Exosomes, small extracellular vesicles secreted by cells, have emerged as pivotal players in cell-to-cell communication. Plant-derived exosomes, in particular, are gaining attention for their potential therapeutic applications in nano-medicine. These vesicles are naturally occurring nanoparticles that carry bioactive molecules such as proteins, lipids, and nucleic acids. Due to their biocompatibility, low toxicity, and ability to traverse biological barriers, plant-derived exosomes present a promising alternative to synthetic nanoparticles for drug delivery, especially in cancer and microbial infection therapy. Exosomes are secreted by almost every cell and are profusely present in all living organisms, making them excellent candidates for a large spectrum of research and applications. This paper describes the highly organized and regulated biosynthesis of exosomes and the prospects of their application in cancer therapy and treatment of microbial infections.

Patients with breast tumours that metastasise to the brain have limited treatment options and a very poor prognosis. More effective therapeutic strategies are desperately needed for this patient population. Recent evidence demonstrates that brain metastases arising from breast tumours display altered energy production that results in enhanced autophagy. Preclinical studies have shown that genetically or pharmacologically disrupting the autophagy pathway significantly decreases the brain metastatic burden, resulting in improved animal survival and increased sensitivity to lapatinib. These findings pave the way for the development of novel strategies targeting autophagy for breast cancer patients with brain metastatic disease.

Plant-derived exosomes (PDEs) are extracellular vesicles (EVs) occurring naturally, which have propitious applications in the development of cost-effective and fruitful cancer therapy with minimum aftereffects and ramifications. Recent advancements in research based on PDEs demonstrate their extraordinary advantages in cancer therapy. The components of PDEs exhibit accomplished cancer prevention activity and having insignificant or negligible toxicity. The conventional methods to deliver drugs to the target have various problems, several of which can be solved by using PDEs for drug delivery. The main constituents of PDEs are proteins, lipids, DNA and RNA. PDEs are believed to revolutionize cancer therapy due to their magnificent attributes, but only a few clinical trials on PDEs are in progress. The mechanisms and regulations by which PDEs execute anticancer properties are yet not completely understood. Hence, research are conducted worldwide to understand the mechanisms of action of cancer antagonist PDEs more comprehensively and perspicuously. Modified PDEs have prospect in evolution of precision medicine which can bring a new dimension in the treatment of cancer.

Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, necessitating innovative treatment strategies. PROTACs (PROteolysis Targeting Chimeras) represent a promising therapeutic approach by targeting and degrading oncogenic proteins via the ubiquitin-proteasome pathway. This study explores the potential of using exosomes as delivery vehicles for PROTACs to enhance treatment efficacy. Exosomes, due to their biocompatibility and inherent targeting capabilities, offer a precise method for delivering PROTACs to CRC cells, potentially overcoming challenges associated with traditional therapies such as drug resistance and off-target effects. By harnessing the advantages of both exosome-based delivery and PROTAC technology, this approach aims to improve targeted protein degradation and therapeutic outcomes in CRC treatment. Further research is required to optimize exosome engineering, ensure efficient PROTAC loading, and validate the safety and efficacy of this novel therapeutic strategy through preclinical and clinical trials.

This study by Okuno et al. successfully identified eight exo-miRNAs through exosome-based discovery and established an exo-miRNA-based liquid biopsy assay for predicting therapeutic response in metastatic gastric cancer (mGC). Exosomes, a subpopulation of extracellular vesicles originating from endosomes, play a crucial role in this context. Liquid biopsy, analyzing blood for circulating tumor cells, extracellular vesicles, or cell-free nucleic acid, has revolutionized cancer diagnosis and monitoring. It significantly contributes to early detection, staging, and relapse detection in various cancers. Numerous studies have highlighted the clinical significance of miRNA and lncRNA within extracellular vesicles. The authors developed a response-prediction model for chemo-responsiveness in mGC patients. This study's model predicts responses robustly, demonstrating its potential efficacy in clinical practice. It offers a non-invasive and accessible method for therapeutic response prediction, crucial for precision medicine in mGC. Successful translation of these findings into clinical applications promises substantial benefits for patient care.

Exosomes, small extracellular vesicles secreted by cells, have gained attention as potential therapeutic agents due to their natural ability to deliver biomolecules and traverse biological barriers. However, their limited targeting specificity and payload capacity necessitate modifications for improved therapeutic efficacy. Click chemistry, known for its high specificity, efficiency, and mild reaction conditions, offers an innovative solution for modifying exosomal surfaces. This technique enables precise attachment of targeting ligands, imaging agents, and therapeutic molecules, enhancing the targeting, delivery, and overall effectiveness of exosome-based therapies. By addressing cancer heterogeneity, click chemistry-modified exosomes can target diverse cancer cell populations within tumors, improving treatment specificity and reducing drug resistance. The development of copper-free click chemistry, such as strain-promoted azide-alkyne cycloaddition (SPAAC), minimizes toxicity, ensuring biocompatibility and safety. As research progresses, this approach holds great promise for personalized and effective cancer treatment, paving the way for next-generation therapeutics and diagnostics.

