Hasil untuk "Pharmacy and materia medica"

Peipei Zhou, Zheng Dong, Insup Lee et al.

This report summarizes the discussions and recommendations from the NSF Workshop on Algorithm-Hardware Co-design for Medical Applications, held on September 26-27, 2024, in Pittsburgh, PA. The workshop assembled an interdisciplinary cohort of researchers, clinicians, and industry leaders to examine foundational challenges and develop a strategic roadmap for algorithm-hardware co-design in medical computing. The workshop focuses on four thematic areas: (1) teleoperations, telehealth, and surgical operations; (2) wearable and implantable medicine, including implantable living pharmacies; (3) home ICU, hospital systems, and elderly care; and (4) medical sensing, imaging, and reconstruction. This report calls for a fundamental shift in how next-generation medical technologies are conceived, designed, validated, and translated into practice. The report recommends that NSF sustain investment in shared standardized data infrastructures and compute infrastructures, develop clinic workflow-aware systems and human-AI collaboration frameworks, promote scalable validation ecosystems grounded in objective, continuous measures, and physics-informed, and enable safe, accountable, and resilient platforms, including virtual-physical healthcare ecosystems, to de-risk translational pathways. The workshop information can be found on the website: https://sites.google.com/view/nsfworkshop.

Reeta S. Tekam, Basant K. Ningawal, Pooja Vaskle et al.

Background: Managing pain after lower abdominal surgery is important for smooth recovery. Regional anesthesia techniques, like the transversus abdominis plane (TAP) block and ilioinguinal–iliohypogastric (II/IH) nerve block, help reduce opioid use. This study compares the effectiveness of these two blocks in pain control, time to first rescue dose, hemodynamic stability, and side effects. Materials and Methods: A comparative study was done on 100 patients having lower abdominal surgeries under spinal anesthesia. Patients were divided into two groups: Group A (n = 50): Received bilateral TAP block with 20 ml of 0.375% ropivacaine per side. Group B (n = 50): Received bilateral II/IH block with the same drug and volume. Pain scores (VAS) were noted at different time points up to 48 hours. Time to first rescue analgesia, vitals, and side effects were recorded. Results: VAS scores at 4 to 24 hours were lower in the TAP group. Time to first rescue dose was longer in the TAP Group A (9.35 ± 0.47 hours) vs. the II/IH Group B (6.97 ± 1.16 hours). Hemodynamics and side effects were similar. Conclusion: TAP block offers better pain relief and longer duration than II/IH block in abdominal surgeries.

Mahdieh Fatemi-Nejad, Maryam Mehrpooya, Davoud Ahmadimoghaddam et al.

Background: Patients with acute coronary syndrome (ACS) are at an increased risk of medication errors due to the complexity of medication regimens, frequent transitions of care, the use of high-risk medications, and their vulnerability to adverse events. Objective: This randomized controlled trial aimed to compare the effectiveness and time efficiency of proactive versus retroactive medication reconciliation models in preventing unintentional medication discrepancies in patients hospitalized with ACS. Methods: Conducted from January to June 2024 at a specialty cardiovascular teaching hospital in West Iran, the study included 162 eligible patients admitted to the coronary care unit (CCU) with a diagnosis of ACS and taking at least five regular medications. Patients were randomly assigned to either the proactive or retroactive reconciliation group (81 each). A clinical pharmacist led both reconciliation models, supported by trained pharmacy interns who conducted patient interviews to obtain detailed medication histories. Primary outcome measures included the number and types of unintentional medication discrepancies identified, as well as their potential harm. Results: A total of 654 medications were reconciled using the proactive approach, compared to 627 with the retroactive method. Among the discrepancies identified, 13 % were unintentional in the proactive group, whereas 44 % were unintentional in the retroactive group (p < 0.001). Additionally, 66.7 % of patients in the retroactive group had at least one discrepancy, compared to 38.3 % in the proactive group (p < 0.001). The average number of unintentional discrepancies per patient was significantly lower in the proactive approach (0.6) than in the retroactive model (1.7; p < 0.001). Over 51 % of errors in the retroactive group had the potential for moderate or severe harm, while most errors in the proactive model were assessed as having only mild harm (86.5 %; p < 0.001). The acceptance rate of pharmacist recommendations regarding unintentional medication discrepancies was higher in the retroactive reconciliation group compared to the retroactive group (68 % vs. 21 %; p < 0.001), and physicians reported greater satisfaction with the proactive method. Furthermore, the proactive model demonstrated superior time efficiency in completing the medication reconciliation process and resolving discrepancies. Conclusions: Our findings demonstrate that the proactive model of medication reconciliation is more time-efficient and effective in preventing unintentional medication discrepancies in patients hospitalized with ACS compared to the retroactive approach. Trial registration: The trial was registered at Iranian Registry of Clinical Trials (https://irct.behdasht.gov.ir/trial/74760, identifier code: IRCT20120215009014N494). Registration date: 2024-01-02.

