Medicinal Herbs: Promising Immunomodulators for the Treatment of Infectious Diseases.

Humans are constantly at high risk of emerging pandemics caused by viral and bacterial infections. The emergence of new pandemics is mainly caused by evolved viruses and bacteria that are highly resistant to existing medications. The rapid evolution of infectious agents demands the urgent investigation of new therapeutic strategies to prevent and treat these infections at an early stage. One of these therapeutic strategies includes the use of medicinal herbs for their antibacterial and antiviral properties. The use of herbal medicines as remedies is very ancient and has been employed for centuries. Many studies have confirmed the antimicrobial activities of herbs against various pathogens in vitro and in vivo. The therapeutic effect of medicinal herbs is mainly attributed to the natural bioactive molecules present in these plants such as alkaloids, flavonoids, and terpenoids. Different mechanisms have been proposed for how medicinal herbs enhance the immune system and combat pathogens. Such mechanisms include the disruption of bacterial cell membranes, suppression of protein synthesis, and limitation of pathogen replication through the inhibition of nucleic acid synthesis. Medicinal herbs have been shown to treat a number of infectious diseases by modulating the immune system's components. For instance, many medicinal herbs alleviate inflammation by reducing pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha (TNF-α), interleukin-1, IL-6) while promoting the production of anti-inflammatory cytokines (e.g., IL-10). Medicinal herbs also play a role in defense against viral and intracellular infections by enhancing the proliferation and functions of natural killer cells, T-helper-1 cells, and macrophages. In this review, we will explore the use of the most common herbs in preventing and treating infectious and non-infectious diseases. Using current and recently published studies, we focus on the immunomodulatory and therapeutic effects induced by medicinal herbs to enhance immune responses during diseases.

Structure-Guided Approach to Discover Tuberosin as a Potent Activator of Pyruvate Kinase M2, Targeting Cancer Therapy.

Metabolic reprogramming is a key attribute of cancer progression. An altered expression of pyruvate kinase M2 (PKM2), a phosphotyrosine-binding protein is observed in many human cancers. PKM2 plays a vital role in metabolic reprogramming, transcription and cell cycle progression and thus is deliberated as an attractive target in anticancer drug development. The expression of PKM2 is essential for aerobic glycolysis and cell proliferation, especially in cancer cells, facilitating selective targeting of PKM2 in cell metabolism for cancer therapeutics. We have screened a virtual library of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) database of Indian medicinal plants to identify potential activators of PKM2. The initial screening was carried out for the physicochemical properties of the compounds, and then structure-based molecular docking was performed to select compounds based on their binding affinity towards PKM2. Subsequently, the ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, PAINS (Pan-assay interference compounds) patterns, and PASS evaluation were carried out to find more potent hits against PKM2. Here, Tuberosin was identified from the screening process bearing appreciable binding affinity toward the PKM2-binding pocket and showed a worthy set of drug-like properties. Finally, molecular dynamics simulation for 100 ns was performed, which showed decent stability of the protein-ligand complex and relatival conformational dynamics throughout the trajectory. The study suggests that modulating PKM2 with natural compounds is an attractive approach in treating human malignancy after required validation.

Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways.

Plant bioactive compounds, particularly apigenin, have therapeutic potential and functional activities that aid in the prevention of infectious diseases in many mammalian bodies and promote tumor growth inhibition. Apigenin is a flavonoid with low toxicities and numerous bioactive properties due to which it has been considered as a traditional medicine for decades. Apigenin shows synergistic effects in combined treatment with sorafenib in the HepG2 human cell line (HCC) in less time and statistically reduces the viability of tumor cells, migration, gene expression and apoptosis. The combination of anti-cancerous drugs with apigenin has shown health promoting potential against various cancers. It can prevent cell mobility, maintain the cell cycle and stimulate the immune system. Apigenin also suppresses mTOR activity and raises the UVB-induced phagocytosis and reduces the cancerous cell proliferation and growth. It also has a high safety threshold, and active (anti-cancer) doses can be gained by consuming a vegetable and apigenin rich diet. Apigenin also boosted autophagosome formation, decreased cell proliferation and activated autophagy by preventing the activity of the PI3K pathway, specifically in HepG2 cells. This paper provides an updated overview of apigenin's beneficial anti-inflammatory, antibacterial, antiviral, and anticancer effects, making it a step in the right direction for therapeutics. This study also critically analyzed the effect of apigenin on cancer cell signaling pathways including the PI3K/AKT/MTOR, JAK/STAT, NF-κB and ERK/MAPK pathways.

Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases.

Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.

Human papillomavirus: present and future perspective in Saudi Arabia.

Human papillomavirus (HPV) is a widely dispersed DNA double-stranded carcinogenic virus worldwide. Many cancers have been attributed to HPV subtypes as a major aetiological factor. Around 90% of cervical cancers have been attributed to the HPV infection, in addition to other cancers such as head and neck cancer, breast cancer and other cancers. As the carcinogenic high risk and low-risk, HPV subtypes are sexually transmitted viruses, and the Saudi community is religiously conservative, lots of measures of the precise burden of the HPV and its related cancers are still obscure. With the absence of cervical-screening programmes and in-depth research in HPV-related cancers, there a lack of literature except for literature pertained to awareness and perceptions. Consequently, the present review is deemed to explore the present state of the HPV-related issues, the future perspective in light of the current scientific evidence, as well as, Saudi community practices, and health policies in this regard. Making accessible data on HPV-related cancers can assist in designing HPV-related early detection and control sustainable programmes. Therefore, this review aimed to discuss the most important magnitudes related to the HPV, concerning the available literature from Saudi Arabia and the data in the neighbouring Arab countries interrelated to Saudi Arabia. The review depended on searching Electronic databases using strongly considered indexes including PubMed, Medline, Web of Science, Scopus, ABSCO, EMBASE, and others. In conclusion, though Saudi Arabia is pronounced as a conservative community with low sexual transmitted diseases, there is an alarming menace of HPV-attributable diseases necessitating a quick intervention.

Screening for PIK3CA mutations among Saudi women with ovarian cancer.

The study aimed to screen for PIK3CA gene mutations among Saudi women with Ovarian Cancer. The study included 298 Saudi women with epithelial ovarian cancers (EOC). DNA sequence analysis was employed to screen for the mutations. DNA sequence analysis of a coding region of exon 9 and 20 of PIK3CA gene revealed mutations in 37/298 (12.4%) EOC patients. About 21/37(56.8%) somatic mutations were identified in exons 9, and 16/37(43.2%) in exon 20. All analysed mutations were missense mutations, the frequencies of which varied from 2.7% to 43.2%. PIK3CA mutation was found to be significantly associated with age (p = .023), grade (p = .001) and histological types (p = .032). Only 6.6% of serous carcinomas and 3.8% of endometrioid had PIK3CA mutation. The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.Impact statementWhat is already known on this subject? The detailed molecular and genetic phenomenon underlying the progression of these tumours is still unclear. Recently, the pathogenesis of ovarian cancer has been attributed to mutations of PIK3CA.What do the results of this study add? Mutation in the PIK3CA gene leads to altered PI3K/AKT signalling pathways responsible for the progression of the epithelial ovarian cancer.What are the implications of these findings for clinical practice and/or further research? The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.

Discovering Promising Biomarkers and Therapeutic Targets for Duchenne Muscular Dystrophy: a Multiomics Meta-Analysis Approach.

