Haem transporter HRG-1 is essential in the barber's pole worm and an intervention target candidate.

Parasitic roundworms (nematodes) have lost genes involved in the de novo biosynthesis of haem, but have evolved the capacity to acquire and utilise exogenous haem from host animals. However, very little is known about the processes or mechanisms underlying haem acquisition and utilisation in parasites. Here, we reveal that HRG-1 is a conserved and unique haem transporter in a broad range of parasitic nematodes of socioeconomic importance, which enables haem uptake via intestinal cells, facilitates cellular haem utilisation through the endo-lysosomal system, and exhibits a conspicuous distribution at the basal laminae covering the alimentary tract, muscles and gonads. The broader tissue expression pattern of HRG-1 in Haemonchus contortus (barber's pole worm) compared with its orthologues in the free-living nematode Caenorhabditis elegans indicates critical involvement of this unique haem transporter in haem homeostasis in tissues and organs of the parasitic nematode. RNAi-mediated gene knockdown of hrg-1 resulted in sick and lethal phenotypes of infective larvae of H. contortus, which could only be rescued by supplementation of exogenous haem in the early developmental stage. Notably, the RNAi-treated infective larvae could not establish infection or survive in the mammalian host, suggesting an indispensable role of this haem transporter in the survival of this parasite. This study provides new insights into the haem biology of a parasitic nematode, demonstrates that haem acquisition by HRG-1 is essential for H. contortus survival and infection, and suggests that HRG-1 could be an intervention target candidate in a range of parasitic nematodes.

The potential mechanism of WT1-associated protein-induced N-6-methyladenosine modification of colony-stimulating factor 2 in the progression of oral squamous cell carcinoma by JAK/STAT3 pathway regulation.

Colony-stimulating factor 2 (CSF2) plays a regulatory role in numerous cancers. However, there is needed to investigate the role of CSF2 in oral squamous cell carcinoma (OSCC) malignant phenotype and the specific mechanisms of CSF2 N-6-methyladenosine (m6A) modification. Therefore, we investigated the regulatory mechanism of m6A-modified CSF2 by WT1-associated protein (WTAP) in OSCC via qRT-PCR, western blot, WTAP and CSF2 overexpression in OSCC. In a panel of OSCCs, Kaplan-Meier plot analysis indicated that high expression of CSF2 was associated with poorer prognosis. Cell functional experiments revealed that enrichment of CSF2 promoted the proliferation and migration of OSCC cells by activating the JAK/STAT3 pathway, whereas the reduced expression of CSF2 resulted in the malignant decline of OSCC cells by blocking the JAK/STAT3 pathway. This study also confirmed that WTAP enhanced the m6A level of CSF2 and facilitated the expression of CSF2 and that CSF2 silencing blocked the invasive phenotype of OSCC cells and reversed the malignancy induced by WTAP overexpression. Overall, this study demonstrated that WTAP mediates the m6A modification of CSF2 and the JAK/STAT3 pathway, which plays an oncogenic role in the development of OSCC and can be a target for the treatment of patients with OSCC.

Meta-analysis of the association between periodontal disease, periodontal treatment and carotid intima-media thickness.

Periodontal disease is a major threat to oral health and would further contribute to systemic diseases without timely control. We aimed to evaluate the relation between periodontal disease, periodontal treatment and carotid intima-media thickness (CIMT) based on available epidemiological and clinical evidence. PubMed and Scopus were searched for relevant studies through May 2021. Observational studies reporting risk estimates with 95% confidence intervals (95% CIs) for the association between periodontal disease (including periodontitis and gingivitis) and risk of increased CIMT (defined as CIMT value that exceeded the cut-off value of clinical and prognostic significance), as well as interventional studies providing mean values with standard deviations of CIMT before and after periodontal intervention, were included. Random-effect models for meta-analysis were used to calculate the summary effect estimates with 95% CIs. A total of 406 citations were retrieved from electronic databases and 45 full-text articles were screened, leaving 11 articles using ultrasound to measure CIMT with 8744 participants included. Pooled results of seven cross-sectional studies involving 8558 participants indicated that compared to those without periodontitis, patients with periodontitis and those with severe periodontitis had an odds ratio of 1.42 (95% CI: 1.16, 1.75) and 1.70 (95% CI: 1.24, 2.33) for increased CIMT, respectively. Although publication bias was detected in these results, odds ratios corrected by the trim-and-fill method were still statistically significant. Results of four non-randomized controlled trials with 186 patients suggested that periodontal intervention may help reduce CIMT in patients with periodontal disease in the short term. Periodontitis, especially severe periodontitis, was significantly associated with the risk of increased CIMT. Periodontal intervention might help slow the progression of carotid intima-media thickening in patients with periodontal disease in the short term.

