[Analysis and prospect of correlation between relative molecular weight and efficacy of polysaccharides from medicinal plant resources].

Polysaccharides from medicinal plant resources are a kind of polymers extracted from medicinal plants. They are complex long chains formed by different monosaccharides connected via glucosidic bonds. These polysaccharides usually have straight chain and branched chain structures, and their relative molecular weight changes greatly. Modern studies have shown that the biological activi-ty of polysaccharides from medicinal plant resources is closely related to their relative molecular weight. This paper first reviewed the preparation and detection methods of polysaccharides from medicinal plant resources with different relative molecular weights. Then, the paper summarized and analyzed the general experience of the correlation between efficacy and relative molecular weight of polysaccharides from medicinal plant resources with different molecular weights. It was considered that polysaccharides with large relative molecular weights(>100 kDa) play a leading role in immune regulation. Polysaccharides with medium relative molecular weights(10-100 kDa) play a leading role in immune regulation and the protection of the liver. Polysaccharides with small relative molecular weights(<10 kDa) play a leading role in anti-oxidation, regulation of intestinal flora, regulation of blood glucose and lipids, anti-fatigue, and the protection of nerves. Therefore, precise development of polysaccharides from medicinal plant resources based on relative molecular weight is expected to improve their biological activity and application value.

Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

[Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway].

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification.

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.

EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis.

Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.

The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification.

Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification was observed when VSMCs were exposed to ECs culture media stimulated by uremic serum or high concentration of inorganic phosphate (3.5 mM Pi). and the pro-calcification effect of the ECs culture media was attenuated by exosome depletion. Exosomes derived from high concentrations of inorganic phosphate-induced ECs (ECsHPi-Exos) could be uptaken by VSMCs and promoted VSMCs calcification. Microarray analysis showed that miR-670-3p was dramatically increased in ECsHPi-Exos compared with exosomes derived from normal concentrations of inorganic phosphate (0.9 mM Pi) induced ECs (ECsNPi-Exos). Mechanistically, insulin-like growth factor 1 (IGF-1) was identified as the downstream target of miR-670-3p in regulating VSMCs calcification. Notably, ECs-specific knock-in of miR-670-3p of the 5/6 nephrectomy with a high-phosphate diet (miR-670-3pEC-KI + NTP) mice that upregulated the level of miR-670-3p in artery tissues and significantly increased artery calcification. Finally, we validated that the level of circulation of plasma exosomal miR-670-3p was much higher in patients with ESRD compared with healthy controls. Elevated levels of plasma exosomal miR-670-3p were associated with a decline in IGF-1 and more severe artery calcification in patients with ESRD. Collectively, these findings suggested that ECs-derived exosomal miR-670-3p could promote arterial calcification by targeting IGF-1, which may serve as a potential therapeutic target for arterial calcification in ESRD patients.

[Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years].

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

[Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage].

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

[Systematic review and Meta-analysis of efficacy and safety of acupuncture therapy on hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.

[Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Alanylglutamine Relieved Asthma Symptoms by Regulating Gut Microbiota and the Derived Metabolites in Mice.

OBJECTIVE: Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. METHODS: Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKß, TGF-ß, and IL-1ß through Western blot or RT-qPCR. RESULTS: It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKß/IKKß, TGF-ß, and IL-1ß, with similar effects from butyric acid. CONCLUSION: The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.

[Effect of glutamine-supplemented enteral nutrition on the apoptosis of colonic mucosal cells in young rats with inflammatory bowl disease].

OBJECTIVE: To study the effect of glutamine-supplemented enteral nutrition in regulating the apoptosis of intestinal mucosal cells and promoting mucosal healing in young rats with inflammatory bowl disease (IBD). METHODS: A total of 80 male Sprague-Dawley rats aged 4-5 weeks were randomly divided into 4 groups: blank control, IBD model, short peptide, and short peptide+glutamine (n=20 each). The IBD model was prepared by a single colon perfusion of 3-nitrobenzene sulfonic acid. At 3 days after modeling, the rats in the short peptide group were fed with short peptide formula (100 mL/kg), and those in the short peptide+glutamine group were fed with short peptide formula (100 mL/kg) and glutamine (0.5 g/kg). The course of intervention was 1 week. General conditions were observed after the experiment and their intestinal mucosal tissue was obtained. Hematoxylin-eosin staining was used to observe the pathological change of the intestinal mucosa. RT-PCR was used to measure the expression of apoptosis-regulating genes (bax and bc1-2) and apoptotic signal transduction factors (Caspase-3 and Caspase-9) in the intestinal mucosa. Western blot was used to measure the expression of insulin-like growth factor-1 (IGF-1) in the colonic mucosa. RESULTS: The IBD model group had poorer general conditions than the other three groups (blank control, short peptide and short peptide+glutamine), and the short peptide+glutamine group had better general conditions than the IBD model and short peptide groups. The IBD model group had significantly higher mRNA expression of bax than the other three groups (P<0.05). There was no significant difference in the mRNA expression of bcl-2, Caspase-3 and Caspase-9 among the 4 groups (P>0.05). The short peptide group had a significantly higher level of IGF-1 than the short peptide+glutamine, blank control and IBD model groups (P<0.05). CONCLUSIONS: Glutamine-supplemented enteral nutrition can effectively improve the general nutritional status of young rats with IBD, but it is not better than exclusive enteral nutrition in inhibiting the apoptosis of colonic mucosal cells and stimulating the synthesis of IGF-1 in the intestinal mucosa.

