The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review.

BACKGROUND: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR). METHODS: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported. RESULTS: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns. CONCLUSIONS: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

CT evaluation of interstitial lung disease related to systemic sclerosis: visual versus automated assessment. A systematic review.

AIM: To identify similarities and differences between visual (VA) and automated assessment (AA) of systemic sclerosis-related interstitial lung disease (SSc-ILD) at chest computed tomography (CT) in terms of clinical applicability. MATERIALS AND METHODS: Medline, Embase, and Web of Science were searched to identify all studies investigating VA and AA for SSc-ILD assessment, from inception to 31 July 2022. Exclusion criteria were manuscripts not in English, absence of full-text, reviews, diseases other than ILD in SSc, CT not analysed with both VA and AA, VA and AA not adopted for the same purpose or not compared, overlap syndromes, SSc-ILD data not extractable, and studies with <10 patients. RESULTS: Ten full-text studies (804 patients) were included. The most adopted VAs were the Warrick or Goh score (four studies each), while densitometry (eight studies) or lung texture analysis (LTA, two studies) were utilised as AAs. The main field of investigation was the correlation with baseline pulmonary function tests (PFT, six studies). Warrick VA showed lower correlations compared to densitometry, while Goh VA demonstrated more heterogeneous results. Compared to LTA, Goh VA obtained lower correlations with lung volumes but similar or stronger coefficients with alveolar diffusibility. CONCLUSIONS: VA and AA may show heterogeneous results comparing their correlations with PFT, probably depending on the specific analysis adopted for each method. More data are needed on VA versus LTA. Comparisons between VA and AA regarding correlation with PFT follow-up and as prognostic elements, or for disease monitoring, are lacking. AAs in progressive fibrosis diagnosis remain to be tested.

Is systemic inflammation a missing link between periodontitis and hypertension? Results from two large population-based surveys.

OBJECTIVE: The primary objective was to investigate the relationship between periodontitis and hypertension in two independent large surveys. The secondary objective was to ascertain whether systemic inflammation had a mediation effect in the association. METHODS: This cross-sectional study analysed representative samples of the US (n = 3460; NHANES 2009/10) and Korean (n = 4539; 2015 KNHANES VI-3) populations. The association between periodontitis (exposure), hypertension (outcome) and inflammatory markers [C-reactive protein (CRP) and white blood cell counts (WBC)] (mediators) was assessed using multivariate linear and logistic regression models and mediation analysis. RESULTS: Participants with periodontitis were more likely to have hypertension (NHANES: OR = 1.3, 95% CI: 1.0-1.6, P = 0.025; KNHANES: OR = 1.2, 95% CI: 1.0-1.4, P = 0.041) and actual systolic blood pressure ≥ 140 mmHg (NHANES: OR = 1.6, 95% CI: 1.1-2.3, P < 0.001; KNHANES: OR = 1.3, 95% CI :1.0-1.6, P < 0.031) than those without the disease. These associations were independent of age, gender, BMI, education level, smoking, alcohol consumption, creatinine, physical activity, presence of other comorbidities and confirmed in participants not taking antihypertensive medications. Diagnosis of periodontitis was directly associated with WBC (in both surveys: NHANES: ß ± SE = 0.3 ± 0.1, P < 0.004; KNHANES: ß ± SE = 0.3 ± 0.1, P < 0.001) and with CRP levels (in one survey: NHANES: ß ± SE = 0.1 ± 0.03, P < 0.007; KNHANES: ß ± SE = 0.1 ± 0.04, P > 0.213). Mediation analyses confirmed that CRP acted as a mediator in the association between periodontitis and hypertension in both populations (mediated effect: NHANES: ß ± SE = 0.010 ± 0.003, P < 0.001; KNHANES: ß ± SE = 0.003 ± 0.001, P = 0.015). WBC acted as a mediator in the KNHANES (mediated effect: ß ± SE = 0.004 ± 0.001, P = 0.004) whilst in the NHANES, its effect was dependent of CRP inclusion in the model (mediated effect WBC + CRP: ß ± SE = 0.002 ± 0.001, P = 0.001). CONCLUSIONS: These findings suggest that periodontitis is closely linked to hypertension and systemic inflammation is, in part, a mediator of this association.