Hsa_circRNA_0001971 contributes to oral squamous cell carcinoma progression via miR-186-5p/Fibronectin type III domain containing 3B axis.

BACKGROUND: Circular RNAs (circRNAs) are closely associated with the progression of oral squamous cell carcinoma (OSCC). circRNA_0001971 has been proved to accelerate the OSCC development. Here, we aim to identify the new molecular mechanism of hsa_circRNA_0001971 (circRNA_0001971) in OSCC. METHODS: The levels of circRNA_0001971, miR-186-5p, and fibronectin type III domain containing 3B (FNDC3B) in tissues and cells were verified by qRT-PCR or Western blotting. The interaction between circRNA_0001971, miR-186-5p, and FNDC3B was identified by bioinformatics analysis, luciferase assay, and RIP assay. The effect of circRNA_0001971/miR-186-5p/FNDC3B axis on OSCC cell proliferation, migration, and invasion by cell functional experiments including CCK8, wound healing, and transwell assays. RESULTS: Our study displayed that circRNA_0001971 and FNDC3B were elevated in OSCC, whereas miR-186-5p was declined in OSCC. Silencing circRNA_0001971 attenuated the malignancy of OSCC cells by suppressing proliferation, migration, and invasion. In OSCC cells, circRNA_0001971 sponged miR-186-5p to enhance FNDC3B. Due to the interaction between circRNA_0001971, miR-186-5p, and FNDC3B, FNDC3B overexpression relieved the negative function of silencing circRNA_0001971 in OSCC cells. CONCLUSION: Overall, our study discovered that circRNA_0001971 was a tumor promoter in OSCC progression by targeting miR-186-5p/FNDC3B axis.

Evaluation Procoagulant Activity and Mechanism of Astragalin.

Astragalin, isolated from flowers of Rosa chinensis Jacq., is a kind of flavonoid, with anti-inflammatory, antioxidant, antiviral, analgesic, antibacterial, antiallergic, and antihepatotoxic effects. However, no studieson the procoagulant effect of astragalin have been reported. This study aimed to investigate the procoagulant activity of astragalin and its mechanism. Its procoagulant effect was investigated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) in vitro, and a rat model established by heparin sodium was used to evaluate the mechanism for the procoagulant effect in vivo. The results showed that astragalin had good procoagulant effects compared with the control group in vitro. Compared with the model group in vivo, astragalin could shorten the coagulation time and significantly increase the number of platelets. Meanwhile, astragalin could significantly reduce the effectual time of PT and APTT and increase the content of FIB. The contents of 6-keto-PGF1α and eNOS significantly decreased. Astragalin could increase whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and packedcell volume (PCV). All of the above revealed that astragalin had good procoagulant effects by promoting the intrinsic and extrinsic coagulation system.

Exosomes from gingival mesenchymal stem cells enhance migration and osteogenic differentiation of pre-osteoblasts.

