Unlocking the Potential of Silver Nanoparticles: From Synthesis to Versatile Bio-Applications.

Silver nanoparticles (AgNPs) are leading the way in nanotechnological innovation, combining the captivating properties of silver with the accuracy of nanoscale engineering, thus revolutionizing material science. Three main techniques arise within the alchemical domains of AgNP genesis: chemical, physical, and biological synthesis. Each possesses its distinct form of magic for controlling size, shape, and scalability-key factors necessary for achieving expertise in the practical application of nanoparticles. The story unravels, describing the careful coordination of chemical reduction, the environmentally sensitive charm of green synthesis utilizing plant extracts, and the precise accuracy of physical techniques. AgNPs are highly praised in the field of healthcare for their powerful antibacterial characteristics. These little warriors display a wide-ranging attack against bacteria, fungi, parasites, and viruses. Their critical significance in combating hospital-acquired and surgical site infections is highly praised, serving as a beacon of hope in the fight against the challenging problem of antibiotic resistance. In addition to their ability to kill bacteria, AgNPs are also known to promote tissue regeneration and facilitate wound healing. The field of cancer has also observed the adaptability of AgNPs. The review documents their role as innovative carriers of drugs, specifically designed to target cancer cells with accuracy, minimizing harm to healthy tissues. Additionally, it explores their potential as cancer therapy or anticancer agents capable of disrupting the growth of tumors. In the food business, AgNPs are utilized to enhance the durability of packing materials and coatings by infusing them with their bactericidal properties. This results in improved food safety measures and a significant increase in the duration that products can be stored, thereby tackling the crucial issue of food preservation. This academic analysis recognizes the many difficulties that come with the creation and incorporation of AgNPs. This statement pertains to the evaluation of environmental factors and the effort to enhance synthetic processes. The review predicts future academic pursuits, envisioning progress that will enhance the usefulness of AgNPs and increase their importance from being new to becoming essential within the realms of science and industry. Besides, AgNPs are not only a subject of scholarly interest but also a crucial component in the continuous effort to tackle some of the most urgent health and conservation concerns of contemporary society. This review aims to explore the complex process of AgNP synthesis and highlight their numerous uses, with a special focus on their growing importance in the healthcare and food business sectors. This review invites the scientific community to explore the extensive possibilities of AgNPs in order to fully understand and utilize their potential.

Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment.

Apigenin is a powerful flavone compound found in numerous fruits and vegetables, and it offers numerous health-promoting benefits. Many studies have evidenced that this compound has a potential role as an anti-inflammatory and antioxidant compound, making it a promising candidate for reducing the risk of pathogenesis. It has also been found to positively affect various systems in the body, such as the respiratory, digestive, immune, and reproductive systems. Apigenin is effective in treating liver, lung, heart, kidney, neurological diseases, diabetes, and maintaining good oral and skin health. Multiple studies have reported that this compound is capable of suppressing various types of cancer through the induction of apoptosis and cell-cycle arrest, suppressing cell migration and invasion, reduction of inflammation, and inhibiting angiogenesis. When used in combination with other drugs, apigenin increases their efficacy, reduces the risk of side effects, and improves the response to chemotherapy. This review broadly analyzes apigenin's potential in disease management by modulating various biological activities. In addition, this review also described apigenin's interaction with other compounds or drugs and the potential role of nanoformulation in different pathogeneses. Further extensive research is needed to explore the mechanism of action, safety, and efficacy of this compound in disease prevention and treatment.

Pharmacological Potential of Kaempferol, a Flavonoid in the Management of Pathogenesis via Modulation of Inflammation and Other Biological Activities.

Natural products and their bioactive compounds have been used for centuries to prevent and treat numerous diseases. Kaempferol, a flavonoid found in vegetables, fruits, and spices, is recognized for its various beneficial properties, including its antioxidant and anti-inflammatory potential. This molecule has been identified as a potential means of managing different pathogenesis due to its capability to manage various biological activities. Moreover, this compound has a wide range of health-promoting benefits, such as cardioprotective, neuroprotective, hepatoprotective, and anti-diabetic, and has a role in maintaining eye, skin, and respiratory system health. Furthermore, it can also inhibit tumor growth and modulate various cell-signaling pathways. In vivo and in vitro studies have demonstrated that this compound has been shown to increase efficacy when combined with other natural products or drugs. In addition, kaempferol-based nano-formulations are more effective than kaempferol treatment alone. This review aims to provide detailed information about the sources of this compound, its bioavailability, and its role in various pathogenesis. Although there is promising evidence for its ability to manage diseases, it is crucial to conduct further investigations to know its toxicity, safety aspects, and mechanism of action in health management.

