Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients.

BACKGROUND: The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM. AIM: To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. METHODS: A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. RESULTS: Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. CONCLUSION: This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

Observation on the effect of platelet-rich plasma combined with drugs in the treatment of herpes zoster neuralgia.

PURPOSE: To observe the effect of ultrasound-guided platelet-rich plasma (PRP) injection in the treatment of herpes zoster neuralgia (HZN). METHODS: Eighty patients with HZN were randomly divided into observation group and control group, with 40 cases in each group. The observation group was treated with ultrasound-guided PRP injection of target nerves combined with drugs. The control group was treated with drugs alone. The pain scores of before treatment (T0), and 1 week (T1), 1 month (T2), 3 months (T3) and 6 months (T4) after treatment were recorded with Numerical Rating Scale (NRS). The sleep quality of patients was assessed with the Athens Insomnia Scale, and the dosage used at each time point, skin lesions, adverse reactions, and the occurrence of postherpetic neuralgia (PHN) were recorded. RESULTS: The NRS score of the two groups after treatment showed a downward trend. Compared with T0 at each time point, the difference was statistically significant (p < 0.05). And the NRS score of the observation group was lower than control group (p < 0.05). The sleep quality of the observation group was better. The dosage of the observation group was less, and the time of herpes dry-up, scab crusting and shedding in the observation group was significantly shorter (p < 0.05). The incidence of dizziness, lethargy, ataxia and PHN in the observation group was significantly reduced (p < 0.05). CONCLUSION: Compared with traditional drug treatment alone, the ultrasound-guided PRP injection has the advantages of better analgesia and fewer side effects, which provides a new idea for the treatment of HZN.

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers.

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.

Background: Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown. Methods: We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment. Results: We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83. Conclusion: Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.

The effect of short-term spinal cord electrical stimulation on patients with postherpetic neuralgia and its effect on sleep quality.

OBJECTIVES: To investigate the effect of short-term spinal cord electrical stimulation (stSCS) on postherpetic neuralgia (PHN) and its effect on sleep quality in patients in Guangxi, China. MATERIAL AND METHODS: 160 patients with acute PHN patients were divided into a control group and an experimental group according to the random number table method, 80 cases each. The experimental group was implanted with percutaneous epidural electrodes and given short-term spinal cord electrical stimulation treatment, while the control group was treated with nerve block therapy to compare the efficacy and sleep quality of the two groups of patients in different periods. Pain Visual Analogue Scale (VAS) score and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the analgesic effect and sleep quality, respectively. RESULTS: The patients in the experimental group had significantly lower visual analog scale (VAS) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1, 2, 3 d, 1 week, and 1 and 3 months after treatment than those in the control group [after treatment 3 months: (0.86±0.31) points to (2.97±0.55) points, (5.4±1.16) score to (7.46±1.27) score], the difference was statistically significant (both P<0.05), and VAS and PSQI scores of the two groups showed a significant downward trend with the increase of treatment time. CONCLUSION: The clinical effect of short-term spinal cord electrical stimulation on PHN is good, and it can play a rapid and effective relief effect on pain in patients. At the same time, it will effectively improve patient's sleep quality, with high safety.

Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1.

Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than 1000 nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes remain to be fully elucidated. Here, we show that histone demethylase LSD1 KO from adult mouse liver (LSD1-LKO) reduces the expression of one-third of all nuclear-encoded mitochondrial genes and decreases mitochondrial biogenesis and function. LSD1-modulated histone methylation epigenetically regulates nuclear-encoded mitochondrial genes. Furthermore, LSD1 regulates gene expression and protein methylation of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), which controls the final step of NAD+ synthesis and limits NAD+ availability in the nucleus. Lsd1 KO reduces NAD+-dependent SIRT1 and SIRT7 deacetylase activity, leading to hyperacetylation and hypofunctioning of GABPß and PGC-1α, the major transcriptional factor/cofactor for nuclear-encoded mitochondrial genes. Despite the reduced mitochondrial function in the liver, LSD1-LKO mice are protected from diet-induced hepatic steatosis and glucose intolerance, partially due to induction of hepatokine FGF21. Thus, LSD1 orchestrates a core regulatory network involving epigenetic modifications and NAD+ synthesis to control mitochondrial function and hepatokine production.

Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice.

Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.

Characteristics of the intestinal flora in patients with peripheral neuropathy associated with type 2 diabetes.

