[Comprehensive therapy of traditional Chinese medicine for erectile dysfunction with damp-heat stasis: A clinical observation of 103 cases].

OBJECTIVE: To assess the clinical effect and safety of comprehensive therapy of traditional Chinese medicine (TCM) in the treatment of erectile dysfunction (ED) with damp-heat stasis. METHODS: We selected 108 cases of ED with damp-heat stasis meeting the inclusion criteria and treated with tadalafil (the control group, n = 54) or tadalafil + comprehensive TCM therapy (the trial group, n = 54) in the First Affiliated Hospital of Henan University of Chinese Medicine in the same period. After 8 weeks of treatment, we recorded the patients' scores on IIEF-5, TCM syndrome, erectile quality (EQS), 9-Item Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Scale 7 (GAD-7). At 16 weeks of our study, we collected the efficacy parameters, safety indicators and adverse reactions by telephone follow-up and compared the data obtained between the two groups of patients. RESULTS: Totally, 103 of the patients completed the study, 51 in the control and 52 in the trial group. Compared with the baseline, the IIEF-5 and EQS scores were both markedly increased after 8 weeks of treatment in the trial group (12.35±3.00 vs 18.36±2.82, P< 0.05; 39.5 ï¼»30.25－43ï¼½ vs 67.5 ï¼»54.5－76.75ï¼½, P< 0.05) and the control (11.96±2.79 vs 15.88±3.86, P< 0.05; 38.0 ï¼»29－42ï¼½ vs 56 ï¼»49－64ï¼½, P< 0.05), even more significantly in the former than in the latter (P< 0.05); the TCM syndrome and GAD-7 scores were remarkably decreased in the trial (9.5 ï¼»8－12ï¼½ vs 4.0 ï¼»2.25－5ï¼½, P< 0.05; 5 ï¼»2.25－6.75ï¼½ vs 2.5 ï¼»1－4.75ï¼½, P< 0.05) and the control group (10.0 ï¼»8－12ï¼½ vs 5.0 ï¼»3－6ï¼½, P< 0.05; 5.0 ï¼»3－6ï¼½ vs 4.0 ï¼»2－5ï¼½, P< 0.05), even more significantly in the former than in the latter (P< 0.05), so were the PHQ-9 scores (P< 0.05), but with no statistically significant difference between the two groups (P > 0.05). The IIEF-5 scores of the two groups remained significantly higher than the baseline during the follow-up (P< 0.05), even higher in the trial than in the control group (17.04±2.60 vs 14.16±3.34, P< 0.05). No obvious abnormal safety indicators or adverse events were observed during the study. CONCLUSION: Comprehensive TCM therapy combined with tadalafil is superior to tadalafil alone in the treatment of ED with damp-heat stasis, and has a better long-term efficacy and a higher safety.

[Yishen Tongluo Prescription for repairing benzo(a)pyrene-induced sperm DNA damage in male rats: Effect and mechanism].

