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2.
RSC Adv ; 14(42): 31227-31242, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39355328

ABSTRACT

The main objective of the present study is to investigate the potency of new synthesized hydroxycarbamoyl phosphinic acid derivatives in modulating cytotoxic fibrillogenesis of hen egg white lysozyme (HEWL), as a common model in protein aggregation studies. Hydroxycarbamoyl phosphinic acid derivatives were prepared by the reaction of α-hydroxyalkylphosphinic acids with isocyanates (or isothiocyanates) in the presence of trimethylsilyl chloride (TMSCl). The designed process involves the condensation reaction leading to formation of new C sp2-P bond formation. The synthesis and purity of novel designed compounds were confirmed by NMR, LC-MS, and HPLC techniques. A range of experiments, including thioflavin T (ThT) and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence assays, Congo red binding measurement, atomic force microscopy imaging, MTT-based cell viability and hemolysis assays were employed to investigate anti-amyloidogenic effects of tested compounds. The obtained results demonstrate that these compounds are able to significantly modulate the self-assembly process of HEWL via shortening of nucleation phase leading to the acceleration of fibrillation and appearance of very large and thick fibrils with decreased surface hydrophobicity and cytotoxicity. Based on ANS binding data, we suggest that increased exposure of hydrophobic patches of oligomeric species is the possible mechanism by which tested compounds promote self-assembly process of HEWL. Fluorescence anisotropy and molecular docking studies indicate the interaction of both synthesized compounds with HEWL, and more specifically with residues that are situated in the highly aggregation-prone ß-domain region of protein. This study unveils the potential of hydroxyalkylphosphinic acids as modulators of amyloid fibrillation highlighting these compounds as a promising approach for targeting protein aggregates associated with neurodegenerative diseases.

3.
Article in English | MEDLINE | ID: mdl-39361012

ABSTRACT

The use of ultrasound for pleural procedures is associated with a decreased risk of complications. Handheld ultrasounds allow for easier evaluation of the pleural space. Limited data exists for the use of such devices for pleural procedures. The primary objective of our study was to assess the effectiveness and safety of handheld ultrasound for pleural procedures. We performed a prospective observational study, including all consecutive patients who underwent pleural procedures using the handheld ultrasound between September 2021 and November 2023. A total of 332 pleural procedures were attempted with handheld ultrasound, of which 329 pleural procedures (99.1%) were successfully performed. The median volume of fluid drained was 500 (interquartile range: 300-800). Thoracentesis was performed in 127 patients (38.5%), tube thoracostomy in 179 patients (54.4%), and medical thoracoscopy in 23 patients (7.0%). Exudative pleural effusions were found in 264 patients (80.0%), of which 152 (46.2%) were determined to be due to infectious etiologies. A total of 4 (1.2%) patients had a complication due to the procedure. 2 patients (0.6%) had a pneumothorax, while 2 patients (0.6%) developed a hemothorax. A total of 101 patients had either low platelets (<50×109/L) or use of anti-platelet or anti-coagulant drugs. 128 patients (38.8%) were on positive pressure support during the pleural procedure. Our study shows that handheld ultrasounds are effective and safe for pleural procedures, including cases with septated pleural effusions and patients on anti-platelet or anti-coagulant drugs.

4.
Bull Emerg Trauma ; 12(2): 73-80, 2024.
Article in English | MEDLINE | ID: mdl-39224470

ABSTRACT

Objective: With the COVID-19 outbreak in countries around the world, the countries' healthcare systems underwent an unprecedented shock. This study aimed to examine the resilience of the medical service delivery system in providing emergency services during the Covid-19 pandemic. Methods: This study was conducted in a reference hospital in Kerman that provided emergency services to trauma patients. It compared service delivery before and after COVID-19, as well as during the COVID-19 peak and non-peak periods. The compared variables were the number of trauma patients admitted to the hospital and the ICU, the number of patients who died in the hospital due to trauma, and the length of stay in the hospital and the ICU. Results: The pre- and post-COVID-19 comparisons showed no significant difference in the number of daily hospital admissions, ICU admissions, and patient deaths. The median length of stay in the ICU was significantly reduced by almost 2 days during the COVID-19 outbreak. However, the length of stay at the hospital was almost the same. Furthermore, a comparison of the COVID-19 peaks and non-peak periods indicated no statistically significant difference in the number of admissions in the ICU, hospital and ICU length of stay, and trauma-induced mortality. Conclusion: Despite the substantial workload imposed by COVID-19 on hospitals, especially during the peak periods of the disease, the provision of medical services to emergency trauma patients did not drop significantly, and the quality of services provided to patients was within the acceptable range.

