Effects of Huzhangoside C on Dextran Sodium Sulfate-Stimulated Colitis in Mice.

Chronic inflammation is a major risk factor for cancer. Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, ultimately leading to a breakdown of intestinal barrier function. Clematis florida var. plena is a folk prescription used to treat inflammation and rheumatism in She pharmacy. The bioactivity of C. florida var. plena is primarily due to triterpene saponins. Huzhangoside C (HZ) is an active component of C. florida var. plena. In this study, the anti-inflammatory effect of HZ on a mouse colitis model induced by dextran sulfate sodium (DSS) was investigated. Result indicated a notable reduction in body weight loss and colon length shortening in HZ-mediated mice compared to DSS-stimulated control mice. Furthermore, inflammatory signaling mechanisms involving interleukin-6 and tumor necrosis factor-α were suppressed in HZ-treated mice. HZ treatment significantly suppressed the expression of nuclear factor kappa B (NF-κB), STAT3, and iNOS in colon tissue. After HZ treatment, malondialdehyde and nitric oxide levels were significantly decreased, while Nrf-2, superoxide dismutase, and glutathione expression levels were notably improved. The result indicated that HZ could activate the Nrf-2 signal cascade, inhibit the expression of NF-κB, eNOS, and STAT3, and enhance the intestinal barrier function of DSS stimulated ulcerative colitis intestinal injury. The results suggest that HZ is potential anti-inflammatory agent for treating IBD.

Radix Angelica dahuricae extract ameliorates oestrogen deficiency-induced dyslipidaemia in ovariectomized (OVX) rats by modulating the gut microbiota and bile acid signalling.

BACKGROUND: Radix Angelica dahuricae (RAD), a well-known traditional Chinese medicine, displays a promising effect on alleviating lipid metabolism. However, the improvement of RAD on oestrogen deficiency-induced dyslipidaemia and the underlying mechanism are unclear. PURPOSE: The aim of this study was to study the effect of RAD on oestrogen deficiency-induced dyslipidaemia in ovariectomized (OVX) rats and investigate the involvement of the gut microbiota and bile acid signalling in the protective effects. METHODS: Bilateral ovariectomy was executed to establish an oestrogen deficiency model. Serum biochemical indexes, liver lipids, inflammatory cytokines and histomorphology were evaluated. Gut microbes were analysed via 16S rRNA sequencing. Faecal short-chain fatty acids (SCFAs) and serum bile acids were quantified by gas chromatography-flame ionization detection (GC-FID) and ultra-high-performance chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. The expression of genes related to bile acid synthesis, metabolism and enterohepatic circulation in the liver and caecum was measured by real-time PCR. RESULTS: The results displayed that RAD administration markedly decreased body weight, TC and TG levels in the serum and liver, and hepatic steatosis and inflammation in OVX rats. RAD administration could significantly regulate the gut microbial composition, increasing the abundance of Lactobacillus, increasing the content of bile salt hydrolase (BSH), and reestablishing the SCFA profile and bile acid metabolism profile in OVX rats. RAD administration could increase the gene expression of HMG-CoA reductase (HMGCR) and cytochrome P450 7A1(CYP7A1) and regulate the gene expression of the related receptors as well as proteins in enterohepatic circulation. CONCLUSIONS: RAD alleviated oestrogen deficiency-induced dyslipidaemia in OVX rats. Modulation of the gut microbiota composition and bile acid signalling may be the underlying mechanism.

Improvements in estrogen deficiency-induced hypercholesterolemia by Hypericum perforatum L. extract are associated with gut microbiota and related metabolites in ovariectomized (OVX) rats.