OBJECTIVE: To investigate the repairing effect of Yishen Tongluo Prescription (YTP) on sperm DNA fragmentation index (DFI) in male rats exposed to benzo(a)pyrene (BaP) and its possible mechanism. METHODS: Thirty Wistar male rats were equally randomized into a blank control, a BaP-exposure and a YTP intervention group, those in the latter two groups exposed to BaP at 20 mg/kg/d for 60 consecutive days, and those in the YTP intervention group treated intragastrically with YTP from the 31st day of BaP exposure for a total of 30 days. After the last administration, the sperm DFI of the rats was detected by sperm chromatin structure analysis, the levels of FSH, LH and T in the serum and superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and adenosine triphosphate (ATP) in the testis were measured by ELISA. RESULTS: Compared with the blank controls, the rats in the BaP-exposure group showed significantly increased DFI ( ï¼»4.23 ± 1.40ï¼½% vs ï¼»12.46 ± 3.07ï¼½%, P < 0.05), serum FSH (ï¼»1.76 ± 0.31ï¼½ vs ï¼»2.53 ± 0.28ï¼½ U/L, P < 0.05) and LH (ï¼»30.59 ± 2.14ï¼½ vs ï¼»39.72 ± 2.80ï¼½ U/L, P < 0.05), decreased levels of serum T (ï¼»5.33 ± 0.43ï¼½ vs ï¼»4.42 ± 0.38ï¼½ nmol/L, P < 0.05) and testicular SOD (ï¼»166.18 ± 3.74ï¼½ vs ï¼»113.23 ± 10.76ï¼½ U/ml, P < 0.05) and ATP (ï¼»41.23 ± 2.21ï¼½ vs ï¼»33.48 ± 2.74ï¼½ mol/L, P < 0.05), and elevated contents of MDA (ï¼»7.55 ± 0.93ï¼½ vs ï¼»10.59 ± 1.17ï¼½ nmol/ml, P < 0.05) and NO (ï¼»44.23±4.47ï¼½ vs ï¼»54.49 ± 3.13ï¼½ mol/L, P < 0.05). All the above parameters returned to normal after YTP intervention (DFI: ï¼»5.73 ± 2.46ï¼½%, FSH: ï¼»2.07 ± 0.45ï¼½ U/L, LH: ï¼»33.94 ± 4.44ï¼½ U/L, T: ï¼»4.96 ± 0.24ï¼½ nmol/L, SOD: ï¼»135.22 ± 7.26ï¼½ U/ml, ATP: ï¼»38.26 ± 2.14ï¼½ mol/L, MDA: ï¼»8.37 ± 1.29ï¼½ nmol/ml, NO: ï¼»48.36 ± 3.98ï¼½ mol/L), with statistically significant difference from those in the BaP-exposure group (all P < 0.05). CONCLUSION: Yishen Tongluo Prescription can repair BaP-induced sperm DNA damage in male rats, which may be attributed to its effects of suppressing oxidative damage.

Comprehensive analysis of clinical prognosis and molecular immune characterization of tropomyosin 4 in pancreatic cancer.

Pancreatic cancer (PC) is one of the most lethal human solid malignancies with devastating prognosis, making biomarker detection considerably important. Immune infiltrates in microenvironment is associated with patients' survival in PC. The role of Tropomyosin 4 (TPM4) gene in PC has not been reported. Our study first identifies TPM4 expression and its potential biological functions in PC. The potential oncogenic roles of TPM4 was examined using the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). We investigated the clinical significance and prognostic value of TPM4 gene based on The Gene Expression Profiling Interactive Analysis (GEPIA) and survival analysis. TIMER and TISIDB databases were used to analyze the correlations between TPM4 gene and tumor-infiltrating immune cells. We found that the expression level of TPM4 was upregulated in PC malignant tissues with the corresponding normal tissues as controls. High TPM4 expression was correlated with the worse clinicopathological features and poor prognosis in PC cohorts. The positive association between TPM4 expression and tumor-infiltrating immune cells was identified in tumor microenvironment (TME). Moreover, functional enrichment analysis suggested that TPM4 might participate in cell adhesion and promote tumor cell migration. This is the first comprehensive study to disclose that TPM4 may serve as a novel prognostic biomarker associating with immune infiltrates and provide a potential therapeutic target for the treatment of PC.

Microvascular Decompression for Trigeminal Neuralgia Due to Venous Compression Alone.

Microvascular decompression (MVD) has been confirmed as an effective treatment of trigeminal neuralgia (TN); however, most previous reports just focused on MVD for TN caused by arterial conflict, there is a paucity of information about its use in venous compression causing TN. In the present study, the authors summarize 5-year experience of MVD for primary TN due to venous compression alone. Thirty-four patients with primary TN caused solely by veins underwent MVD. The presenting symptoms, key operative notes, surgical outcomes together with complications were reviewed. Of all the 34 patients, 19 (55.9%) patients occurred as typical TN. The V2 division was the most commonly affected area. Most of the venous conflicts were grade III (20/34, 58.8%). Deep superior petrosal venous system was the most frequent offending vessel (21/34, 61.8%). The venous conflicts were located at the trigeminal root entry zone in 10 (29.4%) patients, the mid cisternal zone in 18 (52.9%) patients, and the porus of Meckel's cave in 11 (32.4%) patients. At the last follow-up, excellent outcome was obtained in 26 (76.5%) patients, 7 (20.6%) patients got good outcome, fair outcome was achieved in 7 (20.6%) patients, and 1 patient unimproved (2.9%). Cerebrospinal fluid leakage was the most common complication (5.9%). In conclusion, MVD is a safe and effective surgical option for TN due to venous compression alone. It is noteworthy to explore the entire nerve and to protect veins as much as possible.