Exosomes can be defined as extracellular vesicles, of size ranging from 30 to 150 nm, secreted from almost all kinds of cells and can also be obtained from the body fluids. Exosomes have different components depending on the type of cell from which they originate. Exosomes are capable of transporting various molecules such as proteins, nucleic acids, chemical compounds and metabolites. Experiments show that exosomes can perform important functions in cell growth, migration, differentiation, neuronal signalling, immune cell modulation. Exosomes can also be used in cancer therapy, as they can be key players in intercellular communication and signalling. Experiments have also demonstrated that exosomes are chief players in viral persistence and dissemination. The reasons why application of exosomes in targeted therapy is gaining significance are their ability to initiate cellular responses, high tolerance levels in host cells and high efficiency in penetrating other cells. Exosomes can be used both as therapeutic agents and escorts of drugs. Even though numerous studies have been performed in search of better anticancer therapies, most of them have come to a halt due to the failure in achieving a therapy best in all parameters. However, both in vitro and in vivo application of exosomes in diagnosis and therapy of tumours are prospective and has a future.

Adenocarcinomas of the stomach and gastroesophageal junction remain one of the most common malignant tumours in humans worldwide, often with a poor prognosis. Particularly in countries without upper gastrointestinal tract screening endoscopy, tumours that have been asymptomatic for a long time are only diagnosed at an advanced stage. This limits the therapeutic options. Often only palliative therapy concepts are available. Great progress has been made in the last two decades. The genetic basis of adenocarcinomas of the stomach and gastroesophageal junction has been deciphered and new targeted drugs have been developed. Cell and tissue-based predictive diagnostics are becoming increasingly important in therapy planning. Here, surgical pathology forms an important link between basic research, clinical trials, and translation into clinical application. This review article summarizes the experiences made in translational tumour research, which point to the problems of spatial and temporal intratumoral heterogeneity of adenocarcinomas of the stomach and gastroesophageal, the development and continuous re-assessment of therapeutically relevant cut-off values, resistance mechanisms, tumour microenvironment, sexual dimorphism and the pitfalls molecular tumour boards may face.

Background: Chronic back pain affected 619 million people globally in 2020 which accounts for a heavy disease burden causing tremendous productivity losses. Current therapies including ibuprofen, duloxetine, and opioids might cause side effects and even severe drug use disorders. Therefore, a non-pharmacologic therapy with better or equivalent efficacy and fewer side effects is needed.

Methods: We did a multi-center, single-blinded, randomized, positive drug controlled, clinical trial. Patients with chronic back pain in moderate severity were randomized into receiving hot stone massage or flurbiprofen plaster group. Both interventions were 2 weeks with a follow-up of 4 weeks. The primary outcome was the change in the score of the Global Pain Scale (GPS) from baseline to week 2. Secondary outcomes included Numerical Rating Scale (NRS), Chronic Pain Acceptance Questionnaire (CPAQ), Pain Self-Efficacy Questionnaire (PSEQ), Hospital Anxiety and Depression Scale (HADS), and Short Form-36 (SF36) from baseline to week 2 and week 6. Exploratory outcome assessment included the muscle thickness measured by ultrasound. Any adverse event was monitored throughout the study period.

Results: A total of 120 patients were enrolled in this trial. At 2 weeks GPS decreased significantly in the hot stone massage group compared to the flurbiprofen group (difference between groups = -8.1 points, 95% confidence interval [CI] -15.8 to -0.3, p = 0.047). Moreover, hot stone massage also showed more improvement at 2 weeks compared to flurbiprofen, including NRS (-0.5 points, 95% CI -1.0 to -0.1, p = 0.029), PSEQ (5.4 points, 95% CI 0.5 to 10.2, p = 0.030), and mental component of Short Form-36 (SF-36) (1.7 points, 95% CI 0.4 to 2.9, p = 0.010), but not in CPAQ (p = 0.131), HADS (p = 0.303 for depression, p = 0.399 for anxiety), or SF-36 (p = 0.129 for physical component, p = 0.246 for social component, p = 0.076 for fatigue component). A total of two participants in the hot stone massage group reported mild pain on skin surface when receiving the procedure at the first intervention session.

Objective: Screening and early diagnosis of gastric cancer (GC) are crucial for improved prognosis. However, gastroscopic screening is not feasible in large populations due to its high cost and invasive nature. The detection of circulating cell-free DNA (cfDNA) provides an attractive minimally-invasive alternative for screening of GC. In this systematic review and meta-analysis, we evaluate the diagnostic value of cfDNA-based markers for GC, including the detection of total concentration, mutations, and methylation alterations.

