COVID-19 vaccine perspectives and uptake among university students three years into the pandemic.

BACKGROUND: University students have been uniquely impacted by the COVID-19 pandemic for the past three years (2020-2023). Understanding their COVID-19 perspectives, beliefs, and vaccine uptake may help to improve future vaccine initiatives and education. METHODS: A cross sectional, confidential, online survey was conducted at four universities in Pennsylvania in spring 2023 to assess undergraduate, graduate, and professional students' perspectives regarding their knowledge of COVID-19 vaccines, importance of COVID-19 vaccines and mandates, number of doses of COVID-19 vaccine received including the recent BA.4/BA.5 bivalent booster, where they were vaccinated, receipt of influenza vaccine, and sources of information used to make decisions about COVID-19 vaccine. RESULTS: Vaccination for COVID-19 was considered important by 75 % of 2223 students surveyed; 68 % agreed with mandating COVID-19 vaccine. Over 89 % were fully COVID-19 vaccinated (≥2 doses), 65 % were up-to-date (≥3 doses), but only 35 % had received the BA.4/BA.5 booster. Students who considered COVID-19 vaccine important were generally older, female, and non-business majors. Higher rates of up-to-date COVID-19 vaccination were found in those who received influenza vaccine in 2022-2023, females, Asians, doctoral or professional students, those attending larger universities, non-US residents, and those interested in learning more about COVID-19 vaccines. Most trusted sources of information on COVID-19 vaccines were the Centers for Disease Control and Prevention, healthcare providers, and parents; the least trusted sources were social media, television, and the internet. CONCLUSIONS: The majority of university students agreed that COVID-19 vaccination is important and supported COVID-19 mandates. While the rate of fully vaccinated and up-to-date students was similar to the US adult population, the latter rate needs improvement. Receipt of the BA.4/BA.5 booster was particularly low. Further education is needed to improve vaccine knowledge, especially as we move to periodic boosters. Business majors, males, and younger students may benefit from increased on-campus vaccine education initiatives.

A critical review on the assessment of the quality and authenticity of Tequila by different analytical techniques: Recent advances and perspectives.

Currently, the authenticity and traceability of Tequila are determined in an inspection process carried out by the Tequila Regulatory Council. However, in recent years, the authorities have seized illegal alcoholic products that are marketed as Tequila without being so, making it necessary to strengthen the current methods of detecting counterfeiting and/or adulteration. Therefore, it is important to establish a review of the current analytical techniques that have been proposed to solve this problem. In this review, emphasis is placed on the analysis of the analytical techniques that have been used to consolidate a profile of authenticity and quality in Tequila, thus highlighting new auxiliary analytical techniques to the current verification process, establishing future validation opportunities in terms of international quality control. The use of isotopic ratios stands out as the most robust technique because it establishes the type of sugar source used and the maturation time of the manufacturing process.

Alcohol-induced aggression in Drosophila.

Alcohol-induced aggression is a destructive and widespread phenomenon associated with violence and sexual assault. However, little is understood concerning its mechanistic origin. We have developed a Drosophila melanogaster model to genetically dissect and understand the phenomenon of sexually dimorphic alcohol-induced aggression. Males with blood alcohol levels of 0.04-mg/ml BAC were less aggressive than alcohol-naive males, but when the BAC had dropped to ~0.015 mg/ml, the alcohol-treated males showed an increase in aggression toward other males. This aggression-promoting treatment is referred to as the post-ethanol aggression (PEA) treatment. Females do not show increased aggression after the same treatment. PEA-treated males also spend less time courting and attempt to copulate earlier than alcohol-naive flies. PEA treatment induces expression of the FruM transcription factor (encoded by a male-specific transcript from the fruitless gene), whereas sedating doses of alcohol reduce FruM expression and reduce male aggression. Transgenic suppression of FruM induction also prevents alcohol-induced aggression. In male flies, alcohol-induced aggression is dependent on the male isoform of the fruitless transcription factor (FruM). Low-dose alcohol induces FruM expression and promotes aggression, whereas higher doses of alcohol suppress FruM and suppress aggression.

Thrombospondin 1 in Metabolic Diseases.

