The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma.

AIMS: Cisplatin (CDDP) is still one of the most commonly used first-line treatments for advanced and recurrent oral squamous cell carcinoma (OSCC) patients in clinical practice. However, the decrease in tumor sensitivity to CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in OSCC. TMEM30A widely exists in biomembranes and regulates the lipid asymmetry of the membrane, but there is no report on its function in OSCC. This study aims to explore the specific mechanism by which METTL3 regulates m6A methylation of TMEM30A and affects the occurrence and development of OSCC, and further investigate the effects of METTL3 and TMEM30A on the anti-tumor activity of CDDP. KEY FINDINGS: In OSCC, METTL3 plays a pro-cancer role and weakens the anti-tumor efficacy of CDDP; METTL3 positively regulates the expression of TMEM30A by m6A methylation modification and binding to TMEM30A; The abnormally high expression of TMEM30A in OSCC not only weakens CDDP sensitivity, but also enhances the malignant evolution of cancer cells, regulates the metabolic balance of ATP and lactate in cells, and is a potential oncogenic gene. SIGNIFICANCE: TMEM30A promotes malignant progression of tumors through METTL3 mediated m6A methylation modification, participates in maintaining the balance of tumor ATP and lactate metabolism, and reduces the anti-tumor activity of CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.

Time-Dependent Electrical Active and Ultrasound-Responsive Calcium Titanate Implant Coating with Immunomodulation, Osteogenesis, and Customized Antibacterial Activity.

Surgical site infection and insufficient osseointegration are notable risks factors associated with oral implant surgery. In this study, the development of a polarized calcium titanate (CT-P) coating for titanium surfaces is proposed as a solution to these problems. The coating generated electrical stimulation (ES) can inhibit pro-inflammatory M1-type macrophage polarization and promote anti-inflammatory M2-type macrophage polarization, resulting in favorable bone immunomodulation. The ES generated by the coating can match the physiological electrical potential that will change during bone repair, thereby promoting osseointegration in vivo. In addition, the system can also achieve on-demand antibacterial activity, mainly depending on the CT-P coating responding to ultrasound (US) irradiation to produce reactive oxygen species (ROS) and remove Staphylococcus aureus (S. aureus) on the surface of the implant. In conclusion, this work provides valuable insights for the development and clinical application of highly efficient electroactive coatings, as well as novel solutions for the selective treatment of bacterial infections in the surgical area.

Regional odontodysplasia diagnosed and treated via multidisciplinary approach: a case report.

Regional odontodysplasia (RO) is a rare non-hereditary dental anomaly associated with dysplasia. Its etiology remains unclear but is known to affect both the mesodermal and ectodermal dental components, as well as deciduous and permanent dentitions. Its young age of onset and complexity has great physical and psychological impact on the affected patients. However, the clinical management of RO remains unified without standardized treatment guidelines. Thus, this study aimed to report an RO case, the first from Jiangxi Province, China, and discuss its clinical diagnosis and treatment to provide a reference to treat similar cases more effectively in the future.

The Role of Gluten in Food Products and Dietary Restriction: Exploring the Potential for Restoring Immune Tolerance.

Wheat is extensively utilized in various processed foods due to unique proteins forming from the gluten network. The gluten network in food undergoes morphological and molecular structural changes during food processing, affecting the final quality and digestibility of the food. The present review introduces the formation of the gluten network and the role of gluten in the key steps of the production of several typical food products such as bread, pasta, and beer. Also, it summarizes the factors that affect the digestibility of gluten, considering that different processing conditions probably affect its structure and properties, contributing to an in-depth understanding of the digestion of gluten by the human body under various circumstances. Nevertheless, consumption of gluten protein may lead to the development of celiac disease (CD). The best way is theoretically proposed to prevent and treat CD by the inducement of oral tolerance, an immune non-response system formed by the interaction of oral food antigens with the intestinal immune system. This review proposes the restoration of oral tolerance in CD patients through adjunctive dietary therapy via gluten-encapsulated/modified dietary polyphenols. It will reduce the dietary restriction of gluten and help patients achieve a comprehensive dietary intake by better understanding the interactions between gluten and food-derived active products like polyphenols.

