Search Results (49)

Poly(acrylic acid) (PAA) and hydroxypropylcellulose (HPC) hydrogels were synthesized in the absence of a crosslinker. Chemical crosslinking between PAA and HPC was demonstrated through free radical polymerization by a precipitation reaction in acetone as the solvent. These hydrogels exhibited smaller swelling ratios (1 to 5 g H₂O/g) than homo PAA hydrogels synthesized in water as the solvent. They were swollen in a 0.1 M NaOH solution and subsequently used to remove Ni²⁺ ions from aqueous solutions with concentrations ranging from 1000 to 4000 ppm. The absorption capacity of these hydrogels ranged from 91 to 340 mg of Ni²⁺/g in a rapid 1 h process, and from 122 to 435 mg of Ni²⁺/g in a 24 h process, demonstrating an improvement in Ni²⁺ absorption compared to previously reported hydrogels. The colored 1000 and 2000 ppm Ni²⁺ solutions became clear after treatment, while the PAA-HPC hydrogels turned green due to the uptake of Ni²⁺ ions, which were partially chelated by carboxylate groups as nickel polyacrylate and partially precipitated as Ni(OH)₂, resulting in an average absorption efficiency of 80%. The hydrogel was able to release the absorbed Ni²⁺ upon immersion in an HCl solution, with an average release percentage of 76.4%, indicating its potential for reuse. These findings support the use of PAA-HPC hydrogels for cleaning Ni²⁺-polluted water. The cost of producing 1 g of these hydrogels in laboratory conditions is approximately 0.2 USD. Full article

Engineered scaffold-based proteins that bind to concrete targets with high affinity offer significant advantages over traditional antibodies in theranostic applications. Their development often relies on display methods, where large libraries of variants are physically contacted with the desired target protein and pools of binding variants can be selected. Herein, we use a novel combined artificial intelligence/physics-based computational framework and phage display approach to obtain ubiquitin based Affilin^® proteins targeting the human epidermal growth factor receptor 3 (HER3) extracellular domain, a relevant tumor target. As traditional antibodies against the receptor have failed so far, we sought to provide molecules in a smaller more versatile format to cover the medical need in HER3 related diseases. We demonstrate that the developed in silico pipeline can generate de novo Affilin^® proteins binding the biochemical HER3 target using a small training set of <1000 sequences. The classical phage display yielded primary candidates with low nanomolar affinities to the biochemical target and HER3-expressing cells. The latter could be further optimized by phage display and computational maturation alike. These combined efforts resulted in four HER3 ligands with high affinity, cell binding, and serum stability with theranostic potential. Full article

Coronavirus disease 2019 (COVID-19) presents with various symptoms, and some patients develop post-COVID-19 condition (PCC). Vitamin D has shown therapeutic potential in COVID-19 and may offer benefits for PCC. The aim of this study was to evaluate the differences associated with two supplementation strategies (bolus and daily) on interleukin-6 (IL-6) levels, glutathione peroxidase (GPx) activity, and clinical outcomes in PCC patients, regardless of whether target 25 (OH) D levels reached the ideal range. We conducted a self-controlled study in which 54 participants with PCC were supplemented with vitamin D₃ (n = 28 bolus and n = 26 daily) for 2 months. Blood samples were collected to measure IL-6 levels and GPx activity using spectrophotometric methods. The Hospital Anxiety and Depression Scale (HADS) was used to assess mental function. Both bolus and daily vitamin D supplementation were significantly associated with increased GPx activity and decreased IL-6 levels. Daily supplementation was additionally associated with a significant reduction in anxiety and depression scores. However, neither regimen was associated with improvements in cough, dyspnea, or fatigue. These findings suggest a potential association between vitamin D supplementation and improvements in antioxidant and neuropsychiatric parameters in PCC, possibly mediated by its immunomodulatory and antioxidant properties. Further placebo-controlled trials are warranted to determine whether these observed associations reflect causal relationships. Full article

