In vivo study on osteogenic efficiency of nHA/ gel porous scaffold with nacre water-soluble matrix.

BACKGROUND/PURPOSE: Nano-hydroxyapatite (nHA)/ gel porous scaffolds loaded with WSM carriers are promising bone replacement materials that can improve osseointegration ability. This investigation aimed to evaluate the osteoinductive activity by implanting the composition of nano-hydroxyapatite (nHA)/ Gel porous scaffolds as a carrier of WSM via an animal model. MATERIALS AND METHODS: WSM was extracted and nHA was added to the matrix to construct porous composite scaffolds. The dose-effect curve of WSM concentration and alkaline phosphatase (ALP) activity was made by culturing rat osteoblasts and examining the absorbance. Three different materials were implanted into critical size defects (CSD) in the skulls of rats, which were further divided into four groups: WSM nHA /Gel group, n-WSM nHA /Gel group, HA powder group, and control group. RESULTS: WSM (150 µg/mL-250µg/mL) effectively improved the activity of ALP in rat osteoblasts. All rats in each group had normal healing. WSM-loaded nHA /Gel group showed better performance on newly-formed bone tissue of rat skull and back at 4th week and 8th week, respectively. At the 4th week, the network of woven bone formed in the WSM-loaded nHA/Gel scaffold material. At 8th week, the reticular trabecular bone in the WSM-loaded scaffold material became dense lamellar bone, and the defect was mature lamellar bone. In the subcutaneous implantation experiment, WSM-loaded nHA/Gel scaffold material showed a better performance of heterotopic ossification than the pure nHA/Gel scaffold material. CONCLUSION: WSM promotes osteoblast differentiation and bone mineralization. The results confirm that the nHA/ Gel Porous Scaffold with Nacre Water-Soluble Matrix has a significant bone promoting effect and can be used as a choice for tissue engineering to repair bone defects.

Network pharmacology-based strategy combined with molecular docking to explore the potential mechanism of agarwood against recurrent aphthous stomatitis.

To explore the antiinflammatory mechanism of agarwood on recurrent aphthous stomatitis (RAS). RAS is the most common mucosal disease in the oral cavity. The clinical application of traditional Chinese medicine found that agarwood has significant curative effect on peptic ulcer, but the effect and mechanism of agarwood on RAS remain unclear. This study is intended to predict the potential antiinflammatory mechanisms by which agarwood acts on RAS through network pharmacology and molecular docking. TCMSP database was used to screen the active components of agarwood. RAS targets were screened in Genecards, DisGeNET, and OMIM database. Venny, an online tool, screens for interacting genes between the two. Cytoscape software was used to construct the gene regulation map of active compounds target of agarwood. String Database building protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were enriched in DAVID database. The key active ingredients and core targets were further verified by molecular docking. There were 9 effective compounds and 186 target genes in agarwood; RAS has 793 target genes. There were 41 interacting genes between agarwood and RAS. Interleukin 6, tumor necrosis factor, interleukin 1 beta, and cellular component motif ligand 2 may be key targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted multiple pathways associated with RAS. Molecular docking results showed that the active compounds of agarwood combined well and stably with the target. The Chinese herbal medicine agarwood can relieve the inflammation of RAS through multiple targets and various ways. Its active compounds may be nominated as candidates for antiinflammatory drugs of RAS.

Mitochondrial damage-associated molecular patterns: A new insight into metabolic inflammation in type 2 diabetes mellitus.

The pathogenesis of diabetes is accompanied by increased levels of inflammatory factors, also known as "metabolic inflammation", which runs through the whole process of the occurrence and development of the disease. Mitochondria, as the key site of glucose and lipid metabolism, is often accompanied by mitochondrial function damage in type 2 diabetes mellitus (T2DM). Damaged mitochondria release pro-inflammatory factors through damage-related molecular patterns that activate inflammation pathways and reactions to oxidative stress, further aggravate metabolic disorders, and form a vicious circle. Currently, the pathogenesis of diabetes is still unclear, and clinical treatment focuses primarily on symptomatic intervention of the internal environment of disorders of glucose and lipid metabolism with limited clinical efficacy. The proinflammatory effect of mitochondrial damage-associated molecular pattern (mtDAMP) in T2DM provides a new research direction for exploring the pathogenesis and intervention targets of T2DM. Therefore, this review covers the most recent findings on the molecular mechanism and related signalling cascades of inflammation caused by mtDAMP in T2DM and discusses its pathogenic role of it in the pathological process of T2DM to search potential intervention targets.

