The incidence of brain trauma caused by road injuries: Results from the Global Burden of Disease Study 2019.

BACKGROUND: Road collisions are a significant source of traumatic brain injury (TBI). We aimed to determine the pattern of road injury related TBI (RI-TBI) incidence, as well as its temporal trends. METHODS: We collected detailed information on RI-TBI between 1990 and 2019, derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPCs) of RI-TBI age standardized incidence rate (ASIR), by sex, region, and cause of road injuries, were assessed to quantify the temporal trends of RI-TBI burden. RESULTS: Globally, incident cases of RI-TBI increased 68.1% from 6,900,000 in 1990 to 11,600,000 in 2019. The overall ASIR increased by an average of 0.43% (95% CI 0.30%-0.56%) per year during this period. The ASIR of RI-TBI due to cyclist, motorcyclist and other road injuries increased between 1990 and 2019; the corresponding EAPCs were 0.56 (95% CI 0.37-0.75), 1.60 (95% CI 1.35-1.86), and 0.75 (95% CI 0.59-0.91), respectively. In contrast, the ASIR of RI-TBI due to motor vehicle and pedestrian decreased with an EAPC of -0.12 and -0.14 respectively. The changing pattern for RI-TBI was heterogeneous across countries and regions. The most pronounced increases were observed in Mexico (EAPC = 3.74), followed by China (EAPC = 2.45) and Lesotho (EAPC = 1.91). CONCLUSIONS: RI-TBI remains a major public health concern worldwide, although road safety legislations have contributed to the decreasing incidence in some countries. We found an unfavorable trend in several countries with a relatively low socio-demographic index, suggesting that much more targeted and specific approaches should be adopted in these areas to forestall the increase in RI-TBI.

A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways.

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes.

The B-box transcription factor IbBBX29 regulates leaf development and flavonoid biosynthesis in sweet potato.

Plant flavonoids are valuable natural antioxidants. Sweet potato (Ipomoea batatas) leaves are rich in flavonoids, regenerate rapidly, and can adapt to harsh environments, making them an ideal material for flavonoid biofortification. Here, we demonstrate that the B-box (BBX) family transcription factor IbBBX29 regulates the flavonoid contents and development of sweet potato leaves. IbBBX29 was highly expressed in sweet potato leaves and significantly induced by auxin (IAA). Overexpression of IbBBX29 contributed to a 21.37%-70.94% increase in leaf biomass, a 12.08%-21.85% increase in IAA levels, and a 31.33%-63.03% increase in flavonoid accumulation in sweet potato, whereas silencing this gene produced opposite effects. Heterologous expression of IbBBX29 in Arabidopsis (Arabidopsis thaliana) led to a dwarfed phenotype, along with enhanced IAA and flavonoid accumulation. RNA-seq analysis revealed that IbBBX29 modulates the expression of genes involved in the IAA signaling and flavonoid biosynthesis pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay indicated that IbBBX29 targets key genes of IAA signaling and flavonoid biosynthesis to activate their expression by binding to specific T/G-boxes in their promoters, especially those adjacent to the transcription start site. Moreover, IbBBX29 physically interacted with developmental and phenylpropanoid biosynthesis-related proteins, such as AGAMOUS-LIKE 21 protein IbAGL21 and MYB308-like protein IbMYB308L. Finally, overexpressing IbBBX29 also increased flavonoid contents in sweet potato storage roots. These findings indicate that IbBBX29 plays a pivotal role in regulating IAA-mediated leaf development and flavonoid biosynthesis in sweet potato and Arabidopsis, providing a candidate gene for flavonoid biofortification in plants.

Antimicrobial mexicanolide limonoids from the seeds of Khaya senegalensis.

Three new mexicanolide limonoids were obtained from the 90% ethanol extract of the seeds of Khaya senegalensis. Their structures were elucidated as senegalenines A-C (1-3) by analysing their 1D/2D NMR and MS spectroscopic analysis. In addition, the isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. Consequently, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 40 µg/ml.

PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis

Abstract Background: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result: When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

Clinical effects of two combinations of olfactory agents on olfactory dysfunction after upper respiratory tract infection during olfactory training.

OBJECTIVE: To compare two combinations of olfactory agents for olfactory training therapy of olfactory dysfunction after upper respiratory tract infection (URTI) and investigate the influencing factors on clinical effects. METHODS: 125 patients with olfactory dysfunction were randomly divided into two groups: test and control. During the olfactory training, four odors were used in both groups. The olfactory training lasted for 24 weeks. Then, participants were tested using Sniffin' Sticks and threshold-discrimination-identification (TDI) composite scoring before treatment and at 1, 3, and 6 months after treatment. The TDI scores were compared at different time points between the groups and within them, and influence factors were analyzed. RESULTS: There was no significant difference in TDI scores between both groups. Furthermore, TDI scores did not significantly change after one month of treatment in either of the groups. After 3 and 6 months of treatment, TDI scores both significantly increased, and the odor discrimination and identification abilities significantly strengthened in both groups; however, the odor thresholds did not improve. The course of the disease was a significant influencing factor on the therapeutic effect of olfactory training for both groups. CONCLUSION: The combination of essential balm, vinegar, alcohol, and rose perfume for olfactory training, which are scents commonly found in daily life, can effectively cure URTI-induced olfactory dysfunction, and significantly improve the odor discrimination and identification abilities. Furthermore, prolonging the treatment time can help with the recovery of olfactory functions, and earlier olfactory training can improve the therapeutic effect.

Co-transfection of hepatocyte growth factor and truncated TGF-ß type II receptor inhibit scar formation.

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-ß plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-ß type II receptor (t-TGF-ßRII) is unable to continue signal transduction but is still capable of binding to TGF-ß, thereby blocking the TGF-ß signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-ßRII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-ßRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-ßRII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-ßRII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.

Co-transfection of hepatocyte growth factor and truncated TGF-ß type II receptor inhibit scar formation

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-β plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-β type II receptor (t-TGF-βRII) is unable to continue signal transduction but is still capable of binding to TGF-β, thereby blocking the TGF-β signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-βRII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-βRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-βRII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-βRII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.

Clinical effects of two combinations of olfactory agents on olfactory dysfunction after upper respiratory tract infection during olfactory training

SUMMARY OBJECTIVE To compare two combinations of olfactory agents for olfactory training therapy of olfactory dysfunction after upper respiratory tract infection (URTI) and investigate the influencing factors on clinical effects. METHODS 125 patients with olfactory dysfunction were randomly divided into two groups: test and control. During the olfactory training, four odors were used in both groups. The olfactory training lasted for 24 weeks. Then, participants were tested using Sniffin' Sticks and threshold-discrimination-identification (TDI) composite scoring before treatment and at 1, 3, and 6 months after treatment. The TDI scores were compared at different time points between the groups and within them, and influence factors were analyzed. RESULTS There was no significant difference in TDI scores between both groups. Furthermore, TDI scores did not significantly change after one month of treatment in either of the groups. After 3 and 6 months of treatment, TDI scores both significantly increased, and the odor discrimination and identification abilities significantly strengthened in both groups; however, the odor thresholds did not improve. The course of the disease was a significant influencing factor on the therapeutic effect of olfactory training for both groups. CONCLUSION The combination of essential balm, vinegar, alcohol, and rose perfume for olfactory training, which are scents commonly found in daily life, can effectively cure URTI-induced olfactory dysfunction, and significantly improve the odor discrimination and identification abilities. Furthermore, prolonging the treatment time can help with the recovery of olfactory functions, and earlier olfactory training can improve the therapeutic effect.

