Comparison of post-resection survival between hepatocellular carcinoma patients in BCLC stage A or B who experience tumor rupture and patients in BCLC stage C who do not.

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication, and patients who experience it are formally assigned to stage T4 in the TNM system, while many clinicians informally assign them to stage C in the more widely used Barcelona Clinic Liver Cancer (BCLC) system. The present study explored whether these re-staging practices are appropriate for HCC patients who suffer tumor rupture. Methods: We retrospectively reviewed the records of 1952 HCC patients who underwent hepatic resection at our hospital between January 2017 and June 2021. We compared recurrence-free and overall survival between 143 patients who had BCLC stage A or B disease at the time of spontaneous rupture and 449 patients who had BCLC stage C disease without rupture. Results: Overall survival rate was significantly higher among the 143 patients (1, 3, 5-year survival rate was 80.3%, 60.4%, 51.4%) with rupture than among the 449 (1, 3, 5-year survival rate was 69.5%, 41.5%, 32.4%) with BCLC stage C disease (hazard ratio 1.65, 95% confidence interval 1.29 to 2.12). The two groups had similar recurrence-free survival (hazard ratio 1.19, 95% confidence interval 0.92 to 1.53), but most patients with rupture were able to receive interventional and potentially curative treatments after recurrence, whereas most patients in BCLC stage C received interventional or supportive care. Similar results were obtained after propensity score matching. Conclusion: HCC patients who experience spontaneous rupture tumor while in BCLC stage A or B have better prognosis than patients in BCLC stage C without rupture. Our results suggest that HCC patients who suffer rupture in BCLC stage A or B should not be assigned to BCLC stage C.

Identifying the effective combination of acupuncture and traditional Chinese medicinal herbs for postmenopausal osteoporosis therapy through studies of their molecular regulation of bone homeostasis.

Worldwide, as the population age, osteoporosis is becoming increasingly common, and osteoporotic fractures have a significant economic burden. Postmenopausal women are the most susceptible to developing osteoporosis and the most critical time to prevent it is during the perimenopausal and early menopausal years. In this regard, we hypothesize rational combination of acupuncture and Traditional Chinese Medicine (TCM) in the form of herbal extract could prevent osteoporosis in women. Estrogen deficiency during menopause causes low-level inflammation that stimulates the formation of osteoclasts, the bone-resorbing cells, and simultaneously inhibits the viability and function of osteoblasts, the bone-forming cells. The most potent inflammatory cytokine in skeletal homeostasis is the receptor activator of nuclear factor kappa B ligand (RANKL) that stimulates osteoclast function. Conversely, the canonical Wnt pathway is essential for osteoblastogenesis and bone formation, and estrogen deficiency leads to diminished functioning of this pathway. TCM and acupuncture could target the RANKL and the Wnt pathway in favorable ways to prevent the accelerated bone loss experienced during the early menopausal stage and promote the gain in bone mass in postmenopausal women. In this review, we propose a rational combination of specific TCM and acupuncture targeting those signaling molecules/pathways by the drugs that are in clinical use for the treatment of postmenopausal osteoporosis. Our rational approach revealed that Danshen (Radix Salviae Miltiorrhizae) could exert a synergistic effect with acupuncture. We then propose a translational path for developing the putative combination in women with postmenopausal osteoporosis to curtail the risk of osteoporotic fractures.

Glioma angiogenesis is boosted by ELK3 activating the HIF-1[Formula: see text]/VEGF-A signaling axis.