The thrombospondin family comprises of five multifunctional glycoproteins, whose best-studied member is thrombospondin 1 (TSP1). This matricellular protein is a potent antiangiogenic agent that inhibits endothelial migration and proliferation, and induces endothelial apoptosis. Studies have demonstrated a regulatory role of TSP1 in cell migration and in activation of the latent transforming growth factor beta 1 (TGFß1). These functions of TSP1 translate into its broad modulation of immune processes. Further, imbalances in immune regulation have been increasingly linked to pathological conditions such as obesity and diabetes mellitus. While most studies in the past have focused on the role of TSP1 in cancer and inflammation, recently published data have revealed new insights about the role of TSP1 in physiological and metabolic disorders. Here, we highlight recent findings that associate TSP1 and its receptors to obesity, diabetes, and cardiovascular diseases. TSP1 regulates nitric oxide, activates latent TGFß1, and interacts with receptors CD36 and CD47, to play an important role in cell metabolism. Thus, TSP1 and its major receptors may be considered a potential therapeutic target for metabolic diseases.

Comparison between subarachnoid morphine and femoral nerve block for analgesia after knee ligament reconstruction: a randomized clinical trial / Comparação entre morfina subaracnoidea e bloqueio do nervo femoral para analgesia após reconstrução ligamentar de joelho: estudo clínico randomizado

Abstract Background and objectives There are no consensus of the ideal technique to provide analgesia in knee ligament reconstructions. The aim of this study was to compare the intensity of postoperative pain in these patients under different modalities of analgesia. Method Randomized and controlled clinical trial of patients undergoing reconstruction of the Anterior Cruciate Ligament (ACL) with flexor tendons between December 2013 and 2014. All patients underwent spinal anesthesia and rescue analgesia with tramadol. The groups C, M, R0,375 and R0,25 was compared with only the previously described technique, subarachnoid morphine (100░µg), or Femoral Nerve Block (BNF) with 25░mL of 0.375% ropivacaine and 0.25%, respectively. Pain intensity at 6, 12 and 24░hours, age, sex, rescue analgesia, adverse reactions and satisfaction were evaluated. Results Among the 83 eligible patients, a predominance of males (85.7%) was observed, between 28 and 31 years. The group C requested more opioid (27.3%) than the other groups, without significance when compared. There were no significant differences in pain intensity at 6, 12 and 24░hours. There was a higher incidence of urinary retention in the M group (23.8%) than in the R0,375 (0%) and prolonged quadriceps motor block in the R0,375 group (30%) than in the M and C groups (0%), with statistical significance (p░<░0.05). Conclusion There was no difference in the intensity of postoperative pain in patients submitted to ACL reconstruction with flexor tendons under the analgesic modalities evaluated, despite the predominance of urinary retention in the M group and motor block in the R0,375 group.

Resumo Justificativa e objetivos Não há consenso sobre qual é a técnica ideal para prover analgesia em reconstruções ligamentares de joelho. Objetivou‐se comparar a intensidade da dor pós‐operatória desses pacientes sob diferentes modalidades de analgesia. Método Ensaio clínico randomizado e controlado de pacientes submetidos à reconstrução do ligamento cruzado anterior com tendões flexores entre dezembro de 2013 e 2014. Todos os pacientes foram submetidos a raquianestesia e analgesia de resgate com tramadol. Compararam‐se os grupos C, M, R0,375 e R0,25; aos quais se ofertou apenas a técnica anteriormente descrita, morfina subaracnóidea (100 µg) ou bloqueio de nervo femoral com 25 mL de ropivacaína 0,375% e 0,25%, respectivamente. Avaliou‐se intensidade da dor em 6, 12 e 24 horas, idade, sexo, analgesia de resgate, reações adversas e satisfação. Resultados Entre os 83 pacientes elegíveis, observou‐se predomínio do sexo masculino (85,7%) entre 28 e 31 anos. O Grupo C solicitou mais opioide (27,3%) do que os demais grupos, sem significância quando comparados. Não houve diferenças significativas na intensidade da dor em 6, 12 e 24 horas. Houve maior incidência de retenção urinária no Grupo M (23,8%) do que no R0,375 (0%) e de bloqueio motor prolongado do quadríceps no Grupo R0,375 (30%) do que nos Grupos M e C (0%), com significância estatística (p< 0,05). Conclusão Não houve diferença na intensidade da dor pós‐operatória nos pacientes submetidos à reconstrução de ligamento cruzado anterior com tendões flexores sob as modalidades analgésicas avaliadas, apesar do predomínio de retenção urinária no Grupo M e bloqueio motor no Grupo R0,375.

