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Willie O Pinheiro,1,2 Maria L Fascineli,1 Gabriel R Farias,1 Frederico H Horst,1 Laise Rodrigues de Andrade,1 Luis Henrique Corrêa,3 Kelly Grace Magalhães,3 Marcelo Henrique Sousa,4 Marcos C de Almeida,1 Ricardo B Azevedo,1 Zulmira GM Lacava1,2 1Department of Genetics and Morphology, Institute of Biological Sciences, CNANO, University of Brasilia, Brasilia, DF 70910-900, Brazil; 2Post-graduation Program in Molecular Pathology, Faculty of Medicine, University of Brasilia, Brasília, DF 70910-900, Brazil; 3Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, Brasilia, DF 70910-900, Brazil; 4Green Nanotechnology Group, Faculty of Ceilandia, University of Brasilia, Brasília, DF 72220-900, Brazil Background: Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce. Purpose: To fill part of this gap, this work aimed to investigate biocompatibility and biodistribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice. Methods: NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods. Results: NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice. Conclusion: Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals’ age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population. Keywords: elderly, nanotoxicity, maghemite nanoparticles, superparamagnetic iron oxide nanoparticles, SPIO, nano-safety, inductively coupled plasma optical emission spectrometry, ICP-OES

Luis Alexandre Muehlmann,* Beatriz Chiyin Ma,* João Paulo Figueiró Longo, Maria de Fátima Menezes Almeida Santos, Ricardo Bentes AzevedoDepartment of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasília/DF, Brazil *These authors contributed equally to this work Abstract: Photodynamic therapy is generally considered to be safer than conventional anticancer therapies, and it is effective against different kinds of cancer. However, its clinical application has been significantly limited by the hydrophobicity of photosensitizers. In this work, a system composed of the hydrophobic photosensitizer aluminum–phthalocyanine chloride (AlPc) associated with water dispersible poly(methyl vinyl ether-co-maleic anhydride) nanoparticles is described. AlPc was associated with nanoparticles produced by a method of solvent displacement. This system was analyzed for its physicochemical characteristics, and for its photodynamic activity in vitro in cancerous (murine mammary carcinoma cell lineage 4T1, and human mammary adenocarcinoma cells MCF-7) and noncancerous (murine fibroblast cell lineage NIH/3T3, and human mammary epithelial cell lineage MCF-10A) cell lines. Cell viability and the elicited mechanisms of cell death were evaluated after the application of photodynamic therapy. This system showed improved photophysical and photochemical properties in aqueous media in comparison to the free photosensitizer, and it was effective against cancerous cells in vitro. Keywords: third-generation photosensitizer, nanoparticles, cancer, photodynamic therapy, drug delivery systems

Danay Dupeyrón,1,2 Monique Kawakami,1 Adriana M Ferreira,1 Paolin Rocio Cáceres-Vélez,3 Jacques Rieumont,4 Ricardo Bentes Azevedo,3 José Carlos T Carvalho1 1Laboratório de Pesquisa em Fármacos, Centro de Ciências Biológicas e da Saúde, Colegiado de Farmácia, Universidade Federal do Amapá, Brazil; 2Programa de Pós-Graduação em Biodiversidade Tropical, Universidade Federal do Amapá, Brazil; 3Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brazil; 4Departamento de Química – Física, Facultad de Química, Universidad de la Habana, Cuba Abstract: Despite recent advances in nonsteroidal anti-inflammatory drug (NSAID) formulations, the design of targeted delivery systems to improve the efficacy and reduce side effects of NSAIDs continues to be a focus of much research. Enteric nanoparticles have been recognized as a potential system to reduce gastrointestinal irritations caused by NSAIDs. The aim of this study was to evaluate the effect of EUDRAGIT® L100, polyethylene glycol, and polysorbate 80 on encapsulation efficiency of indomethacin within enteric nanoparticles. Formulations were developed based on a multilevel factorial design (three factors, two levels). The amount of polyethylene glycol was shown to be the factor that had the greatest influence on the encapsulation efficiency (evaluated response) at 95% confidence level. Some properties of nanoparticles like process yield, drug–polymer interaction, particle morphology, and in vitro dissolution profile, which could affect biological performance, have also been evaluated. Keywords: nonsteroidal anti-inflammatory, indomethacin, enteric polymer, polyethylene glycol, nanoparticles

Mariana Campos da Paz,1 Maria de Fátima M Almeida Santos,1 Camila MB Santos,2 Sebastião W da Silva,2 Lincoln Bernardo de Souza,3 Emília CD Lima,3 Renata C Silva,1 Carolina M Lucci,1 Paulo César Morais,2 Ricardo B Azevedo,1 Zulmira GM Lacava11Instituto de Ciências Biológicas; 2Instituto de Física, Universidade de Brasília, Brasília, DF, Brazil; 3Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, BrazilAbstract: Nanosized maghemite particles were synthesized, precoated (with dimercaptosuccinic acid) and surface-functionalized with anticarcinoembryonic antigen (anti-CEA) and successfully used to target cell lines expressing the CEA, characteristic of colorectal cancer (CRC) cells. The as-developed nanosized material device, consisting of surface decorated maghemite nanoparticles suspended as a biocompatible magnetic fluid (MF) sample, labeled MF-anti-CEA, was characterized and tested against two cell lines: a high-CEA expressing cell line (LS174T) and a low-CEA expressing cell line (HCT116). Whereas X-ray diffraction was used to assess the average core size of the as-synthesized maghemite particles (average 8.3 nm in diameter), dynamic light scattering and electrophoretic mobility measurements were used to obtain the average hydrodynamic diameter (550 nm) and the zeta-potential (−38 mV) of the as-prepared and maghemite-based nanosized device, respectively. Additionally, surface-enhanced Raman spectroscopy (SERS) was used to track the surface decoration of the nanosized maghemite particles from the very first precoating up to the attachment of the anti-CEA moiety. The Raman peak at 1655 cm−1, absent in the free anti-CEA spectrum, is the signature of the anti-CEA binding onto the precoated magnetic nanoparticles. Whereas MTT assay was used to confirm the low cell toxicity of the MF-anti-CEA device, ELISA and Prussian blue iron staining tests performed with both cell lines (LS174T and HCT116) confirm that the as-prepared MF-anti-CEA is highly specific for CEA-expressing cells. Finally, transmission electron microscopy analyses show that the association with anti-CEA seems to increase the number of LS174T cells with internalized maghemite nanoparticles, whereas no such increase seems to occur in the HCT116 cell line. In conclusion, the MF-anti-CEA sample is a biocompatible device that can specifically target CEA, suggesting its potential use as a theragnostic tool for CEA-expressing tumors, micrometastasis, and cancer-circulating cells.Keywords: magnetic nanoparticles, anti-CEA antibody, targeted delivery, diagnostic, Raman, biocompatible device

