Oral mucosal diseases and psychosocial factors: progress in related neurobiological mechanisms.

The aetiology of oral mucosal diseases, such as recurrent aphthous ulcer (RAU), oral lichen planus (OLP) and burning mouth syndrome (BMS), involves many factors, and it remains difficult for clinicians to effectively relieve disease symptoms and formulate coping strategies. With the rapid development of psychology, the role of mental and psychological factors in RAU, OLP and BMS has gradually attracted researchers attention, but the specific mechanism has not been completely determined. This narrative review describes the potential neurobiological mechanism of oral mucosal diseases and detailed psychological factors after introducing relevant research into psychological factors and oral mucosal diseases. Future research strategies and innovations needed to understand and treat oral mucosal diseases and psychological factors, as well as how to prevent oral mucosal diseases by regulation of the neuroendocrine system, are also discussed.

Repairing Effect and Mechanism of Hydroxysafflor Yellow A and Sodium Hyaluronate for Knee Osteoarthritis in Rabbits.

Context: KOA characterized by recurrent joint pain and progressive joint dysfunction. Is the present clinical common chronic progressive degenerative osteoarthropathy, how long the disease is difficult to cure and easy to relapse. Exploring new therapeutic approaches and mechanisms is important for the treatment of KOA. One of the main applications for sodium hyaluronate (SH) in the medical field is treatment of osteoarthritis. However, the effects of SH alone in the treatment of KOA are limited. Hydroxysafflor yellow A (HSYA) may have therapeutic effects for KOA. Objective: The study intended to investigate the therapeutic effects and possible mechanisms of action HSYA+SH for cartilage tissue of rabbits with KOA and to provide a theoretical basis for the treatment of KOA. Design: The research team performed an animal study. Setting: The study that took place at Liaoning Jijia Biotechnology, Shenyang, Liaoning, China. Animals: The animals were 30 healthy, adult, New Zealand white rabbits, weighing 2-3 kg. Intervention: The research team randomly divided the rabbits into three groups, with 10 rabbits in each group: (1) a control group, for which the research team didn't induce KOA and provided no treatment; (2) the HSYA+SH group, the intervention group, for which the research team induced KOA and injected the rabbits with the HSYA+SH treatment; and (3) the KOA group, for which the research team induced KOA and injected the rabbits with saline. Outcome Measures: The research team: (1) observed the morphological changes in the cartilage tissue using hematoxylin-eosin (HE) staining; (2) measured levels of serum inflammatory factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interferon gamma (IFN-γ), IL-6, and IL-17 using an enzyme-linked immunosorbent assay (ELISA); (3) measured cartilage-cell apoptosis using "terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling" (TUNEL); and (4) used Western Blot to detect the expression of proteins related to the "neurogenic locus notch homolog protein 1" (Notch1) signaling pathway. Results: Compared with the control group, morphological changes had occurred to the cartilage tissue in the KOA group. Compared with the control group, that group's level of apoptosis was higher, the levels of serum inflammatory factors were significantly higher (P < .05), and the protein expression related to the Notch1 signaling pathway was also significantly higher (P < .05). The morphology of the cartilage tissue in the HSYA+SH was better than that of the KOA group but not as good as that of the control group. Compared with the KOA group, the HSYA+SH group's level of apoptosis was lower, the levels of serum inflammatory factors were significantly lower (P < .05), and the protein expression related to the Notch1 signaling pathway was also significantly lower (P < .05). Conclusions: HSYA+SH can reduce the cellular apoptosis in the cartilage tissue of rabbits with KOA, downregulate the levels of inflammatory factors, and protect against KOA-induced cartilage tissue injury, and the mechanism may be related to the regulation of the Notch1 signaling pathway.

Traits variation of acorns and cupules during maturation process in Quercus variabilis and Quercus aliena.

Quercus variabilis and Quercus aliena are two native tree species in China, which have similar habitats, and their regeneration mainly depends on acorn dispersal. This study analyzed the contents of water, soluble sugar, starch, soluble protein, and total phenolics in acorns and cupules during the whole development process to explore the difference between species. Thereinto, starch and total phenol occupied the dominant roles as their high contents. The acorn starch contents increased sharply during development in both species, but the contents in Q. variabilis were almost twice those of Q. aliena when mature. Similarly, high expression levels of starch synthase, soluble starch synthase 2 (SSS2) were also found in the acorns of Q. variabilis. The total phenol contents in Q. variabilis acorns were high at the early stages, and decreased sharply to similar contents in Q. aliena when mature. Additionally, the cupules in Q. variabilis had high contents of total phenols during the whole development period. Similar trends were also found in the expression patterns of UGT84A13 and SDH. The high total phenols in acorns and cupules of Q. variabilis probably protect the acorns from Mechoris ursulus, as only Q. aliena suffered a severe pest infestation in the early development stages. This study not only clarifies the interspecific difference between storage and defense substances during the development process in acorns and cupules, but also deepens understanding the specialized mechanisms of plant-pest/animal interactions in Quercus.

