Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective.

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.

Quality by Design Perspective for Designing Foam-based Formulation: Current State of Art.

Foam-based delivery systems contain one or more active ingredients and dispersed solid or liquid components that transform into gaseous form when the valve is actuated. Foams are an attractive and effective delivery approach for medical, cosmetic, and pharmaceutical uses. The foams-based delivery systems are gaining attention due to ease of application as they allow direct application onto the affected area of skin without using any applicator or finger, hence increasing the compliance and satisfaction of the patients. In order to develop foam-based delivery systems with desired qualities, it is vital to understand which type of material and process parameters impact the quality features of foams and which methodologies may be utilized to investigate foams. For this purpose, Quality-by-Design (QbD) approach is used. It aids in achieving quality-based development during the development process by employing the QbD concept. The critical material attributes (CMAs) and critical process parameters (CPPs) were discovered through the first risk assessment to ensure the requisite critical quality attributes (CQAs). During the initial risk assessment, the high-risk CQAs were identified, which affect the foam characteristics. In this review, the authors discussed the various CMAs, CPPs, CQAs, and risk factors associated in order to develop an ideal foam-based formulation with desired characteristics.

Persistent facial pain in post-stroke patients, a hospital-based cohort study; experience from North India.

Background: Post-stroke pain is common after a stroke and might be underreported. We describe Persistent Facial Pain (PFP) developed in post-stroke patients. Method: ology: This was a prospective hospital-based cohort study of stroke patients, and patients were followed up. Out of 415 stroke patients, 26 developed PFP. Result: Out of all PFP patients, six patients had an ischemic stroke, and 20 had a hemorrhagic stroke. 57.7% of patients had hypertension, while 34.6 patients had diabetes. The stroke location was left-sided in 12 patients and right-sided in 14 patients. 46.15% of patients responded to venlafaxine, 30.77% responded to amitriptyline, and 23.08% responded to pregabalin. Conclusion: Persistent facial pain is a pain syndrome that might be missed in patients post-stroke. It might be more common in hemorrhagic stroke patients than in ischemic stroke patients. It responds adequately to antidepressants. A high index of suspicion is required to diagnose and appropriately manage these patients.

Enhanced Reactivity through Equatorial Sulfur Coordination in Nonheme Iron(IV)-Oxo Complexes: Insights from Experiment and Theory.

Sulfur ligation in metalloenzymes often gives the active site unique properties, whether it is the axial cysteinate ligand in the cytochrome P450s or the equatorial sulfur/thiol ligation in nonheme iron enzymes. To understand sulfur ligation to iron complexes and how it affects the structural, spectroscopic, and intrinsic properties of the active species and the catalysis of substrates, we pursued a systematic study and compared sulfur with amine-ligated iron(IV)-oxo complexes. We synthesized and characterized a biomimetic N4S-ligated iron(IV)-oxo complex and compared the obtained results with an analogous N5-ligated iron(IV)-oxo complex. Our work shows that the amine for sulfur replacement in the equatorial ligand framework leads to a rate enhancement for oxygen atom and hydrogen atom transfer reactions. Moreover, the sulfur-ligated iron(IV)-oxo complex reacts through a different reaction mechanism as compared to the N5-ligated iron(IV)-oxo complex, where the former reacts through hydride transfer with the latter reacting via radical pathways. We show that the reactivity differences are caused by a dramatic change in redox potential between the two complexes. Our studies highlight the importance of implementing a sulfur ligand into the equatorial ligand framework of nonheme iron(IV)-oxo complexes and how it affects the physicochemical properties of the oxidant and its reactivity.

Long-Term Efficacy of Successful Excisional Goniotomy with the Kahook Dual Blade.

