Vaccine-based therapeutic interventions in lung cancer management: A recent perspective.

The incidence of lung cancer continues to grow globally, contributing to an ever-increasing load on healthcare systems. Emerging evidence has indicated lowered efficacy of conventional treatment strategies, such as chemotherapy, surgical interventions and radiotherapy, prompting the need for exploring alternative interventions. A growing focus on immunotherapy and the development of personalized medicine has paved the way for vaccine-based delivery in lung cancer. With various prominent targets such as CD8+T cells and PD-L1, immune-targeted, anti-cancer vaccines have been evaluated in both, pre-clinical and clinical settings, to improve therapeutic outcomes. However, there are a number of challenges that must be addressed, including the scalability of such delivery systems, heterogeneity of lung cancers, and long-term safety as well as efficacy. In addition to this, natural compounds, in combination with immunotherapy, have gained considerable research interest in recent times. This makes it necessary to explore their role in synergism with immune-targeted agents. The authors of this review aim to offer an overview of recent advances in our understanding of lung cancer pathogenesis, detection and management strategies, and the emergence of immunotherapy with a special focus on vaccine delivery. This finding is supported with evidence from testing in non-human and human models, showcasing promising results. Prospects for phytotherapy have also been discussed, in order to combat some pitfalls and limitations. Finally, the future perspectives of vaccine usage in lung cancer management have also been discussed, to offer a holistic perspective to readers, and to prompt further research in the domain.

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions.

Gastrointestinal (GI) cancers are a significant global health concern with diverse etiologies and limited treatment options. Ellagic acid (EA), a natural polyphenolic compound, exhibits promising anticancer properties against various GI malignancies. In this article, we have reviewed recent research on the anticancer potential of EA across esophageal, gastric, colorectal, pancreatic, and liver cancers. In esophageal cancer, EA inhibits the formation of O6-methylguanine (O6-meGua) adducts induced by carcinogens like N-nitrosomethylbenzylamine (NMBA), thereby suppressing tumor growth. Additionally, EA inhibits STAT3 signaling and stabilizes tumor suppressor proteins, showing potential as an anti-esophageal cancer agent. In gastric cancer, EA regulates multiple pathways involved in cell proliferation, invasion, and apoptosis, including the p53 and PI3K-Akt signaling pathways. It also demonstrates anti-inflammatory and antioxidant effects, making it a promising therapeutic candidate against gastric cancer. In colorectal cancer (CRC), EA inhibits cell proliferation, induces apoptosis, and modulates the Wnt/ß-catenin and PI3K/Akt pathways, suggesting its efficacy in preventing CRC progression. Furthermore, EA has shown promise in pancreatic cancer by inhibiting nuclear factor-kappa B, inducing apoptosis, and suppressing epithelial-mesenchymal transition. In liver cancer, EA exhibits radio-sensitizing effects, inhibits inflammatory pathways, and modulates the tumor microenvironment, offering potential therapeutic benefits against hepatocellular carcinoma. Studies on EA potential in combination therapies and the development of targeted delivery systems are required for enhanced efficacy against gastrointestinal cancers.

Immune-Related Long Non-Coding RNA Signature Determines Prognosis and Immunotherapeutic Coherence in Esophageal Cancer.

Objectives: Aim of this study was to explore the immune-related lncRNAs having prognostic role and establishing risk score model for better prognosis and immunotherapeutic coherence for esophageal cancer (EC) patients. Methods: To determine the role of immune-related lncRNAs in EC, we analyzed the RNA-seq expression data of 162 EC patients and 11 non-cancerous individuals and their clinically relevant information from the cancer genome atlas (TCGA) database. Bioinformatic and statistical analysis such as Differential expression analysis, co-expression analysis, Kaplan Meier survival analysis, Cox proportional hazards model, ROC analysis of risk model was employed. Results: Utilizing a cutoff criterion (log2FC > 1 + log2FC < -1 and FDR < 0.01), we identified 3737 RNAs were significantly differentially expressed in EC patients. Among these, 2222 genes were classified as significantly differentially expressed mRNAs (demRNAs), and 966 were significantly differentially expressed lncRNAs (delncRNA). Through Pearson correlation analysis between differentially expressed lncRNAs and immune related-mRNAs, we identified 12 immune-related lncRNAs as prognostic signatures for EC. Notably, through Kaplan-Meier analysis on these lncRNAs, we found the low-risk group patients showed significantly improved survival compared to the high-risk group. Moreover, this prognostic signature has consistent performance across training, testing and entire validation cohort sets. Using ESTIMATE and CIBERSORT algorithm we further observed significant enriched infiltration of naive B cells, regulatory T cells resting CD4+ memory T cells, and, plasma cells in the low-risk group compared to high-risk EC patients group. On the contrary, tumor-associated M2 macrophages were highly enriched in high-risk patients. Additionally, we confirmed immune-related biological functions and pathways such as inflammatory, cytokines, chemokines response and natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathways, JAK-STAT signaling pathways, chemokine signaling pathways significantly associated with identified IRlncRNA signature and their co-expressed immune genes. Furthermore, we assessed the predictive potential of the lncRNA signature in immune checkpoint inhibitors; we found that programed cell death ligand 1 (PD-L1; P-value = .048), programed cell death ligand 2 (PD-L2; P-value = .002), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3; P-value = .045) expression levels were significantly higher in low-risk patients compared to high-risk patients. Conclusion: We believe this study will contribute to better prognosis prediction and targeted treatment of EC in the future.