For cancer patients with a high risk of ovarian tissue metastasis, ovarian autotransplantation is not advised due to the potential spread of malignant cells. Ex vivo purging of ovarian fragments may offer a more suitable alternative for fertility restoration. Eradicating malignant cells should be done selectively without affecting follicles or ovarian stromal cells (SCs). As a clinically licensed method, photodynamic therapy (PDT) is a minimally invasive treatment to destroy cancer cells. This study evaluates the effectiveness of nanoemulsions (NE) containing two phthalocyanine photosensitizers; aluminum (III) phthalocyanine (AlPc) and zinc (II) phthalocyanine (ZnPc) in eliminating cancer cells. Human leukemic malignant (HL-60) and ovarian stromal cells (SCs) were treated with AlPc/ZnPc loaded NEs with or without diode laser irradiation. HL-60 leukemia cells in 2D culture were eliminated by treatment with 10 nM AlPc-NE or 0.1 µM ZnPc-NE, while no toxicity was observed in SCs. In 3D culture models, although the cells showed more resistance to the NEs as a result of limited oxygen and photosensitizer penetration, the treatment remained selective for cancer cells. These approaches have the potential to eliminate malignant cells from ovarian tissue fragments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christiani A. Amorim reports financial support was provided by Louvain Foundation. Saba Nikanfar reports financial support was provided by FSR Belgium. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Iron oxide nanoparticles (FeO-NPs) are widely used in scientific and technological fields. Environmental concerns have been raised about residual FeO-NPs levels as their toxicity and bioaccumulative potential are not well understood. Oreochromis niloticus were exposed to nanoparticles of γ-Fe2O3 and Fe3O4. Micro-CT 3D image and grayscale graphic assessments revealed the accumulation of radiopaque material in the digestive tract of fish exposed to FeO-NPs. Histological analysis showed the presence of such NPs in the hepatopancreas, gills, kidneys, and muscles. No genotoxicity occurred, through micronucleus test and comet assay in peripheral erythrocytes. Body clearance was confirmed by iron-content reduction in organisms exposed to FeO-NPs after recovery period. No tissue injuries were observed in the exposed animals which may be attributed to the absence or low toxicity of iron oxide nanoparticles under the study conditions. O. niloticus showed tolerance to sublethal exposures to FeO-NPs.

Melanoma, the most aggressive form of skin cancer, presents a major clinical challenge due to its tendency to metastasize and recalcitrance to traditional therapies. Despite advances in surgery, chemotherapy, and radiotherapy, the outlook for advanced melanoma remains bleak, reinforcing the urgent need for more effective treatments. Photodynamic therapy (PDT) has emerged as a promising alternative, leading to targeted tumor destruction with minimal harm to surrounding tissues. In this study, the direct and abscopal antitumor effects of PDT in a bilateral murine melanoma model were evaluated. Although only one of the two tumors was treated, effects were observed in both. Our findings revealed significant changes in systemic inflammation and alterations in CD4 + and CD8 + T cell populations in treated groups, as evidenced by blood analyses and flow cytometry. High-throughput RNA sequencing (RNA-Seq) further unveiled shifts in gene expression profiles in both treated and untreated tumors. This research sheds light on the novel antitumor and abscopal effects of nanoemulsion of aluminum chloride phthalocyanine (AlPcNE)-mediated PDT in melanoma, highlighting the potential of different PDT protocols to modulate immune responses and to achieve more effective and targeted cancer treatments.

Combination therapy integrated with nanotechnology offers a promising alternative for breast cancer treatment. The inclusion of pequi oil, anacardic acid (AA), and docetaxel (DTX) in a nanoemulsion can amplify the antitumor effects of each molecule while reducing adverse effects. Therefore, the study aims to develop pequi oil-based nanoemulsions (PeNE) containing DTX (PDTX) or AA (PAA) and to evaluate their cytotoxicity against triple-negative breast cancer cells (4T1) in vitro. The PeNE without and with AA (PAA) and DTX (PDTX) were prepared by sonication and characterized by ZetaSizer ® and electronic transmission microscopy. Viability testing and combination index (CI) were determined by MTT and Chou-Talalay methods, respectively. Flow cytometry was employed to investigate the effects of the formulations on cell structures. PeNE, PDTX, and PAA showed hydrodynamic diameter < 200 nm and a polydispersity index (PdI) of 0.3. The association PDTX + PAA induced a greater decrease in cell viability (~70%, p < 0.0001) and additive effect (CI < 1). In parallel, an association of the DTX + AA molecules led to antagonism (CI > 1). Additionally, PDTX + PAA induced an expressive morphological change, a major change in lysosome membrane permeation and mitochondria membrane permeation, cell cycle blockage in G2/M, and phosphatidylserine exposure. The study highlights the successful use of pequi oil nanoemulsions as delivery systems for DTX and AA, which enhances their antitumor effects against breast cancer cells. This nanotechnological approach shows significant potential for the treatment of triple-negative breast cancer.

This study describes the synthesis and characterization of chlorambucil (CLB)-functionalized mesoporous silica nanoparticles (MSNs) for potential application in cancer therapy. The nanoparticles were designed with a diameter between 20 and 50 nm to optimize cellular uptake and avoid rapid clearance from the bloodstream. The synthesis method involved modifying a previously reported technique to reduce particle size. Successful functionalization with CLB was confirmed through various techniques, including Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The cytotoxicity of the CLB-functionalized nanoparticles (MSN@NH 2 -CLB) was evaluated against human lung adenocarcinoma cells (A549) and colon carcinoma cells (CT26WT). The results suggest significantly higher cytotoxicity of MSN@NH 2 -CLB compared to unbound CLB, with improved selectivity towards cancer cells over normal cells. This suggests that MSN@NH 2 -CLB holds promise as a drug delivery system for targeted cancer therapy.

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major . Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group ( p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.

