Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

Neoadjuvant immunotherapy: new horizon for lymph node preservation.

The study by Rahim et al., focusing on preoperative immunotherapy, highlights the pivotal role of CD8+ T cells within lymph nodes in response to neoadjuvant immunotherapy, suggesting that preserving lymph node integrity could bolster the treatment's efficacy by activating antitumor T cells. This underlines the importance of lymph node preservation and supports the use of immunotherapy as a neoadjuvant approach in cancer treatment.

Comparative analysis of GoPro and digital cameras in head and neck flap harvesting surgery video documentation: an innovative and efficient method for surgical education.

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

Enhancing cancer therapy: The role of drug delivery systems in STAT3 inhibitor efficacy and safety.

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment.

Application of PRI-E-a combined learning method in oral and maxillofacial oncology education.

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Revolutionizing lymph node metastasis imaging: the role of drug delivery systems and future perspectives.

The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development.

Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation­induced cardiomyocyte injury based on network pharmacology and in vitro validation.

Liquiritin (LIQ) is a flavonoid known for its cardioprotective properties, extracted from Glycyrrhiza uralensis Fisch. The purpose of the present study was to investigate the protective mechanism of LIQ against hypoxia/reoxygenation (H/R) injury through in vitro experiments, with the goal of enhancing its pharmacological effects. Initially, network pharmacology was employed to explore the targets and mechanisms of LIQ. Subsequently, an in vitro H/R model was established using H9c2 cells. Potential targets for LIQ and myocardial ischemia-reperfusion injury (MIRI) were identified through online databases. The STRING, Cytoscape and DAVID databases were used to extract intersecting targets and mechanisms. In vitro experiments were conducted to validate these findings, assessing cardiac enzymes, oxidative stress indicators, mitochondrial fluorescence, apoptotic fluorescence, inflammation and related protein expression. The network pharmacological analysis revealed that the protective effects of LIQ on MIRI involve oxidative stress, inflammation and apoptosis. The results of in vitro experimental validation demonstrated that LIQ significantly reduced the activities of lactated dehydrogenase and creatine kinase isoenzyme-MB (P<0.05 or 0.01), as well as the level of malondialdehyde (P<0.01). It also inhibited the production of reactive oxygen species (P<0.01), the release of inflammatory factors (P<0.05 or 0.01) and apoptosis (P<0.01). By contrast, the LIQ pre-treatment group exhibited a significant increase in mitochondrial membrane potential level (P<0.05 or 0.01) and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (P<0.05 or 0.01). Furthermore, LIQ reduced the protein expressions of TNF-α receptor type 1 (TNFR1) and MMP9, along with the level of NF-κB phosphorylation (P<0.05 or 0.01). In conclusion, LIQ mitigated H/R-induced cardiomyocyte injury through mechanisms that may involve antioxidants, anti-apoptotic effects, protection against mitochondrial damage and suppression of inflammatory levels. These effects are achieved via inhibition of the TNFR1/NF-κB/MMP9 pathway.

Seizing the fate of lymph nodes in immunotherapy: To preserve or not?

Lymph node dissection has been a long-standing diagnostic and therapeutic strategy for metastatic cancers. However, questions over myriad related complications and survival outcomes are continuously debated. Immunotherapy, particularly neoadjuvant immunotherapy, has revolutionized the conventional paradigm of cancer treatment, yet has benefited only a fraction of patients. Emerging evidence has unveiled the role of lymph nodes as pivotal responders to immunotherapy, whose absence may contribute to drastic impairment in treatment efficacy, again posing challenges over excessive lymph node dissection. Hence, centering around this theme, we concentrate on the mechanisms of immune activation in lymph nodes and provide an overview of minimally invasive lymph node metastasis diagnosis, current best practices for activating lymph nodes, and the prognostic outcomes of omitting lymph node dissection. In particular, we discuss the potential for future comprehensive cancer treatment with effective activation of immunotherapy driven by lymph node preservation and highlight the challenges ahead to achieve this goal.

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors.

Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN-targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future-oriented discussion, offering critical insights into the field.