Role of ursolic acid in preventing gastrointestinal cancer: recent trends and future perspectives.

Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, anti-proliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment.

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vaccines, utilizes the host's immune system to selectively target and eradicate malignant cells while minimizing harm to normal tissue. The development of targeted medicines like kinase inhibitors and monoclonal antibodies has allowed for more targeted and less harmful approaches to treating cancer. With the help of genomics and molecular profiling, "precision medicine" customizes therapies to each patient's unique genetic makeup to maximize therapeutic efficacy while minimizing unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, and an increasing emphasis on combination therapy with synergistic effects further broaden the therapeutic landscape. Multiple-stage clinical trials are essential for determining the safety and efficacy of these novel drugs, allowing patients to gain access to novel treatments while also furthering scientific understanding. The future of cancer therapy is rife with promise, as the integration of artificial intelligence and big data has the potential to revolutionize early detection and prevention. Collaboration among researchers, and healthcare providers, and the active involvement of patients remain the bedrock of the ongoing battle against cancer. In conclusion, the dynamic and evolving landscape of cancer therapy provides hope for improved treatment outcomes, emphasizing a patient-centered, data-driven, and ethically grounded approach as we collectively strive towards a cancer-free world.

Luteolin: A promising modulator of apoptosis and survival signaling in liver cancer.

Due to the increasing incidence of cancer and the difficulties in determining the safety profile of existing therapeutic approaches, cancer research has recently become heavily involved in the search for new therapeutic approaches. The therapeutic significance of natural substances, especially flavonoids, against the onset and progression of cancer has been emphasized in traditional food-based medicine. Interestingly, the flavone luteolin possesses biological effects that have been linked to its anti-inflammatory, antioxidant, and anticancer effects. Luteolin interacts with several downstream chemicals and signaling pathways, including those involved in apoptosis, autophagy, cell cycle progression, and angiogenesis, to exert its anticancer effects on various cancerous cells. A complete understanding of both intrinsic and extrinsic apoptotic pathways, autophagy, and, most critically, the nanodelivery of luteolin in liver cancer is provided in the current review.

Garcinol in gastrointestinal cancer prevention: recent advances and future prospects.

Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.

Advancements and recent explorations of anti-cancer activity of chrysin: from molecular targets to therapeutic perspective.

In recent times, there have been notable advancements in comprehending the potential anti-cancer effects of chrysin (CH), a naturally occurring flavonoid compound found abundantly in various plant sources like honey, propolis, and certain fruits and vegetables. This active compound has garnered significant attention due to its promising therapeutic qualities and minimal toxicity. CH's ability to combat cancer arises from its multifaceted mechanisms of action, including the initiation of apoptosis and the inhibition of proliferation, angiogenesis, metastasis, and cell cycle progression. CH also displays potent antioxidant and anti-inflammatory properties, effectively counteracting the harmful molecules that contribute to DNA damage and the development of cancer. Furthermore, CH has exhibited the potential to sensitize cancer cells to traditional chemotherapy and radiotherapy, amplifying the effectiveness of these treatments while reducing their negative impact on healthy cells. Hence, in this current review, the composition, chemistry, mechanisms of action, safety concerns of CH, along with the feasibility of its nanoformulations. To conclude, the recent investigations into CH's anti-cancer effects present a compelling glimpse into the potential of this natural compound as a complementary therapeutic element in the array of anti-cancer approaches, providing a safer and more comprehensive method of combating this devastating ailment.

Allicin: a promising modulator of apoptosis and survival signaling in cancer.