Oxoaporphine Pr(III) complex inhibits hepatocellular carcinoma progression and metastasis by disrupting tumor cell-macrophage crosstalk.

Tumor cells and macrophages communicate through the secretion of various cytokines to jointly promote the malignant development of cancers. We synthesized and characterized an oxoaporphine Pr(III) complex (PrL3(NO3)3) and found that it inhibits hepatocellular carcinoma (HCC) progression and metastasis by disrupting HCC cell-macrophage crosstalk. PrL3(NO3)3 treatment upregulated CD86, TNF-α, and IL-1ß and downregulated CD163, CD206, CCL2, and VEGFA in macrophages. Our mRNA-Seq results demonstrated that PrL3(NO3)3 inhibited macrophage M2-like polarization by inhibiting the AMPK pathway and activating the NF-κB pathway by upregulating RelA/p65 Ser536 phosphorylation. This kind of macrophage polarization significantly inhibited HCC cell proliferation, migration, and invasion. In addition, PrL3(NO3)3 inhibited the migration, invasion, and chemotaxis of HCC cells by downregulating the expression of EMT-related markers and CCL2. hTFtarget database analysis revealed that PrL3(NO3)3 inhibited NF-κB nuclear translocation by upregulating RelA/p65 Ser536 phosphorylation in HCC cells, thereby downregulating the expression of Snail and CCL2. HCC tissue microarray analysis revealed that downregulation of RelA/p65 Ser536 phosphorylation is a driving event in HCC malignant progression. In conclusion, PrL3(NO3)3 effectively inhibits HCC cell-macrophage crosstalk by upregulating RelA/p65 Ser536 phosphorylation. This is the first report of a lanthanide complex exerting regulatory effects on both tumors and tumor-associated macrophages, providing a new strategy for the development of effective antitumor drugs.

Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis.

TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60-Com) via its N-terminus. Non-acetylated TWIST1-K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1-acK73/76 binds BRD8, a component of TIP60-Com that also binds histone H4-acK5/8, to recruit TIP60-Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60-Com interaction and TIP60-Com recruitment to TWIST1-activated genes, resulting in decreasing TWIST1-activated target gene expression and cancer metastasis. Both TWIST1/NuRD and TWIST1/TIP60-Com complexes are required for TWIST1 to promote EMT, proliferation, and metastasis at full capacity. Therefore, the diacetylation status of TWIST1-K73/76 dictates whether TWIST1 interacts either with NuRD to repress epithelial genes, or with TIP60-Com to activate mesenchymal genes and MYC. Since BRD8 is essential for TWIST1-acK73/76 and TIP60-Com interaction, targeting BRD8 could be a means to inhibit TWIST1-activated gene expression.

Identification of an endoplasmic reticulum stress-related prognostic risk model with excellent prognostic and clinical value in oral squamous cell carcinoma.

BACKGROUND: Recently, endoplasmic reticulum stress related gene (ERS) markers have performed very well in predicting the prognosis of tumor patients. METHODS: The differentially expressed genes in Oral squamous cell carcinoma (OSCC) were obtained from TCGA and GTEx database. Three prognosis-related and differentially expressed ERSs were screened out by Least Absolute Selection and Shrinkage Operator (Lasso) regression to construct a prognostic risk model. Receiver Operating Characteristic Curve (ROC), riskplots and survival curves were used to verify the model's accuracy in predicting prognosis. Multi-omics analysis of immune infiltration, gene mutation, and stem cell characteristics were performed to explore the possible mechanism of OSCC. Finally, we discussed the model's clinical application value from the perspective of drug sensitivity. RESULTS: Three genes used in the model (IBSP, RDM1, RBP4) were identified as prognostic risk factors. Bioinformatics analysis, tissue and cell experiments have fully verified the abnormal expression of these three genes in OSCC. Multiple validation methods and internal and external datasets confirmed the model's excellent performance in predicting and discriminating prognosis. Cox regression analysis identified risk score as an independent predictor of prognosis. Multi-omics analysis found strong correlations between risk scores and immune cells, cell stemness index, and tumor mutational burden (TMB). It was also observed that the risk score was closely related to the half maximal inhibitory concentration of docetaxel, gefitinib and erlotinib. The excellent performance of the nomogram has been verified by various means. CONCLUSION: A prognostic model with high clinical application value was constructed. Immune cells, cellular stemness, and TMB may be involved in the progression of OSCC.