Duchenne muscular dystrophy (DMD) is a genetic disorder that causes muscle weakness and degeneration. In this study, we identified potential biomarkers and drug targets for DMD through a comprehensive meta-analysis of mRNA profiles. We conducted an in-depth analysis of three microarray datasets from the GEO database, utilizing the Affymetrix platform. A rigorous data pre-processing pipeline encompassed background correction, normalization, log2 transformation and probe-to-gene symbol mapping. Robust multi-array average method followed by Limma package in R was employed to ensure differential expression analysis within individual datasets, yielding gene-specific p-values. We identified 63 genes exhibiting statistically significant differential expression across the three datasets (p < 0.05) and an absolute log fold change > 1.5. Functional enrichment analyses of these differentially expressed genes were done, followed by pathway analyses. Our results suggested pertinent biological processes, molecular functions and cellular components associated with DMD. Finally, eight hub genes-COL6A3, COL1A1, COL3A1, COL1A2, POSTN, TIMP1, THBS2 and SPP1-were pinpointed as central players in the network. Two differentially expressed genes with substantial absolute log-fold changes, namely, DMD, downregulated and MYH3, upregulated, were identified as potential therapeutic candidates. In light of these findings, our work contributes not only to understanding DMD at the molecular level but also presents potential targets for therapeutic strategies. Finally, our study facilitates the development of therapeutic interventions that can effectively control and mitigate the impact of DMD.

A review on mechanistic insights into structure and function of dystrophin protein in pathophysiology and therapeutic targeting of Duchenne muscular dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive and severe muscle weakening and degeneration. Among the various forms of muscular dystrophy, it stands out as one of the most common and impactful, predominantly affecting boys. The condition arises due to mutations in the dystrophin gene, a key player in maintaining the structure and function of muscle fibers. The manuscript explores the structural features of dystrophin protein and their pivotal roles in DMD. We present an in-depth analysis of promising therapeutic approaches targeting dystrophin and their implications for the therapeutic management of DMD. Several therapies aiming to restore dystrophin protein or address secondary pathology have obtained regulatory approval, and many others are ongoing clinical development. Notably, recent advancements in genetic approaches have demonstrated the potential to restore partially functional dystrophin forms. The review also provides a comprehensive overview of the status of clinical trials for major therapeutic genetic approaches for DMD. In addition, we have summarized the ongoing therapeutic approaches and advanced mechanisms of action for dystrophin restoration and the challenges associated with DMD therapeutics.

Pharmacological features, health benefits and clinical implications of honokiol.

Honokiol (HNK) is a natural polyphenolic compound extracted from the bark and leaves of Magnolia grandiflora. It has been traditionally used as a medicinal compound to treat inflammatory diseases. HNK possesses numerous health benefits with a minimal level of toxicity. It can cross the blood-brain barrier and blood-cerebrospinal fluid, thus having significant bioavailability in the neurological tissues. HNK is a promising bioactive compound possesses neuroprotective, antimicrobial, anti-tumorigenic, anti-spasmodic, antidepressant, analgesic, and antithrombotic features . HNK can prevent the growth of several cancer types and haematological malignancies. Recent studies suggested its role in COVID-19 therapy. It binds effectively with several molecular targets, including apoptotic factors, chemokines, transcription factors, cell surface adhesion molecules, and kinases. HNK has excellent pharmacological features and a wide range of chemotherapeutic effects, and thus, researchers have increased interest in improving the therapeutic implications of HNK to the clinic as a novel agent. This review focused on the therapeutic implications of HNK, highlighting clinical and pharmacological features and the underlying mechanism of action.Communicated by Ramaswamy H. Sarma.

Antioxidative and ROS-dependent apoptotic effects of Cuscuta reflexa Roxb. stem against human lung cancer: network pharmacology and in vitro experimental validation.

