Atypical chemokine receptor 4 (ACKR4/CCX-CKR): A comprehensive exploration across physiological and pathological landscapes in contemporary research.

Atypical chemokine receptor 4 (ACKR4), also known as CCX-CKR, is a member of the chemokine receptor family that lacks typical G protein signaling activity. Instead, ACKR4 functions as a scavenger receptor that can bind and internalize a wide range of chemokines, influencing their availability and activity in the body. ACKR4 is involved in various physiological processes, such as immune cell trafficking and the development of thymus, spleen, and lymph nodes. Moreover, ACKR4 has been implicated in several pathological conditions, including cancer, heart and lung diseases. In cancer, ACKR4 plays a complex role, acting as a tumor suppressor or promoter depending on the type of cancer and the stage of the disease. For instance, ACKR4 may inhibit the growth and metastasis of breast cancer, but it may also promote the progression of hepatocellular carcinoma and gastric cancer. In inflammatory situations, ACKR4 has been found to modulate the recruitment and activation of immune cells, contributing to the pathogenesis of diseases such as myocardial infraction and pulmonary sarcoidosis. The study of ACKR4 is still ongoing, and further research is needed to fully understand its role in different physiological and pathological contexts. Nonetheless, ACKR4 represents a promising target for the development of novel therapeutic strategies for various diseases.

A phenanthroline-based erbium (III) complex: molecular docking, DNA/BSA -binding and biological evaluation.

With the help of both theoretical as well as experimental research, in vitro binding research with CT-DNA (calf thymus) and BSA (bovine serum albumin) were carefully examined to figure out the chemotherapeutic and pharmacokinetic facets of the Erbium complex, which contains 1,10-phenanthroline (Phen). The binding characteristics and the mechanism of complex's interaction with DNA as well as the protein were determined utilizing fluorescence quenching method. Findings indicated that the complex's interaction with DNA via groove binding into DNA's minor grooves, with their binding constants falling within the 104 M-1 range. Furthermore, thermodynamic characteristics and the fluorescence emission of the tryptophan residues of the protein were obtained through fluorescence quenching studies at different temperatures. According to the results of the binding constants, the protein's interactions with the Er- complex were moderate, demonstrating that the compound may be transported effectively by the protein. Molecular docking results supported that of the experimental research. The HeLa and MCF-7 cancer cell lines, along with the normal human fibroblast cell line, were used in an MTT assay evaluation of the Er-complex cytotoxicity. The Er-complex displayed a selective inhibitory effect on the proliferation of different cancer cells.Communicated by Ramaswamy H. Sarma.

Identification of ZINC08101049 as a potential IL1ß inhibitor through molecular docking and MD simulations for cancer therapeutics.

Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1ß) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1ß activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1ß inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1ß target, and the top ten small molecules were selected based on their binding energy. The small molecule named 'ZINC08101049' was prioritized based on binding energy (-9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1ß. Next, IL1ß alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1ß, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics.Communicated by Ramaswamy H. Sarma.

Cichorium intybus L. significantly alleviates cigarette smoke-induced acute lung injury by lowering NF-κB pathway activation and inflammatory mediators.

Background: Cigarette smoke (CS) is one of the primary causes of acute lung injury (ALI) via provoking pulmonary inflammation and oxidative stress. Despite substantial studies, no effective treatment for ALI is presently available. Purpose: New prospective treatment options for ALI are required. Thus, this project was designed to investigate the in vivo and in vitro protective effects of 70 % methanolic-aqueous crude extract of whole plant of Cichorium intybus (Ci.Mce) against CS-induced ALI. Study design: /methods: Initially, male Swiss albino mice were subjected to whole-body CS exposure for 10 continuous days to prepare CS-induced ALI models. Normal saline (10 mL/kg), Ci.Mce (100, 200, 300 mg/kg), and Dexamethasone (1 mg/kg) were orally administered to respective animal groups 1 h prior to CS-exposure. 24 hrs after the last CS-exposure, BALF and lungs were harvested to study the key characteristics of ALI. Next, HPLC analysis was done to explore the phytoconstituents. Results: Ci.Mce exhibited significant reductions in lung macrophage and neutrophil infiltration, lung weight coefficient, and albumin exudation. Additionally, it effectively ameliorated lung histopathological alterations and hypoxemia. Notably, Ci.Mce exerted inhibitory effects on the excessive generation of IL-6, IL-1ß, and KC in both CS-induced ALI murine models and CSE-stimulated RAW 264.7 macrophages. Noteworthy benefits included the attenuation of oxidative stress induced by CS, evidenced by decreased levels of MDA, TOS, and MPO, alongside enhanced TAC production. Furthermore, Ci.Mce demonstrated a marked reduction in CS-induced NF-κB expression, both in vivo and in vitro. Conclusion: Consequently, Cichorium intybus could be a therapeutic option for CS-induced ALI due to its ability to suppress inflammatory reactions, mitigate oxidative stress, and quell NF-κB p65 activation.

