Smart responsive in situ hydrogel systems applied in bone tissue engineering.

The repair of irregular bone tissue suffers severe clinical problems due to the scarcity of an appropriate therapeutic carrier that can match dynamic and complex bone damage. Fortunately, stimuli-responsive in situ hydrogel systems that are triggered by a special microenvironment could be an ideal method of regenerating bone tissue because of the injectability, in situ gelatin, and spatiotemporally tunable drug release. Herein, we introduce the two main stimulus-response approaches, exogenous and endogenous, to forming in situ hydrogels in bone tissue engineering. First, we summarize specific and distinct responses to an extensive range of external stimuli (e.g., ultraviolet, near-infrared, ultrasound, etc.) to form in situ hydrogels created from biocompatible materials modified by various functional groups or hybrid functional nanoparticles. Furthermore, "smart" hydrogels, which respond to endogenous physiological or environmental stimuli (e.g., temperature, pH, enzyme, etc.), can achieve in situ gelation by one injection in vivo without additional intervention. Moreover, the mild chemistry response-mediated in situ hydrogel systems also offer fascinating prospects in bone tissue engineering, such as a Diels-Alder, Michael addition, thiol-Michael addition, and Schiff reactions, etc. The recent developments and challenges of various smart in situ hydrogels and their application to drug administration and bone tissue engineering are discussed in this review. It is anticipated that advanced strategies and innovative ideas of in situ hydrogels will be exploited in the clinical field and increase the quality of life for patients with bone damage.

Recent advances in hematopoietic cell kinase in cancer progression: Mechanisms and inhibitors.

Hematopoietic cell kinase (Hck), a non-receptor tyrosine kinase belonging to the Src kinase family, is intricately linked to the pathogenesis of numerous human diseases, with a particularly pronounced association with cancer. Hck not only directly impacts the proliferation, migration, and apoptosis of cancer cells but also interacts with JAK/STAT, MEK/ERK, PI3K/AKT, CXCL12/CXCR4, and other pathways. Hck also influences the tumor microenvironment to facilitate the onset and progression of cancer. This paper delves into the functional role and regulatory mechanisms of Hck in various solid tumors. Additionally, it explores the implications of Hck in hematological malignancies. The review culminates with a summary of the current research status of Hck inhibitors, the majority of which are in the pre-clinical phase of investigation. Notably, these inhibitors are predominantly utilized in the therapeutic management of leukemia, with their combinatorial potential indicating promising avenues for future research. In conclusion, this review underscores the significance of the mechanism of Hck in solid tumors. This insight is crucial for comprehending the current research trends regarding Hck: targeted therapy against Hck shows great promise in both diagnosis and treatment of malignant tumors. Further investigation into the role of Hck in cancer, coupled with the development of specific inhibitors, has the potential to revolutionize approaches to cancer treatment.

Lysis-Free Isolation and Direct Amplification of Pathogenic Bacterial DNA Using Diatom Frustules.

DNA has been implicated as an important biomarker for the diagnosis of bacterial infections. Herein, we developed a streamlined methodology that uses diatom frustules (DFs) to liberate and capture bacterial DNA and allows direct downstream amplification tests without any lysis, washing, or elution steps. Unlike most conventional DNA isolation methods that rely on cell lysis to release bacterial DNA, DFs can trigger the oxidative stress response of bacterial cells to promote bacterial membrane vesicle formation and DNA release by generating reactive oxygen species in aqueous solutions. Due to the hierarchical porous structure, DFs provided high DNA capture efficiency exceeding 80% over a wide range of DNA amounts from 10 pg to 10 ng, making only 10 µg DFs sufficient for each test. Since laborious liquid handling steps are not required, the entire DNA sample preparation process using DFs can be completed within 3 min. The diagnostic use of this DF-based methodology was illustrated, which showed that the DNA of the pathogenic bacteria in serum samples was isolated by DFs and directly detected using polymerase chain reaction (PCR) at concentrations as low as 102 CFU/mL, outperforming the most used approaches based on solid-phase DNA extraction. Furthermore, most of the bacterial cells were still alive after DNA isolation using DFs, providing the possibility of recycling samples for storage and further diagnosis. The proposed DF-based methodology is anticipated to simplify bacterial infection diagnosis and be broadly applied to various medical diagnoses and biological research.

Effect and mechanism of natural composite hydrogel from fish scale intercellular matrix on diabetic chronic wound repair.

