Potentials of Ulva spp.-derived sulfated polysaccharides as gelling agents with promising therapeutic effects.

Ulvan, a sulfated polysaccharide extracted from Ulva spp., has garnered significant attention in the food and pharmaceutical industries due to its potential health benefits. These include immunomodulation, antiviral, anti-inflammatory, anti-hyperlipidemic, and anti-cancer effects. Nonetheless, practical applications in these fields remain limited due to an incomplete understanding of its gelation mechanisms. Additionally, the underlying mechanisms of its gelation have not been completely understood and thoroughly reviewed. The primary objective is to provide current insights into ulvan's gelling mechanisms and potential health impacts. This review also delves into the existing applications of ulvan polysaccharides. By unraveling these aspects, the information provided in this work is expected to deepen our understanding of ulvan's gelation mechanisms and its prospective role in enhancing health, holding promise for advancements in the fields of food science and disease prevention. This work's theoretical insights contribute significantly to a deeper understanding of these aspects, which holds paramount importance in unleashing the full potential of ulvan and elevating its scientific significance.

Bronchial epithelial gene expression and interstitial lung abnormalities.

INTRODUCTION: Interstitial lung abnormalities (ILA) often represent early fibrotic changes that can portend a progressive fibrotic phenotype. In particular, the fibrotic subtype of ILA is associated with increased mortality and rapid decline in lung function. Understanding the differential gene expression that occurs in the lungs of participants with fibrotic ILA may provide insight into development of a useful biomarker for early detection and therapeutic targets for progressive pulmonary fibrosis. METHODS: Measures of ILA and gene expression data were available in 213 participants in the Detection of Early Lung Cancer Among Military Personnel (DECAMP1 and DECAMP2) cohorts. ILA was defined using Fleischner Society guidelines and determined by sequential reading of computed tomography (CT) scans. Primary analysis focused on comparing gene expression in ILA with usual interstitial pneumonia (UIP) pattern with those with no ILA. RESULTS: ILA was present in 51 (24%) participants, of which 16 (7%) were subtyped as ILA with a UIP pattern. One gene, pro platelet basic protein (PPBP) and seventeen pathways (e.g. TNF-α signalling) were significantly differentially expressed between those with a probable or definite UIP pattern of ILA compared to those without ILA. 16 of these 17 pathways, but no individual gene, met significance when comparing those with ILA to those without ILA. CONCLUSION: Our study demonstrates that abnormal inflammatory processes are apparent in the bronchial airway gene expression profiles of smokers with and without lung cancer with ILA. Future studies with larger and more diverse populations will be needed to confirm these findings.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Construction of a Nomogram Prediction Model for Prognosis in Patients with Large Artery Occlusion-Acute Ischemic Stroke.