Moxibustion as an adjunctive treatment for rheumatoid arthritis and its effects on the serum levels of SOST and ß-catenin. / è‰¾ç¸è¾ åŠ©æ²»ç–—ç±»é£Žæ¹¿å ³èŠ‚ç‚ŽåŠå¯¹æ‚£è€ è¡€æ¸ SOST、ß-catenin含量的影响.

OBJECTIVES: To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and ß-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients. METHODS: Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, ß-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups. RESULTS: Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, ß-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum ß-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group. CONCLUSIONS: In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of ß-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/ß-catenin signaling pathway.

Revealing the mechanism of quinoa on type 2 diabetes based on intestinal flora and taste pathways.

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

Network pharmacology and molecular docking-based investigation on traditional Chinese medicine Astragalus membranaceus in oral ulcer treatment.

To analyze the mechanism of Astragalus membranaceus (AM) in molecular level in the oral ulcer (OU) treatment with reference to network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used in screening the AM active components and AM action targets; GeneCards database was used to screen OU targets; the common target were screened by Venny online tool; Cytoscape software was applied to construct the target gene regulation map of AM active components; STRING database was used to construct the protein-protein interaction network and the key targets were screened as per degree value; gene ontology enrichment and KEGG pathway enrichment of interactive genes were calculated through David database. There were 17 active ingredients and 429 target spots in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. There are 606 target genes for OU in GeneCards database. There are 67 common targets, including 10 key targets: IL10, IL6, TNF, IL1B, CXCL8, CCL2, TLR4, IL4, ICAM1, and IFNG. It involves 30 gene ontology terms and 20 KEGG signal channels. The molecular docking results showed that quercetin and kaempferol had a good binding activity with IL6, IL1B, TNF, and CCL2. Network pharmacological analysis shows that AM can regulate multiple signal pathways through multiple targets to treat OU.

[Regulatory effect of moxibustion on LTB4/MMP-9 in serum of patients with rheumatoid arthritis].

OBJECTIVE: To observe the effects of moxibustion on the contents of leukotriene B4 (LTB4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase -9 (MMP-9) in serum, and explore the protection mechanisms of moxibustion in the patients with rheumatoid arthritis (RA). METHODS: A total of 64 patients with RA were randomly divided into treatment group (n=31) and control group (n=33). The patients in the control group were treated with conventional medication for consecutive 5 weeks. Based on the treatment in the control group, the patients in the treatment group were treated with moxibustion at bilateral Shenshu (BL23), Zusanli (ST36) and Ashi points, 3 times a week, for consecutive 5 weeks. Separately, the visual analogue scale (VAS) score, morning stiffness score, the number of tender joints, the number of swollen joints, the score of the disease activity score of 28 joints (DAS28) were observed; the contents of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reative protein (CRP) in serum were determined by biochemical method; and the contents of LTB4, IL-17, TNF-α and MMP-9 in serum were detected by using ELISA before and after treatment in the patients of both groups. RESULTS: After treatment, VAS score, morning stiffness score, the number of tender joints, the number of swollen joints, DAS28 score, the contents of serum RF in both groups, and contents of serum CRP, ESR, LTB4, IL-17, TNF-α and MMP-9 in the treatment group were significantly reduced when compared with those before treatment (P<0.01, P<0.05). After treatment, VAS score, morning stiffness score, the number of tender joints, the number of swollen joints, DAS28 score, and the levels of LTB4, IL-17 and MMP-9 in serum were obviously lower in the treatment group when compared with the control group (P<0.01, P<0.05). In the treatment group, the changes before and after treatment in the levels of LTB4, IL-17 and TNF-α were positively correlated with that of MMP-9 (P<0.05, r>0). CONCLUSION: Moxibustion at BL23 and ST36 combined with conventional medication significantly relieves joint pain and reduce disease activity in RA patients, which may be related to the modulation of LTB4, IL-17 and MMP-9 by moxibustion.

Moringa oleifera leaf attenuate osteoporosis in ovariectomized rats by modulating gut microbiota composition and MAPK signaling pathway.

