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The utilization of medicinal plant extracts in therapeutics has been hindered by various challenges, including poor bioavailability and stability issues. Nanovesicular delivery systems have emerged as promising tools to overcome these limitations by enhancing the solubility, bioavailability, and targeted delivery of bioactive compounds from medicinal plants. This review explores the applications of nanovesicular delivery systems in antibacterial and anticancer therapeutics using medicinal plant extracts. We provide an overview of the bioactive compounds present in medicinal plants and their therapeutic properties, emphasizing the challenges associated with their utilization. Various types of nanovesicular delivery systems, including liposomes, niosomes, ethosomes, and solid lipid nanoparticles, among others, are discussed in detail, along with their potential applications in combating bacterial infections and cancer. The review highlights specific examples of antibacterial and anticancer activities demonstrated by these delivery systems against a range of pathogens and cancer types. Furthermore, we address the challenges and limitations associated with the scale-up, stability, toxicity, and regulatory considerations of nanovesicular delivery systems. Finally, future perspectives are outlined, focusing on emerging technologies, integration with personalized medicine, and potential collaborations to drive forward research in this field. Overall, this review underscores the potential of nanovesicular delivery systems for enhancing the therapeutic efficacy of medicinal plant extracts in antibacterial and anticancer applications, while identifying avenues for further research and development.

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Preserving a functional mitochondrial network is crucial for cellular well-being, considering the pivotal role of mitochondria in ensuring cellular survival, especially under stressful conditions. Mitophagy, the selective removal of damaged mitochondria through autophagy, plays a pivotal role in preserving cellular homeostasis by preventing the production of harmful reactive oxygen species from dysfunctional mitochondria. While the involvement of mitophagy in neurodegenerative diseases has been thoroughly investigated, it is becoming increasingly evident that mitophagy plays a significant role in cancer biology. Perturbations in mitophagy pathways lead to suboptimal mitochondrial quality control, catalyzing various aspects of carcinogenesis, including establishing metabolic plasticity, stemness, metabolic reconfiguration of cancer-associated fibroblasts, and immunomodulation. While mitophagy performs a delicate balancing act at the intersection of cell survival and cell death, mounting evidence indicates that, particularly in the context of stress responses induced by cancer therapy, it predominantly promotes cell survival. Here, we showcase an overview of the current understanding of the role of mitophagy in cancer biology and its potential as a target for cancer therapy. Gaining a more comprehensive insight into the interaction between cancer therapy and mitophagy has the potential to reveal novel targets and pathways, paving the way for enhanced treatment strategies for therapy-resistant tumors in the near future.

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Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.

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Apoptosis is the cell's natural intrinsic regulatory mechanism of normal cells for programmed cell death, which plays an important role in cancer as a classical mechanism of tumor cell death causing minimal inflammation without causing damage to other cells in the vicinity. Induction of apoptosis by activation of caspases is one of the primary targets for cancer treatment. Over the years, a diverse range of natural, synthetic, and semisynthetic compounds and their derivatives have been investigated for their caspase-mediated apoptosis-induced anticancer activities. The review aims to compile the preclinical evidence and highlight the critical mechanistic pathways related to caspase-induced cell apoptosis in cancer treatment. The focus is placed on the key components of the mechanisms, including their chemical nature, and specific attention is given to phytochemicals derived from natural sources and synthetic and semisynthetic compounds. 180+ compounds from the past two decades with potential as anticancer agents are discussed in this review article. By summarizing the current knowledge and advancements in this field, this review provides a comprehensive overview of potential therapeutic strategies targeting apoptosis in cancer cells. The findings presented herein contribute to the ongoing efforts to combat cancer and stimulate further research into the development of effective and targeted anticancer therapies.

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Skin toxicities are very common in patients undergoing cancer treatment and have been found to occur with all types of cancer therapeutic interventions (cytotoxic chemotherapy, targeted therapies, immunotherapy, and radiotherapy). Further, skin toxicities can lead to interruption or even discontinuation of anticancer treatment in some patients, translating to suboptimal outcomes. Dermocosmetics (or cosmeceuticals)-defined as skincare solutions incorporating dermatologically active ingredients (beyond vehicle effects) that directly improve symptoms of various skin conditions-are increasingly being used in cancer care to prevent and manage skin toxicities. The active ingredients in these products have a measurable biological action in skin; they typically improve skin integrity (barrier function/hydration and other factors) while relieving skin symptoms. The Association Francophone des Soins Oncologiques de Support (AFSOS) and Multinational Association of Supportive Care in Cancer (MASCC) partnered to select a multidisciplinary group of healthcare professionals involved in the management of patients with cancer and skin toxicities. The group reviewed existing literature and created a summary of recommendations for managing these toxicities through online meetings and communication. In this publication, the group (1) reviews new skin toxicities seen with oncology drugs and (2) evaluates the role of dermocosmetics in improving patient outcomes and minimizing cancer treatment interruptions. We provide general recommendations for initiation and selection of skin care in all oncology patients as well as recommendations for what factors should be considered when using dermocosmetics in specific types of skin toxicities.