Potent Zinc(II)-Based Immunogenic Cell Death Inducer Triggered by ROS-Mediated ERS and Mitochondrial Ca2+ Overload.

Zn1 and Zn2 are Zn-based complexes that activate the immunogenic cell death (ICD) effect by Ca2+-mediated endoplasmic reticulum stress (ERS) and mitochondrial dysfunction. Compared with Zn1, Zn2 effectively caused reactive oxidative species (ROS) overproduction in the early phase, leading to ERS response. Severe ERS caused the release of Ca2+ from ER to cytoplasm and further to mitochondria. Excessive Ca2+ in mitochondria triggered mitochondrial dysfunction. The damage-associated molecular patterns (DAMPs) of CRT, HMGB1, and ATP occurred in T-24 cells exposed to Zn1 and Zn2. The vaccination assay demonstrated that Zn1 and Zn2 efficiently suppressed the growth of distant tumors. The elevated CD8+ cytotoxic T cells and decreased Foxp3+ cells in vaccinated mice supported our conclusion. Moreover, Zn1 and Zn2 improved the survival rate of mice compared with oxaliplatin. Collectively, our findings provided a new design strategy for a zinc-based ICD inducer via ROS-induced ERS and mitochondrial Ca2+ overload.

A ferroptosis-related prognostic model with excellent clinical performance based on the exploration of the mechanism of oral squamous cell carcinoma progression.

As a hot topic today, ferroptosis is closely involved in the progression and treatment of cancer. Accordingly, we built a prognostic model around ferroptosis to predict the overall survival of OSCC patients. We used up to 6 datasets from 3 different databases to ensure the credibility of the model. Then, through differentially expressed, Univariate Cox, and Lasso regression analyses, a model composed of nine prognostic-related differently expressed ferroptosis-related genes (CISD2, DDIT4, CA9, ALOX15, ATG5, BECN1, BNIP3, PRDX5 and MAP1LC3A) were constructed. Moreover, Kaplan-Meier curves, Receiver Operating Characteristic curves and principal component analysis used to verify the model's predictive ability showed the model's superiority. To deeply understand the mechanism of ferroptosis affecting the occurrence, development and prognosis of OSCC, we performed enrichment analysis in different risk groups identified by the model. The results showed that numerous TP53-related, immune-related and ferroptosis-related functions and pathways were enriched. Further immune microenvironment analysis and mutation analysis have once again revealed the correlation between risk score and immunity and TP53 mutation. Finally, the correlation between risk score and OSCC clinical treatment, as well as Nomogram show the brilliant clinical application prospects of the prognostic model.

Efficacy of indocyanine green fluorescence imaging-guided lymphadenectomy in radical gastrectomy for gastric cancer: A systematic review and meta-analysis.

Background: Indocyanine green (ICG) imaging-guided lymphadenectomy has been introduced in gastric cancer (GC) surgery and its clinical value remains controversial. The aim of this study is to evaluate the efficacy of ICG fluorescence imaging-guided lymphadenectomy in radical gastrectomy for GC. Methods: Studies comparing lymphadenectomy in radical gastrectomy between use and non-use of ICG fluorescence imaging up to July 2022 were systematically searched from PubMed, Web of Science, Embase and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, the number of retrieved lymph nodes (LNs), the number of metastatic LNs and surgical outcomes as well as oncological outcomes. RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted. Results: 17 studies with a total of 2274 patients (1186 in the ICG group and 1088 in the control group) undergoing radical gastrectomy and lymphadenectomy were included. In the pooled analysis, the baseline features were basically comparable. However, the number of retrieved LNs in the ICG group was significantly more than that in the control group (MD = 7.41, 95% CI = 5.44 to 9.37, P < 0.00001). No significant difference was found between the ICG and control groups in terms of metastatic LNs (MD = -0.05, 95% CI = -0.25 to 0.16, P = 0.65). In addition, the use of ICG could reduce intraoperative blood loss (MD = -17.96, 95% CI = -27.89 to -8.04, P = 0.0004) without increasing operative time (P = 0.14) and overall complications (P = 0.10). In terms of oncological outcomes, the use of ICG could reduce the overall recurrence rate (OR = 0.50; 95% CI 0.28-0.89; P = 0.02) but could not increase the 2-year overall survival rate (OR = 1.25; 95% CI 0.72-2.18; P = 0.43). Conclusions: ICG imaging-guided lymphadenectomy is valuable for complete LNs dissection in radical gastrectomy for GC. However, more high-quality randomized controlled trials are needed to confirm this benefit.

