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Browsing by Author "Zacconi, Flavia C. M."

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Advances in nanotechnology-based drug delivery in targeting PI3K signaling in respiratory diseases
(FUTURE MEDICINE LTD, 2021) Chan, Yinghan; MacLoughlin, Ronan; Zacconi, Flavia C. M.; Tambuwala, Murtaza M.; Pabari, Ritesh M.; Singh, Sachin Kumar; Pinto Andreoli, Terezinha de Jesus; Gupta, Gaurav; Chellappan, Dinesh Kumar; Dua, Kamal
Assessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy
(2021) Xavier, Aline; Zacconi, Flavia C. M.; Santana Romo, Fabián Mauricio; Eykyn, Thomas R.; Lavin, Begona; Phinikaridou, Alkystis; Botnar, Rene; Uribe, Sergio; Esteban Oyarzun, Juan; Cabrera, Daniel; Arrese, Marco; Andia, Marcelo E.
Abstract: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). Methods: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. Results: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. Conclusion: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review
(2019) Charbe, N.; Zacconi, Flavia C. M.; Amnerkar, N.; Murtaza, R.; Tambuwala, M.; Clementi, E.
Background: Several clinical trials, as well as observational statistics, have exhibited that the advantages of antiretroviral [ARV] treatment for humans with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome HIV/AIDS exceed their risks. Therapeutic drug monitoring [TDM] plays a key role in optimization of ARV therapy. Determination of ARV's in plasma, blood cells, and other biological matrices frequently requires separation techniques capable of high effectiveness, specific selectivity and high sensitivity. High-performance liquid chromatography [HPLC] coupled with ultraviolet [UV], Photodiode array detectors [PDA], Mass spectrophotometer [MS] detectors etc. are the important quantitative techniques used for the estimation of pharmaceuticals in biological samples. Objective: This review article is aimed to give an extensive outline of different bio-analytical techniques which have been reported for direct quantitation of ARV's. This article aimed to establish an efficient role played by the TDM in the optimum therapeutic outcome of the ARV treatment. It also focused on establishing the prominent role played by the separation techniques like HPLC and UPLC along with the detectors like UV and Mass in TDM. Methods: TDM is based on the principle that for certain drugs, a close relationship exists between the plasma level of the drug and its clinical effect. TDM is of no value if the relationship does not exist. The analytical methodology employed in TDM should: 1) distinguish similar compounds; 2) be sensitive and precise and 3) is easy to use Results: This review highlights the advancement of the chromatographic techniques beginning from the HPLC-UV to the more advanced technique like UPLC-MS/MS. TDM is essential to ensure adherence, observe viral resistance and to personalize ARV dose regimens. It is observed that the analytical methods like immunoassays and liquid chromatography with detectors like UV, PDA, Florescent, MS, MS/MS and Ultra performance liquid chromatography (UPLC)-MS/MS have immensely contributed to the clinical outcome of the ARV therapy. Assay methods are not only helping physicians in limiting the side effects and drug interactions but also assisting in monitoring patient's compliance. Conclusion: The present review revealed that HPLC has been the most widely used system irrespective of the availability of more sensitive chromatographic technique like UPLC.
Bio-click chemistry: a bridge between biocatalysis and click chemistry
(2022) Rodríguez Sánchez, Diego Fernando; Moglie, Yanina; Ramírez Sarmiento, César Antonio; Singh, Sachin Kumar; Dua, Kamal; Zacconi, Flavia C. M.
The fields of click chemistry and biocatalysis have rapidly grown over the last two decades. The development of robust and active biocatalysts and the widespread use of straightforward click reactions led to significant interactions between these two fields. Therefore the name bio-click chemistry seems to be an accurate definition of chemoenzymatic reactions cooperating with click transformations. Bio-click chemistry can be understood as the approach towards molecules of high-value using a green and sustainable approach by exploiting the potential of biocatalytic enzyme activity combined with the reliable nature of click reactions. This review summarizes the principal bio-click chemistry reactions reported over the last two decades, with a special emphasis on small molecules. Contributions to the field of bio-click chemistry are manifold, but the synthesis of chiral molecules with applications in medicinal chemistry and sustainable syntheses will be especially highlighted.
