Development of a Silk Fibroin-Small Intestinal Submucosa Small-Diameter Vascular Graft with Sequential VEGF and TGF-ß1 Inhibitor Delivery for In Situ Tissue Engineering.

Proper endothelialization and limited collagen deposition on the luminal surface after graft implantation plays a crucial role to prevent the occurrence of stenosis. To achieve these conditions, a biodegradable graft with adequate mechanical properties and the ability to sequentially deliver therapeutic agents isfabricated. In this study, a dual-release system is constructed through coaxial electrospinning by incorporating recombinant human vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) inhibitor into silk fibroin (SF) nanofibers to form a bioactive membrane. The functionalized SF membrane as the inner layer of the graft is characterized by the release profile, cell proliferation and protein expression. It presents excellent biocompatibility and biodegradation, facilitating cell attachment, proliferation, and infiltration. The core-shell structure enables rapid VEGF release within 10 days and sustained plasmid delivery for 21 days. A 2.0-mm-diameter vascular graft is fabricated by integrating the SF membrane with decellularized porcine small intestinal submucosa (SIS), aiming to facilitate the integration process under a stable extracellular matrix structure. The bioengineered graft is functionalized with the sequential administration of VEGF and TGF-ß1, and with the reinforced and compatible mechanical properties, thereby offers an orchestrated solution for stenosis with potential for in situ vascular tissue engineering applications.

Incidence and factors influencing neck shortening after screw fixation of femoral neck fractures with the femoral neck system.

OBJECTIVE: To investigate the effects of postoperative femoral neck shortening in patients with femoral neck fractures fixed with femoral neck system screws (FNS) and to explore the factors influencing femoral neck shortening. METHOD: To retrospectively analyze the data of 113 patients with femoral neck fractures admitted to the Second Hospital of Fuzhou City, affiliated with Xiamen University, between December 2019 and January 2022. Of these, 87 patients were followed up for more than 12 months, 49 men and 38 women: 36 cases of Garden I and II fractures and 51 cases of Garden III and IV fractures, to record the patient's hip Harris score at 12 months postoperatively. Patients were divided into femoral neck shortening group and femoral neck no shortening group according to their regular postoperative follow-up radiographic measurements. To count the incidence of femoral neck shortening, a comparison of postoperative complication rates and hip Harris scores between the two groups was made. Statistical comparison of the two groups and a multifactorial logistic regression analysis were also performed to analyze the factors affecting femoral neck shortening. RESULTS: All 87 patients were followed up for more than 12 months after surgery. In 34 of these cases, neck shortening occurred, and the incidence rate was 39.1%. 15 cases of severe shortening, incidence of 17.2%; fracture healing 84 cases, fracture healing rate of 96.5%. The hip Harris score was 83.99 (81.95, 89.20) in the neck shortening group at 12 months postoperatively, 90.87 (87.95, 94.80) for the group without neck shortening; the difference between the two groups was statistically significant (P < 0.01). 32 cases of fracture healing in the neck shortening group at 12 months after surgery, fracture healing rate of 94.1%; 52 cases healed without neck shortening group, fracture healing rate of 98.1%. The difference between the two groups was not statistically significant (P = 0.337). High incidence of neck shortening after FNS fixation of femoral neck fractures, cortical comminution of the severed end, fracture fractionation and quality of reduction were significantly correlated with neck shortening. CONCLUSION: High incidence of postoperative neck shortening after internal fixation of femoral neck fractures with the femoral neck system, the cortical comminution, the type of fracture, and the quality of fracture reduction are the influencing factors; femoral neck shortening can affect postoperative hip function, but does not affect fracture healing.

Comparison of open and laparoscopic inguinal-hernia repair in octogenarians.