Renata Maria Bianca Langfelder, Roberto Langella, Cinzia D’Angelo et al.

<b>Background</b>: Biosimilars represent a fundamental advancement in global healthcare, offering significant cost containment while maintaining both therapeutic efficacy and safety in the management of chronic diseases. The cost savings generated by adopting biosimilars could be reinvested to foster innovation in the healthcare sector and enhance patient access to advanced therapies. <b>Methods</b>: A comprehensive analysis was conducted within an Italian healthcare organization which, through its hospital network, serves over 3.5 million individuals. Usage patterns, expenditure, and patient coverage for the principal biosimilar agents across various therapeutic areas were examined. Data were extracted from institutional registries, and a year-over-year comparison from 2022 to 2024 was performed to evaluate trends in consumption, biosimilar adoption among treatment-naïve patients, incurred costs, potential and actual savings, as well as therapeutic switching profiles. <b>Results</b>: The analysis revealed a marked shift towards biosimilar formulations for the majority of the evaluated biological agents between 2022 and 2024. However, for certain active substances, a reduced market penetration of biosimilars was observed, and critical issues persist that will necessitate future interventions. <b>Conclusions</b>: The results demonstrate a consistent upward trajectory in biosimilar adoption, underscoring significant progress toward their integration into routine clinical practice—a transition that has generated substantial savings over the three-year period considered. Assuming a complete transition to biosimilars, the cumulative potential savings over the three-year period would amount to EUR 7,172,372.99 in 2022, EUR 6,209,289.05 in 2023, and EUR 23,536,824.05 in 2024. This trend aligns with strategic objectives to enhance the sustainability of the Italian National Health Service (SSN) through optimized resource allocation and improved patient access.

Mukesh Soni, Shivani Mishra, Madhu S. Ratre et al.

Background: The accumulation of microbial biofilm around dental implants remains a significant concern in maintaining peri-implant health. Ineffective cleaning of the peri-implant mucosa can result in peri-implantitis, jeopardizing implant longevity. This study evaluates the influence of different peri-implant mucosa cleaning protocols on microbial biofilm formation. Materials and Methods: A total of 60 patients with dental implants were included in this randomized controlled trial. Participants were divided into three groups (n = 20 per group) based on the cleaning protocol: Group 1 (manual brushing with soft bristles), Group 2 (ultrasonic cleaning), and Group 3 (air polishing). Biofilm accumulation was assessed at baseline, 1 month, and 3 months using the Plaque Index (PI) and microbial colony-forming units (CFU). Statistical analysis was performed using one-way ANOVA to determine significant differences between groups. Results: At the end of the study, Group 3 (air polishing) demonstrated the least biofilm accumulation, with a mean PI score reduction of 70% compared to baseline. Group 2 (ultrasonic cleaning) showed a 50% reduction, whereas Group 1 (manual brushing) exhibited a 30% reduction. Microbial analysis revealed the lowest CFU counts in Group 3 (1500 ± 200 CFU), followed by Group 2 (3200 ± 300 CFU) and Group 1 (5000 ± 400 CFU). Statistically significant differences (P < 0.05) were observed between the groups at 1 and 3 months. Conclusion: Air polishing proved to be the most effective peri-implant mucosa cleaning protocol for reducing microbial biofilm formation, followed by ultrasonic cleaning. Manual brushing alone showed limited efficacy in controlling biofilm. Implementing efficient cleaning protocols is crucial for preventing peri-implant diseases and enhancing implant success.

Colin M. Meulblok, Amitesh Singh, Matthieu Labousse et al.

