Periplaneta americana extract attenuates hepatic fibrosis progression by inhibiting collagen synthesis and regulating the TGF-ß1/Smad signaling pathway.

INTRODUCTION: Liver fibrosis is the damage repair response following chronic liver diseases. Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells and key regulators in liver fibrosis. Periplaneta americana shows prominent antifibrotic effects in liver fibrosis; however, the underlying mechanisms remain undetermined. This study aimed to elucidate the therapeutic effects of P. americana extract (PA-B) on liver fibrosis based on the regulation of the TGF-ß1/Smad signal pathway. MATERIAL AND METHODS: HSCs and Sprague Dawley rats were treated with TGF-ß1 and CCl4, respectively, to establish the hepatic fibrosis model in vitro and in vivo. The effect of PA-B on liver rat fibrosis was evaluated by biochemical (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA), laminin (LN), collagen type IV (Col-IV), pro-collagen type III (PC-III)) and histological examinations. Further, fibrogenic markers expression of alpha smooth muscle actin (α-SMA), collagen type I (Col-I), and collagen type III (Col-III), and the TGF-ß1/Smad pathway-related factors were assessed by immunofluorescence (IF), real time quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB). RESULTS: Treatment of HSC-T6 cells with PA-B suppressed the expression of α-SMA, Col-I, and Col-III, downregulated the expression of TGF-ß1 receptors I and II (TßR I and TßR II, respectively), Smad2, and Smad3, and upregulated Smad7 expression. PA-B mitigates pathologic changes in the rat model of liver fibrosis, thus alleviating liver index, and improving liver function and fibrosis indices. The effects of PA-B on the expression of α-SMA, Col-I, Col-III, TßR I, TßR II, Smad2, Smad3, and Smad7 were consistent with the in vitro results, including reduced TGF-ß1 expression. CONCLUSIONS: The therapeutic effect of PA-B on liver fibrosis might involve suppression of the secretion and expression of TGF-ß1, regulation of the TGF-ß1/Smad signaling pathway, and inhibition of collagen production and secretion.

Dietary Eggshell Membrane Powder Improves Survival Rate and Ameliorates Gut Dysbiosis in Interleukin-10 Knockout Mice.

Inflammatory bowel disease (IBD) is known to be associated with compositional and metabolic changes in the gut microbiota. The aim of this study was to investigate whether dietary eggshell membrane (ESM) improves survival rate or ameliorates gut dysbiosis in a spontaneous IBD model of interleukin-10 knockout (IL10-/-) mice. Female C57BL/6J wild-type (WT) and IL10-/- mice (KO) were fed an AIN-93G basal diet or an ESM diet (KOE) for 19 weeks. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and short-chain fatty acids in cecal content were analyzed with high-performance liquid chromatography. The results demonstrated that ESM supplementation significantly improved the survival rate and body composition in KO mice. Alpha diversity analysis of the microbiota revealed that ESM supplementation significantly increased gut microbial diversity, which was decreased in IL10-/- mice. The Firmicutes/Bacteroidetes ratio was recovered to a normal level by ESM supplementation, suggesting that ESM helps maintain the compositional balance of the gut microbiota. ESM increased relative abundance of commensal bacterial Ruminococcus and Bacteroidales S24-7 and reduced the abundance of the proinflammatory-related bacterium, Enterobacteriaceae. Additionally, ESM supplementation promoted the production of butyrate in cecal contents and downregulated the expression of proinflammatory genes, including interleukin-1ß (Il-1ß) and tumor necrosis factor-α (Tnf-α) in IL10-/- mice colon, indicating anti-inflammatory functions. These findings suggest that ESM may be used as a beneficial dietary intervention for IBD.

Identification of anti-hepatic fibrosis components in Periplaneta americana based on spectrum-effect relationship and chemical component separation.

