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Precision medicine has revolutionized modern cancer therapeutic management by targeting specific molecular aberrations responsible for the onset and progression of tumorigenesis. ROS proto-oncogene 1 (ROS1) is a receptor tyrosine kinase (RTK) that can induce tumorigenesis through various signaling pathways, such as cell proliferation, survival, migration, and metastasis. It has emerged as a promising therapeutic target in various cancer types. However, there is very limited availability of specific ROS1 inhibitors for therapeutic purposes. Exploring repurposed drugs for rapid and effective treatment is a useful approach. In this study, we utilized an integrated approach of virtual screening and molecular dynamics (MD) simulations of repurposing existing drugs for ROS1 kinase inhibition. Using a curated library of 3648 FDA-approved drugs, virtual screening identified drugs capable of binding to ROS1 kinase domain. The results unveil two hits, Midostaurin and Alectinib with favorable binding profiles and stable interactions with the active site residues of ROS1. These hits were subjected to stability assessment through all-atom MD simulations for 200 ns. MD results showed that Midostaurin and Alectinib were stable with ROS1. Taken together, the study showed a rational framework for the selection of repurposed Midostaurin and Alectinib with ROS1 inhibitory potential for therapeutic management after further validation.

BackgroundSevere complications from COVID-19 and poor responses to SARS-CoV-2 vaccination were commonly reported in cancer patients compared to those without cancer. Therefore, the identification of predisposing factors to SARS-CoV-2 infection in cancer patients would assist in the prevention of COVID-19 and improve vaccination strategies. The literature lacks reports on this topic from the Kingdom of Saudi Arabia (KSA). Therefore, we studied clinical and laboratory data of 139 cancer patients from King Abdulaziz Medical City, Riyadh, KSA.MethodsThe cancer patients fall into three categories; (i) uninfected with SARS-CoV-2 pre-vaccination and remained uninfected post-vaccination (control group; n = 114; 81%), (ii) pre-vaccination infected group (n = 16; 11%), or (iii) post-vaccination infected group (n = 9; 6%). Next, the clinical and lab data of the three groups of patients were investigated.ResultsComorbidity factors like diabetes and hemodialysis were associated with the risk of infection in cancer patients before the vaccination (pConclusionCollectively, this is the first study from KSA to report potential risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination. Further investigations on these risk factors in a larger cohort are worthwhile to draw a definitive conclusion about their roles in predisposing cancer patients to the infection.

BackgroundPrevalence of different respiratory allergies is increasing in the Kingdom of Saudi Arabia (KSA). Environmental risk factors of respiratory allergy vary regionally, hence the prevalence. This necessitates the needs for regional studies. This article reports prevalence and symptoms of respiratory allergies in the Qassim region, and the factors associated with the prevalence.MethodsEight hundred and fifty individuals aged ≥18 years and were living in the Qassim region filled up our structured online questionnaire between September and December 2020. We estimated the prevalence of different respiratory allergies with 95% confidence intervals. Multi-variable logistic regression analyses were performed to investigate the risk factors of respiratory allergies.FindingsThe prevalence of any respiratory allergy in the Qassim region was 28.8%. Most families (58.1%) had at least one member with respiratory allergy. The prevalence of allergic rhinitis and bronchial asthma were 13.5% and 11.2% 4.1% respectively. The reported symptoms included runny nose (13.6%), red, watery, and itchy eyes (10.4%), difficulty sleeping at night (10.2%), difficulty breathing in cold weather (9.2%), noisy breathing (8.5%), sneezing (8%), repeated coughing (7.5%) and shortness of breath (6.4%). Individuals with a family history were more likely to report any respiratory allergy (OR: 7.8), bronchial asthma (OR: 4.2) and allergic rhinitis (OR: 8.1) compared to the individuals without such family history. Odds of respiratory allergies was higher among males (OR: 1.5). Saudi nationals were less likely to report allergic rhinitis than the non-Saudis (OR: 0.4). Among those who reported a respiratory allergy, most (73.5%) received treatment and majority (61.7%) demonstrated compliance to the treatment, 8.8% needed hospitalization, and 23.1% needed emergency nebulization.ConclusionsPrevalence reported in our study is different than that reported in other regions. Variability in the environmental exposures might explain this. We recommend a meta-analysis to estimate the national prevalence of respiratory allergies.