INTRODUCTION: Although the advantages of laparoscopic inguinal hernia repair in the general population have been reported, its role in octogenarians has yet to be elucidated. This retrospective study was designed to compare the outcomes of open and laparoscopic inguinal hernia repairs in octogenarians. MATERIALS AND METHODS: The data of octogenarians who underwent laparoscopic (n = 81) or open (n = 121) inguinal hernia repair were collected from January 2017 to December 2019. Statistical analysis variables included basic epidemiological data of patients, surgical procedures, comorbidities, postoperative pain, complications, recurrence, and other data. RESULTS: There were no significant differences between the two groups in terms of sex, body mass index, recurrent hernias, comorbidities, postoperative complications, and recurrence. The American Society of Anesthesiologists (ASA) class and the proportion of scrotal hernias in the open group were higher than those of the laparoscopic group, whereas the proportion of bilateral hernias in the laparoscopic group was higher than that in the open group. The postoperative pain scores of the laparoscopic group were lower than those of the open group. CONCLUSIONS: In octogenarians, both laparoscopic and open inguinal hernia repairs are safe and feasible, but an appropriate surgical plan is crucial for obtaining better treatment effect.

Effect of tai-ji practice on the health of the elderly / Efeito da prática de tai-ji sobre a saúde dos idosos / Efecto de la práctica de tai-ji en la salud de las personas mayores

ABSTRACT Introduction: The practice of Tai-ji has shown a positive effect on the physical functions of the elderly and has been promoted as a recommended daily activity for middle-aged and elderly individuals. However, there is still no scientific evidence about its cardiorespiratory benefits. Objective: Study the effect of Tai-ji on the cardiorespiratory function and physical fitness of the elderly. Methods: A group of elderly people from the same community and in good health, considered suitable for sports experiments was divided into the experimental group for Tai-ji exercise and the control group for vigorous walking exercise. Each week, the Tai-ji exercise with eight steps and the vigorous walking exercise was performed three times in each group. Results: After six weeks of Tai-ji exercise with eight steps of five methods, the vital capacity, maximal oxygen consumption, maximal voluntary ventilation, and oxygen pulse of the experimental group were significantly increased, and the systolic and diastolic pressures were significantly reduced, evidencing an improvement in the performance of the cardiopulmonary function. Conclusion: Tai-ji exercise is beneficial for the cardiopulmonary function and physical health of the elderly and is scientifically useful for improving the mental health level and quality of life of the elderly. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A prática do Tai-ji tem demonstrado um efeito positivo nas funções físicas dos idosos, tendo sido promovida como atividade diária recomendada aos indivíduos de meia-idade e idosos. Porém ainda não há evidências científicas sobre seus benefícios cardiorrespiratórios. Objetivo: Estudar o efeito do Tai-ji sobre a função cardiorrespiratória e a aptidão física do idoso. Métodos: Um grupo de idosos da mesma comunidade e boa saúde, considerados adequados para os experimentos esportivos foi dividido em grupo experimental para o exercício de Tai-ji e no grupo de controle para o exercício de caminhada vigorosa. A cada semana, o exercício de Tai-ji com oito etapas e o vigoroso exercício de caminhada foram realizados três vezes em cada grupo. Resultados: Após seis semanas de exercício Tai-ji com oito etapas do método de cinco, a capacidade vital, o consumo máximo de oxigênio, a ventilação voluntária máxima e o pulso de oxigênio do grupo experimental foram significativamente aumentados, e as pressões sistólica e diastólica foram significativamente reduzidas, evidenciando uma melhora no desempenho da função cardiopulmonar. Conclusão: O exercício de Tai-ji é benéfico para a função cardiopulmonar e a saúde física dos idosos, mostrando-se cientificamente útil para melhorar o nível de saúde mental e a qualidade de vida dos idosos. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La práctica del Tai-ji ha demostrado un efecto positivo en las funciones físicas de las personas mayores, habiéndose promovido como actividad diaria recomendada a los individuos de mediana y avanzada edad. Sin embargo, aún no existen pruebas científicas sobre sus beneficios cardiorrespiratorios. Objetivo: Estudiar el efecto del Tai-ji sobre la función cardiorrespiratoria y la forma física de los ancianos. Métodos: Un grupo de ancianos de la misma comunidad y en buen estado de salud, considerados aptos para experimentos deportivos, se dividió en el grupo experimental para el ejercicio Tai-ji y el grupo de control para el ejercicio de caminata vigorosa. Cada semana, se realizaron ejercicios de Tai-ji con ocho pasos y ejercicios de caminata vigorosa tres veces en cada grupo. Resultados: Después de seis semanas de ejercicio Tai-ji con ocho pasos de cinco métodos, la capacidad vital, el consumo máximo de oxígeno, la ventilación voluntaria máxima y el pulso de oxígeno del grupo experimental aumentaron significativamente, y las presiones sistólica y diastólica se redujeron significativamente, lo que evidencia una mejora en el rendimiento de la función cardiopulmonar. Conclusión: El ejercicio Tai-ji es beneficioso para la función cardiopulmonar y la salud física de los ancianos, y está científicamente demostrado que mejora el nivel de salud mental y la calidad de vida de los ancianos. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Incorporation of magnesium oxide nanoparticles into electrospun membranes improves pro-angiogenic activity and promotes diabetic wound healing.

