Traditional Chinese medication for oral submucous fibrosis: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of various drug therapy methods for treating oral submucous fibrosis (OSF) in terms of increasing mouth opening, reducing VAS score, decreasing lesion area, minimizing side effects, and determining effective proportion. METHOD: A database search was conducted. Only randomized clinical trials were included, and Cochrane checklist was used for assessing the risk of bias. Stata.17 software was employed and effective treatment ranking was used. RESULTS: Thirty-one RCT studies, with a total of 2986 patients, were included in the period of 2010-2022. The combination of oral Chinese herbal medicine formulas (OC) and intralesional Salvia miltiorrhiza (ISM) was found to be the most effective treatment in improving mouth opening. For reducing the burning pain, the combination of intralesional steroids (IS) and oral Salvia miltiorrhiza (OSM) was found to be more effective than the others. In terms of lesion area, IS combined with OC was more effective than the others. IS combined with ISM had the highest effective proportion while having the lowest incidence of side effects which mentioned the incidence of side effects. CONCLUSION: This study indicates that OC and SM can be employed by clinicians for treating OSF effectively.

DEC1 is a potential marker of early metastasis in Oral squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the role of differentiated embryonic-chondrocyte expressed gene 1 (DEC1) in early oral squamous cell carcinoma (OSCC) metastasis. METHODS AND MATERIALS: This study collected normal oral mucosas (NOM) and OSCC tissues from Xiangya Hospital for immunohistochemistry to detect the expressions of DEC1 and epithelial-mesenchymal transition (EMT) -related molecules. Correlation analysis between the expressions of the cytoplasmic DEC1 and EMT-related molecules was performed. Kaplan-Meier analysis was conducted to estimate Recurrence-free survival (RFS). After knocking down DEC1, cell migration and the expressions of EMT-related molecules were evaluated in HN6 cells by cell scratch assay, qRT-PCR, and western blot. RESULTS: Immunohistochemistry showed that the subcellular location of DEC1 expression was different between OSCC and NOM tissues. The cytoplasmic expression of DEC1 in OSCC tissues was significantly higher than in NOM tissues, and its expression was highest in early OSCC patients with metastasis. In addition, the cytoplasmic DEC1 was negatively correlated with the E-cadherin and ß-catenin, but positively correlated with the N-cadherin in OSCC and NOM tissues. In vitro assays showed that DEC1 knockdown inhibited cell migration and EMT in HN6 cells. CONCLUSION: DEC1 could serve as a potential predictive marker for early OSCC metastasis.

Overexpression of DEC1 in the epithelium of OSF promotes mesenchymal transition via activating FAK/Akt signal axis.

BACKGROUND: Previous studies on oral submucous fibrosis (OSF) mostly focused on the activation of fibroblasts and collagen metabolism, while little involved in the epithelium. As we have reported the role of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in oral cancer and other precancerous lesions, this research aimed to explore its role in the OSF epithelium. METHODS: Expression of DEC1 and other proteins were investigated in tissue array constructed with 33 OSF and 14 normal oral mucosa (NOM) tissues. Human oral keratinocytes treated with arecoline and/or hypoxia were used to simulate OSF epithelium and detected for morphological and protein alterations. Inhibition of DEC1 was used to explore its mediating role. Finally, animal models of OSF constructed by locally arecoline injecting in buccal mucosa were used to verify our findings. RESULTS: DEC1 overexpression could be detected in the epithelium of OSF compared with that in NOM followed by phosphorylated FAK and Akt, and DEC1 showed a significant positive correlation with them. Cytology experiment revealed that OSF-like treatment could upregulate DEC1 expression followed by phosphorylated FAK, Akt, but inhibit E-cadherin, while knockdown of DEC1 could suppress the effects. In addition, OSF mice revealed higher expression of DEC1 in the epithelium of buccal mucosa, along with synchronized alterations of phosphorylated FAK and Akt. CONCLUSION: In the epithelium of OSF, overexpression of DEC1 induced activation of FAK/Akt signal axis, caused mesenchymal transition in epithelial cells, and may promote malignant transformation of OSF. Targeting DEC1 in OSF could be promising a new target for the diagnosis and treatment of this process.