RESUMO OBJETIVO Comparar duas combinações de agentes olfativos para uso em terapia de treinamento olfativo no tratamento de disfunção olfatória após infecção do trato respiratório superior (ITRS) e investigar os fatores que influenciam os efeitos clínicos. METODOLOGIA 125 pacientes com disfunção olfativa foram divididos aleatoriamente em dois grupos: teste e controle. Durante o treinamento olfativo, quatro odores foram utilizados em ambos os grupos. O treinamento olfativo durou 24 semanas. Em seguida, os participantes foram testados usando Sniffin' Sticks e o escore de discriminação, limiar e identificação (TDI) antes do tratamento e 1, 3 e 6 meses após o ele. Os escores de TDI foram comparados em momentos diferentes, entre os grupos e dentro deles, e os fatores de influência foram analisados. RESULTADOS Não houve diferença significativa nos escores de TDI entre os dois grupos. Além disso, os escores de TDI não demonstração nenhuma alteração significa após um mês de tratamento em ambos os grupos. Após 3 e 6 meses de tratamento, ambos os escores de TDI aumentaram significativamente, e as habilidades de identificação e discriminação de odores melhoraram significativamente em ambos os grupos; contudo, os limiares de odor não demonstraram melhora. O curso da doença foi um importante fator de influência no efeito terapêutico do treinamento olfativo em ambos os grupos. CONCLUSÃO A combinação de bálsamo essencial, vinagre, álcool, e perfume de rosas no treinamento olfativo, todos aromas comumente encontrados na vida cotidiana, podem efetivamente curar disfunção olfativa induzida por ITRS e melhorar significativamente as habilidades de discriminação e identificação de odores. Além disso, a prolongamento do tempo de tratamento pode ajudar na recuperação das funções olfativas, e o início antecipado do treinamento olfativo pode melhorar o efeito terapêutico.

Ly6C+ Inflammatory Monocyte Differentiation Partially Mediates Hyperhomocysteinemia-Induced Vascular Dysfunction in Type 2 Diabetic db/db Mice.

OBJECTIVE: Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown. Approach and Results: Here, we demonstrate that hyperhomocysteinemia was induced by a high methionine diet in control mice (homocysteine 129 µmol/L), which was further worsened in T2DM db/db mice (homocysteine 180 µmol/L) with aggravated insulin intolerance. Hyperhomocysteinemia potentiated T2DM-induced mononuclear cell, monocyte, inflammatory monocyte (CD11b+Ly6C+), and M1 macrophage differentiation in periphery and aorta, which were rescued by folic acid-based homocysteine-lowering therapy. Moreover, hyperhomocysteinemia exacerbated T2DM-impaired endothelial-dependent aortic relaxation to acetylcholine. Finally, transfusion of bone marrow cells depleted for Ly6C by Ly6c shRNA transduction improved insulin intolerance and endothelial-dependent aortic relaxation in hyperhomocysteinemia+T2DM mice. CONCLUSIONS: Hyperhomocysteinemia potentiated systemic and vessel wall inflammation and vascular dysfunction partially via inflammatory monocyte subset induction in T2DM. Inflammatory monocyte may be a novel therapeutic target for insulin resistance, inflammation, and cardiovascular complications in hyperhomocysteinemia+T2DM.

Combined application of arbuscular mycorrhizal fungi and steel slag improves plant growth and reduces Cd, Pb accumulation in Zea mays.

Little attention has been paid to the combined use of arbuscular mycorrhizal fungus (AMF) and steel slag (SS) for ameliorating heavy metal polluted soils. A greenhouse pot experiment was conducted to study the effects of SS and AMF-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on plant growth and Cd, Pb uptake by maize grown in soils added with 5 mg Cd kg-1 and 300 mg Pb kg-1 soil. The combined usage of AMF and SS (AMF + SS) promoted maize growth, and Gv + SS had the most obvious effect. Meanwhile, single SS addition and AMF + SS decreased Cd, Pb concentrations in maize, and the greater reductions were found in combined utilization, and the lowest Cd, Pb concentrations of maize appeared in Gv + SS. Single SS amendment and AMF + SS enhanced soil pH and decreased soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd, Pb concentrations. Furthermore, alone and combined usage of AMF and SS increased contents of soil total glomalin. Our research indicated a synergistic effect between AMF and SS on enhancing plant growth and reducing Cd, Pb accumulation in maize, and Gv + SS exerted the most pronounced effect. This work suggests that AMF inoculation in combination with SS addition may be a potential method for not only phytostabilization of Pb-Cd-contaminated soil but maize safety production.