Deficient angiogenesis is the major abnormality impairing the healing process of diabetic wounds. Electrospun nanofiber membranes have shown promise for wound dressing. A prerequisite for electrospun membranes to treating diabetic wounds is the capacity to promote angiogenesis of wounds. Current approaches are mainly focused on the use of pro-angiogenic growth factors to enhance the angiogenic properties of electrospun membranes. Despite improved angiogenesis, both the incorporation of growth factors into electrospun nanofibers and maintenance of its activity in the long term is of technical difficulty. We herein report an electrospun membrane made of polycaprolactone (PCL)/gelatin/magnesium oxide (MgO) nanoparticles (PCL/gelatin/MgO), which releases magnesium ions (Mg2+) to enhance angiogenesis. MgO-incorporated membranes promote the proliferation of human umbilical vein endothelial cells and upregulate vascular endothelial growth factor (VEGF) production in vitro. Subcutaneous implantation study in a rat model demonstrates that the MgO-incorporated membrane shows a faster degradation profile and elicits moderate immune responses that gradually resolve. Upon subcutaneous implantation, PCL/gelatin/MgO membranes allow robust blood vessel formation as early as one week after surgery, and the newly formed capillary networks enrich within the degrading membrane over time. PCL/gelatin/MgO membranes significantly accelerated diabetic wound healing by suppressing inflammatory responses, promoting angiogenesis, and boosting granulation formation. Taken together, these results are implicative to rationally designing magnesium-incorporated electrospun membranes with improved pro-angiogenic activity for treating diabetic wounds.

A study of the "Swiss-roll" folding method for placement of self-gripping mesh in TAPP.

BACKGROUND: Using self-gripping mesh eliminates the need for additional mechanical fixation in laparoscopic groin hernia repair when surgeons plan to fix it. However, the mesh's 'self-gripping' characteristic makes it much more difficult to unfold and place. Here, the novel "Swiss-roll" placement method of folding self-gripping mesh is introduced and compared to the common folding placement method. MATERIAL AND METHODS: The cohort of this prospective randomized controlled study included 100 patients who underwent transabdominal preperitoneal (TAPP) groin hernia repair in the Department of Hernia and Abdominal Wall Surgery of Shanghai East Hospital between January and December 2018. The patients were randomly assigned to the "Swiss-roll" folding group or the common folding group. The time required for mesh placement, total surgical duration, and the incidences of postoperative pain and complications were compared. RESULTS: The times required for mesh placement in the "Swiss-roll" and common folding groups were 155.10 ± 48.66 and 202.80 ± 61.05 sec, respectively. The "Swiss-roll" folding method significantly shortened the time required for mesh placement (p = 0.000). There were no significant differences in total surgical duration and the incidences of postoperative pain and complications between the two groups. CONCLUSIONS: The "Swiss-roll" folding method facilitates self-gripping mesh placement without increasing the incidence of complications and recurrences in TAPP.

The evaluation of functional small intestinal submucosa for abdominal wall defect repair in a rat model: Potent effect of sequential release of VEGF and TGF-ß1 on host integration.

Ineffective vessel penetration and extracellular matrix (ECM) remodeling are responsible for the failure of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. Combined growth factors could be used as directing signals in a nature-mimicking strategy to improve this repair through mesh functionalization. In this work, vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) were incorporated into a silk fibroin membrane via coaxial aqueous electrospinning to exploit their benefits of biological interactions. The membrane was sandwiched into the SIS bilayer as a functional mesh to repair partial-thickness defects in a rat model. Membrane characterization demonstrated that the core-shell structure ensured the independent distribution and sequential release of two regulators and protection of their bioactivities, which were confirmed by cell viability and protein expression. The mesh was further assessed to facilitate vasculature formation and collagen secretion in vitro, and exhibited better host integration than VEGF- or TGF-ß1-containing mesh and developed reinforced mechanical properties compared with the VEGF-containing mesh after 28 days in vivo. Determination of the underlying biological interactions revealed that rapid VEGF release promotes angiogenesis and collagen secretion but initially potentiates the inflammatory response. Sustained TGF-ß1 release at relatively low concentrations promoted VEGF for vessel permeation and maturation and steadily induced ECM remodeling under milder foreign body reactions. The functionalization of SIS improves repair by sufficient integration with timely remodeling and helps elucidate the related regulatory interactions.

