Experimental observation of cavity-free ice-free isochoric vitrification via combined pressure measurements and photon counting x-ray computed tomography.

Isochoric (constant-volume or volumetrically confined) vitrification has shown potential as an alternative cryopreservation-by-vitrification technique, but the complex processes at play within the chamber are yet poorly characterized, and recent investigations have prompted significant debate around whether a truly isochoric vitrification process (in which the liquid remains completely confined by solid boundaries) is indeed feasible. Based on a recent thermomechanical simulation of a high-concentration Me2SO solution, Solanki and Rabin (Cryobiology, 2023, 111, 9-15.) argue that isochoric vitrification is not feasible, because differential thermal contraction of the solution and container will necessarily drive generation of a cavity, corrupting the rigid confinement of the liquid. Here, we provide direct experimental evidence to the contrary, demonstrating cavity-free isochoric vitrification of a ∼3.5 M vitrification solution by combined isochoric pressure measurement (IPM) and photon-counting x-ray computed tomography (PC-CT). We hypothesize that the absence of a cavity is due to the minimal thermal contraction of the solution, which we support with additional volumetric analysis of the PC-CT reconstructions. In total, this study provides experimental evidence both demonstrating the feasibility of isochoric vitrification and highlighting the potential of designing vitrification solutions that exhibit minimal thermal contraction.

Cymbopogon proximus and Petroselinum crispum seed ethanolic extract/Gum Arabic nanogel emulsion: Preventing ethylene glycol and ammonium chloride-induced urolithiasis in rats.

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.

Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) kunth. Ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats.

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.

Exploration of antiproliferative potential of modified triazole-benzohydrazone scaffold: Multitarget approach.

A novel series of triazole-benzohydrazone hybrids was efficiently designed and synthesized as antiproliferative agents, targeting different kinases. All compounds were screened via the National Cancer Institute (NCI) against 60 cancer cell lines, where compounds 16, 17, and 18 exhibited growth inhibition percent (GI%) of various leukemia subpanels with values of 70.33%, 64.13%, and 76.03%, respectively. Compound 18 showed broad-spectrum antiproliferative efficacy toward most cancer cells, with outstanding potency regarding melanoma (MALME-3M GI% = 101.82%) and breast cancer cell lines (MCF7 GI% = 85.87%), while proving safe toward the WI-38 normal cell line, compared to doxorubicin. Multikinase investigation including vascular endothelial growth factor receptor 2 (VEGFR-2), mesenchymal epithelial transition factor (c-Met), proto-oncogene B-Raf, mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, and phosphoinositide 3-kinase was accomplished to reveal its plausible mechanism of action, giving the ultimate potency against both VEGFR-2 and c-Met with IC50 values of 0.055 and 0.042 µM, respectively, while displaying moderate to good inhibition concerning the remaining kinases. DNA binding capability was excluded using the methyl green colorimetric assay. Further, it exhibited both early and late apoptotic induction by about 16- and 9.4-fold over the control, respectively, triggering cell cycle arrest in the G2/M phase. Physicochemical properties and bioavailability radar plot inferred drug-likeness characteristics for compound 18. The molecular docking study assessed the binding pattern with the active sites of c-Met and VEGFR-2.

All silicon MIR super absorber using fractal metasurfaces.

Perfect absorbers can be used in photodetectors, thermal imaging, microbolometers, and thermal photovoltaic solar energy conversions. The spectrum of Mid-infrared (MIR) wavelengths offers numerous advantages across a wide range of applications. In this work, we propose a fractal MIR broadband absorber which is composed of three layers: metal, dielectric, and metal (MDM), with the metal being considered as n-type doped silicon (D-Si) and the dielectric is silicon carbide (SiC). The architectural design was derived from the Sierpinski carpet fractal, and different building blocks were simulated to attain optimal absorption. The 3D finite element method (FEM) approach using COMSOL Multiphysics software is used to obtain numerical results. The suggested fractal absorber exhibits high absorption enhancement for MIR in the range between 3 and 9 µm. D-Si exhibits superior performance compared to metals in energy harvesting applications that utilize plasmonics at the mid-infrared range. Typically, semiconductors exhibit rougher surfaces than noble metals, resulting in lower scattering losses. Moreover, silicon presents various advantages, including compatibility with complementary metal-oxide-semiconductor (CMOS) and simple manufacturing through conventional silicon fabrication methods. In addition, the utilization of doped silicon material in the mid-IR region facilitates the development of microscale integrated plasmonic devices.

Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits.

Hand hygiene is considered to be the key factor in controlling and preventing infection, either in hospital care settings or in the community. Alcohol-based hand sanitizers are commonly used due to their rapid action and broad spectrum of microbicidal activity, offering protection against bacteria and viruses. However, their frequent administration during COVID-19 pandemic was associated with serious hazards, such as skin toxicity, including irritation, skin dermatitis, skin dryness or cracking, along with peeling redness or itching, with the higher possibility of getting infections. Thus, there is a need to find alternative and novel approaches for hand sanitation. In our previous publications, we reported that rhamnolipids nano-micelles had a comparable antibacterial activity to alcohol-based hand sanitizer and a lower cytotoxicity against human dermal fibroblast cells. In the current study, we investigated the antiviral activity of rhamnolipids nano-micelles against SARS-CoV-2. There was no cytotoxic effect on Vero cells noted at the tested concentrations of rhamnolipids nano-micelles. The rhamnolipids nano-micelles solution at 20, 78, and 312 µg/mL all demonstrated a significant (p < 0.05) decrease of virus infectivity compared to the virus only and the blank vehicle sample. In addition, an acute irritation test was performed on rabbits to further ascertain the biosafety of rhamnolipids nano-micelles. In the eye and skin irritation tests, no degree of irritation was recorded after topical application of rhamnolipids nano-micelles. In addition, histopathological, biomarker, and hematological analyses from animals treated with rhamnolipids nano-micelles were identical to those recorded for untreated animal. From the above, we can conclude that rhamnolipids nano-micelles are a good candidate to be used as a hand sanitizer instead of alcohol-based hand sanitizers. However, they must still be tested in the future among healthcare workers (HCW) in a health care setting to ascertain their antimicrobial efficacy and safety compared to alcohol-based hand sanitizers.

Investigating the Antibacterial Activity and Safety of Zinc Oxide Nanoparticles versus a Commercial Alcohol-Based Hand-Sanitizer: Can Zinc Oxide Nanoparticles Be Useful for Hand Sanitation?

Hand hygiene is the key factor to control and prevent the spread of infections, for example, hospital-acquired infections (HAIs). People commonly use alcohol-based hand sanitizers to assure hand hygiene. However, frequent use of alcohol-based hand sanitizers in a pandemic situation (e.g., COVID-19) was associated with serious drawbacks such as skin toxicity including irritation, skin dermatitis, and skin dryness or cracking, along with peeling, redness, or itching with higher possibility of infection. This demands the development of alternative novel products that are effective as alcohol-based hand sanitizers but have no hazardous effects. Zinc oxide nanoparticles (ZnO-NPs) are known to have broad-spectrum antimicrobial activity, be compatible with the biological system and the environment, and have applicable and economic industrial-scale production. Thus, ZnO-NPs might be a good candidate for hand sanitation. To the best of our knowledge, the antibacterial activity of ZnO-NPs in comparison to alcohol-based hand sanitizers has not yet been studied. In the present work, a comparative study of the antibacterial activity of ZnO-NPs vs. Sterillium, a commercial alcohol-based hand sanitizer that is commonly used in Egyptian hospitals, was performed against common microorganisms known to cause HAIs in Egypt, including Acinetobacter baumannii, Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus. The safety profiles of ZnO-NPs and Sterillium were also assessed. The obtained results demonstrated the superior antibacterial activity and safety of ZnO-NPs compared to Sterillium. Therefore, ZnO-NPs could be a promising candidate for hand sanitation in comparison to alcohol-based hand sanitizers; however, several studies related to long-term toxicity and stability of ZnO-NPs and investigations into their antimicrobial activity and safety in healthcare settings are still required in the future to ascertain their antimicrobial activity and safety.

Benzimidazole-based protein kinase inhibitors: Current perspectives in targeted cancer therapy.