Moringa oleifera leaf (MLP) contains abundant complex nutrients with anti-osteoporosis potential. However, its efficacy and mechanisms against osteoporosis remain unknown. The purpose of this research is to investigate MLP's anti-osteoporotic effects and mechanisms. Animal experiments were used in this work to validate MLP's anti-osteoporotic efficacy. We investigated the mode of action of MLP, analyzed its impact on the gut microbiota, and predicted and validated its anti-osteoporosis-related molecular targets and pathways through network pharmacology, molecular docking, and western blotting. In an ovariectomized osteoporosis rat model, MLP significantly increased bone mineral density and improved bone metabolism-related indicators, bone microstructure, and lipid profile. Moreover, it improved gut microbiota composition and increased the expression of Occludin and Claudin-1 protein in the duodenum. Network pharmacology identified a total of 97 active ingredients and 478 core anti-osteoporosis targets. Of these, MAPK1 (also known as ERK2), MAPK3 (also known as ERK1), and MAPK8 (also known as JNK) were successfully docked with the active constituents of MLP. Interestingly, MLP increased ERK and VAV3 protein expression and decreased p-ERK and JNK protein expression in the femur. These findings confirm MLP's anti-osteoporotic efficacy, which could be mediated via regulation of gut microbiota and MAPK signaling.

[Moxibustion for rheumatoid arthritis and its effect on related negative emotions].

OBJECTIVE: To observe the clinical efficacy of moxibustion on rheumatoid arthritis (RA) and its effect on related negative emotions, and to explore the possible mechanism. METHODS: A total of 70 patients with RA were randomized into an observation group (35 cases, 1 case dropped off) and a control group (35 cases, 2 cases dropped off). Conventional western medication therapy was adopted in the control group. On the basis of the treatment in the control group, moxibustion at Zusanli (ST 36), Shenshu (BL 23) and ashi points was adopted in the observation group, once every other day, 3 times a week, and totally 5-week treatment was required in the two groups. Before and after treatment, the scores of visual analogue scale (VAS), morning stiffness, 28-joint disease activity score (DAS28), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed and levels of serum 5-hydroxytryptamine (5-HT), glucocorticoid receptor (GR) and interleukin (IL)-1ß were detected by ELISA method in the two groups respectively. RESULTS: Compared before treatment, the scores of VAS and DAS28 were decreased after treatment in both groups (P<0.01, P<0.05), and the scores of morning stiffness, SAS, SDS and the serum levels of 5-HT, GR, IL-1ß were decreased after treatment in the observation group (P<0.01). After treatment, the scores of VAS, morning stiffness, DAS28, SAS, SDS and the serum levels of GR, IL-1ß in the observation group were lower than those in the control group (P<0.05, P<0.01). The clinical symptoms of RA (scores of VAS, morning stiffness and DAS28) were positively correlated with negative emotions (scores of SAS and SDS, r=0.439, P<0.01), the VAS score was positively correlated with serum levels of 5-HT (r=0.189, P<0.05) and IL-1ß (r=0.189, P<0.05). CONCLUSION: Moxibustion can improve the clinical symptoms and negative emotions in patients with RA by regulating the inflammatory reactions.

Quinoa Reduces High-Fat Diet-Induced Obesity in Mice via Potential Microbiota-Gut-Brain-Liver Interaction Mechanisms.