5.
Ann Biomed Eng ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39230788

ABSTRACT

PURPOSE: Ultrasound imaging is key in the management of patients with an abdominal aortic aneurysm (AAA). It was recently shown that the cyclic diameter variations between diastole and systole, which can be quantified with US imaging, increase significantly with the strength of the applied probe pressure on the patient's abdomen. The goal of this study is to investigate this effect more thoroughly. METHODS: With finite-element modeling, pulsatile blood pressure and probe pressure are simulated in three patient-specific geometries. Two distinct models for the aortic wall were simulated: a nonlinear hyperelastic and a linear elastic model. In addition, varying stiffness was considered for the surrounding tissues. The effect of light, moderate, and firm probe pressure was quantified on the stresses and strains in the aortic wall, and on two in vivo stiffness measures. In addition, the Elasticity Loss Index was proposed to quantify the change in stiffness due to probe pressure. RESULTS: Firm probe pressure decreased the measured aortic stiffness, and material stiffness was affected only when the wall was modeled as nonlinear, suggesting a shift in the stress-strain curve. In addition, stiffer surrounding tissues and a more elongated aneurysm sac decreased the responsiveness to the probe pressure. CONCLUSION: The effect of probe pressure on the AAA wall stiffness was clarified. In particular, the AAA wall nonlinear behavior was found to be of primary importance in determining the probe pressure response. Thus, further work will intend to make use of this novel finding in a clinical context.

6.
Chem Asian J ; : e202400873, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258583

ABSTRACT

Stimuli-responsive hydrogels (HGs) have shown promise for smart drug delivery applications. Specifically, glucose-responsive HGs having phenylboronic acid (PBA) functional groups are extensively pursued for insulin delivery in hyperglycemia. Current polymeric glucose-responsive HGs are cumbersome to fabricate and show a limited insulin release profile. Herein, we develop a straightforward fabrication of glucose-responsive multipolymer HGs (MPHGs) using a three-component in situ mixing. Molecular cargo, such as insulin, was loaded during the gelation. Heterobifunctional formylphenylboronic acid (FPBA) crosslinkers were used to interconnect PVA and PEI via boronate ester and imine bonds, respectively. Three positional isomers of FPBA (2FPBA, 3FPBA, and 4FPBA) resulted in HGs with distinct viscoelastic behaviors under the same conditions. HGs derived from 4FPBA exhibited more solid-like properties compared to 2FPBA and 3FPBA due to a higher crosslinking density. All the HGs exhibited glucose-responsive dissolution and release of embedded insulin cargo without disrupting the native structure. Insulin release profiles show a higher glucose-responsive release from 4FPBA-derived MPHGs. All the HGs were injectable, self-healing, and noncytotoxic below 10 µg/ml concentrations. The MPHGs developed in this study uncover new directions in creating glucose-responsive matrices for self-regulating drug delivery applications. In the future, detailed in vivo studies will be performed for clinical applications.