Diabetes mellitus is a chronic metabolic disease with prolonged low-grade inflammation and impaired cellular function, leading to poor wound healing. The treatment of diabetic wounds remains challenging due to the complex wound microenvironment. In view of the prominence of fish scales in traditional Chinese medicine and their wide application in modern medicine, we isolated the intercellular components in the scales of sea bass, obtained a natural composite hydrogel, fish scales gel (FSG), and applied it to diabetic chronic wounds. FSG was rich in collagen-like proteins, and possessed low-temperature gelation properties. In vitro, FSG was biocompatible and promoted fibroblast proliferation by approximately 40 %, endothelial cell migration by approximately 20 % and activated the M1 macrophages. In addition, FSG restored the function of fibroblasts and vascular endothelial cells damaged by high glucose. Importantly, FSG normalized the acute inflammatory response to impaired macrophages in a high-glucose microenvironment. Transcriptome analysis implies that this mechanism may involve enhanced cell signaling and cellular communication, improved sensitivity to cytokines, and activation of the TNF signaling pathway. Animal experiments confirmed that FSG significantly improved wound closure by approximately 15 % in diabetic rats, showing similar effects to acute wounds. In conclusion, the regulation of multiple cellular functions by FSG, especially the counterintuitive ability to induce acute inflammation, promoted diabetic wound healing and provides a novel therapeutic strategy for wound repair in diabetic patients.

Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

One-pot reaction for the preparation of diatom hemostatic particles with effective hemostasis and economic benefits.

Effective hemostatic materials have been in demand for rapid pre-hospital hemostasis in emergency situations, which can significantly reduce accidental deaths. The development of emergency hemostatic materials with rapid hemostasis, biosafety, and economical preparation is a great challenge. In this study, Ca(OH)2-complexed diatom powder hemostatic particles (Ca(OH)2-Php) were prepared based on a one-pot reaction by directly mixing various raw materials and by rotary granulation. High-temperature calcination was able to carbonate and consume the organic matter in the hemostatic particles. The crosslinked hydrogen bonds in those particles were converted to silica-oxygen bonds, the particles became more stable, and the porous structure of diatom biosilica (DBs) was exposed. Ca(OH)2-Php has high porosity, can quickly adsorb the water in blood (water absorption: 75.85 ± 6.93%), and exhibits rapid hemostasis capacity (clotting time was shortened by 43% compared with that of the control group), good biocompatibility (hemolysis rate <7%, no cytotoxicity), and simplicity of handling (conveniently debride, no residues, no tissue inflammation). This study provides a new idea for the preparation of emergency hemostatic materials, and Ca(OH)2-Php prepared by one-pot reaction has various high-quality characteristics including rapid hemostasis, wide applicability, economical preparation, and potential for large-scale production.

Thermo-sensitive hydroxybutyl chitosan/diatom biosilica hydrogel with immune microenvironment regulatory for chronic wound healing.

This study proposes a chronic wound therapeutic strategy based on extracellular matrix (ECM) biomimetics and immune regulation. The hydroxybutyl chitosan/diatom biosilica hydrogel (H/D) which can regulate the immune microenvironment, is prepared from hydroxybutyl chitosan (HBC) as matrix to construct the bionic ECM and diatom biosilica (DB) as structural active unit. The hierarchical porous structure of DB provides strong anchoring interface effect to enhance the mechanical strength of hydrogel, while maintaining its favorable temperature phase transition behavior, improving the material's fit to the wound and convenience of clinical use. Silicates released from DB in H/D accelerate the transition of wounds from inflammation to proliferation and remodeling. In cellular and diabetic rat models, H/D reduces inflammation (induces conversion of M1-type macrophages to M2-type), induces angiogenesis (1.96-fold of control), promotes fibroblast proliferation (180.36 % of control), collagen deposition, keratinocyte migration (47.34 % more than control), and re-epithelialization. This study validates a possible biological mechanism for H/D bioactive hydrogel-mediated regulation of the immune microenvironment and provides a simple synergistic dressing strategy.

The Art of Exploring Diatom Biosilica Biomaterials: From Biofabrication Perspective.

Diatom is a common single-cell microalgae with large species and huge biomass. Diatom biosilica (DB), the shell of diatom, is a natural inorganic material with a micro-nanoporous structure. Its unique hierarchical porous structure gives it great application potential in drug delivery, hemostat materials, and biosensors, etc. However, the structural diversity of DB determines its different biological functions. Screening hundreds of thousands of diatom species for structural features of DB that meet application requirements is like looking for a needle in a seaway. And the chemical modification methods lack effective means to control the micro-nanoporous structure of DB. The formation of DB is a typical biomineralization process, and its structural characteristics are affected by external environmental conditions, genes, and other factors. This allows to manipulate the micro-nanostructure of DB through biological regulation method, thereby transforming the screening mode of the structure function of DB from a needle in a seaway to biofabrication mode. This review focuses on the formation, biological modification, functional activity of DB structure, and its application in biomaterials field, providing regulatory strategies and research idea of DB from the perspective of biofabrication. It will also maximize the possibility of using DB as biological materials.