Lung cancer remains a formidable global health challenge, necessitating the exploration of novel therapeutic approaches. This study investigates the potential of Cuscuta reflexa Roxb. stem extract as an anticancer agent against human lung cancer, focusing on its antioxidative and ROS-dependent apoptotic effects. Utilizing a combination of network pharmacology and in-vitro experimental validation, we delineate the multifaceted molecular mechanisms underlying the observed effects. The antioxidant potential of C. reflexa stem extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS•+) and ferric reducing/antioxidant power (FRAP), hydroxyl free radical scavenging, reactive nitrogen oxide scavenging and super oxide anion radical scavenging assays. Furthermore, the antiproliferative and proapoptotic effect of C. reflexa stem extract was evaluated against A549 lung adenocarcinoma cell line using the consecrated sulforhodamine B (SBR) and Annexin V-PI assays. Additionally, the mitochondrial membrane potential (MMP) and the total reactive oxygen species (ROS) estimation assays were performed. As a result, network pharmacology analysis revealed a complex interaction network between the bioactive constituents of C. reflexa and key proteins implicated in lung cancer progression. The C. reflexa stem extract showed dose-dependent antioxidant activity against DPPH• (IC50 - 87.38 µg/mL), reactive nitrogen oxide (IC50 - 318.34 µg/mL), FRAP (IC50 - 359.96 µg/mL), hydroxy free radicals (IC50 - 526.12 µg/mL) than ABTS●+ (IC50 - 698.45 µg/mL) and super oxide anion (IC50 - 892.71 µg/mL) as well as cytotoxic activity against A549 cells (IC50 - 436.80 µg/mL). Observations of morphological features in treated cells have revealed hallmark of apoptosis properties. Furthermore, as a result of treatment with C. reflexa stem extract, ROS generation and mitochondrial depolarization were increased in A549 cells, suggesting that this treatment has significant apoptotic properties. . These findings highlight the potential utility of this natural extract as an innovative therapeutic strategy for lung cancer treatment. The integration of network pharmacology and experimental validation enhances our understanding of the underlying mechanisms and provide the way for further translational research.Communicated by Ramaswamy H. Sarma.

Identification of novel c-Kit inhibitors from natural sources using virtual screening and molecular dynamics simulations.

The Mast/Stem cell growth factor receptor Kit (c-Kit), a Proto-oncogene c-Kit, is a tyrosine-protein kinase involved in cell differentiation, proliferation, migration, and survival. Its role in developing certain cancers, particularly gastrointestinal stromal tumors (GISTs) and acute myeloid leukemia (AML), makes it an attractive therapeutic target. Several small molecule inhibitors targeting c-Kit have been developed and approved for clinical use. Recent studies have focused on identifying and optimizing natural compounds as c-Kit inhibitors employing virtual screening. Still, drug resistance, off-target side effects, and variability in patient response remain significant challenges. From this perspective, phytochemicals could be an important resource for discovering novel c-Kit inhibitors with less toxicity, improved efficacy, and high specificity. This study aimed to uncover possible c-Kit inhibitors by utilizing a structure-based virtual screening of active phytoconstituents from Indian medicinal plants. Through the screening stages, two promising candidates, Anilinonaphthalene and Licoflavonol, were chosen based on their drug-like features and ability to bind to c-Kit. These chosen candidates were subjected to all-atom molecular dynamics (MD) simulations to evaluate their stability and interaction with c-Kit. The selected compounds Anilinonaphthalene from Daucus carota and Licoflavonol from Glycyrrhiza glabra showed their potential to act as selective binding partners of c-Kit. Our results suggest that the identified phytoconstituents could serve as a starting point to develop novel c-Kit inhibitors for developing new and effective therapies against multiple cancers, including GISTs and AML. The use of virtual screening and MD simulations provides a rational approach to discovering potential drug candidates from natural sources.Communicated by Ramaswamy H. Sarma.

Desmodin and isopongachromene as potential inhibitors of cyclin-dependent kinase 5: phytoconstituents targeting anticancer and neurological therapy.

Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine-threonine protein kinase vital for neuronal cell cycle arrest and differentiation. It activates by binding with p35 and p39 and is important for the functioning of the nervous system. A growing body of evidence suggests that CDK5 contributes to the onset and progression of neurodegeneration and tumorigenesis and represents itself as a potential therapeutic target. Our research illustrates virtual screening of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) library to search for potential inhibitors of CDK5. Initially, the compounds from the parent library were filtered out via their physicochemical properties following the Lipinski rule of five. Then sequentially, molecular docking-based virtual screening, PAINS filter, ADMET, PASS analysis, and molecular dynamics (MD) simulation were done using various computational tools to rule out adversities that can cause hindrances in the identification of potential inhibitors of CDK5. Finally, two compounds were selected via the extensive screening showing significant binding with CDK5 ATP-binding pocket and ultimately were selected as potent ATP-competitive inhibitors of CDK5. Finally, we propose that the elucidated compounds Desmodin and Isopongachromene can be used further in the drug discovery process and act as therapeutics in the medical industry to treat certain complex diseases, including cancer and neurodegeneration.Communicated by Ramaswamy H. Sarma.

Targeting inhibition of microtubule affinity regulating kinase 4 by Harmaline: Strategy to combat Alzheimer's disease.

Microtubule-affinity regulating kinase 4 (MARK4) is linked with the development of cancer, diabetes and neurodegenerative diseases. Due to its direct role in the hyperphosphorylation of tau protein, MARK4 is considered as an attractive target to fight Alzheimer's disease (AD) and neuroinflammation. In the present study, we have selected Harmaline (HAR), an alkaloid of Paganum harmala, to investigate its MARK4 inhibitory potential and its binding mechanism. Molecular docking and fluorescence binding studies were carried out to estimate the binding affinity of the HAR with the MARK4. We observed an excellent binding affinity of HAR to the MARK4 (K = 107 M-1), further complemented by isothermal titration calorimetric measurements. In addition, HAR significantly inhibits the kinase activity of MARK4 (IC50 value of 4.46 µM). Structural investigations suggested that HAR binds to the active site pocket and forms several non-covalent interactions with biologically important residues of MARK4. All-atom molecular dynamics simulation studies further advocated that the MARK4-HAR complex is stabilized throughout the trajectory of 200 ns and causes a little conformational change. All these findings suggest that HAR is a potential MARK4 inhibitor that can be implicated in managing MARK4-associated diseases, including AD.

A virtual screening investigation to identify bioactive natural compounds as potential inhibitors of cyclin-dependent kinase 9.

Cyclin-dependent kinase 9 (CDK9) is a transcription-associated protein involved in controlling the cell cycle and is often deregulated in stress conditions. CDK9 is being studied as a well-known druggable target for developing effective therapeutics against a wide range of cancer, cardiac dysfunction and inflammatory diseases. Owing to the significance of CDK9 in the etiology of hematological and solid malignancies, its structure, biological activity, regulation and its pharmacological inhibition are being explored for therapeutic management of cancer. We employed a structure-based virtual high-throughput screening of bioactive compounds from the IMPPAT database to discover potential bioactive inhibitors of CDK9. The preliminary results were obtained from the Lipinski criteria, ADMET parameters and sorting compounds without any PAINS patterns. Subsequently, binding affinity and selectivity analyses were used to find effective CDK9 hits. This screening resulted in the identification of two natural compounds, Glabrene and Guggulsterone with high affinity and specificity for the CDK9 binding site. Both compounds exhibit drug-like characteristics, as projected by ADMET analysis, physicochemical data and PASS evaluation. Both compounds preferentially bind to the ATP-binding pocket of CDK9 and interact with functionally important residues. Further, the dynamics and consistency of CDK9 interaction with Glabrene and Guggulsteron were evaluated through all-atom molecular dynamic (MD) simulations which suggested the stability of both complexes. The results might be deployed to introduce novel CDK9 inhibitors that may treat life-threatening diseases, including cancer.Communicated by Ramaswamy H. Sarma.

Discovering Gummadiol and Isoarboreol as potential inhibitors of sphingosine kinase 1: virtual screening and MD simulation studies.

