RESUMEN

Rituximab occasionally induces reactivation of hepatitis C virus (HCV) in patients with resolved HCV infection, sometimes with fatal consequences. As rituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) and is more widely used, there is a lack of studies reporting the effectiveness and safety of rituximab in patients with PLA2R-associated MN and resolved HCV infection. A single-center retrospective study was conducted on PLA2R-associated membranous nephropathy (MN) patients who were HCVAb positive but HCV-RNA negative and treated with rituximab. A total of 598 adult patients with PLA2R-associated MN who underwent rituximab therapy were screened. General clinical information, including gender, age, pathological data, and previous treatment plans, was collected from medical records. Routine blood tests, liver and kidney function assessments, blood lipid profiles, 24-h urine protein levels, anti-PLA2R antibody titers, circulating B-cell counts, and HCV viral loads were measured at the time of rituximab infusion and repeated at intervals of 1-3 months post-rituximab administration. A total of 8 patients were enrolled, with a median follow-up period of 19.00 (range: 16.00-25.25) months. Among the 8 patients, 5 were male, and the mean age was 50.13 ± 4.29 years. Histological findings indicated that tubuloreticular inclusions, mesangial deposits, intramembranous deposits, and subendothelial deposits were not observed in any of the 8 patients. The overall 1-year remission rate for these patients was 75%, accompanied by a significant reduction in proteinuria. Additionally, blood albumin levels increased significantly, and renal function remained stable. No increase in HCV viral load and stable liver function tests were observed throughout the entire follow-up period. This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and resolved HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials.

Asunto(s)

RESUMEN

The low melt strength and brittleness of polylactic acid (PLA) significantly limit its application in high-performance and functional films. In this study, we successfully prepared ternary thermoplastic vulcanizates (TPVs) comprising of PLA, poly(caprolactone) (PCL) and natural rubber (NR), which exhibit co-continuous structure. During the peroxide-induced dynamic vulcanization process, PLA chains were effectively grafted and anchored to the cross-linked rubber network, thereby enhancing the melt strength of the material. This improvement allowed the ternary TPVs to be continuously and stably blown into films. The films exhibited excellent mechanical properties due to the synergistic effect of ductile PCL and elastic NR. Both the elongation at break and tear strength improved greatly. Interestingly, during the film blowing process, the highly stretched continuous NR crosslinked network stored large amounts of elastic energy, endowing the film with excellent heat shrinkage performance. With 15 phr NR, the heat shrinkage exceeded 35 %, which is sufficient for practical needs. This biodegradable film with heat-shrinkage properties can be processed on a large scale, offering a potential strategy to the urgent issue of plastic film pollution.

RESUMEN

Phospholipase A2 (PLA2) is a superfamily of phospholipase enzymes that dock at the water/oil interface of phospholipid assemblies, hydrolyzing the ester bond at the sn-2 position. The enzymatic activity of these enzymes differs based on the nature of the substrate, its supramolecular assemblies (micelle, liposomes), and their composition, reflecting the interfacial nature of the PLA2s and requiring assays able to directly quantify this interaction of the enzyme(s) with these supramolecular assemblies. We developed and optimized a simple, universal assay method employing the pH-sensitive indicator dye bromothymol blue (BTB), in which different POPC (3-palmitoyl-2-oleoyl-sn-glycero-1-phosphocholine) self-assemblies (liposomes or mixed micelles with Triton X-100 at different molar ratios) were used to assess the enzymatic activity. We used this assay to perform a comparative analysis of PLA2 kinetics on these supramolecular assemblies and to determine the kinetic parameters of PLA2 isozymes IB and IIA for each supramolecular POPC assembly. This assay is suitable for assessing the inhibition of PLA2s with great accuracy using UV-VIS spectrophotometry, being thus amenable for screening of PLA2 enzymes and their substrates and inhibitors in conditions very similar to physiologic ones.