Targeted therapy has emerged to be the cornerstone of advanced cancer treatment, allowing for more selectivity and avoiding the common drug toxicity and resistance. Identification of potential targets having vital role in growth and survival of cancer cells got much easier with the aid of the recent advances in high throughput screening approaches. Various protein kinases came into focus as valuable targets in cancer therapy. Meanwhile, benzimidazole-based scaffolds have gained significant attention as promising protein kinase inhibitors with high potency and varied selectivity. Great diversity of these scaffolds has inspired the medicinal chemists to inspect the effect of structural changes upon inhibitory activity on the molecular level through modeling studies. The present review gathers all the considerable attempts to develop benzimidazole-based compounds; designed as protein kinase inhibitors with anticancer activity since 2015; that target aurora kinase, CDK, CK2, EGFR, FGFR, and VEGFR-2; to allow further development and progression regarding benzimidazoles.

Promoted inhibition of TLR4/miR-155/ NFkB p65 signaling by cannabinoid receptor 2 agonist (AM1241), aborts inflammation and progress of hepatic fibrosis induced by thioacetamide.

The endocannabinoid system plays a pivotal role, whether it is promoting or dampening hepatic fibrosis. This study investigated the role of Cannabinoid receptor 2 (CB2) activation by the synthetic analog (AM1241) on revoking the progress of liver fibrosis. Thioacetamide (TAA) was used to induce liver fibrosis in rats for three weeks followed by its concurrent administration with AM1241 at two different doses for another three weeks. Markers for liver function and oxidative stress, hepatic TNF-α, IL-1ß and IL-6, qRT-PCR expression of Toll like receptor 4 (TLR4), TGF-ß1, α-SMA and microRNA-155 (miR-155) genes, Western blot for protein levels of Vimentin and E-cadherin, immunohistochemical expression of NFκB p65 and histopathology of liver tissue were all investigated. AM1241 administration significantly maintained liver function markers and decreased; malondialdehyde, Vimentin, TLR4, TGF-ß1, α-SMA and miR-155 genes expression, NFκB p65 immune-expression and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6). Additionally, AM1241 significantly increased E-Cadherin level, GSH and SOD content. Histologically, AM1241 limited fibroplasia extension, and broke the itinerary of bridging fibrosis. In conclusion, activation of the CB2 receptors by AM1241 promoted liver regeneration and overrun the progression of liver fibrosis through; inhibition of TLR4/miR-155/NFκB p65 pathway, suppression of pro-inflammatory IL-6, IL-1ß and TNF-α, reducing TGF-ß1, α-SMA, Vimentin and up-regulating E-Cadherin.

Comparative analysis of antibiotic exposure association with clinical outcomes of chemotherapy versus immunotherapy across three tumour types.

BACKGROUND: In solid tumours, antibiotic use during immune checkpoint inhibitor (ICI) treatment is associated with shorter survival. Following allogeneic haematopoietic cell transplantation (allo-HCT), antibiotic-induced gut microbiome alterations are associated with risk of relapse and mortality. These findings suggest that the gut microbiota can modulate antitumour immune response across tumour types, though it is not clear if the impact on outcomes is specific to immune therapy. An important limitation of previous studies is that the analysis combined all antibiotic exposures irrespective of the antibiotic spectrum of activity. Whether antibiotic exposure during induction chemotherapy in acute myeloid leukaemia (AML) affects risk of relapse is also unknown. PATIENTS AND METHODS: We performed a single-centred retrospective analysis of antibiotic exposures in metastatic/advanced non-small cell lung cancer (NSCLC) and renal cell cancer (RCC) receiving ICI and newly diagnosed AML patients receiving induction chemotherapy achieving a complete remission 1. Antibiotic use within 4 weeks before and 6 weeks after the ICI initiation were included. In AML patients, antibiotic exposures between days 1 and 28 of induction were collected. Antibiotics were a priori stratified based on spectrum of activity. Primary outcomes of interest were progression-free survival (PFS), overall survival (OS) in NSCLC and RCC and relapse-free survival (RFS) in AML. RESULTS: 140 patients with NSCLC, 55 with RCC and 143 with AML were included. In multivariable analysis, PFS and OS were shorter in NSCLC patients who received broad-spectrum anti-anaerobes (PFS, HR=3.2, 95% CI 1.6 to 6.2, p<0.01; OS, HR=1.7, 95% CI 0.8 to 3.6, p=0.19) or 'other' antibiotics (vancomycin-predominant) (PFS, HR=2.4, 95% CI 1.3 to 4.6, p<0.01; OS, HR=2.4, 95% CI 1.2 to 4.7, p=0.01). In RCC, patients who received penicillins/penicillin-class/early-generation cephalosporins had shorter PFS (HR=3.6, 95% CI 1.7 to 7.6, p<0.01) but similar OS (p=0.37). In the AML cohort, none of the exposures were associated with RFS. CONCLUSION: In contrast to AML, antibiotic exposures in solid tumours affected clinical outcomes. The presence of an allogeneic effect (allo-HCT) or an augmented immune system (checkpoint blockade) may be necessary for microbiota mediation of relapse risk.

Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats.

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-ß cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor ß-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

Carbetapentane citrate.

Carbetapentane citrate, a non-opioid centrally-acting antitussive drug, is a common treatment for cough associated with other diseases such as common cold and respiratory tract infections. Its mode of action is very close to that of atropine; since it acts at the level of the peripheral parasympathetic nerve endings. The drug reaches its maximum plasma concentration (Cmax) 2h after administration, and it has a plasma half-life of 2.3h in case of oral administration. Due to its clinical importance, there are many analytical methods in the literature for carbetapentane determination. In addition, it is crucial to collect its analytical results in a single chapter so as to allow researchers to easily interpret their experimental data. Here, we provide the analytical profile of carbetapentane citrate with a brief description/interpretation of each analysis.

Exploring the influence of particle shape and air velocity on the flowability in the respiratory tract: a computational fluid dynamics approach.

Dry powder inhalers (DPIs) are considered a main drug delivery system through pulmonary route. The main objective of this work is to study the flow of differently shaped microparticles in order to find the optimum shape of drug particles that will demonstrate the best flow to the deep lung. The flowability of particles in air or any fluid depends particularly on the drag force which is defined as the resistance of the fluid molecules to the particle flow. One of the most important parameters that affect the drag force is the particles' shape. Computational simulations using COMSOL Multi Physics 5.2 software were performed for investigating the particles flow in the air pathways of lung, and the drag force was calculated for different particles shapes. This was accomplished by screening a set of 17 possible shapes that are expected to be synthesized easily in the micro-scale. In addition, the macro-scale behavior of the investigated shapes was also simulated so as to compare the behavior of the flowing particles in both cases. A very big difference was found between the behavior of particles' flow in the micro and macro scales, but a similar behavior can be obtained if the flow velocity of the microparticles is very high. It was also found that the micro-triangle with aspect ratio 2:1 has the least drag force in both deep and upper lung; so, it should be the shape of choice during the process of particle synthesis for pulmonary drug delivery.

Patterns of infectious complications in acute myeloid leukemia and myelodysplastic syndromes patients treated with 10-day decitabine regimen.

Decitabine has been explored as a reduced-intensity therapy for older or unfit patients with acute myeloid leukemia (AML). To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection-related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10-day cycles of decitabine at Washington University School of Medicine. Culture results were available for 163 infection-related complications that occurred in 70 patients: 90 (55.2%) events were culture-negative, 32 (19.6%) were gram-positive bacteria, 20 (12.3%) were gram-negative bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1 (0.6%) was mycobacterial. Infection-related mortality occurred in 3/24 (13%) of gram-negative events, and 0/51 gram-positive events. On average, nearly one third of patients experienced an infection-related complication with each cycle, and the incidence did not decrease during later cycles. In summary, in patients receiving 10-day decitabine, infectious complications are common and may occur during any cycle of therapy. Although febrile events are commonly culture-negative, gram-positive infections are the most frequent source of culture-positive infections, but gram-negative infections represent a significant risk of mortality in AML and MDS patients treated with decitabine.

The Role of Biomarkers in the Diagnosis and Risk Stratification of Acute Graft-versus-Host Disease: A Systematic Review.

Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used curative modality for hematologic malignancies and other benign conditions. Attempts to reduce morbidity and mortality and improve survival in patients undergoing HCT are crucial. The ability to diagnose acute graft-versus-host disease (aGVHD) in a timely manner, or to even predict aGVHD before clinical manifestations, along with the accurate stratification of these patients, are critical steps to improve the treatment and outcomes of these patients. Many novel biomarkers that may help achieve these goals have been studied recently. This overview is intended to assist clinicians and investigators by providing a comprehensive review and analytical interpretation of the current knowledge concerning aGVHD and biomarkers likely to prove useful in diagnosis and risk stratification of this condition, along with the difficulties that hamper this approach.