High-throughput screening and in vitro evaluation of CSB-0914; a novel small molecule NF-κB inhibitor attenuating inflammatory responses through NF-κB, Nrf2 and HO-1 cross-talk.

Unpleasant side effects of standard inflammatory drugs urges search for novel therapeutic candidates. This study aims in identifying novel anti-inflammatory NF-κB inhibitor by high-throughput computational and in-vitro pre-clinical approaches. Lead candidate selection was conducted by the use of computational docking molecular-dynamic simulations. The RBL-2H3 cell line, derived from rat basophils, was used to evaluate the release of cytokines and degranulation. The study focused on the study of neutrophil elastase and its role in cellular motility. Flow cytometry was utilized to evaluate the activation of basophils and the expression of critical signaling proteins. High throughput screening identified CSB-0914 to stably bind NF-κB-p50 subunit. Dose based loss in T NF-α and IL-2 release were observed in RBL-2H3 cells in addition to degranulation inhibition by CSB-0914. The compound demonstrated significant efficacy in reducing basophil activation assay induced by FcεRI receptors, with an IC50 value of 98.41 nM.. A dose dependent decrease in neutrophil migration and elastase were observed when treated with CSB- 0914. The compound was effective in decreasing. Upon stimulation, RBL-2H3 cells exhibited phosphorylation of NF-κB p-65 as well as upregulation of the Nrf2 and HO-1 signaling pathways. Collectively, our study has successfully identified a novel inhibitor called CSB-0914 that effectively regulates inflammatory responses. These reactions are primarily mediated by the interplay between NF-κB, Nrf2, and HO-1. The findings of this study provide support for the need to conduct more research on CSB-0914 with the aim of its development as a pharmaceutical agent for anti-inflammatory purposes.Communicated by Ramaswamy H. Sarma.

Antibacterial activity and DNA interaction of triazine iron and ruthenium complexes: spectroscopic, voltammetric and theoretical studies.

The 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz), [Ru(µ-tptz)2]Cl2 and [Fe(µ-tptz)2]Cl2, complexes containing Ru (1) and Fe (2) are created. Using electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, viscosity measurement and electrochemistry, as well as two complexes with Fish Salmon DNA (FS-DNA), the binding interactions of these complexes were investigated. According to binding assays, complexes bind to DNA through a mild intercalation mechanism, most likely via the DNA helix's base pairs being intercalated by the tptz ligand. Additionally, complex (2) is more capable of binding than complex (1). The electrochemical method offers a quick and easy way to determine the binding constant (Kb). The antibacterial performance of these complexes versus Gram-positive and Gram-negative bacteria was examined using the zone of inhibition test, MIC, and MBC method, and the results revealed that complex (2) exhibits strong antibacterial activity against these bacteria. The outcomes of this investigation will help in understanding DNA interaction mechanisms as well as the creation of a prospective one. Additionally, the density functional theory (DFT) computation included probes of DNA structure and conformation as well as potential pharmacological regulators for particular disorders to fully explain the experimental results.

Inflammatory diseases: Function of LncRNAs in their emergence and the role of mesenchymal stem cell secretome in their treatment.