Intravenous misplacement of nephrostomy tube following percutaneous nephrolithotomy: Three new cases and review of seven cases in the literature.

PURPOSE: We investigated the characteristics and management of patients with intravenous misplacement of a nephrostomy tube. MATERIALS AND METHODS: Between July 2007 and July 2013, 4148 patients with urolithiasis underwent percutaneous nephrolithotomy (PCNL) in our hospital. Intravenous misplacement of a nephrostomy tube occurred in two of these patients. Another patient with intravenous misplacement of a nephrostomy tube, who underwent PCNL in another hospital, was transferred to our hospital. The data of the three patients were retrospectively analyzed. RESULTS: The incidence of intravenous misplacement of a nephrostomy tube following PCNL was 0.5% (2/4148) at our hospital. A solitary kidney was present in one of the three patients. The tip of tube was located into the inferior vena cava (IVC) in two patients and into the renal vein in one patient. All three patients were successfully managed with strict bed rest, intravenous antibiotics and one-step (one patient) or two-step (two patients) tube withdrawal under close monitoring. None of the patients underwent antithrombotic therapy. The original operations were performed successfully under close observation in two patients and changed to another operation in one patient. All patients were discharged uneventfully. CONCLUSIONS: The incidence of intravenous misplacement of a nephrostomy tube following PCNL is 0.5% at our hospital. Intravenous nephrostomy tube misplacement is an uncommon complication of PCNL. A solitary kidney may render patients susceptible to this complication. Most patients may be managed conservatively with strict bed rest, intravenous antibiotics and one-step or two-step tube withdrawal under close monitoring.

Graft pathology at the time of harvest: impact on long-term survival / Patologia do enxerto no momento da coleta: impacto na sobrevida a longo prazo

Objective: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. Methods: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. Results: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients’ long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. Conclusion: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts. .

Objetivo: Este estudo tem como objetivo apresentar a patologia do enxerto no momento da coleta e do impacto na sobrevida a longo prazo. Métodos: Os remanescentes de pontes de safena de 66 pacientes consecutivos com doença arterial coronária que receberam uma cirurgia de revascularização coronariana foram investigados patologicamente, e os fatores de risco preditivos e a sobrevivência foram analisados. Resultados: Alterações degenerativas da artéria medial, com ou sem proliferação da íntima estavam presentes em 36,8%, 37,8% e 35,6% de pontes da artéria torácica interna esquerda (ATIE), artéria radial e veia safena. Houve dois (3,0%) óbitos hospitalares e nove (14,1%) óbitos tardios. A regressão logística multinomial revelou que alterações patológicas na ATIE, dislipidemia, história de angioplastia/stent implantação coronariana transluminal percutânea e Y-enxerto foram significativos fatores de risco preditivos que influenciam negativamente a sobrevivência a longo prazo dos pacientes. Análise de sobrevida de Kaplan- Meier revelou que a sobrevivência a longo prazo de pacientes com alterações patológicas da ATIE foi significativamente reduzida em comparação com aqueles sem (74,1% vs. 91,4%, P=0,002), considerando que não foram observadas diferenças na sobrevivência de longo prazo entre pacientes com e sem alterações patológicas dos enxertos da artéria radial ou de veia safena. Conclusão: As alterações patológicas podem se desenvolver na revascularização no momento da coleta. As modificações ultraestruturais sutis e as expressões de reguladores do tônus vascular podem ser responsáveis pela patência tardia do enxerto. As alterações patológicas da ATIE no momento da coleta, em vez do enxerto da artéria radial ou da veia safena, podem afetar significativamente a sobrevida de longo prazo. Manobra não traumática da ATIE na coleta, bom controle da dislipidemia e para evitar uso de enxertos compostos pode ser útil na manutenção da arquitetura dos enxertos. .

