Osteosarcoma (OS) is a fatal malignant tumor that occurs in bone, whose main treatment is surgical resection. With anti-tumor and osteogenic effects, Magnesium (Mg) is a promising biodegradable metal for postoperative treatment in OS, however, its anti-OS effect and mechanism still need to be explored. Here, while holding the ability to promote osteogenesis, Mg metal at the same time significantly reduces the proliferation, migration and invasion of various OS cells (UMR106, 143B, K7M2) in vitro. Similarly, it inhibits the growth and lung metastasis of UMR106 induced tumors in xenograft models in vivo. The mRNA-seq analysis shows that Mg significantly inhibits Wnt-pathway (increased APC, Axin2 and GSK3β to induce degradation of β-catenin) in typical OS, which is further verified by western blotting and immunofluorescence analyses. A Mg2+ concentration of 240 mg/L, either from Mg metal extract or Mg salt (MgCl2), equivalently exhibits significantly increased APC, Axin2, GSK3β and decreased β-catenin, and then inhibits tumorigenicity of typical OS cells. This work reveals that a local high concentration of Mg can inhibit OS by down-regulating Wnt-pathway, and meanwhile favors for normal health bone, which demonstrates a new approach and mechanism in the treatment of OS with Mg-based biodegradable metals.

Cervical cancer remains a critical global health concern, demanding the development of innovative therapies to address the limitations of conventional chemotherapeutics, including systemic toxicity and lack of specificity. Silver nanoparticles synthesized using Gracilaria edulis (GE-AgNPs) present a novel therapeutic strategy, exhibiting selective cytotoxicity against the HEK293 normal epithelial cell line and HeLa cervical cancer cell line. Phytochemical analysis of Gracilaria edulis identified bioactive compounds such as 4-Benzaldehyde and 1H-1,3-Benzimidazole-1-acetonitrile, both associated with potent anticancer activities. Comprehensive characterization of GE-AgNPs through spectroscopy and microscopy revealed distinctive physicochemical properties, including an absorption peak at 332 nm and a hexagonal crystalline structure. Cytotoxicity assays confirmed that GE-AgNPs induce apoptosis in HeLa cells exhibit a concentration-dependent response, with an IC50 value of 54.05 μg/mL, while GE-AgNPs exhibited no significant toxicity to HEK293 cells at the tested concentrations, as evidenced by a higher IC50 value of 83.6 μg/mL. The pro-apoptotic effect was mediated through the development of reactive oxygen species (ROS), validated using dual staining and Hoechst assays, which demonstrated chromatin condensation indicative of apoptosis. Molecular analysis further elucidated the mechanism of action, highlighting significant inhibition of the PI3K/AKT signaling pathway. This was evidenced by downregulation of PI3K, AKT, and mTOR genes alongside the upregulation of PTEN, a critical tumor suppressor. Zebrafish embryo toxicity assays provided insights into the biocompatibility of GE-AgNPs, revealing low toxicity at therapeutic concentrations but developmental abnormalities and neurotoxicity at higher doses. These findings underscore the promise of GE-AgNPs as a targeted therapy option for cervical cancer, effectively modulating the PI3K/AKT pathway while maintaining manageable toxicity profiles. Further investigations into optimizing dosing regimens and exploring synergistic effects with existing treatments could enhance their clinical applicability.

The toxicity of chemicals and drugs is a common crisis worldwide. Therefore, the search for protective compounds is growing. Natural compounds such as indole-3-carbinol (I3C) derived from cruciferous vegetables are preferred since they are safe for humans and the environment. This review focuses on I3C potential role in preventing and repairing damage caused by chemicals and drugs. Interestingly, I3C ameliorates hepatotoxicity induced by carbon tetrachloride (CCl4), diethylnitrosamine (DENA), alcohol, gold nanoparticles, and microbial toxins. Additionally, it inhibits carcinogenesis induced by different chemicals and prevents the deleterious effects of different antineoplastic drugs including cisplatin, doxorubicin (DOX), and trabectidin on normal tissues. Moreover, it reduces fetal malformation and protects against micronuclei formation and calstogenecity induced by cyclophosphamide (CP) in bone marrow cells. It also attenuates methotrexate (MTX)-induced hepatotoxicity, mitigates neurotoxicity caused by thioacetamide and clonidine, and protects against aspirin side effects in gastric mucosa. Furthermore, its nanoparticles inhibit neuronal damage caused by glutamate and rotenone. Thus, I3C prevents the toxicities caused by chemicals in the surrounding environment as well as those of consumed drugs.

Antibodies are crucial tools in various biomedical applications, including immunotherapy. In this study, we focused on designing and engineering antibodies to enhance their structural dynamics and functional properties. By employing advanced computational techniques and experimental validation, we gained crucial insights into the impact of specific mutations on the engineered antibodies. This study investigates the design and engineering of antibodies to improve their structural dynamics and functional properties. Structural attributes, such as protein compactness and solvent accessibility, were assessed, revealing interesting trends in anti-CD3 and anti-HER2 antibodies. Mutations in CD3 antibodies resulted in a more stable conformation, while mutant HER2 antibodies exhibited altered interaction with the target. Analysis of secondary structure assignments demonstrated significant changes in the folding and stability of the mutant antibodies compared to the wild-type counterparts. The conformational landscape of the engineered antibodies was explored, providing insights into folding pathways and binding mechanisms. Overall, the current study highlights the significance of antibody design and engineering in modulating structural dynamics and functional properties. The findings contribute to developing improved immunotherapeutic strategies by optimising antibody-based therapeutics for targeted diseases with enhanced efficacy and precision.

Cancer treatments often exploit oxidative stress to selectively kill tumour cells by disrupting their lipid peroxidation membranes and inhibiting antioxidant enzymes. However, lipid peroxidation plays a dual role in cancer progression, acting as both a tumour promoter and a suppressor. Balancing oxidative stress through antioxidant therapy remains a challenge, as excessive antioxidant activity may compromise the efficacy of chemotherapy and radiotherapy.

This review explores the role of antioxidants in mitigating lipid peroxidation in cancer therapy while maintaining treatment efficacy. It highlights recent advancements in nanotechnology-based targeted antioxidant delivery to optimize therapeutic outcomes.

A comprehensive literature review was conducted using reputable databases, including PubMed, Scopus, Web of Science, and ScienceDirect. The search focused on publications from the past five years (2020-2025), supplemented by relevant studies from earlier years. Keywords such as "antioxidants," "lipid peroxidation," "nanotechnology in cancer therapy," and "oxidative stress" were utilized. Relevant articles were critically analysed, and graphical illustrations were created.