Abstract Bruton's tyrosine kinase (BTK) is a non-receptor protein kinase that plays a crucial role in various biological processes, including immune system function and cancer development. Therefore, inhibition of BTK has been proposed as a therapeutic strategy for various complex diseases. In this study, we aimed to identify potential inhibitors of BTK by using a drug repurposing approach. To identify potential inhibitors, we performed a molecular docking-based virtual screening using a library of repurposed drugs from DrugBank. We then used various filtrations followed by molecular dynamics (MD) simulations, principal component analysis (PCA), and Molecular Mechanics Poisson Boltzmann Surface Area (MM-PBSA) analysis to further evaluate the binding interactions and stability of the top-ranking compounds. Molecular docking-based virtual screening approach identified several repurposed drugs as potential BTK inhibitors, including Eltrombopag and Alectinib, which have already been approved for human use. All-atom MD simulations provided insights into the binding interactions and stability of the identified compounds, which will be helpful for further experimental validation and optimization. Overall, our study demonstrates that drug repurposing is a promising approach to identify potential inhibitors of BTK and highlights the importance of computational methods in drug discovery.

The available antiviral drugs against coronavirus disease 2019 (COVID-19) are limited. Oral drugs that can be prescribed to non-hospitalized patients are required. The 4′-fluoruridine, a nucleoside analog similar to remdesivir, is one of the promising candidates for COVID-19 oral therapy due to its ability to stall viral RdRp. Available data suggested that 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Although 4'-fluorouridine is considered as strong candidates, further studies are required to determine its efficacy in the patients and it’s genetic effects on humans. In this review, we the antiviral activity of 4′-fluorouridine is reviewed and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is compiled and discussed.

Abstract Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p

Background: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged in 2019 and caused a global pandemic in 2020, manifesting in the coronavirus disease 2019 (COVID-19). The majority of patients exhibit a mild form of the disease with no major complications; however, moderate to severe and fatal cases are of public health concerns. Predicting the potential prognosis of COVID-19 could assist healthcare workers in managing cases and controlling the pandemic in an effective way. Therefore, the objectives of the study were to search for biomarkers associated with COVID-19 mortality and predictors of the overall survival (OS). Methods: Here, clinical data of 6026 adult COVID-19 patients admitted to two large centers in Saudi Arabia (Riyadh and Hafar Al-Batin cities) between April and June 2020 were retrospectively analysed. Results: More than 23% of the study subjects with available data have died, enabling the prediction of mortality in our cohort. Markers that were significantly associated with mortality in this study were older age, increased d-dimer in the blood, higher counts of WBCs, higher percentage of neutrophil, and a higher chest X-ray (CXR) score. The CXR scores were also positively associated with age, d-dimer, WBC count, and percentage of neutrophil. This supports the utility of CXR scores in the absence of blood testing. Predicting mortality based on Ct values of RT-PCR was not successful, necessitating a more quantitative RT-PCR to determine virus quantity in samples. Our work has also identified age, d-dimer concentration, leukocyte parameters and CXR score to be prognostic markers of the OS of COVID-19 patients. Conclusion: Overall, this retrospective study on hospitalised cohort of COVID-19 patients presents that age, haematological, and radiological data at the time of diagnosis are of value and could be used to guide better clinical management of COVID-19 patients.