BACKGROUND: Clinical studies have shown that first-line use of anti-angiogenetic therapy can prolong progression-free survival but little progress has been made in extending the overall survival of the patients. We explored the role of ELK3 in glioma angiogenesis to improve and design more efficacious therapies. METHODS: A tissue microarray and immunohistochemistry analysis were used to determine the expression of ELK3 protein in 400 glioma patients. Cell proliferation, metastasis, cell cycle, and apoptosis were monitored in U87 and U251 cells using CCK-8, EdU, transwell assays, and flow cytometry. A tube-formation assay, a rat aorta ring sprouting assay, and a matrigel plug assay were performed to examine the antiangiogenic activity of ELK3. An ELISA, Western blot, and correlation analysis of the CGGA dataset were used to detect the association between ELK3 and VEGF-A or ELK3 and HIF-1[Formula: see text]. Besides, orthotopic transplantation in nude mice and histopathological and immunological analysis of in vitro tumors were used to explore the effect of ELK3 on tumor progression and median survival. RESULTS: ELK3 was upregulated in glioma tissues and associated with a poor prognosis. In vitro, ELK3 promoted cell proliferation and cell cycle progression, induced metastasis, and suppressed apoptosis. Then, silencing ELK3 inhibited VEGF-A expression and secretion by facilitating HIF-1[Formula: see text] degradation via ubiquitination. Finally, knockdown ELK3 inhibited tumor progression and angiogenesis in vitro and in vivo, as well as prolonged nude mice's median survival. CONCLUSIONS: Our findings first evidenced that ELK3 is crucial for glioma because it promotes angiogenesis by activating the HIF-1[Formula: see text]/VEGF-A signaling axis. Therefore, we suggest that ELK3 is a prognostic marker with a great potential for glioma angiogenesis and ELK3-targeted therapeutic strategies might hold promise in improving the efficacy of anti-angiogenic therapies.

Metformin suppressed tendon injury-induced adhesion via hydrogel-nanoparticle sustained-release system.

Tendon adhesion is one of the sequelae of tendon injury and can lead to disability in severe cases. Metformin is a commonly used antidiabetic drug. Some studies had shown that metformin could reduce tendon adhesion as well. Considering the characteristic of low absorption rate and short half-life, we established a sustained-release system, i.e., hydrogel-nanoparticle system to deliver metformin. In vitro, metformin could effectively suppress TGF-ß1-induced cell proliferation and accelerate cell apoptosis, according to cell counting kit-8, flow cytometry, and 5-ethynyl-2'-deoxyuridine (EdU) staining studies. In vivo, hydrogel-nanoparticle/metformin system could significantly lower adhesion scores and improve the gliding function of repaired flexor tendons, as well as decrease the expression of fibrotic proteins Col1a1, Col3a1, and α-smooth muscle actin (α-SMA). Histological staining revealed that the inflammation had subsided and that the gap between the tendon and the surrounding tissue was wider in the hydrogel-nanoparticle/metformin treatment group. Finally, we speculated that effect of metformin on reducing tendon adhesion might be achieved by regulating both Smad and MAPK-TGF-ß1 signaling pathways. In conclusion, metformin delivered through hydrogel-nanoparticle sustained-release system may be a promising strategy for coping with tendon adhesion.

A Systematic Review and Meta-Analysis of Minimally Invasive Partial Nephrectomy Versus Focal Therapy for Small Renal Masses.

Background: Minimally invasive partial nephrectomy (MIPN) and focal therapy (FT) are popular trends for small renal masses (SRMs). However, there is currently no systematic comparison between MIPN and FT of SRMs. Therefore, we systematically study the perioperative, renal functional, and oncologic outcomes of MIPN and FT in SRMs. Methods: We have searched the Embase, Cochrane Library, and PubMed for articles between MIPN (robot-assisted partial nephrectomy and laparoscopic partial nephrectomy) and FT {radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (CA), irreversible electroporation, non-thermal [irreversible electroporation (IRE)] ablation, and stereotactic body radiation therapy (SBRT)}. We calculated pooled mean difference (MD), odds ratios (ORs), and 95% confidence intervals (CIs) (CRD42021260787). Results: A total of 26 articles (n = 4,420) were included in the study. Compared with MIPN, the operating time (OP) of FT had significantly lower (SMD, -1.20; CI, -1.77 to -0.63; I2 = 97.6%, P < 0.0001), estimated blood loss (EBL) of FT had significantly less (SMD, -1.20; CI, -1.77 to -0.63; I2 = 97.6%, P < 0.0001), length of stay (LOS) had shorter (SMD, -0.90; CI, -1.26 to -0.53; I2 = 92.2%, P < 0.0001), and estimated glomerular filtration rate (eGFR) of FT was significantly lower decrease (SMD, -0.90; CI, -1.26 to -0.53; I2 = 92.2%, P < 0.0001). However, FT possessed lower risk in minor complications (Clavien 1-2) (OR, 0.69; CI, 0.45 to 1.07; I2 = 47%, P = 0.023) and overall complications (OR, 0.71; CI, 0.51 to 0.99; I2 = 49.2%, P = 0.008). Finally, there are no obvious difference between FT and MIPN in local recurrence, distant metastasis, and major complications (P > 0.05). Conclusion: FT has more advantages in protecting kidney function, reducing bleeding, shortening operating time, and shortening the length of stay. There is no difference in local recurrence, distant metastasis, and major complications. For the minimally invasive era, we need to weigh the advantages and disadvantages of all aspects to make comprehensive choices. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier PROSPERO (CRD42021260787).