Methods: We performed a systematic search of four literature databases (PubMed, Embase, Web of Science, and Cochrane Library) for articles published before November 2022. The revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of included studies. PROSPERO registration number: CRD42021210830.

Results: A total of 15 original articles involving 2849 individuals were included in this meta-analysis, comprising five studies on concentration, nine studies on methylation alterations, and one study on mutation biomarkers of cfDNA. Among these studies, seven selected early-stage GC subjects. For the diagnoses of overall stages and early-stage GC, the pooled sensitivities with 95% confidence interval were 0.74 (0.66–0.82) and 0.64 (0.51–0.76), and the pooled specificities were 0.92 (0.84–0.96) and 0.94 (0.87–0.98) with summary areas under the curve (SAUCs) of 0.89 (0.86–0.91) and 0.86 (0.83–0.89), respectively.

Conclusions: This meta-analysis suggests that cfDNA-based biomarkers show diagnostic value for GC early detection.

Exosomes, are a subpopulation of extracellular vesicles, that originate from endosomes. The major role of exosomes is cellular communication (in this process exosomes display the status of the parental cell's nature, healthy or the cell suffers any pathological complication). In recent decades, research evidence highlighted that exosomes are the masterminds of cancer development and they appear as smart solutions for early diagnosis, prognosis and therapeutic (eg. stem cell, plant and immune cell-derived exosomes) approaches. Exosomes transform the cancer liquid biopsy into a new orientation. Several biofluids (blood, plasma, serum, saliva, urine, CSF (Cerebrospinal Fluid) and cancer tissue are used for exosome-based cancer biomarkers detection. Liquid biopsy becomes more efficient for exosomes, compared to tissue biopsy. Exosomes biocompatibility, low toxicity, and ability to cross biological membranes make it a potential tool for cancer therapeutic development. Exosome-based cancer therapeutics introduce a cutting-edge era of cell-free cancer therapy. This article explores the critical role of exosomes in cancer development, progression, treatment, and clinical trials. Exosome-based clinical trials indicate that we are close to cancer precision medicine.

Human Immunodeficiency Virus (HIV) significantly increases the risk of various cancers due to chronic immune suppression and viral oncogenes. Traditional therapies, including antiretroviral therapy (ART), chemotherapy, and radiation, often face limitations such as drug resistance and systemic toxicity. PROteolysis TArgeting Chimeras (PROTACs) have emerged as a promising approach for targeted protein degradation, offering significant advantages over conventional treatments. However, effective delivery remains a challenge. This paper explores the innovative use of tear exosome-based delivery systems for PROTACs in treating HIV-mediated cancers. Tear exosomes, due to their natural origin, biocompatibility, and inherent targeting capabilities, present a novel and effective platform for delivering PROTACs, enhancing therapeutic specificity and reducing adverse effects. Integrating the unique properties of tear exosomes with the therapeutic potential of PROTACs could revolutionize the treatment of HIV-mediated cancers by overcoming current therapeutic challenges and improving patient outcomes.

Cancer stem cells (CSCs) are a small subset of tumor cells, efficient in self-renewal within the tumor and also play a vital role in cancer resistance and metastasis. Recent cancer research has focused on exosomes, a tiny subpopulation of extracellular vesicles (EVs), known for their role in intercellular communication, and significantly contributing to tumor development and metastasis (Tumor derived exosomes-TEXs). These exosomes complicate cancer treatment by promoting tumor and CSC formation and developing drug and therapeutic resistance. This article explores how tumor-derived exosomes impact CSC survival, proliferation, and resistance to therapies, leading to tumor recurrence. In a tumor microenvironment (TME), exosomes facilitate tumor growth and metastasis. Targeting exosomes could disrupt CSC communication and improve cancer treatment efficacy. Current studies highlight the role of CSCs exosomes in cancer progression and therapeutic resistance. Understanding CSCs exosome-based cell-to-cell communication in tumor opens a new horizon in cancer therapeutics development.

Preeclampsia, a hypertensive disorder of pregnancy, poses significant risks to maternal and fetal health. Recent research highlights the potential of vertical circulating exosomes (VCEs) as biomarkers for early detection and monitoring of preeclampsia. Exosomes, small extracellular vesicles involved in intercellular communication, carry bioactive molecules that are messengers of the parental cell status (healthy or undergoing any pathological condition). In preeclampsia, alterations in the cargo of VCEssuch as proteins, lipids, and nucleic acids play the role of biomarkers in pathophysiology complications. These exosomal contents can provide insights into the underlying mechanisms, including endothelial dysfunction, immune response dysregulation, and placental abnormalities. Early identification of specific exosomal biomarkers may facilitate timely therapeutic interventions, improving outcomes for both mother and child. This article explores the emerging role of VCEs in preeclampsia, emphasizing their diagnostic and prognostic potential, and underscores the need for further research to validate these biomarkers and integrate them into clinical practice.