Emerging evidence suggests that nanoparticles, including liposomes, polymeric nanoparticles, metal-organic frameworks, and others, can effectively encapsulate and control the release of antioxidants in tumour cells while minimizing systemic toxicity. Stimuli-responsive carriers with tumour-specific targeting mechanisms further enhance antioxidant delivery. Studies indicate that these strategies help preserve normal cells, mitigate oxidative stress-related damage, and improve treatment efficacy. However, challenges such as bioavailability, stability, and potential interactions with standard therapies remain.

Integrating nanotechnology with antioxidant-based interventions presents a promising approach for optimizing cancer therapy. Future research should focus on refining lipid peroxidation modulation strategies, assessing oxidative stress profiles during treatment, and employing biomarkers to determine optimal antioxidant dosing. A balanced approach to antioxidant use may enhance therapeutic efficacy while minimizing adverse effects.

Differentiation arrest and dependence on oxidative metabolism are features shared among genetically diverse acute myeloid leukemias (AMLs). A phenotypic CRISPR-CRISPR-associated protein 9 screen in AML identified dependence on phosphoseryl-transfer RNA kinase (PSTK), an atypical kinase required for the biosynthesis of all selenoproteins. In vivo, PSTK inhibition (PSTKi) impaired AML cell growth and leukemic stem cell self-renewal. Notably, timed pharmacologic PSTKi effectively targeted chemotherapy-resistant AML in murine and patient-derived xenograft models, showing selectivity for malignant cells over normal hematopoietic cells. Mechanistically, PSTKi-induced reactive oxygen species (ROS) triggering mitochondrial DNA release into the cytosol and activated cyclic GMP-AMP Synthase-Stimulator of interferon genes (cGAS-STING). This activation, in turn, disrupted iron metabolism, augmenting ROS generation, and amplifying ferroptosis. Together, these findings reveal a self-reinforcing PSTK-cGAS-STING-ROS loop, culminating in an oxidative crisis and ferroptotic cell death of leukemic stem cells. These data highlight the potential for augmenting standard cancer chemotherapies using timed metabolic intervention to eliminate chemotherapy-persisting cells and thereby impede disease relapse.

Platinum-based chemotherapy has been the first-line treatment for advanced bladder cancer for decades, but its durability and safety remain important challenges. Targeted delivery and other precision medicine bring hope to fight cancer. In this study, we present a novel targeted therapy utilizing a biotin receptor-targeting lipid PtIV prodrug amphiphile, which encapsulates a CDK4/6 inhibitor into BPtIV@Rib. CDK4/6 inhibitors have the potential to combat breast cancer and enhance sensitivity to cisplatin, thereby improving its therapeutic efficacy. Our findings demonstrate that BPtIV@Rib also exhibits excellent bladder tumor-targeting capability, resulting in increased accumulation of Pt and ribociclib (Rib) at the tumor site. The combination of PtIV and Rib leads to substantial tumor growth suppression while minimizing synergistic toxicity compared to conventional therapies. In conclusion, this combination therapy represents a promising strategy for enhanced targeted treatment of bladder cancer, potentially improving patient outcomes while reducing adverse effects.

ShenJiaoLingCao Decoction (SJLCD) is derived from the classic Chinese medicine prescription, which consists of ten kinds of herbs. In China, SJLCD has been used as an immunomodulator in clinical practice for more than ten years. However, no relevant studies have been done to clarify the pharmacodynamic underpinnings of its regulation of the body's immune system and its related processes.

This study aims to assess the immunomodulatory effects of SJLCD.

Ultra performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap MS) was utilized to characterize the chemical constituents in SJLCD and establish its fingerprint profile. Predicting potential bioactive compounds in SJLCD for immunomodulatory effects and elucidating their mechanisms of action using artificial intelligence technology. Experiments at the animal level were carried out to verify the accuracy of the predictions. Firstly, an immunocompromised model was constructed by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX) into rats for 3 consecutive days, and SJLCD was administered by oral administration for 14 days. The immunomodulatory effect of SJLCD on immune organs was verified by evaluating the immune organ index and histopathological examinations using hematoxylin and eosin (H&E) staining. The effect of SJLCD on relevant immune cells was examined by measuring erythrocytes, leukocytes and lymphocytes. The effect of SJLCD on relevant immune molecules was assessed by detecting the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP9), cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8). Western blot was used to verify and analyze the possible immunomodulatory mechanisms of SJLCD. Finally, serum untargeted metabolomics was used to detect the differential metabolites of SJLCD in immunocompromised rats.

In this study, a total of 91 compounds were identified in the SJLCD, and the results showed a high degree of similarity (S1-S11 > 0.935) among the 11 samples in positive ion mode. Artificial intelligence computer techniques predicted that quercetin, kaempferol, and fumarine in SJLCD bound better to core targets, especially MAPK1. On animal-level validation, it was found that from an immune organ perspective, SJLCD ameliorated CTX-induced thymus and spleen damage. From an immune cell perspective, SJLCD significantly increased peripheral erythrocyte, leukocyte and lymphocyte counts in immunocompromised rats. From the immune molecular level, SJLCD down-regulated the levels of TNF-α, IL-6, IL-1β, MMP9, CD8 and up-regulated the level of CD3 and CD4 which normalize its secretion. Mechanistically, SJLCD regulates immunity possibly through the MEK/ERK signaling pathway and by affecting amino acid metabolism.

In the present study, we found that SJLCD has satisfactory immunomodulatory activity, which may be achieved by affecting the MEK/ERK signaling pathway and amino acid metabolism of the body.

Dietary interventions can influence tumor growth by restricting tumor-specific nutritional requirements, altering the nutrient availability in the tumor microenvironment, or enhancing the cytotoxicity of anticancer drugs. Metabolic reprogramming of tumor cells, as a significant hallmark of tumor progression, has a profound impact on immune regulation, severely hindering tumor eradication. Dietary interventions can modify tumor metabolic processes to some extent, thereby further improving the efficacy of tumor treatment. In this review, we emphasize the impact of dietary patterns on tumor progression. By exploring the metabolic differences of nutrients in normal cells versus cancer cells, we further clarify how dietary patterns influence cancer treatment. We also discuss the effects of dietary patterns on traditional treatments such as immunotherapy, chemotherapy, radiotherapy, and the gut microbiome, thereby underscoring the importance of precision nutrition.

