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Purpose To compare the results of three-snip punctoplasty with the placement of three everting interrupted sutures versus three-snip punctoplasty with mini-Monoka stent in managing punctual stenosis. Patients and methods Fifty adult patients underwent three-snip punctoplasty with three everting interrupted sutures in one eye (right eye) (group A), and the other eye (left eye) (group B) underwent three-snip punctopasty with mini-Monoka stent. The sutures and stent were removed 6 weeks after the surgery. Epiphora, punctal opening, tear height meniscus, fluorescein and disappearance test results were analyzed and compared to preoperative information. Results Hundred eyes of 50 patients with a median age of 59 years, and females accounted for 56% of the sample. Anatomical and functional success in the right eye (group A) was 87.8 and 85.7%, respectively. On the other hand, the left eye (group B) anatomical and functional success were 89.7 and 87.7%, respectively. Regarding epiphora, there was a statistically significant difference between presurgical and postsurgical follow-up examinations in both right and left groups regarding Munk score. Tear Meniscus Height (TMH) decreased all through the follow-up visits between the two groups, almost to half, with no significant difference between both groups. Conclusion Both three-snip punctoplasty with everting sutures and three-snip punctoplasty with mini-Monoka stent are successful techniques in the management of punctal stenosis.

Abstract Analysis of drugs clinically and their identification in biological samples are of utmost importance in the process of therapeutic drug monitoring, also in pharmacokinetic investigations and tracking of illicit medications. These investigations are carried out using a variety of analytical methods, including potentiometric electrodes. Potentiometric electrodes are a wonderful solution for researchers because they outperform other methods in terms of sustainability, greenness, and cost effectiveness. In the current study, ion-selective potentiometric sensors were assembled for the aim of quantification of the anticancer drug Letrozole (LTZ). The first step was fabrication of a conventional sensor based on the formation of stable host–guest inclusion complex between the cationic drug and 4-tert-butylcalix-8-arene (TBCAX-8). Two additional sensors were prepared through membrane modification with graphene nanocomposite (GNC) and polyaniline (PANI) nanoparticles. Linear responses of 1.00 × 10–5–1.00 × 10–2, 1.00 × 10–6–1.00 × 10–2 and 1.00 × 10–8–1.00 × 10–3 with sub-Nernstian slopes of 19.90, 20.10 and 20.30 mV/decade were obtained for TBCAX-8, GNC, and PANI sensors; respectively. The developed sensors were successful in determining the drug LTZ in bulk powder and dosage form. PANI modified sensor was used to determine LTZ in human plasma with recoveries ranging from 88.00 to 96.30%. IUPAC recommendations were followed during the evaluation of the electrical performance of the developed sensors. Experimental conditions as temperature and pH were studied and optimized. Analytical Eco-scale and Analytical GREEness metric were adopted as the method greenness assessment tools.

Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases (4–9) were employed in the synthesis of selenium nanoparticle forms (4NPs–9NPs). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound 4 showed effective anti-proliferative activity against MCF-7(IC50 3.14 ± 0.04 µM), HepG-2(IC50 1.07 ± 0.03 µM), and A549(IC50 1.53 ± 0.01 µM) cell lines, while its selenium nanoform 4NPs showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, 4NPs outperformed 4 in selectivity against the Vero cell line by 4.5-fold. Furthermore, 4NPs exhibited strong inhibition of CDK1(IC50 0.47 ± 0.3 µM) and tubulin polymerase(IC50 0.61 ± 0.04 µM), outperforming 4 and being comparable to roscovitine (IC50 0.27 ± 0.03 µM) and combretastatin-A4(IC50 0.25 ± 0.01 µM), respectively. Moreover, both 4 and 4NPs arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that 4 and 4NPs were able to inhibit CDK1 and tubulin polymerase binding sites.

Novel series of aminopyrimidines bearing a biologically active cyclohexenone 3a–f and oxo-selaneylidene moiety 4, besides selenadiazolopyrimidines (5a–e and 7), were synthesised using 5,6-diaminouracils as starting materials. Compound 3a exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC50 14.31 ± 0.83 µM), A-549 (IC50 30.74 ± 0.76 µM), and MCF-7 (IC50 27.14 ± 1.91 µM). Also, it was four times more selectively cytotoxic against WI-38 cell lines than doxorubicin. Furthermore, Topoisomerase II (IC50 4.48 ± 0.65 µM) and HSP90 (IC50 1.78 ± 0.11 µM) were both strongly inhibited in vitro by 3a. The cell cycle was halted at the G1-S phase, and total apoptotic cells were 65 times more than control Hep-G2 cells. Besides, it increased caspase-3 gene expression, triggering mitochondrial cell death. Molecular docking study indicated that it could bind to Topoisomerase II and HSP90 binding sites in an inhibitory mode. Its geometric properties were investigated using the density functional theory (DFT). Furthermore, compound 3a demonstrated in silico good oral bioavailability.