Asunto(s)

RESUMEN

In this work, the resistance of polylactide-based non-wovens produced by solution blow spinning to environmental factors was investigated. An average contact angle of up to 136° was achieved with an average fiber diameter of 340 nm at the optimal material density and nozzle-substrate distance. When exposed to ultraviolet (UV) radiation, the polylactide non-wovens rapidly lose their hydrophobic properties due to changes in surface morphology resulting from fiber melting. It was demonstrated that the influence of surface structural features on hydrophobicity is greater than that of the material itself. The stability of the wetting properties under UV irradiation was assessed using the derivative parameters of the Owens-Wendt technique, which can serve as an additional method for estimating surface polarity.

RESUMEN

This study investigates the enhancement of polylactic acid (PLA) properties through the incorporation of graphene nanoplatelets (GNPs) and carbon black (CB) for applications in 3D printing and injection molding. The research reveals that GNPs and CB improve the electrical conductivity of PLA, although conductivity remains within the insulating range, even with up to 10% wt of nanoadditives. Mechanical characterization shows that nanoparticle addition decreases tensile strength due to stress concentration effects, while dispersants like polyethylene glycol enhance ductility and flexibility. This study compares the properties of materials processed by injection molding and 3D printing, noting that injection molding yields isotropic properties, resulting in better mechanical properties. Thermal analysis indicates that GNPs and CB influence the crystallization behavior of PLA with small changes in the melting behavior. Dynamic Mechanical Thermal Analysis (DMTA) results show how the glass transition temperature and crystallization behavior fluctuate. Overall, the incorporation of nanoadditives into PLA holds potential for enhanced performance in specific applications, though achieving optimal conductivity, mechanical strength, and thermal properties requires careful optimization of nanoparticle type, concentration, and dispersion methods.

RESUMEN

In four-dimensional additive manufacturing (4DAM), specific external stimuli are applied in conjunction with additive manufacturing technologies. This combination allows the development of tailored stimuli-responsive properties in various materials, structures, or components. For shape-changing functionalities, the programming step plays a crucial role in recovery after exposure to a stimulus. Furthermore, precise tuning of the 4DAM process parameters is essential to achieve shape-change specifications. Within this context, this study investigated how the structural arrangement of infill patterns (criss-cross and concentric) affects the shape memory effect (SME) of compression cold-programmed PLA under a thermal stimulus. The stress-strain curves reveal a higher yield stress for the criss-cross infill pattern. Interestingly, the shape recovery ratio shows a similar trend across both patterns at different displacements with shallower slopes compared to a higher shape fixity ratio. This suggests that the infill pattern primarily affects the mechanical strength (yield stress) and not the recovery. Finally, the recovery force increases proportionally with displacement. These findings suggest a consistent SME under the explored interval (15-45% compression) despite the infill pattern; however, the variations in the mechanical properties shown by the stress-strain curves appear more pronounced, particularly the yield stress.

RESUMEN

This study investigates the performance of different poly(lactic acid) (PLA) composites incorporating agri-food waste additives and commercial lignin, comparing their properties with those of virgin PLA. The following composites were prepared using a single-screw extruder: PLA with 20% rice husk, PLA with 20% wheat straw and PLA with 20% olive pit. Additionally, PLA was blended with commercial lignin at the maximum feasible proportion using the same methodology. The resulting composites were injection-molded into specimens for analysis of their mechanical, thermal and morphological behavior. The primary objectives were to assess the dispersion of the additives within the PLA matrix and to evaluate the mechanical properties of the composites. The results indicate that the addition of high percentages of agricultural residues does not significantly compromise the mechanical properties of the composites. Notably, in the case of the PLA with 20% rice husk composite, the elastic modulus surpassed that of virgin PLA, despite the evident heterogeneity in filler particle sizes. It was feasible to incorporate a higher percentage of agricultural residues compared to commercial lignin, attributed to the larger volume occupied by the latter.