Astragalus mongholicus Bunge [Fabaceae; Astragali radix] is an herb widely used in traditional Chinese medicine. It has diuretic, anti-aging, antihypertensive, immune-boosting, liver-protective, anti-stress and other extensive pharmacological effects. In recent years, Astragalus and its extract have been used to treat lung and stomach qi deficiency as well as general qi deficiency. This paper summarizes the mode of action and mechanisms of Astragalus in treating various diseases, and provides valuable insights for the future application, development, and improvement of Astragalus. In this paper, literature on the use of Astragalus in treating related diseases over the past five years was collected from PubMed and CNKI databases, and the pathogenic mechanisms of Astragalus and its extracts were reviewed. Its mechanism of action is primarily involved in antioxidant protection, anti-inflammatory effects, and anti-apoptotic properties. This provides a new research direction for future studies and clinical treatments using Astragalus.

Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy, offering the potential to reduce disease-causing proteins that have traditionally been challenging to target using conventional small molecules. Despite significant advances made with TPD technologies, challenges such as high molecular weight, difficulties in identifying suitable ligands, suboptimal absorption, and metabolic instability remain unresolved. Recently, aptamers - single-stranded DNA or RNA oligonucleotides known for their high specificity and affinity for protein targets - have introduced novel opportunities to expand the scope of TPD, a strategy now referred to as aptamer-based TPD. This approach has demonstrated considerable promise in treating various diseases, such as cancer and ocular disorders. For example, an aptamer-proteolysis-targeting chimera (PROTAC) conjugate (APC) improved tumor targeting and reduced toxicity in a breast cancer model, and a vascular endothelial growth factor-degrading (VED)-lysosome-targeting chimera (LYTAC) molecule effectively inhibited abnormal vascular growth in vascular retinal diseases. These examples highlight the practical relevance and potential in advancing drug discovery efforts. In this review we provide a comprehensive overview of the latest advances in aptamer-based TPD strategies, including proteolysis-targeting and lysosome-targeting chimeras, emphasizing their applications, potential therapeutic benefits, as well as the challenges that must be overcome to fully harness their clinical potential. © 2025 The Pathological Society of Great Britain and Ireland.

Women's health management plays a crucial role in modern healthcare, encompassing the prevention, detection, and treatment of female diseases. However, existing technologies often face challenges, such as the invasiveness and discomfort associated with serological testing and injection-based therapies. Microneedles, as an emerging technology in biomedical engineering, demonstrate significant advantages. These micron-sized transdermal devices are applicable in a range of applications, from drug delivery to interstitial fluid sampling, and their painless, minimally invasive nature significantly enhances medication compliance. In recent years, microneedles have been widely utilized in women's health management, showing promising results in early disease prevention and subsequent treatment. Although there are reviews about microneedles applied in disease treatment management, few of them focus on the application of microneedles in the prevention and early detection of women's disease. Herein, we present a comprehensive overview of the current application status of microneedles in women's health management, with a special emphasis on their design and mechanism for disease prevention, and treatment in women. Finally, we discuss the advantages and limitations of microneedles in women's health management, and propose suggestions for future research direction.

Cancer immunotherapy has transformed the landscape of oncological treatment by employing various strategies to teach the immune system to eliminate tumors. Among these, cancer nanovaccines are an emerging strategy that utilizes nanotechnology to enhance immune activation in response to tumor antigens. This review addresses the principles behind the different technologies in this field aimed at generating a robust and effective immune response. The diversity of strategies adopted for the design of nanovaccines is discussed, including the types of active agents, nanocarriers, their functionalizations, and the incorporation of adjuvants. Furthermore, strategies to optimize nanoparticle formulations to enhance the antigen presentation, target immune cells, and organs and promote strong and durable antitumor responses are explored. Finally, we analyze the current state of clinical application, highlighting ongoing clinical trials and the future potential of cancer nanovaccines. The insights presented in this review aim to guide future research and development efforts in the field, contributing to the advancement of more effective and targeted nanovaccines in the fight against cancer.

Galectin-1 (Gal-1), a member of the β-galactoside-binding soluble lectin family, is a double-edged sword in immunity. On one hand, it plays a crucial role in regulating diverse immune cell functions, including the apoptosis of activated T cells. These processes are key in resolving inflammation and preventing autoimmune diseases. On the other hand, Gal-1 has significant implications in cancer, where tumor cells and the tumor microenvironment (TME) (e.g., tumor-associated fibroblasts, myeloid-derived suppressor cells) secrete Gal-1 to evade immune surveillance and promote cancer cell growth. Within the TME, Gal-1 enhances the differentiation of tolerogenic dendritic cells, induces the apoptosis of effector T cells, and enhances the proliferation of regulatory T cells, collectively facilitating tumor immune escape. Therefore, targeting Gal-1 holds the potential to boost anti-tumor immunity and improve the efficacy of cancer immunotherapy. This review provides insights into the intricate role of Gal-1 in immune cell regulation, with an emphasis on T cells, and elucidates how tumors exploit Gal-1 for immune evasion and growth. Furthermore, we discuss the potential of Gal-1 as a therapeutic target to augment current immunotherapies across various cancer types.

Cancer is currently the second most common cause of death worldwide and is often treated with chemotherapy. Music therapy is a widely used adjunct therapy offered in oncology settings to attenuate negative impacts of treatment on patient's physical and mental health; however, music therapy research during chemotherapy is relatively scarce. The aim of this study is to evaluate the impact of group music therapy sessions with patients and caregivers on their perceived anxiety, stress, and wellbeing levels and the perception of chemotherapy-induced side effects for patients.

This is a retrospective cohort study following the STROBE guidelines. From April to October 2022, 41 group music therapy sessions including 141 patients and 51 caregivers were conducted. Participants filled out pre- and post-intervention Visual Analogue Scales (VAS) assessing their anxiety, stress, and wellbeing levels, and for patients the intensity of chemotherapy-induced side effects.

The results show a statistically significant decrease of anxiety and stress levels (p < .001), an increase in well-being of patients and caregivers (p < .001, p = .009), and a decrease in patients' perceived intensity of chemotherapy-induced side effects (p = .003). Calculated effect sizes were moderate for anxiety, stress, and well-being levels, and small for chemotherapy-induced side effects.

This is the first study regarding group music therapy sessions for cancer patients and their caregivers during chemotherapy in Colombia. Music therapy has been found to be a valuable strategy to reduce psychological distress in this population and to provide opportunities for fostering self-care and social interaction.

Music therapy should be considered as a valuable complementary therapy during chemotherapy. However, it is crucial to conduct prospective studies with parallel group designs to confirm these preliminary findings.

