Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study.

INTRODUCTION: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. METHODS: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). RESULTS: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0-73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8-82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. CONCLUSIONS: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2014-003860-19.

Country-specific net-zero strategies of the pulp and paper industry.

The pulp and paper industry is an important contributor to global greenhouse gas emissions1,2. Country-specific strategies are essential for the industry to achieve net-zero emissions by 2050, given its vast heterogeneities across countries3,4. Here we develop a comprehensive bottom-up assessment of net greenhouse gas emissions of the domestic paper-related sectors for 30 major countries from 1961 to 2019-about 3.2% of global anthropogenic greenhouse gas emissions from the same period5-and explore mitigation strategies through 2,160 scenarios covering key factors. Our results show substantial differences across countries in terms of historical emissions evolution trends and structure. All countries can achieve net-zero emissions for their pulp and paper industry by 2050, with a single measure for most developed countries and several measures for most developing countries. Except for energy-efficiency improvement and energy-system decarbonization, tropical developing countries with abundant forest resources should give priority to sustainable forest management, whereas other developing countries should pay more attention to enhancing methane capture rate and reducing recycling. These insights are crucial for developing net-zero strategies tailored to each country and achieving net-zero emissions by 2050 for the pulp and paper industry.

Lipid compartments and lipid metabolism as therapeutic targets against coronavirus.

Lipids perform a series of cellular functions, establishing cell and organelles' boundaries, organizing signaling platforms, and creating compartments where specific reactions occur. Moreover, lipids store energy and act as secondary messengers whose distribution is tightly regulated. Disruption of lipid metabolism is associated with many diseases, including those caused by viruses. In this scenario, lipids can favor virus replication and are not solely used as pathogens' energy source. In contrast, cells can counteract viruses using lipids as weapons. In this review, we discuss the available data on how coronaviruses profit from cellular lipid compartments and why targeting lipid metabolism may be a powerful strategy to fight these cellular parasites. We also provide a formidable collection of data on the pharmacological approaches targeting lipid metabolism to impair and treat coronavirus infection.

Lipid droplets in Zika neuroinfection: Potential targets for intervention?

Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence in various cell types in the brain and for their suggested involvement in neurodevelopment and neurodegenerative diseases. Only recently have the roles of LD in neuroinfections begun to be explored. Recent findings reveal that lipid remodelling and increased LD biogenesis play important roles for Zika virus (ZIKV) replication and pathogenesis in neural cells. Moreover, blocking LD formation by targeting DGAT-1 in vivo inhibited virus replication and inflammation in the brain. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development. Here, we review the progress in understanding LD functions in the central nervous system in the context of the host response to Zika infection.

Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells.

Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development.

Lipid droplets in Zika neuroinfection: Potential targets for intervention?

Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence in various cell types in the brain and for their suggested involvement in neurodevelopment and neurodegenerative diseases. Only recently have the roles of LD in neuroinfections begun to be explored. Recent findings reveal that lipid remodelling and increased LD biogenesis play important roles for Zika virus (ZIKV) replication and pathogenesis in neural cells. Moreover, blocking LD formation by targeting DGAT-1 in vivo inhibited virus replication and inflammation in the brain. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development. Here, we review the progress in understanding LD functions in the central nervous system in the context of the host response to Zika infection.

The Endolysosomal System: The Acid Test for SARS-CoV-2.

This review aims to describe and discuss the different functions of the endolysosomal system, from homeostasis to its vital role during viral infections. We will initially describe endolysosomal system's main functions, presenting recent data on how its compartments are essential for host defense to explore later how SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) and other coronaviruses subvert these organelles for their benefit. It is clear that to succeed, pathogens' evolution favored the establishment of ways to avoid, escape, or manipulate lysosomal function. The unavoidable coexistence with such an unfriendly milieu imposed on viruses the establishment of a vast array of strategies to make the most out of the invaded cell's machinery to produce new viruses and maneuvers to escape the host's defense system.

Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts.

Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying statins protection against SARS-CoV-2 remains elusive. Here we reported for the first-time experimental evidence of the protective effects of simvastatin treatment both in vitro and in vivo. We found that treatment with simvastatin significantly reduced the viral replication and lung damage in vivo, delaying SARS-CoV-2-associated physiopathology and mortality in the K18-hACE2-transgenic mice model. Moreover, simvastatin also downregulated the inflammation triggered by SARS-CoV-2 infection in pulmonary tissue and in human neutrophils, peripheral blood monocytes, and lung epithelial Calu-3 cells in vitro, showing its potential to modulate the inflammatory response both at the site of infection and systemically. Additionally, we also observed that simvastatin affected the course of SARS-CoV-2 infection through displacing ACE2 on cell membrane lipid rafts. In conclusion, our results show that simvastatin exhibits early protective effects on SARS-CoV-2 infection by inhibiting virus cell entry and inflammatory cytokine production, through mechanisms at least in part dependent on lipid rafts disruption.

