Biogenic silver nanoparticles are synthesized through silver(I) reduction, which is promoted by biomolecules available in the biological world and mostly obtained from plant extracts, fungal bioproduction, and some bacteria. The exact mechanisms accounting for such oxidoreduction processes are not fully known. However, some studies have already mentioned oxidoreductases, cofactors (nicotinamide adenine dinucelotide hydrogen (NADH), dihydroflavine-adenine dinucleotid (FADH2)), and phenolic compounds, as the main reductive species engaged in the formation of silver(0) and silver nanoparticles (silver NPs) synthesis. Biosynthesis is a one-pot process that leads to stable silver NP colloids that, regarding their size, shape, and uniformity, can be successfully controlled; and show great stability when one takes into account their surface capping by some biomolecules that as well take part in their synthesis. Although great efforts have been made to feature capping biomolecules and their interactions with silver NP surfaces, knowledge of the quantity (exact number per cm2) and type of biomolecules that cap or surround silver NPs remains limited. The literature provides detailed information on protein capping, but it still shows gaps regarding many aspects of fine biophysical protein featuring. The reason why certain proteins prefer to interact with silver NP surface and form chemical bonds, whereas others rather have intermolecular interaction with the first layer of proteins remains unknown. Assessing capping proteins’ involvement in the bioactivity of biogenic silver NPs is another relevant research field. Certain proteins enhance bioactivity of silver NPs and lower toxicity; however, the way antimicrobial processes benefit from protein capping is yet to be discovered. Finally, biogenic silver NPs can be found both in the environment and in water; moreover, their additional activity and behavior must be known or, at least, hypothesized.

ABSTRACT Purpose: Despite high success rates in the treatment of urinary incontinence, complications related to the use of polypropylene (PP) meshes are still a concern, especially in vaginal prolapses surgeries. The objective of this study was to assess the effect of autologous platelet-rich plasma (PRP) coating on the integration of PP meshes implanted in the vaginal submucosa of rabbits. Materials and Methods: Thirty adult New Zealand rabbits were randomly divided into two groups (n=15): PP, implanted with conventional PP meshes; and PRP, implanted with autologous PRP coated PP meshes. Animals in both groups (n=5) were euthanized at 7, 30 and 90 days postoperatively, the vaginas extracted and sent to immunohistochemical analysis for the assessment of the pro-inflammatory agent TNF-α, anti-inflammatory agents TGF-β and IL-13, collagen metabolism marker MMP-2, and angiogenesis marker CD-31. AxioVision™ image analysis was used for the calculation of the immunoreactive area and density. Statistical analysis was performed with ANOVA followed by Tukey test (p <0.05). Results: Animals in the PRP group showed significantly increased expression of the angiogenesis agent CD-31 at all experimental times when compared to the PP group (p <0.0001). However, no differences concerning the expression of the other markers were observed between the groups. Conclusion: The addition of autologous PRP gel to PP meshes can be simply and safely achieved and seems to have a positive effect on implantation site angiogenesis. Further investigations are required to ascertain PPR coated meshes clinical efficacy in prolapses and stress urinary incontinence surgeries.

Many well-known commercial pharmaceuticals have been used in the therapy against SARS-CoV-2, although in a random and experimental way, since this use is only based on the knowledge about culture cells in vitro. But, it is widely known that it is not correlated with assays in vivo conducted with in animals or with clinical trials in humans. Knowledge about treatments applied to previous pandemic infections caused by viruses such as MERS and SARS may be the most interesting strategy used to screen products with potential to act against SARS-CoV-2. Mechanistic aspects of virus infections and antiviral action mechanisms were herein analyzed based on the assumption that these commercial pharmaceuticals can eliminate the virus. Perspectives about these procedures, as well as about finished clinical trials and the ones yet in progress, were also addressed in the current study.

Muchos productos farmacéuticos comerciales bien conocidos se han utilizado en la terapia contra el SARS-CoV-2, aunque de manera aleatoria y experimental, ya que este uso solo se basa en el conocimiento sobre células de cultivo in vitro. Pero, es ampliamente conocido que no está correlacionado con ensayos in vivo realizados con animales o con ensayos clínicos en humanos. El conocimiento sobre los tratamientos aplicados a infecciones pandémicas previas causadas por virus como MERS y SARS puede ser la estrategia más interesante utilizada para detectar productos con potencial para actuar contra el SARS-CoV-2. Los aspectos mecanicistas de las infecciones por virus y los mecanismos de acción antivirales se analizaron en este documento basándose en el supuesto de que estos productos farmacéuticos comerciales pueden eliminar el virus. Las perspectivas sobre estos procedimientos, así como sobre los ensayos clínicos terminados y los que aún están en progreso, también se abordaron en el estudio actual.