Bioactive compounds in Apis mellifera monofloral honeys
(2021) Viteri Espinoza, Rafael Antonio; Zacconi, Flavia C. M.; Montenegro Rizzardini, Gloria; Giordano Villatoro, Ady Iveth
Honey is a natural product with a sweet flavor. Honey is made by the honeybee (Apis mellifera L.) from the nectar of flowers or other plant secretions that are collected near the hive. These products are mixed with bee saliva and stored. Several studies have demonstrated that honey exhibits antioxidant, antimicrobial, nematicidal, antifungal, anticancer, and anti-inflammatory activities. These properties are influenced by the plants from which the secretions are harvested, from the naturally occurring compounds present in the nectar. Studies of the properties and applications of honey have distinguished honey from other natural products due to the presence of certain compounds and due its bioactive properties. The focus of this review is to discuss the identified and isolated compounds from monofloral honey produced by A. mellifera, with specific emphasis on antioxidant and antimicrobial properties of honey and its therapeutic health benefits.
Biocatalysts
(2013) Zacconi, Flavia C. M.; Arias, Hugo R.
Biological databases and tools for neurological disorders
(IMR Press Limited, 2022) Usman, M.B.; Ojha, S.; Jha, S.K.; Chellappan, D.K.; Gupta, G.; Singh, S.K.; Dua, K.; Roychoudhury, S.; Kumar, N.; Khan, F.A.; Dureja, H.; Upadhye, V.; Zacconi, Flavia C. M.; Prasanna, P.; Kesari, K.K.; Ashraf, G.M.; Alexiou, A.; Jha, N.K.
Computational approaches to study of neuronal impairment is rapidly evolving, as experiments and intuition alone do not explain the complexity of the brain system. An overwhelming increase in the amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals is imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. This review seeks to outline the biological databases and analytical tools along with their applications. It is envisaged that such knowledge could provide a ''training recipe'' for young scientists and a guide for professionals and researchers in neuroscience.
Biomedical Applications of polymeric micelles in the treatment of diabetes mellitus: Current success and future approaches
(2022) Kaur, Jaskiran; Gulati, Monica; Zacconi, Flavia C. M.; Dureja, Harish; Loebenberg, Raimar; Ansari, Md Salahuddin; AlOmeir, Othman; Alam, Aftab; Chellappan, Dinesh Kumar; Gupta, Gaurav; Jha, Niraj Kumar; Pinto, Terezinha de Jesus Andreoli; Morris, Andrew; Choonara, Yahya E.; Adams, Jon; Dua, Kamal; Singh, Sachin Kumar
Introduction Diabetes mellitus (DM) is the most common metabolic disease and multifactorial, harming patients worldwide. Extensive research has been carried out in the search for novel drug delivery systems offering reliable control of glucose levels for diabetics, aiming at efficient management of DM. Areas covered Polymeric micelles (PMs) as smart drug delivery nanocarriers are discussed, focusing on oral drug delivery applications for the management of hyperglycemia. The most recent approaches used for the preparation of smart PMs employ molecular features of amphiphilic block copolymers (ABCs), such as stimulus sensitivity, ligand conjugation, and as a more specific example the ability to inhibit islet amyloidosis. Expert opinion PMs provide a unique platform for self-regulated or spatiotemporal drug delivery, mimicking the working mode of pancreatic islets to maintain glucose homeostasis for prolonged periods. This unique characteristic is achieved by tailoring the functional chemistry of ABCs considering the physicochemical traits of PMs, including sensing capabilities, hydrophobicity, etc. In addition, the application of ABCs for the inhibition of conformational changes in islet amyloid polypeptide garnered attention as one of the root causes of DM. However, research in this field is limited and further studies at the clinical level are required.