Zinc-mineralized diatom biosilica/hydroxybutyl chitosan composite hydrogel for diabetic chronic wound healing.

For sustained and stable improvement of the diabetic wound microenvironment, a temperature-sensitive composite hydrogel (ZnDBs/HBC) composed of inorganic zinc mineralized diatom biosilica (ZnDBs) and hydroxybutyl chitosan (HBC) was developed. The interfacial anchoring effect between ZnDBs and HBC enhanced the mechanical strength of the hydrogel. The mechanical strength of the composite hydrogel containing 3 wt% ZnDBs was increased by nearly 2.3times. The hydrogel can be used as a carrier for sustained release of Zn2+ for at least 72 h. In diabetic rats models, ZnDBs/HBC composite hydrogel could accelerate the inflammatory process by regulating the expression of pro-inflammatory factor IL-6 and anti-inflammatory factor IL-10, and also promote tissue cell proliferation and collagen deposition, thereby restoring the normal healing process and accelerating wound healing. The wound contraction rate of the composite hydrogel group was more than 2 times that of the control group. Therefore, ZnDBs/HBC composite hydrogel has the potential to be used as a therapeutic dressing for diabetic chronic wounds.

Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis.

Intranasal administration has been widely explored as a potential treatment for allergic rhinitis, and improving intranasal penetration and retention of drugs is a challenging requirement to further improve efficacy. Delivery strategies of nanocarriers that enhance mucosal adhesion or mucus penetration have been proposed to improve nasal drug delivery; however, delivery efficiency remains limited by excessive pulmonary deposition and nonspecific cell phagocytosis. In this work, a "nasal in situ assembly" strategy was presented to construct intranasal morphology transformation nanomedicines with enhanced effective drug concentration for long-term intervention of allergic rhinitis. The polymer-polypeptide nanomedicine (PHCK) with a CCR3 antagonistic peptide (C) and a pH-responsive polyethylene glycol (H) was developed, encapsulating ketotifen (KT). PHCK nanoparticles displayed nasal mucosa permeability and transformed to nanofibers in the acidic environment of the nasal cavity, realizing responsive burst release of KT simultaneously. The fibrotic reassembly reduced the cellular internalization of nanomedicine and increased the CCR3 blockade on the eosinophil (EOS) membranes. Both in vitro and in vivo data indicated that PHCK achieved improved drug accumulation and retention in the nasal cavity and decreased pulmonary deposition, then effectively inhibited mast cell degranulation and EOS chemotaxis. This study demonstrates that the "nasal in situ assembly" strategy can improve drug delivery efficiency upon nasal responsive morphologic transformation, providing exploratory perspectives for nasal delivery platforms establishment and boosting therapeutic effect of allergic rhinitis.

The emerging roles of metabolism in the crosstalk between breast cancer cells and tumor-associated macrophages.

Breast cancer is the most common cancer affecting women worldwide. Investigating metabolism in breast cancer may accelerate the exploitation of new therapeutic options for immunotherapies. Metabolic reprogramming can confer breast cancer cells (BCCs) with a survival advantage in the tumor microenvironment (TME) and metabolic alterations in breast cancer, and the corresponding metabolic byproducts can affect the function of tumor-associated macrophages (TAMs). Additionally, TAMs undergo metabolic reprogramming in response to signals present in the TME, which can affect their function and breast cancer progression. Here, we review the metabolic crosstalk between BCCs and TAMs in terms of glucose, lipids, amino acids, iron, and adenosine metabolism. Summaries of inhibitors that target metabolism-related processes in BCCs or TAMs within breast cancer have also served as valuable inspiration for novel therapeutic approaches in the fight against this disease. This review provides new perspectives on targeted anticancer therapies for breast cancer that combine immunity with metabolism.

Downregulated circPOKE promotes breast cancer metastasis through activation of the USP10-Snail axis.

