Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

[Relationship between Oral Microbiota and Alzheimer's Disease].

Alzheimer's disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious problems for individuals, families and the society. However, the etiology and pathogenesis of AD are still not fully understood. Age, genetics, environment and other factors are all relevant to AD, and treatment has not achieved satisfactory results. Recent studies have found that oral dysbiosis is closely related to the pathogenesis of AD, and that oral bacterial infection may be one of the causes of AD. Oral cavity is the largest microbial ecosystem of human body, and its homeostasis is critical to health. Bacterial infections caused by oral dysbiosis can directly and indirectly induce the metabolic imbalance of amyloid ß-protein (Aß) in the brain and the hyperphosphorylation of Tau protein. Then, the precipitation forms senile plaques and neurofibrillary tangles (NFTs) that damage neurons. Based on the latest research findings, we herein discussed the correlation between oral microbiota and the pathogenesis of AD and the mechanisms involved, as well as the pathogenic mechanism of main oral bacteria. In addition, we explored the potential application prospects of oral microbiota-targeted therapy.

Taurine ameliorates axonal damage in sciatic nerve of diabetic rats and high glucose exposed DRG neuron by PI3K/Akt/mTOR-dependent pathway.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and axonopathy is its main pathological feature. Previous studies suggested an advantage of taurine against diabetes. However, there are few reports which study the effect of taurine against axonopathy. In this study, we confirmed that taurine significantly decreased blood glucose level, mitigated insulin resistance and improved dysfunctional nerve conduction in diabetic rats. Taurine corrected damaged axonal morphology of sciatic nerve in diabetic rats and induced axon outgrowth of Dorsal root ganglion (DRG) neurons exposed to high glucose. Taurine up-regulated phosphorylation levels of PI3K, Akt, and mTOR in sciatic nerve of diabetic rats and DRG neurons exposed to high glucose. However, Akt and mTOR inhibitors (MK-2206 and Rapamycin) blocked the effect of taurine on improving axonal damage. These results indicate that taurine ameliorates axonal damage in sciatic nerve of diabetic rats by activating PI3K/Akt/mTOR signal pathway. Our findings provide taurine as a potential candidate for axonopathy and a new evidence for elucidating protective mechanism of taurine on DPN.

Taurine inhibits neuron apoptosis in hippocampus of diabetic rats and high glucose exposed HT-22 cells via the NGF-Akt/Bad pathway.

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.

Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Diabetes causes memory loss. Hippocampus is responsible for memory and increased apoptosis was found in diabetes patients. Taurine improved memory in diabetes condition. However, mechanism is unclear. In current study, hippocampal cell line HT-22 cells were subjected to analysis as five groups i.e. Control, High glucose (HG) at concentration of 150 mM, HG + 10 mM (T1), 20 mM (T2) and 40 mM (T3) taurine solution. TUNEL assay showed that HG increased the number of apoptotic cell significantly while taurine reduced apoptosis. Taurine increased phosphorylation of Akt in HT-22 cell treated with HG, and increased phosphorylation of Bad (p-Bad) was seen suggesting involvement of Akt/Bad signaling pathway. Expression of Bcl-2 was reduced in HG group but taurine improved this. Bax expression showed opposite trend. This indicated that taurine may reduce apoptosis by controlling balance of Bcl-2 and Bax. When the activation of Akt was blocked by using of perifosine, the effect of taurine disappears either partially or altogether. Thus, it was clear that taurine reduces apoptosis via Akt/Bad pathway in HT-22 cells exposed to HG which further improves downstream balance of Bcl-2 and Bax. This mechanism may be involved in apoptosis of hippocampus cells in diabetic condition.

Correction to: Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Affiliations of authors Muhammad Shahbaz and Shahid Alam were incorrect in the published book. This has now been corrected as below.

A colorimetric aptasensor for sulfadimethoxine detection based on peroxidase-like activity of graphene/nickel@palladium hybrids.