Biomedical applications of three-dimensional bioprinted craniofacial tissue engineering
(WILEY, 2022) Charbe, Nitin Bharat; Tambuwala, Murtaza; Palakurthi, Sushesh Srivatsa; Warokar, Amol; HronniC-JahjefendiC, Altijana; Bakshi, Hamid; Zacconi, Flavia C. M.; Mishra, Vijay; Khadse, Saurabh; Aljabali, Alaa A.; El-Tanani, Mohamed; Serrano-Aroca, Angel; Palakurthi, Srinath
Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle-like structures. However, the existing method still has limitations in building large, highly vascular tissue with clinical application. With the advance in the three-dimensional (3D) bioprinting technique, scientists and clinicians now can produce the functional implants of skeletal muscles and bones that are more patient-specific with the perfect match to the architecture of their craniofacial defects. Craniofacial tissue regeneration using 3D bioprinting can manage and eliminate the restrictions of the surgical transplant from the donor site. The concept of creating the new functional tissue, exactly mimicking the anatomical and physiological function of the damaged tissue, looks highly attractive. This is crucial to reduce the donor site morbidity and retain the esthetics. 3D bioprinting can integrate all three essential components of tissue engineering, that is, rehabilitation, reconstruction, and regeneration of the lost craniofacial tissues. Such integration essentially helps to develop the patient-specific treatment plans and damage site-driven creation of the functional implants for the craniofacial defects. This article is the bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue. We also discussed current challenges in craniofacial bone vascularization and gave our view on the future direction, including establishing the interactions between tissue-engineered skeletal muscle and the peripheral nervous system.
Channelling carbon flux through the meta-cleavage route for improved poly(3-hydroxyalkanoate) production from benzoate and lignin-based aromatics in Pseudomonas putida H
(2020) Borrero de Acuña, J.M.; Gutierrez Urrutia, I.; Hidalgo Dumont, C.; Aravena Carrasco, C.; Orellana Saez, M.; Palominos Gonzalez, N.; van Duuren, J. B. J. H.; Wagner, V.; Gläser, L.; Zacconi, Flavia C. M.; Becker, J.; Kohlstedt, M.; Wittmann, C.; Poblete Castro, I.
Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: a new dimension to an anticancer drug
(Elsevier B.V., 2022) Sharma, D.S.; Wadhwa, S.; Gulati, M.; Kumar, B.; Vishwas, S.; Khursheed, R.; Saini, S.; Kumar, A.; Parveen, S.R.; Singh, S.K.; Dua, K.; Chitranshi, N.; Gupta, V.K.; Alrouji, M.; Alhajlah, S.; AlOmeir, O.; Gupta, G.; Zacconi, Flavia C. M.; Chellappan, D.K.; Morris, A.; Loebenberg, R.
Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.
Chitosan/poly-octanoic acid 2-thiophen-3-yl-ethyl ester blends as a scaffold to maintain myoblasts regeneration potential in vitro
(2017) Padilla C.; Ramos, A.; González N.; Isaacs Casanova, Mauricio; Zacconi, Flavia C. M.; Olguín Marín, Hugo César; Valenzuela Roediger, Loreto Margarita
Co-synthesis of medium-chain-length polyhydroxyalkanoates and CdS quantum dots nanoparticles in Pseudomonas putida KT2440
(2017) Oliva Arancibia, Bárbara; Ordenes Aenishanslins, Nicolás; Bruna, Nicolás; Ibarra, Paula S.; Zacconi, Flavia C. M.; Pérez Donoso, José M.; Poblete Castro, Ignacio
Cold-adaptation of a methacrylamide gelatin towards the expansion of the biomaterial toolbox for specialized functionalities in tissue engineering
(2019) Zaupa, A.; Byres, N.; Dal Zovo, C.; Acevedo, C.A.; Angelopoulos, I.; Terrazaa, C.; Nestle, N.; Abarzua-Illanes, P.N.; Quero, F.; Zacconi, Flavia C. M.; Diaz-Calderon, P.; Olguin, Y.; Akentjew, T.L.; Wilkens, C.A.; Padilla, C.; Pino-Lagos, K.; Blaker, U.J.; Khoury, M.; Enrione, J.; Acevedo, J.P.