Collagen Nanofilm-Coated Partially Deproteinized Bone Combined With Bone Mesenchymal Stem Cells for Rat Femoral Defect Repair by Bone Tissue Engineering.

BACKGROUND: The advantages of good biocompatibility, low degradation and low antigenicity of collagen, and the osteogenic differentiation characteristics of bone mesenchymal stem cells (BMSCs) were used to promote the recovery of bone defects using partially deproteinized bone (PDPB) by bone tissue engineering (BTE). METHODS: The BMSCs were identified by examining their potential for osteogenic, lipogenic, and chondrogenic differentiation. The prepared pure PDPB was ground into bone blocks 4 × 2 × 2 mm in size, which were divided into the following groups: PDPB group, PDPB + collagen group, PDPB + collagen + BMSC group, PDPB with a composite collagen nanofilm, and BMSCs injected into the tail vein. At 2, 4, 6, and 8 weeks after surgery, the effects of the implants in the different groups on bone defect repair were continuously and dynamically observed through x-ray examination, gross specimen observation, histological evaluation, and microvascularization detection. RESULTS: Postoperative x-ray examination and gross specimen observation revealed that, after 4 to 8 weeks, the external contour of the graft was gradually weakened, and the transverse comparison showed that the absorption of the graft and fusion of the defect were more obvious in PDPB + collagen + BMSC group than in PDPB group and PDPB + collagen group, and the healing was better (P < 0.05). Hematoxylin and eosin staining of histological sections showed very active proliferation of trabecular hematopoietic cells in groups PDPB + collagen + BMSC and PDPB + collagen. Masson's trichrome staining for evaluation of bone defect repair showed that the mean percent area of collagen fibers was greater in PDPB + collagen + BMSC group than in the PDPB group, with degradation of the scaffold material and the completion of repair. Immunofluorescence staining showed significantly enhanced expression of the vascular marker CD31 in group C (P < 0.05). CONCLUSIONS: The proposed hybrid structure of the collagen matrix and PDPB provides an ideal 3-dimensional microenvironment for patient-specific BTE and cell therapy applications. The results showed that collagen appeared to regulate MSC-mediated osteogenesis and increase the migration and invasion of BMSCs. The combination of collagen nanofilm and biological bone transplantation with BMSC transplantation enhanced the proliferation and potential of the BMSCs for bone regeneration, successfully promoting bone repair after implantation at the defect site. This method may provide a new idea for treating clinical bone defects through BTE.

An Isoxazole Derivative SHU00238 Suppresses Colorectal Cancer Growth through miRNAs Regulation.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Isoxazoline and isoxazole derivatives represent an important class of five-membered heterocycles, which play a pivotal role in drug discovery. In our previous study, we developed a series of isoxazole derivatives with an efficient method. In this study, we evaluated their effects on tumor cell growth. HCT116 cells were treated with isoxazole derivatives; an cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 (half maximal inhibitory concentration) of each derivative. Compound SHU00238, which was obtained by the copper nitrate-mediated [2+2+1] cycloaddition reaction of olefinic azlactone with naphthalene-1,4-dione, has a lower IC50; we analyzed its inhibitory activity in further assays. Cell apoptosis was estimated by flow cytometry analysis in vitro. SHU00238 injection was used to treat tumor-bearing mice. We found that SHU00238 suppressed cell viability and promoted cell apoptosis in vitro. SHU00238 treatment significantly inhibited colonic tumor growth in vivo. Furthermore, we compared the miRNAs expression changes in HCT116 cells before and after SHU00238 treatment. MiRNA profiling revealed that SHU00238 treatment affected cell fate by regulating a set of miRNAs. In conclusion, SHU00238 impedes CRC tumor cell proliferation and promotes cell apoptosis by miRNAs regulation.