7.
Sci Rep ; 14(1): 20995, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39251629

ABSTRACT

It is commonly known that a number of variables, including price, supply levels, time, and green level, affect how quickly certain things are in demand. Furthermore, the inventory carrying cost is considered to be a nonlinear representation of time and is subject to variation throughout time. More precisely, it rises with time since longer storage times necessitate more costly warehouse space. This study presents a fully backlogged situation inventory system for a single commodity where the product's selling price, green level, and time are used to simultaneously compute the demand rate in accordance with a power pattern. Purchase price is determined by the product's nonlinear green level. Complete backorders are available for shortages. The impact of the product's selling price, green level and time power function are combined to determine the product's demand. Moreover, the holding cost also rises as the product is stored for a longer period of time. The primary goal is to determine the best inventory policy to maximise total profit per unit of time. Though the problem is highly nonlinear in nature. Hence, we cannot solve it analytically. To overcome these difficulties, we have applied several well-known popular metaheuristic algorithms (Water Cycle Algorithm (WCA), Artificial Electric Field Algorithm (AEFA), Teaching Learning Based Optimization Algorithm (TLBOA), Grey Wolf Optimizer Algorithm (GWOA), Sparrow Search Algorithm (SSA), Whale Optimizer Algorithm (WOA), Prairie Dog Optimization Algorithm (PDOA), Gazelle Optimization Algorithm (GOA), A Sinh Cosh Optimizer Algorithm (SCHOA) and White Sherk Optimizer Algorithm (WSOA), Archimedes Optimization Paradigm Algorithm (AOPA), Marine Predator Optimization Algorithm (MPOA), Geyser Inspired Algorithm (GIA), Runge Kutta Optimization Algorithm (RKOA), Lungs Performance-based Optimization Algorithm (LPOA) and Dwarf Mongoose Optimization Algorithm (DMOA)). It is observed that WCA perform better than other algorithms with respect to the convergence rate. A numerical example is taken in order to validate the proposed model. Finally, a post optimality analysis is performed in order to make a fruitful conclusion.

8.
ACS Omega ; 9(37): 39188-39194, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39310157

ABSTRACT

A colorimetric sensor array has been developed to differentiate various micro- and nanoplastic particles (MNPs), both pristine and those coated with a protein corona, in buffered water. This array utilizes five distinct cross-reactive chemo-responsive dyes, which exhibit changes in visible optical absorbance upon interaction with MNPs. Although no single dye responds exclusively to either pristine or protein-corona-coated MNPs, the collective shifts in color across all dyes create a unique molecular fingerprint for each type of MNP. This method demonstrates high sensitivity, capable of detecting MNPs of various sizes (50 nm, 100 nm, and 2 µm) and differentiating them from controls at concentrations as low as 10 ng/mL using standard chemometric techniques, ensuring accurate results without error. Additionally, the method can effectively distinguish between pristine and protein-corona-coated polystyrene MNPs. This colorimetric approach offers a rapid, cost-effective, and accurate method for monitoring MNP pollution and assessing their prior interactions with biological systems.

9.
Daru ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39312086

ABSTRACT

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.

10.
Phys Rev Lett ; 133(10): 106601, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39303240

ABSTRACT

We propose heterostructures that realize first and second order topological superconductivity with vanishing net magnetization by utilizing altermagnetism. Such platforms may offer a significant improvement over conventional platforms with uniform magnetization since the latter suppresses the superconducting gap. We first introduce a 1D semiconductor-superconductor structure in proximity to an altermagnet that realizes end Majorana zero modes (MZMs) with vanishing net magnetization. Additionally, a coexisting Zeeman term provides a tuning knob to distinguish topological and trivial zero modes. We then propose 2D altermagnetic platforms that can realize chiral Majorana fermions or higher order corner MZMs. Our Letter paves the way toward realizing Majorana boundary states with an alternative source of time-reversal breaking and zero net magnetization.

11.
Phys Rev Lett ; 133(10): 106701, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39303256

ABSTRACT

Quantum geometry plays a pivotal role in the second-order response of PT-symmetric antiferromagnets. Here we study the nonlinear response of 2D altermagnets protected by C_{n}T symmetry and show that their leading nonlinear response is third order. Furthermore, we show that the contributions from the quantum metric and Berry curvature enter separately: the longitudinal response for all planar altermagnets only has a contribution from the quantum metric quadrupole (QMQ), while transverse responses in general have contributions from both the Berry curvature quadrupole (BCQ) and QMQ. We show that for the well-known example of d-wave altermagnets the Hall response is dominated by the BCQ. Both longitudinal and transverse responses are strongly dependent on the crystalline anisotropy. While altermagnets are strictly defined in the limit of vanishing spin orbit coupling (SOC), real altermagnets exhibit weak SOC, which is essential to observe this response. Specifically, SOC gaps the spin-group protected nodal line, generating a response peak that is sharpest when SOC is weak. Two Dirac nodes also contribute a divergence to the nonlinear response, whose scaling changes as a function of SOC. Finally, we apply our results to thin films of the 3D altermagnet RuO_{2}. Our work uncovers distinct features of altermagnets in nonlinear transport, providing experimental signatures as well as a guide to disentangling the different components of their quantum geometry.