Periplaneta americana (PA) is used as a traditional medicine for hepatic diseases such as hepatic fibrosis in China. However, the relationship between the corresponding therapeutic effect and the chemical composition is still unclear. In this study, spectrum-effect relationship and chemical component separation were used to discover the potential of anti-hepatic fibrosis components of PA. The fingerprints of 10 batches of samples were established using HPLC, and the anti-hepatic fibrosis effect was determined using HSC-T6 cells. The spectrum-effect relationship between common peaks and efficacy values was established using partial least squares analysis. Partial peaks in the fingerprints were identified, including X4 (9,12-heptadecanedenoic acid glyceride), X5 (nonadecanoic acid methyl ester), X6 (glyceryl oleate), X7 (13,16,19-eicosatrienoic acid), X9 (linoleic acid), X10 (9,12,15-octadecatrienoic acid glyceride), X12 (hexadecanoic acid), X13 (oleic acid), and X14 (octadecanoic acid), and their anti-hepatic fibrosis activity was tested to verify the results of spectrum-effect relationships. The results showed that X4 , X6 , X7 , and X10 were the active ingredients of PA. This work successfully identified the partial anti-hepatic fibrosis components of PA, which can be used to explain the material basis for the PA anti-hepatic fibrosis effect.

Amaranth Supplementation Improves Hepatic Lipid Dysmetabolism and Modulates Gut Microbiota in Mice Fed a High-Fat Diet.

Diet-induced obesity is often associated with gut microbiota dysbiosis, lipid metabolism disorders, and chronic inflammation. Consumption of the pseudocereal Amaranthus mangostanus has multiple nutritional benefits. We investigated the effects of dietary amaranth on lipid metabolism and gut microbiota in high-fat (HF) diet-fed mice. C57BL/6J mice were provided either a control diet, HF diet, or HF diet containing 10% amaranth powder (Ama) for 8 weeks. Ama supplementation significantly reduced the levels of triglycerides, total cholesterol, and phospholipids in the liver. Moreover, Ama supplementation downregulated the expression of lipogenesis-related genes including Hmgcr, Fdt1, and Sgle in the liver. The gut microbiota analysis showed that Ama supplementation reversed HF diet-induced reduction in bacterial diversity and richness. Additionally, beta diversity analysis of the inter-group variability in community structure showed a clear separation between the HF and Ama groups. Linear discriminant analysis effect size analysis revealed that 11 taxa were enriched in the Ama group, whereas 9 taxa were increased in the HF group. We found that family Porphyromonadaceae and unclassified S24-7 showed a strong positive and negative correlation with the lipid parameters, respectively. Taken together, these results indicated that dietary Ama may attenuate HF diet-induced deterioration of gut microbiota structure and hepatic lipid metabolism.

Dynamic Optimization Method for Broadband ADCP Waveform with Environment Constraints.

Broadband acoustic Doppler current profiler (ADCP) is widely used in agricultural water resource explorations, such as river discharge monitoring and flood warning. Improving the velocity estimation accuracy of broadband ADCP by adjusting the waveform parameters of a phase-encoded signal will reduce the velocity measurement range and water stratification accuracy, while the promotion of stratification accuracy will degrade the velocity estimation accuracy. In order to minimize the impact of these two problems on the measurement results, the ADCP waveform optimization problem that satisfies the environment constraints while keeping high velocity estimation accuracy or stratification accuracy is studied. Firstly, the relationship between velocity or distance estimation accuracy and signal waveform parameters is studied by using an ambiguity function. Secondly, the constraints of current velocity range, velocity distribution and other environmental characteristics on the waveform parameters are studied. For two common measurement applications, two dynamic configuration methods of waveform parameters with environmental adaptability and optimal velocity estimation accuracy or stratification accuracy are proposed based on the nonlinear programming principle. Experimental results show that compared with the existing methods, the velocity estimation accuracy of the proposed method is improved by more than 50%, and the stratification accuracy is improved by more than 22%.

Does the Gut Microbiota Modulate Host Physiology through Polymicrobial Biofilms?