Background: Patients with chronic kidney disease (CKD) exhibit changes in leukocyte dynamics, leading to altered hematological and biochemical parameters and deteriorating kidney function. In this study, we aim to investigate the correlation between leukocyte subpopulations and hematological and biochemical parameters in patients with end-stage CKD undergoing hemodialysis. Methods: This descriptive, analytical, cross-sectional study included 20 end-stage CKD patients on hemodialysis. Leukocyte subpopulations, including classical monocytes (CD14⁺⁺/CD16⁻), intermediate monocytes (CD14⁺⁺/CD16⁺), non-classical monocytes (CD14⁺/CD16⁺⁺), CD4 T lymphocytes (CD3⁺/CD4⁺), CD8 T lymphocytes (CD3⁺/CD8⁺), B lymphocytes (CD3⁻/CD19⁺), NK cells (CD56⁺/CD16⁺), and iNKT cells (CD3⁺/CD56⁺), were analyzed using flow cytometry. Results: Patients with end-stage CKD on hemodialysis have decreased classical monocytes and increased non-classical monocytes frequency. A positive correlation was observed between non-classical monocytes and total lymphocytes (Rho-Spearman: R = 0.495, p = 0.027) as well as B lymphocytes (R = 0.567, p < 0.05). We discerned the immunological characteristics of diabetic kidney disease (DKD) and CKD due to other causes in this balanced cohort: B lymphocytes negatively correlate with alkaline phosphatase (R = −0.764, p < 0.05), parathyroid hormone (R = −0.929, p < 0.05), and ferritin (R = −0.893, p < 0.05). Additionally, in DKD, non-classical monocytes positively correlate with eosinophils (R = +0.691; p = 0.019) and classic monocytes with neutrophils (R = +0.627, p = 0.039). Meanwhile, a correlation between either total T lymphocytes or helper T lymphocytes and serum albumin was detected on patients with nephropathy due to other causes. Conclusions: CKD alters classical and non-classical monocyte frequency, whilst T and B lymphocyte frequency positively correlates to the proinflammatory non-classical monocytes. In DKD patients, the uremic environment increases classic monocytes, CD16+ inflammatory monocytes, neutrophils, eosinophils, and B lymphocytes. The described leukocyte dynamic correlates with alkaline phosphatase, parathyroid hormone, iron, and serum albumin serological concentration. Full article

Background: The callus cultures from the fronds of the lycophyte Phlegmariurus taxifolius produce the huperzine A (HupA) alkaloid, which is used in Alzheimer’s disease treatment. This study aimed to establish the growth kinetics and HupA production by the newly HupS21 cell line grown in 250 mL flasks and in a 2 L airlift bioreactor. Methods: Batch-type kinetics were carried out for 60 days in 250 mL flasks and for 20 days in a 2 L airlift bioreactor. Measurements of dry weight (DW), specific growth rate (μ), doubling time (dt), pH, carbohydrate consumption, and HupA quantification were performed. The acetylcholinesterase (AChE) inhibitory assay of the HupS21 alkaloidal extract was determined. Results: The 250 mL flasks kinetic reached a maximum cell growth of 8.17 g/L DW, with a μ of 0.045 day⁻¹ and a dt of 15.40 days. The maximum HupA production was of 2.03 μg/g DW at day 45. In the 2 L airlift reactor, a maximum growth of 16.70 g/L DW, a μ of 0.062 day⁻¹, a dt of 11.20 days, and HupA production of 2.48 μg/g DW at day 15 were obtained. The alkaloidal extract from the HupS21 cell line at 100 μg/mL showed an AChE inhibitory activity of 85.6 ± 1.27%. Conclusions: The airlift reactor outperformed the flask cultures in maximum cell growth, specific growth rate, doubling time, and HupA production. To our knowledge, this research is the first report on the establishment of suspension cell cultures of P. taxifolius in shaken flasks and in an airlift bioreactor, providing a foundation for scaling up HupA production for pharmaceutical use. Full article

Background/Objectives: Addressing health research priorities in public institutions is crucial for efficient resource allocation and policy impact. This study aims to describe the development of Peru’s Social Health Insurance (ESSALUD) 2023–2025 research portfolio, which aligns with institutional priorities and focuses on improving decision-making for population health. Methods: The Health Research Directorate (DIS) of ESSALUD led a structured three-phase process, engaging multidisciplinary teams and utilizing a group model-building approach to generate research ideas. Twelve working groups were established, corresponding to ESSALUD’s prioritized health topics, to identify key institutional challenges and propose research ideas. Results: A total of 338 research ideas were generated from 217 identified problems. These ideas were classified using the UK Health Research Classification System (HRCS) and scored based on nine dimensions to prioritize execution. Research ideas primarily focused on health services (57.7%) and disease management (16.9%). High-priority topics included cancer, mental health, malnutrition, and antimicrobial resistance. As a result of this implementation, ESSALUD resources were positively concentrated in the HRCS research activities ‘Health and social care services research’ (51.85%) and ‘Etiology’ (44.44%) for the period 2023–2025. Conclusions: The development of ESSALUD’s research portfolio identified key areas such as health services, health economics, and prevention, essential for evidence-based decisions and sustainability. Multidisciplinary participation ensured solutions aligned with real needs, promoting equity and continuous improvement in Peru’s health system. Full article