Gingival mesenchymal stem cells (GMSCs) have great potential in bone tissue regeneration. However, it is not well known how on exosomes derived from GMSCs affect the functions of bone-related cells. In this study, we explored the impact of GMSCs-derived exosomes (GMSCs-Exos) on pre-osteoblast MC3T3-E1 proliferation, migration and osteogenic differentiation. Results of CCK-8 assay showed that GMSCs-Exos had no effect on proliferation of pre-osteoblasts. Further, we found that GMSCs-Exos promoted the migration of pre-osteoblasts and osteogenic differentiation of MC3T3-E1 as revealed by enhanced Alizarin red staining, elevated alkaline phosphatase (ALP) activity and upregulated expression of osteogenic genes. This study provides new insights into the potential exosome-mediated paracrine mechanism of GMSCs in bone regeneration.

Long noncoding RNA MORT overexpression inhibits cancer cell proliferation in oral squamous cell carcinoma by downregulating ROCK1.

Long noncoding RNA (lncRNA) mortal obligate RNA transcript (MORT) was downregulated many types of cancer tissues, while its functionality in cancer biology is unclear. In the present study, we systemically investigated the involvement of lncRNA MORT in oral squamous cell carcinoma (OSCC). In the present study, we found that lncRNA MORT was downregulated, while rho-associated coiled-coil containing protein kinase 1 (ROCK1) messenger RNA was upregulated in cancer tissues than in adjacent healthy tissues of OSCC patients. In addition, expression levels of lncRNA MORT and ROCK1 were inversely correlated in both tumor tissues and healthy tissues. Follow-up study showed that low MORT level was significantly correlated with poor survival. Overexpression of lncRNA MORT inhibited the proliferation of OSCC cells and downregulated ROCK1. ROCK1 overexpression led to significantly promoted cell proliferation but showed no significant effect on MORT expression. In addition, ROCK1 overexpression attenuated the inhibitory effects of lncRNA MORT overexpression on the proliferation of OSCC cells. Therefore, lncRNA MORT overexpression may inhibit cancer cell proliferation in OSCC cells by downregulating ROCK1.

Development of novel prognostic models based on dynamic changes in risk factors for hepatitis B associated acute-on-chronic liver failure:a 10-year retrospective study.

Background/Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality, and early prediction is critical to reduce the deaths of ACLF patients. To date, however, the prognostic accuracy of current models for ACLF is unsatisfactory, particularly, in patients with hepatitis B virus (HBV) infection. This study aims to develop novel prognostic models based on the dynamic changes in variables to predict the short-term mortality of HBV-associated ACLF (HBV-ACLF). Methods: A retrospective cohort study was conducted, with the population comprised in whom ACLF was confirmed.319 patients were enrolled and their clinical data were collected on Days 1 and 7 following hospital admission. Univariate and multivariate analyses were performed to identify risk factors for 28 and 90-day mortality. The dynamic alterations in the risk factors were further analyzed, and Days 1 and 7 prognostic models were constructed. Receiver operating characteristic (ROC) analysis were used to identify and compared the predictors of prognosis among our model. Results: Univariate and multivariate analyses revealed significant risk factors at Days 1 and 7, which when combined with the clinically important parameters, were used to establish the Days 1 and 7 prognostic models. For 28-day mortality, the predictive accuracy of the Day 1 prognostic model was significantly higher than that of the albumin-bilirubin (ALBI) model. For 90-day mortality, the predictive accuracy of the Days 1 and 7 prognostic models was significantly higher than that of the Model of End-Stage Liver Disease (MELD), MELD-sodium (MELD-Na), and ALBI prognostic models. Conclusions: The prognostic models established in this study were superior to the existing prognostic scoring systems to accurately predict short-term mortality, and therefore, could be potential novel prognostic tools for HBV-ACLF.

Genome-wide RNA interference of the nhr gene family in barber's pole worm identified members crucial for larval viability in vitro.