Clinical decision-making in anterior resin composite restorations: a multicenter evaluation.

OBJECTIVE: This study investigated whether a sample of anterior resin composite restorations could be differently evaluated in different centers of evaluation by clinical and lay evaluators. METHODS: Anterior resin composite restorations on high-quality intraoral digital photography were evaluated using FDI criteria (1-5 score) by pairs of clinical and lay evaluators in Brazil (BR), France (FR), Peru (PE), and the United States of America (USA). Scores were allocated as maintenance (1, 2, 3), repair (4) and replacement (5) when comparing clinical evaluators and, as acceptable (1, 2, 3) and unacceptable (4, 5) when comparing clinical vs. lay evaluators and lay vs. lay evaluators. The Chi-square test compared the frequencies of scores among the centers. RESULTS: The frequencies of maintaining, repairing, or replacing anterior resin composite restorations given by clinical evaluators varied depending on the evaluation center. BR and PE showed the highest frequencies for repair and replacement, while FR and USA showed the highest frequencies for maintenance. The comparison of frequencies of anterior resin composite restorations accepted or unaccepted by the clinical vs lay evaluators in the same centers showed a significantly higher frequency of acceptable dental restorations coming from clinical evaluators. Comparison between lay evaluators from different centers showed significant higher frequency of unacceptable dental restorations by BR, compared to other centers. CONCLUSIONS: In the evaluation of anterior resin composite restorations, the maintenance, repair, or replacement trends can vary among different centers. The unacceptable rate came more frequently from lay than from clinical evaluators. Lay evaluators from different centers differed significantly. CLINICAL SIGNIFICANCE: Clinical and lay evaluators in distant evaluation centers can present different trends when assessing anterior resin composite restoration. Multicenter evaluations can help to understand such differences and it is important because clinical decision-making based on scientific evidence comes from clinical studies done in different research centers.

Peripheral leptin signaling persists in innate immune cells during diet-induced obesity.

Leptin is a pleiotropic adipokine that regulates immunometabolism centrally and peripherally. Obese individuals present increased levels of leptin in the blood and develop hypothalamic resistance to this adipokine. Here we investigated whether leptin effects on the periphery are maintained despite the hypothalamic resistance. We previously reported that leptin injection induces in vivo neutrophil migration and peritoneal macrophage activation in lean mice through TNF-α- and CXCL1-dependent mechanisms. However, leptin effects on leukocyte biology during obesity remain unclear. In this study, we investigated the in vivo responsiveness of leukocytes to i.p. injected leptin in mice with diet-induced obesity (DIO). After 14-16 wk, high-sucrose, high-fat diet (HFD)-fed mice showed hyperglycemia, hyperleptinemia, and dyslipidemia compared to normal-sucrose, normal-fat diet (ND). Exogenous leptin did not reduce food intake in DIO mice in contrast to control mice, indicating that DIO mice were centrally resistant to leptin. Regardless of the diet, we found increased levels of TNF-α and CXCL1 in the animals injected with leptin, alongside a pronounced neutrophil migration to the peritoneal cavity and enhanced biogenesis of lipid droplets in peritoneal macrophages. Supporting our in vivo results, data from ex vivo leptin stimulation experiments confirmed hypothalamic resistance in DIO mice, whereas bone marrow cells responded to leptin stimulation through mTOR signaling despite obesity. Altogether, our results show that leukocytes responded equally to leptin in ND- or HFD-fed mice. These results support a role for leptin in the innate immune response also in obesity, contributing to the inflammatory status that leads to the development of metabolic disease.

Digital photography vs. clinical assessment of resin composite restorations.

PURPOSE: To compare direct clinical and indirect digital photographic assessment of resin composite restorations. Ninety-two posterior resin composite restorations were classified using World Dental Federation (FDI) criteria by two different clinical examiners (C1 and C2). In the same appointment of clinical assessment, intraoral high-quality digital photographs were taken and posteriorly two different digital examiners (D1 and D2) classified the images of each restoration. Restorations of each patient were assessed once by C1 and C2 independently. D1 and D2 assessed the digital images from different locations and in different time. Data were analyzed using the Cohen's kappa coefficient, Kruskal-Wallis non-parametric test and Dunn's multiple shared test, with 95% confidence. Agreement levels varied from very good (0.81-1.00) to fair (0.21-0.40). Statistically significant differences (p < 0.05) between assessments were found for surface lustre, staining, color match and translucency, esthetic anatomical form, fracture of material and retention and marginal adaptation. The classification of the resin composite restorations varied significantly according to clinical or high-quality digital photographic assessments. Overall, clinical assessment detected more demand for repair or replacement.

Clinical, double blind, randomized controlled trial of experimental adhesive protocols in caries-affected dentin.