The sequential response of frustrated materials - ranging from crumpled sheets and amorphous media to metamaterials - reveals their memory effects and emergent computational potential. Despite their spatial extension, most studies rely on a single global stimulus, such as compression, effectively reducing the problem to scalar driving. Here, we introduce vectorial driving by applying multiple spatially localized stimuli to explore path-dependent, sequential responses. We uncover a wealth of phenomena absent in scalar driving, including non-Abelian responses, mixed-mode behavior, and chiral loop transients. We find that such path dependencies arise from elementary motifs linked to fold singularities, which connect triplets of states - ancestor, descendant, and sibling; and develop a general framework using pt-graphs to describe responses under any vectorial driving protocol. Leveraging binarized vectorial driving, we establish a natural connection to computation, showing that a single sample can encode multiple sequential Boolean circuits, which are selectable by driving strength and reprogrammable via additional inputs. Finally, we introduce graph-based motifs to manage the complexity of high-dimensional driving. Our work paves the way for strategies to explore, harness, and understand complex materials and memory, while advancing embodied intelligence and in-materia computing.

Zechao Jiang, Liyiming Tao, Xiuyuan Yang et al.

The evaporation of liquid droplets often results in a ring-like deposition pattern of particles, presenting challenges for applications requiring highly uniform patterns. Despite extensive efforts to suppress the coffee ring effect, achieving a uniform particle distribution remains a great challenge due to the complex and non-equilibrium nature of the evaporation process. In this work, we introduce and demonstrate a one-step drying method for binary droplets (water and 2-methoxyethanol) that produces uniform deposition of nano- and micro-particles. By adjusting the initial water volume fraction, we effectively control the interplay between capillary and Marangoni flows, resulting in deposition patterns that vary from coffee ring to uniform and to volcano-like. Through both theoretical and experimental analyses, we determine the conditions necessary for achieving such high uniformity. This approach requires no special substrate treatment, particle modification, or controlled environments, and works for various particles, including silica and polystyrene. Our method provides a robust solution for fabricating uniform patterns that are crucial for many practical applications, ranging from printing to microelectronics to bio-pharmacy.

Hiroyuki Uchida, Koji Mori, Hiroshi Tomida et al.

We present a summary of the in-orbit performance of the soft X-ray imaging telescope Xtend onboard the XRISM mission, based on in-flight observation data, including first-light celestial objects, calibration sources, and results from the cross-calibration campaign with other currently-operating X-ray observatories. XRISM/Xtend has a large field of view of $38.5'\times38.5'$, covering an energy range of 0.4--13 keV, as demonstrated by the first-light observation of the galaxy cluster Abell 2319. It also features an energy resolution of 170--180 eV at 6 keV, which meets the mission requirement and enables to resolve He-like and H-like Fe K$α$ lines. Throughout the observation during the performance verification phase, we confirm that two issues identified in SXI onboard the previous Hitomi mission -- light leakage and crosstalk events -- are addressed and suppressed in the case of Xtend. A joint cross-calibration observation of the bright quasar 3C273 results in an effective area measured to be $\sim420$ cm$^{2}$@1.5 keV and $\sim310$ cm$^{2}$@6.0 keV, which matches values obtained in ground tests. We also continuously monitor the health of Xtend by analyzing overclocking data, calibration source spectra, and day-Earth observations: the readout noise is stable and low, and contamination is negligible even one year after launch. A low background level compared to other major X-ray instruments onboard satellites, combined with the largest grasp ($Ω_{\rm eff}\sim60$ ${\rm cm^2~degree^2}$) of Xtend, will not only support Resolve analysis, but also enable significant scientific results on its own. This includes near future follow-up observations and transient searches in the context of time-domain and multi-messenger astrophysics.

Juan Carlos Romero-Benavides, Evelyn Guaraca-Pino, Rodrigo Duarte-Casar et al.

The species <i>Chenopodium quinoa</i> Willd. and <i>Amaranthus hybridus</i> L. are Andean staples, part of the traditional diet and gastronomy of the people of the highlands of Colombia, Ecuador, Peru, Bolivia, northern Argentina and Chile, with several ethnopharmacological uses, among them anticancer applications. This review aims to present updated information on the nutritional composition, phytochemistry, and antimicrobial and anticancer activity of Quinoa and Amaranth. Both species contribute to food security due to their essential amino acid contents, which are higher than those of most staples. It is highlighted that the biological activity, especially the antimicrobial activity in <i>C. quinoa</i>, and the anticancer activity in both species is related to the presence of phytochemicals present mostly in leaves and seeds. The biological activity of both species is consistent with their phytochemical composition, with phenolic acids, flavonoids, carotenoids, alkaloids, terpenoids, saponins and peptides being the main compound families of interest. Extracts of different plant organs of both species and peptide fractions have shown in vitro and, to a lesser degree, in vivo activity against a variety of bacteria and cancer cell lines. These findings confirm the antimicrobial and anticancer activity of both species, <i>C. quinoa</i> having more reported activity than <i>A. hybridus</i> through different compounds and mechanisms.