Microbes inhabit various environments, such as soil, water environments, plants, and animals. Humans harbor a complex commensal microbial community in the gastrointestinal tract, which is known as the gut microbiota. The gut microbiota participates not only in various metabolic processes in the human body, it also plays a critical role in host immune responses. Gut microbes that inhabit the intestinal epithelial surface form polymicrobial biofilms. In the last decade, it has been widely reported that gut microbial biofilms and gut microbiota-derived products, such as metabolites and bacterial membrane vesicles, not only directly affect the host intestinal environment, but also indirectly influence the health of the host. In this review, we discuss the most recent findings from human and animal studies on the interactions between the gut microbiota and hosts, and their associations with various disorders, including inflammatory diseases, atopic dermatitis, metabolic disorders, and psychiatric and neurological diseases. The integrated approach of metabologenomics together with biofilm imaging may provide valuable insights into the gut microbiota and suggest remedies that may lead to a healthier society.

Low-Dose Ethanol Has Impacts on Plasma Levels of Metabolites Relating to Chronic Disease Risk in SAMP8 mice.

The effects of low-dose alcohol on experimental animals are unclear. This study examined plasma metabolites in senescence-accelerated mice 8 (SAMP8) given low-dose ethanol, and compared them with aging progress and skeletal muscle strength. Male SAMP8 mice (10-wk-old) were given drinking water containing 0% (control), 1%, 2%, or 5% (v/v) ethanol for 14 wk. Compared with the control group, only mice who consumed 1% ethanol experienced a lower senescence score at 18 and 23 wk, as well as an increased limb grip strength at 21 wk. Plasma metabolites of control, 1% and 2% ethanol groups were analyzed by capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS). Among the 7 metabolites affected by ethanol, notewhorthy is the positive association of the ethanol levels in drinking water with the levels of α-ketoglutarate (antioxidant and anti-inflammatory metabolite) and hippurate (antioxidant and microbial co-metabolite) (p<0.05). Intriguingly, the levels of 2-hydroxyisobutyrate (the biomarker of energy metabolism and microbial co-metabolite) were higher in the 1% ethanol group (p<0.05), but not in the 2% ethanol group as compared to the control. Furthermore, the levels of some of the metabolites affected were correlated with some variables in the grading score of senescence and muscle strength. This study provides a novel insight into how low-dose ethanol in SAMP8 mice modulates the levels of circulating metabolites relating to chronic disease risk.

Consumption of Low-Dose of Ethanol Suppresses Colon Tumorigenesis in 1,2-Dimethylhydrazine-Treated Rats.

The effect of low-dose of ethanol consumption on the development of colon cancer is unclear. This study aimed to investigate the effects of low-dose ethanol (0.5%, 1%, and 2% [v/v] ethanol in drinking water) for 28 wk on colon tumor incidence in rats injected with 1,2-dimethylhydrazine. Body weight, fluid and food consumption, and the total numbers of colon adenomas (mild-, moderate-, and severe-grade dysplasia) per rat were unaffected by ethanol consumption. However, the numbers of severe-grade dysplasia were significantly reduced by 1% ethanol compared with the control (0% ethanol; -93%) but not by 0.5% and 2% ethanol. Although the numbers of total adenocarcinomas were unaffected, those of total of adenomas and adenocarcinomas together were significantly reduced by 0.5% and 1% ethanol (-39% and -41%, respectively). Intriguingly, real-time PCR assay indicated the abundance of cecal Clostridium leptum (a putative immunosuppressor) was the least in rats received 1% ethanol. Furthermore, 1% ethanol markedly increased colonic mRNA of IL-6, a putative suppressor of regulatory T-cells and cytoprotector. This study provides the first evidence for the potential of 1% ethanol, but not 2% ethanol, to prevent colon tumorigenesis in rats, supporting the J-curve hypothesis of the effect of low-dose alcohol on health. Further, the modulation of C. leptum and expression of IL-6, potentially linking to carcinogenesis, by 1% ethanol may provide an insight into the underlying mechanisms of the anti-colon tumor effect.