OBJECTIVE: To study the characteristics of the intestinal flora in patients with diabetic peripheral neuropathy (DPN) and analyze the association between the intestinal flora and clinical indicators. METHODS: We classified 80 subjects into three groups: patients with DPN (n = 45), patients type 2 diabetes without DPN (n = 21), and healthy controls (n = 14). The intestinal flora composition was compared among the three groups, and the correlation between the intestinal flora and clinical indicators was analyzed. RESULTS: At the phylum level, the richness of Firmicutes and Actinobacteria was elevated in the DN group, and that of Bacteroidetes was decreased. At the genus level, the richness of Bacteroides and Faecalibacterium was significantly decreased in the DPN group, whereas that of Escherichia-Shigella, Lachnoclostridium, Blautia, Megasphaera, and Ruminococcus torques group was increased. The homeostasis model assessment insulin resistance index was positively correlated with Megasphaera richness. Glycine ursodeoxycholic acid was positively correlated with Ruminococcus gnavus group and Phascolarctobacterium richness. Tauroursodeoxycholic acid was positively correlated with Ruminococcus gnavus group and Parabacteroides richness. CONCLUSION: There was obvious intestinal microbiota disorder in patients with DPN, which may be related to insulin resistance. These changes may have important roles in the development of DPN.

Overexpression of novel long intergenic non­coding RNA LINC02454 is associated with a poor prognosis in papillary thyroid cancer.

It has been revealed from microarray data analysis that long intergenic non­coding RNA 02454 (LINC02454) is highly expressed in papillary thyroid cancer (PTC). The aim of the present study was to explore the potential role of LINC02454 in the tumorigenesis of PTC. The mRNA expression levels of LINC02454 were assessed using data from The Cancer Genome Atlas (TCGA) and the GSE66783 cohort in thyroid cancer, and were validated using reverse transcription­quantitative PCR in 104 patients with PTC recruited in the present study. The association between the LINC02454 mRNA expression levels and the clinicopathological features of the 104 patients with PTC were also analyzed. Functional enrichment analyses were conducted on the differentially expressed genes in the high and low LINC02454 expression groups that were identified from the TCGA cohort. RNA interference, using short interfering (si)RNA against LINC02454, was used to investigate the role of LINC02454 in the biological functions of PTC cells in vitro. The expression level of LINC02454 was significantly increased in PTC tissues (P=0.0011) and was significantly associated with a larger tumor size, T stage, an advanced TNM stage and an increased lymph node metastasis (P<0.05), which was consistent with that in the TCGA and GSE66783 cohort. High expression levels of LINC02454 were observed in patients with PTC that also had BRAF mutations (P<0.001), and were significantly associated with a poorer disease­free survival in the TCGA cohort (P<0.05). Functional enrichment analysis indicated that LINC02454­related genes were significantly enriched in Gene Ontology terms, such as 'positive regulation of cell proliferation', 'positive regulation of cell division' and 'cell adhesion', and the following Kyoto Encyclopedia of Genes and Genomes pathways: 'Pathways in cancer' 'proteoglycans in cancer' and 'ECM­receptor interaction'. In vitro, the knockdown of LINC02454 markedly arrested the cells in the G0/G1 phase of the cell cycle, and also led to an overall increase in apoptosis, as well as to an unexpected decrease in cell proliferation. LINC02454 may thus potentially function as an oncogene, which inhibits the apoptosis and enhances proliferation of PTC cells. Thus, as suggested by the findings of the present study, LINC02454 may be used as a diagnostic and prognostic biomarker for PTC in the future.

Visual Saliency Detection for Over-Temperature Regions in 3D Space via Dual-Source Images.

To allow mobile robots to visually observe the temperature of equipment in complex industrial environments and work on temperature anomalies in time, it is necessary to accurately find the coordinates of temperature anomalies and obtain information on the surrounding obstacles. This paper proposes a visual saliency detection method for hypertemperature in three-dimensional space through dual-source images. The key novelty of this method is that it can achieve accurate salient object detection without relying on high-performance hardware equipment. First, the redundant point clouds are removed through adaptive sampling to reduce the computational memory. Second, the original images are merged with infrared images and the dense point clouds are surface-mapped to visually display the temperature of the reconstructed surface and use infrared imaging characteristics to detect the plane coordinates of temperature anomalies. Finally, transformation mapping is coordinated according to the pose relationship to obtain the spatial position. Experimental results show that this method not only displays the temperature of the device directly but also accurately obtains the spatial coordinates of the heat source without relying on a high-performance computing platform.

The feasibility of b-value maps based on threshold DWI for detection of breast cancer: A case-control STROBE compliant study.