Natural Polyphyllins (I, II, D, VI, VII) Reverses Cancer Through Apoptosis, Autophagy, Mitophagy, Inflammation, and Necroptosis.

Cancer is the second leading cause of mortality worldwide. Conventional therapies, including surgery, radiation, and chemotherapy, have limited success because of secondary resistance. Therefore, safe, non-resistant, less toxic, and convenient drugs are urgently required. Natural products (NPs), primarily sourced from medicinal plants, are ideal for cancer treatment because of their low toxicity and high success. NPs cure cancer by regulating different pathways, such as PI3K/AKT/mTOR, ER stress, JNK, Wnt, STAT3, MAPKs, NF-kB, MEK-ERK, inflammation, oxidative stress, apoptosis, autophagy, mitophagy, and necroptosis. Among the NPs, steroid saponins, including polyphyllins (I, II, D, VI, and VII), have potent pharmacological, analgesic, and anticancer activities for the induction of cytotoxicity. Recent research has demonstrated that polyphyllins (PPs) possess potent effects against different cancers through apoptosis, autophagy, inflammation, and necroptosis. This review summarizes the available studies on PPs against cancer to provide a basis for future research.

Alantolactone induces apoptosis in THP-1 cells through STAT3, survivin inhibition, and intrinsic apoptosis pathway.

Cancer is the second foremost cause of mortality in the world, and THP-1 cells play an important role in cancer progression. Alantolactone (ALT), a sesquiterpene lactone compound derived from Inula helenium, has a number of biological activities including antibacterial, antifungal, and anticancer. The current study was conducted to investigate the effects of ALT on THP-1 cells and its underlying molecular mechanisms. THP-1 cells were cultured and treated with ALT (20, 40 µM) for 12 hr, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell morphology, live/dead, and apoptosis assays were performed. The gene expressions at the protein level were checked through Western blot. Results show that ALT decreased cell viability and increased cell death and apoptosis. We found that ALT inhibited STAT3 and survivin expression. Furthermore, ALT induced mitochondrial-dependent apoptosis through a decrease in B-cell lymphoma-2 (Bcl-2) and Bcl-xL and increase in Bax expression, resulting in the release of cytochrome c (Cyt-c) from mitochondria. Cyt-c release from mitochondria further increased cleaved (cl) caspase-3 and cl-PARP expression and led the cells to apoptosis. Therefore, ALT might be a good therapy for the progression due to THP-1 cells.

The application and value of continuous nursing in patients after coronary artery bypass grafting.

OBJECTIVE: To investigate the application and value of continuous nursing after coronary artery bypass grafting. METHODS: The clinical data of 62 patients after coronary artery bypass grafting from January 2016 to January 2018 were analyzed retrospectively. According to the nursing mode, the patients were divided into two groups: the continuous nursing group (n = 30) and the conventional nursing group (n = 32). All patients completed Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) at admission and 1 year after operation. All patients completed Seattle Angina Pectoris Questionnaire (SAQ) at discharge and 1 year after operation. RESULTS: All patients were followed up for more than one year. One year after operation, SAQ score in five items in continuous nursing group was significantly better than that in conventional nursing group.(P < 0.05) The continuous nursing group exhibited significantly decreased SAS and SDS scores 1 year after surgery compared to the preoperative SAS and SDS scores.(P < 0.05) The SAS and SDS scores of the continuous nursing group were significantly better than those of the conventional nursing group 1 year after surgery.(P < 0.05) Then incidence rate of chest tightness or chest pain and coronary restenosis in continuous nursing group were significantly less than that in conventional nursing group.(P < 0.05). CONCLUSION: Continuous nursing improved patient compliance with treatment and reduces the occurrence of complications. The patient also receives proper psychological evaluations, which relieve patient anxiety and depression and improve the quality of life.