Hypericum perforatum L. (HP), a well-known natural medicine, has a potential effect on menopausal hypercholesterolemia. However, the effect of HP extract on gut microbiota and related metabolites, which play vital roles in metabolic disease occurrence, in the context of estrogen deficiency have not yet been reported. The aims of the present study were to investigate the effects of HP extract on gut microbial composition and related metabolite profiles in ovariectomized (OVX) rats and reveal the relationships between pathological indicators and alterations in both gut microbial composition at the genus level and metabolites. Body weight, serum parameters, liver lipids and histomorphology were determined. Microbial composition was analyzed using 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and serum bile acids were quantitatively measured. Correlations between pathological indicators and alteration in gut microbiota and metabolites were investigated using Spearman's rank correlation test. Gene expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 27-hydroxylase (CYP27A1) in the liver and G protein-coupled receptors (GPCRs; GPR43 and GPR41), ZO-1 and occludin in the cecum were determined by PCR. Microbial composition and metabolite profiles were significantly changed in OVX rats compared with sham rats. Twelve bacterial genera, 5 SCFAs and 12 bile acids were identified as differential biomarkers. Differential genera, SCFAs and bile acids were closely associated with weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In OVX rats, HP administration can significantly reverse the pathological symptoms of body weight gain, serum lipid disorders and hepatic steatosis, at the meanwhile, reestablish gut microbial composition and metabolite profiles. Moreover, HP administration significantly upregulated the levels of CYP7A1, GPR43 and GPR41. In conclusion, HP can ameliorate estrogen deficiency-induced hypercholesterolemia. The underlying mechanism may be associated with improvements in gut microbiota composition and the profile of related metabolites as well as increases in bile acid secretion.

Natural products action on pathogenic cues in autoimmunity: Efficacy in systemic lupus erythematosus and rheumatoid arthritis as compared to classical treatments.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-targeted and cytokines receptors-targeted therapy, cannot completely cure SLE and RA, and are always accompanied by unexpected side effects. Therefore, more studies have explored new methods for therapy and found that the herbal medicine as well as its natural products (NPs) exhibited promising therapeutic value through exerting effects of immunomodulation, anti-inflammation, anti-oxidation, and anti-apoptosis, etc. via regulating abnormal responses in kidney, innate and adaptive immune systems, intestine, synoviocytes, as well as bone system including chondrocytes, osteoclasts, joints and paw tissues. In the present review, we will elucidate the current mainstream drugs and therapies for SLE and RA, and summarize the efficacy and mechanisms of NPs in the treatment of SLE and RA based on available findings including in vitro and in vivo animal models, as well as clinical studies, and further analyze the existing challenges, in order to provide comprehensive evidence for improvement of SLE and RA therapy by NPs and to promote management of these two autoimmune diseases.

P2X7 receptor: A potential therapeutic target for autoimmune diseases.

P2X7 receptor (P2X7R), a distinct ligand-gated ion channel, is a member of purinergic type 2 receptor family with ubiquitous expression in human body. Previous studies have revealed a pivotal role of P2X7R in innate and adaptive immunity. Once activated, it will meditate some vital cascaded responses including the assembly of nucleotide-binding domain (NOD) like receptor protein 3 (NLRP3) inflammasome, non-classical secretion of IL-1ß, modulation of cytokine-independent pathways in inflammation such as P2X7R- transglutaminase-2 (TG2) and P2X7R-cathepsin pathway, activation and regulation of T cells, etc. In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis. Recently, numerous evidences further suggested the significance of P2X7R in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), etc. In this review, we will succinctly discuss the biological characteristics and summarize the recent progress of the involvement of P2X7R in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

Effect of Comprehensive Therapy based on Chinese Medicine Patterns on Self-Efficacy and Effectiveness Satisfaction in Chronic Obstructive Pulmonary Disease Patients.

OBJECTIVE: To evaluate the effect of comprehensive therapy based on Chinese medicine (CM) patterns on self-efficacy and satisfaction with its effectiveness in patients with chronic obstructive pulmonary disease (COPD). METHODS: A total of 216 patients were randomly divided into the trial group (n =108) and the control group (n=108) based on the stratified and block randomization design. Patients in the trial group were treated with conventional Western medicine combined with Bufei Jianpi Granules (), Bufei Yishen Granules (), and Yiqi Zishen Granules () according to the CM patterns respectively, and patients in the control group were treated with conventional Western medicine. The COPD Self-Efficacy Scale (CSES) and the Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD) were employed in a 6-month treatment and in further 6 month follow-up visit. RESULTS: Among the 216 patients, 191 patients (97 in the trial group and 94 in the control group) fully completed the study. After 12-month treatment and follow-up, the mean scores of the trial group all continued to increase over time, which were significantly higher than those of the control group (P <0.05), and the improvement in the following trial group domain: negative affect domain (12.13%), intense emotional arousal domain (12.21%), physical exertion domain (11.72%), weather/environmental domain (13.77%), behavioral risk domain (7.67%) and total score (10.65%). The trial group also exhibited significantly higher mean scores in the ESQ-COPD (P <0.05) and the improvement in the following domain: capacity for life and work domain (30.59%), clinical symptoms domain (53.52%), effect of therapy domain (35.95%), convenience of therapy domain (35.54%), and whole effect domain (52.47%). CONCLUSIONS: Bufei Jianpi Granules, Bufei Yishen Granules and Yiqi Zishen Granules can improve the self-efficacy and satisfaction of COPD patients.