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Phytochemicals are abundantly occurring natural compounds extracted from plant sources. Rosmarinic acid (RA) is an abundant phytochemical of Lamiaceae species with various therapeutic implications for human health. In recent years, natural compounds have gained significant attention as adjuvant and complementary therapies to existing medications for various diseases. RA has gained popularity due to its anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes, etc. The present review aims to offer a comprehensive insight into the multifaceted therapeutic properties of RA, including its potential as an anticancer agent, neuroprotective effects, and antidiabetic potential. Based on the available evidences, RA could be considered a potential dietary component for treating various diseases, including cancer, diabetes and neurodegenerative disorders.

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Despite several treatment options for blood cancer, mortality remains high due to relapse and the disease's aggressive nature. Elevated levels of HSP90, a molecular chaperone essential for protein folding, are associated with poor prognosis in leukemia and lymphoma. HSP90 as a target for chemotherapy has been met with limited success due to toxicity and induction of heat shock. This study tested the activity of an HSP90 inhibitor, SP11, against leukemic cells, mouse lymphoma allograft, and xenograft models. SP11 induced cytotoxicity in vitro in leukemic cell lines and induced cell death via apoptosis, with minimal effect on normal cells. SP11 induced cell death by altering the status of HSP90 client proteins both in vitro and in vivo. SP11 reduced the tumor burden in allograft and xenograft mouse models without apparent toxicity. The half-life of SP11 in the plasma was approximately 2 h. SP11 binding was observed at both the N-terminal and C-terminal domains of HSP90. C-terminal binding was more potent than N-terminal binding of HSP90 in silico and in vitro using isothermal calorimetry. SP11 bioavailability and minimal toxicity in vivo make it a potential candidate to be developed as a novel anticancer agent.

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Reactive oxygen species (ROS) are common products of normal cellular metabolism, but their elevated levels can result in nucleotide modifications. These modified or noncanonical nucleotides often integrate into nascent DNA during replication, causing lesions that trigger DNA repair mechanisms such as the mismatch repair machinery and base excision repair. Four superfamilies of sanitization enzymes can effectively hydrolyze noncanonical nucleotides from the precursor pool and eliminate their unintended incorporation into DNA. Notably, we focus on the representative MTH1 NUDIX hydrolase, whose enzymatic activity is ostensibly nonessential under normal physiological conditions. Yet, the sanitization attributes of MTH1 are more prevalent when ROS levels are abnormally high in cancer cells, rendering MTH1 an interesting target for developing anticancer treatments. We discuss multiple MTH1 inhibitory strategies that have emerged in recent years, and the potential of NUDIX hydrolases as plausible targets for the development of anticancer therapeutics.

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Previous studies have shown that mitochondria play core roles in not only cancer stem cell (CSC) metabolism but also the regulation of CSC stemness maintenance and differentiation, which are key regulators of cancer progression and therapeutic resistance. Therefore, an in-depth study of the regulatory mechanism of mitochondria in CSCs is expected to provide a new target for cancer therapy. This article mainly introduces the roles played by mitochondria and related mechanisms in CSC stemness maintenance, metabolic transformation, and chemoresistance. The discussion mainly focuses on the following aspects: mitochondrial morphological structure, subcellular localization, mitochondrial DNA, mitochondrial metabolism, and mitophagy. The manuscript also describes the recent clinical research progress on mitochondria-targeted drugs and discusses the basic principles of their targeted strategies. Indeed, an understanding of the application of mitochondria in the regulation of CSCs will promote the development of novel CSC-targeted strategies, thereby significantly improving the long-term survival rate of patients with cancer.

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Exosomes are intrinsic membrane-based vesicles that play a key role in both normal and pathological processes. Since their discovery, exosomes have been investigated as viable drug delivery systems and clinical indicators because of their magnitude and effectiveness in delivering biological components to targeted cells. Exosome characteristics are biocompatible, prefer tumor recruitment, have tunable targeting efficiency, and are stable, making them outstanding and eye-catching medication delivery systems for cancer and other disorders. There is great interest in using cell-released tiny vesicles that activate the immune system in the age of the fast development of cancer immunotherapy. Exosomes, which are cell-derived nanovesicles, have a lot of potential for application in cancer immunotherapy due to their immunogenicity and molecular transfer function. More significantly, exosomes can transfer their cargo to specified cells and so affect the phenotypic and immune-regulation capabilities of those cells. In this article, we summarize exosomes' biogenesis, isolation techniques, drug delivery, applications, and recent clinical updates. The use of exosomes as drug-delivery systems for small compounds, macromolecules, and nucleotides has recently advanced. We have tried to give holistic and exhaustive pieces of information showcasing current progress and clinical updates of exosomes.