Temporal-spatial differences in and influencing factors of agricultural eco-efficiency in Shandong Province, China / Diferenças temporal-espacial e fatores de influência da ecoeficiência agrícola na Província de Shandong, China

ABSTRACT: Based on the panel data of 134 counties (cities and districts) from 1998 to 2017, the temporal-spatial variation characteristics and influencing factors of agricultural eco-efficiency in Shandong Province were analyzed by using various methods, such as the super-efficiency SBM (slacks-based measure) model considering undesired output and the STIRPAT (stochastic impacts by regression on population, affluence, and technology) model, which helps clarify the improvements needed for agricultural eco-efficiency and provides a basis for the development of ecological agriculture in Shandong Province. Results showed the following: (1) During 1998-2017, the agricultural eco-efficiency of Shandong Province showed a fluctuating increasing tendency, but the overall efficiency value wasrelatively low. (2) The agricultural eco-efficiency of Shandong Province had a significant regional disparity, and its spatial agglomeration gradually weakened. The spatial distribution had a sporadic distribution of high value areas at first and then gradually formed the "low-high-low-high" zonal distribution from west to east. (3) The net income per capita of farmers and the added value of the primary industry had a significantly positive correlation with the agricultural eco-efficiency of Shandong Province, while the mechanization level, the planting area per capita, the level of financial support to agriculture and the planting structure exhibited a mainly negative correlation with the agricultural eco-efficiency of Shandong Province. Moreover, the added value of the primary industry and the financial support to agriculture in the 0.75 quantile had no significant influence on the agricultural eco-efficiency of Shandong Province, and the planting structure in the 0.25 and 0.75 quantiles also had no significant influence.

RESUMO: Com base nos dados do painel de 134 municípios (cidades, distritos) na província de Shandong de 1998 a 2017, as características de variação espacial e temporal da ecoeficiência agrícola na província de Shandong foram analisadas usando vários métodos, como o modelo SBM (Medida baseada EM estacas) supereficiente. Considerando indesejados produção e modelo STIRPAT (Impactos estocásticos da regressão da população, da afluência e da tecnologia), ajudará a esclarecer a direção da melhoria da eco eficiência agrícola na província de Shandong e fornecerá uma base para o desenvolvimento da agricultura ecológica. Os resultados mostraram que (1) em 1998-2017, a ecoeficiência agrícola da província de Shandong mostrou uma tendência ascendente na flutuação, mas o valor geral da eficiência foi baixo. (2) A distribuição espacial da distribuição esporádica inicial da área de alto valor se formou gradualmente de oeste para leste, distribuição zonal " "baixo-alto-baixo-alto"" (3) O lucro líquido per capita dos agricultores e o valor acrescentado da indústria primária foram significativamente correlacionados positivamente com a ecoeficiência agrícola da província de Shandong. O nível de mecanização, a área de plantio per capita, o apoio financeiro ao nível agrícola e a estrutura de plantio, entre eles, o valor acrescentado da indústria primária e o apoio financeiro à agricultura em 0,75 quantil, a estrutura de plantio em 0,25 e 0,75 quantil na ecoeficiência agrícola da província de Shandong não é significativa.

A near-infrared biothiol-specific fluorescent probe for cancer cell recognition.

Cancer is a global health issue and a leading cause of death. The discrimination of cancer cells from normal cells is of significant importance for the early diagnosis of cancers. As one of the useful biomarkers for developing cancer diagnosis and chemotherapy resistance systems, biothiols not only play an essential role in physiological and pathological processes but also exhibit cytoprotective effects in the susceptibility to carcinogenesis. It would be highly desirable to explore near-infrared biothiol-specific fluorescent probes for cancer diagnosis with outstanding specificity. In this study, a novel near-infrared fluorescent probe BPO-THAZ decorated with thiazole as a recognition site was presented for sensitive and selective detection of endogenous biothiols. BPO-THAZ can be used to not only evaluate the biothiol level in living HeLa cells upon treatment with H2O2 or anti-cancer drugs but also assess endogenous biothiols in stem cells. Furthermore, BPO-THAZ was successfully utilized to discriminate cancer cells from normal cells showing great promise for cancer diagnosis.

Atorvastatin Protects Against Cerebral Aneurysmal Degenerative Pathology by Promoting Endothelial Progenitor Cells (EPC) Mobilization and Attenuating Vascular Deterioration in a Rat Model.