According to the World Health Organization, cancer is the foremost cause of mortality globally. Various phytochemicals from natural sources have been extensively studied for their anticancer properties. Allicin, a powerful organosulfur compound derived from garlic, exhibits anticancer, antioxidant, anti-inflammatory, antifungal, and antibacterial properties. This review aims to update and evaluate the chemistry, composition, mechanisms of action, and pharmacokinetics Allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells. Safety and clinical aspects are meticulously scrutinized, providing insights into the tolerability and adverse effects associated with allicin administration, along with an overview of current clinical trials evaluating its therapeutic potential. In conclusion, this review underscores the promising prospects of allicin as a dietary-derived medicinal compound for cancer therapy. It emphasizes the need for further research to elucidate its precise mechanisms of action, optimize delivery strategies, and validate its efficacy in clinical settings.

Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability.

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives.

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

A current review on P2X7 receptor antagonist patents in the treatment of neuroinflammatory disorders: a patent review on antagonists.

Chronic inflammation is defined by an activated microglial state linked to all neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (a motor neuron disease that affects the brain and spinal cord). P2X7 receptors (P2X7R) are ATP-activated ion-gated channels present on microglial surfaces. Prolonged ATP release under pathological settings results in sustained P2X7R activation, which leads to inflammasome development and cytokine release. P2X7R and its enabling roles have recently been linked to neurodegenerative diseases, making it a potential research subject. This research provides an overview of current patents for chemicals, biologics, and medicinal applications. The World Intellectual Property Organization (WIPO), European Patent Office (EPO, Espacenet), and the United States Patent and Trademark Office (USPTO) databases were searched for patents using the keywords "P2X7R and Neuroinflammation." During the study period from 2015 to 2021, 103 patents were examined. The countries that protected these innovations were the United States, PCT (Patent Cooperation Treaty states), Europe, Canada, Australia, and India. Janssen Pharmaceutica NV had the most applications, followed by Acetelion Pharmaceuticals LTD., Renovis Inc., Kelly Michael G, Kincaid Jhon, Merck Patent GMBH, H Lundbeck A/S, and many more. The P2X7R is a possible diagnostic and therapeutic target for cancer, pain disorders, and inflammation. For P2X7 R, several compounds have been discovered and are presently the subject of clinical trial investigations. This study featured patents for P2X7R antagonists, which help treat conditions including neuroinflammation.

Sesamol as a potent anticancer compound: from chemistry to cellular interactions.

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements.

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.

Temozolomide and flavonoids against glioma: from absorption and metabolism to exosomal delivery.

Patients with glioblastoma multiforme and anaplastic astrocytoma are treated with temozolomide. Although it has been demonstrated that temozolomide increases GBM patient survival, it has also been connected to negative immune-related adverse effects. Numerous research investigations have shown that flavonoids have strong antioxidant and chemo-preventive effects. Consequently, it might lessen chemotherapeutic medicines' side effects while also increasing therapeutic effectiveness. The need for creating innovative, secure, and efficient drug carriers for cancer therapy has increased over time. Recent research indicates that exosomes have enormous potential to serve as carriers and cutting-edge drug delivery systems to the target cell. In recent years, researchers have been paying considerable attention to exosomes because of their favorable biodistribution, biocompatibility, and low immunogenicity. In the present review, the mechanistic information of the anti-glioblastoma effects of temozolomide and flavonoids coupled with their exosomal delivery to the targeted cell has been discussed. In addition, we discuss the safety aspects of temozolomide and flavonoids against glioma. The in-depth information of temozolomide and flavonoids action via exosomal delivery can unravel novel strategies to target Glioma.

Emerging role of microRNAs as regulators of protein kinase C substrate MARCKS and MARCKSL1 in cancer.

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in diverse cellular processes, including the development and progression of cancer. Among the numerous proteins influenced by miRNAs, the MARCKS/MARCKSL1 protein, a key regulator of cellular cytoskeletal dynamics and membrane-cytosol communication, has garnered significant attention due to its multifaceted involvement in various cancer-related processes, including cell migration, invasion, metastasis, and drug resistance. Motivated by the encouraging early clinical success of peptides targeting MARCKS in several pathological conditions, this review article delves into the intricate interplay between miRNAs and the MARCKS protein in cancer. Herein, we have highlighted the latest findings on specific miRNAs that modulate MARCKS/MARCKSL1 expression, providing a comprehensive overview of their roles in different cancer types. We have underscored the need for in-depth investigations into the therapeutic feasibility of targeting the miRNA-MARCKS axis in cancer, taking cues from the successes witnessed in related fields. Unlocking the full potential of miRNA-mediated MARCKS regulation could pave the way for innovative and effective therapeutic interventions against various cancer types.

Melittin: a possible regulator of cancer proliferation in preclinical cell culture and animal models.

BACKGROUND: Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. PURPOSE: This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. METHODS: We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. CONCLUSION: In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.