Intravenous misplacement of nephrostomy tube following percutaneous nephrolithotomy: Three new cases and review of seven cases in the literature

Purpose We investigated the characteristics and management of patients with intravenous misplacement of a nephrostomy tube. Materials and Methods Between July 2007 and July 2013, 4148 patients with urolithiasis underwent percutaneous nephrolithotomy (PCNL) in our hospital. Intravenous misplacement of a nephrostomy tube occurred in two of these patients. Another patient with intravenous misplacement of a nephrostomy tube, who underwent PCNL in another hospital, was transferred to our hospital. The data of the three patients were retrospectively analyzed. Results The incidence of intravenous misplacement of a nephrostomy tube following PCNL was 0.5% (2/4148) at our hospital. A solitary kidney was present in one of the three patients. The tip of tube was located into the inferior vena cava (IVC) in two patients and into the renal vein in one patient. All three patients were successfully managed with strict bed rest, intravenous antibiotics and one-step (one patient) or two-step (two patients) tube withdrawal under close monitoring. None of the patients underwent antithrombotic therapy. The original operations were performed successfully under close observation in two patients and changed to another operation in one patient. All patients were discharged uneventfully. Conclusions The incidence of intravenous misplacement of a nephrostomy tube following PCNL is 0.5% at our hospital. Intravenous nephrostomy tube misplacement is an uncommon complication of PCNL. A solitary kidney may render patients susceptible to this complication. Most patients may be managed conservatively with strict bed rest, intravenous antibiotics and one-step or two-step tube withdrawal under close monitoring. .

Hyperhomocysteinemia potentiates hyperglycemia-induced inflammatory monocyte differentiation and atherosclerosis.

Hyperhomocysteinemia (HHcy) is associated with increased diabetic cardiovascular diseases. However, the role of HHcy in atherogenesis associated with hyperglycemia (HG) remains unknown. To examine the role and mechanisms by which HHcy accelerates HG-induced atherosclerosis, we established an atherosclerosis-susceptible HHcy and HG mouse model. HHcy was established in mice deficient in cystathionine ß-synthase (Cbs) in which the homocysteine (Hcy) level could be lowered by inducing transgenic human CBS (Tg-hCBS) using Zn supplementation. HG was induced by streptozotocin injection. Atherosclerosis was induced by crossing Tg-hCBS Cbs mice with apolipoprotein E-deficient (ApoE(-/-)) mice and feeding them a high-fat diet for 2 weeks. We demonstrated that HHcy and HG accelerated atherosclerosis and increased lesion monocytes (MCs) and macrophages (MØs) and further increased inflammatory MC and MØ levels in peripheral tissues. Furthermore, Hcy-lowering reversed circulating mononuclear cells, MC, and inflammatory MC and MC-derived MØ levels. In addition, inflammatory MC correlated positively with plasma Hcy levels and negatively with plasma s-adenosylmethionine-to-s-adenosylhomocysteine ratios. Finally, l-Hcy and d-glucose promoted inflammatory MC differentiation in primary mouse splenocytes, which was reversed by adenoviral DNA methyltransferase-1. HHcy and HG, individually and synergistically, accelerated atherosclerosis and inflammatory MC and MØ differentiation, at least in part, via DNA hypomethylation.

Graft pathology at the time of harvest: impact on long-term survival.

OBJECTIVE: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. METHODS: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. RESULTS: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients' long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. CONCLUSION: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts.

Chondrocyte-specific inhibition of ß-catenin signaling leads to dysplasia of the caudal vertebrae in mice.

