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Abstract 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

Abstract Cancer immunotherapy is a novel therapeutic regimen because of the specificity and durability of immune modulations to treat cancers. Current cancer immunotherapy is limited by some barriers such as poor response rate, low tumor specificity and systemic toxicities. Porous nanomaterials (PNMs) possess high loading capacity and tunable porosity, receiving intense attention in cancer immunotherapy. Recently, novel PNMs based drug delivery systems have been employed in antitumor immunotherapy to enhance tissue or organ targeting and reduce immune-related adverse events. Herein, we summarize the recent progress of PNMs including inorganic, organic, and organic–inorganic hybrid ones for cancer immunotherapy. The design of PNMs and their performance in cancer immunotherapy are discussed in detail, with a focus on how those designs can address the challenges in current conventional immunotherapy. Lastly, we present future directions of PNMs for cancer immunotherapy including the challenges and research gaps, providing new insights about the design of PNMs for efficient cancer immunotherapy with better performance as powerful weapons against tumors. Finally, we discussed the relevant challenges that urgently need to be addressed in clinical practice, coupled with corresponding solutions to these problems.

Hypoxia plays a critical role in head and neck squamous cell carcinoma (HNSCC) prognosis. However, till now, robust and reliable hypoxia-related prognostic signatures have not been established for an accurate prognostic evaluation in HNSCC patients. This article focused on establishing a risk score model to evaluate the prognosis and guide treatment for HNSCC patients. RNA-seq data and clinical information of 502 HNSCC patients and 44 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database. 433 samples from three Gene Expression Omnibus (GEO) datasets were incorporated as an external validation cohort. In the training cohort, prognostic-related genes were screened and LASSO regression analyses were performed for signature establishment. A scoring system based on SRPX, PGK1, STG1, HS3ST1, CDKN1B, and HK1 showed an excellent prediction capacity for an overall prognosis for HNSCC patients. Patients were divided into high- and low-risk groups, and the survival status of the two groups exhibited a statistically significant difference. Subsequently, gene set enrichment analysis (GSEA) was carried out to explore the underlying mechanisms for the prognosis differences between the high- and low-risk groups. The tumor immune microenvironment was evaluated by CIBERSORT, ESTIMATE, TIDE, and xCell algorithm, etc. Then, we explored the relationships between this prognostic model and the levels of immune checkpoint-related genes. Cox regression analysis and nomogram plot indicated the scoring system was an independent predictor for HNSCC. Moreover, a comparison of predictive capability has been made between the present signature and existing prognostic signatures for HNSCC patients. Finally, we detected the expression levels of proteins encoded by six-HRGs via immunohistochemical analysis in tissue microarray. Collectively, a novel integrated signature considering both HRGs and clinicopathological parameters will serve as a prospective candidate for the prognostic evaluation of HNSCC patients.

Abstract Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, discovered in the cytoplasm of almost all types of mammalian cells, plays a significant role in biological functions. The duration of STAT3 activation in normal tissues is a transient event and is strictly regulated. However, in cancer tissues, STAT3 is activated in an aberrant manner and is induced by certain cytokines. The continuous activation of STAT3 regulates the expression of downstream proteins associated with the formation, progression, and metastasis of cancers. Thus, elucidating the mechanisms of STAT3 regulation and designing inhibitors targeting the STAT3 pathway are considered promising strategies for cancer treatment. This review aims to introduce the history, research advances, and prospects concerning the STAT3 pathway in cancer. We review the mechanisms of STAT3 pathway regulation and the consequent cancer hallmarks associated with tumor biology that are induced by the STAT3 pathway. Moreover, we summarize the emerging development of inhibitors that target the STAT3 pathway and novel drug delivery systems for delivering these inhibitors. The barriers against targeting the STAT3 pathway, the focus of future research on promising targets in the STAT3 pathway, and our perspective on the overall utility of STAT3 pathway inhibitors in cancer treatment are also discussed.

Abstract Extracellular vesicles (EVs) are lipid‐bilayer membrane structures secreted by most cell types. EVs act as messengers via the horizontal transfer of lipids, proteins, and nucleic acids, and influence various pathophysiological processes in both parent and recipient cells. Compared to EVs obtained from body fluids or cell culture supernatants, EVs isolated directly from tissues possess a number of advantages, including tissue specificity, accurate reflection of tissue microenvironment, etc., thus, attention should be paid to tissue‐derived EVs (Ti‐EVs). Ti‐EVs are present in the interstitium of tissues and play pivotal roles in intercellular communication. Moreover, Ti‐EVs provide an excellent snapshot of interactions among various cell types with a common histological background. Thus, Ti‐EVs may be used to gain insights into the development and progression of diseases. To date, extensive investigations have focused on the role of body fluid‐derived EVs or cell culture‐derived EVs; however, the number of studies on Ti‐EVs remains insufficient. Herein, we summarize the latest advances in Ti‐EVs for cancers and non‐cancer diseases. We propose the future application of Ti‐EVs in basic research and clinical practice. Workflows for Ti‐EV isolation and characterization between cancers and non‐cancer diseases are reviewed and compared. Moreover, we discuss current issues associated with Ti‐EVs and provide potential directions.

This study aimed to investigate the effects of the oat hay feeding method and compound probiotics (CMP) on the growth, health, serum antioxidant and immune indicators, rumen fermentation, and bacteria community of dairy calves from 3 to 5 months of age. Forty-eight female Holstein calves (80 ± 7 days of age, 93.71 ± 5.33 kg BW) were selected and randomly divided into four groups. A 2 × 2 factorial design was adopted for the experiment, with the factors of the oat hay feeding method (fed as free-choice or 16.7% in the diet) and compound probiotics (CMP) inclusion (0.15% or 0%) in the pelleted starter. The results showed that, compared with giving oat hay as free-choice, feeding a diet of 16.7% oat hay increased the pelleted starter intake at 1–84 d (p < 0.05), with an average daily gain (ADG) at 61–84 d (p = 0.02); adding CMP to the pelleted starter did not significantly affect body weight, and reduced the fecal index (p < 0.05). Feeding 16.7% oat hay increased the concentration of IgA, IgG, and IgM (p < 0.01), while adding CMP increased the catalase (p < 0.01) and decreased the concentration of malondialdehyde (p < 0.01) in serum. Feeding 16.7% oat hay increased the ruminal concentration of propionic acid (p < 0.05) and isobutyric acid (p = 0.08), and decreased the ruminal pH (p = 0.08), the concentration of acetic acid (p < 0.05), and the ratio of acetic acid to propionic acid (p < 0.01). Feeding 16.7% oat hay reduced the relative abundance of ruminal Firmicutes, Unidentified-Bacteria, Actinobacteria, Prevotella, NK4A214-group, Olsenella, and Actinobacteriota (p < 0.05); adding CMP increased the relative abundance of ruminal Prevotella, Rikenellaceae-RC9-gut-group, Ruminococcus, NK4A214-group, and Ruminococcus (p < 0.05), and decreased the abundance of Desulfobacterora, Prevotella-7, and Erysipelotricaceae-UCG-002 (p < 0.05). In conclusion, feeding a diet of 16.7% oat hay increased the pelleted starter intake and average daily gain, while slightly reducing the ruminal pH values; adding CMP to the pelleted starter resulted in reduced diarrhea incidence, increased serum antioxidant capacity and immunity, as well as ruminal richness and diversity of microorganisms in dairy calves from 3 to 5 months of age.