Effects and Mechanisms of Luteolin, a Plant-Based Flavonoid, in the Prevention of Cancers via Modulation of Inflammation and Cell Signaling Molecules.

Luteolin, a flavonoid, is mainly found in various vegetables and fruits, including carrots, cabbages, onions, parsley, apples, broccoli, and peppers. Extensive research in vivo and in vitro has been performed to explore its role in disease prevention and treatment. Moreover, this compound possesses the ability to combat cancer by modulating cell-signaling pathways across various types of cancer. The studies have confirmed that luteolin can inhibit cancer-cell survival and proliferation, angiogenesis, invasion, metastasis, mTOR/PI3K/Akt, STAT3, Wnt/ß-catenin, and cell-cycle arrest, and induce apoptosis. Further, scientific evidence describes that this compound plays a vital role in the up/down-regulation of microRNAs (miRNAs) in cancer therapy. This review aims to outline the anti-cancer mechanisms of this compound and its molecular targets. However, a knowledge gap remains regarding the studies on its safety and efficacy and clinical trials. Therefore, it is essential to conduct more research based on safety, efficacy, and clinical trials to explore the beneficial role of this compound in disease management, including cancer.

Structural insights into the mechanism of resistance to bicalutamide by the clinical mutations in androgen receptor in chemo-treatment resistant prostate cancer.

Despite advanced diagnosis and detection technologies, prostate cancer (PCa) is the most prevalent neoplasms in males. Dysregulation of the androgen receptor (AR) is centrally involved in the tumorigenesis of PCa cells. Acquisition of drug resistance due to modifications in AR leads to therapeutic failure and relapse in PCa. An overhaul of comprehensive catalogues of cancer-causing mutations and their juxta positioning on 3D protein can help in guiding the exploration of small drug molecules. Among several well-studied PCa-specific mutations, T877A, T877S and H874Y are the most common substitutions in the ligand-binding domain (LBD) of the AR. In this study, we combined structure as well as dynamics-based in silico approaches to infer the mechanistic effect of amino acid substitutions on the structural stability of LBD. Molecular dynamics simulations allowed us to unveil a possible drug resistance mechanism that acts through structural alteration and changes in the molecular motions of LBD. Our findings suggest that the resistance to bicalutamide is partially due to increased flexibility in the H12 helix, which disturbs the compactness, thereby reducing the affinity for bicalutamide. In conclusion, the current study helps in understanding the structural changes caused by mutations and could assist in the drug development process.Communicated by Ramaswamy H. Sarma.

Integrated virtual screening and molecular dynamics simulation approaches revealed potential natural inhibitors for DNMT1 as therapeutic solution for triple negative breast cancer.

Triple negative breast cancers (TNBC) are clinically heterogeneous but mostly aggressive malignancies devoid of expression of the estrogen, progesterone, and HER2 (ERBB2 or NEU) receptors. It accounts for 15-20% of all cases. Altered epigenetic regulation including DNA hypermethylation by DNA methyltransferase 1 (DNMT1) has been implicated as one of the causes of TNBC tumorigenesis. The antitumor effect of DNMT1 has also been explored in TNBC that currently lacks targeted therapies. However, the actual treatment for TNBC is yet to be discovered. This study is attributed to the identification of novel drug targets against TNBC. A comprehensive docking and simulation analysis was performed to optimize promising new compounds by estimating their binding affinity to the target protein. Molecular dynamics simulation of 500 ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between compound and binding pockets of DNMT1. In a nutshell, our study uncovered that Beta-Mangostin, Gancaonin Z, 5-hydroxysophoranone, Sophoraflavanone L, and Dorsmanin H showed maximum binding affinity with the active sites of DNMT1. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with TNBC, but, experimental validation is needed to ensure their safety.Communicated by Ramaswamy H. Sarma.

Role of Mangiferin in Management of Cancers through Modulation of Signal Transduction Pathways.