Abstract Cancers are regarded as one of the main causes of death and result in high health burden worldwide. The management of cancer include chemotherapy, surgery and radiotherapy. The chemotherapy, which involves the use of chemical agents with cytotoxic actions is utilised as a single treatment or combined treatment. However, these managements of cancer such as chemotherapy poses some setbacks such as cytotoxicity on normal cells and the problem of anticancer drug resistance. Therefore, the use of other therapeutic agents such as antidiabetic drugs is one of the alternative interventions used in addressing some of the limitations in the use of anticancer agents. Antidiabetic drugs such as sulfonylureas, biguanides and thiazolidinediones showed beneficial and repurposing actions in the management of cancer, thus, the activities of these drugs against cancer is attributed to some of the metabolic links between the two disorders and these includes hyperglycaemia, hyperinsulinemia, inflammation, and oxidative stress as well as obesity. Furthermore, some studies showed that the use of antidiabetic drugs could serve as risk factors for the development of cancerous cells particularly pancreatic cancer. However, the beneficial role of these chemical agents overweighs their detrimental actions in cancer management. Hence, the present review indicates the metabolic links between cancer and diabetes and the mechanistic actions of antidiabetic drugs in the management of cancers.

Each biopharmaceutical research and new drug development investigation is targeted at discovering novel and potent medications for managing specific ailments. Thus, to discover and develop new potent medications, it should be performed sequentially or step by step. This is because drug development is a lengthy and risky work that requires significant money, resources, and labor. Breast and lung cancer contributes to the death of millions of people throughout the world each year, according to the report of the World Health Organization, and has been a public threat worldwide, although the global medical sector is developed and updated day by day. However, no proper treatment has been found until now. Therefore, this research has been conducted to find a new bioactive molecule to treat breast and lung cancer—such as natural myricetin and its derivatives—by using the latest and most authentic computer-aided drug-design approaches. At the beginning of this study, the biological pass prediction spectrum was calculated to select the target protein. It is noted that the probability of active (Pa) score is better in the antineoplastic (Pa: 0.788–0.938) in comparison with antiviral (Pa: 0.236–0.343), antibacterial (Pa: 0.274–0.421), and antifungal (Pa: 0.226–0.508). Thus, cancerous proteins, such as in breast and lung cancer, were picked up, and the computational investigation was continued. Furthermore, the docking score was found to be -7.3 to -10.4 kcal/mol for breast cancer (standard epirubicin hydrochloride, -8.3 kcal/mol), whereas for lung cancer, the score was -8.2 to -9.6 kcal/mol (standard carboplatin, -5.5 kcal/mol). The docking score is the primary concern, revealing that myricetin derivatives have better docking scores than standard chemotherapeutic agents epirubicin hydrochloride and carboplatin. Finally, drug-likeness, ADME, and toxicity prediction were fulfilled in this investigation, and it is noted that all the derivatives were highly soluble in a water medium, whereas they were totally free from AMES toxicity, hepatotoxicity, and skin sensitization, excluding only ligands 1 and 7. Thus, we proposed that the natural myricetin derivatives could be a better inhibitor for treating breast and lung cancer.

The coastal regions of some states (Kerala, Tamil Nadu, Andhra Pradesh and Orissa) in India are known to have plenty of thorium-rich minerals, therefore possess high external gamma radiation fields, and are identified as Natural High Background Radiation Areas. There are concerns about congenital malformations due to the high background radiation prevailing in the region. Therefore, scientists find interest to study the possible biological effects of low-level exposures on the local populace who are living with generations under these extraordinary radiation fields. The present study is an attempt to find the correlation between the incidences of certain congenital malformations through a 1:3 matched case-control study. A total of 75 subjects (58 mental retardation cases and 17 Cleft lip/palate cases) along with 225 controls were selected for the investigations. Indoor and outdoor gamma dose rates were measured using a halogen-quenched GM tube-based survey meter, while the indoor inhalation dose rates were measured based on the radon and progeny measurements using the twin cup dosimeters equipped with LR-115 Type II solid-state nuclear track detectors. Conditional logistic regression analysis was used to find out the correlation between the radiation dose with congenital malformation. This study found an insignificant risk of cleft lip/palate (but not for mental retardation) from the exposures to natural high external gamma radiation fields in the study area. Therefore, the results of the investigation indicate no explicit risk of congenital malformations by the high background natural radiation prevailing in the region.

