechanisms of action of safflower in the treatment of endometritis induced by incomplete abortion in rats. A rat model of endometrial inflammation by incomplete abortion was established. The rats were treated with safflower total flavonoids (STF) based on forecasting results, serum levels of inflammatory cytokines were analysed, and immunohistochemistry, Western blots, and 16S rDNA sequencing were performed to investigate the effects of the active ingredient and the treatment mechanism. The network pharmacology prediction results showed 20 active components with 260 targets in safflower, 1007 targets related to endometritis caused by incomplete abortion, and 114 drug-disease intersecting targets, including TNF, IL6, TP53, AKT1, JUN, VEGFA, CASP3 and other core targets, PI3K/AKT, MAPK and other signalling pathways may be closely related to incomplete abortion leading to endometritis. The animal experiment results showed that STF could significantly repair uterine damage and reduce the amount of bleeding. Compared with the model group, STF significantly down-regulated the levels of pro-inflammatory factors (IL-6, IL-1β, NO, TNF-α) and the expression of JNK, ASK1, Bax, caspase3, and caspase11 proteins. At the same time, the levels of anti-inflammatory factors (TGF-β and PGE2) and the protein expression of ERα, PI3K, AKT, and Bcl2 were up-regulated. Significant differences in the intestinal flora were seen between the normal group and the model group, and the intestinal flora of the rats was closer to the normal group after the administration of STF. The characteristics of STF used in the treatment of endometritis induced by incomplete abortion were multi-targeted and involved multiple pathways. The mechanism may be related to the activation of the ERα/PI3K/AKT signalling pathway by regulating the composition and ratio of the gut microbiota. [Display omitted] [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) affects people's quality of life because of its high incidence rate and mortality. The Xianglian Pill (XLP) is a traditional Chinese medicine (TCM) prescription used to treat gastrointestinal (GI） diseases. Its anti-tumor effect has been found in recent years, but it's bioactive compounds and mechanism of action in treating GC are remain unknown. This study reveals the bioactive compounds and mechanisms of XLP in the treatment of GC through network pharmacology analysis and experimental verification. The main compounds in XLP were searched and the active compounds with anti-GC activity were selected. Compounds targets and GC- related targets were predicted, and common targets were obtained. Subsequently, a protein-protein interaction (PPI) network of common targets is constructed, while GO and KEGG enrichment analyses were performed on common targets. Finally, the anti-GC effects of active compounds in XLP were verified in GC cell lines MGC-803 and HGC-27 by wound healing assay, cell cycle assay, cell apoptosis assay and western blotting (WB) assay. A total of 33 active compounds of XLP were obtained. MTT assay showed that dehydrocostus lactone (DHL) and berberrubine (BRB) had lower IC 50 value in GC cells HGC-27 and MGC-803, and has a less inhibitory effect on normal gastric epithelial cells. Further, 73 common targets were obtained after the total target of DHL and BRB intersected with GC. Among them, CASP3, AKT1, SRC, STAT3,and CASP9 were the most associated genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vitro experiment revealed that DHL and BRB inhibited GC cell viability via inducing cell cycle arrest at G2/M phase, and promoting cell apoptosis by up-regulating the caspase3 expression and down-regulating the expression of Bcl2/Bax. DHL and BRB are the two main anti-GC active compounds in XLP, and their mechanism is mainly to inhibit cell cycle and promote cell apoptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Mangiferin (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) is a bioactive ingredient predominantly isolated from the mango tree, with potent antioxidant activity and multifactorial pharmacological effects, including antidiabetic, antitumor, lipometabolism regulating, cardioprotective, anti-hyperuricemic, neuroprotective, antioxidant, anti-inflammatory, antipyretic, analgesic, antibacterial, antiviral and immunomodulatory effects. Therefore, it possesses several health-endorsing properties and is a promising candidate for further research and development. However, low solubility, mucosal permeability and bioavailability restrict the development of mangiferin as a clinical therapeutic, and chemical and physical modification is required to expand its application. This review comprehensively analyzed and collectively summarized the primary pharmacological actions of mangiferin that have been demonstrated in the literature, to support the potential future development of mangiferin as a novel therapeutic drug. [ABSTRACT FROM AUTHOR]