Nuclear hormone receptors (NHRs) are emerging target candidates against nematode infection and resistance. However, there is a lack of comprehensive information on NHR-coding genes in parasitic nematodes. In this study, we curated the nhr gene family for 60 major parasitic nematodes from humans and animals. Compared with the free-living model organism Caenorhabditis elegans, a remarkable contraction of the nhr family was revealed in parasitic species, with genetic diversification and conservation unveiled among nematode Clades I (10-13), III (16-42), IV (33-35) and V (25-64). Using an in vitro biosystem, we demonstrated that 40 nhr genes in a blood-feeding nematode Haemonchus contortus (clade V; barber's pole worm) were responsive to host serum and one nhr gene (i.e., nhr-64) was consistently stimulated by anthelmintics (i.e., ivermectin, thiabendazole and levamisole); Using a high-throughput RNA interference platform, we knocked down 43 nhr genes of H. contortus and identified at least two genes that are required for the viability (i.e., nhr-105) and development (i.e., nhr-17) of the infective larvae of this parasitic nematode in vitro. Harnessing this preliminary functional atlas of nhr genes for H. contortus will prime the biological studies of this gene family in nematode genetics, infection, and anthelmintic metabolism within host animals, as well as the promising discovery of novel intervention targets.

Resveratrol-loaded co-axial electrospun poly(ε-caprolactone)/chitosan/polyvinyl alcohol membranes for promotion of cells osteogenesis and bone regeneration.

The guided bone regeneration (GBR) membranes currently used in clinics are usually compromised by their limited osteogenic induction potential. In this study, we fabricate a core-shell poly(ε-caprolactone)/chitosan/polyvinyl alcohol (PCL/CS/PVA) GBR membrane with different amount of resveratrol (RSV), endowing the PCL/CS/PVA GBR membrane with superior osteogenic induction ability, which was not attained by the regular GBR membrane. The prepared GBR membranes were characterized by scanning electron microscopy, transmission electron microscopy, and CCK-8 and live-dead staining assays, and their osteogenic induction ability was evaluated using Col-I immunofluorescence staining, micro-computed tomography, haematoxylin and eosin staining and immunohistochemical staining. Results of the in vitro release experiment confirmed that the membranes exhibited a continuous RSV release profile for 15 days. Furthermore, the cumulative releasing of RSV was increased from 39.68 ± 2.09 µg to 65.8 ± 2.91 µg with increasing contents of RSV from 0.1 % to 0.5 % (w/v) in the core layer of GBR membranes. In particular, the PCL/CS/PVA GBR membrane loading with 0.5 % RSV most efficiently release RSV in a sustained and controlled manner, which significantly induced osteogenic differentiation of pre-osteoblasts in vitro and bone regeneration in vivo. Based on the in vivo histological findings, newly formed bone tissues with 82.46 ± 9.86 % BV/TV and 0.70 ± 0.07gcm-3 BMD were generated in the defect sites treated by the GBR membrane loaded with 0.5 % RSV, which were the largest values among those for all three groups after 12 weeks of post implantation. Overall, the PCL/CS/PVA GBR membrane loaded with 0.5 % RSV has significant potential for bone regeneration.

Application of Nanocellulose-Based Aerogels in Bone Tissue Engineering: Current Trends and Outlooks.

The complex or compromised bone defects caused by osteomyelitis, malignant tumors, metastatic tumors, skeletal abnormalities, and systemic diseases are difficult to be self-repaired, leading to a non-union fracture. With the increasing demands of bone transplantation, more and more attention has been paid to artificial bone substitutes. As biopolymer-based aerogel materials, nanocellulose aerogels have been widely utilized in bone tissue engineering. More importantly, nanocellulose aerogels not only mimic the structure of the extracellular matrix but could also deliver drugs and bioactive molecules to promote tissue healing and growth. Here, we reviewed the most recent literature about nanocellulose-based aerogels, summarized the preparation, modification, composite fabrication, and applications of nanocellulose-based aerogels in bone tissue engineering, as well as giving special focus to the current limitations and future opportunities of nanocellulose aerogels for bone tissue engineering.

Comparative Study on the Clinical Effects of Different Surgical Methods in the Treatment of Gastrointestinal Stromal Tumors.