Local functional connectivity alterations in schizophrenia, bipolar disorder, and major depressive disorder.

BACKGROUND: Local functional connectivity (FC) indicates local or short-distance functional interactions and may serve as a neuroimaging marker to investigate the human brain connectome. Local FC alterations suggest a disrupted balance in the local functionality of the whole brain network and are increasingly implicated in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). METHODS: We aim to examine the similarities and differences in the local FC across SZ, BD, and MDD. In total, 537 participants (SZ, 126; BD, 97; MDD, 126; and healthy controls, 188) completed resting-state functional magnetic resonance imaging at a single site. The local FC at resting state was calculated and compared across SZ, BD, and MDD. RESULTS: The local FC increased across SZ, BD, and MDD within the bilateral orbital frontal cortex (OFC) and additional region in the left OFC extending to putamen and decreased in the primary visual, auditory, and motor cortices, right supplemental motor area, and bilateral thalami. There was a gradient in the extent of alterations such that SZ > BD > MDD. LIMITATIONS: This cross-sectional study cannot consider medications and other clinical variables. CONCLUSIONS: These findings indicate a disrupted balance between network integration and segregation in SZ, BD, and MDD, including over-integration via increased local FC in the OFC and diminished segregation of neural processing with the weakening of the local FC in the primary sensory cortices and thalamus. The shared local FC abnormalities across SZ, BD, and MDD may shed new light on the potential biological mechanisms underlying these disorders.

Effects and Mechanism of Combination of Rhein and Danshensu in the Treatment of Chronic Kidney Disease.

Traditional Chinese medicine (TCM) plays a systemic role in disease treatment, targeting multiple etiological factors simultaneously. Based on clinical experience, rhubarb and Salvia miltiorrhiza are commonly prescribed together for the treatment of chronic kidney disease (CKD) and have been proven to be very effective. However, the rationale of the combination remains unclear. The major active ingredients of these two herbs are rhein (RH) and danshensu (DSS), respectively. The aim of this paper is to investigate the renoprotective effects of RH and DSS in vitro and in vivo, and the underlying mechanism. A total of 5/6 nephrectomy rats and HK-2 cells were subjected to chronic renal injury. The combination of RH and DSS conferred a protective effect, as shown by a significant improvement in the renal function, blood supply, and fibrotic degree. Proinflammatory cytokines and adhesion molecules were suppressed by RH and DSS through NK-κB signaling. The combination also inhibited apoptosis by up-regulating Bcl-2 and down-regulating Bax. Inhibiting the TGF-ß/Smad3 pathway was at least in part involved in the antifibrotic mechanism of the combination treatment of RH and DSS. This study demonstrates for the first time the renoprotective effect and the mechanism of RH and DSS combination on chronic renal injury. It could provide experimental evidence to support the rationality of the combinatorial use of TCM in clinical practices.

Effects of Two Traditional Chinese Cooking Oils, Canola and Pork, on pH and Cholic Acid Content of Faeces and Colon Tumorigenesis in Kunming Mice.

Faecal pH and cholate are two important factors that can affect colon tumorigenesis, and can be modified by diet. In this study, the effects of two Chinese traditional cooking oils (pork oil and canola/rapeseed oil) on the pH and the cholic acid content in feces, in addition to colon tumorigenesis, were studied in mice. Kunming mice were randomized into various groups; negative control group (NCG), azoxymethane control group (ACG), pork oil group (POG), and canola oil Ggroup (COG). Mice in the ACG were fed a basic rodent chow; mice in POG and COG were given 10% cooking oil rodent chow with the respective oil type. All mice were given four weekly AOM (azoxymethane) i.p. injections (10 mg/kg). The pH and cholic acid of the feces were examined every two weeks. Colon tumors, aberrant crypt foci and organ weights were examined 32 weeks following the final AOM injection. The results showed that canola oil significantly decreased faecal pH in female mice (P<0.05), but had no influence on feces pH in male mice (P>0.05). Pork oil significantly increased the feces pH in both male and female mice (P<0.05). No significant change was found in feces cholic acid content when mice were fed 10% pork oil or canola oil compared with the ACG. Although Kunming mice were not susceptible to AOM-induced tumorigenesis in terms of colon tumor incidence, pork oil significantly increased the ACF number in male mice. Canola oil showed no influence on ACF in either male or female mice. Our results indicate that cooking oil effects faecal pH, but does not affect the faecal cholic acid content and thus AOM-induced colon neoplastic ACF is modified by dietary fat.

Insulinotropic effect of Chikusetsu saponin IVa in diabetic rats and pancreatic ß-cells.