Celocentesis for early prenatal diagnosis of hemoglobinopathy.

OBJECTIVE: Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis. METHODS: In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of ß-thalassemia or sickle cell disease trait. We assessed procedure-related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow-up. RESULTS: First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9-9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild-to-moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out < 10 weeks' gestation. Seventh, in 97.1% (298/307) of the continuing pregnancies there was live birth, in seven (2.3%) there was miscarriage and in two (0.7%) there was loss to follow-up. Eighth, fetal abnormalities were diagnosed in three (1%) cases, including unilateral transverse amputation of the forearm, unilateral moderate hydronephrosis and small-bowel duplication. All neonates were examined by a pediatrician and were found to be phenotypically normal, except for the three cases with a prenatally diagnosed defect. CONCLUSIONS: Celocentesis can be used for early prenatal diagnosis of genetic abnormalities, and the procedure-related risk of pregnancy complications appears to be low. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Chemical composition and morphology study of bovine enamel submitted to different sterilization methods.

OBJECTIVES: The morphology and chemical composition of enamel submitted to different sterilization methods was studied. METHODS: X-ray photoelectron spectroscopy (XPS), field emission gun scanning electron microscopy (FEG-SEM), and energy-dispersive X-ray spectroscopy (EDS) were performed to evaluate 50 bovine enamel specimens sterilized using four methods: microwaving (MI), gamma irradiation (GI), ethylene oxide (EO), and steam autoclave (SA). Non-sterilized specimens were used as control. RESULTS: XPS indicated that the concentration of P (phosphorus), CO3 (carbonate), and CO3/P was not changed in all groups. GI produced no significant change on elemental composition. SA produced the major decrease in calcium (Ca), Ca/P ratio, and increase in N (nitrogen). MI was found to decrease Ca, Ca/P ratio and O (oxygen), and increase in C (carbon) and N. EO produced decrease in Ca and O with increased C concentration. FEG-SEM revealed surface and in-depth morphological changes on SA specimens. Minor surface alterations were observed for EO and for MI groups, and no alteration was observed on GI group. EDS indicated no difference on elemental composition of enamel bulk among groups. CONCLUSIONS: SA produced mineral loss and morphological alterations on surface and in depth. MI and EO sterilization caused mineral loss showing only slight alteration on enamel surface. GI sterilization preserves the morphological characteristics of enamel. The sterilization methods could be classified from lower to high damage as GI < MI < EO < SA. CLINICAL RELEVANCE: This is a comprehensive comparative study where different methods for enamel sterilization were investigated in terms of chemical changes. The results presented here may help researchers to choose the most appropriate method for their research setting and purpose.

One year in review 2015: spondyloarthritis.

Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. Recently, novel insights into the epidemiology, pathogenesis and treatment of these diseases have been provided. Herewith, we provide an overview of the most significant literature contributions published over the year.

Monitoring a CuO gas sensor at work: an advanced in situ X-ray absorption spectroscopy study.

X-ray absorption near edge structure (XANES) and electrical measurements were used to elucidate the local structure and electronic changes of copper(II) oxide (CuO) nanostructures under working conditions. For this purpose, a sample holder layout was developed enabling the simultaneous analysis of the spectroscopic and electrical properties of the sensor material under identical operating conditions. The influence of different carrier gases (e.g., air and N2) on the CuO nanostructures behavior under reducing conditions (H2 gas) was studied to analyze how a particular gas atmosphere can modify the oxidation state of the sensor material in real time.

Breast-conservative surgery with and without radiotherapy in patients aged 55-75 years with early-stage breast cancer: a prospective, randomized, multicenter trial analysis after 108 months of median follow-up.

