Nano guardians of the heart: A comprehensive investigation into the impact of silver nanoparticles on cardiovascular physiology.

Globally, cardiovascular diseases (CVDs) constitute the leading cause of death at the moment. More effective treatments to combat CVDs are urgently required. Recent advances in nanotechnology have opened the door to new avenues for cardiovascular health treatment. Silver nanotechnology's inherent therapeutic powers and wide-ranging applications have made it the center of focus in recent years. This review aims to analyze the chemical, physical, and biological processes ofproducing AgNPs and determine their potential utility as theranostics. Despite significant advances, the precise mechanism by which AgNPs function in numerous biological systems remains a mystery. We hope that at the end of this review, you will better understand how AgNPs affect the cardiovascular system from the research done thus far. This endeavor thoroughly investigates the possible toxicological effects and risks associated with exposure to AgNPs. The findings shed light on novel applications of these versatile nanomaterials and point the way toward future research directions. Due to a shortage of relevant research, we will limit our attention to AgNPs as they pertain to CVDs. Future research can use this opportunity to investigate the many medical uses of AgNPs. Given their global prevalence, we fully endorse academics' efforts to prioritize nanotechnological techniques in pursuing risk factor targeting for cardiovascular diseases. The critical need for innovative solutions to this widespread health problem is underscored by the fact that this technique may help with the early diagnosis and treatment of CVDs.

Journey into tomorrow: cardiovascular wellbeing transformed by nano-scale innovations.

Worldwide, cardiovascular diseases (CVDs) account for the vast majority of deaths and place enormous financial strains on healthcare systems. Gold nanoparticles, quantum dots, polymeric nanoparticles, carbon nanotubes, and lipids are innovative nanomaterials promising in tackling CVDs. In the setting of CVDs, these nanomaterials actively impact cellular responses due to their distinctive properties, including surface energy and topographies. Opportunities to more precisely target CVDs have arisen due to recent developments in nanomaterial science, which have introduced fresh approaches. An in-depth familiarity with the illness and its targeted mechanisms is necessary to use nanomaterials in CVDs effectively. We support the academic community's efforts to prioritize Nano-technological techniques in addressing risk factors linked with cardiovascular diseases, acknowledging the far-reaching effects of these conditions. The significant impact of nanotechnology on the early detection and treatment of cardiovascular diseases highlights the critical need for novel approaches to this pressing health problem, which is affecting people worldwide.

Convalescing Mandibular Anterior Crowding through Piezocision and the Micro-Osteoperforation Surgical Procedure-A Clinical Comparative Study.

BACKGROUND: Minimally invasive periodontic (perio) surgical procedures, piezocision, and micro-osteoperforation are useful techniques for accelerating tooth movement. These techniques also offer advantages in the orthodontic (ortho) and aesthetic domains. This study aimed to evaluate and compare the rates of lower anterior decrowding with piezocision and micro-osteoperforation. METHODS: This clinical study included 24 patients requiring fixed orthodontic treatments. Two periodontic techniques (piezocision (PZ) and micro-osteoperforation (MOP)) were considered for the orthodontic treatments. Each patient was randomly allocated to either the piezocision (PZ) group or the micro-osteoperforation (MOP) group. The piezocision group received five radiographically guided incisions on the labial surface of the alveolar bone, whereas the micro-osteoperforation group received one to three MOPs each using a mini-implant drill between the six lower anterior teeth, and later, an initial arch wire was ligated to each bracket. Little's irregularity index (LII) was calculated using a digital vernier caliper on study models every four weeks until decrowding was achieved. The difference in the rates of lower anterior crowding between the piezocision and micro-osteoperforation groups was analyzed to determine the statistical significance. RESULTS: The rates of irregularity index change during decrowding were 4.38 ± 0.61 in the piezocision group and 3.82 ± 0.47 in the micro-osteoperforation group. Piezocision was found to be 1.2 times faster than micro-osteoperforation in terms of the rate of decrowding. CONCLUSION: The advanced perio-ortho combination technique was advantageous in accelerated decrowding. In comparison to MOP, there was an increase in the rate of decrowding with PZ. Decrowding can be completed quickly with PZ, and it can thus be used to treat crowding effectively in a limited time frame.

Preparation, Characterization, and Evaluation of Physcion Nanoparticles for Enhanced Oral Bioavailability: An Attempt to Improve Its Antioxidant and Anticancer Potential.