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related death among females. Metastasis accounts for the majority of BC related deaths. One feasible strategy to solve this challenging problem is to disrupt the capabilities required for tumor metastasis. Herein, we verified a novel metastasis suppressive circRNA, circPOKE in BC. circPOKE was downregulated in primary and metastatic BC tissues and overexpression of circPOKE inhibited the metastatic potential but not the proliferative ability of BC cells in vitro and in vivo. Mechanistically, circPOKE competitively binds to USP10, and reduces its binding to Snail, a key transcriptional regulator of EMT, thereby inhibiting Snail stability via the protein-ubiquitination degradation pathway. In addition, we found that circPOKE could be secreted into the extracellular space via exosomes and that exosome-carried circPOKE significantly inhibited the invasive capabilities of BC cells in vitro and in vivo. Furthermore, the levels of circPOKE, USP10 and Snail are clinically relevant in BC, suggesting that circPOKE may be used as a potential therapeutic target for patients with BC metastasis.

FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3ß/GLI1 pathway.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3ß and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

Diatom-Inspired Bionic Hydrophilic Polysaccharide Adhesive for Rapid Sealing Hemostasis.

Diatoms are typical marine biofouling organisms that secrete extracellular polymers (EPS) to achieve strong underwater adhesion. Here, we report a diatom-inspired bionic hydrophilic polysaccharide adhesive composed of diatom biosilica (DB) and bletilla striata polysaccharide (BSP) for rapid sealing hemostasis. The hierarchical porous structure of DB with rich surface silanol groups provides a strong anchored interface effect for BSP, which can significantly enhance cross-linking density and interaction strength of the hydrophilic macromolecular network. BSP/DB adhesive offers 6 times greater mechanical strength and viscosity over BSP under different temperature conditions. The aggregation effect of DBs interface for BSP avoided the washout of BSP/DB adhesive during application in a wet environment before cross-linking occurs. This strengthened the adhesion ability of BSP/DB adhesive to biological tissue that brought out complete sealing hemostasis without blood loss in a rat liver injury model. The dry BSP/DB prepared by lyophilization inherited excellent clotting ability of BSP/DB adhesive, which could realize rapidly the cruor of anticoagulant whole blood within 1 min. The results of animal studies confirmed that dry BSP/DB exhibited superior hemostatic performance over silicate-based inorganic Quikclot, in terms of hemostatic rate, blood loss, dosage, and multiscroll wound closure.

Sequential treatment for diabetic foot ulcers in dialysis patients: A case report.

BACKGROUND: Diabetic foot ulcers (DFUs) are common in patients with diabetes, especially those undergoing hemodialysis. In severe cases, these ulcers can cause damage to the lower extremities and lead to amputation. Traditional treatments such as flap transposition and transfemoral amputation are not always applicable in all cases. Therefore, there is a need for alternative treatment methods. CASE SUMMARY: This report describes a 62-year-old female patient who was admitted to the hospital with plantar and heel ulcers on her left foot. The patient had a history of renal failure and was undergoing regular hemodialysis. Digital subtraction angiography showed extensive stenosis and occlusion in the left superficial femoral artery, left peroneal artery and left posterior tibial artery. Following evaluation by a multidisciplinary team, the patient was diagnosed with type 2 DFUs (TEXAS 4D). Traditional treatments were deemed unsuitable, and the patient was treated with endovascular surgery in the affected area, in addition to supportive medical treatment, local debridement, and sequential repair using split-thickness skin and tissue-engineered skin grafts combined with negative pressure treatment. After four months, the wound had completely healed, and the patient was able to walk with a walking aid. CONCLUSION: This study demonstrates a new treatment method for DFUs was successful, using angioplasty, skin grafts, and negative pressure.

An improved blood hemorrhaging treatment using diatoms frustules, by alternating Ca and light levels in cultures.

Hemorrhage control requires hemostatic materials that are both effective and biocompatible. Among these, diatom biosilica (DBs) could significantly improve hemorrhage control, but it induces hemolysis (the hemolysis rate > 5%). Thus, the purpose of this study was to explore the influence of Ca2+ biomineralization on DBs for developing fast hemostatic materials with a low hemolysis rate. Here, CaCl2 was added to the diatom medium under high light (cool white, fluorescent lamps, 67.5 µmol m-2 s-1), producing Ca-DBs-3 with a particle size of 40-50 µm and a Ca2+ content of Ca-DBs-3 obtained from the higher concentration CaCl2 group (6.7 mmol L-1) of 0.16%. The liquid absorption capacity of Ca-DBs-3 was 30.43 ± 0.57 times its dry weight; the in vitro clotting time was comparable to QuikClot® zeolite; the hemostatic time and blood loss using the rat tail amputation model were 36.40 ± 2.52 s and 0.39 ± 0.12 g, which were 40.72% and 19.50% of QuikClot® zeolite, respectively. Ca-DBs-3 showed no apparent toxicity to L929 cells (cell viability > 80%) and was non-hemolysis (the hemolysis rate < 2%). This study prepared Ca-DBs-3 with a rapid hemostatic effect and good biocompatibility, providing a path to develop diatom biosilica hemostatic materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00180-3.