One of the best treatments for inflammatory diseases such as COVID-19, respiratory diseases and brain diseases is treatment with stem cells. Here we investigate the effect of stem cell therapy in the treatment of brain diseases.Preclinical studies have shown promising results, including improved functional recovery and tissue repair in animal models of neurodegenerative diseases, strokes,and traumatic brain injuries. However,ethical implications, safety concerns, and regulatory frameworks necessitate thorough evaluation before transitioning to clinical applications. Additionally, the complex nature of the brain and its intricate cellular environment present unique obstacles that must be overcome to ensure the successful integration and functionality of genetically engineered MSCs. The careful navigation of this path will determine whether the application of genetically engineered MSCs in brain tissue regeneration ultimately lives up to the hype surrounding it.

Bioinspired fabrication of zinc hydroxide-based nanostructure from lignocellulosic biomass Litchi chinensis leaves and its efficacy evaluation on antibacterial, antioxidant, and anticancer activity.

Zinc-based nanostructures are known for their numerous potential biomedical applications. In this context, the biosynthesis of nanostructures using plant extracts has become a more sustainable and promising alternative to effectively replace conventional chemical methods while avoiding their toxic impact. In this study, following a low-temperature calcination process, a green synthesis of Zn-hydroxide-based nanostructure has been performed using an aqueous extract derived from the leaves of Litchi chinensis, which is employed as a lignocellulose waste biomass known to possess a variety of phytocompounds. The biogenic preparation of Zn-hydroxide based nanostructures is enabled by bioactive compounds present in the leaf extract, which act as reducing and capping agents. In order to evaluate its physicochemical characteristics, the produced Zn-hydroxide-based nanostructure has been subjected to several characterization techniques. Further, the multifunctional properties of the prepared Zn-hydroxide-based nanostructure have been evaluated for antioxidant, antimicrobial, and anticancer activity. The prepared nanostructure showed antibacterial efficacy against Bacillus subtilis and demonstrated its anti-biofilm activity as evaluated through the Congo red method. In addition, the antioxidant activity of the prepared nanostructure has been found to be dose-dependent, wherein 91.52 % scavenging activity could be recorded at 200 µg/ml, with an IC50 value of 45.22 µg/ml, indicating the prepared nanostructure has a high radical scavenging activity. Besides, the in vitro cytotoxicity investigation against HepG2 cell lines explored that the as-prepared nanostructure exhibited a higher cytotoxic effect and 73.21 % cell inhibition could be noticed at 25.6 µg/ml with an IC50 of 2.58 µg/ml. On the contrary, it was found to be significantly lower in the case of HEK-293 cell lines, wherein ~47.64 % inhibition could be noticed at the same concentration. These findings might be further extended to develop unique biologically derived nanostructures that can be extensively evaluated for various biomedical purposes.

The neuroprotective effect of quercetin nanoparticles in the therapy of neuronal damage stimulated by acrolein.

A gradual loss of neuronal function or structure causes neurodegenerative disorders such as Parkinson's and Alzheimer's. Neurological damage might cause cell death. Acrolein is a high-risk air and water contaminant that causes neurodegenerative disorders. Quercetin has several strategies for treating neurodegenerative disorders but has limited bioavailability inside the body. One of the hypotheses offered to improve quercetin's bioavailability is to convert it into quercetin nanoparticles. This study aims to comprehend the immunohistochemical devastation that might arise in the cerebellum because of acrolein treatment. Furthermore, the protective and ameliorative roles of quercetin nanoparticles against oxidative stress and neurotoxicity induced in mice by acrolein were assessed. Ninety male albino rats weighing 120 to 200 g were used in the present investigation. The animals were split up into the following six groups: the control group, the acrolein-treated group: animals were given acrolein (3 mg/kg) for 30 days, quercetin nanoparticles treated group: animals were given quercetin nanoparticles (30 mg/kg) for 30 days. The administration of acrolein was found to be connected to immunohistochemical abnormalities in the cerebellum. Marked differences were observed in Bax, Bcl-2, TNF-α, and GFAP expressions in the cerebellum. Treatment of rats with quercetin nanoparticles either before or after treatment with acrolein has been found to preserve the cerebellum tissues from the toxic impacts and oxidative stress induced by acrolein. This may open the door to more nanomedicine studies and a new avenue for employing nanoparticles as a therapeutic intervention in neurodegenerative illnesses.

