The Landscape of Gut Microbiota and Its Metabolites: A Key to Understanding the Pathophysiology of Pattern in Chinese Medicine.

Liver Stagnation and Spleen Deficiency (LSSD) is a Chinese Medicine (CM) pattern commonly observed in gastrointestinal (GI) diseases, yet its biological nature remains unknown. This limits the global use of CM medications for treating GI diseases. Recent studies emphasize the role of gut microbiota and their metabolites in the pathogenesis and treatment of LSSD-associated GI diseases. There is increasing evidence supporting that an altered gut microbiome in LSSD patients or animals contributes to GI and extra-intestinal symptoms and affects the effectiveness of CM therapies. The gut microbiota is considered to be an essential component of the biological basis of LSSD. This study aims to provide an overview of existing research findings and gaps for the pathophysiological study of LSSD from the gut microbiota perspective in order to understand the relationship between the CM pattern and disease progression and to optimize CM-based diagnosis, prevention, and therapy.

Altered gut microbiota-host bile acid metabolism in IBS-D patients with liver depression and spleen deficiency pattern.

BACKGROUND: Dysregulation of gut microbiota-host bile acid (BA) co-metabolism is a critical pathogenic factor of diarrhea-predominant irritable bowel syndrome (IBS-D). Traditional Chinese Medicine (TCM), instructed by pattern differentiation, is effective in treating IBS-D, in which liver depression and spleen deficiency (LDSD) is the most prevalent pattern. Still, it is unclear the linkage between the LDSD pattern and the BA metabolic phenotype. PURPOSE: This study aimed to uncover the biological basis of the LDSD pattern from the BA metabolic perspective. METHODS: Patients with IBS-D completed questionnaires regarding the irritable bowel severity scoring system (IBS-SSS), stool frequency, Stool Bristol scale, and Self-Rating Scales of mental health. Fasting blood and morning feces were collected to analyze the gut metagenome and BA-related indices/metabolites. RESULTS: IBS-D patients with LDSD had a higher incidence of BA overexcretion (41% vs. 23% non-LDSD) with significant elevations in fecal total BAs and serum BA precursor 7α-hydroxy-4-cholesten-3-one levels. Compared to controls or non-LDSD patients, LDSD patients had a featured fecal BA profile, with higher proportions of deoxycholic acid (DCA), 7-ketodeoxycholic acid, and lithocholic acid. It is consistent with the BA-metabolizing genomic changes in the LDSD gut microbiota characterized by overabundances of 7-dehydroxylating bacteria and BA-inducible genes (baiCD/E/H). The score of bowel symptoms (stool frequency and abdominal pain) showing greater severity in the LDSD pattern were positively correlated with bai-expressing bacterial abundances and fecal DCA levels separately. CONCLUSION: We clarified a differed BA metabolic phenotype in IBS patients with LDSD, which closely correlates with the severity of bowel symptoms. It demonstrates that gut microbiota and host co-metabolism of BAs would provide crucial insight into the biology of the LDSD pattern and its internal relationship with IBS progression.

Hypolipidemic effects of macadamia oil are related to AMPK activation and oxidative stress relief: In vitro and in vivo studies.

Macadamia oil is rich in monounsaturated fatty acids, especially a high level of palmitoleic acid, which may have beneficial health effects by lowering blood lipid levels. In our study, the hypolipidemic effects of macadamia oil and its potential mechanisms of action were investigated using a combination of in vitro and in vivo assays. The results showed that macadamia oil significantly reduced lipid accumulation, and improved triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in oleic acid-induced high-fat HepG2 cells. The macadamia oil treatment also exhibited antioxidant effects, as seen by its ability to reduce reactive oxygen species and malondialdehyde (MDA) levels, and increase superoxide dismutase (SOD) activity. The effects of 1000 µg/mL of macadamia oil were comparable to that of 4.19 µg/mL simvastatin. The results of qRT-PCR and western blotting analyses indicated that macadamia oil effectively inhibited hyperlipidemia by reducing the expression levels of SREBP-1c, PPAR-γ, ACC and FAS and by enhancing the expression levels of HO-1, NRF2 and γ-GCS, via AMPK activation and oxidative stress relief, respectively. In addition, different doses of macadamia oil were found to significantly improve liver lipid accumulation, reduce serum and liver TC, TG, and LDL-C levels, increase HDL-C levels, increase antioxidant enzyme (SOD, GSH-Px, and T-AOC) activity, and decrease the MDA content of mice on a high-fat diet. These results indicated that macadamia oil had a hypolipidemic effect and provide insights that might facilitate the development of functional food and dietary supplements.