Diffusion-weighted imaging (DWI) plays an important role in the diagnosis of breast cancer as well as the evaluation of treatment effects. A novel technique named b-value map based on thresholded DWI images has been proposed and can achieve good contrast for demonstrating prostate lesions only by manipulating the window width and center of the images. Its application on the breast has not yet explored, so the aim of the study was to investigate the feasibility of b-value maps based on threshold DWI for detection of breast cancer. A total of 25 patients with pathologically proven invasive ductal breast carcinoma were included and underwent preoperative magnetic resonance imaging (MRI) examinations including DWI at 3T. The capabilities to display lesions of DWIb=800, b-value maps and optimal computed DWI (cDWI) images were evaluated by using a 4-point method of scoring. Apparent diffusion coefficient (ADC) values of lesions were measured for the breast carcinoma. Mean scores indicating the display capability were compared among DWIb=800, optimal cDWI and b-value maps by using Kruskal-Wallis test followed by Nemenyi test. The scores of both b-value maps (3.92 ±â€Š0.28) and optimal cDWI images (3.80 ±â€Š0.41) were higher than that of DWIb=800 (3.48 ±â€Š0.51), with statistical differences (P = .001 and P = .033, respectively). The optimal b values for manifesting breast carcinoma based on cDWI were 1000 to 1200 s/mm. The b-value map enables fast identification for breast lesions and shows similar performance to the optimal cDWI images.

Opposite effects of vitamin C and vitamin E on the antifungal activity of honokiol.

The aim of the present study was to evaluate the effects of two well-known natural antioxidants vitamin C (VC) and vitamin E (VE) on the antifungal activity of honokiol against Candida albicans. The broth microdilution method was employed to test the antifungal activities of honokiol with or without antioxidants in the medium against C. albicans strain. Intracellular reactive oxygen species (ROS) and lipid peroxidation were determined by fluorescence staining assay. Mitochondrial dysfunction was assessed by detecting the mitochondrial DNA and the mitochondrial membrane potential. We observed that VC could significantly potentiate the antifungal activities of honokiol while VE reduced the effectiveness of honokiol against C. albicans. In addition, VC accelerated honokiol-induced mitochondrial dysfunction and inhibited glycolysis leading to a decrease in cellular ATP. However, VE could protect against mitochondrial membrane lipid peroxidation and rescue mitochondrial function after honokiol treatment. Our research provides new insight into the understanding of the action mechanism of honokiol and VC combination against C. albicans.

Fecal microbiota transplantation relieve painful diabetic neuropathy: A case report.

RATIONALE: Fecal microbiota transplantation (FMT) has been used in a wide variety of diseases. In this article, we reported a 46-year-old female with diabetic neuropathy (DN) achieved remission by the treatment of FMT. PATIENT CONCERNS: The patient with an 8-year history of diabetes and hypertension was admitted to hospital due to sensitive pain of her right thigh and poor blood glucose control. The traditional hypoglycemic and analgesic treatment were useless to her symptoms. DIAGNOSIS: Diabetic-induced neuropathy was considered. INTERVENTIONS: This patient received twice FMTs for 3 months. OUTCOMES: After twice FMTs, the clinical response of patient was pleasant. The glycemic control was improved, with a remarkable relief of the symptoms of painful DN in particular. No obvious adverse effects were observed during the FMTs and follow-up observation-testing. LESSONS: We proposed that FMT could be a promising treatment in patients with diabetes or diabetes-related complications like DN. FMT also appeared to be definitely safer and more tolerable than the pharmacologic treatment in patients with DN.

Dysregulation of lncRNAs GM5524 and GM15645 involved in high­glucose­induced podocyte apoptosis and autophagy in diabetic nephropathy.

Diabetic nephropathy (DN) is an important microvascular complication of diabetes, and one of the leading causes of end­stage kidney disease. However, the mechanism of the DN pathogenic process remains unclear. Recently, long non­coding (lnc)RNA dysregulation has been regarded to cause the occurrence and development of various human diseases, although the functions of lncRNAs in human DN are poorly understood. The authors' previous study using microarray analysis identified hundreds of dysregulated lncRNAs in DN, although the functions of these lncRNAs were not demonstrated. Out of those dysregulated lncRNAs, Gm5524 was significantly upregulated in response to DN, while Gm15645 was significantly downregulated in response to DN. In the present study, this result was further validated by reverse transcription­quantitative polymerase chain reaction assays, and downregulating or overexpressing Gm5524 and Gm15645 in mouse podocytes. Notably, knockdown of Gm5524 and overexpression of Gm15645 induced mouse podocyte apoptosis and decreased cell autophagy in high­glucose culture conditions. In conclusion, the results of the present study revealed the roles of lncRNAs Gm5524 and Gm15645 in high­glucose induced podocyte apoptosis and autophagy during DN, which may further the understanding of the involvement of lncRNAs in DN, and provide a potential novel therapeutic target for this disease.

LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote gastric cancer cells proliferation.