[Identification of endophytic bacteria BZJN1 and research on biological control of root rot of Atractylodes macrocephala].

In this study， an endophytic bacteria strain BZJN1 was isolated from Atractylodes macrocephala， and identified as Bacillus subtilis by physiological and biochemical tests and molecular identification. Strain BZJN1 could inhibit the growth of mycelia of Ceratobasidium sp. significantly， and the inhibition rate was more than 70%. The mycelium growth deformity with bulge as spherical and partially exhaustible in apex or central with microscopic observation. The inhibitory rates under 3% and 6% concentrations of the cell free fermentation were 22.7% and 38.7% expectively. The field test proved that the control efficacy of treatment of 1×108 cfu·mL⁻¹ is 75.27% and 72.37% after 10 and 20 days. All the treatments of strain BZJN1 was able to promote the growth of A. macrocephala， the treatment of 1×108 cfu·mL⁻¹ could able to increase the yield to 14.1%.

Different mechanisms in learning different second languages: Evidence from English speakers learning Chinese and Spanish.

Word reading has been found to be associated with different neural networks in different languages, with greater involvement of the lexical pathway for opaque languages and greater invovlement of the sub-lexical pathway for transparent langauges. However, we do not know whether this language divergence can be demonstrated in second langauge learners, how learner's metalinguistic ability would modulate the langauge divergence, or whether learning method would interact with the language divergence. In this study, we attempted to answer these questions by comparing brain activations of Chinese and Spanish word reading in native English-speaking adults who learned Chinese and Spanish over a 2 week period under three learning conditions: phonological, handwriting, and passive viewing. We found that mapping orthography to phonology in Chinese had greater activation in the left inferior frontal gyrus (IFG) and left inferior temporal gyrus (ITG) than in Spanish, suggesting greater invovlement of the lexical pathway in opaque langauges. In contrast, Spanish words evoked greater activation in the left superior temporal gyrus (STG) than English, suggesting greater invovlement of the sublexical pathway for transparant languages. Furthermore, brain-behavior correlation analyses found that higher phonological awareness and rapid naming were associated with greater activation in the bilateral IFG for Chinese and in the bilateral STG for Spanish, suggesting greater language divergence in participants with higher meta-linguistic awareness. Finally, a significant interaction between the language and learning condition was found in the left STG and middle frontal gyrus (MFG), with greater activation in handwriting learning than viewing learning in the left STG only for Spanish, and greater activation in handwriting learning than phonological learning in the left MFG only for Chinese. These findings suggest that handwriting facilitates assembled phonology in Spanish and addressed phonology in Chinese. In summary, our study suggests different mechanisms in learning different L2s, providing important insights into neural plasticity and important implications in second language education.

Neural signatures of phonological deficits in Chinese developmental dyslexia.

There has been debate on whether phonological deficits explain reading difficulty in Chinese, since Chinese is a logographic language which does not employ grapheme-phoneme-correspondence rules and remote memorization seems to be the main method to acquire reading. In the current study, we present neuroimaging evidence that the phonological deficit is also a signature of Chinese dyslexia. Specifically, we found that Chinese children with dyslexia (DD) showed reduced brain activation in the left dorsal inferior frontal gyrus (dIFG) when compared to both age-matched controls (AC) and reading-matched controls (RC) during an auditory rhyming judgment task. This suggests that the phonological processing deficit in this region may be a signature of dyslexia in Chinese, rather than a difference due to task performance or reading ability, which was matched on DD and RC. At exactly the same region of the left dIFG, we found a positive correlation between brain activation and reading skill in DD, suggesting that the phonological deficit is associated with the severity of dyslexia. We also found increased brain activation in the right precentral gyrus in DD than both AC and RC, suggesting a compensation of reliance on articulation. Functional connectivity analyses revealed that DD had a weaker connection between the left superior temporal gyrus (STG) and fusiform gyrus (FG) than the two control groups, suggesting that the reduced connection between phonology and orthography is another neural signature of dyslexia. In contrast, DD showed greater connectivity between the left dIFG and the left inferior parietal lobule (IPL) than both control groups, suggesting a reduced segregation between the language network and default mode network in dyslexic children. We also found that connectivity between the left STG and the left dIFG was sensitive to task performance and/or reading skill rather than being dyslexic or not, because AC was greater than both RC and DD, while the connectivity between the left middle occipital gyrus (MOG) and left STG was sensitive to age, because both AC and DD were greater than RC. In summary, our study provides the very first neurological evidence of phonological deficits in Chinese developmental dyslexia and we successfully distinguished variations of brain activity/functional connectivity due to age, performance, and dyslexia by comparing AC, RC, and DD.