Purpose: To report clinical outcomes of successful excisional goniotomy with the Kahook Dual Blade (KDB), through 60 months. Patients and methods: This was a noncomparative, single-surgeon, retrospective review of eyes receiving successful KDB goniotomy with or without concomitant phacoemulsification between October 2015 and January 2016 with five years of uninterrupted follow-up. Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), and complications were recorded. Primary outcomes included changes from baseline in IOP, medication use, and BCVA, through five years. Results: Fifty-two eyes of 28 patients were analyzed. Most eyes had mild primary open angle glaucoma (73%). Of the eyes analyzed, 41 underwent combined surgery and 11 underwent standalone surgery. With all eyes combined, mean (standard deviation) baseline IOP was 21.0 (4.1) mmHg and mean baseline medication use was 1.8 (1.1) medications per eye. Across time points at months 6, 12, 24, 36, 48, and 60, mean postoperative IOP ranged from 13.0 to 13.7 mmHg, representing mean reductions of 7.3-8.0 mmHg (34.7-38.3%; p <0.0001 at every time point). Similarly, mean medication use ranged from 0.4 to 0.6 medications per eye, representing mean reductions of 1.2-1.4 medications (66-75.5%; p <0.0001 at every time point). Mean logMAR BCVA improved from 0.321 (0.177) preoperatively to 0.015 (0.035) at month 60 (p < 0.0001). Conclusion: In eyes not requiring secondary surgical procedures (eg, long-term surgical successes), excisional goniotomy provided clinically and statistically significant reductions in both IOP and the need for medications that were highly consistent through five years of follow-up. KDB goniotomy appears to be highly successful in Caucasian patients with open angle glaucoma on ≥1 IOP-lowering medications at baseline and with no history of prior ocular surgery. Successful excisional goniotomy with the KDB can be expected to improve long-term glaucoma-related visual outcomes through IOP reduction and to improve quality of life through medication reduction.

Microbubbles: Revolutionizing Biomedical Applications with Tailored Therapeutic Precision.

BACKGROUND: Over the past ten years, tremendous progress has been made in microbubble-based research for a variety of biological applications. Microbubbles emerged as a compelling and dynamic tool in modern drug delivery systems. They are employed to deliver drugs or genes to targeted regions of interest, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. OBJECTIVE: The objective of this article is to review the microbubble compositions and physiochemical characteristics in relation to the development of innovative biomedical applications, with a focus on molecular imaging and targeted drug/gene delivery. METHODS: The microbubbles are prepared by using various methods, which include cross-linking polymerization, emulsion solvent evaporation, atomization, and reconstitution. In cross-linking polymerization, a fine foam of the polymer is formed, which serves as a bubble coating agent and colloidal stabilizer, resulting from the vigorous stirring of a polymeric solution. In the case of emulsion solvent evaporation, there are two solutions utilized in the production of microbubbles. In atomization and reconstitution, porous spheres are created by atomising a surfactant solution into a hot gas. They are encapsulated in primary modifier gas. After the addition of the second gas or gas osmotic agent, the package is placed into a vial and sealed after reconstituting with sterile saline solution. RESULTS: Microbubble-based drug delivery is an innovative approach in the field of drug delivery that utilizes microbubbles, which are tiny gas-filled bubbles, act as carriers for therapeutic agents. These microbubbles can be loaded with drugs, imaging agents, or genes and then guided to specific target sites. CONCLUSION: The potential utility of microbubbles in biomedical applications is continually growing as novel formulations and methods. The versatility of microbubbles allows for customization, tailoring the delivery system to various medical applications, including cancer therapy, cardiovascular treatments, and gene therapy.

Marine-derived polysaccharides and their therapeutic potential in wound healing application - A review.

Polysaccharides originating from marine sources have been studied as potential material for use in wound dressings because of their desirable characteristics of biocompatibility, biodegradability, and low toxicity. Marine-derived polysaccharides used as wound dressing, provide several benefits such as promoting wound healing by providing a moist environment that facilitates cell migration and proliferation. They can also act as a barrier against external contaminants and provide a protective layer to prevent further damage to the wound. Research studies have shown that marine-derived polysaccharides can be used to develop different types of wound dressings such as hydrogels, films, and fibres. These dressings can be personalised to meet specific requirements based on the type and severity of the wound. For instance, hydrogels can be used for deep wounds to provide a moist environment, while films can be used for superficial wounds to provide a protective barrier. Additionally, these polysaccharides can be modified to improve their properties, such as enhancing their mechanical strength or increasing their ability to release bioactive molecules that can promote wound healing. Overall, marine-derived polysaccharides show great promise for developing effective and safe wound dressings for various wound types.

Role of vascular endothelial growth factor in tuberculous meningitis: A prospective study from a tertiary care center in North India.