Today, treating cancer patients with monoclonal antibodies (mAbs), by targeting immune checkpoints, is one of the most outstanding immunotherapeutic methods. Immune checkpoints are special molecules having regulatory role in immune system responses. Once these molecules are presented on cancer cells, these cells will be capable of evading the immune system through their own specific pathways. This Evasion can be prevented by counterbalancing immune system responses with immune checkpoints related antibodies.

The current study aimed to highlight immunotherapy and its methods, describe the immune checkpoints pathways, outline the immune checkpoint inhibitors (ICIs), and recent advances in this field, and sketch an outlook on the best treatment options for the most prevalent cancers.

This research implemented a narrative review method. A comprehensive literature review on the history, molecular and cellular biology, and the clinical aspects of immune checkpoint molecules was performed to illustrate the pathways involved in various cancers. Also, currently-available and future potential immunotherapies targeting these pathways were extracted from the searched studies.

The immune checkpoint family consists of many molecules, including CTLA-4, PD-1, PD-L1, LAG-3, TIM-3, and TIGIT. Attempts to modify these molecules in cancer treatment led to the development of therapeutic monoclonal antibodies. Most of these antibodies have entered clinical studies and some of them have been approved by the Food and Drug Administration (FDA) to be used in cancer patients' treatment plans.

With these novel treatments and the combination therapies they offer, there is also hope for better treatment outcomes for the previously untreatable metastatic cancers. In spite of the beneficial aspects of immune checkpoint therapy, similar to other treatments, they may cause side effects in some patients. Therefore, more studies are needed to reduce the probable side effects and uncover their underlying mechanism.

Based on the data shown in this review, there is still a lack of knowledge about the complete properties of ICIs and the possible combination therapies that we may be able to implement to achieve a better treatment response in cancer patients.

This study aimed to examine how mesoporous silica nanoparticles-chitosan-folic acid impacted the release of recombinant Azurin within the tumor environment. The goal was to trigger apoptosis and stimulate immune responses against both transformed and normal cells in BALB/c mice. The study found that the use of rAzu-MSNs-CS-FA, a specific formulation containing mesoporous silica nanoparticles-chitosan-folic acid, resulted in pH-responsive behavior and slower release of rAzurin compared to other groups. This formulation inhibited MCF7 cells at higher concentrations, induced apoptosis in cells, and caused DNA degradation. It also increased the uptake efficiency of rAzurin and stimulated the secretion of TNF-α, INF-γ, and IL-4 while inhibiting the secretion of IL-6. Furthermore, it regulated the expression of specific genes (upregulating tlr3 and downregulating tlr2, 4, and 9). In animal studies with BALB/c mice, the rAzu-MSNs-CS-FA formulation led to tumor regression and decreased tumor volume over 21 days. Overall, this formulation showed promising results in inducing cytotoxic effects against cancer cells, promoting apoptosis, and eliciting appropriate immune responses, suggesting its potential as a valuable therapy for breast cancer.

Combination therapy, involving the concurrent use of multiple medications, has become crucial for managing complex diseases with diverse pathological mechanisms. Fixed-Dose Combinations (FDCs) are formulated to leverage the synergistic effects of multiple drugs, thereby enhancing therapeutic outcomes. However, conventional FDCs typically maintain therapeutic effects for only up to 24 h and require frequent dosing, which often results in patient non-compliance and inconsistent treatment responses, especially in chronic diseases. This highlights the urgent need for long-acting FDCs that can provide sustained drug release over extended periods-weeks, months, or even years-thereby reducing dosing frequency and enhancing patient adherence. Microspheres, with their ability to encapsulate and release multiple medications in predefined patterns, are highly advantageous for developing long-acting FDC drugs. This review emphasizes the increasing demand for long-acting FDC drugs that ensure sustained drug release, reduce dosing frequency, and ultimately improve patient adherence. We also highlight the potential of microsphere technology, which enables precise encapsulation and sustained release of multiple medications, as a promising approach for revolutionizing long-acting FDCs with enhanced therapeutic outcomes.

Lipid nanoparticles are obtaining significant attention in cancer treatment because of their efficacy at delivering drugs and reducing side effects. These things are like a flexible platform for getting anticancer drugs to the tumor site, especially upon HA modification, a polymer that is known to target tumors overexpressing CD44. HA is promising in cancer therapy because it taregtes tumor cells by binding onto CD44 receptors, which are often upregulated in cancer cells. Lipid nanoparticles are not only beneficial in improving solubility and stability of drugs; they also use the EPR effect, meaning they accumulate more in tumor tissue than in healthy tissue. Adding HA to these nanoparticles expands their biocompatibility and makes them more accurate and specific towards tumor cells. Studies show that HA-modified nanoparticles carrying drugs such as paclitaxel or doxorubicin improve how well cells absorb the drugs, reduce drug resistance, and make tumor shrinking. These nanoparticles can respond to tumor microenvironment stimuli in targeted delivery. This targeted delivery diminishes side effects and improves anti-cancer activity of drugs. Thus, lipid-based nanoparticles conjugated with HA are a promising way to treat cancer by delivering drugs effectively, minimizing side effects, and giving us better therapeutic results.

In this article, we develop nonparametric inference methods for comparing survival data across two samples, beneficial for clinical trials of novel cancer therapies where long-term survival is critical. These therapies, including immunotherapies and other advanced treatments, aim to establish durable effects. They often exhibit distinct survival patterns such as crossing or delayed separation and potentially leveling-off at the tails of survival curves, violating the proportional hazards assumption and rendering the hazard ratio inappropriate for measuring treatment effects. Our methodology uses the mixture cure framework to separately analyze cure rates of long-term survivors and the survival functions of susceptible individuals. We evaluated a nonparametric estimator for the susceptible survival function in a one-sample setting. Under sufficient follow-up, it is expressed as a location-scale-shift variant of the Kaplan-Meier estimator. It retains desirable features of the Kaplan-Meier estimator, including inverse-probability-censoring weighting, product-limit estimation, self-consistency, and nonparametric efficiency. Under insufficient follow-up, it can be adapted by incorporating a suitable cure rate estimator. In the two-sample setting, in addition to using the difference in cure rates to measure long-term effects, we propose a graphical estimand to compare relative treatment effects on susceptible subgroups. This process, inspired by Kendall's tau, compares the order of survival times among susceptible individuals. Large-sample properties of the proposed methods are derived for inference and their finite-sample properties are evaluated through simulations. The methodology is applied to analyze digitized data from the CheckMate 067 trial.

