Silica nanoparticle conjugation with gallic acid towards enhanced free radical scavenging capacity and activity on osteosarcoma cells in vitro.

Gallic acid (GA), derived from land plants, possesses diverse physiological benefits, including anti-inflammatory and anticancer effects, making it valuable for biomedical applications. In this study, GA was used to modify the surface of dendritic mesoporous silica nanoparticles (DMSNs) via carbamate (DMSN-NCO-GA) or amide (DMSN-NH-GA) bonds, using a post-grafting technique. To explore GA-conjugated materials' potential in modulating cancer cell redox status, three variants of osteosarcoma cells (U2-OS) were used. These variants comprised the wild-type cells (NEO), the cells overexpressing the wild-type human Golgi anti-apoptotic protein (hGAAP), and the null mutant of hGAAP (Ct-mut), as this protein was previously demonstrated to play a role in intracellular reactive oxygen species (ROS) accumulation and cell migration. In the absence of external ROS triggers, non-modified DMSNs increased intracellular ROS in Ct-mut and NEO cells, while GA-conjugated materials, particularly DMSN-NH-GA, significantly reduced ROS levels, especially pronounced with higher GA concentrations and notably in hGAAP cells with inherently higher ROS levels. Additionaly, NH-GA conjugates were less cytotoxic, more effective in reducing cell migration, and had higher ROS buffering capacity compared to DMSN-NCO-GA materials. However, in the presence of the external stressor tert-butyl-hydroperoxide (TBHP), NCO-GA conjugates showed more efficient reduction of intracellular ROS. These findings suggest that varying chemical decoration strategies of nanomaterials, along with the accessibility of functional groups to the cellular environment, significantly influence the biological response in osteosarcoma cells. Highlighting this, GA-conjugation is a promising method for implementing antioxidant properties and inhibiting cancer cell migration, warranting further research in anticancer treatment and drug development.

Click Chemistry in Polymersome Technology.

Polymersomes, self-assembled nanoparticles composed of amphiphilic block copolymers, have emerged as promising versatile nanovesicles with various applications, such as drug delivery, medical imaging, and diagnostics. The integration of click chemistry reactions, specifically the copper [I]-catalysed azide-alkyne cycloaddition (CuAAC), has greatly expanded the functionalisation and bioconjugation capabilities of polymersomes and new drugs, being this synergistic combination explored in this review. It also provides up-to-date examples of previous incorporations of click-compatible moieties (azide and alkyne functional groups) into polymer building blocks, enabling the "click" attachment of various functional groups and ligands, delving into the diverse range of click reactions that have been reported and employed for polymersome copolymer synthesis and the modification of polymersome surfaces, including ligand conjugation and surface modification. Overall, this review explores the current state-of-the-art of the combinatory usage, in recent years, of polymersomes with the click chemistry reaction, highlighting examples of studies of their synthesis and functionalisation strategies.

Antitumoral Activity of Cecropia Pachystachya Leaves Extract in Vitro and in Vivo Model of Rat Glioma: Brain and Blood Effects.

The aim of this study was to investigate the antiglioma effect of Cecropia pachystachya Trécul (CEC) leaves extract against C6 and U87 glioblastoma (GB) cells and in a rat preclinical GB model. The CEC extract reduced in vitro cell viability and biomass. In vivo, the extract decreased the tumor volume approximately 62%, without inducing systemic toxicity. The deficit in locomotion and memory and an anxiolytic-like behaviors induced in the GB model were minimized by CEC. The extract decreased the levels of reactive oxygen species, nitrites and thiobarbituric acid reactive substances and increased the activity of antioxidant enzymes in platelets, sera and brains of GB animals. The activity of NTPDases, 5'-nucleotidase and adenosine deaminase (ADA) was evaluated in lymphocytes, platelets and serum. In platelets, ATP and AMP hydrolysis was reduced and hydrolysis of ADP and the activity of ADA were increased in the control, while in CEC-treated animals no alteration in the hydrolysis of ADP was detected. In serum, the reduction in ATP hydrolysis was reversed by CEC. In lymphocytes, the increase in the hydrolysis of ATP, ADP and in the activity of ADA observed in GB model was altered by CEC administration. The observed increase in IL-6 and decrease in IL-10 levels in the serum of GB animals was reversed by CEC. These results demonstrate that CEC extract is a potential complementary treatment to GB, decreasing the tumor size, while modulating aspects of redox and purinergic systems.