Anthocyanin Biosynthesis Associated with Natural Variation in Autumn Leaf Coloration in Quercus aliena Accessions.

Quercus aliena is an economically important tree species and one of the dominant native oak species in China. Although its leaves typically turn yellow in autumn, we observed natural variants with red leaves. It is important to understand the mechanisms involved in leaf color variation in this species. Therefore, we compared a Q. aliena tree with yellow leaves and three variants with red leaves at different stages of senescence in order to determine the causes of natural variation. We found that the accumulation of anthocyanins such as cyanidin 3-O-glucoside and cyanidin 3-O-sambubiglycoside had a significant effect on leaf coloration. Gene expression analysis showed upregulation of almost all genes encoding enzymes involved in anthocyanin synthesis in the red-leaved variants during the early and main discoloration stages of senescence. These findings are consistent with the accumulation of anthocyanin in red variants. Furthermore, the variants showed significantly higher expression of transcription factors associated with anthocyanin synthesis, such as those encoded by genes QaMYB1 and QaMYB3. Our findings provide new insights into the physiological and molecular mechanisms involved in autumn leaf coloration in Q. aliena, as well as provide genetic resources for further development and cultivation of valuable ornamental variants of this species.

Effects of silkworm excrement and water management on the accumulation of Cd and As in different varieties of rice and an assessment of their health risk.

Rice (Oryza sativa L.) consumption represents a major route for the exposure to cadmium (Cd) and arsenic (As) in many countries. Two varieties of rice that were grown in soils contaminated with Cd and As were evaluated for the accumulation of these toxins in rice grains and the risks of exposure of local residents to Cd and As when treated with different amounts of silkworm excrement and types of water management. Silkworm excrement, water management and the variety of rice significantly affected the accumulation of Cd and As in rice. The combination of multiple measures can be more effective at reducing heavy metals than the use of single measure, i.e., silkworm excrement management, water management, and the selection of low accumulation variety. The use of a variety that accumulates low amounts of Cd combined with 1% silkworm excrement management can effectively increase the soil pH and electrical conductivity (EC) and decrease the contents of soil available Cd and the transfer coefficients of Cd in rice, subsequently reducing the concentrations of Cd in rice grains and lowering the health risks of the intake of Cd. Similarly, the use of a conventional rice variety combined with alternating periods of drying and wetting in the three weeks before and after the heading stage decreased the contents of soil available As and the transfer coefficient of As in rice, subsequently reducing the accumulation of As in the grains and lowering the health risk of the intake of As. The significantly lower concentrations of Cd and As in rice grains and the risk of intake of Cd and As from rice was observed using a conventional rice variety combined with alternating drying-wetting in the three weeks before and after the heading stage and 1% silkworm excrement management. Thus, the combination of multiple measures in the coexistence of Cd and As in contaminated soils can be a promising strategy to avoid serious health risks and ensure the safety of food for local residents.

Effects of a novel biflavonoid of Lonicera japonica flower buds on modulating apoptosis under different oxidative conditions in hepatoma cells.

BACKGROUND: In our previous work, we purified a novel biflavonoid named Japoflavone D (JFD) from Lonicera japonica flower buds. Biflavonoids are chemical compounds characterized by their high levels of antioxidative activity. PURPOSE: The present study aimed to investigate the function and molecular mechanism of JFD under different oxidative conditions in hepatoma cells. METHODS: MTT assay and apoptosis assay were used to evaluate the cytotoxic effect of JFD. The activities of SOD and CAT were detected to evaluate the oxidative level. Oxidative stress was induced by H2O2 stimulation. The molecular mechanism of JFD was investigated by analyzing relative signaling pathway. RESULTS: JFD inhibited cell viability in all hepatoma cell lines we examined. Under quiescent conditions, JFD treatment of SMMC-7721 cells resulted in upregulation of AKT/mTOR signal pathway and ERK activities and downregulation of KEAP1/NRF2/ARE signaling axis, together with apoptosis. However, under oxidative stress, JFD played a quite different role. Treatment of JFD suppressed the activation of ERK and mTOR and activated the KEAP1/NRF2/ARE signaling axis, which is a predominant regulator of cytoprotective responses to oxidative stress, thereby lessening the damage caused by excess reactive oxygen species (ROS). A molecular docking analysis suggested that JFD may interrupt the interaction between KEAP1 and NRF2 by competitively anchoring to the NRF2 binding site on KEAP1. CONCLUSION: The results indicate that JFD functions as a potent antioxidant and plays dual roles in modulating apoptosis under different oxidative conditions. JFD has the potential to be developed as a protective drug for diseases related with excess ROS.

A new meroterpenoid functions as an anti-tumor agent in hepatoma cells by downregulating mTOR activation and inhibiting EMT.