Breast cancer (BC) is the most prevalent form of cancer in women worldwide and the main cause of cancer-related fatalities in females. BC can be classified into various types based on where cancer has begun to grow or spread, specific characteristics that influence how cancer behaves, and treatment choices. BC is multifaceted, and due to its diverse nature, the mechanisms involved are complex and have not yet been understood. Overexpression and expression of various factors involved in the functioning of mechanisms lead to abnormal changes, providing an environment supporting cancer cell growth. Understanding BC risk factors and early diagnosis through screening techniques like mammography and diagnostic techniques such as imaging and biopsies has advanced significantly. A wide range of treatment options, including surgery, radiation, chemotherapy, targeted treatments, and hormonal therapies, are now available. Daily advancements are being made in the clinical treatment of BC. Still, BC drug resistance cases remain highly prevalent and are currently one of the biggest problems faced by medical science. To increase response rates and possibly lengthen survival, there is a critical requirement for novel medicines with minimal sensitivity to overcome drug resistance. This review classifies different mechanisms that are involved in the development of BC and workable pharmacological targets and explains how they relate to the development of BC drug resistance. By concentrating on the mechanisms covered in this review, we can have a deep understanding of different mechanisms and learn innovative ways to develop novel therapeutics for the disease to combat medication resistance.

Immunosuppression increases disease risk, and the natural compound polydatin (PD) has been reported to modulate immune-related disorders. In cyclophosphamide-induced immunosuppressed mice, PD was evaluated for its immunomodulatory effects. Immune organ indices were measured, while H&E staining and ELISA assessed spleen pathology and serum cytokine levels. The proliferation of splenic lymphocytes, both total and subpopulation, was determined using concanavalin A or lipopolysaccharide stimulation, with flow cytometry analyzing peripheral blood and splenic lymphocytes, thymic T cell subtypes, cell cycling, and bromodeoxyuridine incorporation. Western blotting was used to assess Ki67, PCNA expression, and MAPK activation. PD significantly alleviated cyclophosphamide-induced reductions in spleen and thymus indices, improved the organization of red and white pulp in the spleen, and restored TNF-α and IFN-γ levels. It reversed cyclophosphamide-induced cell cycle arrest, characterized by increased PCNA and decreased Ki67, and corrected the diminished numbers of B and T cells and the reduced CD4+/CD8+ ratio in the thymus. In vitro, PD directly promoted splenic lymphocyte proliferation and cell cycling via MAPK activation. Overall, our findings demonstrated that PD alleviated mouse immunosuppression by activating splenic lymphocyte proliferation and re-organizing thymic T cell development and differentiation.

Marine microorganisms are a promising source of innovative compounds for medical applications. The present study aimed to investigate anticancer potential of oversulfated low molecular weight derivatives, named OSIDs, prepared from infernan, a marine bacterial exopolysaccharide. In order to identify a lead, OSIDs with different sulfate contents and molecular weights were firstly evaluated in vitro in a large series of human and murine tumor cell lines. Among all derivatives tested, OSID4 was the most effective, showing a significant dose-dependent inhibitory effect on the viability of cancer cells. OSID4 was then able to significantly slow down progression of lung and melanoma tumor growth in immunocompetent tumor-bearing mouse models. In immunodeficient mice bearing a human lung carcinoma, a notable inhibitory effect of OSID4, comparable to doxorubicin, was observed. In combination with doxorubicin, OSID4 did not exhibit any drug interaction. The activity of OSID4 was confirmed by its modulatory effect on the transcriptomic profile of human lung cancer cells. Finally, toxicity and pharmacokinetic parameters disclosed that OSID4 presented no toxicity and no bleeding risk. In conclusion, by combining its notable anticancer and moderate anticoagulant activities, OSID4 may be promising for treatment of cancers associated with a high risk of thromboembolic events.

Antidiabetic biologicals (ADBs) have revolutionized the treatment of diabetes mellitus, once considered incurable through conventional medicine. These biological products, derived from natural sources via extraction, semi-synthesis, or recombinant DNA technology, include insulin and its analogs, GLP-1 receptor agonists, amylin analogs, and the recently approved monoclonal antibody teplizumab. Regulatory authorities worldwide have established QC parameters outlined in pharmacopoeias, alongside analytical techniques to ensure their safety and efficacy. This review focuses on the analytical techniques used to assess QC parameters of ADBs, including chromatographic methods, spectroscopic techniques, capillary electrophoresis, immunoassays, and endotoxin testing. Key parameters such as identification, potency, purity, and impurity profiling are thoroughly examined. The paper provides a comprehensive and up-to-date compilation of QC requirements and methodologies, along with a detailed comparison of analytical techniques. In doing so, it highlights their advantages and limitations, offering valuable insights for researchers and regulatory professionals involved in selecting suitable methods for QC assessment and understanding the complexities of ADBs evaluation. Furthermore, the article discusses the paramount importance of QC and future perspectives, emphasizing the transition to advanced versions of current techniques driven by the need for efficiency and reliability in quality testing.

Genetic information, which is mostly encoded in the form of DNA sequence, is the basis of life. Its deviations are often the cause of the most deadly diseases such as cancer. Accordingly, the development of methods to control the transcription of certain DNA parts is an important direction of modern pharmacological and biological research. Within the scope of this work, we are investigating the second generation of a polyintercalating agent that we developed earlier, potentially capable of recognizing 16-bp DNA sequences. In order to confirm its ability for advanced selective DNA recognition a series of simulation experiments was conducted. We differentially investigated the stability of HASDI-G2 complexes with mutated targeting sequences and their native variants. Firstly, we confirmed the ability of HASDI-G2 to clearly discriminate the target sequence (EBNA1) from a random site in the human genome (KCNH2). That repeated the experiment of the polyintercalator's previous version and additionally showed better results of the next-generation structure. Next, we examined HASDI-G2 under conditions where the target sequence differed from the random one increasingly slightly. And we found that even a one-nucleotide mismatch leads to a similar complex destabilization as a mismatch of 3 or 4 nucleotides. Such complexes showed significant conformational rearrangements, accompanied by a sharp decrease in the hydrogen bonds quantity, a drop in the binding free energy, and local melting of the DNA duplex. Moreover, the latter applied not only to sites of direct incompatibility, but also to parts where HASDI-G2 fully corresponded to the sequence of intercalation.