[Comparison between subarachnoid morphine and femoral nerve block for analgesia after knee ligament reconstruction: a randomized clinical trial]. / Comparação entre morfina subaracnoidea e bloqueio do nervo femoral para analgesia após reconstrução ligamentar de joelho: estudo clínico randomizado.

BACKGROUND AND OBJECTIVES: There is no consensus of the ideal technique to provide analgesia in knee ligament reconstructions. The aim of this study was to compare the intensity of postoperative pain in these patients under different modalities of analgesia. METHOD: Randomized and controlled clinical trial of patients undergoing reconstruction of the anterior cruciate ligament (ACL) with flexor tendons between December 2013 and 2014. All patients underwent spinal anesthesia and rescue analgesia with tramadol. The Groups C, M, R0,375 and R0,25 were compared with only the previously described technique, subarachnoid morphine (100 µg) or femoral nerve block with 25 mL of 0.375% ropivacaine and 0.25%, respectively. Pain intensity at 6, 12 and 24hours, age, sex, rescue analgesia, adverse reactions and satisfaction were evaluated. RESULTS: Among the 83 eligible patients, a predominance of males (85.7%) was observed, between 28 and 31 years. The Group C requested more opioid (27.3%) than the other groups, without significance when compared. There were no significant differences in pain intensity at 6, 12 and 24hours. There was a higher incidence of urinary retention in the Group M (23.8%) than in the R0,375 (0%) and prolonged quadriceps motor block in the R0,375 Group (30%) than in the M and C Groups (0%), with statistical significance (p < 0.05). CONCLUSION: There was no difference in the intensity of postoperative pain in patients submitted to anterior cruciate ligament reconstruction with flexor tendons under the analgesic modalities evaluated, despite the predominance of urinary retention in the M Group and motor block in the R0,375 Group.

Towards understanding of heterogeneous Fenton reaction using carbon-Fe catalysts coupled to in-situ H2O2 electro-generation as clean technology for wastewater treatment.

Iron-supported catalyst on granular activated carbon was prepared for its use in heterogeneous Fenton reaction coupled to an in situ H2O2 electro-generation. For this process, an electrolysis cell was employed, using carbon felt as cathode and graphite as anode. A solution of H2O2 (electrogenerated at a rate of 30 mg L-1 h-1) was obtained using a current intensity of 12 mA. In order to promote the decomposition of H2O2 to OH, a Carbon-Fe catalyst was used. This catalyst was prepared by incipient wet impregnation using FeSO4 as precursor salt to obtain samples with 9% wt of iron. Samples were characterized by EDX, FTIR and XPS spectroscopy before and after wastewater treatment using phenol as model molecule. Two iron oxidation states on the samples were found, Fe2+ and Fe3+. The ratio between Fe2+/Fe3+ was 1.29 which was later reduced to 0.92 after Fenton process; this might be associated with the metal oxidation (Fe2+ to Fe+3) occurring during Fenton-reaction, thus indicating that H2O2 decomposition was carried out by Fe2+ on carbon surface. Detection and quantification of hydroxyl radical were carried out by fluorescence spectroscopy, obtaining a radical concentration of 3.5 µM in solution. Iron in solution were determined, showing a concentration of 0.1 mg L-1, making evident that the supported metal is stable and the reaction is carried out in a heterogeneous phase. Results showed an environmentally friendly process that can generate reagents in situ, with high efficiencies in the degradation of pollutants and minimizing the formation of toxic byproducts, which are common in conventional treatments.

Expression of WIF-1 in inflammatory bowel disease.