The hierarchical porous structures of diatom biosilica-based hemostat: From selective adsorption to rapid hemostasis.

Here, we developed a Ca2+ modified diatom biosilica-based hemostat (DBp-Ca2+) with a full scale hierarchical porous structure (pore sizes range from micrometers to nanometers). The unique porous size in stepped arrangement of DBp-Ca2+give it selective adsorption capacity during coagulation process, resulted in rapid hemorrhage control. Based on in vitro and in vivo studies, it was confirmed that the primary micropores of DBp-Ca2+gave it high porosity to hold water (water absorption: 78.46 ± 1.12 %) and protein (protein absorption: 83.7 ± 1.33 mg/g). Its secondary mesopores to macropores could reduce of water diffusion length to accelerate blood exchange (complete within 300 ms). The tertiary stacking pores of DBp-Ca2+ could absorb platelets and erythrocytes to reduce more than 50 % of thrombosis time, and provided enough contact between Ca active site and coagulation factors for triggering clotting cascade reaction. This work not only developed a novel DBs based hemostat with efficient hemorrhage control, but also provided new insights to study procoagulant mechanism of inorganic hemostat with hierarchical porous structure from selective adsorption to rapid hemostasis.

Pathophysiology of obesity and its associated diseases.

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment, induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.

Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2.

Background: Solute carrier family 35 member A2 (SLC35A2), which belongs to the SLC35 solute carrier family of human nucleoside sugar transporters, has shown regulatory roles in various tumors and neoplasms. However, the function of SLC35A2 across human cancers remains to be systematically assessed. Insights into the prediction ability of SLC35A2 in clinical practice and immunotherapy response remains limited. Materials and methods: We obtained the gene expression and protein levels of SLC35A2 in a variety of tumors from Molecular Taxonomy of Breast Cancer International Consortium, The Cancer Genome Atlas, Gene Expression Omnibus, Chinese Glioma Genome Atlas, and Human Protein Atlas databases. The SLC35A2 level was validated by immunohistochemistry. The predictive value for prognosis was evaluated by Kaplan-Meier survival and Cox regression analyses. Correlations between SLC35A2 expression and DNA methylation, genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and tumor microenvironment were performed using Spearman's correlation analysis. The possible downstream pathways of SLC35A2 in different human cancers were explored using gene set variation analysis. The potential role of SLC35A2 in the tumor immune microenvironment was evaluated via EPIC, CIBERSORT, MCP-counter, CIBERSORT-ABS, quanTIseq, TIMER, and xCell algorithms. The difference in the immunotherapeutic response of SLC35A2 under different expression conditions was evaluated by the tumor immune dysfunction and exclusion (TIDE) score as well as four independent immunotherapy cohorts, which includes patients with bladder urothelial carcinoma (BLCA, N = 299), non-small cell lung cancer (NSCLC, N = 72 and N = 36) and skin cutaneous melanoma (SKCM, N = 25). Potential drugs were identified using the CellMiner database and molecular docking. Results: SLC35A2 exhibited abnormally high or low expression in 23 cancers and was significantly associated with the prognosis. In various cancers, SLC35A2 expression and mammalian target of rapamycin complex 1 signaling were positively correlated. Multiple algorithmic immune infiltration analyses suggested an inverse relation between SLC35A2 expression and infiltrating immune cells, which includes CD4+T cells, CD8+T cells, B cells, and natural killer cells (NK) in various tumors. Furthermore, SLC35A2 expression was significantly correlated with pan-cancer immune checkpoints, TMB, MSI, and TIDE genes. SLC35A2 showed significant predictive value for the immunotherapy response of patients with diverse cancers. Two drugs, vismodegib and abiraterone, were identified, and the free binding energy of cytochrome P17 with abiraterone was higher than that of SLC35A2 with abiraterone. Conclusion: Our study revealed that SLC35A2 is upregulated in 20 types of cancer, including lung adenocarcinoma (LUAD), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). The upregulated SLC35A2 in five cancer types indicates a poor prognosis. Furthermore, there was a positive correlation between the overexpression of SLC35A2 and reduced lymphocyte infiltration in 13 cancer types, including BRCA and COAD. Based on data from several clinical trials, patients with LUAD, LUSC, SKCM, and BLCA who exhibited high SLC35A2 expression may experience improved immunotherapy response. Therefore, SLC35A2 could be considered a potential predictive biomarker for the prognosis and immunotherapy efficacy of various tumors. Our study provides a theoretical basis for further investigating its prognostic and therapeutic potentials.