Muitos fármacos comerciais bem conhecidos têm sido utilizados na terapia contra SARS-CoV-2, embora de maneira aleatória e experimental, uma vez que esse uso é baseado apenas no conhecimento sobre cultura de células in vitro. Entretanto, sabe-se o que não está correlacionado com ensaios in vivo realizados com animais ou com ensaios clínicos em humanos. O conhecimento sobre tratamentos aplicados a infecções pandêmicas anteriores causadas por vírus como MERS e SARS pode ser a estratégia mais interessante usada para rastrear produtos com potencial para agir contra o SARS-CoV-2. Aspectos mecanísticos de infecções por vírus e mecanismos de ação antiviral foram aqui analisados com base no pressuposto de que esses produtos farmacêuticos comerciais podem eliminar o vírus. As perspectivas sobre esses procedimentos, bem como sobre os ensaios clínicos concluídos e os que ainda estão em andamento, também foram abordados no presente estudo.

Silver nanoparticles (AgNPs) have important antimicrobial activity. These nanoparticles are present in several commercial products, leading to human and environmental exposure. This review presents a critical view of the toxic effects of Ag NPs on in vitro and in vivo biological models. It is noteworthy that the toxicity of AgNPs is dependent on several parameters, such as the preparation mode of the colloidal suspension of the nanoparticles, their state of aggregation, the chemical nature of the nanoparticles, surface size, morphology, dose, cell type, nature of the living organism, among others. In general, low concentrations of AgNPs do not present significant toxicity in in vitro and in vivo assays, however with the increase of the concentration of AgNPs there is a significant increase of nanoparticle toxicity and its accumulation in diverse tissues/organs. It should be emphasized that in living organisms, exposure routes should be taken into account, such as ingestion and inhalation. At high concentrations, inhalation or ingestion of AgNPs can cause adverse effects and even lead to human death. In this context, the importance of further studies of the toxicity of AgNPs in several in vitro and in vivo models is emphasized.

The primary treatment for high-grade non-muscle invasive bladder cancer (NMIBC) is based on surgery by transurethral resection of bladder tumor (TURBT), followed by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) to prevent recurrence and to reduce the tumor progression. However, BCG therapy shows several undesirable effects. The current treatment on NMIBC is doxorubicin (DOX), but with high toxicity. Our nanotechnology strategy was done through scaffolds for the NMIBC treatment: graphene oxide (GO) and a nanostructured lipid carrier (NLC). A GO hybrid for administration of DOX and small interfering RNA (siRNA) was developed. This hybrids administered in vivo against NMIBC in rats gave absence of lesions. NLC was prepared by using a mixture of two lipids stabilized by a surfactant and DOX by high homogenization pressure technique. In this case showed a 20% of the animals exhibited benign lesions (papillary hyperplasia), however, in the presence of siRNA reached 40% of rats with benignant lesions. These two scaffolds are potential new drugs for DOX for bladder cancer treatment without any cardiotoxicity problems.

ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.

ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.

OBJETIVO: Apresentar aspectos anatômicos fundamentais e habilidades técnicas necessárias para cateterismo da uretra e bexiga em ratos e camundongos fêmeas. MÉTODOS: Cateterismo vesical tem sido amplamente utilizado na pesquisa do câncer e carcinogênese, além de várias outras aplicações, desde fins toxicológicos, condições inflamatórias e infecciosas até aspectos funcionais como a dinâmica vesical e refluxo vesico-ureteral, entre muitos outros. RESULTADOS: Os modelos animais estão no centro da investigação de translação e os roedores são os mais importantes devido a várias vantagens, incluindo reprodutibilidade humana, o fácil manuseio e baixo custo. CONCLUSÕES: Apesar de permitir o desenvolvimento da investigação pré-clínica do trato urinário inferior, o modelo se restringe aos animais do sexo feminino, de modo que avanços futuros são necessários.

PURPOSE: To present fundamental anatomical aspects and technical skills necessary to urethra and urinary bladder catheterization in female mice and rats. METHODS: Urethral and bladder catheterization has been widely utilized for carcinogenesis and cancer research and still remains very useful in several applications: from toxicological purposes as well as inflammatory and infectious conditions to functional aspects as bladder dynamics and vesicoureteral reflux, among many others. RESULTS: Animal models are in the center of translational research and those involving rodents are the most important nowadays due to several advantages including human reproducibility, easy handling and low cost. CONCLUSIONS: Although technical and anatomical pearls for rodent urethral and bladder access are presented as tackles to the advancement of lower urinary tract preclinical investigation in a broaden sight, restriction to female animals hampers the male microenvironment, demanding future advances.