Cancer is a life-threatening disease caused by the uncontrolled division of cells, which culminates in a solid mass of cells known as a tumor or liquid cancer. It is the leading cause of mortality worldwide, and the number of cancer patients has been increasing at an alarming rate, with an estimated 20 million cases expected by 2030. Thus, the use of complementary or alternative therapeutic techniques that can help prevent cancer has been the subject of increased attention. Garlic, the most widely used plant medicinal product, exhibits a wide spectrum of biological activities, including antibacterial, hypo-lipidemic, antithrombotic, and anticancer effects. Diallyl disulfide (DADS) is a major organosulfur compound contained within garlic. Recently, several experimental studies have demonstrated that DADS exhibits anti-tumor activity against many types of tumor cells, including gynecological cancers (cervical cancer, ovarian cancer), hematological cancers (leukemia, lymphoma), lung cancer, neural cancer, skin cancer, prostate cancer, gastrointestinal tract and associated cancers (esophageal cancer, gastric cancer, colorectal cancer), hepatocellular cancer cell line, etc. The mechanisms behind the anticancer action of DADS include epithelial-mesenchymal transition (EMT), invasion, and migration. This article aims to review the available information regarding the anti-cancer potential of DADS, as well as summarize its mechanisms of action, bioavailability, and pharmacokinetics from published clinical and toxicity studies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners’ safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics’ data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.

Eco-friendly synthesis of silver nanoparticles (SN) by using a naturally occurring plant, such as Nitrosalsola (Salsola) vermiculata (SV), could be a novel way for appropriate wound healing. AgNO3 was reduced by SV to produce safe SN (SN-SV) extract and hasten the wound healing process. The obtained SN-SV were characterized by size, charge, wavelength, and surface morphology. The optimized formulation was dispersed in O/W cosmetic cream. Then, it was characterized in terms of pH, viscosity, homogeneity, and permeability. The ex vivo and in vivo studies have been conducted in a rat animal model to assess the potential of SN-SV cream on skin tissue regeneration. A skin punch biopsy was obtained to investigate the histopathological (HP) changes in the skin lesions of all rats by the H&E staining and PCNA immunostaining methods. The skin wounds in all subgroups were examined on days 5, 11, and 15 to analyze the effectiveness of SN-SV cream for treating surgical skin wounds. The prepared SN-SV had a particle size of 37.32 ± 1.686 nm, a charge of −1.4 ± 0.7 mV, non-aggregated SN-SV, and a λmax of 396.46 nm. The formed SN-SV cream showed a pH near the skin’s pH, with suitable viscosity and homogeneity and an apparent permeability of 0.009 ± 0.001. The HP changes in the SN-SV subgroups revealed a substantial reduction in wound size and improvement in wound granulation tissue formation and epidermal re-epithelialization (proliferation) compared to the healing in the SN subgroups. The current work revealed that SN-SV could be a novel skin-wound-healing agent with a practical application as a wound-healing platform.

Background: Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. Results: We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) ≤ 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing ≤ 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p

Background: Although vaccination is underway, antiviral drugs against coronavirus disease 2019 (COVID-19) are lacking. Remdesivir, a nucleoside analog that works by inhibiting the viral RNA-dependent RNA polymerase (RdRp), is the only fully approved antiviral for the treatment of COVID-19. However, it is limited to intravenous use and is usually recommended only for hospitalized patients with severe COVID-19; therefore, oral drugs that can be prescribed even to non-hospitalized patients are required. According to a recent study, 4′-fluoruridine, a nucleoside analog similar to remdesivir, is a promising candidate for COVID-19 oral therapy due to its ability to stall viral RdRp. Methods: We examined the antiviral activity of 4′-fluorouridine and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been compiled and discussed in this review. Results: The 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vitro studies have shown that SARS-CoV-2 is susceptible to 4'-fluorouridine, with the half-maximal effective concentration (EC 50) of 0.2 to 0.6 M, and that the 4′-fluorouridine derivative, 4′-fluorouridine-5′-triphosphate, inhibited RdRp via a mechanism distinct from that of the already approved COVID-19 oral drug, molnupiravir. In addition, an in vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Conclusions: Concerns about the genetic effects of molnupiravir may be resolved by the use of 4′-fluorouridine and its derivative, which, unlike molnupiravir, do not alter genetics, but inhibit RdRp instead. Although they are currently considered as strong candidates, further studies are required to determine the antiviral activity of 4′-fluorouridine and its derivative against SARS-CoV-2 and their genetic effects on humans.