Objective: The objective is to compare the clinical efficacy of laparoscopic resection (LAP), endoscopic full-thickness resection (EFR), and endoscopic submucosal dissection (ESD) in the treatment of gastrointestinal stromal tumors. Methods: The clinical data of 105 patients who were treated in our hospital and diagnosed with GIST by pathology after surgery from March 2019 to March 2021 were collected. Patients were divided into the LAP group, EFR group, and ESD group according to different surgical methods. The clinical data, surgical conditions, complications, and postoperative conditions of the patients were recorded retrospectively. Patients were followed up closely after surgery. Results: The operation time of the EFR group and ESD group was shorter than that of the LAP group, and the operation time of the EFR group was shorter than that of the ESD group (P < 0.05). The amount of intraoperative blood loss in the EFR group and ESD group was lower than that in the LAP group (P < 0.05). There was no significant difference in the complete resection rate among the three groups (P > 0.05). There was no significant difference in the total incidence of complications among the three groups (P > 0.05). The postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs of the EFR group and ESD group were lower than those of the LAP group (P < 0.05). No recurrence or metastasis cases were found in the three groups during the follow-up period, and there were no GIST-related deaths in the three groups. Conclusion: LAP, EFR, and ESD have good curative effect, good safety, and good prognosis in the treatment of GIST. But compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization cost.

Shade-Tolerant Soybean Reduces Yield Loss by Regulating Its Canopy Structure and Stem Characteristics in the Maize-Soybean Strip Intercropping System.

The shading of maize is an important factor, which leads to lodging and yield loss of soybean in the maize-soybean strip intercropping system, especially in areas with low solar radiation. This study was designed to explore how shade-tolerant soybean reduces yield loss by regulating its canopy structure and stem characteristics in the maize-soybean strip intercropping system. The soybean cultivars Tianlong No.1 (TL-1, representative of shade-tolerant plants) and Chuandou-16 (CD-16, representative of shade-intolerant plants) were grown in monocropping and intercropping systems from 2020 to 2021 in Chongzhou, Sichuan, China. Regardless of shade-intolerant or shade-tolerant soybean, the canopy and stem of soybean in strip intercropping were weaker than those of the corresponding monoculture. But compared with shade-intolerant soybean, the shade-tolerant soybean slightly changed its spatial structure of canopy and stem morphology and physiology in maize-soybean strip intercropping system, especially in the later growth stages. On the one hand, the canopy of shade-tolerant soybean showed relatively high transmission coefficient (TC) and relatively low leaf area index (LAI) and mean leaf angle (MLA). On the other hand, the stem of shade-tolerant soybean was obviously stronger than that of shade-intolerant soybean in terms of external morphology, internal structure, and physiological characteristics. Additionally, compared with shade-intolerant soybean, shade-tolerant soybean showed higher APnWP (the average net photosynthetic rate of the whole plant) and seed yield in the strip intercropping. The results showed that shade-tolerant soybean increased light energy capture and photosynthesis in the different canopy levels to promote the morphological and physiological development of the stem and ultimately reduce the yield loss of the strip intercropping system. However, the molecular mechanism of low radiation regulating soybean canopy structure (LAI, TC, and MLA) needs further in-depth research to provide theoretical guidance for cultivating plants with ideal canopy shape that can adapt to changing light environment in intercropping system.

Long non-coding RNA TTN-AS1/microRNA-199a-3p/runt-related transcription factor 1 gene axis regulates the progression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) has a high degree of malignancy, which affects the quality of life and prognosis of patients with OSCC. Our study aimed to reveal the function of long non-coding RNA TTN-AS1/microRNA-199a-3p (miR-199a-3p)/runt-related transcription factor 1 (RUNX1) axis in OSCC progression, thereby providing a novel OSCC effective strategy. Real-time quantitative polymerase chain reaction and western blotting were performed to detect the expression of TTN-AS1, miR-199a-3p, and RUNX1 in OSCC. Several cell functional experiments, including Cell Counting Kit-8, flow cytometry, and cell adhesion assays, were used to assess cell proliferation, apoptosis, adhesion, and migration. A luciferase assay was performed to confirm the interaction between TTN-AS1, miR-199a-3p, and RUNX1. Our results revealed that TTN-AS1 and RUNX1 were upregulated in OSCC tissues and cells, whereas miR-199a-3p expression was downregulated. Knockdown of TTN-AS1 or RUNX1 suppressed cell proliferation, adhesion, and migration but induced apoptosis. Additionally, miR-199a-3p inhibitor partly relieved the effects of silencing TTN-AS1 and RUNX1 in OSCC cells due to their targeting relationship. In conclusion, TTN-AS1 and RUNX1 could promote OSCC progression and miR-199a-3p partly relieved the effects of TTN-AS1 and RUNX1.