Surface modification of a screen-printed electrode with a flower-like nanostructure to fabricate a guanine DNA-based electrochemical biosensor to determine the anticancer drug pemigatinib.

The present study developed a DNA biosensor to determine pemigatinib for the first time. Three-dimensional carnation flower-like Eu3+:ß-MnO2 nanostructures (3D CF-L Eu3+:ß-MnO2 NSs) and a screen-printed electrode (SPE) modified with polyaniline (PA) were employed. The double-stranded DNA was also immobilized completely on the PA/3D CF-L Eu3+:ß-MnO2 NSs/SPE. Then, electrochemical techniques were used for characterizing the modified electrode. After that, the interaction between pemigatinib and DNA was shown by a reduction in the oxidation current of guanine using differential pulse voltammetry (DPV). According to the analysis, the dynamic range of pemigatinib was between 0.001 and 180.0 µM, indicating the new electrode has a low limit of detection (LOD = 0.23 nM) for pemigatinib. Afterwards, pemigatinib in real samples was measured using the PA/3D CF-L Eu3+:ß-MnO2 NSs/SPE loaded with ds-DNA. The proposed DNA biosensor showed good selectivity toward pemigatinib in the presence of other interference analytes, such as other ions, structurally related pharmaceuticals, and plasma proteins. In addition, the interaction site of pemigatinib with DNA was predicted by molecular docking, which showed the interaction of pemigatinib with the guanine bases of DNA through a groove binding mode. Finally, we employed the t-test to verify the capability of the ds-DNA/PA/3D CF-L Eu3+:ß-MnO2 NSs/SPE for analyzing pemigatinib in real samples.

Double-edged sword role of miRNA-633 and miRNA-181 in human cancers.

Understanding the function and mode of operation of microRNAs (miRNAs) in cancer is of growing interest. The short non-coding RNAs known as miRNAs, which target mRNA in multicellular organisms, are described as controlling essential cellular processes. The miR-181 family and miR-633 are well-known miRNAs that play a key role in the development and metastasis of tumor cells. They may facilitate either tumor-suppressive or oncogenic function in malignant cells, according to mounting evidence. Metastatic cells that are closely linked to cancer cell migration, invasion, and angiogenesis can be identified by abnormal levels of miR-181 and miR-633. Numerous studies have demonstrated their capacity to control drug resistance, cell growth, apoptosis, and the epithelial-mesenchymal transition (EMT) and metastasis process. Interestingly, the levels of miR-181 and miR-633 and their potential target genes in the basic cellular process can vary depending on the type of cancer cells and their gene expression profile. Such miRNAs' interactions with other non-coding RNAs such as long non-coding RNAs and circular RNAs can influence tumor behaviors. Herein, we concentrated on the multifaceted roles of miR-181 and miR-633 and potential targets in human tumorigenesis, ranging from cell growth and metastasis to drug resistance.

Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines.

Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin-gefitinib nanoparticles (Dox-Gefit NPs) and folate conjugated Dox-Gefit NPs (Dox-Gefit NPs-F). Dox-Gefit NPs and Dox-Gefit NPs-F were characterized by multiple techniques including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1H NMR), and transmission electron microscopy (TEM). In vitro release profiles were measured at both physiological and tumor endosomal pH. The cytotoxicity of the Dox-Gefit NP formulations was measured against C6 and U87 glioma cell lines. A hemolysis assay was performed to investigate biocompatibility of the formulations, and distribution of the drugs in different organs was also estimated. The Dox-Gefit NPs and Dox-Gefit NPs-F were 109.45 ± 7.26 and 120.35 ± 3.65 nm in size and had surface charges of -18.0 ± 3.27 and -20.0 ± 8.23 mV, respectively. Dox-Gefit NPs and Dox-Gefit NPs-F significantly reduced the growth of U87 cells, with IC50 values of 9.9 and 3.2 µM. Similarly, growth of the C6 cell line was significantly reduced, with IC50 values of 8.43 and 3.31 µM after a 24 h incubation, in Dox-Gefit NPs and Dox-Gefit NPs-F, respectively. The percentage drug releases of Dox and Gefit from Dox-Gefit NPs at pH 7.4 were 60.87 ± 0.59 and 68.23 ± 0.1%, respectively. Similarly, at pH 5.4, Dox and Gefit releases from NPs were 70.87 ± 0.28 and 69.24 ± 0.12%, respectively. Biodistribution analysis revealed that more Dox and Gefit were present in the brain than in the other organs. The functionalized NPs inhibited the growth of glioma cells due to high drug concentrations in the brain. Folate conjugated NPs of Dox-Gefit could be a treatment option in glioma therapy.