The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin.

Manganese(III) porphyrin MnTnBuOE-2-PyP5+ (MnBuOE, BMX-001) is a third-generation redox-active cationic substituted pyridylporphyrin-based drug with a good safety/toxicity profile that has been studied in several types of cancer. It is currently in four phase I/II clinical trials on patients suffering from glioma, head and neck cancer, anal squamous cell carcinoma and multiple brain metastases. There is yet an insufficient understanding of the impact of MnBuOE on lung cancer. Therefore, this study aims to fill this gap by demonstrating the effects of MnBuOE on non-small cell lung cancer (NSCLC) A549 and H1975 cell lines. The cytotoxicity of MnBuOE alone or combined with cisplatin was evaluated by crystal violet (CV) and/or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-Tetrazolium (MTS) reduction assays. Intracellular ROS levels were assessed using two fluorescent probes. Furthermore, the impact of MnBuOE alone or in combination with cisplatin on collective cell migration, individual chemotactic migration and chemoinvasion was assessed using the wound-healing and transwell assays. The expression of genes related to migration and invasion was assessed through RT-qPCR. While MnBuOE alone decreased H1975 cell viability at high concentrations, when combined with cisplatin it markedly reduced the viability of the more invasive H1975 cell line but not of A549 cell line. However, MnBuOE alone significantly decreased the migration of both cell lines. The anti-migratory effect was more pronounced when MnBuOE was combined with cisplatin. Finally, MnBuOE alone or combined with cisplatin significantly reduced cell invasion. MnBuOE alone or combined with cisplatin downregulated MMP2, MMP9, VIM, EGFR and VEGFA and upregulated CDH1 in both cell lines. Overall, our data demonstrate the anti-metastatic potential of MnBuOE for the treatment of NSCLC.

Mixed Edge Activators in Ibuprofen-Loaded Transfersomes: An Innovative Optimization Strategy Using Box-Behnken Factorial Design.

Transfersomes have been highlighted as an interesting nanotechnology-based approach to facilitate the skin delivery of bioactive compounds. Nevertheless, the properties of these nanosystems still need to be improved to enable knowledge transfer to the pharmaceutical industry and the development of more efficacious topical medicines. Quality-by-design strategies, such as Box-Behnken factorial design (BBD), are in line with the current need to use sustainable processes to develop new formulations. Thus, this work aimed at optimizing the physicochemical properties of transfersomes for cutaneous applications, by applying a BBD strategy to incorporate mixed edge activators with opposing hydrophilic-lipophilic balance (HLB). Tween® 80 and Span® 80 were used as edge activators and ibuprofen sodium salt (IBU) was selected as the model drug. After the initial screening of the IBU solubility in aqueous media, a BBD protocol was implemented, and the optimized formulation displayed appropriate physicochemical properties for skin delivery. By comparing the optimized transfersomes to equivalent liposomes, the incorporation of mixed edge activators was found to be beneficial to upgrade the storage stability of the nanosystems. Furthermore, their cytocompatibility was shown by cell viability studies using 3D HaCaT cultures. Altogether, the data herein bode well for future advances in the use of mixed edge activators in transfersomes for the management of skin conditions.

Measurement of particulate matter in a heritage building using optical counters: Long-term and spatial analyses.