Differentiated embryo chondrocyte 1, induced by hypoxia-inducible factor 1α, promotes cell migration in oral squamous cell carcinoma cell lines.

OBJECTIVE: This study aimed to explore the correlation between differentiated embryo chondrocyte 1 (DEC1) and hypoxia-inducible factor 1α (HIF-1α) in oral squamous cell carcinoma (OSCC) and how they participate in tumor progression. STUDY DESIGN: An immunohistochemical staining method was used to detect the expression of HIF-1α and DEC1 in 64 OSCC specimens, and the correlation between HIF-1α and DEC1 was analyzed. The expression of HIF-1α and DEC1 in OSCC cells under normoxic and hypoxic environments was assessed and analyzed by Western blotting and immunofluorescence. Furthermore, the DEC1 gene was silenced by siRNA and treated with cobalt chloride (CoCl2) to analyze the effects that DEC1 and hypoxia might have on the migration ability of OSCC cells. RESULTS: The expression of HIF-1α and DEC1 in OSCC was positively correlated. Using CoCl2 to simulate a hypoxic environment increased the protein levels of HIF-1α and DEC1 in OSCC cells. The HIF-1α inhibitor LW6 decreased HIF-1α and DEC1 expression in OSCC cells in a hypoxic environment. Silencing the DEC1 gene reduced the migration ability of OSCC cells. CONCLUSION: The hypoxic environment in OSCC could upregulate the expression of DEC1 by increasing the protein level of HIF-1α, and this process might be involved in the migration of tumor cells.

Efficacy of Standardised Treatments Combined with Ubenimex in Patients with Malignant Tumors.

Ubenimex is widely used as an immunomodulator in the treatment of leukemia and non-small cell lung cancer to improve the anti-tumor treatment effect. However, there has not been any multicenter randomised controlled trials to study its impact on the prognosis of cancer patients. The authors aimed to conduct a meta-analysis to initially study these issues. Pubmed, Cochrane Library and EMbase were searched. Randomised controlled trials of the effects of ubenimex on the survival rate of malignant tumor patients were included in the meta-analysis. Survival rate ratio (OR) and 95% confidence interval (95% CI) between two groups were used to evaluate the efficacy of ubenimex. Fixed effects models were used for meta-analysis. A total of 1,372 cases (684 in the ubenimex group and 688 in the control group) of five studies were included. Between the ubenimex group and the control group, the 1-year OR was 1.40 (95% CI = 1.06 to 1.85), the 2-year OR was 1.43 (95% CI = 1.08 to 1.89) and the 3-year OR was 1.39 (95% CI = 1.07 to 1.81). Standardised treatments combined with ubenimex may improve the survival rate of patients with malignant tumors. Key Words: Malignant tumors, Ubenimex, Randomised controlled trials, Meta-analysis.

Paeonol ameliorates CFA-induced inflammatory pain by inhibiting HMGB1/TLR4/NF-κB p65 pathway.

The enhanced release of inflammatory cytokines mediated by high mobility group box1 (HMGB1) leads to pain sensation, and has been implicated in the etiology of inflammatory pain. Paeonol (PAE), a major active phenolic component in Cortex Moutan, provides neuroprotective efficacy via exerting anti-inflammatory effect. However, the role and mechanism of PAE in inflammatory pain remain to be fully clarified. In this study, we showed that PAE treatment significantly ameliorated mechanical and thermal hyperalgesia of mice induced by complete Freund's adjuvant (CFA). The analgesic effect of PAE administration was associated with suppressing the enhanced expression of HMGB1 as well as the downstream signaling molecules including toll-like receptor 4 (TLR4), the nuclear NF-κB p65, TNF-α and IL-1ß after CFA insult in the anterior cingulate cortex (ACC), a key brain region responsible for pain processing. Furthermore, inhibition of HMGB1 activity by glycyrrhizin (GLY), an HMGB1 inhibitor, alleviated CFA-induced pain and also facilitated PAE-mediated analgesic effect in mice along with the decreased expression of TLR4, NF-κB p65, TNF-α and IL-1ß upon CFA injury. Collectively, we showed PAE exerted analgesic effect through inhibiting the HMGB1/TLR4/NF-κB p65 pathway and subsequent generation of cytokines TNF-α and IL-1ß in the ACC.