BACKGROUND Endothelial injury is the early pathological change of cerebral aneurysm (CA) formation. In addition to its lipid-lowering activity, atorvastatin (ATR) also reportedly promotes vascular repair via mobilizing endothelial progenitor cells (EPC). Here, we investigated the influence of ATR on vascular worsening after CA induction in rats. MATERIAL AND METHODS Adult male Sprague-Dawley rats were randomly assigned to 3 groups: a control (CTR) group, a CA group, and a CA+ATR treatment group. Circulating EPC level and hematological and lipid profiles were measured 3 months after CA induction. Verhoeff-Van Gieson staining and transmission electron microscopy were performed to assess pathological changes in the artery wall. RT-PCR was also performed to evaluate the expression of inflammation-related genes in the aneurysmal wall. RESULTS ATR significantly restored the impaired level of circulating EPC without changing hematological and lipid profiles 3 months after CA induction. ATR markedly inhibited endothelial injury, media thinning, and CA enlargement, accompanied by reduced vascular inflammation. CONCLUSIONS Our preliminary results demonstrate that the mobilization of EPC and improvement of endothelial function by ATR contribute to the prevention of cerebral aneurysm. Further studies are warranted to investigate the detailed mechanism.

A Unified Level Set Framework Combining Hybrid Algorithms for Liver and Liver Tumor Segmentation in CT Images.

Accurate and reliable segmentation of liver tissue and liver tumor is essential for the follow-up of hepatic diagnosis. In this paper, we present a method for liver segmentation and a method for liver tumor segmentation. The two methods are grounded on a novel unified level set method (LSM), which incorporates both region information and edge information to evolve the contour. This level set framework is more resistant to edge leakage than the single-information driven LSMs for liver segmentation and surpasses many other models for liver tumor segmentation. Specifically, for liver segmentation, a hybrid image preprocessing scheme is used first to convert an input CT image into a binary image. Then with manual setting of a few seed points on the obtained binary image, the following region-growing is performed to extract a rough liver region with no leakage. The unified LSM is proposed at last to refine the segmentation result. For liver tumor segmentation, a local intensity clustering based LSM coupled with hidden Markov random field and expectation-maximization (HMRF-EM) algorithm is applied to construct an enhanced edge indicator for the unified LSM. With this development, expected segmentation results can be obtained via the unified LSM, even for complex tumors. The two methods were evaluated with various datasets containing a local hospital dataset, the public datasets SLIVER07, 3Dircadb, and MIDAS via five measures. The proposed liver segmentation method outperformed other previous semiautomatic methods on the SLIVER07 dataset and required less interaction. The proposed liver tumor segmentation method was also competitive with other state-of-the-art methods in both accuracy and efficiency on the 3Dircadb database. Our methods are evaluated to be accurate and efficient, which allows their adoptions in clinical practice.

The Serum Pepsinogen Test as a Predictor of Kazakh Gastric Cancer.

Gastric cancer (GC) is one of the most common malignant tumors and the Kazakh population in Xinjiang has been reported to be one of the highest incidence of GC in the world. Serum pepsinogen (PG) test provides a valuable method for detecting GC, but little study about the role of PG in Kazakh GC. Therefore, we aimed to investigate the role of PG in Kazakh GC and to elucidate the usefulness of the serum PG test method. The serum PG concentration were measured using the flow fluorescence assay and ELISA methods in patients with superficial gastritis, atrophic gastritis and GC. The most suitable cut off point was a PG I concentration ≤64 ng/ml and PG I/II ratio (PGR) ≤4.5. Using this cut off point, the sensitivity and specificity of pepsinogen screening for Kazakh GC were 80.5% and 89.8%, respectively. The area under the curve (AUC) of the PGR for GC diagnosis was 0.949, which was significantly higher than that of combined tumor markers. Moreover, PGR in Kazakh early GC was statistically significantly lower than in SG and AG. These findings suggest that serum PG test can serve as a noninvasive biomarker for the diagnosis of Kazakh GC.

Inhibition of EZH2 expression is associated with the proliferation, apoptosis and migration of SW620 colorectal cancer cells in vitro.

Epigenetic changes have been recently recognized as important in many human cancers. Enhancer of zeste homologue 2 (EZH2) gene has shown overexpression in various human cancers, consistent with a straightforward role of EZH2 as an oncogene, but its function in carcinogenesis is partly contradictory. The role of EZH2 in development of human colorectal cancer (CRC) has not yet been clarified. In present study, we observed up-regulation of EZH2 expression in tumor tissues from CRC patients. The expression of EZH2 in CRC cell lines is consistent with the trend in cancer tissues using RT-PCR. We showed that TNM stage and lymph node metastasis in CRC patients are significantly correlated with EZH2 expression levels. EZH2 level of transcription and protein was inhibited by small interfering RNA (siRNA). More importantly, EZH2-siRNA inhibited the proliferation and migration of SW620 cells while promoting their apoptosis, and inducing G0/G1 cell cycle arrest of CRC cells. Collectively, our results suggest that up-regulated EZH2 expression may contribute to the progression of the patients with CRC. A comprehensive study of epigenetic mechanisms and the relevance of EZH2 in CRC is important for fully understanding this disease and as a basis for developing new treatment options in patients with CRC.