Synthesis and characterization of novel denosumab/magnesium-based metal organic frameworks nanocomposite prepared by ultrasonic route as drug delivery system for the treatment of osteoporosis.

Introduction: The metal-organic frameworks (MOF) have shown fascinating possibilities in biomedical applications, and designing a drug delivery system (DDS) based on the MOF is important. This work aimed at developing a suitable DDS based on Denosumab-loaded Metal Organic Framework/Magnesium (DSB@MOF (Mg)) for attenuating osteoarthritis. Materials and Methods: The MOF (Mg) (Mg3(BPT)2(H2O)4) was synthesized using a sonochemical protocol. The efficiency of MOF (Mg) as a DDS was evaluated by loading and releasing DSB as a drug. In addition, the performance of MOF (Mg) was evaluated by releasing Mg ions for bone formation. The MOF (Mg) and DSB@MOF (Mg) cytotoxicity towards the MG63 cells were explored by MTT assay. Results: MOF (Mg) characterized by using XRD, SEM, EDX, TGA, and BET. Drug loading, and releasing experiments proved that DSB was loaded on the MOF (Mg) and approximately 72% DSB was released from it after 8 h. The characterization techniques showed that MOF (Mg) was successfully synthesized with good crystal structure and thermal stability. The result of BET showed that MOF (Mg) had high surface areas and pore volume. This is the reason why its 25.73% DSB was loaded in the subsequent drug-loading experiment. Drug release and ion release experiments indicated DSB@MOF (Mg) had a good controlled release of DSB and Mg ions in solution. Cytotoxicity assay confirmed that the optimum dose of it had excellent biocompatibility and could stimulate the proliferation of MG63 cells as time went on. Conclusion: Due to the high loading amount of DSB and releasing time, DSB@MOF (Mg) can be promising as a suitable candidate for relieving bone pain caused by osteoporosis, with ossification-reinforcing functions.

Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway.

BACKGROUND: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. METHODS: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells. RESULTS: In silico observation revealed that moricin is a potential anticancer peptide, and protein-protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ƙB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells. CONCLUSIONS: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug.

Coconut waste valorization to produce biochar catalyst and its application in cellulose-degrading enzymes production via SSF.

Solid waste management and waste valorization are key concerns and challenges around the globe. Solid wastes generated by food industries are found in a diverse variety, are key sources of enormously valuable compounds, and can be effectively transformed into useful products for broad industrial applications. Biomass-based catalysts, industrial enzymes, and biofuels are some of the very prominent and sustainable products that are developed using these solid wastes. The aims of the current study are therefore centered on the multiple valorizations of coconut waste (CWs) to develop biochar as a catalyst and its application in fungal enzyme production in solid-state fermentation (SSF). Biochar as a catalyst using CWs has been prepared via a calcination process lasting 1 h at 500 °C and characterized through X-ray diffraction, Fourier-transformed infrared spectroscopy, and scanning electron microscope techniques. The produced biochar has been implemented for boosting enzyme production through SSF. In addition, studies have been performed on enzyme production with varying time and temperature, and it is found that the maximum 92 IU/gds BGL enzyme could be produced at a 2.5 mg concentration of biochar-catalyst at 40 °C in 72 h.

Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages.

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co-localized with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche.

Synthesis of New Zirconium Magnetic Nanocomposite as a Bioactive Agent and Green Catalyst in the Four-Component Synthesis of a Novel Multi-Ring Compound Containing Pyrazole Derivatives.

New nanocomposites containing zirconium were synthesized using microwave irradiation. Their structure was confirmed by vibrating sample magnetometer (VSM) curves, X-ray diffraction (XRD) patterns, scanning electron microscope (SEM) and transmission electron microscopy (TEM) images, Fourier transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET) N2 adsorption/desorption isotherms. After the structure confirmation of the zirconium magnetic nanocomposite, the catalytic properties in the synthesis of pyrazole derivatives were investigated. Next, the biological activities of the zirconium magnetic nanocomposite, such as the antibacterial and antifungal activities, were investigated. The research results showed that the zirconium magnetic nanocomposite has high catalytic properties and can be used as a magnetic nanocatalyst for synthesizing heterocyclic compounds such as pyrazole derivatives in addition to having high biological properties. The unique properties of the nanoparticles can be attributed to their synthesis method and microwave radiation.

A Mathematical Model of Vaccinations Using New Fractional Order Derivative.

Purpose: This paper studies a simple SVIR (susceptible, vaccinated, infected, recovered) type of model to investigate the coronavirus's dynamics in Saudi Arabia with the recent cases of the coronavirus. Our purpose is to investigate coronavirus cases in Saudi Arabia and to predict the early eliminations as well as future case predictions. The impact of vaccinations on COVID-19 is also analyzed. Methods: We consider the recently introduced fractional derivative known as the generalized Hattaf fractional derivative to extend our COVID-19 model. To obtain the fitted and estimated values of the parameters, we consider the nonlinear least square fitting method. We present the numerical scheme using the newly introduced fractional operator for the graphical solution of the generalized fractional differential equation in the sense of the Hattaf fractional derivative. Mathematical as well as numerical aspects of the model are investigated. Results: The local stability of the model at disease-free equilibrium is shown. Further, we consider real cases from Saudi Arabia since 1 May−4 August 2022, to parameterize the model and obtain the basic reproduction number R0v≈2.92. Further, we find the equilibrium point of the endemic state and observe the possibility of the backward bifurcation for the model and present their results. We present the global stability of the model at the endemic case, which we found to be globally asymptotically stable when R0v>1. Conclusion: The simulation results using the recently introduced scheme are obtained and discussed in detail. We present graphical results with different fractional orders and found that when the order is decreased, the number of cases decreases. The sensitive parameters indicate that future infected cases decrease faster if face masks, social distancing, vaccination, etc., are effective.

Mechanisms of Actions Involved in The Antinociceptive Effect of Estragole and its ß-Cyclodextrin Inclusion Complex in Animal Models.

(1) Background: estragole is a monoterpene found in the essential oils of several aromatic plants, which can be used for several pharmacological activities. The aim of this study was to evaluate the antinociceptive effect of estragole (Es) and its ß-cyclodextrins inclusion complex (Es/ß-CD). (2) Methods: the effects of Es and Es/ß-CD on the central nervous system (CNS) were evaluated through open field and rota-rod assays, and the antinociceptive effect in formalin models, abdominal writhing induced by acetic acid, hot plate, tail flick test and plantar mechanical hyperalgesia. (3) Results: Es and Es/ß-CD showed no alterations on the CNS evaluated parameters and the results suggested there was an antinociceptive action in the formalin, abdominal writhing, hot plate, tail flick tests and plantar mechanical hyperalgesia, proposing the involvement of the nitric oxide, glutamatergic signaling pathways, cyclic guanosine monophosphate and vanilloid pathways. (4) Conclusion: the results suggest that Es and Es/ß-CD have a promising antinociceptive potential as a possible alternative for the pharmacological treatment of pain, also showing that the encapsulation of Es in ß-cyclodextrins probably improves its pharmacological properties, since the complexation process involves much lower amounts of the compound, contributing to better bioavailability and a lower probability of adverse effect development.