Cancer is a major public health concern worldwide in terms of mortality. The exact reason behind the development of cancer is not understood clearly, but it is evidenced that alcohol consumption, radiation, and exposure to chemicals are main players in this pathogenesis. The current mode of treatments such as surgery, chemotherapy, and radiotherapy are effective, but, still, cancer is a major problem leading to death and other side effects. However, safer and effective treatment modules are needed to overcome the adverse effects of current treatment modules. In this regard, natural compounds have been recognized to ameliorate diseases by exerting anti-inflammatory, anti-oxidative, and anti-tumor potential through several mechanisms. Mangiferin, a xanthone C-glucoside, is found in several plant species including Mangifera indica (mango), and its role in disease prevention has been confirmed through its antioxidant and anti-inflammatory properties. Furthermore, its anti-cancer-potential mechanism has been designated through modulation of cell signaling pathways such as inflammation, angiogenesis, PI3K/AKT, apoptosis, and cell cycle. This article extensively reviews the anticancer potential of mangiferin in different cancers through the modulation of cell signaling pathways. Moreover, the synergistic effects of this compound with some commonly used anti-cancer drugs against different cancer cells are discussed. More clinical trials should be performed to reconnoiter the anti-cancer potential of this compound in human cancer treatment. Further, understanding of mechanisms of action and the safety level of this compound can help to manage diseases, including cancer.

Innovative Strategies of Reprogramming Immune System Cells by Targeting CRISPR/Cas9-Based Genome-Editing Tools: A New Era of Cancer Management.

The recent developments in the study of clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) system have revolutionized the art of genome-editing and its applications for cellular differentiation and immune response behavior. This technology has further helped in understanding the mysteries of cancer progression and possible designing of novel antitumor immunotherapies. CRISPR/Cas9-based genome-editing is now often used to engineer universal T-cells, equipped with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR). In addition, this technology is used in cytokine stimulation, antibody designing, natural killer (NK) cell transfer, and to overcome immune checkpoints. The innovative potential of CRISPR/Cas9 in preparing the building blocks of adoptive cell transfer (ACT) immunotherapy has opened a new window of antitumor immunotherapy and some of them have gained FDA approval. The manipulation of immunogenetic regulators has opened a new interface for designing, implementation and interpretation of CRISPR/Cas9-based screening in immuno-oncology. Several cancers like lymphoma, melanoma, lung, and liver malignancies have been treated with this strategy, once thought to be impossible. The safe and efficient delivery of CRISPR/Cas9 system within the immune cells for the genome-editing strategy is a challenging task which needs to be sorted out for efficient immunotherapy. Several targeting approaches like virus-mediated, electroporation, microinjection and nanoformulation-based methods have been used, but each procedure offers some limitations. Here, we elaborate the recent updates of cancer management through immunotherapy in partnership with CRISPR/Cas9 technology. Further, some innovative methods of targeting this genome-editing system within the immune system cells for reprogramming them, as a novel strategy of anticancer immunotherapy is elaborated. In addition, future prospects and clinical trials are also discussed.

Myricetin: A Significant Emphasis on Its Anticancer Potential via the Modulation of Inflammation and Signal Transduction Pathways.

Cancer is a major public health concern worldwide and main burden of the healthcare system. Regrettably, most of the currently used cancer treatment approaches such as targeted therapy, chemotherapy, radiotherapy and surgery usually cause adverse complications including hair loss, bone density loss, vomiting, anemia and other complications. However, to overcome these limitations, there is an urgent need to search for the alternative anticancer drugs with better efficacy as well as less adverse complications. Based on the scientific evidences, it is proven that naturally occurring antioxidants present in medicinal plants or their bioactive compounds might constitute a good therapeutic approach in diseases management including cancer. In this regard, myricetin, a polyhydroxy flavonol found in a several types of plants and its role in diseases management as anti-oxidant, anti-inflammatory and hepato-protective has been documented. Moreover, its role in cancer prevention has been noticed through modulation of angiogenesis, inflammation, cell cycle arrest and induction of apoptosis. Furthermore, myricetin plays a significant role in cancer prevention through the inhibition of inflammatory markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2). Moreover, myricetin increases the chemotherapeutic potential of other anticancer drugs through modulation of cell signaling molecules activity. This review elaborates the information of myricetin role in cancer management through modulating of various cell-signaling molecules based on in vivo and in vitro studies. In addition, synergistic effect with currently used anticancer drugs and approaches to improve bioavailability are described. The evidences collected in this review will help different researchers to comprehend the information about its safety aspects, effective dose for different cancers and implication in clinical trials. Moreover, different challenges need to be focused on engineering different nanoformulations of myricetin to overcome the poor bioavailability, loading capacity, targeted delivery and premature release of this compound. Furthermore, some more derivatives of myricetin need to be synthesized to check their anticancer potential.