D-dopachrome tautomerase is over-expressed in pancreatic ductal adenocarcinoma and acts cooperatively with macrophage migration inhibitory factor to promote cancer growth.

Previous studies have established the important role of MIF in the development of pancreatic ductal adenocarcinoma (PDAC) for both therapeutic and diagnostic perspectives, but little is known about the expression and function of D-dopachrome tautomerase (DDT), a functional homolog of MIF, in PDAC. In the present study, we demonstrated that DDT was over-expressed in PDAC tissues in a pattern correlated with MIF. In the pancreatic cancer cell lines, PANC-1, BXPC-3 and ASPC-1, both DDT and MIF were expressed and co-localized with each other in the endosomal compartments and plasma membrane. Knockdown of DDT and MIF in PANC-1 cells cooperatively inhibited ERK1/2 and AKT phosphorylation, increased p53 expression, and reduced cell proliferation, invasion and tumor formation. These effects were rescued by the re-expression of MIF or DDT, but not by the forced expression of the tautomerase-deficient mutants of DDT and MIF, P1G-DDT and P1G-MIF. Finally, we observed that 4-iodo-6-phenylpyrimidine (4-IPP), a covalent tautomerase inhibitor of both DDT and MIF, attenuated PANC-1 cell proliferation and colony formation in vitro and tumor growth in vivo. Thus, targeting the tautomerase sites of both MIF and DDT may offer more efficient therapeutic benefits to PDAC patients.

CD4(+)CD25 (+) regulatory T cells are not required for mesenchymal stem cell function in fully MHC-mismatched mouse cardiac transplantation.

Although the immunomodulative properties of mesenchymal stem cells (MSCs) open up attractive possibilities in solid-organ transplantation, information concerning the optimal dose, route, timing of administration, major histocompatibility complex (MHC)-restriction and relevant mechanisms is currently lacking. Therefore, better characterization of MSC immunoregulatory activity and elucidation of its mechanisms are crucial. In this study, we confirmed that MSCs did not elicit proliferation by allogeneic CD4(+) T cells, suggesting that MSCs were not immunogenic. By using C57BL/6 mouse MSCs as donor-derived or recipient-derived or as third-party MSCs, we discovered that MSCs suppressed CD4(+) T cell proliferation and prolonged mouse cardiac allograft survival in a dose-dependent and non-MHC-restricted manner. We also found that intraperitoneal administration favored survival prolongation, although this prolongation was weaker than that via the intravenous route. Only infusion at earlier time points favored survival prolongation. Depletion of CD4(+)CD25(+) T cells did not affect the immunosuppression of MSCs on CD4(+) T cells. Moreover, MSCs did not induce regulatory T cells. The in vivo data revealed that MSCs did not increase the percentage of CD4(+)CD25(+) T cells and FoxP3 expression. More importantly, we demonstrated for the first time that depletion of CD4(+)CD25(+) T cells did not hinder MSC-induced survival prolongation, indicating that CD4(+)CD25(+) regulatory T cells were not essential for the prolongation of MSC-mediated allograft survival.

De Garengeot hernia: the ultrasound and computed tomographic findings in an 81-year-old woman.

The presence of appendix within a femoral hernia is a rare condition in an incarcerated femoral hernia. It has a characteristic groin mass, and the diagnosis of appendicitis is mainly made intraoperatively. A specific imaging appearance (ultrasonography, computed tomography [CT]) allows accurate prospective diagnosis. The recognition of this rare femoral hernia helps us to choose appropriate therapeutic approach. We report a case of an 81-year-old woman who present with painful and nonreducible groin mass. The ultrasonography and CT characteristic imaging features successfully diagnosed de Garengeot hernia. To our knowledge, this is the first description of a combination of CT and ultrasound in the preoperative diagnosis.