Metformin reduces the increased risk of oral squamous cell carcinoma recurrence in patients with type 2 diabetes mellitus: A cohort study with propensity score analyses.

BACKGROUND: To investigate the impact of type 2 diabetes mellitus (T2DM) and metformin treatment on the prognosis of oral squamous cell carcinoma (OSCC) patients received radical surgical treatment. METHODS: Eight hundred and fifty-two patients with OSCC between January 2011 and January 2015 were included in the cohort study. Propensity score analysis was used to balance the characteristics of patients with or without T2DM and those of patients with T2DM treated with or without metformin. Five-year OSCC-free survival (OFS) was used to evaluate the prognosis of OSCC patients. RESULTS: Two hundred and sixty-nine patients without T2DM and 138 patients with T2DM were selected after the propensity score matching. The 5-year OFS of patients with T2DM was significantly lower than that of those without T2DM, both before (P = 0.019) and after (P = 0.014) the propensity score matching. Forty-four metformin users of OSCC patients with T2DM and 44 patients never users were further compared after the propensity score matching. The 5-year OFS of metformin users was significantly higher than that of metformin never users both before (P = 0.005) and after (P = 0.002) the propensity score matching. CONCLUSIONS: T2DM is associated with a higher risk of OSCC recurrence that can be reduced by metformin treatment.

CD147 promotes proliferation and migration of oral cancer cells by inhibiting junctions between E-cadherin and ß-catenin.

BACKGROUND: Although association between oral squamous cell carcinoma (OSCC) with epithelial-mesenchymal transition (EMT) has been demonstrated, we found CD147, one transmembrane protein we previously studied in oral submucous fibrosis, was correlated with E-cadherin, one marker of EMT. Here, we investigated CD147 expression in the different stages of OSCC and assessed its association with epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: CD147 and E-cadherin expression in tissue microarrays containing 48 OSCC specimens and matched adjacent tissues was analysed using immunohistochemistry. CD147 was overexpressed or knocked down using exogenous cloning vector and RNA interference, respectively, in OSCC cell lines. Cell proliferation and migration were measured using the CCK8 assay and scratch test, respectively. The expression and localization of EMT-associated proteins was analysed by Western blotting and immunofluorescence. RESULTS: CD147 expression in OSCC tissues was significantly higher than that in adjacent tissues and was markedly higher in cancer tissues with metastasis (P < .05). CD147 expression showed significant negative correlation with E-cadherin expression. CD147 overexpression downregulated E-cadherin and inhibited its complex with ß-catenin and then upregulated N-cadherin and vimentin. Additionally, alterations in CD147 protein expression affected proliferation and migration ability in OSCC cells and were related to ß-catenin nuclear translocation. CONCLUSION: CD147 plays an important role in tumorigenesis and metastasis by promoting EMT progression in OSCC. It may be considered as a novel potential diagnostic and therapeutic target for OSCC.

DEC1: a potential biomarker of malignant transformation in oral leukoplakia.

The purpose of this study was to analyze the differential expression of DEC1 in oral normal mucosa (NM), oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Surgically excised specimens from patients with OLK (n = 47), OSCC (n = 30) and oral normal mucosa (n=11) were immunostained for DEC1. The expression of DEC1 protein was evaluated, and its association with the clinicopathological features was analyzed. The expression of DEC1 in NM, OLK and OSCC tissues increased in turn, and significant differences were observed among the groups (P < 0.0001). In terms of the association between DEC1 expression and epithelial dysplasia, DEC1 expression was lower in hyperkeratosis without dysplasia (H-OLK) than in OLK with moderate to severe dysplasia (S-OLK), and these differences were significant (p < 0.05). The expression of DEC1 in OSCC with OLK was significantly higher than that in OSCC without OLK (p < 0.01). Therefore, DEC1 could be a potential biomarker of malignant transformation in the carcinogenesis of OSCC, which may provide a new research direction for the transformation of oral potentially malignant disorders (OPMDs) into OSCC.

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2.