The updated affiliation information can be seen in the affiliation part of this correction [...]

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.

Attention-deficit hyperactivity disorder (ADHD) seriously affects children’s health, and the gut microbiome has been widely hypothesized to play a role in the regulation of ADHD behavior. The present study aims to the biosynthesize of zinc oxide nanoparticles (ZnONPs) by using Acinetobacter johnsonii strain RTN1, followed by their characterization through state-of-the-art material characterization techniques, viz., UV–vis spectroscopy, Fourier transform infrared spectroscopy, and transmission and scanning electron microscopic analyses with energy dispersive spectrometry. Moreover, we investigated and compared the population composition of gut microbiota and their susceptibility to biogenic ZnONPs between healthy and ADHD children based on the traditional plate method and 16S rRNA amplicon sequence analysis. The antibacterial effect of ZnONPs against gut bacteria was also determined by measurement of live cell number, living/dead bacterial staining test, and flow cytometry observation. The present study revealed that the number of live gut bacteria in healthy children was more than 10-fold higher than that in ADHD children; however, the community structure of gut bacteria has changed, while greater diversity was found in gut bacteria from ADHD children. In addition, we found that the number of live gut bacteria in healthy and ADHD children was reduced by ZnONPs, which shows an increased and reduced effect in composition of gut bacteria from healthy and ADHD children, respectively. It was also noted that the main mechanism of ZnONPs may be to inhibit the growth of gut bacteria rather than to kill them, while the nanoparticle-resistant strains in healthy children is also different from that in ADHD children. Some representative bacteria, in particular nanoparticle-resistant bacteria, were successfully isolated and identified. Overall, this study revealed the potential correlation of ADHD with gut bacteria and provided a new possibility to prevent ADHD by the combination of nanoparticle and its resistant bacteria.

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP’s). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer’s disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson’s disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of −6.9 kcal/mol forming interactions with binding pocket’s critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M−1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Lettuce is one of the most famous leafy vegetables worldwide with lots of applications from food to other specific uses. There are different types in the lettuce group for consumers to choose from. Additionally, lettuce is an excellent source of bioactive compounds such as polyphenols, carotenoids, and chlorophyll with related health benefits. At the same time, nutrient composition and antioxidant compounds are different between lettuce varieties, especially for green and red lettuce types. The benefit of lettuce consumption depends on its composition, particularly antioxidants, which can function as nutrients. The health benefits rely on their biochemical effect when reaching the bloodstream. Some components can be released from the food matrix and altered in the digestive system. Indeed, the bioaccessibility of lettuce is measuring the quantity of these compounds released from the food matrix during digestion, which is important for health-promoting features. Extraction of bioactive compounds is one of the new trends observed in lettuce and is necessarily used for several application fields. Therefore, this review aims to demonstrate the nutritional value of lettuce and its pharmacological properties. Due to their bioaccessibility and bioavailability, the consumer will be able to comprehensively understand choosing a healthier lettuce diet. The common utilization pattern of lettuce extracted nutrients will also be summarized for further direction.

