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.

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.

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.

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.

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.

Exploiting BRAF mutations in the therapeutic approach towards oral and maxillofacial tumors.

Oral and maxillofacial tumors pose a significant clinical challenge due to their tendency to recur, despite advancements in surgical removal techniques. The jaw's intricate structure further complicates treatments and affects patient quality of life. Consequently, emphasis has shifted towards pharmacological interventions, to potentially reduce invasive surgical procedures. One promising approach targets BRAF mutations, specifically the common V600E mutation. BRAF, a critical protein kinase, regulates cell growth and differentiation via the RAS-RAF-MEK-ERK-MAP kinase pathway. A specific nucleotide change at position 1799, swapping Thymine (T) for Adenine (A), results in the V600E mutation, causing unchecked cell growth. This mutation is common in certain oral and maxillofacial tumors like ameloblastoma. A recent neoadjuvant therapy targeting BRAF, involving the use of dabrafenib and trametinib, has showcased a promising, safe, and effective strategy for organ preservation in the treatment of mandibular ameloblastoma. This convergence of molecular insights and targeted therapies holds the key to managing BRAF-mutated oral and maxillofacial tumors effectively, promising improved patient outcomes.

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.

Bullying victimization and mental health of Chinese adolescents: The chain of tragedy effect of belief in a just world and health promoting lifestyle.

BACKGROUND: Experiences of being bullied in school can impair adolescents' subjective well-being and elevate the risk of psychopathology, suggesting the necessity of identifying factors that may protect against the deleterious effects of being bullied. This study expands upon prior research by examining the relationship between bullying victimization and adolescent mental health, specifically from the perspective of individual perceptions of justice and healthy lifestyles in the Chinese cultural context. METHODS: A total of 3873 Chinese adolescents in grades 7-11 (51.85 % female) completed bullying victimization, belief in a just world, health promoting lifestyle, depressive symptoms, and subjective well-being measures, and provided information on their demographics, including gender, grade, family structure, parents' educational background. RESULTS: After adjusting for demographic variables, bullying victimization was directly and positively related to depression, while directly and negatively related to subjective well-being. Bullying victimization also influenced depression and subjective well-being through three mediation pathways, with belief in a just world and health promoting lifestyle playing multiple mediating roles in the relationship between bullying victimization and mental health outcomes. LIMITATIONS: The data used in this study were self-reported by adolescents and measured via cross-sectional designs, thus precluding statistical examination of temporal causal relationships, and assessments of whether reported affects are stable over time. CONCLUSIONS: The study suggests that belief in a just world and health promoting lifestyle are important factors in understanding the impact of bullying victimization on adolescent mental health, and underscores the need for targeted bullying interventions for at-risk adolescents.

Conceptualizing Peace: A Qualitative Study Among Afghan Adolescents Living in Intractable Conflict.

Purpose: Adolescents living in protracted conflict areas have mostly been perceived as passive recipients of the impact of events in their surroundings who are rarely considered agents of social transformation. But a growing body of research on adolescents' psychological development indicates that adolescents actively perceive concepts like peace and their roles and responsibilities toward creating conditions for peace. Applying the Phenomenological Variant of Ecological Systems Theory, this study focuses on understanding how adolescents from Afghanistan with lifelong exposure to intractable conflict conceptualize peace. Methods: The study was conducted in the Bagrami, Paghman and Dih Sabz districts of Kabul City in Afghanistan. A semi-structured open-ended questionnaire was used to interview 63 male and female adolescents aged 13-19. The participants belonged to different ethnic groups, such as Pashtun, Hazara and Tajik. An inductive approach was applied to analyze the data using thematic analysis. Results: Three distinct themes about peace emerged from the data: peace based on individual emotions, social relations, and larger societal structures. Peace for adolescents had both personal and inner and social or outer dimensions. Afghan adolescents' conceptualization of peace is primarily based on their interaction with the micro-system. Home and family provided perceived calmness and normalcy, which characterized peace as individual emotion. Social relations, often determined by good communication, community cohesiveness, and social support between family members, neighbours, and ethnic groups, constituted adolescents' concepts about peace. Adolescents also demonstrated awareness of larger societal structures, such as the role of community leaders and government in ensuring perceived safety and security, forming their concepts of peace. Conclusion: Adolescents have meaningful voices capable of forming perceptions about peace. The microsystem of an adolescent's environment has a significant influence in the conceptualization of peace. This study contributes to expanding the knowledge on the underpinnings of peace by relating to developmental and peace psychology.

Metformin Attenuates TGF-ß1-Induced Fibrosis in Salivary Gland: A Preliminary Study.

Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-ß1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin's anti-fibrotic properties. Elevated levels of TGF-ß1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-ß1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.

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.

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.

Identification of Immune Infiltration in Odontogenic Keratocyst by Integrated Bioinformatics Analysis.

BACKGROUND: Odontogenic keratocyst (OKC) is a relatively common odontogenic lesion characterized by local invasion in the maxillary and mandibular bones. In the pathological tissue slices of OKC, immune cell infiltrations are frequently observed. However, the immune cell profile and the molecular mechanism for immune cell infiltration of OKC are still unclear. We aimed to explore the immune cell profile of OKC and to explore the potential pathogenesis for immune cell infiltration in OKC. METHODS: The microarray dataset GSE38494 including OKC and oral mucosa (OM) samples were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in OKC were analyzed by R software. The hub genes of OKC were performed by protein-protein interaction (PPI) network. The differential immune cell infiltration and the potential relationship between immune cell infiltration and the hub genes were performed by single-sample gene set enrichment analysis (ssGSEA). The expression of COL1A1 and COL1A3 were confirmed by immunofluorescence and immunohistochemistry in 17 OKC and 8 OM samples. RESULTS: We detected a total of 402 differentially expressed genes (DEGs), of which 247 were upregulated and 155 were downregulated. DEGs were mainly involved in collagen-containing extracellular matrix pathways, external encapsulating structure organization, and extracellular structure organization. We identified ten hub genes, namely FN1, COL1A1, COL3A1, COL1A2, BGN, POSTN, SPARC, FBN1, COL5A1, and COL5A2. A significant difference was observed in the abundances of eight types of infiltrating immune cells between the OM and OKC groups. Both COL1A1 and COL3A1 exhibited a significant positive correlation with natural killer T cells and memory B cells. Simultaneously, they demonstrated a significant negative correlation with CD56dim natural killer cells, neutrophils, immature dendritic cells, and activated dendritic cells. Immunohistochemistry analysis showed that COL1A1 (P = 0.0131) and COL1A3 (P < 0.001) were significantly elevated in OKC compared with OM. CONCLUSIONS: Our findings provide insights into the pathogenesis of OKC and illuminate the immune microenvironment within these lesions. The key genes, including COL1A1 and COL1A3, may significantly impact the biological processes associated with OKC.

Romantic relationship satisfaction and phubbing: The role of loneliness and empathy.

This study investigates the effects of loneliness and empathy on romantic relationship satisfaction and phubbing. Loneliness plays a mediating role in romantic relationship satisfaction and phubbing. The level of empathy moderates these mediating effects. Five hundred and four Chinese adults completed tests of romantic relationship satisfaction, phubbing, loneliness, and empathy. The results show that romantic relationship satisfaction is negatively correlated with phubbing. Loneliness mediates this process. Specifically, lower romantic relationship satisfaction leads to more phubbing by increasing loneliness. Our study also shows that the mediating relationship is moderated by the level of empathy. To be more specific, the higher the level of empathy, the stronger the impact of romantic relationship satisfaction on loneliness, and the more phubbing individuals exhibit.