This study aims to enhance the dissolution rate of a poorly water-soluble drug physcion by producing its nanoparticles (NPs) using an antisolvent precipitation with a syringe pump (APSP) method and to assess its antioxidant and cytotoxic potential. The NPs were prepared using a simple and cost-effective APSP method and subsequently characterized by different analytical techniques including dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray powder diffractometry (XRD). They were also subjected to solubility and dissolution studies, and different parameters such as dissolution efficiency (DE), mean dissolution time (MDT), and difference (f1) and similarity factors (f2) were determined. Furthermore, physcion and its NPs were investigated for antioxidant and cytotoxic effects using various in vitro assays. SEM and DLS analysis indicated that the average size of physcion NPs was 110 and 195 ± 5.6 nm, respectively. The average ζ-potential and polydispersibility index (PDI) of the prepared NPs were -22.5 mV and 0.18, respectively, showing excellent dispersibility. XRD confirmed the amorphous nature of physcion NPs. The solubility and dissolution rates of NPs were significantly higher than those of the original powder. The antioxidant potential studied by the (DPPH), FRAP, and H2O2 assays was greater for physcion NPs than that for the raw powder. The IC50 values of physcion NPs against the aforementioned models were 57.56, 22.30, and 22.68 µg/mL, respectively. Likewise, the cytotoxic potential investigated through the MTT assay showed that physcion NPs were more cytotoxic to cancer cell lines A549 (IC50 4.12 µg/mL), HepG2 (IC50 2.84 µg/mL), and MDA-MB-231 (IC50 2.97 µg/mL), while it had less effect on HPAEpiC (IC50 8.68 µg/mL) and HRPTEpiC (IC50 10.71 µg/mL) normal human epithelial cells. These findings have proved that the APSP method successfully produced physcion NPs with enhanced solubility, dissolution rate, and antioxidant and cytotoxic activities.

The role of capsule aperture size on the dispersion of carrier-based formulation at different air flowrates.

The effect of capsule aperture size on the aerosol performance of lactose blend formulation was studied using Foradil® (containing 12 µg of formoterol fumarate (FF1) and 24 mg of lactose) dispersed with a powder inhaler Aerolizer® at increasing air flowrates. Apertures sizes of 0.4, 1.0, 1.5, 2.5, and 4.0 mm were introduced at the opposite ends of the capsule. The formulation was dispersed into a Next Generation Impactor (NGI) at 30, 60 and 90 L/min, with the fine particle fractions (FPFrec and FPFem) measured by chemical assay of FF and lactose using high-performance liquid chromatography. Particle size distribution (PSD) of FF particles dispersed in wet media was also characterized by laser diffraction. FPFrec showed a stronger dependency on the flowrate than the capsule aperture size. The most efficient dispersion was achieved at 90 L/min. At a given flowrate, FPFem remained broadly constant across different aperture sizes. The laser diffraction studies demonstrated the presence of large agglomerates.

One-pot green synthesis of gold nanoparticles using Sarcophyton crassocaule, a marine soft coral: Assessing biological potentialities of antibacterial, antioxidant, anti-diabetic and catalytic degradation of toxic organic pollutants.

Marine bio-resources are being extensively researched as a priceless supply of substances with therapeutic potential. This work report the first time attempt made towards the green synthesis of gold nanoparticles (AuNPs) using the aqueous extract of marine soft coral (SCE), Sarcophyton crassocaule. The synthesis was conducted under optimized conditions and the visual coloration of reaction mixture changed from yellowish to ruby red at 540 nm. The electron microscopic (TEM, SEM) studies exhibited spherical and oval shaped SCE-AuNPs in the size ranges of 5-50 nm. The organic compounds present in SCE were primarily responsible for the biological reduction of gold ions validated by FT-IR while the zeta potential confirmed the overall stability of SCE-AuNPs. The synthesized SCE-AuNPs exhibited variety of biological efficacies like antibacterial, antioxidant and anti-diabetic in nature. The biosynthesized SCE-AuNPs demonstrated remarkable bactericidal efficacy against clinically significant bacterial pathogens with inhibition zones of mm. Additionally, SCE-AuNPs exhibited greater antioxidant capacity in terms of DPPH: 85 ± 0.32% and RP: 82 ± 0.41%). The ability of enzyme inhibition assays to inhibit α-amylase (68 ± 0.21%) and α-glucosidase (79 ± 0.2%) was quite high. The study also highlighted the spectroscopic analysis of the biosynthesized SCE-AuNPs' catalytic effectiveness of 91% in the reduction processes of the perilous organic dyes, exhibiting pseudo-first order kinetics.

KRAS G12C-Mutant Non-Small-Cell Lung Adenocarcinoma: First Documented Report in the Arabian Gulf.

We report the first documented case series of two lung adenocarcinoma patients demonstrating Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations by reverse transcription-polymerase chain reaction techniques from Saudi Arabia. Both patients were males aged 64 and 76 years. The first had a heavy smoking history, while the second did not report any history of smoking. The tumor subtype was identified to be non-mucinous lung adenocarcinoma in both cases. The younger patient presented with generalized lymphadenopathy and a right-sided lung mass lesion, while the older patient exhibited stage III-A left lung adenocarcinoma that required rapid response. An initial examination of the first case showed a right-sided mediastinal shift, bilateral neck lymphadenopathy, and poorly differentiated neoplasm from a right supraclavicular core biopsy, leading to treatment with palliatives along with regular checkups. The second case was afebrile after being confirmed to be vitally stable and laboratory testing (Neutr 100). Further studies, specifically on large numbers of patients from the Arabian Gulf, are needed to confirm significant differences between the national and international populations. Additionally, future studies should investigate more differences in the differentiation of KRAS-mutant lung adenocarcinoma between patients from the Arabian Gulf and others.