INTRODUCTION: The status of vascular endothelial-derived growth factor (VEGF) in the pathogenesis of tuberculous meningitis (TBM) remains far from clear. We prospectively evaluated the role of serum and cerebrospinal fluid (CSF) VEGF in TBM. PATIENTS AND METHODS: This prospective study was conducted at a tertiary care center in North India from January 2018 to June 2019. Consecutive drug-naive patients (n = 82) of TBM diagnosed on the basis of modified Ahuja's criteria were included in the study. The results were compared with 49 control subjects (n = 49). Serum and CSF VEGF were done in all the cases and controls. Follow-up serum VEGF levels were done in 34 patients after 3 months of completion of antitubercular therapy. The VEGF levels were estimated using the human VEGF enzyme-linked immunosorbent assay kit. RESULTS: The mean age was 29.9 ± 13.1 years. The study group consisted of 33 (40.2%) men and 49 (59.8%) women. BACTEC MGIT960 was positive in 15 (18%) patients while multiplex tuberculosis polymerase chain reaction was positive in 73 (89%) patients. Levels of VEGF in serum and CSF of TBM patients were not elevated when compared to controls. There was no association between final outcome in TBM and decrease in serum levels of VEGF at follow-up. CONCLUSION: VEGF may not be playing a significant role in the pathogenesis of TBM. Future studies with larger sample size may clarify the status of VEGF further in TBM.

Nano-platform Strategies of Herbal Components for the management of Rheumatoid Arthritis: A Review on the Battle for Next-Generation Formulations.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that initially affects small joints and then spreads to the bigger joints. It also affects other organs of the body such as the lungs, eyes, kidneys, heart, and skin. In RA, there is destruction of cartilage and joints, and ligaments and tendons become brittle. Damage to the joints leads to abnormalities and bone degradation, which may be quite painful for the patient. METHOD: The nano-carriers such as liposomes, phytosomes, nanoparticles, microcapsules, and niosomes are developed to deliver the encapsulated phytoconstituents to targeted sites for the better management of RA. RESULTS: The phytoconstituents loaded nano-carriers have been used in order to increase bioavailability, stability and reduce the dose of an active compound. In one study, the curcumin-loaded phytosomes increase the bioavailability of curcumin and also provides relief from RA symptoms. The drug-loaded nano-carriers are the better option for the management of RA. CONCLUSION: In conclusion, there are many anti-arthritic herbal and synthetic medicine available in the market that are currently used in the treatment of RA. However, chronic use of these medications may result in a variety of side effects. Because therapy for RA is frequently necessary for the rest of ones life. The use of natural products may be a better option for RA management. These phytoconstituents, however, have several disadvantages, including limited bioavailability, low stability, and the need for a greater dosage. These problems can be rectified by using nano-technology.

Electronic, optical and spectroscopic properties of N-dialkyl-imidazolium hexafluorophosphate (CNMIM.PF6) ionic liquid crystal molecules investigated by computational methods.

In this present work, we calculate the electronic, spectroscopic and nonlinear optical properties (NLO) of N-dialkyl-imidazolium hexafluorophosphate (CNMIM.PF6, where N = 10, 12, 14, 16, 18, 20) ionic liquid crystal molecules under the effect of alkyl chain length variation in cation moiety [CNMIM]+ with fixed anion [PF6]-. CONTEXT: The majority of research on ionic liquid crystal to date has been focused on experiments, while theoretical studies on the optical properties of ionic liquid crystal have been extremely rare. Nonlinear phenomena in optical devices have attracted many researchers. Therefore, results of NLO properties may favor facile synthesis and fabrication of novel-type of materials as well as optoelectronic devices. Spectroscopic studies elucidate further insight into ionic liquid crystal behavior. The results demonstrate that variations in alkyl chain length have an impact on the conformers' electrical, spectroscopic, and NLO properties as well as their stability. The stability of ionic liquid crystal molecules increases with increase in the alkyl chain length and the energy band gap range is 6.64-6.29 eV. Understanding ionic liquid crystal's physical behavior requires an understanding of their dipole moments and NLO features, which are covered in this article. The results of NLO characteristics for all ionic liquid crystal molecules show that their first-order hyperpolarizabilities are higher than the reference molecule (urea). METHODS: The electronic (molecular energy band gap, electrostatic potential map, as well as HOMO-LUMO orbitals) and spectroscopic (IR-RAMAN, UV) properties were evaluated with the help of theoretical model at B3LYP/6-31G(d) while the NLO study has been performed using B3LYP and M06-2X with different basis sets 6-31G(d) and 6-311++G(d,p), as implemented in Gaussian09 software.