A sensitive, rapid and label-free colorimetric aptasensor for sulfadimethoxine (SDM) detection was developed based on the tunable peroxidase-like activity of graphene/nickel@palladium nanoparticle (Gr/Ni@Pd) hybrids. The addition of the SDM aptamer could inhibit the peroxidase-like catalytic activity of the hybrids. However, the target SDM and aptamer could be triggered tightly and recover the catalytic activity of the Gr/Ni@Pd hybrids. Due to the peroxidase-like catalytic activity, Gr/Ni@Pd could catalyze the decomposition of H2O2 with releasing hydroxyl radicals which further oxidized reagent 3, 3', 5, 5'-Tetramethylbenzidine (TMB) to oxTMB accompanied with a colorless-to-blue color change. The original color change could be applied to obtain quantitative detection of SDM, due to the relationship between the concentration of the target and the color difference. As a result, this approach performed a linear response for SDM from 1 to 500 ng/mL with a limit detection of 0.7 ng/mL (S/N = 3) under the optimized conditions and realized the detection of SDM in spiked lake water samples. Therefore, this colorimetric aptasensor was an alternative assay for SDM detection in real water. Moreover, with its design principle, this work might be applied to detecting other small molecule by employing appropriate aptamer.

Investigation of germanium quantum-well light sources.

In this paper, we report a broad investigation of the optical properties of germanium (Ge) quantum-well devices. Our simulations show a significant increase of carrier density in the Ge quantum wells. Photoluminescence (PL) measurements show the enhanced direct-bandgap radiative recombination rates due to the carrier density increase in the Ge quantum wells. Electroluminescence (EL) measurements show the temperature-dependent properties of our Ge quantum-well devices, which are in good agreement with our theoretical models. We also demonstrate the PL measurements of Ge quantum-well microdisks using tapered-fiber collection method and quantify the optical loss of the Ge quantum-well structure from the measured PL spectra for the first time.

Changes in dental plaque microbial richness and oral behavioral habits during caries development in young Chinese children.

OBJECTIVE: To detect changes in the microbial richness of dental plaque and oral behaviors during caries development in young Chinese children. METHODS: Supragingival plaque samples and a survey of oral behaviors of 130 children aged 3 at baseline were analyzed at 6 months and 12 months. Total DNA was isolated from all samples and PCR-denaturing gradient gel electrophoresis analysis was conducted. RESULTS: In the follow-up, 44 children had caries or cavity fillings at 6 months, a further 28 children had caries or cavity fillings at 12 months. The other 58 children remained caries-free at 12 months. According to the changes in caries status at the 12-month follow-up, all participants were divided into three groups: caries-free, caries at 6 months and caries at 12 months. The changes in oral behaviors during the 12-month follow-up were not significantly different in the three groups. The frequency of eating sweets and eating sweets before sleeping was significantly different among the three groups at baseline. At baseline, the average detectable bands of caries in the 12-month caries group were similar to those of the caries-free group; both of them were higher than that of the 6-month caries group. At 6 months, the average detectable bands of the 12-month caries group were significantly lower than that of the caries-free group although the children of the 12-month caries group were caries-free at that time. CONCLUSIONS: For young Chinese children, the high frequency of eating sweets and eating sweets before sleeping are risk factors of caries onset, and the decrease in microbial richness could occur 6 months before the onset of caries.

[Retracted] Isoquercitrin inhibits bladder cancer progression in vitro and in vivo by regulating the PI3K/Akt and PKC signaling pathways.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the agarose gel electrophoretic bands shown in Fig. 4A for PKC were strikingly similar to bands that had already appeared in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 165­172, 2016; DOI: 10.3892/or.2016.4794].

Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells.

The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.

Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study.

BACKGROUND: The female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota. METHODS: A total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects. RESULTS: We found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles. CONCLUSIONS: Our study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.

Zinc sensitizes prostate cancer cells to sorafenib and regulates the expression of Livin.

In prostate carcinogenesis, normal zinc-accumulating epithelial cells are transformed into malignant cells that do not accumulate zinc. Increased levels of zinc have been shown to induce apoptosis through a caspase-dependent mechanism with down-regulated anti-apoptotic proteins in prostate cancer cells. Our previous study showed that, as a member of the inhibitor of apoptosis proteins (IAPs) family, Livin could play an important role in the initiation of human prostate cancer and promote cell proliferation by altering the G1-S cell cycle transition. In the present study, we measured the apoptosis sensitivity of prostate cancer cells to zinc and sorafenib and found that zinc sensitized prostate cancer cells to sorafenib-induced apoptosis. Surprisingly, we also found that, unlike its counterparts Survivin and cIAP2, Livin was not decreased all the time; instead, it was compensatively increased in zinc-mediated apoptosis at 48 h in prostate cancer cells. Our results offer potential treatment combinations that may augment the effect of sorafenib, and also reveal, for the first time, that increased Livin expression may play a role in the early cell death response of prostate cancer cells to zinc.