Sphingosine kinase 1 (SphK1) dysfunction is well-known to be linked to various severe diseases, including breast, lung, prostate, and hematological cancers. Due to its crucial function in the onset of cancer and its progression, it is considered a notable drug target for anticancer therapy. Small molecule inhibitors with high specificity and efficacy towards SphK1 are needed for their therapeutic use. In order to find possible SphK1 inhibitors, we conducted a stepwise structure-based virtual screening of plant-based molecules available from the IMPPAT library. A multi-step virtual screening, including physicochemical and ADMET evaluation, PAINS, molecular docking, PASS analysis followed by molecular dynamics (MD) simulation and principal component analysis, identifies two compounds, Gummadiol and Isoarboreol, against SphK1. All-atom MD simulations were performed for 100 ns which examined the structural changes and stability of the docked complexes in the aqueous environment. The time evolution data of structural deviations and compactness, PCA and free energy landscapes suggested that the binding of Gummadiol and Isoarboreol with SphK1 is considerably stable throughout the trajectory. The study highlighted the use of phytochemicals in anticancer therapeutics and presented Gummadiol and Isoarboreol as promising inhibitors of SphK1.Communicated by Ramaswamy H. Sarma.

Integrating network pharmacology approaches for the investigation of multi-target pharmacological mechanism of 6-shogaol against cervical cancer.

Traditional treatment of cancer has been plagued by a number of obstacles, such as multiple drug resistance, toxicity and financial constraints. In contrast, phytochemicals that modulate a variety of molecular mechanisms are garnering increasing interest in complementary and alternative medicine. Therefore, an approach based on network pharmacology was used in the present study to explore possible regulatory mechanisms of 6-shogaol as a potential treatment for cervical cancer (CC). A number of public databases were screened to collect information on the target genes of 6-shogaol (SuperPred, Targetnet, Swiss target prediction and PharmMapper), while targets pertaining to CC were taken from disease databases (DisGeNet and Genecards) and gene expression omnibus (GEO) provided expression datasets. With STRING and Cytoscape, protein-protein interactions (PPI) were generated and topology analysis along with CytoNCA were used to identify the Hub genes. The Gene Ontology (GO) database Enrichr was used to annotate the target proteins, while, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, signaling pathway enrichment analysis was conducted. Molecular docking and survival analysis for the Hub genes revealed four genes (HSP90AA1, HRAS, ESR1 and EGFR) with lowest binding energy and majority of the Hub genes (EGFR, SRC, CASP-3, HSP90AA1, MTOR, MAPK-1, MDM2 and ESR1) were linked with the overall survival of CC patients. In conclusion, the present study provides the scientific evidence which strongly supports the use of 6-shogoal as an inhibitor of cellular proliferation, growth, migration as well as inducer of apoptosis via targeting the hub genes involved in the growth of CC.Communicated by Ramaswamy H. Sarma.

Identifying Isoononin and Candidissiol as Rho-associated protein kinase 1 (ROCK1) inhibitors: a combined virtual screening and MD simulation approach.

Rho-associated protein kinase 1 (ROCK1) is a member of the AGC family which plays crucial roles in inflammatory diseases and cancer progression. Elevated expression of ROCK1 has been reported in multiple cancer types, and thus it has emerged as a potential drug target for cancer therapeutics. In this study, we performed a structure-based virtual screening of the natural compounds taken from the IMPPAT database to find some potential molecules as inhibitors of ROCK1. For the first step, we selected the compounds based on the Lipinski rule of five, and then we filtered them based on their ADMET properties and PAINS value. After this, other parameters like binding affinities, docking score, biological properties and selectivity were calculated to find appropriate hits against ROCK1. Finally, we identified two natural compounds, Isoononin and Candidissiol, with appreciable binding affinity and selectivity towards ROCK1. Furthermore, all-atom molecular dynamics simulations were carried out on ROCK1 with the elucidated compounds, which suggested stability throughout the simulated trajectories of 100 ns. Taken together, Isoononin and Candidissiol could be considered as potential inhibitors of ROCK1 for developing anticancer therapeutics.Communicated by Ramaswamy H. Sarma.