STUDY DESIGN: To inhibit ß-catenin specifically signaling in chondrocytes Col2-ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected during embryonic and postnatal stages of Col2-ICAT transgenic mice. OBJECTIVE: To determine the role of canonical ß-catenin signaling in caudal vertebral development. SUMMARY OF BACKGROUND DATA: ß-catenin signaling plays a critical role in skeletal development. Col2-ICAT transgenic mice were generated to selectively block ß-catenin signaling by overexpression of the ICAT gene in chondrocytes. METHODS: Tails of E16.5 transgenic embryos and adult Col2-ICAT transgenic mice and their wild-type littermates were collected and analyzed. Skeletal preparation, 3-dimensional micro-computed tomographic and histological analyses were performed to evaluate changes in the structure of caudal vertebrae. Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte proliferation in caudal vertebrae. RESULTS: Skeletal preparation and 3-dimensional micro-computed tomographic analyses revealed bone deformation and angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological studies revealed abnormal bone development and dysplastic caudal vertebrae in Col2-ICAT transgenic mice. Inhibition of ß-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU labeling revealed a decreased chondrocyte proliferation in both cartilageous templates of transgenic embryos and the growth plate of adult Col2-ICAT transgenic mice. CONCLUSION: Wnt/ß-catenin signaling plays an important role in vertebral development. Inhibition of ß-catenin signaling in chondrocytes results in caudal vertebra deformity in mice, which may occur as early as in the stage of sclerotome formation. LEVEL OF EVIDENCE: N/A.

Expresión de p73 en relación con factores clínicos, patológicos y biológicos en tumores colorrectales / p73 expression in relation to factors clinical, pathological and biological colorectal tumors

Background: The p73 can inhibit cell growth and induce apoptosis, indicating that p73 is a p53-like tumour suppressor. However, studies have shown that either loss of heterozygosity (LOH) or mutation of p73 is not a common genetic event in tumour development. Material, methods and results: Western blotting was used for confirming the specificity of the p73 antibody. p73 expression was evaluated by using immunohistochemistry in 58 normal colorectal mucosa samples, 221 primary cancers and 58 lymph node metastases. PCR-restriction fragment length polymorphism was used for determining LOH in 52 primary tumours. The results showed that the frequency and the intensity of p73 immunostaining were markedly increased from normal tissue to primary tumour and to metastasis (p < 0.05). p73 overexpression predicted a worse prognosis outcome (p = 0.03), even after adjustment for patient's sex, age, tumour stage, growth pattern, and differentiation (p = 0.01). There was no LOH in primary tumours. Conclusion: The expression of p73 protein was up-regulated during the development from the normal mucosa to primary and to metastatic tumours. Furthermore, the overexpression of p73 was a predictor of poor prognosis in colorectal cancer patients. However, LOH of the gene was not an important factor in colorectal cancer development.

Antecedentes: La p73 puede inhibir el crecimiento celular e inducir apoptosis, lo cual indica que es un supresor de tumores, del tipo de p53. Sin embargo, los estudios demostraron que la pérdida de la heterocigotia (loss of heterozygosity, LOH) o la mutación de p73 no es un evento genético común en el desarrollo tumoral. Material, métodos y resultados: Para confirmar la especificidad del anticuerpo p73 se utilizó inmunotransferencia. Mediante inmunohistoquímica se evaluó la expresión de p73 en 58 muestras de mucosa colorrectal normal, en 221 muestras de cánceres primarios y en 58 muestras de ganglios linfáticos metastásicos. Se usó reacción en cadena de polimerasa y estudio de longitud de fragmentos de restricción para determinar LOH en 52 tumores primarios. Los resultados mostraron que la frecuencia y la intensidad de fijación de p73 aumentaron significativamente desde la evolución de tejido normal a tumores primarios y a metástasis (p < 0.05). La expresión exagerada de p73 predijo un pronóstico más desfavorable (p = 0.03) aun después del ajuste por sexo, edad, estadio tumoral, patrón de crecimiento y diferenciación (p = 0.01). No hubo LOH en tumores primarios. Conclusión: La expresión de la proteína p73 estuvo aumentada durante el pasaje de mucosa normal a tumores primarios y a metástasis. Más aun, la mayor expresión de p73 fue un factor predictivo de pronóstico desfavorable en pacientes con cáncer colorrectal. Sin embargo, la LOH del gen no fue un factor importante en la aparición de cáncer colorrectal.