ETHNOPHARMACOLOGICAL RELEVANCE: As a well-known traditional Chinese medicine the root bark of Aralia taibaiensis has traditionally been used as the medicine considered alleviating several disorders including diabetes mellitus (DM). Chikusetsu saponin IVa (CHS) has been defined as a major active ingredient of triterpenoid saponins extracted from Aralia taibaiensis. The scientific evidence of anti-diabetic effect for CHS remains unknown and the purpose of our study was to study its hypoglycemic and insulin secretagogue activities. MATERIALS AND METHODS: In vivo studies were performed on type 2 diabetic mellitus (T2DM) rats given CHS for 28 days to test the antihyperglycemic activity. The in vitro effects and possible mechanisms of CHS on the insulin secretion in pancreatic ß-cell line ßTC3 were determined. RESULTS: Oral administration of CHS dose-dependently increased the level of serum insulin and decreased the rise in blood glucose level in an in vivo treatment. In vitro, CHS potently stimulated the release of insulin from ßTC3 cells at both basal and stimulatory glucose concentrations, the effect which was changed by the removal of extracellular Ca(2+). Two methods showed that CHS enhanced the intracellular calcium levels in ßTC3 cells. CHS was capable of enhancing the phosphorylation of extracellular signal-regulated protein kinases C (PKC), which could be reversed by a PKC inhibitor (RO320432), and the insulin secretion induced by CHS was also inhibited by RO320432. Further study also showed that the insulinotropic effect, intracellular calcium levels and the phosphorylation of PKC were reduced by inhibiting G protein-coupled receptor 40 (GPR40) by a GPR40 inhibitor (DC126026). CONCLUSION: These observations suggest that the signaling of CHS-induced insulin secretion from ßTC3 cells via GPR40 mediated calcium and PKC pathways and thus CHS might be developed into a new potential for therapeutic agent used in T2DM patients.

Canola oil influence on azoxymethane-induced colon carcinogenesis, hypertriglyceridemia and hyperglycemia in Kunming mice.

Azoxymethane (AOM) is a potent genotoxic carcinogen which specifically induces colon cancer. Hyperlipidemia and diabetes have several influences on colon cancer development, with genetic and environmental exposure aspects. Here, we investigated plasma lipid and glucose concentrations in Kunming mice randomized into four groups; control (no AOM or oil exposure), AOM control, AOM + pork oil, and AOM + canola oil. Aberrant crypt foci (ACF), plasma cholesterol, plasma triglyceride, plasma glucose and organ weight were examined 32 weeks after AOM injection. Results revealed that AOM exposure significantly increased ACF number, plasma triglyceride and glucose level. Further, male mice displayed a much higher plasma triglyceride level than female mice in the AOM control group. Dietary fat significantly inhibited AOM-induced hypertriglyceridemia, and canola oil had stronger inhibitory effect than pork oil. AOM-induced hyperglycemia had no sex-difference and was not significantly modified by dietary fat. However, AOM itself not change plasma cholesterol level. AOM significantly increased liver and spleen weight in male mice, but decreased kidney weight in female mice. On the other hand, mice testis weight decreased when fed canola oil. AOM could induce colorectal carcinogenesis, hypertriglyceridemia and hyperglycemia in Kunming mice at the same time, with subsequent studies required to investigate their genome association.

Antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: As a well-known traditional Chinese medicine the root bark of Aralia taibaiensis has multiple pharmacological activities, including relieving rheumatism, promoting blood circulation to arrest pain, inducing diuresis to reduce edema, and antidiabetic action. It has long been used as a folk medicine for the treatment of traumatic injury, rheumatic arthralgia, nephritis, edema, hepatitis and diabetes mellitus in China. AIM OF STUDY: To evaluate the antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis (SAT) in experimental type 2 diabetic mellitus (T2DM) rats. MATERIALS AND METHODS: Acute toxicity was studied in rats to determine the safe oral dose of SAT. Then, SAT was given orally to normal and streptozotocin-nicotinamide induced T2DM rats at 80, 160 and 320 mg/kg doses for a series of 28 days to determine the antihyperglycemic activity. Glibenclamide (600 µg/kg), a standard antidiabetic drug, was used as a positive control drug. At the end of treatment, biochemical parameters and antioxidant levels were measured to evaluate the hypolipidemic and antioxidant activities of SAT. RESULTS: Oral administration of SAT did not exhibit toxicity and death at a dose not more than 2000 mg/kg. SAT dose-dependently improved the symptoms of polydipsia, polyuria, polyphagia and weight loss in diabetic rats. Compared with diabetic control group, administration of 320 mg/kg SAT resulted in significant (P<0.05) fall in the levels of fasting blood glucose, glycosylated hemoglobin, creatinine, urea, alanine transarninase, aspartate aminotransferase, total cholesterol, triglycerides, low density lipoprotein cholesterol and malondialdehyde, but significant (P<0.05) increase in the levels of serum insulin, superoxide dismutase and reduced glutathione. However, SAT did not have any effect on the normal rats. CONCLUSIONS: SAT had excellent antihyperglycemic, hypolipidemic and antioxidant activities in T2DM rats and might be a promising drug in the therapy of diabetes mellitus and its complications.