Feeding Aspergillus protease preparation combined with adequate protein diet to rats increases levels of cecum gut-protective amino acids, partially linked to Bifidobacterium and Lactobacillus.

Our recent study indicated that dietary Aspergillus oryzae-derived protease preparation (AP), through its enzymatic activity, exerted a bifidogenic effect in rats. We hypothesized that dietary AP links to protein degradation and subsequently elevates gut-protective amino acids (AAs) in rats fed adequate protein diet. In this study, dietary AP markedly increased the relative abundance of Bifidobacterium and Lactobacillus and the levels of free threonine, alanine, proline, taurine, ornithine, phenylalanine, cystine, and γ-aminobutyric acid in the cecum contents of rats fed with an adequate protein diet, but not in those fed with a low-protein diet. The elevated AAs, except ornithine and phenylalanine, potentially have gut-related health benefits. Some of the AP-modulated free AAs appeared to be associated with the relative abundance of Bifidobacterium and Lactobacillus. Thus, AP combined with adequate protein diet is likely to increase the levels of cecum beneficial free AAs, which is partially associated with the relative abundance of the probiotics.

Increased intestinal ethanol following consumption of fructooligosaccharides in rats.

Previous studies have suggested that ethanol is a fermentation product of microflora. However, it is unknown whether this ethanol production is elevated by intake of prebiotics. Prebiotics are considered to enhance the production of short-chain fatty acids (SCFAs) as a fermentation product of beneficial bacteria. In the present study, the effect of fructooligosaccharides (FOS) consumption on intestinal ethanol levels was investigated. Rats were fed a diet with or without 10% FOS for two weeks. Consequently, FOS intake significantly increased ethanol levels per gram of ileum and cecum digesta of the rats (3.5-fold and 1.9-fold, respectively, P<0.01). The numbers of cecum Bifidobacterium (producer of ethanol and lactate) were significantly increased by FOS intake (P<0.05) and correlated with the cecum ethanol levels per gram of cecum (r=0.626, P<0.05). FOS intake also led to a significant increase in the cecum levels of SCFAs, namely lactate, propionate and n-butyrate (P<0.05). Furthermore, ethanol levels were significantly correlated with lactate levels (r=0.691, P<0.01), but not with propionate or n-butyrate levels (r=0.449 and 0.493, respectively, P>0.05). The current study, to the best of our knowledge, is the first to indicate that FOS intake significantly increases the level of intestinal ethanol. Therefore, dietary FOS may affect the intestinal health status of animals by elevating their ethanol levels, without direct ethanol consumption.

Beneficial Effects of Dietary Tempeh Prepared with Rhizopus stolonifer on Liver Function in Rats Fed with a High-Fat Diet.

The regional standard for tempeh established by the Codex Alimentarius defines the use of Rhizopus oligosporus, R. oryzae, and/or R. stolonifer as soybean tempeh starters. However, comparative studies on the functions of tempeh prepared with these Rhizopus species are scarce. In the present study, we examined the effects of dietary tempeh prepared with these three Rhizopus species using rats fed with a high-fat diet. Compared to the control diet, consumption of tempeh prepared with R. stolonifer significantly suppressed serum levels of aspartate transaminase, total bilirubin, and ammonium (indices of liver function). However, less or no suppression was observed with tempeh prepared with R. oligosporus or R. oryzae. Serum levels of triglyceride, total cholesterol, HDL cholesterol, and glucose were unaffected. Liver levels of free cholesterol, a parameter relating to liver injury, were significantly decreased by the three types of the tempeh examined; however, there was no difference in the free cholesterol levels among the tempeh groups. We conclude that the ingestion of tempeh prepared with R. stolonifer might have beneficial effects pertaining to the liver function in rats fed with high-fat diets.

Gender Difference and Dietary Supplemental Vitamin B6: Impact on Colon Luminal Environment.