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Anticancer drug resistance is a significant impediment in current cancer treatment. Extracellular vesicles (EVs) derived from cancer cells were recently acknowledged as a critical mechanism of drug resistance, tumor progression, and metastasis. EVs are enveloped vesicles comprising a lipid bilayer that transfers various cargo, including proteins, nucleic acids, lipids, and metabolites, from an originating cell to a recipient cell. Investigating the mechanisms whereby EVs confer drug resistance is still in the early stages. In this review, I analyze the roles of EVs derived from triple-negative breast cancer cells (TNBC-EVs) in anticancer drug resistance and discuss strategies to overcome TNBC-EV-mediated drug resistance.

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Background: Cell fate and microenvironmental changes resulting from aberrant expression of specific proteins in tumors are one of the major causes of inadequate anti-tumor immune response and poor prognosis in head and neck cancer (HNC). Eukaryotic initiation factor 3C (eIF3c) has emerged as a promising therapeutic target for HNC due to its ability to regulate protein expression levels in tumor cells, but its drug development is difficult to achieve by targeting traditional protein-protein interactions. siRNA has emerged as a highly promising modality for drug development targeting eIF3c, while its application is hindered by challenges pertaining to inadequate stability and insufficient concentration specifically within tumor sites. Method: We employed a method to convert flexible siRNAs into stable and biologically active infinite Auric-sulfhydryl coordination supramolecular siRNAs (IacsRNAs). Through coordinated self-assembly, we successfully transformed eIF3C siRNAs into the carrier-free HNC nanotherapeutic agent Iacs-eif3c-RNA. The efficacy of this agent was evaluated in vivo using HNC xenograft models, demonstrating promising antitumor effects. Results: Iacs-eif3c-RNA demonstrated the ability to overcome the pharmacological obstacle associated with targeting eIF3C, resulting in a significant reduction in eIF3C expression within tumor tissues, as well as effective tumor cell proliferating suppression and apoptosis promotion. In comparison to monotherapy utilizing the chemotherapeutic agent cisplatin, Iacs-eif3c-RNA exhibited superior anti-tumor efficacy and favorable biosafety. Conclusion: The utilization of Iacs-eif3c-RNA as a carrier-free nanotherapeutic agent presents a promising and innovative approach for addressing HNC treating challenges. Moreover, this strategy demonstrates potential for the translation of therapeutic siRNAs into clinical drugs, extending its applicability to the treatment of other cancers and various diseases.

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Programmed cell death (PCD) is an evolutionarily conserved mechanism of cell suicide that is controlled by various signaling pathways. PCD plays an important role in a multitude of biological processes, such as cell turnover, development, tissue homeostasis and immunity. Some forms of PCD, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis and necroptosis, contribute to carcinogenesis and cancer development, and thus have attracted increasing attention in the field of oncology. Recently, increasing research-based evidence has demonstrated that PCD acts as a critical modulator of tumor immunity. PCD can affect the function of innate and adaptive immune cells, which leads to distinct immunological consequences, such as the priming of tumor-specific T cells, immunosuppression and immune evasion. Targeting PCD alone or in combination with conventional immunotherapy may provide new options to enhance the clinical efficacy of anticancer therapeutics. In this review, we introduce the characteristics and mechanisms of ubiquitous PCD pathways (e.g., apoptosis, autophagy-dependent cell death, pyroptosis and ferroptosis) and explore the complex interaction between these cell death mechanisms and tumor immunity based on currently available evidence. We also discuss the therapeutic potential of PCD-based approaches by outlining clinical trials targeting PCD in cancer treatment. Elucidating the immune-related effects of PCD on cancer pathogenesis will likely contribute to an improved understanding of oncoimmunology and allow PCD to be exploited for cancer treatment.

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As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.

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The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various types of Leukemia/Blood malignancies.

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B cell lymphoma 2 (BCL2) overexpression in a range of human tumors is often related to chemotherapy resistance and poor prognosis. GC-rich regions upstream of the P1 promoter in human BCL2 can form G-quadruplex (G4) structures through the stacking of four Hoogsteen-paired guanine bases. Stabilizing the G4 fold implies the inhibition of BCL2 expression and, thus, small molecules that selectively bind to the G4 are promising anticancer candidates. In this review, we discuss the structural aspects, binding affinity, selectivity, and biological activity of well-characterized BCL2 G4 binding ligands in vitro and in vivo. We also explore future directions in the research and development of G4-based anticancer therapeutics.