OBJECTIVES: Breast-conserving therapy (BCT), including postoperative whole breast irradiation (WBI), is generally accepted as the treatment of choice for most patients with early-stage breast cancer. The question whether WBI is mandatory in all patients remains one of the most controversial issues in BCT. To answer this question, a randomized, prospective, multicentre study was launched in January 2001. Primary endpoints of the study were to assess the cumulative incidence of in-breast-recurrences (IBR) and overall survival (OAS) after conservative surgery (BCS) with or without WBI. METHODS: From January 2001 until December 2005, 749 patients with unifocal infiltrating breast cancer up to 25 mm, 0-3 positive axillary lymph nodes, no extensive intraductal component or lymphvascular invasion from 11 centres in Italy, were randomly assigned to BCS+WBI (arm 1:373 patients) or BCS alone (arm 2:376 patients). Treatment arms were well balanced in terms of baseline characteristics. Systemic adjuvant therapy was administered according to the institutional policies. Kaplan-Meier method was used for survival analysis and log-rank test to evaluate the difference between the two arms. RESULTS (Last analysis 31.12.2012): After median follow-up of 108 months, 12 (3.4%) IBR were observed in arm 1 and 16 (4.4%) in arm 2. OAS was 81.4% in arm 1 and 83.7% in arm 2. There was no statistically significant difference regarding IBR and death in the two treatment groups. CONCLUSIONS: These data are promising and suggest that WBI after BCS can be omitted in selected patients with early stage breast cancer without exposing them to an increased risk of local recurrence and death. Longer follow-up is needed to further consolidate these results.

Controlled synthesis of layered Sn3O4 nanobelts by carbothermal reduction method and their gas sensor properties.

This paper reports both the controlled synthesis of Sn3O4 nanobelts by carbothermal reduction method and the gas sensor properties of these nanostructures. The synthesized material was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy and gas sensor measurements. The results showed that the Sn3O4 nanobelts grow in a layered way and the careful control of experimental parameters is fundamental for stabilization of the correct phase. From the gas sensor measurements using oxygen as analyte gas, it was observed that the Sn3O4 nanobelts exhibit n-type behavior and both the sensitivity and the response time are dependent on the oxygen concentration. A model based on molecules adsorption was proposed to illustrate the mechanism of gas detection of these nanostructures. In summary, these results indicate that Sn3O4 nanobelts synthesized by carbothermal reduction method are promising to be applied as gas sensors.

Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for patients with locally advanced pancreatic carcinoma, and can be combined with radiochemotherapy and intra-arterial plus systemic chemotherapy. METHODS: This observational study compared two groups of patients with locally advanced pancreatic carcinoma treated with either primary RFA (group 1) or RFA following any other primary treatment (group 2). RESULTS: Between February 2007 and May 2010, 107 consecutive patients were treated with RFA. There were 47 patients in group 1 and 60 in group 2. Median overall survival was 25·6 months. Median overall survival was significantly shorter in group 1 than in group 2 (14·7 versus 25·6 months; P = 0·004) Patients treated with RFA, radiochemotherapy and intra-arterial plus systemic chemotherapy (triple-approach strategy) had a median overall survival of 34·0 months. CONCLUSION: RFA after alternative primary treatment was associated with prolonged survival. This was further extended by use of a triple-approach strategy in selected patients. Further evaluation of this approach seems warranted.

A round robin exercise in archaeometry: analysis of a blind sample reproducing a seventeenth century pharmaceutical ointment.

Chemical analysis of ancient residues of pharmaceutical or cosmetic preparations such as balms or ointments is made problematic by the high complexity of these mixtures, composed of organic and inorganic materials. Consequently, a multi-analytical approach and special caution in the interpretation of the results are necessary. In order to contribute to the improvement of analytical strategies for the characterization of complex residues and to reconstruct ancient medical practices, a replica of a pharmaceutical formulation of the seventeenth century was prepared in the laboratory according to a historically documented recipe. In a round robin exercise, a portion of the preparation was analysed as a blind sample by 11 laboratories using various analytical techniques. These included spectroscopic, chromatographic and mass spectrometric methods. None of the laboratories was able to completely reconstruct the complex formulation, but each of them gave partial positive results. The round robin exercise has demonstrated that the application of a multi-analytical approach can permit a complete and reliable reconstruction of the composition. Finally, on the basis of the results, an analytical protocol for the study of residues of ancient medical and pharmaceutical preparations has been outlined.

[Syncope and work: role of the occupational physician and global risk stratification]. / Sincope e rischio lavorativo: ruolo del medico del lavoro e stratificazione globale del rischio.