RESUMEN

This study presents the development of multifunctional protective clothing for disabled individuals using PBAT/PLA biopolymeric-based electrospun nanofibrous membranes. The fabric consists of a superhydrophobic electrospun nanofibrous cloth reinforced with silica nanoparticles. The resulting nanofiber membranes were characterized using FE-SEM, a CA goniometer, breathability and hydrostatic pressure resistance tests, UV-vis spectroscopy, thermal infrared photography, tensile tests, and nanoindentation. The results demonstrated the integration of superhydrophobicity, breathability, and mechanical improvements in the protective clothing. The nanofibrous porous structure of the fabric allowed breathability, while the silica nanoparticles acted as an effective infrared reflector to keep the wearer cool on hot days. The fabric's multifunctional properties make it suitable for various products, such as outdoor clothing and accessories for individuals with disabilities. This study highlights the importance of selecting appropriate textiles for protective clothing and the challenges faced by disabled individuals in terms of mobility, eating, and dressing. The innovative and purposeful design of this multifunctional protective clothing aimed to enrich the lives of individuals with disabilities.

RESUMEN

Polymer additive manufacturing has advanced from prototyping to producing essential parts with improved precision and versatility. Despite challenges like surface finish and wear resistance, new materials and metallic reinforcements in polymers have expanded its applications, enabling stronger, more durable parts for demanding industries like aerospace and structural engineering. This research investigates the tribological behaviour of FFF surfaces by integrating copper and aluminium reinforcement particles into a PLA (polylactic acid) matrix. Pin-on-disc tests were conducted to evaluate friction coefficients and wear rates. Statistical analysis was performed to study the correlation of the main process variables. The results confirmed that reinforced materials offer interesting characteristics despite their complex use, with the roughness of the fabricated parts increasing by more than 300%. This leads to an increase in the coefficient of friction, which is related to the variation in the material's mechanical properties, as the hardness increases by more than 75% for materials reinforced with Al. Despite this, their performance is more stable, and the volume of material lost due to wear is reduced by half. These results highlight the potential of reinforced polymers to improve the performance and durability of components manufactured through additive processes.

RESUMEN

Heat shock factor 2 (HSF2) is a versatile transcription factor that regulates gene expression under stress conditions, during development, and in disease. Despite recent advances in characterizing HSF2-dependent target genes, little is known about the protein networks associated with this transcription factor. In this study, we performed co-immunoprecipitation coupled with mass spectrometry analysis to identify the HSF2 interactome in mouse testes, where HSF2 is required for normal sperm development. Endogenous HSF2 was discovered to form a complex with several adhesion-associated proteins, a finding substantiated by mass spectrometry analysis conducted in human prostate carcinoma PC-3 cells. Notably, this group of proteins included the focal adhesion adapter protein talin-1 (TLN1). Through co-immunoprecipitation and proximity ligation assays, we demonstrate the conservation of the HSF2-TLN1 interaction from mouse to human. Additionally, employing sequence alignment analyses, we uncovered a TLN1-binding motif in the HSF2 C terminus that binds directly to multiple regions of TLN1 in vitro. We provide evidence that the 25 C-terminal amino acids of HSF2, fused to EGFP, are sufficient to establish a protein complex with TLN1 and modify cell-cell adhesion in human cells. Importantly, this TLN1-binding motif is absent in the C-terminus of a closely related HSF family member, HSF1, which does not form a complex with TLN1. These results highlight the unique molecular characteristics of HSF2 in comparison to HSF1. Taken together, our data unveil the protein partners associated with HSF2 in a physiologically relevant context and identifies TLN1 as the first adhesion-related HSF2-interacting partner.

RESUMEN

The polylactic acid (PLA) coatings of different crystallinity were prepared on biodegradable Mg-2.2Zn-0.3Ca alloy wires to improve the long-term anti-corrosion properties. The composition characteristics and microstructure of the samples were investigated by differential scanning calorimetry (DSC), Fourier transform infrared spectroscope (FTIR), wide angle X-ray diffraction (WAXD) and scanning electron microscope (SEM). The corrosion resistance of all samples was investigated by immersion tests and electrochemical techniques in vitro simulated body fluid (SBF). The results indicated heat treatment improved the crystallinity of PLA coating and heated-coating performed protective behaviors in the short and long-term immersion. The corrosion rate of heated samples was lower than that of unheated samples and exhibited superior long term protective effect for Mg alloy wires. The lifetime of heated sample (H2) increased significantly from 33 to 55 days. The initial electrochemical performance of unheated coating was better than heated coating, but it declined more rapidly during the long-term immersion. These results indicated that PLA coating could not ignore the effect of its crystallinity to anti-corrosion ability, and only the suit heat treatment makes PLA coating more ordering and achieves higher corrosion resistance in vitro immersion. Therefore, it has promising potential by controlling effectively the PLA ordering for surgical implant applications.