The gut microbiota is important in the occurrence and development of obesity. It can not only via its metabolites, but also through microbiota-gut-brain-liver interactions, directly or indirectly, influence obesity. Quinoa, known as one kind of pseudocereals and weight loss food supplements, has been high-profile for its high nutritional value and broad applications. In this context, we produced high-fat diet-induced (HFD) obese mouse models and assessed the efficacy of quinoa with saponin and quinoa without saponin on obesity. We explored the potential therapeutic mechanisms of quinoa using methods such as 16S rRNA, Western blotting, Immunohistochemical (IHC). Our results indicated that quinoa can improve the obese symptoms significantly on HFD mice, as well as aberrant glucose and lipid metabolism. Further analyses suggest that quinoa can regulate microbiota in the colon and have predominantly regulation on Bacteroidetes, Actinobacteria and Desulfovibrio, meanwhile can decrease the F/B ratio and the abundance of Blautia. Contemporaneously, quinoa can upregulate the expression of TGR5 in the colon and brain, as well as GLP-1 in the colon, liver and brain. while downregulate the expression of TLR4 in the colon and liver, as well as markers of ER stress and oxidative stress in livers and serums. Beyond this, tight junctional proteins in colons and brains are also increased in response to quinoa. Therefore, quinoa can effectively reduce obesity and may possibly exert through microbiota-gut-brain-liver interaction mechanisms. IMPORTANCE Gut microbiota has been investigated extensively, as a driver of obesity as well as a therapeutic target. Studies of its mechanisms are predominantly microbiota-gut-brain axis or microbiota-gut-liver axis. Recent studies have shown that there is an important correlation between the gut-brain-liver axis and the energy balance of the body. Our research focus on microbiota-gut-brain-liver axis, as well as influences of quinoa in intestinal microbiota. We extend this study to the interaction between microbiota and brains, and the result shows obvious differences in the composition of the microbiome between the HFD group and others. These observations infer that besides the neurotransmitter and related receptors, microbiota itself may be a mediator for regulating bidirectional communication, along the gut-brain-liver axis. Taken together, these results also provide strong evidence for widening the domain of applicability of quinoa.

[Effects of baldrinal of Valeriana jatamansi on expression of CRF, TPH1 mRNA and 5-HT in rats with irritable bowel syndrome].

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.

[Textual research for Tibetan medicine Qumazi].

Qumazi is a commonly used Tibetan medicine. With a long history, it can be found in the Four Medical Tantras written by gYu-thog rNying-ma Yon-tan mGon-po since the 8th century AD. Qumazi grows in mudflats and fields, including species growing in highlands, lowlands, mountains and farmlands. According to records in Crystal Beads Materia Medica, it features green sword-shaped leaves, thin stems with red veins, inserted panicles, white chicken-like flowers and copper needle row-like roots. However, there are many inconsistent morphological descriptions for Qumazi plants in many Chinese versions of Tibetan medicine books. In this article, after studying ancient and modern Tibetan medicine books, consulting experts and conducting surveys, the authors confirmed that Qumazi belongs to Rheum of Polygonaceae, including Rheum nobile Hook. f. et. Thoms, R. globulosum Gage, R. alexandrae Hook. f. et. Thoms, R. pumilum Maxim and R. delavayi Franch. In some regions, Qumazi is substituted by R. spiciforme Royle and R. przewalskyi Losinsk. After the Chinese version of Qinghai-Tibet Plateau Drug Illustrations was published in 1972, Qumazi has been miswritten as P. sibiricum Laxm in many Chinese versions of Tibetan medicine books, perhaps because P. sibiricum Laxm has many similar features with Qumazi as described in Crystal Beads Materia Medica and then is mistranslated from Tibetan to Chinese versions. According to records, Qumazi can reduce edema and is mainly applied to treat the minamata disease in clinic.

[Mutation in the UBIAD1 gene of a Chinese family with Schnyder crystal corneal dystrophy].

OBJECTIVE: To investigate the genetic feature of Schnyder corneal dystrophy identified in a four-generation Chinese family. METHOD: Ophthalmologic examinations were performed in 3 affected members and 2 unaffected members of a family with Schnyder corneal dystrophy and controls. Genomic DNA was extracted from peripheral blood. The coding regions, 3'UTR and 5'UTR of UBIAD1 gene from all samples were screened by polymerase chain reaction (PCR) and direct DNA sequencing using the primers designed according to the sequence of UBIAD1, and comparatively analyzed with data from Genebank. RESULT: The family has 15 members over 4 generations with similar signs and symptoms among proband and affected members. All affected members of the family demonstrated central discoid crystalline deposition with arcus lipoide. Confocal microscopy examination showed multiple depositions of crystalline materials in anterior stroma. OCT showed the high reflective material localized within the anterior stroma. A missense mutation c.305A > G in 1 exon of UBIAD1 gene resulting in a substitution of Asparagine to Serine at codon 102 (p.Asn102Ser) was found in all affected members of the family who were clinically diagnosed as Schnyder corneal dystrophy while not in the unaffected members of the family and controls. CONCLUSION: The missense mutation c.305A > G(p.Asn102Ser) of UBIAD1 gene may cause the disease of the family. Gene screen can assist clinicians in making definitive diagnosis, presymptomatic diagnosis and prenatal diagnosis.