Colon diseases can be affected by several factors such as gender difference and dietary supplemental vitamin B6 (B6). The nutritional status of B6 is affected by gender difference, leading us to hypothesize that gender difference affects colon luminal environment, which is dependent on B6 status. To investigate this hypothesis, we fed male and female rats a diet containing 1 mg, 7 mg, or 35 mg pyridoxine HCl/kg diet for 6 wk. We found significantly higher fecal mucin levels in female rats compared to those in male rats. Supplemental B6 significantly increased fecal mucins and was particularly profound in the female rats. The abundances of cecal and fecal Akkermansia muciniphila (mucin degrader) were unaffected. The fecal mucin levels were significantly correlated with colonic free threonine and serine and with gene expression of colon MUC16, implying that the combined effect of gender and dietary B6 on fecal mucins was mediated by the alteration in the levels of such amino acids and MUC16 expression. This study further showed the significant effects of gender difference on colonic free amino acids such as threonine, ornithine, asparagine/aspartate ratio, and glutamine/glutamate ratio, cecal and fecal Lactobacillus spp. levels, and colonic gene expressions of MUC16 and TLR8, the factors relating to colon health and diseases. Therefore, our findings suggest that gender difference and dietary B6 may have an impact on colon diseases by modulating these parameters.

Targeting gut microbiome: A novel and potential therapy for autism.

Autism spectrum disorder (ASD) is a severely neurodevelopmental disorder that impairs a child's ability to communicate and interact with others. Children with neurodevelopmental disorder, including ASD, are regularly affected by gastrointestinal problems and dysbiosis of gut microbiota. On the other hand, humans live in a co-evolutionary association with plenty of microorganisms that resident on the exposed and internal surfaces of our bodies. The microbiome, refers to the collection of microbes and their genetic material, confers a variety of physiologic benefits to the host in many key aspects of life as well as being responsible for some diseases. A large body of preclinical literature indicates that gut microbiome plays an important role in the bidirectional gut-brain axis that communicates between the gut and central nervous system. Moreover, accumulating evidences suggest that the gut microbiome is involved in the pathogenesis of ASD. The present review introduces the increasing evidence suggesting the reciprocal interaction network among microbiome, gut and brain. It also discusses the possible mechanisms by which gut microbiome influences the etiology of ASD via altering gut-brain axis. Most importantly, it highlights the new findings of targeting gut microbiome, including probiotic treatment and fecal microbiota transplant, as novel and potential therapeutics for ASD diseases.

Consumption of an acid protease derived from Aspergillus oryzae causes bifidogenic effect in rats.

A marked elevation in the abundance of Bifidobacterium was found in the cecum of rats that were fed a high-fat diet supplemented with an Amano protease preparation (derived from Aspergillus oryzae). The protease preparation contains several digestive enzymes, including acid protease (AcP), alkaline protease, and amylase. We hypothesized that the elevation in the abundance of Bifidobacterium by Amano protease preparation is associated with the digestive enzymes involved in the protease preparation. To test this hypothesis, this study was conducted to investigate if such bifidogenic effect is because of the AcP. Rats were fed a high-fat diet containing purified AcP obtained from the Amano protease preparation for 2 weeks. The numbers of Bifidobacterium in the cecum and feces of rats were markedly elevated by the dietary supplementation of 1 g/kg Amano protease. Bifidobacterium numbers were unaffected by supplementation with purified AcP (0.096 g/kg) at the level equivalent to the AcP amount found in the 1-g/kg Amano protease diet. Bifidobacterium numbers in the cecum and feces, and lactate levels in the cecum were significantly (P<.05) elevated when rats were fed a diet containing 0.384 g/kg AcP (4-fold higher amount of AcP than that used in the 1-g/kg Amano protease diet). Thus, the bifidogenic effect of 1 g/kg Amano protease diet could not be explained by the AcP. However, intriguingly, supplemental AcP was found to cause a significant bifidogenic effect at the dose that is 4-fold higher than that used in the 1-g/kg Amano protease diet.

Feeding of the water extract from Ganoderma lingzhi to rats modulates secondary bile acids, intestinal microflora, mucins, and propionate important to colon cancer.