​​​​​​​The so-called arc of deforestation is a major agricultural and industrial frontier in southern Amazonia and northern Cerrado of Brazil. As arboreal mammals, the primates in this region are therefore threatened by forest loss and fragmentation. At the same time, knowledge about the taxonomic diversity and distribution ranges of these taxa is incomplete, which might hamper efficient conservation measurements. New species have been recently discovered in this region, and their ranges remain imprecise because only a few occurrence records are available for each species. Here we present 192 new records of 22 species and subspecies of Alouatta , Aotus , Ateles , Cebus , Chiropotes , Lagothrix , Leontocebus , Pithecia , Plecturocebus , Saimiri , and Sapajus , collected in 56 different localities during 10 field expeditions across the arc of deforestation between 2015 and 2018. Based on these new records, we extend the ranges of Alouatta puruensis , Ateles chamek , and Saimiri collinsi ; identify potential hybridization zones between A. puruensis and A. discolor , and between At. chamek and At. marginatus ; redefine the range of Plecturocebus moloch ; and clarify the ranges of P. baptista and P. hoffmannsi . Moreover, these results and the dataset are valuable for further research on, for example, species distribution and habitat use modeling, for assessing species extinction risks, and for supporting efforts for the conservation of species increasingly threatened on a global deforestation frontier., Competing Interests: At least one of the (co-)authors is a member of the editorial board of Primate Biology. The peer-review process was guided by an independent editor, and the authors also have no other competing interests to declare., (Copyright: © 2024 Rodrigo Costa-Araújo et al.)

Melanoma, a severe form of skin cancer intricately linked to genetic and environmental factors, is predicted to reach 100,000 new cases worldwide by 2040, underscoring the need for effective and safe treatment options. In this study, we assessed the efficacy of a photosensitizer called Chlorophyll A (Chl-A) incorporated into hydrogels (HGs) made of chitosan (CS) and poloxamer 407 (P407) for Photodynamic Therapy (PDT) against the murine melanoma cell line B16-F10. The HG was evaluated through various tests, including rheological studies, SEM, and ATR-FTIR, along with cell viability assays. The CS- and P407-based HGs effectively released Chl-A and possessed the necessary properties for topical application. The photodynamic activity of the HG containing Chl-A was evaluated in vitro, demonstrating high therapeutic potential, with an IC 50 of 25.99 µM-an appealing result when compared to studies in the literature reporting an IC 50 of 173.8 µM for cisplatin, used as a positive control drug. The developed formulation of CS and P407-based HG, serving as a thermosensitive system for topical applications, successfully controlled the release of Chl-A. In vitro cell studies associated with PDT exhibited potential against the melanoma cell line.

Breast cancer comprises approximately 20% of all malignant neoplasm cases globally. Due to the limitations associated with conventional therapeutic approaches, extensive investigations have been undertaken to develop novel treatments that exhibit enhanced specificity and minimized adverse effects. Consequently, the application of polymeric nanoformulations for targeted drug delivery has gained significant attention within the biomedical field. Therefore, the primary objective of this study was to explore the inherent advantages and efficacy of employing polymeric nanoformulations for drug delivery in breast cancer treatment, as compared to traditional therapies. A comprehensive literature search was conducted across prominent databases including PubMed/MEDLINE, Embase, and Scopus, utilizing specific search strings. This meticulous approach yielded a total of 12 relevant articles for in-depth analysis and discussion. The findings from the selected studies underscore the effectiveness of employing polymeric nanoparticles as a drug delivery strategy, showcasing noteworthy improvements in cellular uptake and sustained intracellular retention of encapsulated therapeutic agents. Additionally, these nanoformulations exhibited superior efficacy, safety, and drug delivery capabilities. The utilization of polymeric nanoparticles in drug delivery has demonstrated a substantial enhancement in treatment efficacy, with the ability to achieve higher concentrations of active ingredients within tumor tissues, augment cellular uptake and drug concentrations, and sustain intracellular retention. Consequently, this innovative approach prolongs drug release in lower quantities, ultimately contributing to improved treatment outcomes., Competing Interests: Conflict of interestThe authors declare no conflicts of interest regarding the publication of this paper., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Study Question: Is it possible to purge leukemia cells from ovarian tissue (OT) fragments before transplantation?, Summary Answer: Our photodynamic therapy (PDT) approach has been shown to efficiently destroy leukemia cells from tumor-infiltration mimicking models (TIMs), indicating the feasibility of this technique to purge OT samples., What Is Known Already: Autotransplantation of cryopreserved OT is the most suitable option to preserve fertility for prepubertal girls and women who require immediate cancer treatment. Up until now, more than 200 live births have already been reported after OT cryopreservation and transplantation. Leukemia is the 12th most common cancer in Europe among prepubertal girls and women of reproductive age and in 2020, the estimated number of new leukemia cases was higher than 33 000 in girls between 0 and 19 years old. Unfortunately, once their health has been restored, autotransplantation of cryopreserved OT for leukemia patients is not advised due to the high risk of transferring malignant cells back to the patient leading to leukemia recurrence., Study Design Size Duration: To safely transplant the OT from leukemia patients and restore their fertility, our goal was to develop a PDT strategy to eliminate leukemia ex vivo . To this end, we designed OR141-loaded niosomes (ORN) to create the most effective formulation for ex vivo purging of acute myelogenous leukemia cells from OT fragments (n = 4). Moreover, to ensure that such treatments are not harmful to follicle survival and development so they can be deemed a potential fertility restoration alternative, the effect of the ORN-based PDT purging procedure on follicles was assessed after xenografting the photodynamic-treated OT in SCID mice (n = 5). The work was carried out between September 2020 and April 2022 at the Catholic University of Louvain., Participants/materials Setting Methods: After establishing the best ORN formulation, our PDT approach was used to eradicate HL60 cells from ex vivo TIMs prepared by microinjection of a cancer cell suspension into OT fragments. The purging efficiency was analyzed by droplet digital polymerase chain reaction and immunohistochemical analyses. Additionally, we evaluated the effect of ORN-based PDT on follicle density, survival and development, and tissue quality in terms of fibrotic areas and vascularization after 7-day xenotransplantation to immunodeficient mice., Main Results and the Role of Chance: The ex vivo purging of TIMs demonstrated that our PDT strategy could selectively eradicate the malignant cells from tissue fragments without affecting OT normal cells, as evidenced by PCR and immunohistochemical analysis. Regarding the effect of our PDT approach on follicle population and OT quality, our results after xenotransplantation revealed no significant difference between the follicle density of control (non-treated, grafted OT) and PDT-treated groups (2.38 ± 0.63 and 3.21 ± 1.94 morphologically normal follicles/mm 2 , respectively). In addition, our findings showed that the control and PDT-treated OT could be equally vascularized (7.65 ± 1.45% and 9.89 ± 2.21%, respectively). Similarly, the proportions of fibrotic area did not differ between the control (15.96 ± 5.94%) and PDT-treated groups (13.32 ± 3.05%)., Large Scale Data: N/A., Limitations Reasons for Caution: This study did not use OT fragments from leukemia patients, but TIMs created after injection of HL60 cells into OT from healthy patients. Therefore, while the results are promising, whether our PDT approach will be equally successful in eliminating malignant cells from leukemia patients remains to be assessed., Wider Implications of the Findings: Our results showed that the purging procedure causes no significant impairment effect on follicle development and tissue quality, suggesting that our novel PDT procedure could be a promising strategy to destroy leukemia cells in fragments of OT, allowing safe transplantation in cancer survivors., Study Funding/competing Interests: This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention grant number T.0004.20 awarded to C.A.A.); Fondation Louvain (awarded to C.A.A.; a Ph.D. scholarship awarded to S.M., as part of a legacy from Mr Frans Heyes, and a Ph.D. scholarship awarded to A.D. as part of a legacy from Mrs. Ilse Schirmer); and Foundation Against Cancer (grant number 2018-042 awarded to A.C.). The authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: This study aimed to evaluate the effects of salmon calcitonin administration as a pharmacological anchoring agent in orthodontics and to determine the influence of locally applied calcitonin on serum calcium levels. The secondary aim was to observe the response of dental and periodontal tissues using light microscopy., Methods: Fourteen healthy male adult Wistar rats with an average weight of 250 g had their teeth moved, seven of which received a local injection of salmon calcitonin in the furcation region of the left upper first molar. Concurrently, the remaining seven were used as controls. In the control group, saline solution was injected in the bifurcation region of tooth 26 to subject these animals to the same stress level as those of the experimental group. After 14 days, a 6 mm diameter orthodontic elastic band was inserted between teeth 26 and 27 in all animals to induce the movement of these teeth. The rats were anaesthetised and exsanguinated on day 21. In both groups, tooth movement and serum calcium levels were measured. The jaws were dissected with straight scissors, and tissue blocks containing gingiva, bone and teeth were identified, fixed and demineralised. Then, the pieces were cut into semi-serial slices, stained with hematoxylin, eosin, and Mallory's trichrome, and analysed under an Axiophot light microscope., Results: There was significantly less tooth movement in the experimental group (X̄; 0,150 mm ± 0,037) than in the control group (0,236 mm ± 0,044; P = 0,003), while there was no significant difference in serum calcium levels between the two groups (controlX̄; 9,53 mg/dl ± 1,53; experimental 10,81 mg/dl ± 1,47; P = 0,15)., Conclusion: While calcitonin did not completely inhibit osteoclast activity, it promoted orthodontic anchorage, apparently, by local action., Competing Interests: None