Tracy Sandritter, Rachel Chevalier, Rebecca Abt et al.

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (<i>TPMT</i>) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug–gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC^®) to highlight relevant drug–gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and <i>TMPT</i> and Nudix hydrolase 15 (<i>NUDT15</i>), and budesonide and tacrolimus and CYP3A5.

Iver Brevik

In cases when it is desirable to transport medication through blood vessels, especially when dealing with brain cancer being confronted with the narrow arteries in the brain, the blood-brain barrier makes the medical treatment difficult. There is a need of expanding the diameters of the arteries in order to facilitate the transport of medicaments. Recent research has pointed to various ways to improve this situation; in particular, the use ultrasound acting on microbubbles in the blood stream has turned out to be a promising option. Here, a different possibility of enlarging the diameters of arteries is discussed, namely to exploit the electrostrictive pressure produced by internal strong, ultrashort and repetitive laser pulses. Each pulse will at first give rise to inward directed optical forces, and once the pulse terminates there will be a hydrodynamical bouncing flow in the outward radial direction giving an outward impulse to the vessel wall. In the absence of friction a symmetric oscillation picture emerges. Clearly, a supply of repetitive pulses will be needed (at parametric resonance) to make the effect appreciable. The effect has to our knowledge not been discussed before. We give an approximate optical and hydrodynamical theory of it. The calculations indicate promising results for the wall pressure, although experimental work is desirable to show whether the idea can be useful in practice. Our calculation is made from a general physical perspective, not necessarily linked to medical applications.

Zheyang Li, Xi Yu

Exploring nonlinear chemical dynamic systems for information processing has emerged as a frontier in chemical and computational research, seeking to replicate the brain's neuromorphic and dynamic functionalities. We have extensively explored the information processing capabilities of a nonlinear chemical dynamic system through theoretical modeling by integrating a non-steady-state proton-coupled charge transport system into reservoir computing (RC) architecture. Our system demonstrated remarkable success in tasks such as waveform recognition, voice identification and chaos system prediction. More importantly, through a quantitative study, we revealed the key role of the alignment between the signal processing frequency of the RC and the characteristic time of the dynamics of the nonlinear system, which dictates the efficiency of RC task execution, the reservoir states and the memory capacity in information processing. The system's information processing frequency range was further modulated by the characteristic time of the dynamic system, resulting in an implementation akin to a 'chemically-tuned band-pass filter' for selective frequency processing. Our study thus elucidates the fundamental requirements and dynamic underpinnings of the non-steady-state charge transport dynamic system for RC, laying a foundational groundwork for the application of dynamic molecular devices for in-materia computing.

Tomasz Cyganek, Michał Widuch, Szymon Mizera et al.

Introduction It is recommended to remove all nail polish before hospital admission to prevent erroneous oximeter readings. Although studies on the effect of color and type of nail polish on pulse oximetry are scarce, some differences were observed depending on the color of nail varnish. In this study we sought to evaluate the impact of the type and color of nail polish on saturation (SpO 2 ) values in healthy female volunteers. Material and methods 169 females with nail polish applied to nails had their SpO 2 measured with a pulse oximeter. After five minutes of rest, SpO 2 was assessed from a finger and, as control, from an earlobe. The differences were subjected to statistical analysis. Results 169 paired measurements were obtained. Statistically significant differences were observed for enameled (p < 0.01) and hybrid (p < 0.01), but not for gel (p = 0.25) nails. As far as the colors are concerned, beige (p < 0.01), red (p < 0.01) and violet (p = 0.047) cover had a significant impact on the SpO 2 readings. The differences in the measurements were 1%. Conclusions Classic nail polish, hybrid polish, and the colours beige, red and violet may affect SpO 2 readings but this effect is low and of no clinical significance.

Mitchell J. Barnett, Tristan Lindfelt, Shadi Doroudgar et al.