Interleukin-8 promotes prostate cancer bone metastasis through upregulation of bone sialoprotein.

The aim of the present study was to investigate whether interleukin-8 (IL-8) enhances the ability of prostate cancer bone metastasis by influencing the coding level of bone sialoprotein (BSP). Cultured prostate cancer cell lines LNCaP (androgen dependent) and DU145 (androgen independent) were divided into three groups: IL-8 treatment group; IL-8 receptor inhibitor (SB225002) treatment group; and control group. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect BSP protein and mRNA expression levels. Matrigel and bone adhesion experiments were used to detect the invasiveness of cancer cells and bone adhesion changes. Compared with the control group, western blotting and RT-qPCR results indicated that BSP protein and mRNA levels in LNCaP and DU145 were significantly upregulated following IL-8 treatment. Matrigel experiments indicated that following IL-8 treatment, the invasiveness of LNCaP and DU145 cells was significantly increased. The results of bone adhesion experiments indicated that following IL-8 treatment, the number of DU145 cells adhered to the surface of the bone was increased, compared with the control group. Following treatment of both cell lines with SB225002, western blotting and RT-qPCR results indicated that the expression levels of BSP protein and mRNA were significantly downregulated. Matrigel experiments indicated that following SB225002 treatment, the invasiveness of LNCaP and DU145 cells was significantly reduced. The number of DU145 cells adhered to the surface of the bone was reduced, compared with the untreated group. Therefore, IL-8 may promote prostate cancer bone metastasis by enhancing BSP regulation.

SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP­2.

The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial. Studies have demonstrated that small integrin­binding ligand N­linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis. SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP­2) and MMP­9 expression. Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells. In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability. A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen­independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen­dependent prostate cancer cells. Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP­2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation. Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP­2 were also inhibited.

Marine fish oil is more potent than plant-based n-3 polyunsaturated fatty acids in the prevention of mammary tumors.

Marine-derived n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit mammary carcinogenesis. However, evidence regarding plant-based α-linolenic acid (ALA), the major n-3 PUFA in the Western diet, remains equivocal. The objective of this study was to examine the effect of lifelong exposure to plant- or marine-derived n-3 PUFAs on pubertal mammary gland and tumor development in MMTV-neu(ndl)-YD5 mice. It is hypothesized that lifelong exposure to n-3 PUFA reduces terminal end buds during puberty leading to delayed tumor onset, volume and multiplicity. It is further hypothesized that plant-derived n-3 PUFAs will exert dose-dependent effects. Harems of MMTV-FVB males were bred with wild-type females and fed either a (1) 10% safflower (10% SF, n-6 PUFA, control), (2) 10% flaxseed (10% FS), (3) 7% safflower plus 3% flaxseed (3% FS) or (4) 7% safflower plus 3% menhaden (3% FO) diet. Female offspring were maintained on parental diets. Compared to SF, 10% FS and 3% FO reduced (P<.05) terminal end buds at 6 weeks and tumor volume and multiplicity at 20 weeks. A dose-dependent reduction of tumor volume and multiplicity was observed in mice fed 3% and 10% FS. Antitumorigenic effects were associated with altered HER2, pHER-2, pAkt and Ki-67 protein expression. Compared to 10% SF, 3% FO significantly down-regulated expression of genes involved in eicosanoid synthesis and inflammation. From this, it can be estimated that ALA was 1/8 as potent as EPA+DHA. Thus, marine-derived n-3 PUFAs have greater potency versus plant-based n-3 PUFAs.

Cytokeratin 19 promoter directs the expression of Cre recombinase in various epithelia of transgenic mice.

Cytokeratin 19 (K19) is expressed in various differentiated cells, including gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here, we generated a transgenic mouse line, K19-Cre, in which the expression of Cre recombinase was controlled by the promoter of K19. To test the tissue distribution and excision activity of Cre recombinase, K19-Cre transgenic mice were bred with Rosa26 reporter strain and a mouse strain that carries PTEN conditional alleles (PTENLoxp/Loxp). At mRNA level, Cre was strongly expressed in the stomach, lung and intestine, while in stomach, lung, and liver at protein level. The immunoreactivity to Cre was strongly observed the cytoplasm of gastric, bronchial and intestinal epithelial cells. Cre activity was detectable in gastric, bronchial and intestinal epithelial cells, according to LacZ staining. In K19-Cre/PTEN Loxp/Loxp mice, PTEN was abrogated in stomach, intestine, lung, liver and breast, the former two of which were verified by in situ PCR. There appeared breast cancer with PTEN loss. These data suggest that K19 promoter may be a useful tool to study the pathophysiological functions of cytokeratin 19-positive cells, especially gastrointestinal epithelial cells. Cell specificity of neoplasia is not completely attributable to the cell-specific expression of oncogenes and cell-specific loss of tumor suppressor genes.