Consumption of reishi mushroom has been reported to prevent colon carcinogenesis in rodents, although the underlying mechanisms remain unclear. To investigate this effect, rats were fed a high-fat diet supplemented with 5% water extract from either the reishi mushroom (Ganoderma lingzhi) (WGL) or the auto-digested reishi G. lingzhi (AWGL) for three weeks. Both extracts markedly reduced fecal secondary bile acids, such as lithocholic acid and deoxycholic acid (colon carcinogens). These extracts reduced the numbers of Clostridium coccoides and Clostridium leptum (secondary bile acids-producing bacteria) in a per g of cecal digesta. Fecal mucins and cecal propionate were significantly elevated by both extracts, and fecal IgA was significantly elevated by WGL, but not by AWGL. These results suggest that the reishi extracts have an impact on colon luminal health by modulating secondary bile acids, microflora, mucins, and propionate that related to colon cancer.

Supplemental fermented plant product ('Manda Koso') reduces succinate and deoxycholate, as well as elevates IgA and mucin levels, in rats fed a high-fat diet.

'Manda Koso' is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that have been fermented for >3 years and 3 months. We hypothesized that FPP intake improves the luminal environment of rats fed a high-fat diet. Thus, the present study examined the effects of consumption of 5% FPP diet for 3 weeks on colonic luminal parameters in rats fed a 30% beef tallow diet. Food intake and body weight gain were unaffected. Consumption of the FPP diet did not influence the proportions of Bifidobacterium, Lactobacillus, Bacteroides, Prevotella or Clostridium in cecal contents. However, the FPP diet caused a significant reduction (-88%) in the level of cecal succinate, a putative inflammatory signal (P<0.01), but did not affect the levels of n-butyrate, propionate, acetate and lactate. The fecal levels of deoxycholate and hyodeoxycholate, which are toxic bile acids, were also significantly reduced by the FPP diet (P<0.05). The FPP diet significantly increased fecal immunoglobulin A and mucins responsible for intestinal immune and barrier functions (P<0.05). The results suggest that the consumption of FPP is beneficial for the colonic luminal environment in rats fed a high-fat diet.

Beneficial effects of protease preparations derived from Aspergillus on the colonic luminal environment in rats consuming a high-fat diet.

The present study investigated the effects of the dietary addition of the protease preparations derived from Aspergillus on the colonic luminal environment. Rats were fed a 30% beef tallow diet with or without the protease preparations, including Amano protease (protease A 'Amano SD', neutral proteases from Aspergillus spp.) or orientase (orientase AY, acid proteases from Aspergillus niger) at the dose of 0.2% for 3 weeks. Cecal Bifidobacterium was significantly elevated in the dietary Amano protease group (194-fold, P<0.05), but not in the orientase group. Lactobacillus was elevated in the two groups (P<0.05). Cecal n-butyrate, propionate and lactate were higher in the Amano protease and orientase groups compared with the controls (P<0.05). Fecal immunoglobulin A and mucins were elevated in the Amano protease group (P<0.05). These results suggest the potential effect of the consumption of Aspergillus-derived protease preparations that are favorable for the colonic luminal environment in rats fed a high-fat diet.

[XI Hong, XI Hong acupuncture school of thought and Xi Hong Fu].

XI Hong, a famous acupuncturist in the Southern Song Dynasty, has an important influence and status in history of Chinese acupuncture and moxibustion. After he moved to Linchuan, Jiangxi province, his descendants passed acupuncture from generation to generation. According to records, it was passed to 12 generations. After the tenth generation, it was also passed to apprentices besides descendants, such as accomplished acupuncturists CHEN Hong-gang, LIU Jin and others, forming XI Hong acupuncture school of thought. The poem of acupuncture and moxibustion XI Hong Fu is the representative work about XI Hong academic thought, which was additionally compiled or written by XI Hong's apprentices according to XI Hong academic thought. The poems are of characteristics in acupuncture application and association of acupoints. The academic thought and therapeutic methods of acupuncture in the poems still are widely used in modern clinical acupuncture practice.