The good conservation of cultural patrimony depends on the quality of the indoor environment where collections and artifacts are kept, being suspended particles one of the key parameters. Among the various methods to study indoor pollution, portable optical counters appear as effective instruments to measure indoor pollution due to their specifications (low visual and acoustic impact). However, it is still one of the least common approaches when assessing the conservation quality in heritage buildings. Therefore, the present study focuses on developing a methodology that uses portable particle counters to monitor particulate matter inside historic buildings and assess indoor conservation quality. Long-term and spatial analyses were conducted using this type of equipment to identify causes of pollution in a case study, the Joanina Library in Coimbra, Portugal. Estimation of night concentrations was carried out as a complementary approach to the monitoring. A new conservation method of classifying indoor pollution was proposed as an alternative to the most common standards. This classification determines four conservation classes (A, B, C, and D) according to particulate matter and the respective percentage of time that measurements are within such classes. As a result, the measurements showed a poor indoor environment quality meeting the requirements of low-level classes, which are those with a greater risk of degradation (Classes C and D). The continuous long-term campaign of four years was decisive for the identification of the main sources and environmental conditions of higher pollution: the exterior pavement, the number of tourists, the use of carpets, and the absence of rain. The spatial results depend on the diameters of the particles and the space's height where the assessment is made. Thus, this type of device and the developed methodology could be used by curators as an effective tool for long-term and spatial assessment in this building typology.

The Dietary Isothiocyanate Erucin Reduces Kidney Cell Motility by Disturbing Tubulin Polymerization.

SCOPE: Epidemiological evidence associates the consumption of cruciferous vegetables with reduced risk of several cancers, including renal cell carcinoma. Erucin can be generated by in vivo reduction of sulforaphane or by enzymatic hydrolysis of glucoerucin. Contrarily to sulforaphane, only limited studies have addressed the anticancer properties of erucin. This study aims at evaluating the impact of erucin on renal cell biology. METHODS AND RESULTS: The effects of erucin were assessed in 786-O and Vero-E6 cells, representative of human renal cancer and non- cancer kidney cells, respectively. Erucin induced a concentration-dependent decrease in cell viability and cell cycle arrest at G2/Mitosis. In Vero-E6 cells erucin modestly reduced intracellular reactive oxygen species levels while in 786-O no effects were detected. After erucin treatment, both cell lines revealed altered morphology, with a concentration-dependent change from an elongated shape towards a smaller round conformation. Moreover, erucin affected cell adhesion and strongly altered the tubulin network structure and specifically microtubule polymerization. These results are in line with the observed decrease in collective and single cell migration and G2/Mitosis arrest. CONCLUSIONS: Overall, erucin may have a beneficial impact in reducing the motility of renal cancer cells. Our results contribute to explore possible dietary approaches for secondary/tertiary renal cancer chemoprevention.

The Golgi Apparatus as an Anticancer Therapeutic Target.

Although the discovery of the Golgi apparatus (GA) was made over 125 years ago, only a very limited number of therapeutic approaches have been developed to target this complex organelle. The GA serves as a modification and transport center for proteins and lipids and also has more recently emerged as an important store for some ions. The dysregulation of GA functions is implicated in many cellular processes associated with cancer and some GA proteins are indeed described as cancer biomarkers. This dysregulation can affect protein modification, localization, and secretion, but also cellular metabolism, redox status, extracellular pH, and the extracellular matrix structure. Consequently, it can directly or indirectly affect cancer progression. For these reasons, the GA is an appealing anticancer pharmacological target. Despite this, no anticancer drug specifically targeting the GA has reached the clinic and few have entered the clinical trial stage. Advances in nanodelivery approaches may help change this scenario by specifically targeting tumor cells and/or the GA through passive, active, or physical strategies. This article aims to examine the currently available anticancer GA-targeted drugs and the nanodelivery strategies explored for their administration. The potential benefits and challenges of modulating and specifically targeting the GA function in the context of cancer therapy are discussed.

MnTnHex-2-PyP5+ Displays Anticancer Properties and Enhances Cisplatin Effects in Non-Small Cell Lung Cancer Cells.