Practice, Knowledge, and Awareness of the Diverse Effects of Diagnostic Radiology among Radiology Staff and Students in Saudi Arabia.

BACKGROUND: Diagnostic radiology has been linked to several health consequences. Thus, the present study aimed to assess the practice, knowledge, and awareness of the diverse effects of diagnostic radiology among radiology staff and students in Saudi Arabia. METHODOLOGY: In this study, 107 participants were recruited from August to December 2020. The study included 56 radiology personnel (staff from Hail City Hospitals) and 51 radiology medical students (students from the University of Ha'il). RESULTS: To the question, "Have you ever been informed of radiation and its effects?" about 6/107 (5.6 %) answered "No," among which 5/6 (83.3 %) were the staff. In response to the question, "In your opinion, how hazardous is radiation to your body?" about 8/104 (7.7 %) indicated it as nonhazardous (3 were staff and 5 were students). To the question, "Do you believe that radiation in medical sites is harmful?" about 20/104 (19.2 %) answered, "No" (8 were staff and 12 were students). CONCLUSION: There is a lack of awareness, knowledge, and practice towards ionizing radiation protection measures among radiology medical students and radiology department staff in Northern Saudi Arabia. The paper notifies the health system advisors to include stressing guidelines regarding radiation hazards. More actions are deemed necessary for the safety of patients and radiation workers.

Naringenin as a potential inhibitor of human cyclin-dependent kinase 6: Molecular and structural insights into anti-cancer therapeutics.

Cancer is one of the major causes of global deaths and needs immediate therapeutic development. So far, several strategies have been undertaken to prevent cancer, including kinase targeting by small-molecule inhibitors. Cyclin dependent kinase 6 (CDK6) plays an essential role in cancer progression and development as its overexpression is associated with tumor development and progression. The present study demonstrated that Naringenin (NAG) binds strongly to CDK6 with a binding affinity of -7.51 kcal/mol. ATPase assay of CDK6 in the presence of NAG shows that it inhibits CDK6 with an IC50 = 3.13 µM. Fluorescence and isothermal titration calorimetry studies demonstrated that NAG binds to CDK6 with the binding constant (K) values of 3.55 × 106 M-1 and 7.06 ± 2.70 × 106 M-1, respectively. The cell-based functional studies showed that NAG decreases the cell viability of human cancer cell lines, induces apoptosis, and reduces their colonization ability. Outcomes of the present in silico and in vitro studies highlighted the significance of NAG for the development of anti-cancer leads in terms of CDK6 inhibitors and provided future implications for combinatorial anti-cancer therapies.

Probiotic Yeast Saccharomyces: Back to Nature to Improve Human Health.

Saccharomyces cerevisiae var. boulardii is best known for its treatment efficacy against different gastrointestinal diseases. This probiotic yeast can significantly protect the normal microbiota of the human gut and inhibit the pathogenicity of different diarrheal infections. Several clinical investigations have declared S. cerevisiae var. boulardii a biotherapeutic agent due to its antibacterial, antiviral, anti-carcinogenic, antioxidant, anti-inflammatory and immune-modulatory properties. Oral or intramuscular administration of S. cerevisiae var. boulardii can remarkably induce health-promoting effects in the host body. Different intrinsic and extrinsic factors are responsible for its efficacy against acute and chronic gut-associated diseases. This review will discuss the clinical and beneficial effects of S. cerevisiae var. boulardii in the treatment and prevention of different metabolic diseases and highlight some of its health-promising properties. This review article will provide fundamental insights for new avenues in the fields of biotherapeutics, antimicrobial resistance and one health.