Celastrol targets IRAKs to block Toll-like receptor 4-mediated nuclear factor-κB activation.

OBJECTIVE: Celastrol has been established as a nuclear factor-κB (NF-κB) activation inhibitor; however, the exact mechanism behind this action is still unknown. Using text-mining technology, the authors predicted that interleukin-1 receptor-associated kinases (IRAKs) are potential celastrol targets, and hypothesized that targeting IRAKs might be one way that celastrol inhibits NF-κB. This is because IRAKs are key molecules for some crucial pathways to activate NF-κB (e.g., the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily). METHODS: The human hepatocellular cell line (HepG2) treated with palmitic acid (PA) was used as a model for stimulating TLR4/NF-κB activation, in order to observe the potential effects of celastrol in IRAK regulation and NF-κB inhibition. The transfection of small interfering RNA was used for down-regulating TLR4, IRAK1 and IRAK4, and the Western blot method was used to detect changes in the protein expressions. RESULTS: The results showed that celastrol could effectively inhibit PA-caused TLR4-dependent NF-κB activation in the HepG2 cells; PA also activated IRAKs, which were inhibited by celastrol. Knocking down IRAKs abolished PA-caused NF-κB activation. CONCLUSION: The results for the first time show that targeting IRAKs is one way in which celastrol inhibits NF-κB activation.

The brain adapts to orthography with experience: evidence from English and Chinese.

Using functional magnetic resonance imaging (fMRI), we examined the process of language specialization in the brain by comparing developmental changes in two contrastive orthographies: Chinese and English. In a visual word rhyming judgment task, we found a significant interaction between age and language in left inferior parietal lobule and left superior temporal gyrus, which was due to greater developmental increases in English than in Chinese. Moreover, we found that higher skill only in English children was correlated with greater activation in left inferior parietal lobule. These findings suggest that the regions associated with phonological processing are essential in English reading development. We also found greater developmental increases in English than in Chinese in left inferior temporal gyrus, suggesting refinement of this region for fine-grained word form recognition. In contrast, greater developmental increases in Chinese than in English were found in right middle occipital gyrus, suggesting the importance of holistic visual-orthographic analysis in Chinese reading acquisition. Our results suggest that the brain adapts to the special features of the orthography by engaging relevant brain regions to a greater degree over development.

Reading acquisition reorganizes the phonological awareness network only in alphabetic writing systems.

It is unknown how experience with different types of orthographies influences the neural basis of oral language processing. In order to determine the effects of alphabetic and nonalphabetic writing systems, the current study examined the influence of learning to read on oral language in English and Chinese speakers. Children (8-12 years olds) and adults made rhyming judgments to pairs of spoken words during functional magnetic resonance imaging (fMRI). Developmental increases were seen only for English speakers in the left hemisphere phonological network (superior temporal gyrus (STG), inferior parietal lobule, and inferior frontal gyrus). The increase in the STG was more pronounced for words with conflicting orthography (e.g. pint-mint; jazz-has) even though access to orthography was irrelevant to the task. Moreover, higher reading skill was correlated with greater activation in the STG only for English speaking children. The effects suggest that learning to read reorganizes the phonological awareness network only for alphabetic and not logographic writing systems because of differences in the principles for mapping between orthographic and phonological representations. The reorganization of the auditory cortex may result in better phonological awareness skills in alphabetic readers.