Retraction of "Effect of Reaction Temperature on Shape Evolution of Palladium Nanoparticles and Their Cytotoxicity against A-549 Lung Cancer Cells".

[This retracts the article DOI: 10.1021/acsomega.9b02776.].

Legionella-Induced Hepatitis: A Case Report.

Legionnaires' disease is caused by a potentially life-threatening infection with the opportunistic Gram-negative bacilli species Legionella pneumophila, which is transmitted via inhalation or aspiration of water droplets. Legionnaires' commonly presents as atypical community-acquired pneumonia with accompanying diarrhea. Although hepatic and renal involvement are relatively uncommon, in this report, we present a case of Legionella pneumonia with acute hepatitis.

Defluorination of Fluorophenols by a Nonheme Iron(IV)-Oxo Species: Observation of a New Intermediate Along the Reaction.

High-valent iron(IV)-oxo intermediates are versatile oxidants in the biotransformation of various substrates by metalloenzymes and catalyze essential reactions for human health as well as in the biodegradation of toxic organic pollutants in the environment. Herein, we report a biomimetic system that efficiently reacts with halophenols through defluorination reactions and characterize various short-lived intermediates along the reaction mechanism. We study the reactivity pattern of a nonheme iron(IV)-oxo species with a series of trihalophenols (X=F, Cl, Br). A combined experimental and computational study reveals that the oxidative dehalogenation of 2,4,6-trifluorophenol is initiated with an H-atom abstraction from the phenolic group by the iron(IV)-oxo species resulting in the formation of a phenolate radical and an iron(III)-hydroxo species. This iron(III)-hydroxo species forms an adduct with the oxidized substrate with λmax at 558 nm which subsequently decays to give quinones as products.

Crohn's Disease Initially Presenting With Anterior Sclerouveitis.

This report examines the case of a 32-year-old male who initially presented with symptoms of eye pain, redness, and vision changes, and was subsequently diagnosed with anterior sclerouveitis. One week after his initial visit, the patient presented to the emergency department (ED) with daily bloody stools and left lower quadrant (LLQ) pain. Further workup and examination revealed a diagnosis of Crohn's disease. This report expands on ocular manifestations of Crohn's disease and touches on the importance of early gastrointestinal examination in patients who present with ocular symptoms.

Quantum mechanical studies of p-azoxyanisole and identification of its electro-optic activity.

Liquid crystals (LCs) are used in displays, visors, navigation systems and many more. Amongst a wide range of LCs, p-azoxyanisole (PAA) is considered to be an active LC. Focusing on different properties of this molecule, in the reported study, the theoretical identification of quantum mechanical parameters and the identification of electro-optic properties are carried out. Different functional theories such as B3LYP, M06-2X and M06L are used along with three basis sets 6-31G**, 6-311G and 6-311G**. A comparative study revealed that the M06-2X method produces higher values of band gap, ionization potential, electronegativity and electronic global hardness while M06L produces lower values and B3LYP gives intermediate values. Nonlinear optical properties of liquid crystals are evaluated. The nonlinear optical properties obtained for a PAA liquid crystal are much higher than those of urea. Due to its high nonlinear optical properties, our liquid crystal can be used in the field of telecommunication and optical interconnection. The order parameter and birefringence are calculated with variable electric field. We found out that the order parameter and birefringence increase with a gradually increasing electric field, which suggests that the PAA liquid crystal can be used for developing electro-optic and tunable metamaterial devices.

Analysis of reported adverse events of pipeline stents for intracranial aneurysms using the FDA MAUDE database.