Cadmium is an extremely dangerous heavy metal that can lead to disastrous consequences in all organisms. Several natural remedies reduce the toxicities of experimentally generated metals in animals. Strawberry Fragaria ananassa contains several bioactive compounds that may mitigate heavy-metal toxicity. The study aim was to evaluate the ability of a strawberry fruit methanol extract (SE) to reduce Cd toxicity and to identify and quantify the active constituents of SE. Forty Wistar rats were classified into four groups: the control group– 1 ml saline IP; SE group– 100 mg of SE/kg rats orally; cadmium (Cd) group–2 mg CdCl2/kg body weight/IP daily; and treated group– SE given 1 hour before Cd administration. Administration of Cd induced several histopathological and immunohistochemical alterations in lung sections. Biochemical analysis of lung homogenates and mRNA levels of antioxidants and inflammatory cytokines indicated significant changes to the risk profile. SE administration significantly decreased the oxidative stress, inflammation, tissue damage, the mean area percentage of collagen fibers, and positive immuno-expressions of TNF-α and NF-κB induced by CdCl2. Moreover, the MDA, TNF-α, GM-CSF, and IL-1β levels in Cd-exposed rat lung tissue were significantly lower in the SE-treated group than in the Cd-group. SE significantly augmented lung GSH, SOD, HO‐1, GPx-2, and Nrf2 levels in Cd-exposed rats. SE mitigated Cd-caused oxidative stress and lung inflammation. Therefore, regularly consuming a strawberry-rich diet could benefit general health and help prevent and treat diseases.

Treatment strategies for steatohepatitis are of special interest given the high prevalence of obesity and fatty liver disease worldwide. This study aimed to investigate the potential therapeutic mechanism of L-carnitine (LC) and Ginkgo biloba leaf extract (GB) supplementation in ameliorating the adverse effects of hyperlipidemia and hepatosteatosis induced by a high-cholesterol diet (HCD) in an animal model. The study involved 50 rats divided into five groups, including a control group, a group receiving only an HCD, and three groups receiving an HCD along with either LC (300 mg LC/kg bw), GB (100 mg GB/kg bw), or both. After eight weeks, various parameters related to lipid and glucose metabolism, antioxidant capacity, histopathology, immune reactivity, and liver ultrastructure were measured. LC + GB supplementation reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, insulin, HOMA-IR, alanine transaminase, and aspartate transaminase levels and increased high-density lipoprotein cholesterol levels compared with those in the HCD group. Additionally, treatment with both supplements improved antioxidant ability and reduced lipid peroxidation. The histological examination confirmed that the combination therapy reduced liver steatosis and fibrosis while also improving the appearance of cell organelles in the ultrastructural hepatocytes. Finally, the immunohistochemical analysis indicated that cotreatment with LC + GB upregulated the immune expression of GLP-1 and β-Cat in liver sections that were similar to those of the control animals. Mono-treatment with LC or GB alone substantially but not completely protected the liver tissue, while the combined use of LC and GB may be more effective in treating liver damage caused by high cholesterol than either supplement alone by regulating hepatic oxidative stress and the protein expression of GLP-1 and β-Cat.

Carbon quantum dots (CQDs) are a versatile class of carbon-based nanomaterial frameworks that have previously been used as a diagnostic device, in sensing for environmental applications, in bioimaging, and for drug delivery systems. Their versatility stems from their ability to be chemically tailored via functionalization to optimize properties for specific applications. In this study, we have synthesized lactic acid-derived nitrogen doped carbon quantum dots (LAdN-CQDs) and examined their ability to intervene in the conversion of soluble, monomeric hen egg-white lysozyme (HEWL) into mature fibrils. Our data indicate that LAdN-CQDs inhibit HEWL fibril formation in a dose-dependent manner (achieving up to 50% inhibition at 2.5 mg mL−1). Furthermore, in a neuroblastoma-derived cell line, LAdN-CQDs were found not to disrupt mitochondrial membrane potential or trigger apoptosis at the same concentration range, suggesting that they are biocompatible. LAdN-CQDs effectively neutralized reactive oxygen species (ROS), with a 50% decrease in ROS levels at just 100 μg mL−1 when challenged with an established free radical generator and protected the cell line from rotenone-induced apoptosis. The ability of LadN-CQDs to inhibit the soluble-to-toxic transformation of HEWL, the tolerance of SHSY-5Y cells to LAdN-CQDs, and their ability to restitute cells from rotenone-induced apoptosis, combined with the biocompatibility findings, suggest that LAdN-CQDs are potentially neuroprotective. The findings indicate that LAdN-CQDs represent a versatile, carbon-based, sustainable nanoplatform that bridges nanotechnology and neuroprotection, promoting the development of green chemistry-based healthcare solutions. [ABSTRACT FROM AUTHOR]

