Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment.

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

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.

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.

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.

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.

Correlation between vitamin D levels in serum and the risk of dental caries in children: a systematic review and meta-analysis.

BACKGROUND: Vitamin D plays a crucial role in oral health, and its deficiency is associated to significant changes in oral health diseases. We aimed to explore the relationship between levels of 25-hydroxyvitamin D (25(OH) D) and dental caries in children. METHODS: Four electronic databases were searched by two investigators including PubMed, Embase, Web of Science, and Cochrane Library. Dental caries results were presented as either prevalence or based on the index of primary and permanent teeth/surfaces with decaying, missing, and filled areas, while vitamin D levels were determined through laboratory testing. Two researchers independently selected studies, collected information, assessed risk of bias, and evaluated the study quality. Any disagreements were resolved through discussion. RESULTS: A total of 13 studies were included, comprising 5 cross-sectional studies, 5 cohort studies, 3 case-control studies, all of which had high methodological quality. Our meta-analysis showed that children with vitamin D deficiency had a 22% higher risk of dental caries than those with normal vitamin D levels, with a relative risk (RR) of 1.22 and a 95% confidence interval (CI) of 1.18 to 1. 25. Further subgroup analysis according to the three types of studies showed that the risk of dental caries in children with vitamin D deficiency was higher than that in normal vitamin D level group (cohort studies: 62%; cross-sectional studies, 19%; and case-control studies, 5%). Additionally, according to age, subgroup analysis also showed that the risk of dental caries in children with vitamin D deficiency was higher than that in normal vitamin D level group (permanent teeth studies, 28%; deciduous teeth studies, 68%; and mixed dentition studies 8%). CONCLUSIONS: Levels of 25 (OH) D have been found negatively associated with dental caries in children, indicating that low vitamin D levels may be considered a potential risk factor to this dental disease.

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.

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.

Lycorine upregulates the expression of RMB10, promotes apoptosis and inhibits the proliferation and migration of cervical cancer cells.

Although there are numerous treatment strategies, including surgery and chemotherapy, the prognosis of cervical cancer remains far from satisfactory. There is an urgent need to develop more effective, more tolerable and safer therapeutics for the treatment of cervical cancer. Lycorine is a natural plantextract that has been previously found to confer anti­tumor activities. Therefore, in the present study, the effects of lycorine and its possible mechanism of action in cervical cancer were investigated. Cell Counting Kit­8, wound healing and Transwell assays were used to verify the proliferation and migration of HeLa cells following lycorine intervention. The results demonstrated that lycorine significantly inhibited the proliferation and migration of HeLa cells. RNA binding motif 10 (RBM10) is a protein associated with apoptosis. It has been suggested that lycorine can affect the expression of RBM10. Flow cytometry demonstrated that lycorine may inhibit the initiation and progression of cervical cancer by promoting apoptosis, which may be mediated through the upregulation of RBM10 expression and increasing TNF­α levels. Xenograft mouse experiments indicated that when lycorine was injected through the tail vein, HeLa tumor growth was inhibited. Mechanistically, western blotting demonstrated that lycorine significantly inhibited the activation of the Akt signaling pathway and potentially reversed epithelial­mesenchymal transition, which was also mediated by RBM10. Furthermore, following RBM10 knockdown with small interfering­RNA, the inhibitory effects of lycorine on cervical cancer was significantly abrogated. Overall, results of the present study suggest that lycorine can upregulate the expression of RBM10 and inhibit the proliferation and migration of cervical cancer cells.

Adipose-derived stem cells postpone the progression of Sjögren's syndrome by upregulating the Hippo signaling pathway.

The aim of the present study was to explore the effect and mechanism of action of adipose-derived stem cells (ADSCs) on Sjögren syndrome (SS) to develop novel and more effective methods for SS treatment. ADSCs, dexamethasone or normal saline was injected into the submandibular gland (SMG) of three 12-week-old non-obese diabetic (NOD) mice. The degree of lymphocyte infiltration was considered as a criterion for judging disease progression, hematoxylin and eosin staining was performed to observe the pathological state, and the expression levels of TAZ, E-cadherin and α-catenin were assessed by western blotting. ADSC transplantation triggered an inhibitory effect on the progression of SS, which was slightly stronger compared with that of dexamethasone treatment. This was found to be related to the Hippo signaling pathway. In addition, TAZ protein expression levels decreased gradually with the progression of the disease; immunofluorescence staining showed that the expression of E-cadherin and TAZ followed similar trends. Notably, the expression of TAZ, p-TAZ, E-cadherin and α-catenin in NOD mice were lower compared with that in Control mice. Similarly, the ratio of p-TAZ/TAZ also decreased, which means that the activation level of Hippo signal pathway decreased. The results suggest that ADSCs may exert a therapeutic effect against SS and may postpone its progression by upregulating the Hippo signaling pathway.

Adipose-derived stem cells promote the proliferation, migration, and invasion of oral squamous cell carcinoma cells by activating the Wnt/planar cell polarity signaling pathway.

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral and maxillofacial region. Adipose-derived stem cells (ADSCs) interact with a variety of malignant tumors to promote their proliferation and metastasis. Abnormalities in Wnt/planar cell polarity (PCP) signaling and overactivation of the signaling pathway are considered to be related to the occurrence and development of various malignant tumors. In order to determine whether ADSC can promote tumorigenesis in OSCC and its molecular mechanism, we conducted a series of studies. Methods: The effect of ADSCs on the occurrence and development of OSCC was studied in vivo and in vitro, and the molecular mechanism was investigated using Western blot and immunofluorescence (IHC) assays. Results: The results revealed that ADSCs could promote the proliferation, invasion, and migration of OSCC cells in a dose- and time-dependent manner. With regard to the mechanism, the expression of collagen triple helix repeat-containing protein 1 (CTHRC1) and phospho-c-Jun (p-c-Jun) increased significantly with enhancement of the interaction between ADSCs and OSCC cells, indicating that the Wnt/PCP signaling pathway was overactivated. Conclusions: ADSCs promote the pathogenesis of OSCC by activating the Wnt/PCP signaling pathway, suggesting that proteins related to this pathway may be potential therapeutic targets for OSCC.

Sesquiterpenes in grapes and wines: Occurrence, biosynthesis, functionality, and influence of winemaking processes.

Grapes are an important global horticultural product, and are mainly used for winemaking. Typically, grapes and wines are rich in various phytochemicals, including phenolics, terpenes, pyrazines, and benzenoids, with different compounds responsible for different nutritional and sensory properties. Among these compounds, sesquiterpenes, a subcategory of the terpenes, are attracting increasing interest as they affect aroma and have potential health benefits. The characteristics of sesquiterpenes in grapes and wines in terms of classification, biosynthesis pathway, and active functions have not been extensively reviewed. This paper summarizes 97 different sesquiterpenes reported in grapes and wines and reviews their biosynthesis pathways and relevant bio-regulation mechanisms. This review further discusses the functionalities of these sesquiterpenes including their aroma contribution to grapes and wines and potential health benefits, as well as how winemaking processes affect sesquiterpene concentrations.