Integrin α3 Mediates Stemness and Invasion of Glioblastoma by Regulating POU3F2.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor. Integrins have been implicated in the malignancy of GBM. A recent study demonstrated that integrin α3 (ITGA3) promoted the invasion of breast cancer cells by regulating transcriptional factor POU3F2. However, whether this also happened in GBM remained unknown. METHODS: Therefore, we explored the relationship between ITGA3 and POU3F2 in GBM. We measured the expression of ITGA3 and POU3F2 in GBM tissues. We generated ITGA3 knockdown and POU3F2 knockdown GBM U87MG cells and the proliferation, migration and invasion, the expression of stemness markers and epithelial to mesenchymal transition (EMT) markers were measured. We transplanted ITGA3 knockdown and POU3F2 knockdown GBM U87MG cells into mice. The mice were treated with anti-ITGA3 antibody. The tumor sizes, the expression of stemness markers and epithelial-to-mesenchymal transition (EMT) markers were measured. RESULTS: Both ITGA3 and POU3F2 were upregulated in GBM tissues. Knocking down ITGA3 resulted in reduced expression of POU3F2. Knocking down ITGA3 and POU3F2 suppressed U87MG cells proliferation, migration and invasion, inhibited the expression of stemness markers and prevented epithelial- to-mesenchymal transition. The transplantation of ITGA3 knockdown and POU3F2 knockdown U87MG cells decreased tumor size. CONCLUSION: Anti-ITGA3 antibody treatment reduced the tumor size. ITGA3 regulates stemness and invasion of glioblastoma through POU3F2.

A Comparison of Robotic Versus Laparoscopic Distal Pancreatectomy for Benign or Malignant Lesions: A Meta-Analysis.

Background: The momentum of robotic surgery is increasing, and it has great prospects in pancreatic surgery. It has been widely accepted and expanding to more and more centers. Robotic distal pancreatectomy (RDP) is the most recent advanced minimally invasive approach for pancreatic lesions and malignancies. However, laparoscopic distal pancreatectomy (LDP) also showed good efficacy. We compared the effect of RDP with LDP using a meta-analysis. Methods: From January 2010 to June 2023, clinical trials of RDP versus LDP were determined by searching PubMed, Medline, and EMBASE. A meta-analysis was conducted to compare the effect of RDP with LDP. This meta-analysis evaluated the R0 resection rate, lymph node metastasis rate, conversion to open surgery rate, spleen preservation rate, intraoperative blood loss, postoperative pancreatic fistula, postoperative hospital stay, 90-day mortality rate, surgical cost, and total cost. Results: This meta-analysis included 38 studies. Conversion to open surgery, blood loss, and 90-day mortality in the RDP group were all significantly less than that in the LDP group (P < .05). There was no difference in lymph node resection rate, R0 resection rate, or postoperative pancreatic fistula between the two groups (P > .05). Spleen preservation rate in the LDP group was higher than that in the RDP group (P < .05). Operation cost and total cost in the RDP group were both more than that in the LDP group (P < .05). It is uncertain which group has an advantage in postoperative hospital stay. Conclusions: To some degree, RDP and LDP were indeed worth comparing in clinical practice. However, it may be difficult to determine which is absolute advantage according to current data. Large sample randomized controlled trials are needed to confirm which is better treatment. PROSPERO ID: CRD4202345576.

Effects of Supplemental Dexmedetomidine Anesthesia on Intracranial Aneurysm Patients Undergoing Intracranial Interventional Embolization.