Arbuscular mycorrhizal (AM) symbiosis, a mutually beneficial interaction between plant roots and AM fungi, plays a key role in plant growth, nutrient acquisition, and stress tolerance, which make it a major focus for sustainable agricultural strategies. This intricate association involves extensive transcriptional reprogramming in host plant cells during the formation of arbuscules, which are specialized fungal structures for nutrient exchange. The symbiosis is initiated by molecular signaling pathways triggered by fungal chitooligosaccharides and strigolactones released by plant roots, which act as chemoattractants and signaling molecules to promote fungal spore germination, colonization, and arbuscule development. Calcium spiking, mediated by LysM domain receptor kinases, serves as a critical second messenger in coordinating fungal infection and intracellular accommodation. GRAS transcription factors are key components that regulate the transcriptional networks necessary for arbuscule development and maintenance, while small RNAs (sRNAs) from both plant and fungi, contribute to modifications in gene expression, including potential bidirectional sRNA exchange to modulate symbiosis. Understanding the molecular mechanisms related to AM symbiosis may provide valuable insights for implementation of strategies related to enhancing plant productivity and resilience. Full article

Lasiodiplodia theobromae is a pathogenic fungus associated with tropical perennial fruit plants worldwide. In apple trees, L. theobromae causes dieback and canker, a disease that affects the architecture of the wood producing the progressive death of branches and stems, from the tips to the base, invading the vascular tissue, manifesting necrotic lesions in the bark, impeding the flow of nutrients and water. The present work reports the whole genome de novo sequencing (WGS) of L. theobromae strain Bot-2018-LT45 isolated from apple trees with dieback symptoms. Genomic DNA of L. theobromae was sequenced using Illumina paired-end short-read technology (NovaSeq6000) and PacBio SMRTbell^TM (Single Molecule, Real-Time) long-read technology. The genome size was 44.17 Mb. Then, assembly and annotation revealed a total of 12,948 genes of which 11,634 encoded proteins. The genome was assembled into 34 contigs with an N50 (Mb) value of 3.23. This study is the first report of the L. theobromae genome de novo obtained from apple trees with dieback and canker symptoms in the Maule Region, Chile. This genetic information may set the basis for future study of the mechanisms of L. theobromae and establish the possibility of specific molecular improvements for the control of dieback and canker. Full article

Electric vehicles (EVs) are a sustainable means of transportation, with their onboard batteries being crucial for both performance and energy management. A modular and reconfigurable power converter topology to connect removable batteries to the main DC bus of an EV is proposed in this paper. By employing Dual Active Bridge (DAB) converters in an Input Parallel Output Series (IPOS) configuration, the proposed topology is compatible with 400 V and 800 V standards without the need for external switches. The research explored the possibility to apply a very simple control strategy based on independent linear regulators. A theoretical analysis of the IPOS DAB converter is presented and the design of independent control regulators which minimize the coupling effect between the control variables is addressed. The stability of the IPOS DAB converter could be ensured using the proposed simplistic approach, enabling us to drastically simplify the regulator design step. The dynamic performance of the system was confirmed by means of a simulation and experimentally. Full article

Background: Chronic kidney disease (CKD) patients often experience dysregulated inflammation, particularly when compounded by comorbidities such as type 2 diabetes (T2D). Objective: The aim of this study was to determine whether T2D influences the profile of memory T lymphocytes, regulatory T cells (Tregs), and the gene expression of transcription factors such as T-bet (Tbx21), GATA3, RORyT (RORC), and FOXP3 in CKD patients. Methods: Twenty-two CKD patients undergoing hemodialysis were selected for the study. Flow cytometry was used to identify naïve T cells, Tregs (CD4+CD25+CD127-), central memory T lymphocytes (CCR7+CD45RA-), effector memory T lymphocytes (CCR7-CD45RA-), and TEMRA cells (CCR7-CD45RA+). The expression of helper T cell differentiation regulatory genes was assessed using real-time RT-PCR. Results: Both helper and cytotoxic effector memory T cell populations were found to be higher than naïve lymphocytes in CKD patients, regardless of T2D status. However, Tregs were significantly more frequent in diabetic CKD patients (5.1 ± 2.6%) compared to non-diabetic patients (2.8 ± 3.1%). In terms of transcription factor expression, a significant correlation was observed between T-bet and FOXP3 in diabetic patients, and between RORyT and FOXP3 in non-diabetic patients. Conclusions: While T2D does not notably alter the distribution of memory T cells in CKD patients, it significantly impacts the frequency of Tregs and their correlation with pro-inflammatory transcription factors like T-bet (Tbx21) and RORyT. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by self-antibody production and widespread inflammation affecting various body tissues. This disease is driven by the breakdown of immune tolerance, which promotes the activation of autoreactive B and T cells. A key feature of SLE is dysregulation in antigen presentation, where antigen-presenting cells (APCs) play a central role in perpetuating immune responses. Dendritic cells (DCs) are highly specialized for antigen presentation among APCs. At the same time, myeloid-derived suppressor cells (MDSCs) can also express MHC-II molecules, although their role in SLE is less understood. Utilizing the SLE model, MRL/MpJ-Fas^lpr/J, we determined the presence of different phenotypes of DCs and MDSCs expressing MHC-II in secondary lymphoid organs, along with the gene expression of ICOSL, CD80 and CD86 in the spleen. Our study determined that the most abundant population of APCs in secondary lymphoid organs corresponds to cDC CD103⁻CD11b⁺ MHC-II⁺ throughout SLE development. Additionally, ICOSL expression increased over time, becoming more preponderant in week 16 in the SLE model, which could indicate that it is a crucial pathway for the development and progression of the pathology. In week 16, we observed a positive correlation between M-MDSC MHC-II and IFN-γ-producing CD4⁺ T cells. Full article