Tissue regeneration is witnessing a significant surge in advanced medicine. It requires the interaction of scaffolds with different cell types for efficient tissue formation post-implantation. The presence of tissue subtypes in more complex organs demands the co-existence of different biomaterials showing different hydrolysis rate for specialized cell-dependent remodeling. To expand the available toolbox of biomaterials with sufficient mechanical strength and variable rate of enzymatic degradation, a cold-adapted methacrylamide gelatin was developed from salmon skin. Compared with mammalian methacrylamide gelatin (GeIMA), hydrogels derived from salmon GelMA displayed similar mechanical properties than the former. Nevertheless, salmon gelatin and salmon Ge1MA-derived hydrogels presented characteristics common of cold-adaptation, such as reduced activation energy for collagenase, increased enzymatic hydrolysis turnover of hydrogels, increased interconnected poly-peptides molecular mobility and lower physical gelation capability. These properties resulted in increased cell remodeling rate in vitro and in vivo, proving the potential and biological tolerance of this mechanically adequate cold-adapted biomaterial as alternative scaffold subtypes with improved cell invasion and tissue fusion capacity.
Copper nanoparticles supported on zinc oxide as efficient catalyst for the N-Arylation of (Hetero)cyclic and acyclic amides
(WILEY-V C H VERLAG GMBH, 2021) Moglie, Yanina; Mascaro, Evangelina; Zacconi, Flavia C. M.; Radivoy, Gabriel
Copper nanoparticles (CuNPs) supported on ZnO are highly active and selective heterogeneous catalyst for the N-arylation of cyclic and acyclic amides (Golberg coupling). The reaction conditions are mild, featuring K3PO4 as a base and N,N'-dimethylethylendiamine (DMEDA) as ligand in refluxing acetonitrile. The CuNPs/ZnO catalyst can be recovered and reused in six cycles with only little loss of activity. The methodology can be successfully scaled up to gram scale without decreasing the catalytic activity.
Direct Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies
(2023) Mariño Ocampo, Nory Johana; Rodríguez Sánchez, Diego Fernando; Daniel Sebastian, Guerra Diaz; Zúñiga Núñez, Daniel; Duarte, Yorley; Fuentealba Patiño, Denis Alberto; Zacconi, Flavia C. M.
Direct FXa inhibitors are an important class of bioactive molecules (rivaroxaban, apixaban,edoxaban, and betrixaban) applied for thromboprophylaxis in diverse cardiovascular pathologies.The interaction of active compounds with human serum albumin (HSA), the most abundant protein inblood plasma, is a key research area and provides crucial information about drugs’ pharmacokineticsand pharmacodynamic properties. This research focuses on the study of the interactions betweenHSA and four commercially available direct oral FXa inhibitors, applying methodologies includingsteady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and moleculardynamics. The HSA complexation of FXa inhibitors was found to occur via static quenching, and thecomplex formation in the ground states affects the fluorescence of HSA, with a moderate bindingconstant of 104 M−1. However, the ITC studies reported significantly different binding constants (103 M−1) compared with the results obtained through spectrophotometric methods. The suspectedbinding mode is supported by molecular dynamics simulations, where the predominant interactionswere hydrogen bonds and hydrophobic interactions (mainly π–π stacking interactions between thephenyl ring of FXa inhibitors and the indole moiety of Trp214). Finally, the possible implications ofthe obtained results regarding pathologies such as hypoalbuminemia are briefly discussed.