Gold Nanoparticle-Incorporated Chitosan Nanogels as a Theranostic Nanoplatform for CT Imaging and Tumour Chemotherapy.

Purpose: The translation of nanocarrier-based theranostics into cancer treatment is limited by their poor cellular uptake, low drug-loading capacity, uncontrolled drug release, and insufficient imaging ability. Methods: In this study, novel hybrid nanogels were fabricated as theranostic nanocarriers by modifying chitosan (CTS)/tripolyphosphate (TPP) nanoparticles (NPs) with polyacrylic acid (PAA) and further conjugating cysteine-functionalized gold nanoparticles (AuNPs). Results: The resultant nanogels, referred to as CTS/TPP/PAA@AuNPs (CTPA), exhibited excellent colloidal stability and a high encapsulation rate of 87% for the cationic drug doxorubicin (DOX). In the tumour microenvironment, the acidic pH and overexpression of lysozyme triggered CTPA@DOX to degrade and emit smaller nanoblocks (30-40 nm), which sequentially released the drug in a tumour-responsive manner. Cellular uptake experiments demonstrated that CTPA facilitates the entry of DOX into the cytoplasm. Furthermore, as visualised through AuNP-mediated computed tomography (CT) imaging, CTPA@DOX enabled favourable accumulation in the tumour. Our in vitro and in vivo data demonstrated that CTPA enabled advanced tumour cell-targeting delivery of DOX, which showed greater anti-tumour activity and biosafety than free DOX. Conclusion: The natural polymer CTS was developed for degradable nanogels, which can precisely track drugs with high antitumour activity. Additionally, the surface adjustment strategy can be assembled to achieve cationic drug loading and high drug-loading capacity, controlled drug release, and sufficient imaging ability. Therefore, multifunctional CTPA enables efficient drug delivery and CT imaging, which is expected to provide a valuable strategy for designing advanced theranostic systems.

Involvement of RUVBL1 in WNT/ß-Catenin Signaling in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of head and neck squamous cell carcinoma (HNSCC), but the causes and molecular mechanisms remain unclear. The wingless-integrated/ß-catenin (WNT/ß-catenin) signaling pathway plays a vital role in cancer cell proliferation, differentiation, and metastasis, including OSCC. To screen potential ß-catenin-associated genes involved in OSCC, the intersection of these genes in the STRING and IMEx databases was assessed using differential expression genes (DEG) from public microarrays, and 22 were further selected to construct a ß-catenin-protein interaction network. The top 14 hub genes (node degree > 10) within the network were selected. Pearson's correlation analysis showed that ß-catenin expression correlated positively with the expression of 11 genes, including AR, BIRC5, CDK6, DKK1, GSK3B, MET, MITF, PARD3, RUVBL1, SLC9A3R1, and SMAD7. A heat map of overall hub gene survival was created, and elevated expression of DKK1 and RUVBL1 was associated with poor survival using the Mantel-Cox test. To identify the function of RUVBL1, colony formation assay, transwell assay, and western blotting revealed that knock-down of RUVBL1 by siRNA decreased H157 and Cal-27 cell proliferation and metastasis by inhibiting ß-catenin signaling. These findings suggest that RUVBL1 may serve as a diagnostic and prognostic biomarker for OSCC, as well as a therapeutic target, and may help to uncover additional molecular mechanisms of ß-catenin-driven OSCC tumorigenesis.

pH/Redox/Lysozyme-Sensitive Hybrid Nanocarriers With Transformable Size for Multistage Drug Delivery.