The WNT/ß-catenin cellular network has been extensively studied in numerous diseases including inflammatory bowel disease (IBD). IBD is a condition that increases the risk of developing colorectal cancer. WIF-1 is an inhibitory protein that acts by blocking the interactions of WNT with its receptor complex, thus leading to downregulation of end products of this pathway. While WIF-1 has been characterized in several cancers, its relationship with IBD has yet to be elucidated. In this study, the expression of WIF-1 in patients with IBD was analyzed in order to provide insights into the pathophysiology and rationale for alternative therapies. Biopsies of both normal and inflamed colonic mucosa from patients with Crohn's disease or ulcerative colitis were histologically examined for the degree of morphologic changes, immune cell infiltration and presence of WIF-1 through immunohistochemistry. No differences were observed in WIF-1 expression linked to a particular condition, but WIF-1 stain was significantly enhanced in the crypts and lamina propria as inflammation increased in biopsies from patients with both, ulcerative colitis and Crohn's disease. These findings could give guidance to new therapeutic applications of the WNT/ß-catenin system and WIF-1 in IBD.

Effects of propolis and gamma-cyclodextrin on intestinal neoplasia in normal weight and obese mice.

Obesity is associated with colorectal cancer (CRC). This effect might be attributed to adipokine-supported signaling. We have established that propolis suppresses survival signaling in CRC cells in vitro; therefore, we ascertained the ability of a propolis supplement to modulate intestinal neoplastic development in C57BL/6J-ApcMin/+/J mice in the lean and obese state. To induce obesity, mice were fed with a Western diet containing 40% fat. Since the propolis supplement includes gamma-cyclodextrin, the interventions included diets supplemented with or without gamma-cyclodextrin. The animals were administered the following diets: (1) control diet, (2) control diet/gamma-cyclodextrin, (3) control diet/propolis, (4) Western diet, (5) Western diet/gamma-cyclodextrin, and (6) Western diet/propolis. Western diet, resulting in obesity, accelerated neoplastic progression, as evidenced by the larger size and higher grade dysplasia of the neoplasms. In the context of normal weight, gamma-cyclodextrin and propolis affected neoplastic progression, as determined by the size of the lesions and their grade of dysplasia. A statistically significant decrease in the number of adenomas was detected in mice fed a control diet with the propolis supplement (61.8 ± 10.6 vs. 35.3 ± 7.6, P = 0.008). Although there was no significant difference in the polyp numbers between the six groups, the mice with the lowest number and size of adenomas were those fed a Western diet with gamma-cyclodextrin. This unexpected outcome might be explained by the increased levels of apoptosis detected in the intestinal tissues of these obese mice. We posit that butyrate derived from the metabolism of gamma-cyclodextrin may contribute to the decreased neoplastic burden in the context of obesity; however, future studies are required to address this possibility.

Saliva DNA quality and genotyping efficiency in a predominantly elderly population.

BACKGROUND: The question of whether DNA obtained from saliva is an acceptable alternative to DNA from blood is a topic of considerable interest for large genetics studies. We compared the yields, quality and performance of DNAs from saliva and blood from a mostly elderly study population. METHODS: Two thousand nine hundred ten DNAs from primarily elderly subjects (mean age ± standard deviation (SD): 65 ± 12 years), collected for the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study, were evaluated by fluorometry and/or spectroscopy. These included 566 DNAs from blood and 2344 from saliva. Subsets of these were evaluated by Sanger sequencing (n = 1555), and by microarray SNP genotyping (n = 94) on an Illumina OmniExpress bead chip platform. RESULTS: The mean age of subjects was 65, and 68 % were female in both the blood and saliva groups. The mean ± SD of DNA yield per ml of requested specimen was significantly higher for saliva (17.6 ± 17.8 µg/ml) than blood (13.2 ± 8.5 µg/ml), but the mean ± SD of total DNA yield obtained per saliva specimen (35 ± 36 µg from 2 ml maximum specimen volume) was approximately three-fold lower than from blood (106 ± 68 µg from 8 ml maximum specimen volume). The average genotyping call rates were >99 % for 43 of 44 saliva DNAs and >99 % for 50 of 50 for blood DNAs. For 22 of 23 paired blood and saliva samples from the same individuals, the average genotyping concordance rate was 99.996 %. High quality PCR Sanger sequencing was obtained from ≥ 98 % of blood (n = 297) and saliva (n = 1258) DNAs. DNA concentrations ≥10 ng/µl, corresponding to total yields ≥ 2 µg, were obtained for 94 % of the saliva specimens (n = 2344). CONCLUSIONS: In spite of inferior purity, the performance of saliva DNAs for microarray genotyping was excellent. Our results agree with other studies concluding that saliva collection is a viable alternative to blood. The potential to boost study enrollments and reduce subject discomfort is not necessarily offset by a reduction in genotyping efficiency. Saliva DNAs performed comparably to blood DNAs for PCR Sanger sequencing.

Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis.

Colorectal Cancer (CRC) is one of the late complications observed in patients suffering from inflammatory bowel diseases (IBD). Carcinogenesis is promoted by persistent chronic inflammation occurring in IBD. Understanding the mechanisms involved is essential in order to ameliorate inflammation and prevent CRC. Thrombospondin 1 (TSP-1) is a multidomain glycoprotein with important roles in angiogenesis. The effects of TSP-1 in colonic tumor formation and growth were analyzed in a model of inflammation-induced carcinogenesis. WT and TSP-1 deficient mice (TSP-1-/-) of the C57BL/6 strain received a single injection of azoxymethane (AOM) and multiple cycles of dextran sodium sulfate (DSS) to induce chronic inflammation-related cancers. Proliferation and angiogenesis were histologically analyzed in tumors. The intestinal transcriptome was also analyzed using a gene microarray approach. When the area containing tumors was compared with the entire colonic area of each mouse, the tumor burden was decreased in AOM/DSS-treated TSP-1-/- versus wild type (WT) mice. However, these lesions displayed more angiogenesis and proliferation rates when compared with the WT tumors. AOM-DSS treatment of TSP-1-/- mice resulted in significant deregulation of genes involved in transcription, canonical Wnt signaling, transport, defense response, regulation of epithelial cell proliferation and metabolism. Microarray analyses of these tumors showed down-regulation of 18 microRNAs in TSP-1-/- tumors. These results contribute new insights on the controversial role of TSP-1 in cancer and offer a better understanding of the genetics and pathogenesis of CRC.

Thrombospondin peptide ABT-898 inhibits inflammation and angiogenesis in a colitis model.

AIM: To evaluate the efficacy of the improved thrombospondin mimetic peptide ABT-898 in a murine model of ulcerative colitis. METHODS: The dextran sodium sulfate (DSS) was used for the induction of colitis in both TSP-1 deficient (TSP-1(-/-)) and wild type (WT) mice during 7 d. While mice were receiving the DSS dissolved in the drinking water, the ABT-898 peptide was dissolved in sterile 5% glucose solution and delivered using mini pumps subcutaneously implanted. Plasma samples were analyzed for interleukin (IL)-6 by ELISA assay and colonic tissues were harvested, fixed and processed for histological evaluation. Immunohistochemistry using antibodies for the detection of CD31 and MECA in endothelial cells was performed. Inflammation was graded in colonic sections and the number of microvessels in each lesion was assessed. Activation of signal transducer and activator of transcription 3 (STAT3) in colonic samples was quantified by immunohistochemistry and Western blotting using antibodies against total STAT3 and phosphorylated STAT3 (pSTAT3) (Ser727). RESULTS: Treatment with ABT-898 considerably diminished the inflammatory response in WT and TSP-1(-/-) mice (P < 0.0001 in both groups vs control). Identification of blood vessels highlighted by CD31/MECA immunohistochemistry, showed significantly reduced vessel counts in colitic lesions of WT and TSP-1(-/-) mice treated with ABT898 (TSP-1(-/-) controls/TSP-1(-/-) treated, P = 0.0002; WT controls/WT treated, P = 0.0005). Consistently, IL-6 was significantly diminished in plasma samples of TSP-1(-/-) and WT treated with the peptide when compared to the control mice (P = 0.0002 and P = 0.0148, respectively). pSTAT3 positive cells were quantified in WT and TSP-1(-/-) treated with ABT-898. A significant decrease in positive cells for pSTAT3 was observed in treated mice (TSP-1(-/-) controls/TSP-1(-/-) treated, P = 0.0089; WT/WT treated, P = 0.0110). These results were confirmed by Western blotting analyses showing lower levels of pSTAT3 in colitic lesions from mice treated with the peptide ABT-898. CONCLUSION: These findings indicate that the new peptide ABT-898 ameliorates inflammation and angiogenesis and might be a therapeutic alternative in IBD and inflammatory diseases.