Triple-Negative Breast Cancer (TNBC) is a highly aggressive subtype of breast cancer (BC) characterized by the absence of estrogen, progesterone, and HER2 receptors, resulting in limited therapeutic options. This article critically examines the role of Artificial Intelligence (AI) in enhancing the diagnosis and treatment of TNBC treatment. We begin by discussing the incidence of TNBC and the fundamentals of precision medicine, emphasizing the need for innovative diagnostic and therapeutic approaches. Current diagnostic methods, including conventional imaging techniques and histopathological assessments, exhibit limitations such as delayed diagnosis and interpretative discrepancies. This article highlights AI-driven advancements in image analysis, biomarker discovery, and the integration of multi-omics data, leading to enhanced precision and efficiency in diagnosis and treatment. In treatment, AI facilitates personalized therapeutic strategies, accelerates drug discovery, and enables real-time monitoring of patient responses. However, challenges persist, including issues related to data quality, model interpretability, and the societal impact of AI implementation. In the conclusion, we discuss the future prospects of integrating AI into clinical practice and emphasize the importance of multidisciplinary collaboration. This review aims to outline key trends and provide recommendations for utilizing AI to improve TNBC management outcomes, while highlighting the need for further research.

Keratins, as essential components of intermediate filaments in epithelial cells, play a crucial role in maintaining cell structure and function. In various malignant epithelial tumors, abnormal keratin expression is frequently observed and serves not only as a diagnostic marker but also closely correlates with tumor progression. Extensive research has demonstrated that keratins are pivotal in multiple stages of tumor metastasis, including responding to mechanical forces, evading the immune system, reprogramming metabolism, promoting angiogenesis, and resisting apoptosis. Here we emphasize that keratins significantly enhance the migratory and invasive capabilities of tumor cells, making them critical drivers of tumor metastasis. These findings highlight the importance of targeting keratins as a strategic approach to combat tumor metastasis, thereby advancing our understanding of their role in cancer progression and offering new therapeutic opportunities.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD. Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Phototherapy based on micro light-emitting diodes (µLEDs) has gained enormous attention in the medical field as a patient-friendly therapeutic method due to its advantages of minimal invasiveness, fewer side effects, and versatile device form factors with high stability in biological environment. Effective cosmetic and medical phototherapy depends on deep light penetration, precise irradiation, and simultaneous multi-site stimulation, facilitated by three-dimensional (3D) optoelectronics specifically designed for complex human matters, defined here as 3D µLEDs. This perspective article aims to present the functionalities and strategies of 3D µLEDs for human-centric phototherapy. This study investigates the effectiveness of phototherapy enabled by three key functionalities such as shape morphing, self-adaptation, and multilayered spatiotemporal mapping of 3D µLEDs. Finally, this article provides future insights of 3D µLEDs for human-centric phototherapy applications.

In recent decades, significant attention has been directed towards gold nanoparticles due to their exceptional properties, capturing the interest of researchers globally. Their unique characteristics, such as localized surface plasmon resonance, high surface area to volume ratio, biocompatibility, and facile surface functionalization, render them highly suitable for diverse applications, ranging from optoelectronics and sensing to surface-enhanced spectroscopies and biomedical uses, particularly in the realm of photothermal therapy. Plasmonic photothermal therapy, an emerging biomedical technology, has garnered substantial interest for its potential in cancer treatment and management. This approach employs photothermal agents, such as gold nanoparticles, which absorb light in the near-infrared region. When these agents accumulate within cancer cells, the absorbed photon energy is converted into heat, inducing local hyperthermia. This localized effect selectively eliminates damaged cells adjacent to nanoparticles while sparing normal cells. Various shapes and sizes of gold nanoparticles have proven well-suited candidates for photothermal therapy. This paper provides an overview of the distinctive properties of gold nanoparticles. It delves into the surface functionalization techniques crucial for ensuring cancer cells' effective retention and targeting of gold nanoparticles. In this context, the present paper reviews diverse applications of gold nanoparticles with different shapes in plasmonic photothermal therapy, encompassing nanospheres, nanorods, nanoshells, nanostars, and nanocages.

This review discusses the literature data on the synthesis, physicochemical properties, and cytotoxicity of composite nanoparticles bearing the mitochondrial protein cytochrome c (cytC), which can act as a proapoptotic mediator in addition to its main function as an electron carrier in the electron transport chain. The introduction of exogenous cytC via absorption of carrier particles, the phagocytosis of colloid particles of submicrometric size, or the receptor-mediated endocytosis of nanoparticles in cancer cells, initiates the process of apoptosis-a multistage cascade of biochemical reactions leading to complete destruction of the cells. CytC-carrier composite particles have the potential for use in the treatment of neoplasms with superficial localization: skin, mouth, stomach, colon, etc. This approach can solve the two main problems of anticancer therapy: selectivity and non-toxicity. Selectivity is based on the incapability of the normal cell to absorb (nano)particles, except for the cells of the immune system. The use of cytC as a protein that normally functions in mitochondria is harmless for the macroorganism. In this review, the factors limiting cytotoxicity and the ways to increase it are discussed from the point of view of the physicochemical properties of the cytC-carrier particles. The different techniques used for the preparation of cytC-bearing colloids and nanoparticles are discussed. Articles reporting the achievement of high cytotoxicity with each of the techniques are critically analyzed.

Patients with advanced cancers visit the emergency room and get hospitalised frequently, with potentially half of these visits being avoidable. Our institution provides comprehensive, low-cost cancer treatment to a safety-net population in Texas. We performed a retrospective review of hospital readmission patterns amongst our oncology patients and developed a posthospitalisation workflow to reduce readmissions.

Following discharge, oncology patients were risk stratified based on their Length of stay, Acuity of admission, Charlson comorbidity index score and Emergency department visits+index in the past 6 months. The higher the score, the quicker the outpatient oncology follow-up. In addition to addressing acute issues related to hospitalisation, patients were also able to receive newly translated resources while in clinic.

The preintervention 30-day-readmission rate was 17.3% (June 2022-December 2022) (95% CI 13.4% to 21.8%). Meanwhile, the postintervention 30-day-readmission rate was 14.7% (June 2023-December 2023) (95% CI 10.9% to 19.2%). While a 2.6% reduction in readmissions was achieved, this decrease was not statistically significant (-2.6%; 95% CI -8.4% to 3.2%; p value=0.375). Emergency use utilisation decreased from 90% to 15%.

Our team was able to facilitate and coordinate outpatient care for oncology patients following hospitalisation. The expedited care allowed providers to ensure that the care plan after hospitalisation was well understood and accessible to the patient. Furthermore, language-appropriate resources were provided to patients at that time. Our intervention was feasible, easy to implement and quick to produce tangible improvements in patient care. More time is needed to determine whether this will create a statistically significant impact on readmission rates.