Hop latent viroid (HLVd), a subviral pathogen from the family Pospiviroidae, is a major threat to the global cannabis industry and is the causative agent for “dudding disease”. Infected plants can often be asymptomatic for a period of growth and then develop symptoms such as malformed and yellowing leaves, as well as stunted growth. During flowering, HLVd-infected plants show reduced levels of valuable metabolites. This study was undertaken to expand our basic knowledge of HLVd infectivity, transmission, and host range. HLVd-specific primers were used for RT-PCR detection in plant samples and were able to detect HLVd in as little as 5 picograms of total RNA. A survey of hemp samples obtained from a diseased production system proved sole infection of HLVd (72%) with no coexistence of hop stunt viroid. HLVd was infectious through successive passage assays using a crude sap or total RNA extract derived from infected hemp. HLVd was also highly transmissible through hemp seeds at rates of 58 to 80%. Host range assays revealed new hosts for HLVd: tomato, cucumber, chrysanthemum, Nicotiana benthamiana, and Arabidopsis thaliana (Col-0). Sequence analysis of 77 isolates revealed only 3 parsimony-informative sites, while 10 sites were detected among all HLVd isolates available in the GenBank. The phylogenetic relationship among HLVd isolates allowed for inferring two major clades based on the genetic distance. Our findings facilitate further studies on host–viroid interaction and viroid management.

A cryptocurrency is a non-centralized form of money that facilitates financial transactions using cryptographic processes. It can be thought of as a virtual currency or a payment mechanism for sending and receiving money online. Cryptocurrencies have gained wide market acceptance and rapid development during the past few years. Due to the volatile nature of the crypto-market, cryptocurrency trading involves a high level of risk. In this paper, a new normalized decomposition-based, multi-objective particle swarm optimization (N-MOPSO/D) algorithm is presented for cryptocurrency algorithmic trading. The aim of this algorithm is to help traders find the best Litecoin trading strategies that improve their outcomes. The proposed algorithm is used to manage the trade-offs among three objectives: the return on investment, the Sortino ratio, and the number of trades. A hybrid weight assignment mechanism has also been proposed. It was compared against the trading rules with their standard parameters, MOPSO/D, using normalized weighted Tchebycheff scalarization, and MOEA/D. The proposed algorithm could outperform the counterpart algorithms for benchmark and real-world problems. Results showed that the proposed algorithm is very promising and stable under different market conditions. It could maintain the best returns and risk during both training and testing with a moderate number of trades.

Structural-based drug design and solvent-free synthesis were combined to obtain three novel series of 5-arylethylidene-aminopyrimidine-2,4-diones (4, 5a–c, 6a,b), 5-arylethylidene-amino-2-thiopyrimidine-4-ones (7,8), and 6-arylpteridines (9,10) as dual BRD4 and PLK1 inhibitors. MTT assays of synthesized compounds against breast (MDA-MB-231), colorectal (HT-29), and renal (U-937) cancer cells showed excellent-to-good cytotoxic activity, compared to Methotrexate; MDA-MB-231 were the most sensitive cancer cells. The most active compounds were tested against normal Vero cells. Compounds 4 and 7 significantly inhibited BRD4 and PLK1, with IC50 values of 0.029, 0.042 µM, and 0.094, 0.02 µM, respectively, which are nearly comparable to volasertib (IC50 = 0.017 and 0.025 µM). Compound 7 triggered apoptosis and halted cell growth at the G2/M phase, similarly to volasertib. It also upregulated the BAX and caspase-3 markers while downregulating the Bcl-2 gene. Finally, active compounds fitted the volasertib binding site at BRD4 and PLK1 and showed ideal drug-like properties and pharmacokinetics, making them promising anticancer candidates.

Background: Hyperglycemia is frequent during steroid therapy and thus it is not uncommon during treatment of lymphoid malignancies. Steroid-induced diabetes (SID) can be complicated by an increased risk of infections, lower chemotherapy efficacy, and even increased mortality. Aim: To determine the prevalence of SID in patients with aggressive lymphoid malignancies during induction therapy and to analyze its impact on treatment outcomes. Methods: The study included 52 patients with lymphoid malignancies; 28 with acute lymphoblastic leukemia (ALL) and 24 with aggressive non-Hodgkin’s lymphomas (NHL). We studied the relation between the development of SID during induction therapy and the rates of complete remission (CR), complication and relapse and survival. Results: Steroid-induced diabetes occurred during induction therapy in 18/28 (64%) and 8/24 (33%) of patients with ALL and NHL, respectively. Older age, and elevated bilirubin level were significantly associated with the development of SID during induction therapy in ALL patients (p = 0.02 and 0.005, respectively), while only older age showed a significant association in NHL patients (p = 0.002). Compared with patients who did not develop SID, those with SID had significantly higher prevalence of febrile neutropenia in the ALL group (p = 0.001) and pneumonia in the NHL group (p = 0.009). Both ALL and NHL patients with SID were significantly less likely to achieve CR and had a significantly worse overall survival. Conclusion: The results of this study suggest that SID is frequent during induction therapy in patients with lymphoid malignancies and associated with more complications and worse treatment outcomes.

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.