Postoperative volume maintenance rate of microvascular free flap in oral and maxillofacial region: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The resorption of flap's volume can be frequently observed in the transplantation of microvascular free flaps, which could significantly affect postoperative function. Therefore, it's essential to comprehend the postoperative flap volume and the mechanisms behind before making clinical decisions. METHODS: Literature search was conducted from database on PubMed, EMBASE, Cochrane Library, Chinese database and Google Scholar. A random effects model meta-analyses and descriptive systematic review were performed. RESULTS: The search identified 420 articles, of which 9 studies included in meta-analysis and 14 studies included in descriptive systematic review. Postoperative flap volume maintenance rate is used to represent the volume change. The pooled mean postoperative flap volume maintenance rate was 62.82 % for soft tissue flap (95 %CI: 58.83 to 66.82, p = 0.076, I2=56.3 %) and 85.96 % for bone flap (95 %CI: 84.19 to 87.73, p = 0.274, I2=20.4 %). Weight loss, muscle atrophy, and decreased serum albumin levels are risk factors for postoperative volume reduction of soft tissue flaps. The bone resorption rate of bone flaps in women is higher than that in men. CONCLUSION: When designing microvascular free flaps for oral and maxillofacial surgery, soft tissue flaps should consider an anticipated postoperative shrinkage of 37 %, while bone flaps should consider an anticipated postoperative shrinkage of 14 %.

Nanotheranostics in cancer lymph node metastasis: The long road ahead.

Lymph node metastasis (LNM) significantly impacts the prognosis of cancer patients. Despite significant advancements in diagnostic techniques and treatment modalities, clinical challenges continue to persist in the realm of LNM. These include difficulties in early diagnosis, limited treatment efficacy, and potential side effects and injuries associated with treatment. Nanotheranostics, a field within nanotechnology, seamlessly integrates diagnostic and therapeutic functionalities. Its primary goal is to provide precise and effective disease diagnosis and treatment simultaneously. The development of nanotheranostics for LNM offers a promising solution for the stratified management of patients with LNM and promotes the advancement of personalized medicine. This review introduces the mechanisms of LNM and challenges in its diagnosis and treatment. Furthermore, it demonstrates the advantages and development potential of nanotheranostics, focuses on the challenges nanotheranostics face in its application, and provides an outlook on future trends. We consider nanotheranostics a promising strategy to improve clinical effectiveness and efficiency as well as the prognosis of cancer patients with LNM.

Charting new frontiers: Co-inhibitory immune checkpoint proteins in therapeutics, biomarkers, and drug delivery systems in cancer care.

Cancer remains a major health concern globally. Immune checkpoint inhibitors (ICIs) target co-inhibitory immune checkpoint molecules and have received approval for treating malignancies like melanoma and non-small cell lung cancer. While CTLA-4 and PD-1/PD-L1 are extensively researched, additional targets such as LAG-3, TIGIT, TIM-3, and VISTA have also demonstrated effective in cancer therapy. Combination treatments, which pair ICIs with interventions such as radiation or chemotherapy, amplify therapeutic outcomes. However, ICIs can lead to diverse side effects, and their varies across patients and cancers. Hence, identifying predictive biomarkers to guide therapy is essential. Notably, expression levels of molecules like PD-1, CTLA-4, and LAG-3 have been linked to tumor progression and ICI therapy responsiveness. Recent advancements in drug delivery systems (DDSs) further enhance ICI therapy efficacy. This review explores predominant DDSs for ICI delivery, such as hydrogel, microparticle, and nanoparticle, which offer improved therapeutic effects and reduced toxicity. In summary, we discuss the future of immune therapy focusing on co-inhibitory checkpoint molecules, pinpoint challenges, and suggest avenues for developing efficient, safer DDSs for ICI transport.

Identification of SEC61G as a Diagnostic and Prognostic Biomarker in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a heterogeneous malignancy originating from the oral mucosal epithelium. Detecting novel biomarkers can offer crucial information on disease aggressiveness and expected clinical outcomes for individual patients. SEC61G, an aberrantly expressed gene in various cancers, has been associated with negative clinical outcomes. However, its expression and clinical significance in OSCC is still unclear. In the present study, we investigated the SEC61G expression level in OSCC using bioinformatic and immunohistochemical analyses. Additionally, our findings revealed a significant correlation between SEC61G expression and clinicopathological characteristics, as well as a worse prognosis in OSCC patients. Notably, flow cytometry analysis on patient samples revealed that SEC61G expression was also linked to decreased immune infiltration in OSCC patients. In conclusion, our study provides evidence supporting SEC61G's role as a potential diagnostic, prognostic, and therapeutic marker in OSCC.

OLR1 Is a Pan-Cancer Prognostic and Immunotherapeutic Predictor Associated with EMT and Cuproptosis in HNSCC.