Background: The manufacture of biologics is a complex, controlled, and reproducible process that results in a product that meets specifications. This should be based on data from batches used to demonstrate manufacturing consistency. Ten batches of originator product (Avastin^®) were analyzed over a 10-year period. Methods: The β-expectation tolerance intervals and the process capability analysis were proposed to establish the specification limits for determining the acceptance criteria of the final product from the manufacturing process. Protein concentration and dimer content were utilized as CQAs. The analytical similarity between three biosimilars authorized in Spain since 2021 (Vegzelma^®, Alymsys^®, and Oyavas^®) and the originator product were evaluated for both CQAs using two methods: the quality range (QR) method, based on one sample per batch, and the QRML one, which takes into account the inter- and intra-batch variability of the originator product. Results: The results indicate that the two main sources of variation are under control; even the level of variability observed is close to the capability of the analytical method. The manufacturing process, therefore, continues under statistical control. Similarity is demonstrated for the bevacizumab concentration regardless of the approach used, whereas similarity is demonstrated for the dimer content for only one of the biosimilar products. Conclusions: The proposed methodologies allow for the analysis of the consistency of the manufacturing process and the variability from batch to batch. Full article

Mucormycosis, an invasive fungal infection caused by members of the order Mucorales, often progresses fulminantly if not recognized in a timely manner. This comprehensive review discusses the latest developments in diagnostic approaches for mucormycosis, from traditional histopathology and culture-based methods to advanced and emerging techniques such as molecular assays, imaging, serology, and metabolomics. We discuss challenges in the diagnosis of mucormycosis and emphasize the importance of rapid and accurate identification of this life-threatening infection. Full article

Non-coding RNAs (ncRNAs) and the innate immune system are closely related, acting as defense mechanisms and regulating gene expression and innate immunity. Both are modulators in the initiation, development and progression of cancer. We aimed to review the major types of ncRNAs, including small interfering RNAs (siRNAs), microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and long non-coding RNAs (lncRNAs), with a focus on cancer, innate immunity, and inflammation. We found that ncRNAs are closely related to innate immunity, epigenetics, chronic inflammation, and cancer and share properties such as inducibility, specificity, memory, and transfer. These similarities and interrelationships suggest that ncRNAs and modulators of trained immunity, together with the control of chronic inflammation, can be combined to develop novel therapeutic approaches for personalized cancer treatment. In conclusion, the close relationship between ncRNAs, the innate immune system, and inflammation highlights their importance in cancer pathways and their potential as targets for novel therapeutic strategies. Full article

Traditional Mexican medicine commonly uses infusions of Ternstroemia spp. to treat insomnia, injuries, and infections. The antibacterial activities of Ternstroemia dentisepala and Ternstroemia lineata were evaluated for the first time against a panel of Gram-positive and Gram-negative bacteria that have implications for human health, including Enterococcus faecalis, Streptococcus agalactiae, Streptococcus pyogenes, Salmonella typhi, Pseudomonas aeruginosa, and Vibrio parahaemolyticus. Furthermore, the scavenging potential of the hydroalcoholic (HAEs) and total phenolic extracts (TPEs) from the leaves of both plants by a 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay (ABTS^•+) was determined. Also, the total phenolic contents of the HAEs using the Folin–Ciocalteu reagent were assayed. T. dentisepala HAE and TPE were active against all bacterial strains tested, with a minimum inhibitory concentration between 1.0 and 6.0 mg/mL, with the last one being the most active. However, the T. lineata extracts only demonstrated effectiveness against S. typhi and P. aeruginosa. The TPEs from T. dentisepala and T. lineata improved the activity by approximately 30% in all bacteria tested in comparison with the HAEs. The T. dentisepala HAE had a higher total phenolic content than the T. lineata extract, which was consistent with its ABTS^•+-scavenging activity. The two HAEs had different chemical profiles, mostly because of the types and amounts of phenolic compounds they contained. These profiles were obtained using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and proton nuclear magnetic resonance (¹H NMR) experiments. Full article