Glume split (GS) refers to the phenomenon that the lemma and palea of a rice seed cannot be fully closed. There is a kind of GS that occurs only under male sterility. Such male sterility‐conditioned GS (mscGS) can severely reduce the quality of hybrid rice seeds and therefore is a serious problem in hybrid rice production. To reveal the genetic basis of mscGS, we employed the method of bulked segregant analysis combined with deep sequencing to map quantitative trait loci (QTLs) conferring mscGS. By analysing a pair of opposite DNA pools made up of 50 extreme individuals each from an F2 population of 509 individuals, we mapped two major QTLs on the long arm terminals of chromosomes 5 and 6, respectively. We named them qmscGS5 and qmscGS6. The two QTLs both function mainly in additive mode, explaining a heritability of 16.98% and 11.96% by their additive effects, respectively. The information obtained in this study will facilitate marker‐assisted breeding of low‐GS male‐sterile lines and positional cloning of genes controlling mscGS in rice. [ABSTRACT FROM AUTHOR]

Erianin, a natural bibenzyl compound, is present in Dendrobium chrysotoxum Lindl. (commonly known as Shihu in China), which is used as an antipyretic and analgesic in traditional Chinese medicine, and has been reported to exert inhibitory effects on cancer cells in vitro. Cervical cancer is the third‑most common cancer in women worldwide, and has the highest morbidity rate of gynecological malignancies. Thus, the identification of effective chemotherapeutical agents to treat this disease is urgent. The aim of the present study was to elucidate the biological functions and molecular mechanism of erianin on HeLa cells. Cellular proliferation was assessed using an MTT assay and flow cytometry assay with propidium iodide (PI) staining. Apoptosis rates were observed using a high content screening system via annexin V‑fluorescein isothiocyanate/PI double staining, and measured by flow cytometry. The protein levels of tumor protein p53, extracellular signal‑regulated kinase 1/2 (ERK1/2), caspase‑3, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2‑associated X (Bax) were assessed by western blot analysis. Erianin inhibited the growth of HeLa cells and induced apoptosis in a dose‑ and time‑dependent manner, inducing cell cycle arrest at the G2/M stage. Erianin treatment also increased the expression of Bax and caspase‑3, but decreased levels of Bcl‑2 and phosphorylated‑ERK1/ 2. Cells treated with paclitaxel were regarded as the positive group. Together, the results of the present study indicated that erianin could be considered as an effective drug candidate; in HeLa cells it inhibited cellular proliferation and promoted apoptosis via regulation of the ERK1/2 signaling and mitochondrial‑based apoptosis pathways. Thus, erianin has the promise to be developed further for cervical cancer therapy. [ABSTRACT FROM AUTHOR]

RamA, a global transcriptional activator, belongs to the AraC/XylS family of regulatory proteins and can regulate multidrug resistance through activating the expression of AcrAB. In Salmonella spp., Klebsiella pneumonia, Enterobacter cloacae and Enterobacter aerogenes , RamR represses the transcription of gene ramA through binding to the upstream sequences of ramA . In this study, we found that the locus and transcription directions of ramA - ramR in S. Typhi GIFU10007 are different from that in S. Typhimurium (SL1344). To study the role of RamR involved in regulation of ramA in S. Typhi, we constructed ramA over-expression strain and ramR deletion mutant, and detected the expression level of ramA, and measured the growth curve of these strain in the presence of ampicillin. The results showed that RamR in S. Typhi neither repressed the expression of ramA , nor affected the bacterial resistance to ampicillin. In summary, RamR is not the repressor of RamA in S. Typhi, which is different from its role in other bacteria, such as S . Typhimurium and K. pneumoniae . [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of isoliquiritigenin were explored. The results proved that isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by isoliquiritigenin treatment in breast cancer. Further study displayed that isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies. [ABSTRACT FROM AUTHOR]