Pequi oil (Caryocar brasiliense) contains bioactive compounds capable of modulating the inflammatory process; however, its hydrophobic characteristic limits its therapeutic use. The encapsulation of pequi oil in nanoemulsions can improve its biodistribution and promote its immunomodulatory effects. Thus, the objective of the present study was to formulate pequi oil-based nanoemulsions (PeNE) to evaluate their biocompatibility, anti-inflammatory, and antinociceptive effects in in vitro (macrophages—J774.16) and in vivo (Rattus novergicus) models. PeNE were biocompatible, showed no cytotoxic and genotoxic effects and no changes in body weight, biochemistry, or histology of treated animals at all concentrations tested (90−360 µg/mL for 24 h, in vitro; 100−400 mg/kg p.o. 15 days, in vivo). It was possible to observe antinociceptive effects in a dose-dependent manner in the animals treated with PeNE, with a reduction of 27 and 40% in the doses of 100 and 400 mg/kg of PeNE, respectively (p < 0.05); however, the treatment with PeNE did not induce edema reduction in animals with carrageenan-induced edema. Thus, the promising results of this study point to the use of free and nanostructured pequi oil as a possible future approach to a preventive/therapeutic complementary treatment alongside existing conventional therapies for analgesia.

Breast cancer is the most frequent cause of cancer death in women, representing the fifth leading cause of cancer death overall. Therefore, the growing search for the development of new treatments for breast cancer has been developed lately as well as drug delivery systems such as biocompatible metal-organic Frameworks (bio-MOFs). These may be promising and attractive for drug incorporation and release. The present study aims to develop a drug carrier system RCA (bioMOF-100 submitted to the activation process) containing incorporated curcumin (CCM), whose material surface is coated with folic acid molecules (FA) to promote the targeting of drug carrier systems to the tumor region. They were synthesized and characterized using several characterization techniques. The materials were submitted to drug encapsulation tests, whose encapsulation efficiency was 32.80% for CCM@RCA-1D. Using the 1 H nuclear magnetic resonance (NMR) spectroscopy technique, it was possible to verify the appearance of signals referring to folic acid, suggesting success in the functionalization of these matrices. In vitro tests such as cell viability and type of cell death were evaluated in both series of compounds (CCM@RCA-1D, CCM@RCA-1D/FA) in breast tumor lines. The results revealed low toxicity of the materials and cell death by late apoptosis. Thus, these results indicate that the matrices studied can be promising carriers in the treatment of breast cancer.

Aim: Investigate the heterogeneous tumor tissue organization and examine how this condition can interfere with the passive delivery of a lipid nanoemulsion in two breast cancer preclinical models (4T1 and Ehrlich). Materials & methods: The authors used in vivo image techniques to follow the nanoemulsion biodistribution and microtomography, as well as traditional histopathology and electron microscopy to evaluate the tumor structural characteristics. Results & conclusion: Lipid nanoemulsion was delivered to the tumor, vascular organization depends upon the subtumoral localization and this heterogeneous organization promotes a nanoemulsion biodistribution to the highly vascular peripherical region. Also, the results are presented with a comprehensive mathematical model, describing the differential biodistribution in two different breast cancer models, the 4T1 and Ehrlich models.

This work presents a long-term follow-up (300 days) of rats after a single intravenous injection of DMSA-coated magnetite nanoparticles (DMSA-MNP). The animals were systematically evaluated by hematological, biochemical, and ultrasound examinations, monitoring the same animal over time. In addition, oxidative stress evaluation, DMSA-MNP biodistribution, computerized tomography for ex vivo organs, and histopathology analysis were performed at the end of the experiment period. Overall, DMSA-MNP administration did not cause serious damage to the rats' health over the course of 300 days post-administration. All animals presented hematological parameters within the normal limits, and no alterations on serum creatinine, urea, ALT, and AST were related to DMSA-MNP administration. Liver and spleen showed no important alterations in any of the examinations. The kidneys of treated animals displayed intermittent pelvis dilation at ultrasound analysis, but without damage to the organ parenchyma after 300 days. The lungs of treated animals presented a light interalveolar septal thickening, but the animals did not present any clinical respiratory symptom. Nanoparticles were not detected in the vital organs of treated animals 300 days after administration. This work represents the first assessment of the long-term effects of DMSA-MNP and goes a step further on the safety of its use for biomedical applications.