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Cancer involves the uncontrolled division of cells resulting in abnormal cell growth due to various gene mutations and is considered the second major cause of death. Due to drug resistance to current anticancer drugs, cancer incidence is rising, and seeking effective treatment is a major concern. Natural products are prospective to yield unique molecules, as nature is a leading source of various drug molecules due to plenty of pharmacologically active molecules. Thymoquinone, a bioactive constituent obtained from Nigella sativa L., has drawn considerable attention among researchers in recent years due to its anticancer potential involving various molecular targets, including initiation of apoptosis initiation, arrest of cell cycle and generation of ROS, besides targeting multiple kinases such as tyrosine kinase, MAPK, and Janus kinase. The current review summarizes the thymoquinone chemistry, sources and anticancer potential involving various molecular targets.

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Numerous studies have examined the role of autophagy in thyroid cancer treatment; however there are discrepancies among the reported data, with some showing the pro-survival and others the anti-survival effects of autophagy. These discrepant results appear to be at least in part due to insufficient analyses or data misinterpretation as well as improper assessments of autophagic activity. Therefore, the present study re-evaluated the regulation of autophagic activity by various anticancer modalities and examined the role of autophagy in thyroid cancer treatment in three thyroid cancer cell lines (TPC1, ACT1 and KTC1). The immunofluorescence and DalGreen findings demonstrated that cisplatin, irradiation and sorafenib were all autophagy inducers as previously reported, but, unlike previous studies using thyroid cancer cells, doxorubicin acted as an inhibitor. KTC1 cells are unique because they only responded to cisplatin. The efficacy of anticancer therapeutics was significantly higher in chloroquine or 3-methyladenine-treated autophagy-defective cells than in autophagy-competent cells, thereby indicating the pro-survival effect of autophagy induced by anticancer therapeutics, which is partly due to inhibition of apoptosis. Thus, the present findings relating to several anticancer therapeutics and three thyroid cancer cell lines demonstrate the pro-survival effect of autophagy in thyroid cancer treatment. Although the present study only involved cell lines, it provides evidence for the beneficial combination of the anticancer therapeutic modalities with autophagy inhibitors, and proposes that autophagy inhibitors may serve as a possible adjunctive therapy for thyroid cancer.

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Cancer metastasis, a process that primary tumor cells disseminate to secondary organs, is the most lethal and least effectively treated characteristic of human cancers. Kisspeptins are proteins encoded by the KISS1 gene that was originally described as a melanoma metastasis suppressor gene. Then, Kisspeptins were discovered as the natural ligands of the G-protein-coupled receptor 54 (GPR54) that is also called KISS1R. The KISS1/KISS1R signaling is essential to control GnRH secretion during puberty and to establish mammalian reproductive function through the hypothalamic-pituitary-gonadal (HPG) axis. Although KISS1 primarily plays a suppressive role in the metastasis progression in several cancer types, emerging evidence indicates that the physiological effect of KISS1/KISS1R in cancer metastasis is tissue context-dependent and still controversial. Here, we will discuss the epigenetic mechanism involved in the regulation of KISS1 gene expression, the context-dependent role of KISS1/KISS1R, prometastasis/anti-metastasis signaling pathways of KISS1/KISS1R, and the perspective anticancer therapeutics via targeting KISS1/KISS1R.

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BACKGROUND: Intrinsic rhythms in host and cancer cells play an imperative role in tumorigenesis and anticancer therapy. Circadian medicine in cancer is principally reliant on the control of growth and development of cancer cells or tissues by targeting the molecular clock and implementing time-of-day-based anticancer treatments for therapeutic improvements. In recent years, based on extensive high-throughput studies, we witnessed the arrival of several drugs and drug-like compounds that can modulate circadian timekeeping for therapeutic gain in cancer management. OBJECTIVE: This perspective article intends to illustrate the current trends in circadian medicine in cancer, focusing on clock-modulating pharmacological compounds and circadian regulation of anticancer drug metabolism and efficacy. Scope and Approach: Considering the critical roles of the circadian clock in metabolism, cell signaling, and apoptosis, chronopharmacology research is exceedingly enlightening for understanding cancer biology and improving anticancer therapeutics. In addition to reviewing the relevant literature, we investigated the rhythmic expression of molecular targets for many anticancer drugs frequently used to treat different cancer types. Key Findings and Conclusion: There are adequate empirical pieces of evidence supporting circadian regulation of drug metabolism, transport, and detoxification. Administration of anticancer drugs at specific dosing times can improve their effectiveness and reduce the toxic effects. Moreover, pharmacological modulators of the circadian clock could be used for targeted anticancer therapeutics such as boosting circadian rhythms in the host can markedly reduce the growth and viability of tumors. All in all, precision chronomedicine can offer multiple advantages over conventional anticancer therapy.

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