The effects of temperature on extracellular secretion of the α-cyclodextrin glucosyltransferase (α-CGTase) from Paenibacillus macerans JFB05-01 by Escherichia coli were investigated. When protein expression was induced at constant temperature, the greatest amount of extracellular recombinant α-CGTase was produced at 25 °C. Higher or lower induction temperatures were not conducive to extracellular secretion of recombinant α-CGTase. To enhance extracellular secretion of α-CGTase by E. coli, a two-stage temperature control strategy was adopted. When expression was induced at 25 °C for 32 h, and then the temperature was shifted to 30 °C, the extracellular α-CGTase activity at 90 h was 45% higher than that observed when induction was performed at a constant temperature of 25 °C. Further experiments suggested that raising the induction temperature can benefit the transport of recombinant enzyme and compensate for the decreased rate of recombinant enzyme synthesis during the later stage of expression. This report provides a new method of optimizing the secretory expression of recombinant enzymes by E. coli. [ABSTRACT FROM AUTHOR]

• The branched structure of short-clustered maltodextrin (SCMD) was observed. • SCMD-protecting yeast had more integral microstructures and higher viability. • The cell membrane fluidity of SCMD-protecting yeast was enhanced. • Protected yeast had a higher relative abundance of unsaturated glycerophospholipid. • SCMD existence promoted the mobility of lipid bilayer at 250 K. Cryoprotective polysaccharides have been extensively explored. We found that short-clustered maltodextrin (SCMD) effectively increased yeast viability. But the specific mechanism of SCMD affecting yeast is still not clear. Here, we detailedly analyze the effects of SCMD addition on cell membrane homeostasis. Firstly, the high-branched structure of SCMD was observed, and the microstructure of SCMD-protecting yeast was more integral. Analysis of membrane physicochemical property and glycerophospholipid metabolism demonstrated the fluidity of cell membrane of SCMD-protecting yeast was enhanced, as the relative abundances of glycerophospholipids with unsaturated acyl chains increased in comparison to Control yeast. Further, molecular dynamics simulations found that simplified SCMD could form more H-bonds with water molecules around lipid bilayers at 250 K to promote the mobility of lipid bilayers. Therefore, the hypothesis of "SCMD existence promotes the membrane fluidity under ice-crystal stress during frozen storage and helps maintain cell membrane homeostasis after thawing, increasing the thawed yeast viability" is proposed. [ABSTRACT FROM AUTHOR]

Phyllanthus reticulatus (Euphorbiaceae) is a medicinal plant that has been used in Zhuang medicine since ancient times. Traditionally, it has the effect of removing toxins and detumescence and can be used to treat hepatitis in China and India. Our previous studies have proved that the ethyl acetate extract of its leaves (PRPE) has an anti-hepatoma effect. To predict targets of an ethyl acetate extract of Phyllanthus reticulatus leaves (PRPE) in hepatoma treatment via network pharmacology and verify the predictions in a mouse model of liver cancer. Chemical constituents and therapeutic targets of P. reticulatus (PRP) were searched and predicted via public databases. A protein-protein interaction network comprising common targets was constructed, and the key gene targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for biological function and pathway enrichment analyses. The effects of PRP on BEL-7404 and HepG 2 cells were determined by MTT assay, apoptosis was measured by flow cytometry and hoechst44432/PI. And a nude mouse xenograft model was established to verify the anti-tumour effect in vivo. The histopathology of tumours was observed by staining with haematoxylin and eosin (H&E). Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine the gene and protein expression levels of phosphoinositide 3-kinase (PI3K), Akt1, p53, caspase-3, Bcl-2 and Bax, respectively. Twenty-seven chemical components and 567 potential therapeutic targets of PRP were identified. GO analysis indicated that these targets are mainly associated with peptidyl-tyrosine phosphorylation and steroid metabolic process. KEGG analysis showed that the targets are mainly located in the PI3K/Akt, apoptosis, mitogen-activated protein kinase (MAPK), Ras and vascular endothelial growth factor (VEGF) signalling pathways. According to the p -adjust value, the PI3K/Akt pathway is the core pathway. In vitro, PRPE could inhibit proliferation and induce apoptosis in hepatoma cells. IC 50 values of PRPE were 2.48 and 6.34 mg/mL for BEL-7404 and hepG 2 cells, respectively. PRPE significantly reduced tumour volume and weight. H&E results showed that PRPE repaired necrotic areas in hepatoma cells. PRPE reduced the protein expression of PI3K, Akt1 and Bcl-2 and increased the protein expression of p53 and Bax. Meanwhile, PRPE reduced the mRNA expression of PI3K, AKT1 and BCL 2 and increased the mRNA expression of TP53, CASP3 and BAX. The targets of PRPE are the PI3K/Akt, apoptosis, MAPK, Ras and VEGF signalling pathways. Passing through the PI3K/Akt pathway to induce apoptosis is the main mechanism of PRPE. [Display omitted] • The targets of PRP are mainly located in the PI3K/Akt and apoptosis signalling pathways. • PRPE could induce apoptosis in hepatoma cells. • PRPE reduced the protein expression of PI3K, Akt1 and Bcl-2 and increased the protein expression of p53 and Bax. [ABSTRACT FROM AUTHOR]