RESUMEN

Background: Pyogenic liver abscess (PLA) could be fatal even after standard treatment with antibiotics and percutaneous drainage. Immune checkpoint inhibitors, bevacizumab or microwave ablation may cause PLA, respectively. This paper presents the first case of PLA secondary to the concomitant use of microwave ablation with atezolizumab and bevacizumab in the treatment of liver cancer. Case Description: A 54-year-old Chinese man with Barcelona Clinic Liver Cancer (BCLC) C-stage liver cancer complained of fever and chills twenty-nine days after concurrent microwave ablation plus atezolizumab and bevacizumab. Post-hospitalization, a computed tomography revealed a rim-enhancing hypodensity within the right lobe of the liver, approximately 8.8 cm in diameter containing foci of gas. Laboratory examination revealed elevated white blood cell count, C-reactive protein and procalcitonin, and blood culture indicated the presence of Escherichia coli bacteremia. The patient was diagnosed with PLA complicated by septic shock, and due to recurrent fever, multiple courses of antibiotics (imipenem/cilastatin sodium, cefoperazone/sulbactam, meropenem, respectively) were administered in combination with five percutaneous drainages over the next 90 days. The patient's fever eventually resolved, and the patient was discharged. The patient was re-treated with two cycles of atezolizumab and bevacizumab initiated in March 2024. An imaging evaluation in May 2023 demonstrated tumor progression. Subsequently, the patient underwent one transarterial chemoembolization procedure and two cycles of atezolizumab and bevacizumab over the subsequent 2 months. Notably, the patient achieved a complete response at the July 2024 imaging evaluation. Conclusions: In patients undergoing atezolizumab and bevacizumab, the potential risk of PLA versus the antitumor benefit of microwave ablation requires to be assessed. The use of multiple courses of antibiotics over a prolonged period did not appear to influence the effectiveness of atezolizumab and bevacizumab. Further studies are, however, needed to substantiate this finding.

RESUMEN

Over the last fifteen years, numerous studies have sought to decipher the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in vascular inflammation-related diseases, notably atherosclerosis. Despite the disappointing results of clinical trials using the Lp-PLA2 inhibitor darapladib, new pathophysiological, epidemiological and genetic data have enabled the development of new inhibitors. Recent studies also show that Lp-PLA2 is involved in vascular inflammation-related diseases other than atherosclerosis (ischemic stroke, Alzheimer's disease and vascular dementia, diabetes, cancers…), and inhibition of Lp-PLA2 could have beneficial therapeutic in these diseases. This review aims to present new data on Lp-PLA2 and to evaluate its current interest as a biomarker but also as a therapeutic target.

RESUMEN

Crotoxin, a phospholipase A2 (PLA2) complex and the major Crotalus venom component, is responsible for the main symptoms described in crotalic snakebite envenomings and a key target for PLA2 inhibitors (PLIs). PLIs comprise the alpha, beta and gamma families, and, due to a lack of reports on beta-PLIs, this study aimed to heterologously express CdtPLI2 from Crotalus durissus terrificus venom gland to improve the knowledge of the neglected beta-PLI family. Thereby, recombinant CdtPLI2 (rCdtPLI2) was produced in the eukaryotic Pichia pastoris system to keep some native post-translational modifications. rCdtPLI2 (~41 kDa) presents both N- and O-linked glycans. Alpha-mannosidase digested-rCdtPLI2 (1 mol) strongly inhibited (73 %) CB-Cdc catalytic activity (5 mol), demonstrating that glycosylations performed by P. pastoris affect rCdtPLI2 action. Digested-rCdtPLI2 also inhibited PLA2s from diverse Brazilian snake venoms. Furthermore, rCdtPLI2 (1 mol) abolished the catalytic activity of Lmr-PLA2 (5 mol) and reduced the CTx-Cdc (5 mol) enzyme activity by 65 %, suppressing basic and acidic snake venom PLA2s. Additionally, crotalic antivenom did not recognize rCdtPLI2, suggesting a lack of neutralization by antivenom antibodies. These findings demonstrate that studying snake venom components may reveal interesting novel molecules to be studied in the snakebite treatment and help to understand these underexplored inhibitors.