[Detection of KRAS gene mutations in colorectal carcinoma: a study of 6 364 patients].

OBJECTIVE: To investigate the mutation rate and types of KRAS gene in colorectal carcinoma of Chinese patients, and to document the regional distribution of the mutation. METHODS: A total of 6 364 colorectal carcinoma tumor specimens were obtained from 27 provinces and autonomous regions in China from 2009 to 2013. Pyrosequencing was used to detect mutations in codons 12 and 13 of KRAS gene. The mutation types of KRAS and the difference of regional distribution were statistically analyzed. RESULTS: KRAS mutation rate in Chinese colorectal carcinoma patients was 37.43 % (2 382/6 364). Ten types of single-base mutations of KRAS codons 12 and 13 were detected, including six common types: 12GGT > GAT (14.77%), 13GGC > GAC (8.19%), 12GGT > GTT (7.89%), 12GGT > TGT (2.20%), 12GGT > AGT (2.00%), and 12GGT > GCT (1.48%). Other four less occurring mutation types (<1%) included 12GGT > CGT, 13GGC > TGC, 13GGC > CGC, and 13GGC > AGC. In addition, 8 other mutation types were identified in 13 tumor samples. The rates of KRAS mutation in patients from different regions were between 35.68% and 38.04% and no significant differences were observed (P > 0.05). CONCLUSIONS: Abundant mutation types of KRAS gene exist in colorectal cancers among Chinese patients. The six common mutation types occur with a frequency of not less than 1%. There are no significant differences of KRAS mutation rate among Chinese patients from various areas. Pyrosequencing provides a rapid and accurate method of KRAS mutation detection for clinical application.

Discovery of a benzofuran derivative (MBPTA) as a novel ROCK inhibitor that protects against MPP⁺-induced oxidative stress and cell death in SH-SY5Y cells.

Parkinson disease (PD) is a neurodegenerative disease with multifactorial etiopathogenesis. The discovery of drug candidates that act on new targets of PD is required to address the varied pathological aspects and modify the disease process. In this study, a small compound, 2-(5-methyl-1-benzofuran-3-yl)-N-(5-propylsulfanyl-1,3,4-thiadiazol-2-yl) acetamide (MBPTA) was identified as a novel Rho-associated protein kinase inhibitor with significant protective effects against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced damage in SH-SY5Y neuroblastoma cells. Further investigation showed that pretreatment of SH-SY5Y cells with MBPTA significantly suppressed MPP(+)-induced cell death by restoring abnormal changes in nuclear morphology, mitochondrial membrane potential, and numerous apoptotic regulators. MBPTA was able to inhibit MPP(+)-induced reactive oxygen species (ROS)/NO generation, overexpression of inducible NO synthase, and activation of NF-κB, indicating the critical role of MBPTA in regulating ROS/NO-mediated cell death. Furthermore, MBPTA was shown to activate PI3K/Akt survival signaling, and its cytoprotective effect was abolished by PI3K and Akt inhibitors. The structural comparison of a series of MBPTA analogs revealed that the benzofuran moiety probably plays a crucial role in the anti-oxidative stress action. Taken together, these results suggest that MBPTA protects against MPP(+)-induced apoptosis in a neuronal cell line through inhibition of ROS/NO generation and activation of PI3K/Akt signaling.

Small cell carcinoma of the urinary bladder diverticulum: a case report and review of the literature.

Small cell carcinoma of the urinary bladder is very rare. Small cell carcinoma of the urinary bladder is a mass with swiftly aggressive and metastatic, and with a poor prognosis. Due to its scarcity, no forward-looking researches assessing the most effective treatment have been issued in the medical literature. It can happen either in connection with urothelial (transitional cell) carcinoma or in a pure form. Its treatment should include surgery, chemotherapy and radiotherapy. In this article,we report a case occurring in a mixed form in the urinary bladder diverticulum and we concisely review the published literature with respect to the clinical manifestation, pathology,differential diagnosis, treatment and prognosis.