The immune costimulatory molecule B7-H3 has been shown to be involved in the regulation of murine bone formation. However, the role of B7-H3 in bone metabolic diseases remains unknown. In our study, matrix metalloproteinase 2 (MMP-2) and soluble B7-H3 (sB7-H3) were found to be correlatively up-regulated in the sera of osteoporosis patients. Furthermore, our results showed that MG63 cells treated with MMP-2 inhibitors produced lower amounts of sB7-H3 while cells with recombinant MMP-2 had an increased membrane B7-H3 (mB7-H3) shedding. Therefore, elevated MMP-2 levels resulted in an elevation of serum sB7-H3 and reduction of osteoblastic mB7-H3. B7-H3 knockdown in MG63 cells significantly decreased osteoblastic markers and substantially decreased the number of mineralized nodules after 21 days. Thus, B7-H3-deficient MG63 cells exhibited impaired bone formation. These results suggest that mB7-H3 is required for the later phases of osteoblast differentiation and that MMP-2/B7-H3 plays a negative regulatory role in osteoporosis. [ABSTRACT FROM AUTHOR]

Liquiritin is a flavonoid derived from Radix et Rhizoma Glycyrrhizae, which is a widely used traditional Chinese medicine with the effects of invigorating spleen qi, clearing heat, resolving toxins, and dispelling phlegm to stop coughs. In this review,the pharmacokinetics and pharmacological activities of liquiritin have been summarized. The information on liquiritin up to 2021 was collected from PubMed, Web of Science, Springer Link, and China National Knowledge Infrastructure databases. The key words were "liquiritin", "nerve", "tumor", "cardiac", etc. The absorption mechanism of liquiritin conforms to the passive diffusion and first-order kinetics while with low bioavailability. Liquiritin can penetrate the blood-brain-barrier. Besides, liquiritin displays numerous pharmacological effects including anti-Alzheimer's disease, antidepressant, antitumor, anti-inflammatory, cardiovascular protection, antitussive, hepatoprotection, and skin protective effects. In addition, the novel preparations, new pharmacological effects,and cdusafty of liquiritin are also discussed in this review. This review provides a comprehensive state of knowledge on the pharmacokinetics and pharmacological activities of liquiritin, and makes a forecast for its research directions and applications in clinic. [Display omitted] [ABSTRACT FROM AUTHOR]

Immunological T cells and associated cytokines have been shown to be involved in the pathogenesis of multiple myeloma (MM). However, the abnormal immune imbalance of T lymphocyte subsets on MM remains unknown. We investigate the proportions of T helper 1 (Th1)/Th2/Th17/T regulatory (Treg) cells in peripheral blood mononuclear cells (PBMCs) by flow cytometry (FCM), and serum levels of relevant cytokines in MM patients and controls were detected by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expression of T-bet, STAT6, RORgammat, and Foxp3 was measured by real-time quantitative polymerase chain reaction (PCR). The CD4+ Th1 and CD4+ Th17 cells in patients with MM were significantly higher than those in health controls as well as the expression of T-bet and RORgammat mRNA. Furthermore, serum levels of interferon gamma (IFN-γ), IL-6, and IL-17A in MM group were greatly increased and significantly associated with each other. Significant differences on Th cells, cytokines, and transcription factors were observed on MM patients. The imbalance of T lymphocyte subsets was thought to contribute to the pathogenesis and underlying mechanisms of MM. [ABSTRACT FROM AUTHOR]