Nutrient controlled release performance of bio-based coated fertilizer enhanced by synergistic effects of liquefied starch and siloxane.

The porous structure and hydrophilicity of coating shells affect the nutrient controlled-release performance of castor oil-based (CO) coated fertilizers. In order to solve these problems, in this study, the castor oil-based polyurethane (PCU) coating material was modified with liquefied starch polyol (LS) and siloxane, and a new coating material with cross-linked network structure and hydrophobic surface was synthesized, and used it to prepare the coated controlled-release urea (SSPCU). The results demonstrated that the cross-linked network formed by LS and CO improved the density and reduced the pores on the surface of the coating shells. The siloxane was grafted on the surface of coating shells to improve its hydrophobicity and thus delayed water entry. The nitrogen release experiment indicated that the synergistic effects of LS and siloxane improved the nitrogen controlled-release performance of bio-based coated fertilizers. Nutrient released longevity of SSPCU with 7 % coating percentage reached >63 days. Moreover, the nutrient release mechanism of coated fertilizer was further revealed by the analysis of the release kinetics analysis. Therefore, the results of this study provide a new idea and technical support for development of efficient and environment-friendly bio-based coated controlled-release fertilizers.

Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier.

Background: Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC. Methods: A mouse cecum orthotopic CRC model combined with high-fat diet (HFD) feeding, was established to mimic liver metastasis in CRC in obese patients. The effects of Dachaihu decoction (DCHD), a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease, and of the conventional prescription medicine obeticholic acid (OCA) were evaluated. HFD-induced obesity, hyperlipidemia, and CRC liver metastasis were assessed, along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues. The effects of DCHD and OCA on HFD-induced outcomes were evaluated, and human umbilical vein endothelial cells (HUVECs) treated with bile acids (BAs) and DCHD were used to study the underlying mechanisms in vitro. Results: HFD-mediated obesity and hyperlipidemia promoted CRC metastasis, accompanied by disruption of the gut vascular barrier (GVB) and altered bile acid (BA) metabolism. DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC, improving overall survival. Those effects of DCHD were equivalent to or better than those of OCA. DCHD regulated the expression of genes of BA metabolism and tight junctions (TJ) to prevent HFD-induced disruption of the GVB. In HUVECs, DCHD prevented the increases in intracellular Ca2+ and accumulation of reactive oxygen species induced by primary conjugated BAs, assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins, thereby maintaining the integrity of the endothelial barrier. Conclusions: The data provide a link between hypernutrition and GVB disruption, which contributes to high liver metastasis in patients with CRC. DCHD may represent a novel therapy in CRC, and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.

Preparation of ethylenediamine-modified pectin/alginate/Fe3O4 microsphere and its efficient Pb2+ adsorption properties.

As a common macromolecular carbohydrate, pectin has a strong affinity for Pb2+. An ethylenediamine modified pectin (EP48) with 48 % of amidation was prepared and exhibited great removal efficiency towards Pb2+ in our previous study. However, the EP48 has drawbacks in adsorption including low mechanical strength and difficulty in separation. In this study, EP48 was compounded with sodium alginate (Alg) and Fe3O4 to synthesize EP48/Alg/Fe3O4 microsphere. The physicochemical properties and Pb2+ adsorption characteristics of microsphere were analyzed. It was found that the microsphere exhibited good thermal stability, mechanical strength, porous structure, as well as acid tolerance. The pseudo-second-order model well described the kinetics of adsorption process, indicating the chemical adsorption is dominant. The Langmuir model fitted the experimental data well, and the maximum adsorption capacity reached 175.19 mg/g. Adsorption-desorption experiments showed that the removal rate of the microsphere maintained over 98.9 % after 10 cycles. The X-ray photoelectron spectroscopy (XPS) analyses revealed that the potential adsorption mechanism included ion-exchange and chelation. The above results suggested its potential use for the removal of Pb2+ from wastewater.

Atractylenolide II prevents radiation damage via MAPKp38/Nrf2 signaling pathway.