The World Health Organizations declaration of the COVID-19 pandemic was a milestone for the scientific community. The high transmission rate and the huge number of deaths, along with the lack of knowledge about the virus and the evolution of the disease, stimulated a relentless search for diagnostic tests, treatments, and vaccines. The main challenges were the differential diagnosis of COVID-19 and the development of specific, rapid, and sensitive tests that could reach all people. RT-PCR remains the gold standard for diagnosing COVID-19. However, new methods, such as other molecular techniques and immunoassays emerged. Also, the need for accessible tests with quick results boosted the development of point of care tests (POCT) that are fast, and automated, with high precision and accuracy. This assay reduces the dependence on laboratory conditions and mass testing of the population, dispersing the pressure regarding screening and detection. This review summarizes the advances in the diagnostic field since the pandemic started, emphasizing various laboratory techniques for detecting COVID-19. We reviewed the main existing diagnostic methods, as well as POCT under development, starting with RT-PCR detection, but also exploring other nucleic acid techniques, such as digital PCR, loop-mediated isothermal amplification-based assay (RT-LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS), and immunoassay tests, and nanoparticle-based biosensors, developed as portable instruments for the rapid standard diagnosis of COVID-19., Competing Interests: Conflict of interest statement The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pequi oil is extracted from the fruit of a Brazilian native plant (Caryocar brasiliense Camb) that contains some molecules with anticancer potential. Due to its hydrophobic property, the administration of pequi oil associated with nanoemulsion systems represents a successful strategy to improve oil bioavailability. Breast cancer is the most frequent type of cancer among women and conventional therapies used are frequently associated with several side effects. Thus, the aim of this study was to investigate the effects of pequi oil-based nanoemulsion (PeNE) on triple-negative breast cancer cells (4T1), in vitro. PeNE presented a dose- and time-dependent cytotoxic effect with lower IC50 than free pequi oil after 48 h of exposure (p < 0.001). At 180 µg/mL, PeNE demonstrated numerous cell alterations, when compared to free pequi oil, such as morphological alterations, reduction in cell proliferation and total cell number, damage to plasmatic membrane, induction of lysosomal membrane permeability and depolarization of mitochondrial membrane, alteration of intracellular ROS production and calcium level, and increase in phosphatidylserine exposure. Taken together, the results suggest an interesting induction of cell death mechanisms involving a combined action of factors that impair nucleus, mitochondria, lysosome, and ER function. In addition, more pronounced effects were observed in cells treated by PeNE at 180 µg/mL when compared to free pequi oil, thereby reinforcing the advantages of using nanometric platforms. These promising results highlight the use of PeNE as a potential complementary therapeutic approach to be employed along with conventional treatments against breast cancer in the future., Competing Interests: Conflict of Interest G. A. Joanitti, V. H. S. Araujo, and R. B Azevedo are named inventors of the following patent application (Provisional Patent: BR 10 2017 025294 9, November 24, 2017, Brazilian Patent Office [Instituto Nacional da Propriedade Industrial – INPI]) regarding the development and use of pequi oil-based nanoemulsions. This patent does not represent a direct conflict of interest to the reported data in this manuscript. All other authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study investigated the fabrication of spherical gold shelled maghemite nanoparticles for use in magnetic hyperthermia (MHT) assays. A maghemite core (14 ± 3 nm) was used to fabricate two samples with different gold thicknesses, which presented gold (g)/maghemite (m) content ratios of 0.0376 and 0.0752. The samples were tested in MHT assays (temperature versus time) with varying frequencies (100-650 kHz) and field amplitudes (9-25 mT). The asymptotic temperatures (T∞) of the aqueous suspensions (40 mg Fe/mL) were found to be in the range of 59-77 °C (naked maghemite), 44-58 °C (g/m=0.0376) and 33-51 °C (g/m=0.0752). The MHT data revealed that T∞ could be successful controlled using the gold thickness and cover the range for cell apoptosis, thereby providing a new strategy for the safe use of MHT in practice. The highest SAR (specific absorption rate) value was achieved (75 kW/kg) using the thinner gold shell layer (334 kHz, 17 mT) and was roughly twenty times bigger than the best SAR value that has been reported for similar structures. Moreover, the time that was required to achieve T∞ could be modeled by changing the thermal conductivity of the shell layer and/or the shape/size of the structure. The MHT assays were pioneeringly modeled using a derived equation that was analytically identical to the Box-Lucas method (which was reported as phenomenological).

This study sought to identify monocyte alterations from septic patients after hospital discharge by evaluating gene expression of inflammatory mediators and monocyte polarization markers. It was hypothesized that sepsis reprograms the inflammatory state of monocytes, causing effects that persist after hospital discharge and influencing patient outcomes., Design: The gene expression patterns of inflammatory receptors, M1 and M2 macrophage polarization markers, NLRP3 inflammasome components, and pro- and anti-inflammatory cytokines in monocytes were assessed., Patients: Thirty-four patients from the University of São Paulo Hospital, during the acute sepsis phase (phase A), immediately after ICU discharge (phase B), and 3 months (phase C), 6 months (phase D), 1 year (phase E), and 3 years (phase F) after discharge, were included. Patients that died during phases A and B were grouped separately, and the remaining patients were collectively termed the survivor group., Measurements and Main Results: The gene expression of toll-like receptor ( TLR ) 2 and TLR4 (inflammatory receptors), NLRP3, NFκB1 , adaptor molecule apoptosis-associated speck-like protein containing a CARD , caspase 1, caspase 11 , and caspase 12 (NLRP3 inflammasome components), interleukin-1α, interleukin-1β , interleukin-18, and high-mobility group box 1 protein (proinflammatory cytokines), interleukin-10 (anti-inflammatory cytokine), C-X-C motif chemokine ligand 10, C-X-C motif chemokine ligand 11, and interleukin-12p35 (M1 inflammatory polarization markers), and C-C motif chemokine ligand 14, C-C motif chemokine ligand 22, transforming growth factor-beta ( TGF-β ), SR-B1 , and peroxisome proliferator-activated receptor γ (M2 anti-inflammatory polarization and tissue repair markers) was upregulated in monocytes from phase A until phase E compared with the control group., Conclusions: Sepsis reprograms the inflammatory state of monocytes, probably contributing to postsepsis syndrome development and mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

(1) Background: Essential oils have long been used as therapeutic agents. Lavender ( Lavandula angustifolia ) oil (LO) is an antispasmodic, anticonvulsant, relaxant, painkilling, and antimicrobial essential oil investigated as a natural substance for biomedical therapies. Nanoparticles have shown significant promise in improving drug delivery and efficacy. Considering these benefits, the aim of this study was to evaluate the toxicity of LO and lavender oil niosomes (LONs) in stem cells and myofibroblast models cultured in vitro. (2) Methods: Adipose tissue-derived stem cells and myometrial cells were cultured with LO or LONs at different concentrations (0, 0.016%, 0.031%, and 0.063%) and toxicity was evaluated with PrestoBlue™ and live/dead assay using calcein and ethidium homodimer. (3) Results: Cell viability was similar to controls in all groups, except in 0.063% LO for myometrial cells, which showed lower viability than the control medium. (4) Conclusion: These results suggest that both LO and LONs are safe for cell culture and may be used for pharmaceutical and biomedical therapies in future applications in regenerative medicine.