Discovery of New Phenylacetone Monooxygenase Variants for the Development of Substituted Indigoids through Biocatalysis
(2022) Núñez Navarro, Nicolás Ernesto; Salazar Muñoz, Javier Alonso; Castillo Suzarte, Francisco Javier; Ramírez Sarmiento, César Antonio; Poblete Castro, Ignacio; Zacconi, Flavia C. M.; Parra, Loreto
Indigoids are natural pigments obtained from plants by ancient cultures. Romans used them mainly as dyes, whereas Asian cultures applied these compounds as treatment agents for several diseases. In the modern era, the chemical industry has made it possible to identify and develop synthetic routes to obtain them from petroleum derivatives. However, these processes require high temperatures and pressures and large amounts of solvents, acids, and alkali agents. Thus, enzyme engineering and the development of bacteria as whole-cell biocatalysts emerges as a promising green alternative to avoid the use of these hazardous materials and consequently prevent toxic waste generation. In this research, we obtained two novel variants of phenylacetone monooxygenase (PAMO) by iterative saturation mutagenesis. Heterologous expression of these two enzymes, called PAMOHPCD and PAMOHPED, in E. coli was serendipitously found to produce indigoids. These interesting results encourage us to characterize the thermal stability and enzyme kinetics of these new variants and to evaluate indigo and indirubin production in a whole-cell system by HPLC. The highest yields were obtained with PAMOHPCD supplemented with L-tryptophan, producing ~3000 mg/L indigo and ~130.0 mg/L indirubin. Additionally, both enzymes could oxidize and produce several indigo derivatives from substituted indoles, with PAMOHPCD being able to produce the well-known Tyrian purple. Our results indicate that the PAMO variants described herein have potential application in the textile, pharmaceutics, and semiconductors industries, prompting the use of environmentally friendly strategies to obtain a diverse variety of indigoids.
Editorial: Open Access
(2013) Zacconi, Flavia C. M.; Arias, Hugo R.
Efficient indium-mediated dehalogenation of aromatics in ionic liquid media
(2013) Cañete Molina, Álvaro; Salas Sánchez, Cristián Osvaldo; Zacconi, Flavia C. M.
Emergence of three dimensional printed cardiac tissue: opportunities and challenges in cardiovascular diseases
(2019) Charbe, Nitin B.; Zacconi, Flavia C. M.; Amnerkar, Nikhil; Pardhi, Dinesh; Shukla, Priyank; Mukattash, Tareq L.; McCarron, Paul A.; Tambuwala, Murtaza M.
Three-dimensional (3D) printing, also known as additive manufacturing, was developed originally for engineering applications. Since its early advancements, there has been a relentless development in enthusiasm for this innovation in biomedical research. It allows for the fabrication of structures with both complex geometries and heterogeneous material properties. Tissue engineering using 3D bio-printers can overcome the limitations of traditional tissue engineering methods. It can match the complexity and cellular microenvironment of human organs and tissues, which drives much of the interest in this technique. However, most of the preliminary evaluations of 3Dprinted tissues and organ engineering, including cardiac tissue, relies extensively on the lessons learned from traditional tissue engineering. In many early examples, the final printed structures were found to be no better than tissues developed using traditional tissue engineering methods. This highlights the fact that 3D bio-printing of human tissue is still very much in its infancy and more work needs to be done to realise its full potential. This can be achieved through interdisciplinary collaboration between engineers, biomaterial scientists and molecular cell biologists. This review highlights current advancements and future prospects for 3D bio-printing in engineering ex vivo cardiac tissue and associated vasculature, such as coronary arteries. In this context, the role of biomaterials for hydrogel matrices and choice of cells are discussed. 3D bio-printing has the potential to advance current research significantly and support the development of novel therapeutics which can improve the therapeutic outcomes of patients suffering fatal cardiovascular pathologies.

Browsing by Author "Zacconi, Flavia C. M."

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