BACKGROUND: Intracranial aneurysm (IA) has been identified in approximately 0.4%-3% of the population and associated with 3%-10% mortality. IA is the major factor attributing to spontaneous subarachnoid hemorrhage. We aim to investigate that whether employing dexmedetomidine (DEX), an α2 adrenergic receptor agonist, as a supplementation could impact the outcomes of patients with intracranial interventional embolization. METHODS: Patients were randomly divided into a control group (n = 48 cases) and a DEX (0.6 µg/kg) supplement group (n = 48 cases). Patients' outcomes were evaluated using the Glasgow Outcome Scale. Serum levels of norepinephrine, cortisol, interleukin-6, C-reactive protein, neuron-specific enolase, and S100ß were determined using enzyme-linked immunoassay. The cognitive function of patients was assessed using the Mini-Mental State Exam and Montreal Cognitive Assessment tests. RESULTS: DEX supplementation during anesthesia reduced adverse reaction, surgical stress, and attenuated cognitive impairment after extubation in IA patients' postintracranial interventional embolization. CONCLUSIONS: Our study demonstrated that employing DEX as supplementation during anesthesia could effectively reduce surgical stress and improve cognitive function, ultimately improving patients' recovery from intracranial interventional embolization.

Clinical study on the treatment of male infertility with Wuwei Fuzheng Yijing decoction based on microplastics: Study protocol for a randomized controlled trial.

BACKGROUND: Environmental pollution and male infertility have become global public health problems. The presence of microplastics (MPs) has been detected in the human body, and it has also been demonstrated that MPs can cause damage to the reproductive system. Wuwei Fuzheng Yijing Decoction (WWFZYJ) is effective in treating male infertility. Therefore, we designed a clinical randomized controlled trial to observe the effect of WWFZYJ on the content of MPs and semen quality in male infertility patients, and to evaluate its security. METHODS: In this randomized controlled study, 66 eligible patients were randomly assigned in a 1:1 ratio to a treatment group (WWFZYJ Decoction) and a control group (Coenzyme Q10 tablets combined with vitamin E soft capsules) for 8 weeks. The content of MPs in semen, sperm DNA Fragmentation Index (DFI), and semen analysis (including sperm density, sperm count, forward motile sperm, sperm motility, etc) will be used as primary indicators, and Traditional Chinese Medicine (TCM) syndrome scores will be used as secondary indicators. Vital signs (such as respiration, heart rate, body temperature, blood pressure, electrocardiogram, etc), blood routine, urine routine, stool routine, liver function, and renal function will be used as safety indicators. The primary and secondary indicators will be performed at 0th and 8th week, and the safety indicators will be performed at 0th, 4th, and 8th week. DISCUSSION: This study will provide evidence for the efficacy and safety of WWFZYJ in treating male infertility and reducing the content of MPs in semen, and further explore the effects of MPs on male fertility.

Clinical study of comprehensive TCM therapy in the treatment of damp and hot stasis erectile dysfunction.

BACKGROUND: The dilemma of male sexual dysfunction has been the focus of the whole society. Erectile dysfunction (ED) is one of the common sexual dysfunctions, and traditional Chinese medicine therapy has shown potential benefits in the treatment of ED. Comprehensive therapy of traditional Chinese medicine (CTTCM) is a comprehensive application of Chinese medicine therapy for auxiliary intervention. Through preliminary clinical observations, we found that CTTCM is simple, safe, and has good efficacy; however, there is a lack of rigorous clinical trials to support its application. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of CTTCM for patients with ED of damp-heat stasis type, and to provide evidence for the clinical application of CTTCM and the construction of a traditional Chinese medicine andrology rehabilitation system. METHODS: In this randomized controlled study, 108 eligible patients were assigned 1:1 to the CTTCM group or the tadalafil group. The treatment period was 8 weeks and the follow-up period was 8 weeks. The primary outcome will be the International Erectile Function Score and traditional Chinese medicine Syndrome Score. Secondary outcomes will include the Erection Quality Score, Patient Health Questionnaire-9, and the 7-item Generalized Anxiety Scale. Safety results will include electrocardiogram, blood tests (including blood, liver and kidney function), urine and stool. International Erectile Function Score-5, traditional Chinese medicine Syndrome Score, Erectile Quality Score, Patient Health Questionnaire-9, 7-item Generalized Anxiety Scale and all Safety outcomes will be conducted at baseline, 2th, 4th, 6th, and 8th week. Follow-up results will be assessed at 8th week after 8 weeks' treatment. DISCUSSION: This study will provide preliminary evidence for the efficacy and safety of traditional Chinese medicine integrated therapy in the treatment of damp-heat stasis ED. In addition, it also provides a basis for the clinical application of Chinese medicine comprehensive therapy and the construction of Chinese medicine andrology rehabilitation system. TRIAL REGISTRATION: Chinese clinical trial registration identifier, ChiCTR2200062016, registered on July 19, 2022.