Metabolism plays a critical role in cancer. OLR1 has been implicated in cardiovascular and metabolic disorders, while its association with tumorigenesis and tumor immunity remains poorly defined in the literature. We conducted comprehensive pan-cancer analyses based on the TCGA database to examine OLR1 expression and its prognostic implications. Correlations between OLR1 expression level and tumor immunity and immunotherapy were investigated by immune infiltration, enrichment, and TIDE analysis methods. Immunohistochemistry detected OLR1 expression in HNSCC. We used the GSEA method to explore the potential signaling pathways in which OLR1 is involved, and a correlation analysis to investigate the relationships between OLR1 and epithelial-mesenchymal transition (EMT) and cuproptosis. In addition, the effects of OLR1 knockdown on the EMT process, invasion, stemness, and cuproptosis of HNSCC cells were examined by scratch, Transwell, CCK8, sphere formation, and flow cytometry, while changes in related proteins were detected using the immunoblotting method. OLR1 is highly expressed in most cancers, and it is associated with patient prognosis. OLR1 expression positively correlates with immunosuppressive cell infiltration and immune checkpoint molecules, while being negatively associated with effector T cells. Moreover, significant correlations are observed between OLR1 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) in some cancers. In HNSCC, OLR1 expression is related to advanced clinicopathological factors and unfavorable outcomes. Patients with high OLR1 expression levels are prone to experience immune escape and benefit less from immune checkpoint inhibitor (ICI) therapy. Moreover, OLR1 expression may affect EMT, stemness, and cuproptosis resistance outcomes. OLR1 is an immune-related prognostic biomarker with potential as a prognostic indicator for immunotherapy, and it may also be involved in regulating the EMT process and cuproptosis in HNSCC.

Single-cell RNA sequencing reveals tumor heterogeneity within salivary gland pleomorphic adenoma: A preliminary study.

BACKGROUND: Salivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton-remodeling-related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial-mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated. METHODS: An analysis of single-cell RNA sequencing (scRNA-seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues. RESULTS: Our analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra-lesional heterogeneity. Cytoskeleton-remodeling-related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA. CONCLUSION: Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.

Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives.

Head and neck tumors (HNTs) constitute a multifaceted ensemble of pathologies that primarily involve regions such as the oral cavity, pharynx, and nasal cavity. The intricate anatomical structure of these regions poses considerable challenges to efficacious treatment strategies. Despite the availability of myriad treatment modalities, the overall therapeutic efficacy for HNTs continues to remain subdued. In recent years, the deployment of artificial intelligence (AI) in healthcare practices has garnered noteworthy attention. AI modalities, inclusive of machine learning (ML), neural networks (NNs), and deep learning (DL), when amalgamated into the holistic management of HNTs, promise to augment the precision, safety, and efficacy of treatment regimens. The integration of AI within HNT management is intricately intertwined with domains such as medical imaging, bioinformatics, and medical robotics. This article intends to scrutinize the cutting-edge advancements and prospective applications of AI in the realm of HNTs, elucidating AI's indispensable role in prevention, diagnosis, treatment, prognostication, research, and inter-sectoral integration. The overarching objective is to stimulate scholarly discourse and invigorate insights among medical practitioners and researchers to propel further exploration, thereby facilitating superior therapeutic alternatives for patients.

Recent advances in targeting myeloid-derived suppressor cells and their applications to radiotherapy.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogenous immature myeloid cells with potent immune suppressive properties that not only constrain anti-tumor immune activation and functions, promote tumor progression, but also contribute to treatment resistance and tumor relapse. Targeting MDSCs may be a promising new cancer treatment method, but there is still a problem of low treatment efficiency. Combined application with radiotherapy may be a potential method to solve this problem. Drug delivery systems (DDSs) provide more efficient targeted drug delivery capability and can reduce the toxicity and side effects of drugs. Recent advance in DDSs targeting development, recruitment, differentiation, and elimination of MDSCs have shown promising effect in reversing immune inhibition and in overcoming radiotherapy resistance. In this review, we systematically summarized DDSs applied to target MDSCs for the first time, and classified and discussed it according to its different mechanisms of action. In addition, this paper also reviewed the biological characteristics of MDSCs and their role in the initiation, progression, and metastasis of cancer. Moreover, this review also summarizes the role of DDSs targeting MDSCs in radiosensitization. Finally, the future development of DDSs targeting MDSCs is also prospected.