OBJECTIVE: Flow diverting stents (FDS) are a validated device in the treatment of intracranial aneurysms, allowing for minimally invasive intervention. However, after its approval for use in the United States in 2011, post-market surveillance of adverse events is limited. This study aims to address this critical knowledge gap by analyzing the FDA Manufacturer and User Facility Device Experience (MAUDE) database for patient and device related (PR and DR) reports of adverse events and malfunctions. METHODS: Using post-market surveillance data from the MAUDE database, PR and DR reports from January 2012-December 2021 were extracted, compiled, and analyzed with R-Studio version 2021.09.2. PR and DR reports with insufficient information were excluded. Raw information was organized, and further author generated classifications were created for both PR and DR reports. RESULTS: A total of 2203 PR and 4017 DR events were recorded. The most frequently reported PR adverse event categories were cerebrovascular (60%), death (11%), and neurological (8%). The most frequent PR adverse event reports were death (11%), thrombosis/thrombus (9%) cerebral infarction (8%), decreased therapeutic response (7%), stroke/cerebrovascular accident (6%), intracranial hemorrhage (5%), aneurysm (4%), occlusion (4%), headache (4%), neurological deficit/dysfunction (3%). The most frequent DR reports were activation/positioning/separation problems (52%), break (9%), device operates differently than expected (4%), difficult to open or close (4%), material deformation (3%), migration or expulsion of device (3%), detachment of device or device component (2%). CONCLUSIONS: Post-market surveillance is important to guide patient counselling and identify adverse events and device problems that were not identified in initial trials. We present frequent reports of several types of cerebrovascular and neurological adverse events as well as the most common device shortcomings that should be explored by manufacturers and future studies. Although inherent limitations to the MAUDE database are present, our results highlight important PR and DR complications that can help optimize patient counseling and device development.

Biotransformation of Bisphenol by Human Cytochrome P450 2C9 Enzymes: A Density Functional Theory Study.

Bisphenol A (BPA, 2,2-bis-(4-hydroxyphenyl)propane) is used as a precursor in the synthesis of polycarbonate and epoxy plastics; however, its availability in the environment is causing toxicity as an endocrine-disrupting chemical. Metabolism of BPA and their analogues (substitutes) is generally performed by liver cytochrome P450 enzymes and often leads to a mixture of products, and some of those are toxic. To understand the product distributions of P450 activation of BPA, we have performed a computational study into the mechanisms and reactivities using large model structures of a human P450 isozyme (P450 2C9) with BPA bound. Density functional theory (DFT) calculations on mechanisms of BPA activation by a P450 compound I model were investigated, leading to a number of possible products. The substrate-binding pocket is tight, and as a consequence, aliphatic hydroxylation is not feasible as the methyl substituents of BPA cannot reach compound I well due to constraints of the substrate-binding pocket. Instead, we find low-energy pathways that are initiated with phenol hydrogen atom abstraction followed by OH rebound to the phenolic ortho- or para-position. The barriers of para-rebound are well lower in energy than those for ortho-rebound, and consequently, our P450 2C9 model predicts dominant hydroxycumyl alcohol products. The reactions proceed through two-state reactivity on competing doublet and quartet spin state surfaces. The calculations show fast and efficient substrate activation on a doublet spin state surface with a rate-determining electrophilic addition step, while the quartet spin state surface has multiple high-energy barriers that can also lead to various side products including C4-aromatic hydroxylation. This work shows that product formation is more feasible on the low spin state, while the physicochemical properties of the substrate govern barrier heights of the rate-determining step of the reaction. Finally, the importance of the second-coordination sphere is highlighted that determines the product distributions and guides the bifurcation pathways.

Experimental study of thermal characteristics of ZrO2/EG nanofluid for application of heat transfer.

In thermal management system, nanofluids will act as robust elements in future for coolants. Nanofluids have remarkable potential during the heat transfer increase reported by researchers from all over the world. Nanofluids have attracted many researchers, and there have been tremendous advances because of the high thermal characteristics and possible applications in certain areas such as the transport sector, aerospace, medical regions, and microelectronics. This current study reports on the thermal characteristics of nanofluid based on ZrO2/EG. The nanoparticles are characterized by XRD and SEM techniques. Nanofluid was prepared by a two-step method in ethylene glycol (EG) using ultra sonication. The thermal conductivity of ZrO2/EG nanofluid was investigated experimentally at various volume concentrations (0.02-0.1vol. %) and temperature range between 35 and 55 °C. The enhancement in thermal conductivity was observed to be 26.2% at 0.1 vol. % which exhibits superior performance as compared to base fluid (EG). The results of the experiment were compared with the three most often utilized model in the literature. The behavior of ZrO2/water-based nanofluid thermal conductivity, viscosity, and stability in various concentrations was studied.