Comprehensive analysis of PLOD family members in low-grade gliomas using bioinformatics methods.

Low-grade gliomas (LGGs) is a primary invasive brain tumor that grows slowly but is incurable and eventually develops into high malignant glioma. Novel biomarkers for the tumorigenesis and lifetime of LGG are critically demanded to be investigated. In this study, the expression levels of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) were analyzed by ONCOMINE, HPA and GEPIA. The GEPIA online platform was applied to evaluate the interrelation between PLODs and survival index in LGG. Furthermore, functions of PLODs and co-expression genes were inspected by the DAVID. Moreover, we used TIMER, cBioportal, GeneMINIA and NetworkAnalyst analysis to reveal the mechanism of PLODs in LGG. We found that expression levels of each PLOD family members were up-regulated in patients with LGG. Higher expression of PLODs was closely related to shorter disease-free survival (DFS) and overall survival (OS). The findings showed that LGG cases with or without alterations were significantly correlated with the OS and DFS. The mechanism of PLODs in LGG may be involved in response to hypoxia, oxidoreductase activity, Lysine degradation and immune cell infiltration. In general, this research has investigated the values of PLODs in LGG, which could serve as biomarkers for diagnosis, prognosis and potential therapeutic targets of LGG patients.

Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma.

Managing low-grade gliomas (LGG) remains a major medical challenge due to the infiltrating nature of the tumor and failure of surgical resection to eliminate the disease. EMILIN/Multimerins contain the gC1q signature, which is involved in many tumor processes. However, the expression and prognostic value of EMILIN/Multimerins in LGG remains unclear. This study used integrated bioinformatics analysis to investigate the expression pattern, prognostic value and function of EMILIN/Multimerins in patients with LGG. We analyzed the transcription levels and prognostic value EMILIN/Multimerins in LGG using the ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN databases. The mutation and co-expression rates of neighboring genes in EMILIN/Multimerins were studied using cBioPortal. TIMER and Metascape were used to reveal the potential function of EMILIN/Multimerins in LGG. According to our analysis, most EMILIN/Multimerins were overexpressed in LGG and shared a clear association with immune cells. GEPIA analysis confirmed that high levels of EMILIN/Multimerins, not including MMRN2, were associated with a poor prognosis in disease-free survival of patients with LGG. Additionally, we discovered that EMILIN/Multimerins may regulate LGG and we found a correlation between their expression patterns and distinct pathological grades. We found that EMILIN/Multimerins serve as possible prognostic biomarkers and high-priority therapeutic targets patients with LGG.

Nobiletin inhibits invasion via inhibiting AKT/GSK3ß/ß-catenin signaling pathway in Slug-expressing glioma cells.

Epithelial-mesenchymal transition (EMT) is a pivotal event in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. In this study, we found that nobiletin, a polymethoxylated flavone, suppressed migration and invasion in both U87 and U251 glioma cells. Expression of epithelial markers (E-cadherin and occludin) was upregulated; mesenchymal markers (N-cadherin, fibronectin) and the transcriptional factor Slug were downregulated after nobiletin treatment. Transforming growth factor ß (TGF-ß) was applied to stimulate EMT and the results showed that nobiletin not only influenced basal level cell migration but also prevented TGF-ß-triggered migration and EMT, with the AKT/GSK3ß/ß-catenin signaling pathway greatly involved. Furthermore, nobiletin remarkably diminished TGF-ß-induced ß-catenin nuclear translocation and the binding to the Slug promoter. It is worth noting that nobiletin almost blocked invasion in Slug-expressing U87 and U251 cells, and only exhibiting faint effect on non-Slug-expressing U343 glioma cells. Reinforced Slug expression in U343 cells by transfecting Slug plasmid was significantly attenuated by nobiletin, demonstrating the essential role of Slug in the anti-metastasis effect of nobiletin. Nobiletin repressed tumor growth in vivo and abrogated EMT in nude mice bearing U87-Luc xenografts, as demonstrated by Xenogen IVIS imaging and immunohistochemistry assay. Our findings suggested that nobiletin might have a great potential for treating glioblastoma.