Background: Changes in demographics and composition of pharmacy faculty, along with faculty perceived stress, work-life balance and career satisfaction have yet to be fully documented. Objective: To compare recent results from a national survey of work-life balance and career satisfaction of United States (U.S.) pharmacy faculty with results obtained from a similar survey from 2012. Methods: A 46-item anonymous survey administered via Qualtrics (Provo, UT) was sent to members of the American Association of Colleges of Pharmacy (AACP) in 2018. Information regarding demographics, stress, work-life balance, career satisfaction and intent to leave academia was collected. Although not part of the previous survey, participant information related to bullying and abuse in the pharmacy academic work was also gathered. While actual p-values are reported for all comparisons, a more conservative p-value of 0.01 was chosen a priori to indicate significance as multiple comparisons were made. Results: A total of 1090 pharmacy faculty completed the survey, comparable to the number obtained in 2012 (n = 811). Overall response rates were similar for both years. The majority of pharmacy faculty in 2018 were female, white, married or with partner, worked in a pharmacy practice department and for a public institution. Notable differences between surveys included an increase in females, more associate professors and an increase in non-white faculty in 2018, relative to 2012. Stress, as measured by mean Perceived Stress Scale (PSS) scores was also significantly higher in 2018 (16.0 ± 6.6 vs. 13.5 ± 6.7, p < 0.01) relative to 2012. Faculty from 2018 were significantly less likely to report an intention to remain in academia (61.8% vs 86.3%, p < 0.01), relative to 2012. A sizable number of pharmacy faculty surveyed in 2018 also reported observing or experiencing hostility in the workplace, which included either bullying or verbal or physical abuse. Conclusions: The makeup of pharmacy educators has evolved quickly over the last several years to comprise more female and associate professors who work within a pharmacy practice department. Also noteworthy is the significant increase in self-reported stress over the six-year timeframe. The direct implications of these findings are unknown but suggest that pharmacy academia is maturing in rank and changing to reflect the current pharmacy workforce (i.e., more females and additional clinical practice roles). Increases in responsibility likely accompany these maturing roles and may, along with other factors, contribute to the observed changes in the reported stress levels among faculty. Further research is called for regarding the reported hostility in pharmacy academic workplace and dovetails with concurrent work being done on citizenship and organizational citizenship behavior among pharmacy faculty. Findings of the study may aid pharmacy school administrators and stakeholders with plans to recruit, develop and retain faculty.

R. N. Hota, B. K. Nanda, B. R. Behera et al.

Abstract Background Limnophila rugosa (Scrophulariaceae) is a perennial aquatic plant used as a diuretic and digestive tonic as well as in the treatment of diarrhea, dysentery, dyspepsia and urinary ailments. Genus Limnophila has been reported as hepatoprotective. The present study was undertaken to evaluate the hepatoprotective activity of the ethanolic extract of L. rugosa aerial part in paracetamol- and carbon tetrachloride-induced (CCl4) hepatotoxicity in albino Wistar rats. Ethanolic extract was subjected to high-performance liquid chromatography (HPLC) analysis for the estimation of phenolic and flavonoid compounds and gas chromatography–mass spectrometry (GC–MS) analysis for phytochemical analysis. The in vitro antioxidant activity was carried out by 2,2-diphenyl-1-picrylhydrazyl, nitric oxide radical and hydrogen peroxide assay. Hepatoprotective potential of L. rugosa was studied in paracetamol (750 mg/mg)- and CCl4 (1.25 ml/kg)-induced liver damage in albino rats at dose 200 and 300 mg/kg using silymarin (100 mg/kg) as standard. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were determined in liver tissue homogenate. Serum biochemical and histopathological examination was performed. Molecular docking analysis was performed to understand the molecular mechanism of hepatoprotective activity. Results HPLC analysis revealed predominance of rutin. GC–MS analysis revealed camphor as principal component. Ethanolic extract exhibited significant concentration-dependent scavenging efficacy. The altered biochemical chemical parameters: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, albumin, globulin and total protein, were significantly improved at 200 and 300 mg/kg in experimental rats. Extract signified hepatoprotective by decreasing lipid peroxidation and upregulating SOD, CAT and GSH. The findings were well supported by histological analysis. 2-Butyl-2, 7-octadien-1-ol (-5.8) and camphor (-4.8) gave the highest docking score on the transforming growth factor-β1. Conclusions The ameliorative effect of L. rugosa in the rat model of hepatotoxicity could be attributed to its antioxidant potential and bioactive principles such as betulin, 5-hydroxy-6,7,4′-trimethoxyflavone (salvigenin), betulinic acid, ursolic acid, 3-octanol, acetophenone, anisylacetone, caryophyllene, cis-anethole and the compounds camphor and 2-butyl-2,7-octadien-1-ol identified from GC–MS analysis.