Spatiotemporal distribution and control measure evaluation of droplets and aerosol clouds in dental procedures.

We evaluated the distributions of dental splatters and the corresponding control measure effects with high-speed videography and laser diffraction. Most of the dental splatters were small droplets (<50 µm). High-volume evacuation combined with a suction air purifier could clear away most of the droplets and aerosols.

Livin regulates prostate cancer cell invasion by impacting the NF-κB signaling pathway and the expression of FN and CXCR4.

Prostate cancer (PCa) has the second highest mortality rate of all tumor-related diseases for males in Western countries, and the incidence of PCa in China is increasing. Previous studies have proven that inhibitor of apoptosis proteins (IAPs) can regulate tumor cell invasion and metastasis. Livin is the most recently identified IAP. Our previous study showed that Livin might play an important role in the initiation of human PCa and that Livin-α might promote cell proliferation by regulating the G1-S cell cycle transition. However, whether Livin, as an IAP, can regulate the invasive ability of PCa cells remains unknown. In this study, we found that the expression of Livin was higher in metastatic PCa tissues than in nonmetastatic tissues and that the expression of Livin was downregulated/upregulated by small interfering RNA/vector, which could inhibit/promote PC-3/LNCaP cell invasion. This action was related to the impact of Livin on nuclear factor-κB (NF-κB) and its downstream signaling pathway, including FN and CXCR4. Together, our findings suggested that Livin might regulate tumor cell invasion in PCa directly, and that Livin might be an ideal candidate for preventing tumor cell invasion.

Livin-α promotes cell proliferation by regulating G1-S cell cycle transition in prostate cancer.

BACKGROUND: Prostate cancer is the third most common cancer and the second leading cause of cancer death for males in US. Livin has recently been described as a cancer-associated member of inhibitor of apoptosis proteins family, highly expressed in prostate cancer. Livin gene encodes two splicing variants, termed Livin-α and Livin-ß. We hypothesized that deregulation of proliferation could be due in part to Livin expression. METHODS: Pathological analysis of Livin was performed in 20 prostate cancer tissues and 5 benign prostatic hyperplasia tissues. The expression of Livin isoforms was also investigated by Western blot in prostate cancer cell lines LNCaP and PC3. The role of Livin-α in vitro was further studied. Using Livin-α knockdown and overexpression models, cell cycle analysis, Ki-67 immunocytostaining, and MTT assay were performed respectively. RESULTS: Livin expression positive ratio was shown to be 5.4%, 23.6%, 52.4%, 73.4% in benign prostatic hyperplasia, low, medium, and high grade of prostate cancer respectively, and Livin was positively correlated with clinical pathological grades of prostate cancer. Livin-α was expressed in both LNCaP and PC3; meanwhile; Livin-ß was only detected in the PC3. Livin-α siRNA not only resulted in G(1)-S cell cycle arrest, but also strongly correlated with the descended proliferation index and survival rate in LNCaP. In comparison, overexpression of Livin-α resulted in an accelerated S phase entry combined with elevated proliferation index and survival in LNCaP. CONCLUSIONS: Livin-α may promote cell proliferation by regulating G(1)-S cell cycle transition and possibly play an important part in initiation of prostate cancer.

Analysis of dose monitoring for external exposure to radiology in hospital workers from 2010 to 2018.

OBJECTIVE: To investigate the individual level of radiation exposure in hospital workers from 2010 to 2018. METHODS: Oral radiology workers in our hospital including medical imaging technicians and radiation therapists from 2010 to 2018 were selected as the subjects of investigation. The oral radiological workers were monitored quarterly according to the level of external exposure via individual dose monitoring standards. The monitoring data were aggregated, analyzed and evaluated. RESULTS: A total of 531 hospital radiology workers were monitored from 2010 to 2018. The rate of effective monitoring per year for medical imaging technicians and radiation therapists was 97.35% and 97.47%, respectively. The average collective effective dose was 8.511 mSv, and annual effective dose per capita was 0.148 mSv. The highest collective effective dose was in 2017, while the highest annual effective dose per capita was in 2010. The annual effective dose per capita for medical imaging technicians was lower than that for radiation therapists. The abnormal rate of personal doses of radiation therapists was higher than that for medical imaging technicians. The collective effective dose changes in the two types of radiation workers were monitored from 2010 to 2018, showing an increased trend. The fluctuations of annual effective dosing per capita monitored from 2010 to 2018 in radiation therapists was more significant than that in medical imaging technicians. CONCLUSIONS: Oral radiation workers monitored were all far below the dose limit of 20 mSv, which indicated that the working environment of oral radiation workers in our hospital was safe with good radiation condition and protection.

