Search

Background: Human papillomavirus (HPV), a leading cause of cervical cancer, is present in most cases of the disease and ranks as the fourth most common cancer in women globally. Among the HPV types, fourteen (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68) are recognized as high-risk (hrHPV), each with varying levels of oncogenic potential. Detecting and genotyping these hrHPV types in cervical lesions is crucial, requiring the development of new diagnostic methods. Methods: This study focuses on a retrospective analysis conducted on 44 women from the Cova da Beira Local Health Unit. We used the Anyplex™ II hrHPV Detection kit for hrHPV genotyping from paraffin-embedded cervical tissue samples. Results: hrHPV types were identified in 38 out of the 44 women. Genotyping revealed HPV-16 (55.3%), HPV-18/39/56/58/59 (5.3%), HPV-31 (21.1%), HPV-35 (7.9%), HPV-51/66 (2.6%), and HPV-52 (10.5%). Conclusions: This study demonstrates that the Anyplex™ II hrHPV Detection kit, originally designed for cervical cancer screening, is also effective for hrHPV genotyping in histological analyses. This methodology offers a simpler and more cost-effective approach for cervical cancer risk stratification. Its implementation in clinical practice could enhance the detection of hrHPV in cervical lesions, thereby contributing to more precise diagnoses and potentially more informed treatment strategies. [ABSTRACT FROM AUTHOR]

Copyright of Apotheke is the property of Universidade do Estado de Santa Catarina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Apotheke is the property of Universidade do Estado de Santa Catarina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The lack of effective delivery systems has slowed the development of mitochondrial gene therapy. Delivery systems based on cell-penetrating peptides (CPPs) like the WRAP (tryptophan and arginine-rich peptide) family conjugated with a mitochondrial targeting sequence (MTS) have emerged as adequate carriers to mediate gene expression into the mitochondria. In this work, we performed the PEGylation of WRAP/pDNA nanocomplexes and compared them with previously analyzed nanocomplexes such as (KH)9/pDNA and CpMTP/pDNA. All nanocomplexes exhibited nearly homogeneous sizes between 100 and 350 nm in different environments. The developed complexes were biocompatible and hemocompatible to both human astrocytes and lung smooth muscle cells, ensuring in vivo safety. The nanocomplexes displayed mitochondria targeting ability, as through transfection they preferentially accumulate into the mitochondria of astrocytes and muscle cells to the detriment of cytosol and lysosomes. Moreover, the transfection of these cells with MTS–CPP/pDNA complexes produced significant levels of mitochondrial protein ND1, highlighting their efficient role as gene delivery carriers toward mitochondria. The positive obtained data pave the way for in vivo research. Using confocal microscopy, the cellular internalization capacity of these nanocomplexes in the zebrafish embryo model was assessed. The peptide-based nanocomplexes were easily internalized into zebrafish embryos, do not cause harmful or toxic effects, and do not affect zebrafish's normal development and growth. These promising results indicate that MTS–CPP complexes are stable nanosystems capable of internalizing in vivo models and do not present associated toxicity. This work, even at an early stage, offers good prospects for continued in vivo zebrafish research to evaluate the performance of nanocomplexes for mitochondrial gene therapy. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression—a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma. [ABSTRACT FROM AUTHOR]

This study presents a cost-effective approach to developing MnO2-based, aiming to understand how modifications with Ce can affect the materials' morphology, properties, and application; thus, we comprehensively studied such properties. Interestingly, when just precursors for MnO2 were used, nanowires were obtained using a hydrothermal method. However, the subsequent doping with varying concentrations of Ce induced notable changes in the material morphology. Although the morphology changed, the surface areas and porous volumes increased with Ce content. X-ray diffraction analysis revealed the presence of the α-MnO2 tetragonal crystal phase in all materials, suggesting uniform Ce distribution and the absence of distinct crystalline phases. Such properties are vital for storage issues; thus, we decided to evaluate the physicochemical properties of the materials in supercapacitor evaluations. When submitted to electrochemical assessments, the materials presented pseudocapacitive behavior; also, tests for pseudosupercapacitors showed an increase in the specific capacitance with Ce-doping. Notably, these materials exhibited remarkable stability, increasing specific capacitance after 1000 charge–discharge cycles at high current rates. After choosing the optimum conditions of Ce-doping quantity, which did not show a tailored morphological control, an asymmetric supercapacitor was prepared; the device demonstrated a broad potential window, excellent rate performance, and the ability to maintain specific capacitance across various current densities. Remarkably, the asymmetric supercapacitor exhibited an energy density of 785.2 Wh kg−1 at a power density of 2880.02 W kg−1, marking a significant advancement in energy storage capabilities. Here, we have shown that the morphological control was not mandatory for the application of the materials. Furthermore, incorporating Ce into MnO2 enhanced supercapacitor performance, suggesting chemical composition is as vital as morphology in high-performance energy storage. [ABSTRACT FROM AUTHOR]

This article investigates contestations over the roles and legitimacy of gangs within the United Nations Mission in South Sudan (UNMISS) Protection of Civilians (PoC) site in Bentiu, South Sudan. Drawing on qualitative interviews, it argues that 'gangs' represented the medium through which everyday struggles and processes of social contestations were negotiated between youth, elders, and protection actors. Prevailing narratives of gangs as violent criminal entities structured conflict with elders and protection actors, but to their affiliates, gangs provided protection, identity, belonging, responsibility, agency, and a route to overcome the limbo of 'waithood' and achieve social adulthood. [ABSTRACT FROM AUTHOR]