RESUMEN

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant tumor characterized by a lack of effective targeted therapeutic strategies. The protein UHRF1 plays a pivotal role in the preservation of DNA methylation and works synergistically with DNMT1. Posttranscriptional modifications (PTMs), such as ubiquitination, play indispensable roles in facilitating this process. Nevertheless, the specific PTMs that regulate UHRF1 in CCA remain unidentified. METHODS: We confirmed the interaction between STUB1 and UHRF1 through mass spectrometry analysis. Furthermore, we investigated the underlying mechanisms of the STUB1-UHRF1/DNMT1 axis via co-IP experiments, denaturing IP ubiquitination experiments, nuclear‒cytoplasmic separation and immunofluorescence experiments. The downstream PLA2G2A gene, regulated by the STUB1-UHRF1/DNMT1 axis, was identified via RNA-seq.  The negative regulatory mechanism of PLA2G2A was explored via bisulfite sequencing PCR (BSP) experiments to assess changes in promoter methylation. The roles of PLA2G2A and STUB1 in the proliferation, invasion, and migration of CCA cells were assessed using the CCK-8 assay, colony formation assay, Transwell assay, wound healing assay and xenograft mouse model. We evaluated the effects of STUB1/UHRF1 on cholangiocarcinoma by utilizing a primary CCA mouse model. RESULTS: This study revealed that STUB1 interacts with UHRF1, resulting in an increase in the K63-linked ubiquitination of UHRF1. Consequently, this facilitates the nuclear translocation of UHRF1 and enhances its binding affinity with DNMT1. The STUB1-UHRF1/DNMT1 axis led to increased DNA methylation of the PLA2G2A promoter, subsequently repressing its expression. Increased STUB1 expression in CCA was inversely correlated with tumor progression and overall survival. Conversely, PLA2G2A functions as a tumor suppressor in CCA by inhibiting cell proliferation, invasion and migration. CONCLUSIONS: These findings suggest that the STUB1-mediated ubiquitination of UHRF1 plays a pivotal role in tumor progression by epigenetically silencing PLA2G2A, underscoring the potential of STUB1 as both a prognostic biomarker and therapeutic target for CCA.

Asunto(s)

RESUMEN

IgG4-related disease is a fibroinflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells affecting multiple organs. Though the most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis, it can rarely present as secondary membranous nephropathy. We present a case of a 75-year-old male with phospholipase A2 receptor-negative membranous nephropathy as an atypical manifestation of IgG4-related disease. The patient presented with nephrotic syndrome and was found to have elevated serum IgG4 levels and IgG4-positive plasma cells in the kidney biopsy. He was successfully treated with corticosteroids and rituximab, resulting in significant improvement in proteinuria and normalization of IgG4 levels. This case highlights the importance of considering IgG4-related disease in patients with phospholipase A2 receptor-negative membranous nephropathy, especially in those with a history of other organ involvement. Early recognition and treatment of IgG4-related disease are crucial to prevent progressive kidney damage and improve patient outcomes.

RESUMEN

This study introduces a novel approach to 4D printing of biocompatible Poly lactic acid (PLA)/poly methyl methacrylate (PMMA) blends using Artificial Neural Network (ANN) and Response Surface Methodology (RSM). The goal is to optimize PMMA content, nozzle temperature, raster angle, and printing speed to enhance shape memory properties and mechanical strength. The materials, PLA and PMMA, are melt-blended and 4D printed using a pellet-based 3D printer. Differential Scanning Calorimetry (DSC) and Dynamic Mechanical Thermal Analysis (DMTA) assess the thermal behavior and compatibility of the blends. The ANN model demonstrates superior prediction accuracy and generalization capability compared to the RSM model. Experimental results show a shape recovery ratio of 100% and an ultimate tensile strength of 65.2 MPa, significantly higher than pure PLA. A bio-screw, 4D printed with optimized parameters, demonstrates excellent mechanical properties and shape memory behavior, suitable for biomedical applications such as orthopaedics and dental implants. This research presents an innovative method for 4D printing PLA/PMMA blends, highlighting their potential in creating advanced, high-performance biocompatible materials for medical use.