OBJECTIVE: To evaluate the clinical performance of posterior resin composite restorations regarding experimental and regular adhesive protocols in caries affected-dentin (CAD). MATERIAL AND METHODS: A total of 92 class I and class II cavities with carious lesions were selected and randomly assigned to the following groups: (1) bioactive glass-ceramic powder/two-step etch and rinse system, (2) control/two-step etch and rinse system, (3) bioactive glass-ceramic powder/two-step self-etching system, and (4) control/two-step self-etching system. Two operators carried out the adhesive protocols and restored the cavities with a nano-hybrid resin composite. Participants were followed up at 1 week and 6, 12, and 18 months for clinical evaluation performed by two blinded examiners and calibrated according to FDI criteria. Data were analyzed using Kruskal-Wallis and Dunn tests with a confidence of 95%. RESULTS: The clinical performance of resin composite restoration was not affected by the experimental use of an adhesive protocol including a bioactive glass-ceramic powder for 18 months post-procedure. However, there was a significant difference between group 2 and group 4 (p < 0.05) for marginal adaptation (18 months). Group 2 was significantly different from group 3 (p < 0.05) for fracture of material/retention (18 months) and marginal adaptation (1 week); group 2 showed a better performance. CONCLUSION: Adhesive protocols can alter the clinical performance of posterior restorations in terms of marginal adaptation and the fracture of material/retention in CAD. CLINICAL SIGNIFICANCE: Adhesive protocols may influence the success of resin composite restorations in CAD; this is important because failure can lead to caries, re-incidence, and/or clinical re-work.

The effect of electronic cigarettes on dental enamel color.

OBJECTIVE: The use of electronic cigarettes (ECIGs) has recently increased as an alternative to conventional smoking tobacco products. The literature is scarce on the effects of ECIGs on dental and oral structures. Therefore, the objective of this study was to observe whether ECIG aerosol could alter the color of dental enamel. MATERIALS AND METHODS: Sixty-three bovine enamel specimens were randomly separated into groups (n = 7) and treated with aerosols with different e-liquid flavors (neutral, menthol, and tobacco) and nicotine content (0, 12, and 18 mg). The initial color assessment was performed using a spectrophotometer (Easy Shade-Vita). Dental enamel was exposed to 20 cycles of ECIG aerosol in a smoking machine, and the final color was measured. The color change was evaluated using ΔEab, ΔE00, and Whiteness Index (WID ) formulae. Differences in L* a* b* coordinates were calculated, and data were analyzed (two-way ANOVA, uncorrected Fisher's LSD post hoc test, α = 0.05). RESULTS: Luminosity (ΔL) was reduced by aerosols with almost all levels of nicotine content and neutral and menthol flavors. Flavored e-liquids caused more color change (P < .05) according to ΔEab and ΔE00. ΔE values from both formulae exceeded the thresholds for perceptible visual alterations of color. WID increased after ECIGs exposure for menthol and tobacco and decreased for neutral flavors. CONCLUSIONS: ECIG aerosol from e-liquids with different nicotine contents and flavors altered enamel color. Menthol and tobacco e-liquids may alter the enamel color decreasing the yellowness of the enamel compared to neutral e-liquid. CLINICAL SIGNIFICANCE: Electronic cigarettes can cause perceptible changes in tooth color, altering dental esthetics.

Leptin Induces Proadipogenic and Proinflammatory Signaling in Adipocytes.

Background: Leptin is an adipokine with well-known effects on the central nervous system including the induction of energy expenditure and satiety. Leptin also has major relevance when activating immune cells and modulating inflammatory response. In obesity, increases in white adipose tissue accumulation and leptin levels are accompanied by hypothalamic resistance to leptin. Even though the adipose tissue is a leptin-rich environment, the local actions of leptin regarding adipogenesis were not thoroughly investigated until now. Here we evaluate the contributions of leptins direct signaling in preadipocytes and adipose tissue-derived stromal cells (ASCs) for adipogenesis. Methods: Adipocytes were differentiated from the murine lineage of preadipocytes 3T3-L1 or ASCs from subcutaneous and visceral (retroperitoneal) fat depots from C57Bl/6J mice. Differentiating cells were treated with leptin in addition to or in replacement of insulin. The advance of adipogenesis was assessed by the expression and secretion of adipogenesis- and lipogenesis-related proteins by Western blot and immunoenzimatic assays, and the accumulation of lipid droplets by fluorescence microscopy. Results: Leptin treatment in 3T3-L1 preadipocytes or ASCs increased the production of the adipogenesis- and lipogenesis-related proteins PLIN1, CAV-1, PPARγ, SREBP1C, and/or adiponectin at earlier stages of differentiation. In 3T3-L1 preadipocytes, we found that leptin induced lipid droplets' formation in an mTOR-dependent manner. Also, leptin induced a proinflammatory cytokine profile in 3T3-L1 and ASCs, modulating the production of TNF-α, IL-10, and IL-6. Since insulin is considered an essential factor for preadipocyte differentiation, we asked whether leptin would support adipogenesis in the absence of insulin. Importantly, leptin induced the formation of lipid droplets and the expression of adipogenesis-related proteins independently of insulin during the differentiation of 3T3-L1 cells and ASCs. Conclusions: Our results demonstrate that leptin induces intracellular signaling in preadipocytes and adipocytes promoting adipogenesis and modulating the secretion of inflammatory mediators. Also, leptin restores adipogenesis in the absence of insulin. These findings contribute to the understanding of the local signaling of leptin in precursor and mature adipose cells. The proadipogenic role of leptin unraveled here may be of especial relevance during obesity, when its central signaling is defective.