The manganese(III) porphyrin MnTnHex-2-PyP5+ (MnTnHex) is a potent superoxide dismutase mimic and modulator of redox-based transcriptional activity that has been studied in the context of different human disease models, including cancer. Nevertheless, for lung cancer, hardly any information is available. Thus, the present work aims to fill this gap and reports the effects of MnTnHex in non-small cell lung cancer (NSCLC) cells, more specifically, A549 and H1975 cells, in vitro. Both cell lines were initially characterized in terms of innate levels of catalase, glutathione peroxidase 1, and peroxiredoxins 1 and 2. To assess the effect of MnTnHex in NSCLC, alone or in combination with cisplatin, endpoints related to the cell viability, cell cycle distribution, cell motility, and characterization of the volatile carbonyl compounds (VCCs) generated in the extracellular medium (i.e., exometabolome) were addressed. The results show that MnTnHex as a single drug markedly reduced the viability of both NSCLC cell lines, with some IC50 values reaching sub-micromolar levels. This redox-active drug also altered the cell cycle distribution, induced cell death, and increased the cytotoxicity pattern of cisplatin. MnTnHex also reduced collective cell migration. Finally, the metabolomics study revealed an increase in the levels of a few VCCs associated with oxidative stress in MnTnHex-treated cells. Altogether these results suggest the therapeutic potential of MnTnHex to be further explored, either alone or in combination therapy with cisplatin, in NSCLC.

Lysyl Oxidases Expression and Breast Cancer Progression: A Bioinformatic Analysis.

LOX (Lysyl oxidase) and LOX like 1-4 (LOXL1-4) are amine oxidases that catalyse the cross-linking of elastin and collagen in the extracellular matrix (ECM). This activity can facilitate cell migration and the formation of metastases. Consequently, inhibition of these enzymes and, in particular of LOXL2, has been suggested as a therapeutic strategy to prevent breast cancer metastasis. Although medicinal chemistry studies have struggled to specifically inhibit LOXL2, the importance of selectivity in this context is not clear. To explore the role of each LOX in breast cancer and consequently their potential as biomarkers or therapeutic targets, a bioinformatic-based approach was followed. The expression profile of LOXs, the putative associations among mRNA expression from each LOX and clinical observations, the correlation between expression of LOX enzymes and other genes, and the association between expression of LOXs and the tumour infiltrates were assessed for breast cancer. Overall, the patient outcome and the characteristics of breast tumours with LOX, LOXL1 and LOXL2 upregulation is distinct from those with high expression of LOXL3 and LOXL4. Additionally, the expression correlation between LOXs and other genes involved in cellular processes relevant for cancer biology, also reveals a similar trend for LOX, LOXL1 and LOX2. This work further supports the relevance of LOXL2 as a breast cancer progression biomarker and therapeutic target. We speculate that while the impact of LOXL3 inhibition may vary with breast cancer subtype, the therapeutical inhibition of LOX, LOXL1 and LOXL2 but not of LOXL4 may be the most beneficial.

Impact of Portuguese propolis on keratinocyte proliferation, migration and ROS protection: Significance for applications in skin products.

OBJECTIVE: Propolis has been used since antiquity, but recent reports of its biological properties hint that it could be employed as a topical pharmaceutical and cosmetic ingredient. This work aims to probe the action of Portuguese propolis extracts on skin cells, providing mechanistic insights into its mode of action and preliminarily assessing its applicability as a skin repair ingredient. METHODS: The total phenolic content of propolis extracts was measured by the Folin Ciocalteu method. The cytotoxic effect of propolis extracts in human keratinocytes was determined and non-cytotoxic concentrations of the extracts were used to study the impact on collective cell migration, cell cycle and intracellular ROS levels. RESULTS: o significant impact was observed in collective cell migration, but one of the extracts mildly increased G2 phase while reducing the % of sub-G1 at a non-cytotoxic concentration. The two extracts with higher phenolic content strongly prevented intracellular cellular ROS accumulation upon exposure to TBHP. Collectively, these results indicate that the putative beneficial effects of propolis extracts in skin repair may not be attributable to induction of collective cell migration but could be partially ascribed to the protection from oxidative stress, which could act in synergy with its well-known antimicrobial activity. CONCLUSION: These data support the applicability of this material in topical and cosmetic formulations and further in vivo assays should be conducted to fully characterize its efficacy and safety.