Liver cancer, also known as primary liver cancer, is cancer that starts in the liver. JNU-144, a new meroterpenoid purified from Lithospermum erythrorhizon, has exhibited promising anticancer activity; however, the molecular mechanisms of action of JNU-144 on malignant cells remain unclear. Our studies revealed that JNU-144 suppressed cell viability and proliferation in hepatoma cells by downregulating mTOR activation. Meanwhile, JNU-144 activated the intrinsic apoptosis pathway and subsequently triggered apoptotic cell death in SMMC-7721 cells. We also found that JNU-144 inhibited the epithelial-mesenchymal transition in both SMMC-7721 and HepG2 cells through reprogramming of epithelial-mesenchymal transition (EMT)-related gene expression or regulating protein instability. These findings indicate that JNU-144 exerts potent anticancer activity in hepatoma cells and may be developed as a potential therapeutic drug.

Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and carcinogenesis in tubular epithelial cells, which may be largely attenuated by renin-angiotensin system blockade, implying the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

Cross-talk between AMP-activated protein kinase and renin-angiotensin system in uninephrectomised rats.

INTRODUCTION: The renal renin-angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. METHODS: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. RESULTS: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. CONCLUSIONS: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats.

Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review.

Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function.Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5-12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old.We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7-33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy.Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney.

Cytokine-induced killer cells efficiently kill stem-like cancer cells of nasopharyngeal carcinoma via the NKG2D-ligands recognition.

Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment failure. Thus, there remains an urgent need for more potent and safer therapies against CSCs for curing cancer. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma (NPC) was fully evaluated in vitro and in vivo. To visualize putative CSCs in vitro by fluorescence imaging, and image and quantify putative CSCs in tumor xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were engineered with CSC detector vector encoding GFP and luciferase (Luc) under control of Nanog promoter. Our study reported in vitro intense tumor-killing activity of CIK cells against putative CSCs of NPC, as revealed by percentage analysis of side population cells, tumorsphere formation assay and Nanog-promoter-GFP-Luc reporter gene strategy plus time-lapse recording. Additionally, time-lapse imaging firstly illustrated that GFP-labeled or PKH26-labeled putative CSCs or tumorspheres were usually attacked simultaneously by many CIK cells and finally killed by CIK cells, suggesting the necessity of achieving sufficient effector-to-target ratios. We firstly confirmed that NKG2D blockade by anti-NKG2D antibody significantly but partially abrogated CIK cell-mediated cytolysis against putative CSCs. More importantly, intravenous infusion of CIK cells significantly delayed tumor growth in NOD/SCID mice, accompanied by a remarkable reduction in putative CSC number monitored by whole-body bioluminescence imaging. Taken together, our findings suggest that CIK cells demonstrate the intense tumor-killing activity against putative CSCs of NPC, at least in part, by NKG2D-ligands recognition. These results indicate that CIK cell-based therapeutic strategy against CSCs presents a promising and safe approach for cancer treatment.

Five COX-2 gene polymorphisms and risk of breast cancer: an updated meta-analysis based on 19 case-control studies.

The correlationship between COX-2 gene polymorphisms and breast cancer has been wildly studied, but the results remain controversial. Hence, the present meta-analysis aimed to investigate the association between COX-2 SNPs (rs5275, rs20417, rs689466, rs5277, rs2206593) and risk of breast cancer. Data were collected from PubMed, Embase and China National Knowledge Infrastructure. Summary odds ratio (OR) with 95 % confidence interval (CI) was applied to assess the relationship. Heterogeneity test, sensitivity analysis and publication bias test were also performed. There were 17 articles that contained 19 studies in this research. Fourteen case-control studies with 15,007 breast cancer cases and 20,005 controls were concerning rs5275 polymorphism, and 8 case-control studies with 10,216 cases and 12,839 controls were about rs20417 polymorphism. Other three polymorphisms (rs689466, rs2206593, rs5277) were studied in 5, 3 and 3 studies, respectively. COX-2-rs20417 CC genotype was significantly associated with increased risk of breast cancer when comparing to G allele [ORs were 1.231 (1.050-1.444) for CC vs. GG, P = 0.01, 1.223 (1.045-1.432) for CC vs. G carrier, P = 0.01]. Furthermore, the results of the subgroup analysis by ethnicity suggested that C allele significantly contributed to the risk of breast cancer for Asians [1.459 (1.182-1.802) for GC vs. GG, 1.472 (1.201-1.805) for C carrier vs. GG]. However, no association was found for rs5275, rs689466, rs5277 and rs2206593 in all comparison modes. This meta-analysis indicated that the COX-2 rs20417 polymorphism contributed to genetic susceptibility of breast cancer. In contrast, COX-2 rs5275, rs689466, rs2206593 and rs5277 polymorphisms might be not associated with the risk of breast cancer.