Sleep disorder has become a prevalent issue in current society and is connected with the deterioration of neurobehaviors such as mood, cognition and memory. Ellagic acid (EA) is a phenolic phytoconstituent extracted from grains and fruits that has potent neuroprotective properties. This research aimed to study the alleviative effect and mechanism of EA on memory impairment and anxiety caused by sleep deprivation (SD). EA ameliorated behavioral abnormalities in SD mice, associated with increased dendritic spine density, and reduced shrinkage and loss of hippocampal neurons. EA reduced the inflammatory response and oxidative stress injury caused by SD, which may be related to activation of the Nrf2/HO-1 pathway and mitigation of the TLR4-induced inflammatory response. In addition, EA significantly reduced the mortality and ROS levels in glutamate (Glu)-induced hippocampal neuron injury, and these effects of EA were enhanced in TLR4 siRNA-transfected neurons. However, knockdown of Nrf2 dramatically restrained the protective impact of EA on Glu-induced toxicity. Taken together, EA alleviated memory impairment and anxiety in sleep-deprived mice potentially by inhibiting TLR4 and activating Nrf2. Our findings suggested that EA may be a promising nutraceutical ingredient to prevent cognitive impairment and anxiety caused by sleep loss.

Corilagin ameliorates sleep deprivation-induced memory impairments by inhibiting NOX2 and activating Nrf2.

Sleep deprivation (SD) can induce cognitive and memory impairments. This impairment is in part due to oxidative stress damage in the hippocampus region of the brain. Corilagin (CL), a polyphenol belonging to the tannin family and extracted from Terminalia chebula and Phyllanthus emblica, shows strong antioxidant and neuroprotective effects. NF-E2-related factor (Nrf2)/heme oxygenase-1 (HO-1) and NADPH oxidase (NOX) are critical targets involved in cellular defense mechanisms against oxidative injury. Thus, we hypothesized that CL could be a preventive treatment for SD-induced memory impairments by inhibiting NOX2 and activating Nrf2. The results from behavioral tests showed that administration of CL resulted in significantly better performance compared to the SD mice. CL significantly normalized the elevated MDA level and the reduced activity of GPx and SOD (P <0.05, p<0.01) caused by SD. In hippocampal tissues, CL effectively activated Nrf2/HO-1 signaling and downregulated NOX2 protein expression compared with SD (P <0.05, P <0.01). Meanwhile, in vitro findings showed that knockdown of Nrf2 blocked the protective effect of CL versus Glu-induced toxicity, while the effect of CL was enhanced in NOX2 siRNA-transfected neurons. Overall, these findings provided evidence that CL ameliorates SD-induced memory impairments in mice by inhibiting NOX2 and activating Nrf2.

Study on the expression and function of smad family member 7 in oral submucous fibrosis and oral squamous cell carcinoma.

OBJECTIVE: To investigate the expression and function of smad family member 7 (SMAD7) in the progress of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). METHODS: Mucosa tissue microarray containing 12 normal oral mucosa samples, 69 OSF samples, 28 OSCC sample and paired adjacent tissues was used to explore the expression levels in OSF and OSCC by immunochemistry. Several online bioinformatics analysis tools were used to explore "transcriptome level" and mostly probable "functions and pathways" of SMAD7 in head and neck squamous cell carcinoma. RESULTS: SMAD7 expression was up-regulated significantly in "OSF" (P < 0.0001) and "OSCC" (P < 0.05). In the status of "OSF and OSCC with OSF", the trends of SMAD7 expression were consistent and up-regulated (P < 0.0001). Based on bioinformatics analysis results, SMAD7 was significantly higher in head and neck squamous cell carcinoma than that of normal tissues. No mutation was found in head and neck squamous cell carcinoma. Pathway analysis results showed three mostly probable functions (extracellular matrix organization, blood vessel development and laminin interactions) and two mostly probable pathways (regulation of actin cytoskeleton and ras-associated protein-1 signaling pathway) that SMAD7 participated in. CONCLUSIONS: In OSF and OSCC, SMAD7 is indicated to be a promoter, as well as a potential diagnostic biomarker.

Use of a submandibular gland flap for closure of oral cutaneous fistula.

We reported a rare case of submandibular oral cutaneous fistula (OCF) in a 27-year-old female. A submandibular gland flap (SMGF) was prepared after fistula resection to fill the dead space under the mouth floor. Based on this case report and a literature review, we discussed the pathogenesis and treatment of OCF, and compared the differences between the SMGF and other types of flaps.

Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study.

Prognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9-month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.

DEC1: a potential biomarker of malignant transformation in oral leukoplakia

Abstract The purpose of this study was to analyze the differential expression of DEC1 in oral normal mucosa (NM), oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Surgically excised specimens from patients with OLK (n = 47), OSCC (n = 30) and oral normal mucosa (n=11) were immunostained for DEC1. The expression of DEC1 protein was evaluated, and its association with the clinicopathological features was analyzed. The expression of DEC1 in NM, OLK and OSCC tissues increased in turn, and significant differences were observed among the groups (P < 0.0001). In terms of the association between DEC1 expression and epithelial dysplasia, DEC1 expression was lower in hyperkeratosis without dysplasia (H-OLK) than in OLK with moderate to severe dysplasia (S-OLK), and these differences were significant (p < 0.05). The expression of DEC1 in OSCC with OLK was significantly higher than that in OSCC without OLK (p < 0.01). Therefore, DEC1 could be a potential biomarker of malignant transformation in the carcinogenesis of OSCC, which may provide a new research direction for the transformation of oral potentially malignant disorders (OPMDs) into OSCC.

Study on the multi-targets mechanism of triphala on cardio-cerebral vascular diseases based on network pharmacology.

BACKGROUND & AIMS: Numerous references made clear that Triphala is revered as a multiuse therapeutic and perhaps even panacea historically. Nevertheless, the protective mechanism of Triphala on cardio-cerebral vascular diseases (CCVDs) remains not comprehensive understanding. Hence, a network pharmacology-based method was suggested in this study to address this problem. METHODS: This study was based on network pharmacology and bioinformatics analysis. Information on compounds in herbal medicines of Triphala formula was acquired from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Then, components of Triphala, candidate targets of each component and known therapeutic targets of CCVDs were collected. Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources. In addition, key targets and pathway enrichment were analyzed by STRING database and DAVID database. Moreover, we verified three of the key targets (PTGS2, MMP9 and IL6) predicted by using western blot analysis. RESULTS: Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening, and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs. And 10 compounds, which actually linked to more than three genes, are determined as crucial chemicals. Core genes in this network were IL6, TNF, VEGFA, PTGS2, CXCL8, TP53, CCL2, IL10, MMP9 and SERPINE1. And pathways in cancer, TNF signaling pathway, neuroactive ligand-receptor interaction, etc. related to CCVDs were identified. In vitro experiments, the results indicated that compared with the control group (no treatment), PTGS2, MMP9 and IL6 were up-regulated by treatment of 10 ng/mL TNF-α, while pretreatment with 20-80 µg/mL Triphala could significantly inhibit the expression of PTGS2, MMP9 and IL6. With increasing Triphala concentration, the expression of PTGS2, MMP9 and IL6 decreased. CONCLUSIONS: This study revealed the complex components and pharmacological mechanism of Triphala, and obtained some potential therapeutic targets of CCVDs, which could provide theoretical basis for the research and development of new drugs for treating CCVDs.

Proteomic Analysis of Hydroxysafflor Yellow A Against Cerebral Ischemia/Reperfusion Injury in Rats.

Hydroxysafflor yellow A (HSYA), an active component from Chinese medicinal herb, has been applied to the prevention and treatment of cerebral ischemia/reperfusion injury (CIRI). To clarify the comprehensive mechanisms HSYA for stroke, we used label-free quantitative proteomic analysis to investigate the modulated proteins of rats subjected to CIRI and their alteration by HSYA. Neurological examination, infarct assessment, and biochemical assay were performed to validate the effects of HSYA, and the results indicated that HSYA played a significant role in brain protection. A total of 13 proteins were identified as overlapped proteins by label-free quantitative proteomic analysis. Gene Ontology and pathway analysis showed that these differentially expressed proteins were mainly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Furthermore, networks were constructed with respect to protein function interactions. The results suggested that seven proteins were identified as hub proteins between model and sham groups, while 25 proteins were identified as hub proteins between HSYA and model groups. In addition, the expressions of three overlapping proteins were validated by Western blot, and their levels were consistent with the results of label-free analysis. In conclusion, Eftud2, mTOR, Rab11, Ppp2r5e, and HIF-1 signaling pathways have been detected as key hub proteins and pathways in HSYA against CIRI through proteomic analysis. Our research has provided convincing explanations for the mechanism of HSYA against CIRI and the identified key proteins and pathways might provide novel therapeutics for CIRI.

Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway.

Classic antidepressants benefit depression patients partially by improving neurogenesis and/or brain-derived neurotrophic factor (BDNF)/TrkB pathway which were impaired in depression. In this study, we demonstrated that Silibinin (SLB), a polyphenolic flavanoid from Silybum marianum, ameliorated reserpinized mouse depressant-like behaviors. The antidepressants of SLB administration was associated with increased neural stem cells (NSCs) proliferation and further confirmed in BDNF/TrkB signaling transduction. SLB treatment reversed the decreased expression levels of BDNF and its receptor TrkB, and the reduced activation of downstream target proteins including phosphorylated extracellular-regulated protein kinase (p-ERK) and phosphorylated cAMP-response element binding protein (p-CREB) in depressived hippocampus. Furthermore, intracerebroventricular injection of GNF5837, a TrkB antagonist, abrogated antidepressant-like effects of SLB in mice along with the improved NSC proliferation, as well as enhanced levels of p-ERK and p-CREB in mice hippocampus. Taken together, these results suggest that SLB may exert antidepressant effects through BDNF/TrkB signaling pathway to improve NSC proliferation in acute depression.

Differential expression of organic cation transporter 3 in oral submucous fibrosis-associated buccal squamous cell carcinoma.

OBJECTIVE: The aim of this study was to examine the expression of organic cation transporter 3 (OCT3) in patients with oral submucous fibrosis (OSF)-associated buccal squamous cell carcinoma (BSCC) and to explore its clinical significance. STUDY DESIGN: A total of 56 tissue specimens were collected from patients, among which there were 13 specimens with normal buccal mucosa (NBM), 13 with oral submucous fibrosis (OSF), 10 with OSF-associated BSCC (BSCC-OSF), 10 with well-differentiated BSCC (BSCC-I), and 10 with poorly to moderately differentiated BSCC (BSCC-II+III), based on pathologic examination. The expression of OCT3 was detected by using immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction. RESULTS: There was a significant difference in both the protein and mRNA expression levels of OCT3 among the NBM, OSF, BSCC-OSF, BSCC-I, and BSCC-II+III groups (protein: F = 82.45 [P < .0001]; mRNA: F = 50.69 [P < .0001]). The expression of OCT3 from NBM to OSF to BSCC-OSF was gradually upregulated. In addition, as BSCC became better differentiated, the expression of OCT3 increased. CONCLUSIONS: The expression of OCT3 was associated with OSF progression and the differentiation of BSCC. OCT3 expression may serve as a molecular marker for the prevention and early diagnosis of OSF and BSCC.

A novel thiazolidinediones ATZD2 rescues memory deficits in a rat model of type 2 diabetes through antioxidant and antiinflammation.

Type 2 diabetes (T2DM) has been associated with learning and memory impairment; however, drugs for diabetes could not prevent the development of cognitive decline in T2DM patients. In the present study, compounds derived from thiazolidinediones (TZD), a PPAR-γ agonist, were synthesized by conjuncting the alkyl-substituted benzimidazole group to TZD group (ATZDs). Based on the in vitro evaluation, the neuroprotection of ATZD2 was further investigated using a streptozotocin-induced T2DM rat model. Pharmacokinetic study showed that ATZD2 could pass the blood-brain barrier (BBB) while the rosiglitazone (RSG, the precursor compound of ATZD2) not. Administration of ATZD2 significantly promoted the survival rate and attenuated fasting blood glucose (FBG) levels as compared to RSG treatment in T2DM rats. Furthermore, ATZD2 treatment ameliorated the impairment of learning and memory by Morris water maze test. The beneficial effects of ATZD2 were associated with the down-regulation of hypoxia induced factor-1α, aldose reductase, and Bax expression which are related to T2DM pathology. ATZD2 treatment also attenuated the expression of inflammatory cytokines and restored the balance of redox in the diabetic hippocampus. These effects were more potent as compared with that of RSG at the same dose. The data indicate that ATZD2 may be a potent agent for the treatment of cognitive dysfunction in T2DM.