Effects of comprehensive therapy based on traditional Chinese medicine patterns in stable chronic obstructive pulmonary disease: a four-center, open-label, randomized, controlled study.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years. This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients. METHODS: A four-center, open-label randomized controlled method was conducted. A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine). The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up. RESULTS: A total of 306 patients completed the study fully. The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306. After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire. There were no differences between the trial and control group in FVC, FEV1% and adverse events. CONCLUSIONS: Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events. TRIAL REGISTRATION: This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406.

Neural correlates of priming effects in children during spoken word processing with orthographic demands.

Priming effects were examined in 40 children (9-15 years old) using functional magnetic resonance imaging (fMRI). An orthographic judgment task required participants to determine if two sequentially presented spoken words had the same spelling for the rime. Four lexical conditions were designed: similar orthography and phonology (O(+)P(+)), similar orthography but different phonology (O(+)P(-)), similar phonology but different orthography (O(-)P(+)), and different orthography and phonology (O(-)P(-)). In left superior temporal gyrus, there was lower activation for targets in O(+)P(+) than for those in O(-)P(-) and higher accuracy was correlated with stronger activation across all lexical conditions. These results provide evidence for phonological priming in children and greater elaboration of phonological representations in higher skill children, respectively. In left fusiform gyrus, there was lower activation for targets in O(+)P(+) and O(+)P(-) than for those in O(-)P(-), suggesting that visual similarity resulted in orthographic priming even with only auditory input. In left middle temporal gyrus, there was lower activation for targets in O(+)P(+) than all other lexical conditions, suggesting that converging orthographic and phonological information resulted in a weaker influence on semantic representations. In addition, higher reading skill was correlated with weaker activation in left middle temporal gyrus across all lexical conditions, suggesting that higher skill children rely to a lesser degree on semantics as a compensatory mechanism. Finally, conflict effects but not priming effects were observed in left inferior frontal gyrus, suggesting that this region is involved in resolving conflicting orthographic and phonological information but not in perceptual priming.

Modality- and task-specific brain regions involved in Chinese lexical processing.

fMRI was used to examine lexical processing in native adult Chinese speakers. A 2 task (semantics and phonology) x 2 modality (visual and auditory) within-subject design was adopted. The semantic task involved a meaning association judgment and the phonological task involved a rhyming judgment to two sequentially presented words. The overall effect across tasks and modalities was used to identify seven ROIs, including the left fusiform gyrus (FG), the left superior temporal gyrus (STG), the left ventral inferior frontal gyrus (VIFG), the left middle temporal gyrus (MTG), the left dorsal inferior frontal gyrus (DIFG), the left inferior parietal lobule (IPL), and the left middle frontal gyrus (MFG). ROI analyses revealed two modality-specific areas, FG for visual and STG for auditory, and three task-specific areas, IPL and DIFG for phonology and VIFG for semantics. Greater DIFG activation was associated with conflicting tonal information between words for the auditory rhyming task, suggesting this region's role in strategic phonological processing, and greater VIFG activation was correlated with lower association between words for both the auditory and the visual meaning task, suggesting this region's role in retrieval and selection of semantic representations. The modality- and task-specific effects in Chinese revealed by this study are similar to those found in alphabetical languages. Unlike English, we found that MFG was both modality- and task-specific, suggesting that MFG may be responsible for the visuospatial analysis of Chinese characters and orthography-to-phonology integration at a syllabic level.

The interaction between orthographic and phonological information in children: an fMRI study.

We examined the neural representations of orthographic and phonological processing in children, while manipulating the consistency between orthographic and phonological information. Participants, aged 9-15, were scanned while performing rhyming and spelling judgments on pairs of visually presented words. The orthographic and phonological similarity between words in the pair was independently manipulated, resulting in four conditions. In the nonconflicting conditions, both orthography and phonology of the words were either (1) similar (lime-dime) or (2) different (staff-gain); in conflicting conditions, words had (3) similar phonology and different orthography (jazz-has) or (4) different phonology and similar orthography (pint-mint). The comparison between tasks resulted in greater activation for the rhyming task in bilateral inferior frontal gyri (BA 45/47), and greater activation for the spelling task in bilateral inferior/superior parietal lobules (BA 40/7), suggesting greater involvement of phonological and semantic processing in the rhyming task, and nonlinguistic spatial processing in the spelling task. Conflicting conditions were more difficult in both tasks and resulted in greater activation in the above regions. The results suggest that when children encounter inconsistency between orthographic and phonological information they show greater engagement of both orthographic and phonological processing.