Potential Therapeutic Targets of Formononetin, a Type of Methoxylated Isoflavone, and Its Role in Cancer Therapy through the Modulation of Signal Transduction Pathways.

Cancer is one of the main causes of death in all developed and developing countries. Various factors are involved in cancer development and progression, including inflammation and alterations in cellular processes and signaling transduction pathways. Natural compounds have shown health-promoting effects through their antioxidant and anti-inflammatory potential, having an important role in the inhibition of cancer growth. In this regard, formononetin, a type of isoflavone, plays a significant role in disease management through the modulation of inflammation, angiogenesis, cell cycle, and apoptosis. Furthermore, its role in cancer management has been proven through the regulation of different signal transduction pathways, such as the signal transducer and activator of transcription 3 (STAT 3), Phosphatidyl inositol 3 kinase/protein kinase B (PI3K/Akt), and mitogen activating protein kinase (MAPK) signaling pathways. The anticancer potential of formononetin has been reported against various cancer types, such as breast, cervical, head and neck, colon, and ovarian cancers. This review focuses on the role of formononetin in different cancer types through the modulation of various cell signaling pathways. Moreover, synergistic effect with anticancer drugs and methods to improve bioavailability are explained. Thus, detailed studies based on clinical trials are required to explore the potential role of formononetin in cancer prevention and treatment.

Integrated molecular modeling and dynamics approaches revealed potential natural inhibitors of NF-κB transcription factor as breast cancer therapeutics.

Breast cancer is a silent killer malady among women and a serious economic burden in health care management. A case of breast cancer is diagnosed among women every 19 s, and every 74 s, a woman dies of breast cancer somewhere in the world. Despite the pop-up of progressive research, advanced treatment approaches, and preventive measures, breast cancer remains amplifying ailment. The nuclear factor kappa B (NF-κB) is a key transcription factor that links inflammation with cancer and is demonstrated as being involved in the tumorigenesis of breast cancer. The NF-κB transcription factor family in mammals consists of five proteins; c-Rel, RelA(p65), RelB, NF-κB1(p50), and NF-κB2(p52). The antitumor effect of NF-κB has also been explored in breast cancer, however, the actual treatment for breast cancer is yet to be discovered. This study is attributed to the identification of novel drug targets against breast cancer by targeting c-Rel, RelA(p65), RelB, NF-κB1(p50), and NF-κB2(p52) proteins. To identify the putative active compounds, a structure-based 3D pharmacophore model to the protein active site cavity was generated followed by virtual screening, molecular docking, and molecular dynamics (MD) simulation. Initially, a library of 45000 compounds were docked against the target protein and five compounds namely Z56811101, Z653426226, Z1097341967, Z92743432, and Z464101066 were selected for further analysis. The relative binding affinity of Z56811101, Z653426226, Z1097341967, Z92743432, and Z464101066 with NF-κB1 (p50), NF-κB2 (p52), RelA (p65), RelB, and c-Rel proteins were -6.8, -8, -7.0, -6.9, and -7.2 kcal/mol, respectively which remained stable throughout the simulations of 200 ns. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with breast cancer, but, experimental validation is needed to ensure their safety.Communicated by Ramaswamy H. Sarma.

Advanced network pharmacology study reveals multi-pathway and multi-gene regulatory molecular mechanism of Bacopa monnieri in liver cancer based on data mining, molecular modeling, and microarray data analysis.