The in vitro and vivo effects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target.

Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0.05) of cancer cells. WT parafibromin transfectants showed the overexpression of Cyclin B1, Cyclin D1, Cyclin E, p38, p53, and AIF in HCT-15 and HCT-116 cells, while MT parafibromin only up-regulated p38 expression. There was lower mRNA expression of bcl-2 in parafibromin transfectants than the control and mock, while higher expression of c-myc, Cyclin D1, mTOR, and Raptor. According to transcriptomic analysis, WT parafibromin suppressed PI3K-Akt and FoxO signaling pathways, while MT one promoted PI3K-Akt pathway, focal adhesion, and regulation of actin cytoskeleton. Parafibromin was less expressed in colorectal cancer than paired mucosa (p<0.05), and inversely correlated with its differentiation at both mRNA and protein levels (p<0.05). These findings indicated that WT parafibromin might reverse the aggressive phenotypes of colorectal cancer cells and be employed as a target for gene therapy. Down-regulated parafibromin expression might be closely linked to colorectal carcinogenesis and cancer differentiation.

SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: An in vitro and vivo study.

To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes' assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells. The treatment with SAHA increased the expression of acetyl-histones 3 and 4, which were recruited to the promoters of p21, p27, Cyclin D1, c-myc and Nanog to down-regulate their transcriptional levels. Expression of acetyl-histones 3 and 4 was higher in gliomas than normal brain tissues. Both drugs' exposure suppressed tumor growth in nude mice by inducing apoptosis and inhibiting proliferation, but increased serum aminotransferase and creatinine. These results indicated that SAHA and/or MG132 may suppress the aggressive phenotypes of glioma cells. They might be employed to treat the glioma if both hepatic and renal injuries are prevented.

The clinicopathological and prognostic features of Chinese and Japanese inpatients with lung cancer.

Here, we retrospectively compared the differences in clinicopathological behaviors and prognosis of lung cancer from the First Affiliated Hospital (CMU1, n=513), Shengjing Hospital (CMUS, n=1021), Tumor Hospital (CMUT, n=5378) of China Medical University, the First Affiliated Hospital of Dalian (DMU, n=2251) and Jinzhou (JMU, n=630) Medical University, Takaoka Kouseiren Hospital (Takaoka, n=163) of Japan. Japanese lung cancer patients showed smaller tumor size, lower TNM staging, lower ratio of squamous cell carcinoma and higher ratio of small and large cell carcinomas than Chinese patients (p<0.05). Survival analysis showed that tumor size was employed as a prognostic factor for the Japanese and Chinese cancer patients (p<0.05). In DMU and CMUS, the ratios of female patients or adenocarcinoma were higher than other hospitals (p<0.05), while the patients from CMUT and CMU1 were younger than the others (p<0.05). The ratios of squamous cell carcinoma from CMUT, CMU1 and JMU were higher than the others, while it was the same for the ratio of large and small cell carcinoma in Takaoka and CMU1 (p<0.05). TNM staging was higher in CMUT than JMU and Takaoka (p<0.05). The female patients of lung cancer showed young prone, large tumor size, a high ratio of adenocarcinoma and advanced TNM staging in comparison to the counterpart (p<0.05). The younger patients of lung cancer displayed smaller tumor size, higher ratio of adenocarcinoma, lower TNM staging than the elder in Takaoka (p<0.05). There were more aggressive behaviors and shorter survival time for Chinese than Japanese lung cancer patients. The prevention of lung cancer should be strengthened by establishing a systematic and effective screening strategy, especially for the young and female patients.

The role of n-3 polyunsaturated fatty acids in the prevention and treatment of breast cancer.

Breast cancer (BC) is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA), are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA), however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research.