The present work aimed to probe into the effect of long non-coding RNA (lncRNA) LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p and its target gene MCL1 Transfected si-LINC00152 was used to down-regulate LINC00152, and cells proliferation was measured by the cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle were analyzed by flow cytometry (FCM). Besides, we also detected the potential functional effects of differential expression of LINC00152 in vivo using nude mouse xenograft model. We overexpressed and downexpressed miR-193a-3p to study the in vitro effect of miR-193a-3p on GC cells proliferation and vitality. And MCL1 was silenced by shRNA to investigate the effect of MCL1 on proliferation of GC cells. In this research, LINC00152 was proven to have a higher expression level in GC tissues than in the adjacent normal tissues. GC cells proliferation was inhibited after LINC00152 was down-regulated. LINC00152 inhibited the expression of miR-193a-3p, which negatively regulated MCL1 In addition, GC cells proliferation was inhibited by cell transfection with shRNA-MCL1, and enhanced by transfection with miR-193a-3p mimics. Our study suggested that LINC00152 was overexpressed in GC tissues, and it down-regulated miR-193a-3p to enhance MCL1 expression thereby promoting GC cells proliferation.

Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy.

Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA-383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucose-induced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR-383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy.

Microarray analysis of long noncoding RNA expression patterns in diabetic nephropathy.

AIMS: Long noncoding RNAs (lncRNAs) are implicated in various biological processes and human diseases. Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). We explored the potential functions of lncRNAs in DN. METHODS: We established a mouse model of DN and compared lncRNA expression patterns between DN model and db/m control mouse kidney tissues using microarray analysis. lncRNA function was predicted by gene ontology enrichment and KEGG pathway analyses of lncRNAs-coexpressed mRNAs. Quantitative reverse-transcription PCR was used for validation. Cis- and trans-regulation analyses were conducted to reveal potential relationships between lncRNAs and their target genes. RESULTS: In DN, 311 lncRNAs were dysregulated. LncRNA-coexpressed mRNAs were mainly targeted to golgi apparatus (ontology: cellular component), catalytic activity (ontology: molecular function), and mitotic nuclear division (ontology: biological process), and were mostly enriched in glutathione metabolism signaling. One hundred forty-seven lncRNAs were regarded as cis-regulatory. Several groups of lncRNAs may participate in biological pathways related to DN via trans-regulation of protein-coding genes. CONCLUSION: Hundreds of lncRNAs are dysregulated in DN. These lncRNAs might be involved in the pathogenesis of DN by modulating multiple molecular pathways. Our findings provide potential candidate biomarkers for predicting or diagnosing DN.

Periprostatic implantation of neural differentiated mesenchymal stem cells restores cavernous nerve injury-mediated erectile dysfunction.

Mesenchymal stem cells (MSCs) have been utilized to restore erectile function in animal models of cavernous nerve injury (CNI). However, transplantation of primary MSCs may lead to unpredictable therapeutic outcomes. In this study, we investigated the efficiency of neural differentiated MSCs (d-MSCs) on the restoration of erectile function in CNI rats. Rat bone marrow MSCs (r-BM-MSCs) were treated with all-trans retinoic acid to induce neural differentiation. Rats were divided into five groups: a sham operation group; a bilateral CNI group that received an intracavernous injection of r-BM-MSCs (IC group); and three groups that received periprostatic implantation of either r-BM-MSCs (IP group), d-MSCs (IP-d group), or PBS (PBS group). The data revealed that IP injection of d-MSCs ameliorated erectile function in a similar manner to an IC injection of MSCs and enhanced erectile function compared to an IP injection of MSCs. An in vivo time course of d-MSCs survival revealed that PKH26-labled d-MSCs were detectable either within or surrounding the cavernous nerve tissue. In addition, the expression of caspase-3 significantly increased in the PBS group and decreased after treatment with MSCs, especially in the IC and IP-d groups. Furthermore, the expression levels of neurotrophic factors increased significantly in d-MSCs. This study demonstrated that periprostatic implantation of d-MSCs effectively restored erectile function in CNI rats. The mechanism might be ascribed to decreases in the frequency of apoptotic cells, as well as paracrine signaling by factors derived from d-MSCs.

Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis.

Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12-24h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy.

Dental education evaluation in China: a systematic review.

BACKGROUND: Accreditation of education is very important for maintaining and improving education quality. With the development of modern dental education, more and more attention is being paid to accreditation of dental education in China. Current accreditation of dental education in China is called "dental education evaluation". By using a systematic review, this paper aims to provide the general profile of the standards and process of dental education evaluation in China (DEEC). METHODS: A systematic review on DEEC was performed, CAJD and VIP databases were employed to identify all literatures which were relevant to DEEC. Profile and features of DEEC were compared with those of the Accreditation Standards for Dental Education Programs of the USA (ASDEPU). RESULTS: The current standards for the evaluation are composed of six modules and twenty-four items, the evaluation process consists of three stages There was some difference between DEEC and its American counterparts. CONCLUSIONS: Accreditation on dental education is very important for the maintenance and improvement of education quality. As the primary form of dental education accreditation, DEEC is basically suitable for current dental education conditions in China, however, in order to keep pace with the changing conditions, both the standards and actions of DEEC should often be revised.