Liver cancer is a malignant tumor that grows on the surface or inside the liver. The leading cause is a viral infection with hepatitis B or C virus. Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer. A list of studies evidences the therapeutic efficacy of Bacopa monnieri against liver cancer, but the precise molecular mechanism is yet to be discovered. This study combines data mining, network pharmacology, and molecular docking analysis to potentially revolutionize liver cancer treatment by identifying effective phytochemicals. Initially, the information on active constituents of B. monnieri and target genes of both liver cancer and B. monnieri were retrieved from literature as well as from publicly available databases. Based on the matching results between B. monnieri potential targets and liver cancer targets, the protein-protein interaction (PPI) network was constructed using the STRING database and imported into Cytoscape for screening of hub genes based on their degree of connectivity. Later, the interactions network between compounds and overlapping genes was constructed using Cytoscape software to analyze the network pharmacological prospective effects of B. monnieri on liver cancer. Gene Ontology (GO) and KEGG pathway analysis of hub genes revealed that these genes are involved in the cancer-related pathway. Lastly, the expression level of core targets was analyzed using microarray data (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790). Further, the GEPIA server and PyRx software were used for survival and molecular docking analysis, respectively. In summary, we proposed that quercetin, luteolin, apigenin, catechin, epicatechin, stigmasterol, beta-sitosterol, celastrol, and betulic acid inhibit tumor growth by affecting tumor protein 53 (TP53), interleukin 6 (IL6), RAC-alpha serine/threonine protein kinases 1 (AKT1), caspase-3 (CASP3), tumor necrosis factor (TNF), jun proto-oncogene (JUN), heat shot protein 90 AA1 (HSP90AA1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), and SRC proto-oncogene (SRC). Through, microarray data analysis, the expression level of JUN and IL6 were found to be upregulated while the expression level of HSP90AA1 was found to be downregulated. Kaplan-Meier survival analysis indicated that HSP90AA1 and JUN are promising candidate genes that can serve as diagnostic and prognostic biomarkers for liver cancer. Moreover, the molecular docking and molecular dynamic simulation of 60ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between the compound and binding pockets of HSP90AA1 and JUN. Despite that, in vivo and in vitro studies are mandatory to unveil pharmacokinetics and biosafety profiles to completely track the candidature status of B. monnieri in liver cancer.

Effects and Mechanisms of Kaempferol in the Management of Cancers through Modulation of Inflammation and Signal Transduction Pathways.

Cancer is the principal cause of death and its incidence is increasing continuously worldwide. Various treatment approaches are in practice to treat cancer, but these treatment strategies may be associated with severe side effects and also produce drug resistance. However, natural compounds have established their role in cancer management with minimal side effects. In this vista, kaempferol, a natural polyphenol, mainly found in vegetables and fruits, has been revealed to have many health-promoting effects. Besides its health-promoting potential, its anti-cancer potential has also been described in in vivo as well as in in vitro studies. The anti-cancer potential of kaempferol has been proven through modulation of cell signaling pathways in addition to the induction of apoptosis and cell cycle arrest in cancer cells. It leads to the activation of tumor suppressor genes, inhibition of angiogenesis, PI3K/AKT pathways, STAT3, transcription factor AP-1, Nrf2 and other cell signaling molecules. Poor bioavailability of this compound is one of the major limitations for its proper and effective disease management actions. Recently, some novel nanoparticle-based formulations have been used to overcome these limitations. The aim of this review is to provide a clear picture regarding the mechanism of action of kaempferol in different cancers through the modulation of cell signaling molecules. Besides this, strategies to improve the efficacy and synergistic effects of this compound have also been described. However, more studies are needed based on clinical trials to fully explore the therapeutic role of this compound, especially in cancer treatment.

Recent Advances in Genome-Editing Technology with CRISPR/Cas9 Variants and Stimuli-Responsive Targeting Approaches within Tumor Cells: A Future Perspective of Cancer Management.

The innovative advances in transforming clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) into different variants have taken the art of genome-editing specificity to new heights. Allosteric modulation of Cas9-targeting specificity by sgRNA sequence alterations and protospacer adjacent motif (PAM) modifications have been a good lesson to learn about specificity and activity scores in different Cas9 variants. Some of the high-fidelity Cas9 variants have been ranked as Sniper-Cas9, eSpCas9 (1.1), SpCas9-HF1, HypaCas9, xCas9, and evoCas9. However, the selection of an ideal Cas9 variant for a given target sequence remains a challenging task. A safe and efficient delivery system for the CRISPR/Cas9 complex at tumor target sites faces considerable challenges, and nanotechnology-based stimuli-responsive delivery approaches have significantly contributed to cancer management. Recent innovations in nanoformulation design, such as pH, glutathione (GSH), photo, thermal, and magnetic responsive systems, have modernized the art of CRISPR/Cas9 delivery approaches. These nanoformulations possess enhanced cellular internalization, endosomal membrane disruption/bypass, and controlled release. In this review, we aim to elaborate on different CRISPR/Cas9 variants and advances in stimuli-responsive nanoformulations for the specific delivery of this endonuclease system. Furthermore, the critical constraints of this endonuclease system on clinical translations towards the management of cancer and prospects are described.