Tyrosine-protein kinase Yes (YES1) belongs to the Tyrosine-protein kinase family and is involved in several biological activities, including cell survival, cell–cell adhesion, cell differentiation, and cytoskeleton remodeling. It is highly expressed in esophageal, lung, and bladder cancers, and thus considered as an attractive drug target for cancer therapy. In this study, we performed a virtual screening of phytoconstituents from the IMPPAT database to identify potential inhibitors of YES1. Initially, the molecules were retrieved on their physicochemical properties following the Lipinski rule of five. Then binding affinities calculation, PAINS filter, ADMET, and PASS analyses followed by an interaction analysis to select safe and clinically better hits. Finally, two compounds, Glabrene and Lupinisoflavone C (LIC), with appreciable affinities and a specific interaction towards the AlphaFold predicted structure of YES1, were identified. Their time-evolution analyses were carried out using an all-atom molecular dynamics (MD) simulation, principal component analysis, and free energy landscapes. Altogether, we propose that Glabrene and LIC can be further explored in clinical settings to develop anticancer therapeutics targeting YES1 kinase.

Micromeria biflora, a traditional medicinal plant, is extensively used for treating various painful conditions, such as nose bleeds, wounds, and sinusitis. A phytochemical investigation of the chloroform fraction of Micromeria biflora led to the isolation of salicylalazine. Salicylalazine was assessed in vivo for analgesia, muscle relaxation, sedative, and anti-inflammatory properties, as well as in vitro for COX-1/2 inhibition activities. It was assessed against a hot plate-induced model at different doses. The muscle relaxant potential of salicylalazine was evaluated in traction and inclined screening models, while sedative properties were determined using an open-field model. The anti-inflammatory potential of salicylalazine was assessed in histamine and carrageenan-induced paw edema screening models. Salicylalazine exhibited significant analgesic potential in a dose-dependent manner. In both screening models, an excellent time-dependent muscle-relaxation effect was observed. Salicylalazine demonstrated excellent sedation at high doses. Its anti-inflammatory activity was determined through the initial and late phases of edema. It exhibited anticancer potential against NCI-H226, HepG2, A498, and MDR2780AD cell lines. In vitro, salicylalazine showed preferential COX-2 inhibition (over COX-1) with an SI value of 4.85. It was less effective in the initial phase, while, in the later phase, it demonstrated significant effects at 15 and 20 mg/kg doses compared with the negative control. Salicylalazine did not exhibit cytotoxicity in the MTT assay, preliminarily indicating its safety.

Alzheimer's disease (AD) is the commonest neurodegenerative disorder with a wide array of manifestations, courses, and contributing causes. Despite being clinically characterized a long time ago; no treatment has been developed that could improve the pathology or slow down the disease manifestation- so far. Indian Catechu methanolic extract (ICME) has proved to have multiple beneficial effects that support its use in several disorders- especially those with complex etiology. In the present study, we evaluated the neuroprotective effect of ICME in a rat model of AD using Aluminum Chloride (AlCl3). The results showed that ICME could have a positive impact on the course of AD through its anticholinesterase effect and significant antioxidant effect which was reflected on the animals both on behavioral tests as well as hallmark pathological findings.

Pineapple peel (PP) is a by-product with the potential to be used as a raw material for functional beverages. Traditional PP fermentation has so far paid little attention to the microbial community and its role in the fermentation process. As a result, the current research looked into the microbial communities and their roles during PP fermentation. A metagenomic approach based on the 16S rRNA sequencing data was used to assess the microbial communities. Subsequent analysis was performed using PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) to analyze the microbial functions in the fermentation system. The microecology of the fermentation process in three samples was predominated by Firmicutes. Furthermore, the well-known probiotic genera Weissella, Lactobacillus, and Lactococcus were found to be predominating in the gumer, promic, and control samples, respectively. It was obvious that microenvironmental differences have an effect on the microbial composition of PP fermentation. Moreover, functional prediction revealed that carbohydrate metabolism was the most prevalent metabolic pathway during the fermentation process. Additionally, it was discovered that all of the bacteria found in the samples played significant roles in carbohydrate, amino acid, vitamin, and co-factor metabolism, which can be inferred to result in the production of beneficial metabolites.