Studies on the orthogonal assembly of ß-cyclodextrin-poly (ε-caprolactone) and ferrocene-poly (ethylene oxide).

A biodegradable multi-arm polymer ß-cyclodextrin-poly (ε-caprolactone) (CD-PCL) with a ``jellyfish-like'' structure was obtained, in which flexible and hydrophobic PCL arms were selectively grafted to the wide side of the hydrophilic torus-shaped ß-CD. The amphiphilic "jellyfish-like'' polymer with a hollow cavity and hydrophobic tails could orthogonally self-assemble into a new amphiphilic supramolecular copolymer CD-PCL/FcPEG with poly (ethylene oxide) end-decorated by ferrocene (FcPEG) in aqueous solution based on terminal hydrophobic interactions. The chemical structures of CD-PCL and CD-PCL/FcPEG were characterized by IR, NMR and UV and their self-assembled structures in water were investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). CD-PCL alone self-assembled into nano vesicles in water, while CD-PCL/FcPEG into nanospheres. The supramolecular nanospheres were further investigated by cyclic voltammogram. The results indicated that the ferrocenyl groups which were embedded into the hydrophobic core of the supramolecular nanospheres could not transmit electrons or carry out electrochemical oxidation and reduction reaction.

[Construction of replication-deficient recombinant adenovirus vector with hTFPI-2 gene by AdMax system and expression in U937 monocytes in vitro].

We tried to construct and identify the recombinant replication-deficient adenovirus vector coding for human tissue factor pathway inhibitor 2 (hTFPI-2) gene by AdMax system in HEK293 cells. Firstly, we obtained hTFPI-2 gene from the recombinant plasmid pIRES2-EGFP-TFPI-2 by PCR using primers with restriction endonuclease site of EcoRI or SacI. After digesting the hTFPI-2 gene and plasmid PDC316-IRES-EGFP shuttle vector, we ligated them with T4 ligase and formed the recombinant shuttle vector PDC316-IRES-EGFP-hTFPI-2. It was confirmed that the ligation product was inserted the gene of hTFPI-2 correctly by sequencing. Then we took cotransfection of HEK293 cells with the recombinant shuttle vector and genomic plasmid pBHGloxdeltaE1,3Cre by liposome lipofectamine2000, and finished the package of recombinant adenovirus Ad-hTFPI-2. The results of the PCR test and restriction endonuclease digestion confirmed the successful construction of the recombinants Ad-hTFPI-2. Furthermore, we measured the titre of Ad-hTFPI-2 with the aid of green fluorescence protein expression after multiplication and purification. The titre was 0.931 x 10(12) pfu/ml. Finally, we infected U937 monocytes by purified Ad-hTFPI-2, and determined the infection efficiency and the TFPI-2's level and activity. The efficiency of Ad-hTFPI-2 infection in U937 cells was 89.33%. After infected by Ad-hTFPI-2, the TFPI-2's level in supernatant increased about 7 fold. Also the TFPI-2 in supernatant had activities of inhibiting trypsin and plasmin. The recombinant adenovirus with the hTFPI-2 gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in antiatherosclerosis.

Recombinant TFPI-2 enhances macrophage apoptosis through upregulation of Fas/FasL.

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor-activated factor VII complex. In addition, TFPI-2 has other functions such as promoting cell migration and inducing apoptosis. In the present study, we investigated if TFPI-2 induced apoptosis in cultured U937-derived macrophages and the possible signal pathways that involved in the apoptotic process. Apoptotic DNA fragment detection and caspase-3,9 activity measurements indicated that rTFPI-2 promoted U937-derived macrophage apoptosis. Hoechst 33342 assay and flow cytometry further showed that rTFPI-2 induced apoptosis in cultured macrophages in a dose-dependent manner. Because death receptors of the TNF family such as Fas are the best-understood death pathways that recruit Fas-associated death domain (FADD) and procaspase-8 to the receptor in macrophages, we investigated the expression of Fas and its ligand (FasL) and downstream signal caspase-8 by Western blot analysis. The results indicated that the process of apoptosis triggered by rTFPI-2 was, at least in part, actively conducted by U937-derived macrophages possibly through Fas/FasL signal pathway. In brief, rTFPI-2 may have the potential usefulness in inducing macrophages apoptosis, which suggest TFPI-2 might have antiatherogenic effects.