The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment.

Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified bioactive compounds have confirmed health-promoting effects as well as cancer-preventive effects. Among these products, flavonoids belong to polyphenols, chiefly found in fruits, vegetables and in various seeds/flowers. It has been considered to be an effective antioxidant, anti-inflammatory and to play a vital role in diseases management. Besides these activities, flavonoids have been revealed to possess anticancer potential through the modulation of various cell signaling molecules. In this regard, fisetin, a naturally occurring flavonoid, has a confirmed role in disease management through antioxidant, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential. As well, its cancer-preventive effects have been confirmed via modulating various cell signaling pathways including inflammation, apoptosis, angiogenesis, growth factor, transcription factor and other cell signaling pathways. This review presents an overview of the anti-cancer potential of fisetin in different types of cancer through the modulation of cell signaling pathways based on in vivo and in vitro studies. A synergistic effect with anticancer drugs and strategies to improve the bioavailability are described. More clinical trials need to be performed to explore the anti-cancer potential and mechanism-of-action of fisetin and its optimum therapeutic dose.

The Multifaceted Role of Baicalein in Cancer Management through Modulation of Cell Signalling Pathways.

The roles of medicinal plants or their purified bioactive compounds have attracted attention in the field of health sciences due to their low toxicity and minimal side effects. Baicalein is an active polyphenolic compound, isolated from Scutellaria baicalensis, and plays a significant role in the management of different diseases. Epidemiologic studies have proven that there is an inverse association between baicalein consumption and disease severity. Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation. Additionally, the anticancer potential of baicalein is chiefly mediated through the modulation of various cell-signaling pathways, such as the induction of apoptosis, autophagy, cell cycle arrest, inhibition of angiogenesis, signal transducer and activator of transcription 3, and PI3K/Akt pathways, as well as the regulation of other molecular targets. Therefore, the current review aimed to explore the role of baicalein in different types of cancer along with mechanisms of action. Besides this, the synergistic effects with other anti-cancerous drugs and the nano-formulation based delivery of baicalein have also been discussed.

SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy.

Cancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after anticancer therapies. This study illuminates the role and efficacy of smac mimetic compound BV6 alone and in co-treatment with death ligands such as TRAIL and TNFα in the regulation of cell death mechanisms, i.e., apoptosis and autophagy. In this study, MTT assays, wound healing assays, and cellular and nuclear morphological studies were done. DAPI staining, AO/EtBr staining and AnnexinV/PI FACS was done to study the apoptosis. The expression of IAPs and autophagy biomarkers was analyzed using Real time-PCR and western blotting. Meanwhile, TEM demonstrated autophagy and cellular autophagic vacuoles in response to the BV6. The result shows a promising anti-cancer effect of BV6 alone as well as in combinational treatment with TRAIL and TNFα, compared to the lone treatment of TRAIL and TNFα in both breast cancer cell lines. The smac mimetic compound might provide an alternative combinational therapy with conventional anticancer therapies to tackle their inefficiency at the advanced stage of cancer, cancer resistance, and reoccurrence. Also, IAPs and autophagic proteins could act as potent target molecules for the development of novel anti-cancer drugs in pathogenesis and the betterment of regimens for cancer.

Current updates of CRISPR/Cas9-mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management.