Preparation and Characterization of Inhalable Ivermectin Powders as a Potential COVID-19 Therapy.

Background: Ivermectin has received worldwide attention as a potential COVID-19 treatment after showing antiviral activity against SARS-CoV-2 in vitro. However, the pharmacokinetic limitations associated with oral administration have been postulated as limiting factors to its bioavailability and efficacy. These limitations can be overcome by targeted delivery to the lungs. In this study, inhalable dry powders of ivermectin and lactose crystals were prepared and characterized for the potential treatment of COVID-19. Methods: Ivermectin was co-spray dried with lactose monohydrate crystals and conditioned by storage at two different relative humidity points (43% and 58% RH) for a week. The in vitro dispersion performance of the stored powders was examined using a medium-high resistance Osmohaler connecting to a next-generation impactor at 60 L/min flow rate. The solid-state characteristics including particle size distribution and morphology, crystallinity, and moisture sorption profiles of raw and spray-dried ivermectin samples were assessed by laser diffraction, scanning electron microscopy, Raman spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption. Results: All the freshly spray-dried formulation (T0) and the conditioned samples could achieve the anticipated therapeutic dose with fine particle dose of 300 µg, FPFrecovered of 70%, and FPFemitted of 83%. In addition, the formulations showed a similar volume median diameter of 4.3 µm and span of 1.9. The spray-dried formulations were stable even after conditioning and exposing to different RH points as ivermectin remained amorphous with predominantly crystalline lactose. Conclusion: An inhalable and stable dry powder of ivermectin and lactose crystals was successfully formulated. This powder inhaler ivermectin candidate therapy appears to be able to deliver doses that could be safe and effective to treat the SARS-COV-2 infection. Further development of this therapy is warranted.

Pharmacokinetics and safety of inhaled ivermectin in mice as a potential COVID-19 treatment.

Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice. Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation. Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.

Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.

Background: Hydroxychloroquine (HCQ) is one of the repurposed drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, all the published clinical trials involve oral administration of the drug, although the disease is primarily a respiratory one. Direct inhaled delivery could reduce the side effects associated with oral use and ensure a high concentration of the drug in the lungs. In this study, inhalable HCQ powders were prepared and characterized for potential COVID-19 therapy. Methods: Hydroxychloroquine sulfate (HCQ-sul) was jet milled (JM) followed by conditioning by storage at different relative humidities (43%, 53%, 58%, and 75% RHs) for 7 days. The solid-state properties, including particle morphology and size distribution, crystallinity, and vapor moisture profiles of HCQ-sul samples, were characterized by scanning electron microscopy, laser diffraction, X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic water vapor sorption. The aerosol performance of the HCQ-sul powders was assessed using a medium-high resistance Osmohaler coupling to a next-generation impactor (NGI) at a flow rate of 60 L/min. Results: The jet-milled powder showed a volume median diameter of 1.7 µm (span 1.5) and retained the same crystalline form as the raw HCQ-sul. A small amount of amorphous materials was present in the jet-milled HCQ-sul, which was convertible to the stable, crystalline state after conditioning at 53%, 58%, and 75% RH. The recovered fine particle fraction (FPF)recovered and the emitted fine particle fraction (FPFemitted) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at ∼43% and 61%, respectively. In contrast, the sample having conditioned at 75%RH showed lower corresponding values at 33% and 26% respectively, due to the formation of solid bridges caused by excessive moisture. Conclusion: Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.

Seasonal influenza vaccination among primary health care workers in Southwestern Saudi Arabia.

Background: Vaccination of primary healthcare workers (PHCWs) help to prevent the spread of influenza among at-risk patients.Objectives: To assesses seasonal influenza vaccination (SIV) coverage and the factors affecting SIV's utilization among PHCWs in Abha city, southwestern Saudi Arabia.Methods: A cross-sectional survey was carried out between June 2018 and August 2018 in all primary healthcare centers in Abha city. It targeted physicians, nurses, technicians, and pharmacists. A self-administered questionnaire was used to collect data regarding SIV status during the 2017-2018 season, obtain knowledge regarding SIV and influenza disease, and identify potential motivators for and barriers to SIV.Results: Of 312 PHCWs, the SIV coverage rate was 45.5% in the 2017-2018 vaccination season. A multivariable logistic regression model showed that the risk groups for non-vaccination were PHCWs less than 40 years old (adjusted Odds Ratio (aOR) = 4.07, 95% CI: 1.50-11.03), technicians (aOR = 3.73, 95% CI: 1.20-11.54), single PHCWs (aOR = 2.36, 95% CI:1.20-4.62), and PHCWs lacking adequate influenza vaccine knowledge (aOR = 4.22, 95% CI: 2.13-8.35). Approximately 23% and 32% of PHCWs were found to have inadequate knowledge about SIV and influenza disease, respectively. PHCWs' awareness about their risk of infection and their need for protection was found to be the most common motivator (77.5%), and a fear of side effects was found to be the most frequent barrier (40%).Conclusion: SIV coverage rate is suboptimal. Knowledge gaps and misconceptions about the influenza vaccine are the main barriers to an adequate coverage.