miR-194-5p serves a suppressive role in human keloid fibroblasts via targeting NR2F2.

Keloids are a skin fibrotic disease that cause a number of problems for reconstructive surgeons. MicroRNAs (miRs) are crucial for the development of keloids. The present study aimed to investigate the function of the miR­194­5p/nuclear receptor subfamily 2 group F member 2 (NR2F2) interactome in human keloid fibroblasts. Microarray analysis was performed to identify key genes that may participate in keloid progression. The expression levels of miR­194­5p and NR2F2 mRNA in normal human skin fibroblasts (HSFs) and human keloid fibroblasts (KEL­FIBs) were measured via reverse transcription­quantitative PCR. Furthermore, cell proliferation, apoptosis, migration and invasion were assessed in KEL­FIB cells. Following NR2F2 knockdown and miR­194­5p inhibition, NR2F2 expression was measured via western blotting. The microarray analysis identified NR2F2 as a key gene related to keloids. The regulatory association between miR­194­5p and NR2F2 was identified using TargetScan Human (version 7.2) and verified by performing a dual­luciferase reporter assay. miR­194­5p expression was decreased in KEL­FIB cells compared with HSF cells, and miR­194­5p overexpression inhibited the aggressive phenotypes of KEL­FIB cells compared with the negative control group. Meanwhile, NR2F2 expression was negatively correlated with miR­194­5p expression. NR2F2 knockdown and miR­194­5p overexpression displayed similar effects on KEL­FIB cells. Moreover, NR2F2 knockdown effectively reversed miR­194­5p inhibitor­mediated effects in keloid fibroblasts. The present study indicated that the novel miR/194­5p/NR2F2 interactome might be involved in the progression of keloid aggression and may serve as a potential therapeutic target for human keloid in the future.

[Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion].

OBJECTIVES: To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells. METHODS: A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay. RESULTS: The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (P<0.05). The positive expression rate of CyPA protein in TNM stage T3+T4, clinical stage Ⅲ+Ⅳ, moderately or poorly differentiated lymph node metastasis was increased (P<0.05). Compared with the negative control and blank groups, the CyPA interference sequence group had decreased relative expression levels of CyPA mRNA and protein (P<0.05); optical density va-lues of cells at 24, 48, 72, and 96 h (P<0.05); and number of cell colonies and invasive cells (P<0.05). CONCLUSIONS: The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.

Inflammatory Response and Oxidative Stress as Mechanism of Reducing Hyperuricemia of Gardenia jasminoides-Poria cocos with Network Pharmacology.

Hyperuricemia (HUA) is a metabolic disease, closely related to oxidative stress and inflammatory responses, caused by reduced excretion or increased production of uric acid. However, the existing therapeutic drugs have many side effects. It is imperative to find a drug or an alternative medicine to effectively control HUA. It was reported that Gardenia jasminoides and Poria cocos could reduce the level of uric acid in hyperuricemic rats through the inhibition of xanthine oxidase (XOD) activity. But there were few studies on its mechanism. Therefore, the effective ingredients in G. jasminoides and P. cocoa extracts (GPE), the active target sites, and the further potential mechanisms were studied by LC-/MS/MS, molecular docking, and network pharmacology, combined with the validation of animal experiments. These results proved that GPE could significantly improve HUA induced by potassium oxazine with the characteristics of multicomponent, multitarget, and multichannel overall regulation. In general, GPE could reduce the level of uric acid and alleviate liver and kidney injury caused by inflammatory response and oxidative stress. The mechanism might be related to the TNF-α and IL-7 signaling pathway.