RESUMEN

Microbial contamination is the leading cause of food spoilage and food-borne disease. Here, we developed a multifunctional surface based on polylactic acid (PLA) bioplastic with antifouling and antibacterial properties via a facile dual-coating approach. The surface was designed with hierarchical micro/nano-scale roughness and low surface energy. Bactericidal agent polyhexamethylene guanidine hydrochloride (PHMG) was incorporated to endow the film with bactericidal activity. The film had good superhydrophobic, antifouling and antibacterial performance, with a water contact angle of 154.3°, antibacterial efficiency against E. coli and S. aureus of 99.9 % and 99.6 %, respectively, and biofilm inhibition against E. coli and S. aureus of 63.5 % and 68.9 %, respectively. Synergistic effects of antibacterial adhesion and contact killing of bacteria contributed to the significant antibacterial performance of the film. The biobased biodegradable film was highly effective in preventing microbial growth when applied as antibacterial food packaging for poultry product, extending the shelf life of fresh chicken breast up to eight days.

RESUMEN

There have been numerous studies on flame retardant modification of natural fiber/PLA composite materials due to the demand for applications. However, the existing flame retardant modification methods mostly involve adding flame retardants, which have a negative impact on the mechanical properties. Based on this, this study aims to introduce sulfonic groups into the cellulose of straw fibers via modification with a sulfamic acid-based deep eutectic solvent (SDES), thereby achieving flame retardance without affecting the inherent mechanical properties of the composite material. The performance enhancement of DS/PLA is manifested in the following specific aspects: the LOI reaches 36.53 %, the thermal stability is improved from 7.8 % of the residual carbon of PS/PLA to 38.4 %, and the tensile modulus is increased by 69.5 %. The preparation scheme for straw/PLA composite materials in this study is simple, economical, and efficient, and the flame retardant performance of the composite material is excellent, providing valuable references for flame retardant modification of natural fiber/plastic composite materials.

RESUMEN

Erosion of biodegradable polymeric excipients, such as polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA), is generally characterized by microbalance for the remaining mass of PLA and/or PLGA and Gel Permeation Chromatography (GPC) for molecular weight (MW) decrease. For polymer erosion studies of intravitreal sustained release brimonidine implants, however, both microbalance and GPC present several challenges. Mass loss measurement by microbalance does not have specificity for excipient polymers and drug substances. Accuracy of the remaining mass by weighing could also be low due to sample mass loss through retrieval-drying steps, especially at later drug release (DR) time points. When measuring the decrease of polymer MW by GPC, trace amounts of polymeric degradants (oligomers and/or monomers) trapped inside the implants during DR tests may not be measurable due to sensitivity limitations of the GPC detector and column MW range. Previous efforts to measure remained PLGA weight of dexamethasone micro-implants using qNMR with external calibration have been performed, however, these measurements do not account for chemical structure changes (i.e. LA to GA ratio changes from time zero) of PLGA implants during drug release tests. Here, a qNMR method with an internal standard was developed to monitor the following changes in micro-implants during drug release tests: 1. The remaining overall PLA/PLGA mass. 2. The remaining lactic acid (LA), glycolic acid (GA) unit and PLGA's lauryl ester end group percentages. 3. The trace content of PLA/PLGA oligomers as degradants retained in the implants. Unlike microbalance analysis, qNMR has both specificity for drug substance, excipient polymer, and accuracy due to minimal implant loss during sample preparation. Compared to the overall PLA/PLGA remaining mass generally monitored in erosion studies, the percentage of remaining LA, GA, and the ester end group provide more information about the microstructure change (such as hydrophobicity) of PLA/PLGA. Additionally, the qNMR method can complement GPC methods by measuring the change of remaining PLA and PLGA oligomer concentrations in brimonidine implants, with tenfold less sample and no MW cutoff. The qNMR method can be used as a sensitive tool for both polymer excipient characterization and kinetics studies of brimonidine implant erosion.