The development of type 2 diabetes (T2D) is largely dependent on the maintenance of pancreatic islet function and mass. Sexual dimorphism in T2D is evident in many areas, such as pathophysiology, treatment, and prevention. Mitogen-activated protein kinase phosphatase-2 (MKP-2) has a distinct role in the regulation of cell proliferation and the development of metabolic disorders. However, whether there is a causal relationship between MKP-2 and diabetes onset is unclear. The aim of this study was to determine the role of MKP-2 in the regulation of whole-body glucose homeostasis and the impact on pancreatic islet function using streptozotocin-induced pancreatic injury. Here, we show that female mice with whole-body deletion of MKP-2 exhibit hyperglycemia in mouse models treated with multiple low doses of streptozotocin (STZ). In comparison, both male MKP-2 wild-type and knockout mice were hyperglycemic. Consistent with the hyperglycemia, female MKP-2-deficient mice exhibited reduced islet size. Under T2D conditions, MKP-2-deficient mice display enhanced pancreatic JNK and ERK phosphorylation that is associated with the downregulation of genes important for pancreatic islet development and function, Pdx-1 and MafA. Furthermore, we found impaired metabolic flux in adipose tissue that is consistent with hyperglycemia and dysfunctional pancreas. MKP-2 deletion results in reduced Akt activation that is associated with increased adiposity and insulin resistance in female MKP-2 KO mice. These studies demonstrate the critical role of MKP-2 in the development of T2D diabetes in vivo. This suggests that MKP-2 may have a gender-specific role in diabetes development. This discovery raises the possibility that postmenopausal prevention of T2D may benefit from the activation of MKP-2 activity in islet cells.

In addition to its direct cytotoxic effects, ablative therapies as electrochemotherapy (ECT) can elicit indirect antitumor effects by triggering immune system responses. Here, we comprehensively analyzed this dual effectiveness of intratumoral ECT with chemotherapeutic drugs bleomycin (BLM), oxaliplatin (OXA), and cisplatin (CDDP). Our aim was to determine if ECT can act as in situ vaccination and thereby induce an abscopal effect. By evaluating ECT's potential for in situ vaccination, our goal was to pave the way for future advancements for its combination with emerging (immuno)therapies, leading to enhanced responses and outcomes.

We employed two mouse tumor models, the immunologically cold B16F10 melanoma and 4T1 mammary carcinoma, to explore both local and systemic (i.e., abscopal) antitumor effects following equieffective intratumoral ECT with BLM, OXA, and CDDP. Through histological analyses and the use of immunodeficient and metastatic (for abscopal effect) mouse models, we identified and compared both the cytotoxic and immunological components of ECT's antitumor efficiency, such as immunologically recognizable cell deaths (immunogenic cell death and necrosis) and immune infiltrate (CD11+, CD4+, CD8+, GrB+).

Differences in immunological involvement after equieffective intratumoral ECT were highlighted by variable kinetics of immunologically recognizable cell deaths and immune infiltrate across the studied tumor models. Particularly, the 4T1 tumor model exhibited a more pronounced involvement of the immune component compared to the B16F10 tumor model. Variances in the antitumor (immune) response were also detected based on the chemotherapeutic drug used in ECT. Collectively, ECT demonstrated effectiveness in inducing in situ vaccination in both tumor models; however, an abscopal effect was observed in the 4T1 tumor model only.

This is the first preclinical study systematically comparing the immune involvement in intratumoral ECT's efficiency using three distinct chemotherapeutic drugs in mouse tumor models. The demonstrated variability in immune response to ECT across different tumor models and chemotherapeutic drugs provides a basis for future investigations aimed at enhancing the effectiveness of combined treatments.

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including Escherichia coli, Salmonella, and Listeria monocytogenes, along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME). These bacteria and their derivatives possess intrinsic properties that stimulate the immune system, enhancing both innate and adaptive immune responses to further amplify therapeutic effects. The ability of bacteria to naturally accumulate in hypoxic tumor regions and their versatility in genetic modifications allow for tailored drug delivery strategies that synergistically enhance the effectiveness of chemotherapy, immunotherapy, and targeted therapies. This review comprehensively examines the fundamental principles of bacterial therapy, focusing on the strategies employed for bacterial engineering, drug loading, and the use of bacteria and their derivatives in targeted tumor therapy. It also discusses the challenges faced in optimizing bacterial delivery systems, such as safety concerns, unintended immune responses, and scalability for clinical applications. By exploring these aspects, this review provides a theoretical framework for improving bacterial-based drug delivery systems, contributing to the development of more effective and personalized cancer treatments.

Applying CAR T-cell therapy to treat solid tumors is especially challenging due to the immunosuppressive tumor microenvironment (TME). While our modular RevCAR system enhances the safety and controllability of CAR T-cell therapy, effectively targeting solid tumors remains difficult. Since PD-L1 is an immune checkpoint frequently upregulated by cancer cells and their microenvironment, it is a relevant target for solid tumors. Here, we introduce a novel PD-L1 RevTM capable of redirecting RevCAR T-cells to specifically target and kill PD-L1-expressing tumor cells, becoming activated and secreting pro-inflammatory cytokines. This is shown in vitro with monolayer and 3D models, including patient-derived cultures, and in vivo. Furthermore, we demonstrate in vitro and in vivo an AND-gated targeting of cells simultaneously expressing PD-L1 and another tumor-associated antigen by the Dual RevCAR system. Our findings suggest that RevCAR-mediated targeting of PD-L1 could be a promising therapeutic approach for modulating the TME and improving solid tumor treatment.

Cancer remains one of the most significant public health challenges globally, contributing to a substantial burden of disease across all populations. Conventional therapies of chemotherapy, radiation, and surgery are commonly used to treat all forms of cancer; however, they all have significant side effects to their use. Immunotherapy has emerged as an effective treatment type for a variety of cancers. As the benefits of immunotherapy in cancer treatment are identified, the interaction between immunotherapy and over-the-counter medication has been explored. Due to the cost and length of time to conduct clinical trials, alternative therapeutics are being examined. Recently, the potential interaction between antihistamines and immunotherapies has gained attention. Six articles were included that analyzed this association. In total 4,171 patients were analyzed with a mean age of 62.66. Cancer types vary between lung (including small-cell and non-small-cell lung cancer), melanoma, hepatobiliary, head and neck, breast, gastrointestinal, renal cell, gynecological, and colon cancers. Among all studies, checkpoint inhibitors were used as a form of immunotherapy. Two studies specifically identified which checkpoint therapies were utilized, including nivolumab, pembrolizumab, ipilimumab, and atezolizumab. All articles found a significant improvement in overall survival rates and longer progression-free rates when antihistamines were added to immunotherapy regimens compared to patients who did not utilize antihistamines. Additionally, some studies also analyzed mortality rates, and each found a significant reduction in mortality rates when antihistamines were paired with immunotherapy. The combination of antihistamines as cancer chemotherapeutics with immunotherapy represents a promising approach to the treatment of cancer. As immunotherapies continue to reshape cancer treatment and as we begin to investigate alternative uses for everyday medications, antihistamines may propose beneficial effects on improving the efficacy of immunotherapy.