12.
Enzymes ; 56: 31-54, 2024.
Article in English | MEDLINE | ID: mdl-39304290

ABSTRACT

Tyrosinases (TYR) play a key role in melanin biosynthesis by catalyzing two reactions: monophenolase and diphenolase activities. Despite low amino acid sequence homology, TYRs from various organisms (from bacteria to humans) have similar active site architectures and catalytic mechanisms. The active site of the TYRs contains two copper ions coordinated by histidine (His) residues. The catalytic mechanism of TYRs involves electron transfer between copper sites, leading to the hydroxylation of monophenolic compounds to diphenols and the subsequent oxidation of these to corresponding dopaquinones. Although extensive studies have been conducted on the structure, catalytic mechanism, and enzymatic capabilities of TYRs, some mechanistic aspects are still debated. This chapter will delve into the structure of the active site, catalytic function, and inhibition mechanism of TYRs. The goal is to improve our understanding of the molecular mechanisms underlying TYR activity. This knowledge can help in developing new strategies to modulate TYR function and potentially treat diseases linked to melanin dysregulation.


Subject(s)
Catalytic Domain , Monophenol Monooxygenase , Humans , Monophenol Monooxygenase/metabolism , Monophenol Monooxygenase/chemistry , Melanins/metabolism , Melanins/biosynthesis , Animals , Catalysis , Biocatalysis , Oxidation-Reduction
13.
Colloids Surf B Biointerfaces ; 244: 114185, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39226848

ABSTRACT

Supramolecular medicine refers to the formulation of therapeutic and diagnostic agents through supramolecular techniques, amid treating, diagnosing, and preventing disease. Recently, there has been growing interest in developing metal nanoparticles (MNPs)-amyloid hybrid materials, which have the potential to revolutionize medical applications. Furthermore, the development of MNPs-amyloid hydrogel/scaffold supramolecules represents a promising new direction in amyloid nanotechnology, with potential applications in tissue engineering and biomedicine. This review first provides a brief introduction to the formation process of protein amyloid aggregates and their unique nanostructures. Subsequently, we focused on recent investigations into the use of MNPs-amyloid hybrid materials in tissue engineering and biomedicine. We anticipate that MNPs-amyloid supramolecular materials will pave the way for new functional materials in medical science, particularly in the field of tissue engineering.


Subject(s)
Amyloidogenic Proteins , Drug Delivery Systems , Metal Nanoparticles , Tissue Engineering , Tissue Engineering/methods , Metal Nanoparticles/chemistry , Drug Delivery Systems/methods , Protein Aggregates , Tissue Scaffolds/chemistry , Amyloidogenic Proteins/chemistry , Protein Folding , Protein Conformation , Humans
14.
PLoS One ; 19(9): e0311122, 2024.
Article in English | MEDLINE | ID: mdl-39321158

ABSTRACT

Visible and near-infrared (Vis-NIR) reflectance spectroscopy has recently emerged as an efficient and cost-effective tool for monitoring soil parameters and provides an extensive array of measurements swiftly. This study sought to predict fundamental biological attributes of calcareous soils using spectral reflectance data in the Vis-NIR range through the application of partial least square regression (PLSR) and stepwise multiple linear regression (SMLR) techniques. The objective was to derive spectrotransfer functions (STFs) to predict selected soil biological attributes. A total of 97 composite samples were collected from three distinct agricultural land uses, i.e., sugarcane, wheat, and date palm, in the Khuzestan Province, Iran. The samples were analyzed using both standard laboratory analysis and proximal sensing approach within the Vis-NIR range (400-2500 nm). Biological status was evaluated by determining soil enzyme activities linked to nutrient cycling including acid phosphatase (ACP), alkaline phosphatase (ALP), dehydrogenase (DEH), soil microbial respiration (SMR), microbial biomass phosphorus (Pmic), and microbial biomass carbon (Cmic). The results indicated that the developed PLSR models exhibited superior predictive performance in most biological parameters compared to the STFs, although the differences were not significant. Specifically, the STFs acceptably accurately predicted ACP, ALP, DEH, SMR, Pmic, and Cmic with R2val (val = validation dataset) values of 0.68, 0.67, 0.65, 0.65, 0.76, and 0.72, respectively. These findings confirm the potential of Vis-NIR spectroscopy and the effectiveness of the associated STFs as a rapid and reliable technique for assessing biological soil quality. Overall, in the context of predicting soil properties using spectroscopy-based approaches, emphasis must be placed on developing straightforward, easily deployable, and pragmatic STFs.