OBJECTIF: la propolis est utilisée depuis l'Antiquité, mais des rapports récents sur ses propriétés biologiques suggèrent qu'elle pourrait être utilisée comme ingrédient pharmaceutique et cosmétique topique. Ce travail de recherche vise à explorer l'effet d'extraits de propolis portugaise sur les cellules cutanées, en fournissant des informations sur le plan mécanique relatives à son mode d'action et en évaluant de manière préliminaire son applicabilité en tant qu'ingrédient de réparation cutanée. MÉTHODES: la teneur en substance phénolique totale d'extraits de propolis a été mesurée par la méthode de Folin-Ciocalteu. L'effet cytotoxique d'extraits de propolis dans les kératinocytes humains a été déterminé, et des concentrations non cytotoxiques de ces extraits ont été utilisées pour étudier l'impact sur la migration cellulaire collective, le cycle cellulaire et les taux de ROS intracellulaires. RÉSULTATS: un impact significatif a été observé sur la migration cellulaire collective, mais l'un des extraits a légèrement augmenté la phase G2 tout en réduisant le % de sub-G1 à une concentration non cytotoxique. Les deux extraits présentant une teneur phénolique plus élevée ont fortement prévenu l'accumulation de ROS intracellulaires lors de l'exposition à l'hydroperoxyde de tert-butyle (TBHP). Collectivement, ces résultats indiquent que les effets bénéfiques présumés des extraits de propolis dans la réparation cutanée pourraient ne pas être attribuables à l'induction de la migration cellulaire collective, mais partiellement à la protection contre le stress oxydatif, qui pourrait agir en synergie avec son activité antimicrobienne bien connue. CONCLUSION: ces données étayent l'applicabilité de cette substance dans les formulations topiques et cosmétiques, et des tests in vivo supplémentaires doivent être réalisés afin de caractériser plus précisément son efficacité et sa sécurité d'emploi.

GOLGI: Cancer cell fate control.

Growing evidence connects many of the Golgi known functions with cellular events related to cancer initiation and progression, including regulation of cell survival/death, proliferation, motility, metabolism and immune evasion. However, a broad and integrated understanding of the impact of the Golgi on cancer cell phenotype has not yet been achieved. Multiple cellular events involving the Golgi are associated with protein and lipid modification and trafficking. However, less explored aspects of this enigmatic organelle also contribute to cell fate decision-making by impacting signal transduction, redox and ion homeostasis. This article focuses on the molecular mechanisms and Golgi proteins underlying the impact of the Golgi on cancer cell phenotype. Special emphasis is given to emerging knowledge on redox and ion homeostasis. Current and potential cancer progression therapeutic strategies associated with this organelle will also be addressed.

Urolithin B: Two-way attack on IAPP proteotoxicity with implications for diabetes.

Introduction: Diabetes is one of the major metabolic diseases worldwide. Despite being a complex systemic pathology, the aggregation and deposition of Islet Amyloid Polypeptide (IAPP), or amylin, is a recognized histopathological marker of the disease. Although IAPP proteotoxicity represents an important trigger of ß-cell dysfunction and ultimately death, its exploitation as a therapeutic tool remains underdeveloped. The bioactivity of (poly)phenols towards inhibition of pathological protein aggregation is well known, however, most of the identified molecules have limited bioavailability. Methods: Using a strategy combining in silico, cell-free and cell studies, we scrutinized a unique in-house collection of (poly)phenol metabolites predicted to appear in the human circulation after (poly)phenols ingestion. Results: We identified urolithin B as a potent inhibitor of IAPP aggregation and a powerful modulator of cell homeostasis pathways. Urolithin B was shown to affect IAPP aggregation pattern, delaying the formation of amyloid fibrils and altering their size and morphology. The molecular mechanisms underlying urolithin B-mediated protection include protein clearance pathways, mitochondrial function, and cell cycle ultimately rescuing IAPP-mediated cell dysfunction and death. Discussion: In brief, our study uncovered urolithin B as a novel small molecule targeting IAPP pathological aggregation with potential to be exploited as a therapeutic tool for mitigating cellular dysfunction in diabetes. Resulting from the colonic metabolism of dietary ellagic acid in the human body, urolithin B bioactivity has the potential to be explored in nutritional, nutraceutical, and pharmacological perspectives.