Clustered regularly interspaced short palindromic repeats-associated protein (CRISPR/Cas9), an adaptive microbial immune system, has been exploited as a robust, accurate, efficient and programmable method for genome targeting and editing. This innovative and revolutionary technique can play a significant role in animal modeling, in vivo genome therapy, engineered cell therapy, cancer diagnosis and treatment. The CRISPR/Cas9 endonuclease system targets a specific genomic locus by single guide RNA (sgRNA), forming a heteroduplex with target DNA. The Streptococcus pyogenes Cas9/sgRNA:DNA complex reveals a bilobed architecture with target recognition and nuclease lobes. CRISPR/Cas9 assembly can be hijacked, and its nanoformulation can be engineered as a delivery system for different clinical utilizations. However, the efficient and safe delivery of the CRISPR/Cas9 system to target tissues and cancer cells is very challenging, limiting its clinical utilization. Viral delivery strategies of this system may have many advantages, but disadvantages such as immune system stimulation, tumor promotion risk and small insertion size outweigh these advantages. Thus, there is a desperate need to develop an efficient non-viral physical delivery system based on simple nanoformulations. The delivery strategies of CRISPR/Cas9 by a nanoparticle-based system have shown tremendous potential, such as easy and large-scale production, combination therapy, large insertion size and efficient in vivo applications. This review aims to provide in-depth updates on Streptococcus pyogenic CRISPR/Cas9 structure and its mechanistic understanding. In addition, the advances in its nanoformulation-based delivery systems, including lipid-based, polymeric structures and rigid NPs coupled to special ligands such as aptamers, TAT peptides and cell-penetrating peptides, are discussed. Furthermore, the clinical applications in different cancers, clinical trials and future prospects of CRISPR/Cas9 delivery and genome targeting are also discussed.

Brain Tumors in Saudi Arabia: An Observational and Descriptive Epidemiological Analysis.

INTRODUCTION: Brain tumors are one of the major causes of death and morbidity around the world. A prospective existential retrospective observational population-cohort study based on the comprehensive research work on brain tumors in the Saudi population was conducted, with statistics drawn from the Saudi Cancer Registry data collected and published by the Ministry of Health, Saudi Arabia, which is a national document prepared and maintained by the National Health Information Center, from 2006 to 2016. For the analysis of the brain tumor distribution and trends in Saudi Arabian inhabitants, the current study outlined the brain tumor incident rates in the age-standardized incidence rates (ASIRs) and crude incidence rates (CIRs) in the inhabitants of Saudi Arabia by distinct age cohorts, the year of diagnosis, and the core administrative regions of Saudi Arabia. METHOD: Statistical tools, such as GraphPad Prism and SPSS 2.0, were used for the analyses of the t-test, Kruskal-Wallis test, and descriptive statistics, including the sex ratio and other demographic features. Between 2006 and 2016, Saudi Arabia recorded 1854 and 1293 cases of brain tumors in males and females, respectively. RESULTS: The highest percentage and mean number of brain tumor cases were recorded among males and females in the age group 0-4 years, and the lowest proportion of brain tumor cases were reported among males and females in the higher age group (55-69 years). The highest mean CIR and ASIR were found in the male and female populations of the Riyadh region, and the highest CIR and ASIR sex ratios were found in the Baha and Naj regions of Saudi Arabia, respectively. Males in the Jazan region had the lowest average CIRs and ASIRs. The Baha and Jazan regions of Saudi Arabia recorded the lowest mean CIR and ASIR among females. CONCLUSION: The Riyadh region had the most significant increases in ASIRs and CIRs for brain tumors in males and females from 2006 to 2016, whereas the Jazan region had the least significant changes in the ASIRs in males and females.

The Potential Role of Apigenin in Cancer Prevention and Treatment.

Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more effective and less side effects-based cancer treatment approaches is still at the primary position of present research. Medicinal plants or their bioactive ingredients act as dynamic sources of drugs due to their having less side effects and also shows the role in reduction of resistance against cancer therapy. Apigenin is an edible plant-derived flavonoid that has received significant scientific consideration for its health-promoting potential through modulation of inflammation, oxidative stress and various other biological activities. Moreover, the anti-cancer potential of apigenin is confirmed through its ability to modulate various cell signalling pathways, including tumor suppressor genes, angiogenesis, apoptosis, cell cycle, inflammation, apoptosis, PI3K/AKT, NF-κB, MAPK/ERK and STAT3 pathways. The current review mainly emphases the potential role of apigenin in different types of cancer through the modulation of various cell signaling pathways. Further studies based on clinical trials are needed to explore the role of apigenin in cancer management and explain the possible potential mechanisms of action in this vista.