Lymphatic vessels are crucial for fluid absorption and the transport of peripheral immune cells to lymph nodes. However, in the small intestine, the lymphatic fluid is rich in diet-derived lipids incorporated into chylomicrons and gut-specific immune cells. Thus, intestinal lymphatic vessels have evolved to handle these unique cargoes and are critical for systemic dietary lipid delivery and metabolism. This Review covers mechanisms of lipid absorption from epithelial cells to the lymphatics as well as unique features of the gut microenvironment that affect these functions. Moreover, we discuss details of the intestinal lymphatics in gut immune cell trafficking and insights into the role of inter-organ communication. Lastly, we highlight the particularities of fat absorption that can be harnessed for efficient lipid-soluble drug distribution for novel therapies, including the ability of chylomicron-associated drugs to bypass first-pass liver metabolism for systemic delivery. In all, this Review will help to promote an understanding of intestinal lymphatic-systemic interactions to guide future research directions.

The evolution of antitumor drug development has transitioned from single-agent chemotherapy to targeted therapy, immunotherapy, and more recently, multispecific drugs. These innovative drugs target multiple cellular or molecular pathways simultaneously, offering a more comprehensive anticancer approach and addressing some of the limitations inherent in traditional monotherapies. However, preclinical assessment of multispecific drugs remains challenging, as conventional tumor models often lack the necessary complexity to accurately reflect the interactions between various cell types and targets. Patient-derived immunocompetent tumor organoids (PDITOs), which incorporate both tumor cells and immune cells, present a promising platform for the evaluation of these drugs. Beyond their use in drug evaluation, PDITOs can also be utilized in personalized drug screening and predicting patient-specific treatment outcomes, thus advancing both multispecific drug development and precision medicine. This perspective discusses the current landscape of multispecific drug development and the methodologies for constructing PDITOs. It also addresses the associated challenges and introduces the concept of employing these organoids to optimize the evaluation and rational design of multispecific drug therapies.

Cancer ranks as the second leading cause of death in the United States and poses a significant health challenge globally. Numerous therapeutic options exist for treating cancer, with chemotherapy being one of the most prominent. Chemotherapy involves the use of antineoplastic drugs, either alone or in combination with other medications, to target and kill cancer cells. However, these drugs can also adversely affect healthy cells, leading to various side effects. Among the most commonly used chemotherapy agents are anthracyclines, which include doxorubicin, daunorubicin, and epirubicin. Doxorubicin is particularly notable for its effectiveness but is also associated with significant cardiotoxicity, a common concern for patients undergoing chemotherapy. Unfortunately, there is currently no definitive treatment to prevent or reverse this cardiotoxicity. The cardiac effects of doxorubicin can manifest in several ways, including changes in electrocardiograms, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, heart failure, and congestive heart failure. These complications may arise during treatment, shortly after it concludes, or even weeks later. Various mechanisms have been proposed to explain doxorubicin-induced cardiotoxicity. Key factors include the inhibition of topoisomerase IIβ, mitochondrial damage, reactive oxygen species (ROS) production due to iron metabolism, increased oxidative stress, heightened inflammatory responses, and elevated rates of apoptosis and necrosis within cardiac tissue. This review article will provide a comprehensive overview of the current state of knowledge regarding doxorubicin-induced cardiomyopathy. We will explore the underlying molecular mechanisms contributing to this condition and discuss emerging therapeutic strategies aimed at mitigating its impact on cancer survivors.

Although cancer therapy has significantly advanced in recent decades, patients and healthcare professionals are still quite concerned about adverse effects due to the non-targeted nature of currently used chemotherapeutics. Results obtained in a large number of recently published experimental studies indicated that mesenchymal stem-cell-derived exosomes (MSC-Exos), due to their biocompatibility, ability to cross biological barriers, and inherent targeting capabilities, could be used as a promising drug-delivery system for anti-cancer therapies. Their lipid bilayer protects cargo of anti-cancer drugs, making them excellent candidates for the delivery of therapeutic agents. MSC-Exos could be engineered to express ligands specific for tumor cells and, therefore, could selectively deliver anti-cancer agents directly in malignant cells, minimizing side effects associated with chemotherapeutic-dependent injury of healthy cells. MSC-Exos can carry multiple therapeutic agents, including anti-cancer drugs, micro RNAs, and small bioactive molecules, which can concurrently target multiple signaling pathways, preventing tumor growth and progression and overcoming resistance of tumor cells to many standard chemotherapeutics. Accordingly, in this review article, we summarized current knowledge and future perspectives about the therapeutic potential of MSCs-Exos in anti-cancer treatment, opening new avenues for the targeted therapy of malignant diseases.

We have introduced Re(I) tricarbonyl complexes (ReL1 - ReL6) [Re(CO)3(N^N)Cl] where N^N=extensive π conjugated imidazo-[4,5-f][1,10]-phenanthroline derivatives that helps in strong DNA intercalation, enhanced photophysical behavior, increase the 3π-π* character of T1 state for PDT and high value of lipophilicity for cell membrane penetration. These complexes exhibited prominent intraligand/ligand-centered (π-π*/1LC) absorption bands at λ 260-350 nm and relatively weak metal-to-ligand charge-transfer (1MLCT) bands within the λ 350-550 nm range. Among the six synthesized complexes, [(CO)3ReICl(K2-N,N-2-(4-(1-benzyl-1H-tetrazol-5-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline] (ReL6) exhibited outstanding potency (IC50~6 μM, PI>9) under yellow light irradiation compared to dark conditions. Importantly, extremely lipophilic complex ReL6 showed effective penetration through the cell membrane and localized primarily in mitochondria (Pearson's correlation coefficient, PCC=0.918) of MDA-MB-231 cells. Complex ReL6 exhibited more than 9 times higher photo-toxicity in normoxic and hypoxic environment of tumor by inducing 1O2 generation (type II PDT), radical generation triggered by NADH oxidation (type I PDT). This complex is a promising candidate for TNBC treatment in hypoxic tumors, with efficacy comparable to photofrin and have demonstrated CO release ability under UV light irradiation.