Expression of Dickkopf-related Protein 1 in Patients with Temporomandibular Osteoarthritis after Treatment with Hyaluronic Acid.

We previously reported that the increased expression of Dickkopf-related protein 1 (DKK1) is positively related to vascular endothelial growth factor in the synovial fluid from patients with temporomandibular joint disorders (TMDs). DKK1 is involved in angiogenic activities in the TMD synovium in vitro, but the expression of DKK1 after treatment of TMD-osteoarthritis (TMD-OA) with hyaluronic acid (HA) remains unknown. In this study, we assessed the expression of DKK1 in the synovial fluid of TMD-OA patients before and after treatment with HA via enzyme-linked immunosorbent assay. We also investigated the role of DKK1 in TMD-OA via immunohistochemical staining. The relationship between the expression of DKK1 and the clinicopathological characteristics was determined by Pearson analysis. The results showed that the expression of DKK1 was significantly decreased after treatment with HA. Correlation analyses indicated that the expression of DKK1 in the TMD-OA samples was closely correlated with mouth opening and pain. These findings suggest that DKK1 could play an important role in the pathogenesis and treatment of TMD. Reduction of the pain by HA treatment may be correlated with the decreased expression of DKK1.

Effects of Nigella sativa seed polysaccharides on type 2 diabetic mice and gut microbiota.

Effect of Nigella sativa seed polysaccharides (NSSP) on type 2 diabetic mice and its gut microbiota was investigated on the type 2 diabetic mice model feed by high-fat diet. Fasting blood glucose (FBG), biochemical parameters, expression levels of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and phosphor-AKT (p-AKT) protein, membrane glucose transporter 4 (GLUT4) in skeletal muscles, as well as the change of gut microbiota profile in mice model were measured. Results showed that the high-dose NSSP could significantly lower the levels of FBG, glycosylated serum protein (GSP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), TNF-α, IL-6 and IL-1ß, and significantly increased insulin (INS), high-density lipoprotein cholesterol (HDLC), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT) and the expression levels of p-AKT and GLUT4 in mice. Besides, the high-dose NSSP has significantly increased the abundance of f_Muribaculaceae_Unclassified and Bacteroides, which were significantly suppressed in the mice gut after the treatment of streptozotocin (STZ). These results indicated that NSSP could improve the abnormal state of diabetic mice by regulating the PI3K/AKT signaling pathway with simultaneous changes of the gut microbiota profile.

Effect of Durio zibethinus rind polysaccharide on functional constipation and intestinal microbiota in rats.

The prevalence of constipation increases rapidly with the increased pressure of some people's life, which seriously affects the quality of life in related patients. In this study, the improvement of functional constipation by Durio zibethinus Murr rind polysaccharide (DZMP) and the effects of DZMP on intestinal microbiota were investigated in a constipation model of Sprague-Dawley (SD) rats established by loperamide hydrochloride. Results showed that DZMP at 200 mg/kg could significantly (P < 0.05) increase the intestinal transit rate, motilin, gastrin, substance P levels and concentration of short-chain fatty acids (SCFAs), reduce the somatostatin levels and improve the gastrointestinal peristalsis of rats. Sequencing showed that the Lachnospiraceae-NK4A136-group in the rats given 200 mg/kg DZMP (16.07%) was significantly higher than that of the model group (10.13%), while the Desulfovibrio was lower (2.99%) than that of the model group (4.19%). Principal co-ordinates analysis (PcoA) revealed a significant difference in intestinal microbiota composition between the model group and the high-dose DZMP group (200 mg/kg). The results demonstrated that DZMP has a regulatory effect of treating functional constipation and regulating intestinal flora in rats.