Safety risk for subjects suffering from syncope while working has not been as yet addressed by occupational medicine. The present study was aimed at evaluating a new developed methodology for job tasks risk stratification in patients with syncope. During a work-shop on syncope and occupational risk, 149 occupational physicians (OP) with about 10 years of clinical experience were asked to fulfil a Visual Analogue Scale (VAS) concerning the doctor's estimated potential damage (D) to the worker and the probability of a damage to occur (P) should syncope take place during the job task. Five job tasks characterized by different risk for safety (1, driving; 2, toxic products handling; 3, job performed closed to hot surfaces o free flames; 4, surgical activity; 5, office job) were identified. OP correctly stratified the risk associated to the different job tasks in patients with syncope. Unexpectedly, task #3 was given a risk similar to that obtained in drivers. This might be of paramount clinical and social importance when patients with syncope have to return to their job tasks.

[Syncope and occupational risk survey: the role of continuing education and multidisciplinary approach]. / Indagine conoscitiva sulla percezione del problema sincope in relazione al rischio lavorativo nella pratica clinica: ruolo della formazione e dell'approccio multidisciplinare.

Syncope is a common disorder characterized most of the times by a positive clinical outcome. However, it may turn to a life threatening event even for working colleagues and third party when occurring during an high risk job. We have recently found that, out of 670 patients admitted to the Emergency Department (ED) for syncope, about 50% were potential workers, being their age between 18 and 65 years. Also, we found that in this group of patients syncope recurrence was as high as 11% at 6 months. It is unknown how physicians address the problem of the occupational risk in patients suffering from syncope and how occupational aspects are taken into account in the clinical judgment before work readmission. One hundred eighty five doctors (149 occupational physicians, OP), participating in a work-shop on syncope, were asked to fulfill a questionnaire about their clinical experience and their attention to the occupational aspects in patients after syncope. Despite long lasting clinical experience, 41% of OP did not scrutinize syncope as a relevant symptom in their daily activity. 65% of the other specialists were used to address the occupational risk aspects in their syncope patients. A multidisciplinary approach involving continuing education on safety at work might reduce work accidents due to syncope relapse and promote a safe and suitable re-employment of patients with syncope. scrutinize syncope as a relevant symptom in their daily activity. 65% of the other specialists were used to address the occupational risk aspects in their syncope patients. A multidisciplinary approach involving continuing education on safety at work might reduce work accidents due to syncope relapse and promote a safe and suitable re-employment of patients with syncope.

Enhanced effects of PPARgamma ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells.

Experimental data from in vitro and in vivo models indicate that peroxisome proliferator-activated receptor (PPAR) ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Thiazolidinediones such as ciglitazone (CGZ) constitute the most well-known synthetic ligands for PPARgamma. We previously reported a remarkable antitumor effect of the retinoid 6-OH-11-O-hydroxyphenantrene (IIF), synthetic retinoid X receptors (RXRs) agonist, on many cancer cell lines. Since PPARs bind to DNA as heterodimers with RXRs, in this study we investigated if IIF potentiates the antitumoral properties of the PPARgamma ligand CGZ in glioblastoma U87MG and melanoma G361 cells. Our results show that either IIF or CGZ inhibited cell growth and tissue invasion ability, but these properties were enhanced by using IIF and CGZ in combined treatment. Since matrix metalloproteinases (MMPs) play a major role in tumor cell invasion, we analyzed the effect of IIF and CGZ on MMP2 and MMP9 activity and expression. The addition of IIF to CGZ resulted in a decrease of MMP2 and MMP9 expression and activity, higher than when each agent was used alone. Furthermore, treatment with IIF and/or CGZ enhanced PPARgamma expression but both agents in combined treatment caused the maximum efficiency. Finally, we demonstrated that IIF can potentiate PPARgamma trascriptional activity induced by CGZ, by evaluation of peroxisome proliferator-responsive element transactivation. In conclusion, these findings suggest that the RXR selective retinoid IIF, in combination with the PPARgamma ligand CGZ, may provide a therapeutic advantage in cancer treatment.

A985G mutation incidence in the medium-chain acyl-CoA dehydrogenase (MCAD) gene in Brazil.