Ionizing radiation (IR) can act as a negative factor for human homeostasis, by causing and even aggravating a series of pathological conditions. To protect the intactness of normal tissues, effective anti-radiation drugs are urgently needed for alleviating the outcomes of radioactive damage. In this study, we demonstrate that atractylenolide II (ATR II), a sesquiterpenoid monomer extracted from traditional Chinese medicine atractylodes macrocephala, can markedly suppress IR damage by promoting the expression of antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone oxido-reductase 1 (NQO-1), which are mediated by nuclear factor-erythroid 2-like 2 (Nrf2) signaling pathway. Furthermore, here we reveal that ATR II effectively upregulates the expression of mitogen-activated protein kinase p38 (MAPKp38), which also acts as a regulator of Nrf2 signaling cascade. Indeed, treatment with a MAPKp38 inhibitor can significantly downregulate the expression of Nrf2 and its downstream target genes HO-1 and NQO-1 and, consequently, abolish the protective effect of ATR II against IR. Consistently, ATR II also has a protective function against IR-induced damage in animal models. In conclusion, our study provides an unexpected function of ATR II in preventing IR-induced damage by modulating MAPKp38/Nrf2 signaling pathway.

Ginger Oleoresin Alleviated γ-Ray Irradiation-Induced Reactive Oxygen Species via the Nrf2 Protective Response in Human Mesenchymal Stem Cells.

Unplanned exposure to radiation can cause side effects on high-risk individuals; meanwhile, radiotherapies can also cause injury on normal cells and tissues surrounding the tumor. Besides the direct radiation damage, most of the ionizing radiation- (IR-) induced injuries were caused by generation of reactive oxygen species (ROS). Human mesenchymal stem cells (hMSCs), which possess self-renew and multilineage differentiation capabilities, are a critical population of cells to participate in the regeneration of IR-damaged tissues. Therefore, it is imperative to search effective radioprotectors for hMSCs. This study was to demonstrate whether natural source ginger oleoresin would mitigate IR-induced injuries in human mesenchymal stem cells (hMSCs). We demonstrated that ginger oleoresin could significantly reduce IR-induced cytotoxicity, ROS generation, and DNA strand breaks. In addition, the ROS-scavenging mechanism of ginger oleoresin was also investigated. The results showed that ginger oleoresin could induce the translocation of Nrf2 to cell nucleus and activate the expression of cytoprotective genes encoding for HO-1 and NQO-1. It suggests that ginger oleoresin has a potential role of being an effective antioxidant and radioprotective agent.

Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts.

Miracle berry is known for its unique characteristic of modifying sour flavours to sweet. Twelve phenolics were identified and quantified in the miracle berry flesh at a level from 0.3 for kaempferol to 17.8 mg/100g FW for epicatechin. Lutein and α-tocopherol were also quantified at a level of 0.4 and 5.8 mg/100g FW, respectively. The TP and TF contents were 1448.3 GA and 9.9 QR mg Equiv/100g FW for the flesh, respectively, compared with 306.7 GA and 3.8 mg QR mg Equiv/100g FW of the seeds. The free radical scavenging and reducing percentage of the flesh extract was 96.3% and 32.5% in DPPH and ABTS assays, respectively. Additionally, the flesh extract had a high FRAP of 22.9 mmol/100g. It significantly inhibited the oxidation of PUFA in fish oil as well. Thus, miracle berry could also serve as an antioxidant-rich fruit to provide health promoting function.

Experimental determination of dosimetry parameters for Sinko (125)I seed source using a modified polystyrene phantom.

Successful treatment for permanent implant brachytherapy is based on accurate measurement of dosimetry parameters for the seed sources. Literature describes the application of various types of phantom to determine the AAPM TG-43 dosimetry parameters for permanent implant seeds. Previously we created a new type of phantom used to measure the dosimetry parameters of a high dose-rate (192)Ir source. In this study, we modified the phantom to suit to a common type of (125)I seed source (Sinko BT-125-1). The dose-rate constant, radial dose function and anisotropy function of this source were measured in detail and compared with the published values of other similar in-design (125)I seed sources. The experimental results exhibit fairly small measurement uncertainties and good self-consistency. The modified phantom is demonstrated on the measurement of dosimetry parameters for the Sinko BT-125-1 (125)I seed, however, it could easily be used for similar measurements of other permanent implantation seed sources.