Kwang-Hoon Chun

Hepatocellular carcinoma (HCC) is one of the leading global causes of cancer mortality. MicroRNAs (miRNAs) are small interfering RNAs that alleviate the levels of protein expression by suppressing translation, inducing mRNA cleavage, and promoting mRNA degradation. miR-122 is the most abundant miRNA in the liver and is responsible for several liver-specific functions, including metabolism, cellular growth and differentiation, and hepatitis virus replication. Recent studies have shown that aberrant regulation of miR-122 is a key factor contributing to the development of HCC. In this review, the signaling pathways and the molecular targets of miR-122 involved in the progression of HCC have been summarized, and the importance of miR-122 in therapy has been discussed.

Fengtian Sun, Yuntong Sun, Feng Wu et al.

As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) and diabetic complications. To overcome the limitations of natural MSC-EVs such as heterogeneity and insufficient function, several modification methods have been established for constructing engineered MSC-EVs with elevated repairing efficiency. In this review, the PubMed library was searched from inception to August 2022, using a combination of Medical Subject Headings (MeSH) and keywords related to MSC-EVs, DM, and diabetic complications. We provide an overview of the major characteristics of MSC-EVs and summarize the recent advances of MSC-EV-based therapy for hyperglycemia-induced tissue damage with an emphasis on MSC-EV-mediated delivery of functional components. Moreover, the potential applications of engineered MSC-EVs in DM-related diseases therapy are discussed by presenting examples, and the opportunities and challenges for the clinical translation of MSC-EVs, especially engineered MSC-EVs, are evaluated.

Haoneng Tang, Yong Ke, Lei Wang et al.

The Omicron variant has swept through most countries and become a dominant circulating strain, replacing the Delta variant. The evolutionary history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that the onset of another variant (possibly another variant of concern (VOC) is inevitable. Therefore, the development of therapeutics that enable treatments for all Omicron-included VOCs/variants of interest (VOIs) and future variants is desired. Recently, the recombinant receptor decoy therapeutic angiotensin-converting enzyme 2 (ACE2)-Fc has exhibited good safety in a phase 1 clinical trial; therefore, its variant-resistant profile needs to be understood. Here, we conducted a comprehensive evaluation of its neutralization breadth against the Omicron variant and other VOCs/VOIs. Furthermore, to evaluate its resistance to future variants, we investigated its ability to neutralize various single-residue mutated variants. Next, we demonstrated its resistance to evasion via an experiment that rapidly and effectively stimulates virus evolution with a replication-competent virus model. In addition, we evaluated its efficacy for cocktail therapy. The combination of ACE2-Fc and neutralizing antibodies showed both efficacy and breadth in the simulation experiment. The underlying mechanism was revealed to be a synergistic effect in the cocktails. Collectively, this study deepens the understanding of the resistance profile of recombinant receptor decoy therapeutics and highlights the potential value of ACE2-Fc and neutralizing antibody cocktails in the subsequent anti-SARS-CoV-2 campaign. Furthermore, we also provide an effective method to study the resistance profile of antiviral agents and rapidly screen for potential cocktails to combat future variants.

Alaa Shafie, Shama Khan, Zehra et al.

Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1α in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1α. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski’s rules and PAINS filter. Further, high-affinity hits against CK1α were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1α binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1α and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1α.

Fátima Fernández-Álvarez, Gracia García-García, José L. Arias

A (core/shell)/shell nanostructure (production performance ≈ 50%, mean diameter ≈ 330 nm) was built using maghemite, PLGA, and chitosan. An extensive characterization proved the complete inclusion of the maghemite nuclei into the PLGA matrix (by nanoprecipitation solvent evaporation) and the disposition of the chitosan shell onto the nanocomposite (by coacervation). Short-term stability and the adequate magnetism of the nanocomposites were demonstrated by size and electrokinetic determinations, and by defining the first magnetization curve and the responsiveness of the colloid to a permanent magnet, respectively. Safety of the nanoparticles was postulated when considering the results from blood compatibility studies, and toxicity assays against human colonic CCD-18 fibroblasts and colon carcinoma T-84 cells. Cisplatin incorporation to the PLGA matrix generated appropriate loading values (≈15%), and a dual pH- and heat (hyperthermia)-responsive drug release behaviour (≈4.7-fold faster release at pH 5.0 and 45 °C compared to pH 7.4 and 37 °C). The half maximal inhibitory concentration of the cisplatin-loaded nanoparticles against human lung adenocarcinoma A-549 cells was ≈1.6-fold less than that of the free chemotherapeutic. Such a biocompatible and tri-stimuli responsive (maghemite/PLGA)/chitosan nanostructure may found a promising use for the effective treatment of lung cancer.