Rosiglitazone exerts neuroprotective effects via the suppression of neuronal autophagy and apoptosis in the cortex following traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity in adults and children worldwide. Recent studies have demonstrated that both apoptosis and autophagy participate in TBI­induced neuronal cell death and functional loss. The peroxisome proliferator­activated receptor­Î³ (PPAR­Î³) agonist rosiglitazone (RSG) is a well­known anti­inflammatory, which carries out its effects via the activation of PPAR­Î³. Previous studies have suggested that RSG may exert neuroprotective effects in animal models of both chronic and acute brain injury; however, whether RSG is involved in autophagic neuronal death following TBI remains to be elucidated. The present study aimed to determine whether RSG carries out its neuroprotective properties via the attenuation of neuronal apoptosis and autophagy, following TBI in a rat model. Furthermore, the role of RSG was investigated with regards to the modulation of inflammation and glutamate excitotoxicity, and the impact of RSG on functional recovery following TBI was determined. The rats were subjected to controlled cortical impact injury, prior to being randomly divided into three groups: A sham­operated group, a TBI group, and an RSG treatment group. The RSG treatment group was intraperitoneally treated with 2 mg/kg RSG immediately after TBI. The results of the present study demonstrated that RSG treatment following TBI significantly reduced neuronal apoptosis and autophagy, and increased functional recovery. These effects were correlated with a decrease in the protein expression levels of tumor necrosis factor α and interleukin­6. However, no significant changes were observed in the protein expression levels of glutamate transporter­1 in the brain cortex. The results of the present study provide in vivo evidence that RSG may exert neuroprotective effects via the inhibition of neuronal apoptosis and autophagy following experimental TBI in rats, and the mechanism underlying these effects may be associated with the anti­inflammatory action of RSG. The present study offers a novel insight into the potential use of RSG as a neuroprotective agent for the treatment of cerebral injuries.

Interference of Notch1 inhibits the growth of glioma cancer cells by inducing cell autophagy and down-regulation of Notch1-Hes-1 signaling pathway.

Glioma is the most common malignant tumors in adult brains, and Notch signaling pathway plays an important role in cell differentiation. The aim of the present study is to investigate the role of Notch1 in the progression of glioma cancers and clarify the mechanism of Notch1 silencing on inhibiting the proliferation of glioma cancer cells. First, endogenous Notch1 expression was interfered with a lentiviral vector of Notch1 shRNA. RT-PCR and western blotting were used for detecting the expression of Notch1 mRNA and protein, respectively. MTT assay results demonstrated that transfection with Notch1 shRNA and treatment with MRK003, a Notch1 inhibitor, both inhibited the proliferation of glioma cancer cells (p < 0.01). The lentiviral vector of Notch1 shRNA transfected into U251 cells induced cell cycle arrest at G0/G1 phase by FACS with PI staining analysis. Meanwhile, the expression levels of LC3-II and Beclin1 significantly increase in Notch1 shRNA-transfected U251 cells, suggesting that cell autophagy was induced when interfering with Notch1 in glioma cells. The downstream transcription factors were also detected by RT-PCR and western blotting analysis, and the data showed that interference with Notch1 increased the expression level of Hes-1, but not Hes-5. Taken together, all the data obviously revealed that Notch1 played an important role in the progression of glioma cancers. The clarification of the mechanism will be helpful for the diagnosis of glioma cancer and would provide new clues to molecular targets for cancer therapy.