In view of the serious consequences of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and the absence of information about its incidence in the Brazilian population, we examined the frequency of the A985G mutation in the MCAD gene. A retrospective analysis was made of data on 1722 individuals (844 females) genotyped for the A985G mutation in the MCAD gene, using genomic DNA extracted from peripheral blood leukocytes and genotyping with PCR-RFLP; 0.41% of these individuals were heterozygous for the A985G mutation. The mutant homozygous genotype was not found. The 985G mutant and 985A normal alleles had allelic frequencies of 0.0020 and 0.9980, respectively. Given the A985G allele frequency, genotyping would be recommended in cases of family history of MCAD deficiency and sudden infant death syndrome, and when there is suspicion of medium-chain fatty acid metabolic alterations; genetic counseling should be offered in cases involving 985GG and A985G individuals and consanguineous marriages.

Growth inhibition and proapoptotic activity induction by IIF and valproic acid on RA-resistant leukemia cells.

All-trans retinoic acid (RA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). Nevertheless, most of these patients develop RA resistance and relapse. In an attemp to mimic clinical conditions for the treatment of leukemia, a stably RA-resistant subclone of the human promyelocytic leukemia cell line HL60 (HL60-R) was developed to study the antiproliferative and proapoptotic effect of the retinoid IIF (6-OH-11-O-hydroxyphenantrene) in comparison with RA. Moreover whether the inhibitor of histone deacetylase (HDAC) activity, valproic acid (VPA), could enhance sensitivity to retinoids in HL60-R cells was evaluated. Finally, the effect of IIF on the expression of multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (P-gp) was evaluated. It was found that IIF strongly suppressed cell proliferation (as measured by growth curves) and induced apoptosis (as measured by DNA fragmentation and Annexin V detection assays), while RA was practically ineffective. The addition of VPA to IIF accentuated the antiproliferative effect of IIF alone and increased apoptosis; the combination of VPA with RA allowed growth arrest. Moreover IIF caused a reduction of transmembrane transporter expression, particularly of P-gp, as shown by Western blotting. Our results suggest that IIF may be useful in controlling the proliferation of RA-resistant leukemia cells, especially in combination with an HDAC inhibitor, such as VPA.

Time-resolved optical spectroscopy of wood.

We have proposed and experimentally demonstrated that picosecond time-resolved optical spectroscopy in the visible/near-infrared (NIR) region (700-1040 nm) is a useful technique for noninvasive characterization of wood. This technique has been demonstrated on both softwood and hardwood samples treated in different ways simulating the aging process suffered by waterlogged woods. In all the cases, alterations of absorption and scattering spectra were observed, revealing changes of chemical and structural composition.

Inhibitory effects of retinoic acid and IIF on growth, migration and invasiveness in the U87MG human glioblastoma cell line.

Glioblastomas, the most malignant and prevalent brain tumors which remain incurable, are characterized by both extensive proliferation and invasive growth. We previously reported a remarkable antitumoral effect of the retinoid 6-OH-11-O-hydroxyphenantrene (IIF) on neuroblastoma, leukemia and colon carcinoma cells. In this study we examined the effect of IIF on proliferation, apoptosis and cell invasion in the human glioblastoma cell line U87MG, in comparison with all-trans-retinoic acid (RA). Our results showed that both retinoids induced cell growth inhibition and apoptosis in a dose- and time-dependent manner. We also demonstrated that the invasive ability of glioblastoma cells decreased after treatment with IIF or RA. Since cell invasion involves a complex system of tightly regulated proteases, matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of MMPs (TIMPs), we analysed the effect of IIF on MMP and TIMP expression in comparison with RA. Treatment with both retinoids resulted in a marked decrease of MMP2 and MMP9 expression and of lytic activity of MMP2. In addition, exposure to IIF led to enhanced expression of TIMP2. Collectively, our results demonstrated the effectiveness of both IIF and RA in inhibiting proliferation, cell migration, and the invasive potential of glioblastoma U87MG cells. Notably, the anticancer activity of IIF, on the whole, was more pronounced than that of RA. Therefore, these findings, besides providing further evidence that IIF may be a powerful tool in the development of cancer treatments, suggest that IIF may have therapeutic potential against the invasiveness of brain tumors.