Diets rich in omega-3 or -6 fatty acids will produce different profiles for cell membranes phospholipid constitutions. Omegas 3 and 6 are part of the diet and can modulate the inflammatory profile. We evaluated the effects of the oral absorption of fish oil, when associated with a lipid nanoemulsion in an experimental pulmonary inflammatory model. Pulmonary fibrosis is a disease associated with excessive extracellular matrix deposition. We determined to investigate the morphophysiological mechanisms in mice that were pretreated after induction with bleomycin (BLM). The pretreatment was for 21 days with saline solution, sunflower oil (SO), fish oil (FO), and fish oil nanoemulsion (NEW3). The animals received a daily dose of 50 mg/Kg of docosahexaenoic acid DHA and 10 mg/Kg eicosapentaenoic (EPA) (100 mg/Kg), represented by a daily dose of 40 µL of NEW3. The blank group was treated with the same amount daily (40 µL) during the 21 days of pretreatment. The animals were treated with SO and FO, 100 mg/Kg (containing 58 mg/Kg of polyunsaturated fats/higher% linoleic acid) and 100 mg/Kg (50 mg/Kg of DHA and 10 mg/Kg EPA), respectively. A single dose of 5 mg/mL (50 μL) bleomycin sulfate, by the intratracheal surgical method in BALB/cAnNTac (BALB/c). NEW3 significantly reduced fibrotic progression, which can be evidenced by the protection from loss of body mass, increase in respiratory incursions per minute, decreased spacing of alveolar septa, decreased severity of fibrosis, and changes in the respiratory system. NEW3 attenuated the inflammatory changes developed in the experimental model of pulmonary fibrosis, while group SO showed a significant increase in inflammatory changes. This concluded that the presented results demonstrated that is possible to positively modulate the immune and inflamamtory response to an external agressor, by changing the nutitional intake of specific fatty acids, such as omega-3 placed in fish oil. Moreover, these benefits can be improved by the nanoencapsulation of fish oil in lipid nanoemulsions.

Aim: To develop a new curcumin carrier consisting of murumuru butter nanoparticles (SLN-Cs). Methods: A phase-inversion temperature method was used to produce SLN-Cs. The interaction of SLN-Cs with murine colon adenocarcinoma (CT26) cells in vitro was analyzed by confocal microscopy. Results: Stable SLN-Cs with a high curcumin-loading capacity were obtained. The SLN-Cs were more toxic to CT26 than free curcumin. Fluorescence microscopy images showed the SLN-Cs to be taken up by CT26 cells in vitro . Conclusion: These results indicate that SLN-Cs are suitable carriers of curcumin in aqueous media.

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs-CRT, HSP70, HSP90, HMGB1, and IL-1β-were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC 50 and a light dose of 25 J/cm 2 exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC 50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC 50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo.

Background: Cardiovascular (CV) risk factors, particularly cardiometabolic, seem to be associated with heightened severity and increased morbimortality in patients infected with the novel Coronavirus disease-2019 (COVID-19)., Methods: A thorough scoping review was conducted to elucidate and summarize the latest evidence for the effects of adverse cardiac metabolic profiles on the severity, morbidity, and prognosis of COVID-19 infection., Results: The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is complex, being characterized by viral-induced immune dysregulation and hypercytokinemia, particularly in patients with critical disease, evolving with profound endothelial dysfunction, systemic inflammation, and prothrombotic state. Moreover, cardiovascular comorbidities such as diabetes are the most prevalent amongst individuals requiring hospitalization, raising concerns towards the clinical evolution and prognosis of these patients. The chronic proinflammatory state observed in patients with cardiovascular risk factors may contribute to the immune dysregulation mediated by SARS-CoV-2, favoring more adverse clinical outcomes and increased severity. Cardiometabolism is defined as a combination of interrelated risk factors and metabolic dysfunctions such as dyslipidemia, insulin resistance, impaired glucose tolerance, and central adiposity, which increase the likelihood of vascular events, being imperative to specifically analyze its clinical association with COVID-19 outcomes., Conclusion: DM and obesity appears to be important risk factors for severe COVID-19. The chronic proinflammatory state observed in patients with excess visceral adipose tissue (VAT) possibly augments COVID-19 immune hyperactivity leading to more adverse clinical outcomes in these patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX. Cell death following L-PTX administration hinted at apoptosis, with most cells undergoing initial apoptosis. A2780 cells exhibited an inhibitory migration profile when analyzed by Wound Healing and real-time cell analysis (xCELLigence) methods after L-PTX administration. This inhibition was related to decreased expression of the zinc finger E-box-binding homeobox 1 (ZEB1) and transforming growth factor 2 (TGF-β2) genes. In vivoL-PTX administration strongly inhibited tumor cell proliferation in ovarian peritoneal carcinomatosis derived from ovarian cancer, indicating higher antitumor activity than PTX. L-PTX formulation did not show toxicity in the mice model. This study demonstrated that liposomal paclitaxel formulations are less toxic to normal tissues than free paclitaxel and are more effective in inhibiting tumor cell proliferation/migration and inducing ZEB1/TGF-β2 gene expression., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Acute kidney injury (AKI) in hospitalized patients with COVID-19 is associated with higher mortality and a worse prognosis. Nevertheless, most patients with COVID-19 have mild symptoms, and about 5% can develop more severe symptoms and involve hypovolemia and multiple organ dysfunction syndrome. In a pathophysiological perspective, severe SARS-CoV-2 infection is characterized by numerous dependent pathways triggered by hypercytokinemia, especially IL-6 and TNF-alpha, leading to systemic inflammation, hypercoagulability, and multiple organ dysfunction. Systemic endotheliitis and direct viral tropism to proximal renal tubular cells and podocytes are important pathophysiological mechanisms leading to kidney injury in patients with more critical infection, with a clinical presentation ranging from proteinuria and/or glomerular hematuria to fulminant AKI requiring renal replacement therapies. Glomerulonephritis, rhabdomyolysis, and nephrotoxic drugs are also associated with kidney damage in patients with COVID-19. Thus, AKI and proteinuria are independent risk factors for mortality in patients with SARS-CoV-2 infection. We provide a comprehensive review of the literature emphasizing the impact of acute kidney involvement in the evolutive prognosis and mortality of patients with COVID-19.