Subject(s)
Soil , Spectroscopy, Near-Infrared , Soil/chemistry , Spectroscopy, Near-Infrared/methods , Feasibility Studies , Soil Microbiology , Iran , Phosphorus/analysis , Least-Squares Analysis , Triticum/growth & development , Biomass , Saccharum
15.
PNAS Nexus ; 3(9): pgae320, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39319327

ABSTRACT

An occupation is comprised of interconnected tasks, and it is these tasks, not occupations themselves, that are affected by Artificial Intelligence (AI). To evaluate how tasks may be impacted, previous approaches utilized manual annotations or coarse-grained matching. Leveraging recent advancements in machine learning, we replace coarse-grained matching with more precise deep learning approaches. Introducing the AI Impact measure, we employ Deep Learning Natural Language Processing to automatically identify AI patents that may impact various occupational tasks at scale. Our methodology relies on a comprehensive dataset of 17,879 task descriptions and quantifies AI's potential impact through analysis of 24,758 AI patents filed with the United States Patent and Trademark Office between 2015 and 2022. Our results reveal that some occupations will potentially be impacted, and that impact is intricately linked to specific skills. These include not only routine tasks (codified as a series of steps), as previously thought but also nonroutine ones (e.g. diagnosing health conditions, programming computers, and tracking flight routes). However, AI's impact on labor is limited by the fact that some of the occupations affected are augmented rather than replaced (e.g. neurologists, software engineers, air traffic controllers), and the sectors affected are experiencing labor shortages (e.g. IT, Healthcare, Transport).

16.
Childs Nerv Syst ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39349775

ABSTRACT

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) primarily affects pediatric patients. Data on the global incidence of DIPG remain sparse, especially in South Asia and low-middle-income countries like Pakistan. METHODS: After exemption from the Ethics Review Committee, a retrospective study was conducted. Records of patients with DIPG at the Aga Khan Hospital in Karachi, from January 2010 to December 2022, were reviewed. RESULTS: A total of 35 pediatric patients were managed for DIPG. The median age of the patients was 9, with 19 (54.3%) males and 16 (45.7%) females. Cranial nerve palsies were the most common complaint and were present in 19 (54.3%) patients, followed by headaches in 18 (51.4%), long tract signs in 14 (40%), ataxia/cerebellar symptoms in 14 (40%), and seizures in 5 (14.3%). MRI was the primary diagnostic tool, used alone or with CT in 32 (94.1%) patients; CT alone was used in only 2 (5.7%) patients. Biopsy was performed in 10 (28.6%) patients. Primary radiation therapy was administered to 14 (40%) patients with 5400 cGy in 30 fractions. All these patients received steroids while none of them received reirradiation. VP shunt surgery for hydrocephalus was performed in 9 (25.7%) patients. Over half (54.3%) refused treatment post-diagnosis, and 71.4% were lost to follow-up. CONCLUSION: Providing timely, quality multi-disciplinary care to DIPG patients within resource constraints remains challenging in Pakistan. However, recent developments show promise for improving DIPG care in the country.

17.
J Vasc Nurs ; 42(3): 177-181, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39244329

ABSTRACT

BACKGROUND: Patients with varicose veins are prevented from prolonged standing. Considering that exercise can be implemented in different positions, the aim of the current study was to compare the effects of training at standing and lying positions on quality of life, and clinical symptoms in women with mild varicose veins. METHODS: Twenty-five women with mild varicose veins aged 35-50 years were randomly assigned to three groups; exercise at standing position (n=10), exercise at lying position (n=8) and control (no treatment) group (n=7). Each exercise program involved 6 weeks of training. Quality of life, pain severity, ankle swelling, and lower leg and ankle circumferences were measured using the Aberdeen Varicose Vein Questionnaire, Visual Analog Scale (VAS), four-point pitting edema grading scale, and tape measure, respectively at baseline and at the end of the study. Data were analyzed using one-way analysis of variance (ANOVA) and the least significant difference (LSD) as post hoc test. RESULTS: Following a 6-week exercise program, there was a significant improvement in the quality of life of the participants in both exercise groups, and a significant reduction in pain, ankle swelling, and lower leg and ankle circumferences compared to pre-training and control group (P <0.05). However, there was no significant difference between two exercise groups in terms of study variables (P >0.05). CONCLUSIONS: The current study showed that exercise program comprising standing position exercises can significantly reduce the symptoms of mild varicose veins.