Molecular analysis of oral microflora in patients with primary Sjögren's syndrome by using high-throughput sequencing.

BACKGROUND: The objective of this study was to characterize the oral microflora profile of primary Sjögren's syndrome (pSS) patients, thereby revealing the connection between oral bacterial composition and dental caries, and to identify the "core microbiome" in the oral cavities of pSS patients and systemic healthy individuals by using a high-throughput sequencing technique. METHODS: Twenty-two pSS patients and 23 healthy controls were enrolled in this study. Their clinical data and oral rinse samples were collected. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene of samples were amplified and analyzed by high-throughput sequencing on the Illumina Miseq PE300 platform. RESULTS: Both two groups were age- and sex-matched. There were significantly higher decayed, missing and filled teeth (DMFT) and decayed, missing and filled surfaces (DMFS) in the pSS group than in the control group (p < 0.01). Alpha diversity was depleted in pSS patients, compared with healthy controls (p < 0.01), while beta diversity between the two groups was not significantly different. Seven discriminative genera (LDA > 4) were found between the two groups in LEfSe (LDA Effect Size) analysis. The relative abundance of Veillonella in pSS patients was fourfold higher, while Actinomyces, Haemophilus, Neisseria, Rothia, Porphyromonas and Peptostreptococcus were significantly lower in pSS patients than in healthy controls. However, the correlation between Veillonella and DMFT/DMFS was not significant (p > 0.05). In Venn diagram analysis, nine genera shared by all samples of two groups, which comprised 71.88% and 67.64% in pSS patients and controls, respectively. DISCUSSION: These findings indicate a microbial dysbiosis in pSS patients; notably, Veillonella might be recognized as a biomarker in pSS patients. The core microbiome in pSS patients was similar to the systemic healthy population. These provide insight regarding advanced microbial prevention and treatment of severe dental caries in pSS patients. This study also provides basic data regarding microbiology in pSS.

Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway.

Emerging evidence has indicated that long non­coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) regulates cell growth, differentiation, apoptosis and cancer progression. However, the expression and function of HOTTIP in the progression of renal cell carcinoma (RCC) remain largely unknown. In this study, we investigated the role of the lncRNA HOTTIP in RCC. The expression levels of HOTTIP in RCC tissues and cell lines were determined by RT­qPCR. The association between HOTTIP expression and clinicopathological characteristics and prognosis was analyzed in patients with RCC from the TCGA database. Loss­of­ function assays were designed and conducted to verify the oncogenic function of HOTTIP in RCC progression. Luciferase assay was performed to explore the mechanisms of the miRNA­lncRNA sponge. The results revealed that HOTTIP expression was upregulated in RCC. An increased HOTTIP expression in RCC was associated with a larger tumor size and a higher clinical stage, lymph node metastasis and vascular invasion. Additionally, patients RCC with a high HOTTIP expression had a significantly shorter overall survival (OS) and disease­free survival (DFS). HOTTIP knockdown significantly inhibited cell proliferation, migration and invasion, and increased the apoptosis of RCC cells in vitro. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for hsa­miR­615­3p, and led to the derepression of its endogenous target, insulin­like growth factor-2 (IGF­2), which is a protein hormone that exerts a stimulatory effect on tumor cell growth. miR­615 inhibition reversed the suppressive effects of HOTTIP knockdown on RCC cell progression. HOTTIP regulated IGF­2 expression in a miR­615­dependent manner in RCC cells. In addition, IGF­2 expression was significantly upregulated in the RCC specimens and a positive association between the expression of HOTTIP and IGF­2 in RCC tissues was detected. The effect of HOTTIP was abolished by the siRNA­mediated silencing of IGF-2 in RCC cells. On the whole, this study demonstrates, for the first time, at least to the best of our knowledge, that the HOTTIP/miR­615/IGF­2 axis plays an important role in RCC progression and potentially contributes to the improvement of RCC diagnosis and therapy.