The majority of current nanocarriers in cancer treatment fail to deliver encapsulated cargos to their final targets at therapeutic levels, which decreases the ultimate efficacy. In this work, a novel core-shell nanocarrier with a biodegradable property was synthesized for efficient drug release and subcellular organelle delivery. Initially, silver nanoparticles (AgNPs) were grafted with terminal double bonds originating from N, N'-bisacrylamide cystamine (BAC). Then, the outer coatings consisting of chitosan (CTS) and polyvinyl alcohol (PVA) were deposited on the surface of modified AgNPs using an emulsion method. To improve the stability, disulfide-containing BAC was simultaneously reintroduced to cross-link CTS. The as-prepared nanoparticles (CAB) possessed the desired colloidal stability and exhibited a high drug loading efficiency of cationic anticancer agent doxorubicin (DOX). Furthermore, CAB was tailored to transform their size into ultrasmall nanovehicles responding to weak acidity, high glutathione (GSH) levels, and overexpressed enzymes. The process of transformation was accompanied by sufficient DOX release from CAB. Due to the triple sensitivity, CAB enabled DOX to accumulate in the nucleus, leading to a great effect against malignant cells. In vivo assays demonstrated CAB loading DOX held excellent biosafety and superior antitumor capacity. Incorporating all the benefits, this proposed nanoplatform may provide valuable strategies for efficient drug delivery.

SP1-Mediated Upregulation of circFAM126A Promotes Proliferation and Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma via Regulation of RAB41.

BACKGROUND: Accumulating evidence indicates that circular RNAs have major roles in the progression of human cancers. Nevertheless, the molecular mechanism and effects of circFAM126A in oral squamous cell carcinoma (OSCC) remain unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect expression levels of circFAM126A in OSCC tumor tissues and cell lines; the effects of circFAM126A small hairpin RNA (shRNA) on the proliferation, migration, and invasion of OSCC cells were detected by MTT, colony formation, and transwell assays; xenograft mouse models were used to determine the effects of circFAM126A shRNA on the growth of OSCC tumors in vivo; the expression of miR-186 and RAB41 in OSCC tissues and cells was examined by qRT-PCR; the targeting relationship between circFAM126A and miR-186 was verified by dual-luciferase reporter and RNA pull-down assays; and the relationship between miR-186 and RAB41 was explored. RESULTS: The expression of circFAM126A was significantly upregulated in OSCC tissues and cells. The transcription factor SP1 transcriptionally activated circFAM126A. However, knockdown of circFAM126A markedly suppressed the proliferation, migration, and invasion of OSCC cells in vitro and inhibited tumor growth and distant metastasis in vivo. Moreover, circFAM126A increased the expression of RAB41 and promoted its mRNA stability via binding to miR-186 and RNA-binding protein FUS. Overexpression of RAB41 antagonized the effects of circFAM126A knockdown and induced an aggressive phenotype of OSCC cells. CONCLUSION: SP1 transcriptionally activated circFAM126A modulated the growth, epithelial-mesenchymal transition (EMT) of OSCC cells via targeting the miR-186/FUS/RAB41 axis, suggesting that circFAM126A is a potential biomarker for the treatment of OSCC.

Biological applications of chiral inorganic nanomaterials.

Chirality is common in nature and plays the essential role in maintaining physiological process. Chiral inorganic nanomaterials with intense optical activity have attracted more attention due to amazing properties in recent years. Over the past decades, many efforts have been paid to the preparation and chirality origin of chiral nanomaterials; furthermore, emerging biological applications have been investigated widely. This review mainly summarizes recent advances in chiral nanomaterials. The top-down and bottom-up preparation methods and chirality origin of chiral nanomaterials are introduced; besides, the biological applications, such as sensing, therapy, and catalysis, will be introduced comprehensively. Finally, we also provide a perspective on the biomedical applications of chiral nanomaterials.

One-pot synthesis of oxoaporphines as potent antitumor agents and investigation of their mechanisms of actions.