Upflow fixed bed bioelectrochemical reactor for wastewater treatment applications.

A cylindrical Upflow Fixed Bed Reactor (UFB-BER) with granular activated carbon, steel mesh electrodes and anaerobic microorganisms, was constructed for analyzing how hydrodynamic parameters affect the reactions involved during wastewater treatment processes for azo dye degradation. Dye removal percentage was not compromised by decreasing HRTm (99-90% upon changing HRTm from 4 to 1h in single pass mode). Using the residence time distribution method for hydrodynamic characterization, it was found that a higher dispersion in the reactor occurs for HRTm=1h, than for HRTm=4h. A kinetic analysis suggests that this dispersion effect could be associated to a higher specific reaction rate dependent on the azo dye concentration.

Development of an activated carbon-packed microbial bioelectrochemical system for azo dye degradation.

A microbial bioelectrochemical reactor (BER) was employed for the degradation of azo dyes without the use of an external electron donor, using activated carbon (GAC) as a redox mediator. Contribution of pH values, open circuit potential (OCP), dye concentration and applied current were individually studied. A batch system and an upflow fixed bed bioreactor were built for analyzing the effect of the applied current on biodegradation of the azo dye Reactive Red 272. The presence of GAC (20% w/v) regulated both pH and OCP values in solution and led to a removal efficiency of 98%. Cyclic voltammetry results indicate a dependence of the electron transfer mechanism with the concentration of the azo compound. With these results, a continuous flow reactor operating with J=0.045 mA cm(-2), led to removal rates of 95% (± 3.5%) in a half-residence time of 1 hour.

Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects.

Thrombospondin-1 (TSP-1) is a matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To ascertain possible functions and evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and microarray analyses on a mouse model of induced colitis. We used dextran sulfate sodium (DSS) to induce colitis in wild-type (WT) mice for 7 days. Simultaneously, mice were injected with either saline or one form of TSP-1 derived recombinant proteins, containing either (1) the three type 1 repeats of the TSP-1 (3TSR), (2) the second type 1 repeat (TSR2), or (3) TSR2 with the RFK sequence (TSR2+RFK). Total RNA isolated from the mice colons were processed and hybridized to mouse arrays. Array data were validated by real-time qPCR and immunohistochemistry. Histological and disease indices reveal that the mice treated with the TSRs show different patterns of leukocytic infiltration and that 3TSR treatment was the most effective in decreasing inflammation in DSS-induced colitis. Transcriptional profiling revealed differentially expressed (DE) genes, with the 3TSR-treated mice showing the least deviation from the WT-water controls. In conclusion, this study shows that 3TSR treatment is effective in attenuating the inflammatory response to DSS injury. In addition, the transcriptomics work unveils novel genetic data that suggest beneficial application of the TSR domains in inflammatory bowel disease.

Thrombospondin-1: multiple paths to inflammation.

Inflammation is a defensive process against tissue injury. Once this self-protective strategy is initiated, an effective resolution of the process is crucial to avoid major and unnecessary tissue damage. If the underlying event inducing inflammation is not addressed and homeostasis is not restored, this process can become chronic and lead to angiogenesis and carcinogenesis. Thrombospondin-1 (TSP-1) is a matricellular protein involved in angiogenesis, cancer, and inflammation. The effects of TSP-1 have been studied in many preclinical tumor models, and mimetic peptides are being tested in cancer clinical trials. However, the molecular mechanisms explaining its role in inflammatory processes are not well understood. This paper will discuss the role of TSP-1 in inflammation and its interaction with key receptors that may explain its functions in that process. Recent literature will be reviewed showing novel mechanisms by which this multifaceted protein could modulate the inflammatory process and impact its resolution.

The role of thrombospondin 1 on intestinal inflammation and carcinogenesis.

Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) quite common in the United States and other Western countries. Patients suffering IBD are at greater risk of developing colorectal adenocarcinoma than the general population. Both, the adenoma-carcinoma and the inflammation-carcinogenesis processes are characterized by active angiogenesis. Recent studies also have shown that anti-angiogenesis might be a novel therapeutic approach for IBD. Thrombospondin 1 (TSP1) is an extracellular protein well known for its anti-angiogenic properties. TSP1 also has key functions in inflammation, which is assumed to be the primary cause for carcinogenesis in IBD. This review is focused on the role of TSP1 in colorectal carcinogenesis. The therapeutic effects of TSP derived-peptides on inhibiting the inflammationcarcinogenesis progression are also discussed.

Thrombospondin 1 and its mimetic peptide ABT-510 decrease angiogenesis and inflammation in a murine model of inflammatory bowel disease.

OBJECTIVE: Vascular abnormalities and expression of proangiogenic factors have been repeatedly reported in inflammatory bowel disease (IBD). Thrombospondin 1 (TSP-1) is a protein well known for its antiangiogenic and anti-inflammatory properties. Using the dextran sulfate sodium (DSS) model, the role of TSP-1 in IBD has been investigated in vivo. METHODS: TSP-1-deficient mice (TSP-1-/-) and WT mice were treated with DSS for 7 days. Disease activity indices, myeloperoxidase activity (MPO) and histology were analyzed. Microvascular density (MVD) was quantified using immunohistochemistry (IMH) with CD31 antibody. TGF-beta(1), basic FGF, VEGF, TNF-alpha and MMPs protein levels were evaluated by IMH and enzyme-linked immunoabsorbent assay (ELISA). Mice were treated with ABT-510 (Abbott Laboratories), an antiangiogenic TSP peptide, using miniosmotic pumps for 7 days. RESULTS: TSP-1(-/-) mice had a worse clinical outcome and exhibited severe signs of rectal bleeding compared to the WT controls. The TSP-1-/- mice showed a higher level of crypt damage and deeper lesions. The grade of inflammation and the levels of MPO activity were also significantly higher in colons of TSP-1-/- mice. TSP-1-/- mice displayed higher MVD in focal areas of the colon after only 3 days of DSS treatment. Furthermore, clinical severity of the colitis and angiogenesis was significantly diminished when mice was treated with ABT-510. CONCLUSIONS: These findings directly link TSP-1 as a protective factor in IBD and suggest antiangiogenesis treatment, including compounds such as ABT-510 as an adjuvant therapy for IBD.

Lack of thrombospondin-1 increases angiogenesis in a model of chronic inflammatory bowel disease.

BACKGROUND AND AIMS: Vascular abnormalities and expression of pro-angiogenic factors are observed in inflammatory bowel diseases (IBD). In this study, the role of thrombospondin-1 (TSP-1), an antiangiogenic protein, was analyzed using the dextran sulfate sodium (DSS) model for IBD. MATERIALS AND METHODS: Wild-type (WT) and thrombospondin-1-deficient (TSP-1(-/-)) mice were subjected to four cycles (7 days) of DSS. Basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGFbeta-1), and pro-apoptotic proteins such as Fas and its ligand (FasL) were determined by enzyme-linked immunosorbent assay. Double immunohistochemistry for cluster of differential 31 (CD31) and panendothelial cell antigen-32 antibodies was performed for detecting blood vessels. The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay was also performed for identifying apoptotic cells. Inflammation, dysplasia, microvascular density (MVD), apoptotic indices (AI), protein 53 (p53), and beta-catenin expression were determined. RESULTS: VEGF and bFGF protein levels and MVD were higher in the TSP-1(-/-) mice (p = 0.0312, p = 0.0246, and p = 0.0085, respectively). AI in the endothelial cells (EC) and FasL levels were significantly lower in TSP-1(-/-) compared to WT mice (p = 0.0042 and p = 0.0362, respectively). Dysplasia was detected in 66% of TSP-1(-/-) mice compared to 14% in WT mice. Hscores of ss-catenin and areas overexpressing p53 were higher in TSP-1(-/-) mice (p = 0.0002 and p = 0.0339, respectively). CONCLUSION: TSP-1 may decrease angiogenesis by reducing the levels of pro-angiogenic factors and inducing apoptosis in EC through the Fas or FasL pathway. These findings, along with the increased overexpression of p53 and beta-catenin in TSP-1(-/-) mice, underline its role in carcinogenesis.