Breastfeeding Versus Bottle Feeding on Malocclusion in Children: A Meta-Analysis Study.

BACKGROUND: Breastfeeding plays an important role in child health. However, there are doubts about its influence on malocclusions. Systematic reviews have yielded contradictory results. Research aim: This study aimed to investigate whether the type and duration of breastfeeding are associated with malocclusions in primary teething. METHODS: The review strategy included several electronic databases, lists of references, reviews, dissertation and thesis websites, experts, and other relevant documents. Published and unpublished observational studies ( N = 42) were reviewed using the Participants (children), Interventions (breastfeeding), Comparisons (bottle feeding), Outcomes (malocclusion), and Study design (observational) strategy, without restrictions on language or locale. Information about the authors, publication year, country of study, setting, study design, sample size, age, type and duration of exclusive and mixed breastfeeding, and malocclusions was recorded by two blinded evaluators. Quantitative meta-analysis ( N = 30) of the studies with available data was performed. RESULTS: Breastfeeding was a protective factor against malocclusions. The odds of association increased with breastfeeding duration. Irrespective of duration, breastfeeding had a protective association with open bite. For those who were breastfed for up to 6 months, breastfeeding protected against overjet, open bite, posterior crossbite, and crowding. Breastfeeding for 12 months or longer was associated with lower odds of overjet, open bite, and posterior crossbite. Breastfeeding exclusively for 6 months was also a protective factor against malocclusions. However, studies on this subject presented low quality, statistical heterogeneity, and only unadjusted measures of association in most of the cases. CONCLUSION: Breastfeeding beneficially affects primary occlusion when practiced for at least 6 months.

Caveolin-1 and Caveolin-2 Can Be Antagonistic Partners in Inflammation and Beyond.

Caveolins, encoded by the CAV gene family, are the main protein components of caveolae. In most tissues, caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are co-expressed, and Cav-2 targeting to caveolae depends on the formation of heterooligomers with Cav-1. Notwithstanding, Cav-2 has unpredictable activities, opposing Cav-1 in the regulation of some cellular processes. While the major roles of Cav-1 as a modulator of cell signaling in inflammatory processes and in immune responses have been extensively discussed elsewhere, the aim of this review is to focus on data revealing the distinct activity of Cav-1 and Cav-2, which suggest that these proteins act antagonistically to fine-tune a variety of cellular processes relevant to inflammation.

GILT--A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin. METHODS: Patients received two cycles of oral vinorelbine (50 mg/m(2) days 1, 8 and 15) + cisplatin (20 mg/m(2) days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m(2) days 1 and 8) + cisplatin (80 mg/m(2) day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS). RESULTS: A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively. DISCUSSION: Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC.

Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.

Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1(-/-)) and Cav-2-deficient mice (Cav-2(-/-)) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2(-/-) mice, but not Cav-1(-/-) mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2(-/-) mice was not associated with alterations in the TGF-ß signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2(-/-) mice. Since Cav-1(-/-) mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process.

Intracultural variation in the knowledge of medicinal plants in an urban-rural community in the atlantic forest from northeastern Brazil.

This study assessed the intracultural knowledge of the use of medicinal plants in an urban-rural community in an Atlantic forest fragment in northeastern Brazil. We examined the importance of native and exotic species and the effects of gender and age on that knowledge. We also compared data obtained from different groups of informants (local experts and general community). We conducted 194 interviews between June 2007 and January 2008, using the freelist technique and semistructured forms to collect ethnobotanical data. Information obtained from the community was compared with that from six local experts who participated in a survey in 2003. From a total of 209 ethnospecies, exotic and herbaceous plants presented higher richness. With respect to the number of citations, women and older informants were shown to know a higher number of medicinal plants. Comparing knowledge of local experts with that of the general community, we noted that experts know a similar wealth of plant families and therapeutic indications, but the community knows a greater species richness. These results indicate that local experts may provide useful information for studies that search for a quick diagnosis of the knowledge of a given community.