Controlling populations of free-roaming dogs and cats poses a huge challenge worldwide. Non-surgical neutering strategies for male animals have been long pursued, but the implementation of the procedures developed has remained limited to date. As submitting the testes to high temperatures impairs spermatogenesis, the present study investigated localized application of magnetic nanoparticle hyperthermia (MNH) to the testicles as a potential non-surgical sterilization method for animals. An intratesticular injection of a magnetic fluid composed of manganese-ferrite nanoparticles functionalized with citrate was administered followed by testicle exposure to an alternate magnetic field to generate localized heat. Testicular MNH was highly effective, causing progressive seminiferous tubule degeneration followed by substitution of the parenchyma with stromal tissue and gonadal atrophy, suggesting an irreversible process with few side effects to general animal health.

Kidney impairment in hospitalized patients with SARS-CoV-2 infection is associated with increased in-hospital mortality and worse clinical evolution, raising concerns towards patients with chronic kidney disease (CKD). From a pathophysiological perspective, COVID-19 is characterized by an overproduction of inflammatory cytokines (IL-6, TNF-alpha), causing systemic inflammation and hypercoagulability, and multiple organ dysfunction syndrome. Emerging data postulate that CKD under conservative treatment or renal replacement therapy (RRT) is an important risk factor for disease severity and higher in-hospital mortality amongst patients with COVID-19. Regarding RAAS blockers therapy during the pandemic, the initial assumption of a potential increase and deleterious impact in infectivity, disease severity, and mortality was not evidenced in medical literature. Moreover, the challenge of implementing social distancing in patients requiring dialysis during the pandemic prompted national and international societies to publish recommendations regarding the adoption of safety measures to reduce transmission risk and optimize dialysis treatment during the COVID-19 pandemic. Current data convey that kidney transplant recipients are more vulnerable to more severe infection. Thus, we provide a comprehensive review of the clinical outcomes and prognosis of patients with CKD under conservative treatment and dialysis, and kidney transplant recipients and COVID-19 infection.

Background: Photodynamic therapy (PDT) using chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) can be effective against New World Leishmania species involved in cutaneous leishmaniasis (CL). The aim of this study is to assay the skin permeation and the antileishmanial effects of a nanoemulsion (NE) containing both ClAlPc and PM in experimental CL by Leishmania ( Viannia ) braziliensis ., Material and Methods: Cremophor ELP/castor oil-based NEs were prepared by a low-energy method and characterized for their physicochemical parameters. The NEs were used to deliver both ClAlPc and PM to leishmania cells. The in vitro toxicity of NEs were tested in vitro against L. ( V. ) braziliensis and THP-1 cells. The in vivo toxicity was assessed in non-infected BALB/c mice. Ex-vivo permeation and retention studies using healthy mice skin were also conducted. Finally, the in vivo activity of NE-PM+ClAlPc after PDT was tested in BALB/c mice infected with parasites., Results: NEs are colloidally stable with average droplet diameter of 30 nm, polydispersity index (PDI) below 0.2, and zeta potential near zero. Both promastigotes and intracellular amastigotes treated with NE-PM, NE-ClAlPc and NE-PM+ClAlPc were inhibited at >50%, >95%, >88%, respectively, after PDT with a phototoxic index (PI) >1.2. No skin ClAlPc permeation was observed. In contrast, PM skin permeation was 80-fold higher using PM-loaded NE formulation in comparison to aqueous PM solution. Topical treatment with NE formulations showed no signs of local toxicity or genotoxicity. In addition, concentrations of PM between 27.3 - 292.5 μM/25 mg of tissue were detected in different organs. In vivo , the NE-PM+ClAlPc treatment did not reduce skin lesions., Conclusion: The Cremophor ELP/castor oil NE formulation increases the permeation of PM through the skin and can be used to co-deliver PM plus ClAlPc for combined PDT protocols. However, the lack of efficacy in the in vivo model evidences that the therapeutical scheme has to be improved., Competing Interests: No conflicts of interest., (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Doxorubicin (DOX) is an anthracycline antibiotic used in the fight against many types of cancer. Although it is quite effective for this purpose, its clinical use is limited by its severe side effects, highlighting the relevance of efforts to identify substances that act to minimize these effects. In this work, we sought to verify the ability of andiroba oil (AO) and a nanoemulsion of andiroba oil (AN) to lessen the side effects of DOX. The animals were separated into 7 groups with 6 animals each: mice treated with AO (2000 mg/kg), AN (2000 mg/kg), the antineoplastic agent DOX (40 mg/kg), AO+DOX, AN+DOX and solvent controls was used of negative control (corn oil and nanoemulsion surfactant). AO and AN were administered for 14 consecutive days orally by gavage and on the 13th day, applied DOX by intraperitoneal route (i.p.), in order to evaluate the protective potential of andiroba. The animals were euthanized on the 15th day. Hematological, biochemical, histological, and immunohistochemical parameters were analyzed. Andiroba reduced several aspects of the severity of lesions caused by DOX, decreasing hematotoxicity and the severity of histological changes in the liver and kidneys, and reducing the frequency of apoptotic cell death. In many cases, AN showed greater efficacy than AO alone, reflecting the feasibility of using this nanotechnology to improve the pharmacokinetics of lipid compounds in the body. The study sheds new light on the therapeutic benefits of andiroba and suggests new ways for investigating how the quantity and quality of lipid compounds affect exposed organisms., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Bacterial resistance has intensified in recent years due to the uncontrolled use of conventional drugs, and new bacterial strains with multiple resistance have been reported. This problem may be solved by using antimicrobial peptides (AMPs), which fulfill their bactericidal activity without developing much bacterial resistance. The rapid interaction between AMPs and the bacterial cell membrane means that the bacteria cannot easily develop resistance mechanisms. In addition, various drugs for clinical use have lost their effect as a conventional treatment; however, the synergistic effect of AMPs with these drugs would help to reactivate and enhance antimicrobial activity. Their efficiency against multi-resistant and extensively resistant bacteria has positioned them as promising molecules to replace or improve conventional drugs. In this review, we examined the importance of antimicrobial peptides and their successful activity against critical and high-priority bacteria published in the WHO list.