An efficient one-pot reaction for the synthesis of oxoaporphine alkaloids has been developed. Twenty-three compounds of oxoaporphine alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, 4B displayed the most potent activity with an IC50 value of 0.5 µM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by -NO2 significantly enhanced the anticancer activity. Mechanism studies indicated that 4 and 4B induced cell cycle arrest at G2/M phase; in contrast, 4V induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of caspase-3/9, were observed in T-24 cells after exposure to compounds 4, 4B and 4V, suggesting that the mitochondrial pathway was involved in the induced apoptosis. Moreover, compound 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24.

Cleidocranial dysplasia: a case report and gene mutation analysis.

Cleidocranial dysplasia is a rare autosomal dominant hereditary disease that mainly affects the skeletal and dental development and has an incidence rate of about 1∶1 000 000. In this study, a case of cranio-clavicular dysplasia was reported, and related literature was reviewed. RUNX2 6p21.1 NM_001024630.3 Exon4 c.534dupAp.(Val179fs) was identified to be a new frameshift mutation by gene analysis.

A Ferroptosis-Related Prognostic Signature Based on Antitumor Immunity and Tumor Protein p53 Mutation Exploration for Guiding Treatment in Patients With Head and Neck Squamous Cell Carcinoma.

Background: Due to the lack of accurate guidance of biomarkers, the treatment of head and neck squamous cell carcinoma (HNSCC) has not been ideal. Ferroptosis plays an important role in tumor suppression and treatment of patients. However, tumor protein p53 (TP53) mutation may promote tumor progression through ferroptosis. Therefore, it is particularly important to mine prognostic-related differentially expressed ferroptosis-related genes (PR-DE-FRGs) in HNSCC to construct a prognostic model for accurately guiding clinical treatment. Methods: First, the HNSCC data obtained from The Cancer Genome Atlas (TCGA) was used to identify PR-DE-FRGs for screening candidate genes to construct a prognostic model. We not only used a variety of methods to verify the accuracy of the model for predicting prognosis but also explored the role of ferroptosis in the development of HNSCC from the perspective of the immune microenvironment and mutation. Finally, we explored the correlation between the prognostic model and clinical treatment and drew a high-precision nomogram to predict the prognosis. Results: Seventeen of the 29 PR-DE-FRGs were selected to construct a prognostic model with good predictive performance. Patients in the low-risk group were found to have a greater number of CD8 + T cells, follicular helper T cells, regulatory T cells, mast cells, T-cell costimulations, and type II interferon responses. A higher tumor mutation burden (TMB) was observed in the low-risk group and was associated with a better prognosis. A higher risk score was found in the TP53 mutation group and was associated with a worse prognosis. The risk score is closely related to the expression of immune checkpoint inhibitors (ICIs)-related genes such as PD-L1 and the IC50 of six chemotherapeutic drugs. The nomogram we constructed performs well in predicting prognosis. Conclusion: Ferroptosis may participate in the progression of HNSCC through the immune microenvironment and TP53 mutation. The model we built can be used as an effective predictor of immunotherapy and chemotherapy effects and prognosis of HNSCC patients.

Structural characteristics and anti-inflammatory activity of UV/H2O2-treated algal sulfated polysaccharide from Gracilaria lemaneiformis.

The study aimed to study the effects on structural characteristics and anti-inflammatory activities of algal sulfated polysaccharides isolated from Gracilaria lemaneiformis (GLP) after a combined treatment of UV irradiation (average irradiance of 6500 mJ/cm2) and H2O2 (50 mmol/L) for various time periods up to 60 min. After a 30-min treatment, the molecular weight and particle size of GLP was decreased by 15 and 2.6 fold, respectively with small but significant decrease in the contents of total sugars, uronic acids and proteins. There seemed to have no starch and the presence of longer side chains of branches in the GLP samples before and after UV/H2O2 treatment based on the I2-KI assay. Scanning electron microscope and atomic force microscope analysis confirmed that the UV/H2O2 treatment could modify the surface morphology of GLP. GLP treated for 5 min possessed the strongest in vitro anti-inflammatory activity by inhibiting the production of nitric oxide, tumor necrosis factor-α and interleukin-6 by 60.49%, 62.81% and 36.29%, respectively in IEC-6 cells when compared to the model. Therefore, UV/H2O2 treatment had the potential to enhance the anti-inflammatory activity of algal sulfated polysaccharides.