LOXL2 Inhibitors and Breast Cancer Progression.

LOX (lysyl oxidase) and lysyl oxidase like-1-4 (LOXL 1-4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (ß-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source. However, novel synthetic compounds that act as LOX/LOXL2 selective inhibitors or as dual LOX/LOX-L inhibitors have been recently developed. In this review, we describe LOX enzymes and their role in promoting cancer development and metastases, with a special focus on LOXL2 and breast cancer progression. Moreover, the recent advances in the development of LOXL2 inhibitors are also addressed. Overall, this work contextualizes and explores the importance of LOXL2 inhibition as a promising novel complementary and effective therapeutic approach for breast cancer treatment.

Impact of the APE1 Redox Function Inhibitor E3330 in Non-small Cell Lung Cancer Cells Exposed to Cisplatin: Increased Cytotoxicity and Impairment of Cell Migration and Invasion.

Elevated expression levels of the apurinic/apyrimidinic endonuclease 1 (APE1) have been correlated with the more aggressive phenotypes and poor prognosis of non-small cell lung cancer (NSCLC). This study aimed to assess the impact of the inhibition of the redox function of APE1 with E3330 either alone or in combination with cisplatin in NSCLC cells. For this purpose, complementary endpoints focusing on cell viability, apoptosis, cell cycle distribution, and migration/invasion were studied. Cisplatin decreased the viability of H1975 cells in a time- and concentration-dependent manner, with IC50 values of 9.6 µM for crystal violet assay and 15.9 µM for 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. E3330 was clearly cytotoxic for concentrations above 30 µM. The co-incubation of E3330 and cisplatin significantly decreased cell viability compared to cisplatin alone. Regarding cell cycle distribution, cisplatin led to an increase in sub-G1, whereas the co-treatment with E3330 did not change this profile, which was then confirmed in terms of % apoptotic cells. In addition, the combination of E3330 and cisplatin at low concentrations decreased collective and chemotactic migration, and also chemoinvasion, by reducing these capabilities up to 20%. Overall, these results point to E3330 as a promising compound to boost cisplatin therapy that warrants further investigation in NSCLC.

Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells.

Medicinal plants are important sources of new bioactive compounds with potential anticancer activity. Parvifloron D (ParvD) is an abietane diterpenoid, isolated in high amounts from Plectranthus ecklonii Benth. Previous reports have suggested potential therapeutic properties for ParvD. ParvD has shown pro-apoptotic and cytotoxic effects in leukemia and melanoma cell lines. However, to the best of our knowledge, there are no studies in triple-negative breast cancer (TNBC) models. TNBC is a breast cancer subtype characterized by an aggressive behavior with poor clinical outcomes and weak overall therapeutic responses to the current treatment options. This work aimed at evaluating the anticancer effect of ParvD in MDA-MB-231 cells, a model of human TNBC. To obtain sufficient amounts of purified ParvD the efficiency of several extraction methods was compared. ParvD (0.1-10 µM) decreased cell viability in a concentration-dependent manner. Treatment with ParvD (5 µM) significantly increased the percentage of apoptotic nuclei and exposure to 3 µM ParvD increased the sub-G1 population. Since altered cell adherence, migration, and invasion are determinant processes for the formation of metastases, the effect of ParvD on these cellular processes was tested. Although treatment with ParvD (1 µM) had no effect on cell-substrate attachment, ParvD (1 µM) significantly reduced cell chemotaxis and invasion. This is the first report describing the proapoptotic effect of ParvD in TNBC cells. Moreover, for the first time we have shown that ParvD reduces cell motility, unraveling potential anti-metastatic properties.

Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism.

The mechanisms by which the Golgi apparatus (GA) impacts on cell invasion are poorly understood. The human Golgi Anti-Apoptotic Protein (hGAAP, also known as TMBIM4) is a highly conserved Golgi cation channel that modulates intracellular Ca2+ fluxes. Human GAAP is expressed in all human tissues, is essential for cell viability and provides resistance against a range of apoptotic stresses. Furthermore, hGAAP enhances adhesion and cell migration by increasing the turnover of focal adhesions due to activation of store-operated Ca2+ entry. Here, we describe a GA-derived mechanism that controls cell invasion. The overexpression of hGAAP stimulates 3-dimensional proteolytic cell invasion by a mechanism that is dependent on the accumulation of intracellular hydrogen peroxide, which might be produced by the hGAAP-dependent stimulation of mitochondrial respiration. These findings provide new insight into the complex mechanisms by which Ca2+ and reactive oxygen species signaling contribute to cell invasion and to the role of the GA in these processes.

An Overview on the Properties of Ximenia Oil Used as Cosmetic in Angola.

Ximenia (Ximeniaamericana L.) is a shrub, or small tree, native from Africa and spread across different continents. In Angola, the seeds oil is used by local populations, to prevent sunburn, to smooth and hydrate the skin, and to give it a pleasant color and elasticity, to prevent stretch marks, in pregnant woman, and also as hair conditioner. Herein, an oil sold in the region (LPO), and two others extracted in laboratory, from seeds collected in the same region, were investigated in terms of their composition, chemical properties, UV transmission. The three oils are similar although the LPO is more acidic, 0.48 mg KOH/g. GC-MS analysis indicated that the major components are the fatty acids, oleic (31.82%), nervonic (11.09%), ximenic (10.22%), and hexacosa-17,20,23-trienoic acids (14.59%). Long chain fatty acids, n ≥ 20, accounted for 51.1% of the total fatty acids. A thin film of the oil showed a reduction in transmittance from 200 to 300 nm. Viscosity studies of the LPO indicated that at normal temperature of skin, the oil can be spread over the skin as a thin film. At concentrations up to 10 µg/mL, the LPO is not toxic to human keratinocytes, suggesting the safety of this oil.

The SOD Mimic MnTnHex-2-PyP5+ Reduces the Viability and Migration of 786-O Human Renal Cancer Cells.

Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer. The importance of oxidative stress in the context of this disease has been described, although there is only little information concerning the role of superoxide dismutase (SOD) enzymes. The importance of SOD in different pathological conditions promoted the development of SOD mimics (SODm). As such, manganese(III) porphyrins can mimic the natural SOD enzymes and scavenge different reactive oxygen species (ROS), thus modulating the cellular redox status. In this study, the exposure of 786-O human renal cancer cells to MnTnHex-2-PyP5+ (MnP), a very promising SODm, led to a concentration and time-dependent decrease in cell viability and in the cell proliferation indices, as well as to an increase in apoptosis. No relevant effects in terms of micronuclei formation were observed. Moreover, the exposure to MnP resulted in a concentration-dependent increase in intracellular ROS, presumably due to the generation of H2O2 by the inherent redox mechanisms of MnP, along with the limited ability of cancer cells to detoxify this species. Although the MnP treatment did not result in a reduction in the collective cell migration, a significant decrease in chemotactic migration was observed. Overall, these results suggest that MnP has a beneficial impact on reducing renal cancer cell viability and migration and warrant further studies regarding SODm-based therapeutic strategies against human renal cancer.