Anisotropy is an important cue for neural organization during morphogenesis and healing, contributing to the mechanical and functional properties of neural tissues. The ability to replicate such anisotropy in vitro holds great promise for the development of effective regeneration strategies. In this work, interfacial polyelectrolyte complexation (IPC) is applied to fabricate microfibers from charged ECM components without any chemical modification. Using flow‐focusing microfluidics, collagen (Col) and glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) or heparin (Hep), form Col/CS and Col/Hep interfacial complexes that coalesce as IPC microfibers. These fibers are flexible and absorb large amounts of water but remain stable under physiological conditions. At these conditions, the tensile strength of the assembled Col/GAG microfibers is similar to the strength of the neural tissue. The fibers are biocompatible and biofunctional; PC12 neural cells adhere and orient longitudinally to the fibers. Moreover, Col/CS microfibers promote the formation of neural processes. The results demonstrate that the microfluidic‐assisted IPC complexation enables the assembly of ECM mimics by synergetic integration of anisotropic, chemical, and mechanical cues that boost the development of neural cells. [ABSTRACT FROM AUTHOR]

Transition systems are often used to describe the behaviour of software systems. If viewed as a graph then, at their most basic level, vertices correspond to the states of a program and each edge represents a transition between states via the (atomic) action labelled. In this setting, systems are thought to be consistent and at each state formulas are evaluated as either true or false. On the other hand, when a structure of this sort—e.g. a map where states represent locations, some local properties are known and labelled transitions represent information available about different routes—is built resorting to multiple sources of information, it is common to find inconsistent or incomplete information regarding what holds at each state, both at the level of propositional variables and transitions. This paper aims at bringing together Belnap's four values, Dynamic Logic and hybrid machinery such as nominals and the satisfaction operator, so that reasoning is still possible in face of contradicting evidence. Proof-theory for this new logic is explored by means of a terminating, sound and complete tableau system. [ABSTRACT FROM AUTHOR]

For brain protection, the blood–brain barrier and blood–cerebrospinal fluid barrier limit the traffic of molecules between blood and brain tissue and between blood and cerebrospinal fluid, respectively. Besides their protective function, brain barriers also limit the passage of therapeutic drugs to the brain, which constitutes a great challenge for the development of therapeutic strategies for brain disorders. This problem has led to the emergence of novel strategies to treat neurological disorders, like the development of nanoformulations to deliver therapeutic agents to the brain. Recently, functional molecular clocks have been identified in the blood–brain barrier and in the blood–cerebrospinal fluid barrier. In fact, circadian rhythms in physiological functions related to drug disposition were also described in brain barriers. This opens the possibility for chronobiological approaches that aim to use time to improve drug efficacy and safety. The conjugation of nanoformulations with chronobiology for neurological disorders is still unexplored. Facing this, here, we reviewed the circadian rhythms in brain barriers, the nanoformulations studied to deliver drugs to the brain, and the nanoformulations with the potential to be conjugated with a chronobiological approach to therapeutic strategies for the brain. [ABSTRACT FROM AUTHOR]

The article offers a nuanced account of how identities are negotiated and contested in South Sudan, by focusing on how Murle and ŋalam identities were deployed in different ways in different places in overlapping periods during a time of armed conflict. As such, it explores the interplay between political violence and the instrumental deployment of ethnicity. Focusing on the 2012–2014 period of war between South Sudan’s government and a largely Murle rebellion, it unpacks the longstanding Murle stereotyping as ‘fierce and hostile’ – an image fostered by the interlocution of more powerful neighbours in the colonial encounters and sustained by their dominance in subsequent governance structures. The article specifically discusses how Murle agricultural communities from Boma found protection strategies by activating temporary subethnic identities and navigating the violence of being Murle. This challenges the “naturalised” linkages between modes of subsistence or ecology, and identity, and demonstrates how spatial movements affect the instrumental narrativisation of ethnic identities. The article argues for the continual interplay of ethnicity in relation to the state and its strategies and opportunities. Identity-making and identitypolitics are dialctical processes – deployed by the state as much as by those on the receiving end as a source of protection from violence. [ABSTRACT FROM AUTHOR]

The circadian clock controls behavior and physiology. Presently, there is clear evidence of a connection between this timing system and cancer development/progression. Moreover, circadian rhythm consideration in the therapeutic action of anticancer drugs can enhance the effectiveness of cancer therapy. Nanosized drug delivery systems (DDS) have been demonstrated to be suitable engineered platforms for drug targeted/sustained release. The investigation of the chronobiology-nanotechnology relationship, i.e., timing DDS performance according to a patient's circadian rhythm, may greatly improve cancer clinical outcomes. In the present work, we synthesized nanosystems based on an octa-arginine (R8)-modified poly(amidoamine) dendrimer conjugated with the anticancer drug paclitaxel (PTX), G4-PTX-R8, and its physicochemical properties were revealed to be appropriate for in vitro delivery. The influence of the circadian rhythm on its cellular internalization efficiency and potential therapeutic effect on human cervical cancer cells (HeLa) was studied. Cell-internalized PTX and caspase activity, as a measure of induced apoptosis, were monitored for six time points. Higher levels of PTX and caspase-3/9 were detected at T8, suggesting that the internalization of G4-PTX-R8 into HeLa cells and apoptosis are time-specific/-regulated phenomena. For a deeper understanding, the clock protein Bmal1—the main regulator of rhythmic activity, was silenced by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. Bmal1 silencing was revealed to have an impact on both PTX release and caspase activity, evidencing a potential role for circadian rhythm on drug delivery/therapeutic effect mediated by G4-PTX-R8. [ABSTRACT FROM AUTHOR]

Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway. [ABSTRACT FROM AUTHOR]