Water is vital for the survival of any species because of its key role in most physiological processes. However, little is known about the non-food-related water sources exploited by arboreal mammals, the seasonality of their drinking behavior and its potential drivers, including diet composition, temperature, and rainfall. We investigated this subject in 14 wild groups of brown howler monkeys (Alouatta guariba clamitans) inhabiting small, medium, and large Atlantic Forest fragments in southern Brazil. We found a wide variation in the mean rate of drinking among groups (range = 0-16 records/day). Streams (44% of 1,258 records) and treeholes (26%) were the major types of water sources, followed by bromeliads in the canopy (16%), pools (11%), and rivers (3%). The type of source influenced whether howlers used a hand to access the water or not. Drinking tended to be evenly distributed throughout the year, except for a slightly lower number of records in the spring than in the other seasons, but it was unevenly distributed during the day. It increased in the afternoon in all groups, particularly during temperature peaks around 15:00 and 17:00. We found via generalized linear mixed modelling that the daily frequency of drinking was mainly influenced negatively by flower consumption and positively by weekly rainfall and ambient temperature, whereas fragment size and the consumption of fruit and leaves played negligible roles. Overall, we confirm the importance of preformed water in flowers to satisfy the howler's water needs, whereas the influence of the climatic variables is compatible with the 'thermoregulation/dehydration-avoiding hypothesis'. In sum, we found that irrespective of habitat characteristics, brown howlers seem to seek a positive water balance by complementing the water present in the diet with drinking water, even when it is associated with a high predation risk in terrestrial sources., Competing Interests: The authors have declared that no competing interests exist.

Bioactive carbon dots (C-dots) with ca. 4 nm were successfully produced with singular photophysical properties, low-toxicity and interesting immunological response. The optical properties of the C-dots were investigated and the "light-up" behaviour enabled them to be explored in glucose detection and bioimaging experiments (mitochondrial selective probe). C-dots were not selective to the tumour region and several fluorescent spots were visualized spread on animal bodies. The histology investigations showed that cancer-bearing mice treated with C-dots presented a large number of regions with necrosis and inflammatory infiltrates, which were not identified for cancer-bearing mice without the treatment. These results suggested that C-dots have the potential to be explored as an immune therapy agent for melanoma skin cancer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To improve the oral absorption of fish oil and test its anti-inflammatory effect, a fish oil nanoemulsion was developed using cis-4,7,10,13,16,19-docosahexaenoic fatty acid as a biomarker for oral administration. The colloidal stability tests of the fish oil nanoemulsion showed an average size of 155.44 nm ± 6.46 (4 °C); 163.04 nm ± 9.97 (25 °C) and polydispersity index 0.22 ± 0.02 (4 °C), 0.21 ± 0.02 (25 °C), indicating systems with low polydispersity and stable droplets. The fish oil nanoemulsion did not alter the cell viability of the RAW 264.7 macrophages and, at a concentration of 0.024 mg/mL, was kinetically incorporated into the cells after 18 h of contact. The nanoemulsion was maintained in the gastrointestinal region for a significantly shorter period of time (p ≤ 0.05) compared to the intake of fish oil in free form. Inflammatory tests demonstrated that nanoemulsion and fish oil showed less (p ≤ 0.05) neutrophil infiltration after 24h of sepsis induction and there was a significant reduction (p ≤ 0.05) in the volume of paw edema in female adult Balb/c mice who received the nanoemulsion diet compared to the other experimental groups (control, formalin, fish oil and sunflower oil). These results indicate that the fish oil nanoemulsion was significantly effective in the dietary conditions tested here, presenting satisfactory responses in the modulation of inflammatory disorders, demonstrating interesting and beneficial nutraceutical effects., (Copyright © 2020. Published by Elsevier Masson SAS.)

Aim: To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Materials & methods: Immunogenic cell death induction by the Pacli/Dox combination was assessed in vitro . Antitumor activity and in vivo safety of Lipo-Pacli/Dox were evaluated using a 4T1 breast cancer mouse model Results : Lipo-Pacli/Dox, with a size of 189 nm and zeta potential of -5.01 mV, promoted immune system activation and partially controlled the progression of pulmonary metastasis. Conclusion: Lipo-Pacli/Dox was useful to control both primary tumor and lung metastasis in breast cancer (4T1) mice model. Additionally, Lipo-Pacli/Dox acts as an immunological modulator for this metastatic breast cancer model.

Objectives: This clinical study was developed to primarily evaluate the Complete Cytopathological Response Rate of Cervical Intraepithelial Neoplasms to PDT using chitosan nanocapsules containing Chlorocyan-aluminum phthalocyanine as a photoactive agent. Analyses of the Free Recurrence Interval, toxicity profile (immediate and late), and complications (immediate and late), were secondarily analyzed., Methods: This study was previously approved by the National Council of Ethics in Research of Brazil (CONEP), on May 28, 2014, under case number 19182113.4.0000.5009. On the surface of the cervix of each selected patient was applied one mL of the formulated gel, and after 30 min, the light was applied. Reports or the identification of adverse effects and/or complications were observed in follow-up visits, in addition to the collection of cervical oncotic cytology., Results: Out of the total group, 11 (91.7%) primarily treated patients evolved with negative cervical oncotic cytology as soon as in the first evaluation following treatment, and one did not achieve any therapeutic benefit, even after reapplication. Two patients with initially positive response presented cytological recurrence determined by histopathology. A new round of PDT was developed, and both evolved with cytological remission three weeks later, remaining negative until the last follow-up. No important side effects were observed in all the patients., Conclusions: Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy.

Aim: Nano-5-aminolevulic acid (NanoALA)-mediated photodynamic therapy (PDT), an oil-in-water polymeric nanoemulsion of ALA, was evaluated in a murine model of breast cancer. Materials & methods: Analysis of ALA-derived protoporphyrin IX production and acute toxicity test, biocompatibility and treatment efficacy, and long-term effect of NanoALA-PDT on tumor progression were performed. Results: The nanoformulation favored the prodrug uptake by tumor cells in a shorter time (1.5 h). As a result, the adverse effects were negligible and the response rates for primary mammary tumor control were significantly improved. Tumor progression was slower after NanoALA-PDT treatment, providing longer survival. Conclusion: NanoALA is a good proactive drug candidate for PDT against cancer potentially applied as adjuvant/neoadjuvant intervention strategy for breast cancer.