Subject(s)
Exercise Therapy , Quality of Life , Varicose Veins , Humans , Female , Varicose Veins/therapy , Middle Aged , Adult , Exercise Therapy/methods , Surveys and Questionnaires , Posture/physiology , Pain Measurement , Standing Position
18.
Nanoscale ; 16(38): 17723-17760, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39258334

ABSTRACT

Two-dimensional transition metal carbides, nitrides, or carbonitrides (MXenes) have garnered remarkable attention in various energy and environmental applications due to their high electrical conductivity, good thermal properties, large surface area, high mechanical strength, rapid charge transport mechanism, and tunable surface properties. Recently, artificial intelligence has been considered an emerging technology, and has been widely used in materials science, engineering, and biomedical applications due to its high efficiency and precision. In this review, we focus on the role of artificial intelligence-based technology in MXene-based devices and discuss the latest research directions of artificial intelligence in MXene-based devices, especially the use of artificial intelligence-based modeling tools for energy storage devices, sensors, and memristors. In addition, emphasis is given to recent progress made in synthesis methods for various MXenes and their advantages and disadvantages. Finally, the review ends with several recommendations and suggestions regarding the role of artificial intelligence in fabricating MXene-based devices. We anticipate that this review will provide guidelines on future research directions suitable for practical applications.

19.
ACS Nano ; 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276099

ABSTRACT

Conventional mass spectrometry (MS)-based bottom-up proteomics (BUP) analysis of the protein corona [i.e., an evolving layer of biomolecules, mostly proteins, formed on the surface of nanoparticles (NPs) during their interactions with biomolecular fluids] enabled the nanomedicine community to partly identify the biological identity of NPs. Such an approach, however, fails to pinpoint the specific proteoforms─distinct molecular variants of proteins in the protein corona. The proteoform-level information could potentially advance the prediction of the biological fate and pharmacokinetics of nanomedicines. Recognizing this limitation, this study pioneers a robust and reproducible MS-based top-down proteomics (TDP) technique for characterizing proteoforms in the protein corona. Our TDP approach has successfully identified about 900 proteoforms in the protein corona of polystyrene NPs, ranging from 2 to 70 kDa, revealing proteoforms of 48 protein biomarkers with combinations of post-translational modifications, signal peptide cleavages, and/or truncations─details that BUP could not fully discern. This advancement in MS-based TDP offers a more advanced approach to characterize NP protein coronas, deepening our understanding of NPs' biological identities. We, therefore, propose using both TDP and BUP strategies to obtain more comprehensive information about the protein corona, which, in turn, can further enhance the diagnostic and therapeutic efficacy of nanomedicine technologies.

20.
Int J Pharm ; : 124765, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39341384

ABSTRACT

The electrospun mats consisting of integrated coelomic fluid (CF) and chitosan (Chs) into polyvinyl alcohol (PVA) nanofibers were produced and evaluated for use as wound dressings. CF was obtained from earthworms (Eisenia andrei (Fetida)) using an electric shock method, while Chs was chemically produced from shrimp chitin and then characterized using titration, Fourier transform infrared (FT-IR) spectroscopy, and viscometry. The wound dressings with different CF contents were evaluated for their antibacterial, antioxidant, and cell viability properties. The dressings infused with CF showed significantly higher antibacterial and antioxidant activity, as well as improved cell viability compared to the control without CF. In vivo studies using adult Wistar albino rats showed that the Chs/PVA/CF wound dressings promoted wound healing and re-epithelialization. Moreover, histological examinations of the injuries coated with Chs/PVA/CF displayed improved re-epithelialization. These results suggest that the Chs/PVA/CF nanofiber has the potential for use as a wound dressing material.

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