BACKGROUND: Patients with large artery occlusion-acute ischemic stroke (LAO-AIS) can experience adverse outcomes, such as brain herniation due to complications. This study aimed to construct a nomogram prediction model for prognosis in patients with LAO-AIS in order to maximize the benefits for clinical patients. METHODS: Retrospective analysis of 243 patients with LAO-AIS from January 2019 to January 2022 with medical history data and blood examination at admission. Univariate and multivariate analyses were conducted through binary logistic regression equation analysis, and a nomogram prediction model was constructed. RESULTS: Results of this study showed that hyperlipidemia (odds ratio [OR] = 2.849, 95% confidence interval [CI] = 1.100-7.375, P = 0.031), right cerebral infarction (OR = 2.144, 95% CI = 1.106-4.156, P = 0.024), D-Dimer>500 ng/mL (OR = 2.891, 95% CI = 1.398-5.980, P = 0.004), and neutrophil-lymphocyte ratio >7.8 (OR = 2.149, 95% CI = 1.093-4.225, P = 0.027) were independent risk factors for poor early prognosis in patients with LAO-AIS. In addition, hypertension (OR = 1.947, 95% CI = 1.114-3.405, P = 0.019), hyperlipidemia (OR = 2.594, 95% CI = 1.281-5.252, P = 0.008), smoking (OR = 2.414, 95% CI = 1.368-4.261, P = 0.002), D-dimer>500 ng/mL (OR = 3.170, 95% CI = 1.533-6.553, P = 0.002), and neutrophil-lymphocyte ratio >7.8 (OR = 2.144, 95% CI = 1.231-3.735, P = 0.007) were independent risk factors for poor long-term prognosis. The early prognosis nomogram receiver operating characteristic curve area under the curve value was 0.688 for the training set and 0.805 for the validation set, which was highly differentiated. The mean error was 0.025 for the training set calibration curve and 0.016 for the validation set calibration curve. Both the training and validation set decision curve analyses indicated that the clinical benefit of the nomogram was significant. The long-term prognosis nomogram receiver operating characteristic curve area under the curve values was 0.697 for the training set and 0.735 for the validation set, showing high differentiation. The mean error was 0.041 for the training set calibration curve and 0.021 for the validation set calibration curve. Both of the training and validation set decision curve analyses demonstrated a substantial clinical benefit of the nomogram. CONCLUSIONS: The nomogram prediction model based on admission history data and blood examination are easy-to-use tools that provide an accurate individualized prediction for patients with LAO-AIS and can assist in early clinical decisions and in obtaining an early prognosis.

Eudragit S100 prepared pH-responsive liposomes-loaded betulinic acid against colorectal cancer in vitro and in vivo.

This study aimed to develop polymer Eudragit S100 for preparing pH-responsive liposomes-loaded betulinic acid (pH-BA-LP) to improve the therapeutic index of chemotherapy for colorectal cancer. BA-loaded liposomes were coated with Eudragit S100 by a thin film dispersion and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and antitumor activity. In particular, pH-BA-LP showed advantages such as lower size (<100 nm), encapsulation efficiency of 90%, high stability, and stably cumulative release. By detecting the antitumor effects of pH-BA-LP in vivo, it showed that the tumor proliferation and cell migration were significantly inhibited in colorectal cancer. The pH-BA-LP also inhibited tumor growth via the regulation of Akt/TLR-mediated signalling and significantly down-regulated the expression of NFAT1 and NFAT4 proteins. It was found that pH-BA-LP can increase NK cells and CD3+ cells in tumor tissues, and the proportion of CD8+ cells in CD3+ cells was also increased, which proved that pH-BA-LP can play an antitumor effect by enhancing the autoimmunity level in tumor-bearing mice. The positive infiltration rates of CD8 and CD68 were increased and CD163 was relatively decreased by using pH-BA-LP, which proved that pH-BA-LP can regulate the immune infiltration levels in tumor-bearing mice. Therefore, the present work provides an effective method to prepare pH-responsive polymer-coated liposomes for colonic delivery with biologically active compounds.

Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, which can involve multiple systems. Patients with RA may have a variety of comorbidities, including cardiovascular disease (CVD), lung cancer, lymphoma, infection, osteoporosis, fatigue, depression, colon cancer, breast cancer, prostate cancer, and Alzheimer's disease. Among these comorbidities, the incidence of CVD, lung cancer, lymphoma, infection, and osteoporosis is higher. CVD is a serious complication of RA. The risk of CVD and associated mortality rate in patients with RA is high, and the treatment rate is low. In addition to traditional risk factors, such as age, sex, blood pressure, and diabetes, RA is also associated with inflammation. Furthermore, therapeutic drugs for RA, including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs, have beneficial or harmful effects on cardiovascular events in patients with RA. This article discusses the effects of therapeutic drugs for RA on cardiovascular events.

Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.

Profiling and bioinformatics analyses reveal differential expression of circular RNA in tongue cancer revealed by high-throughput sequencing.

Circular RNAs (circRNA) are special noncoding RNAs. They are widely present, but with unknown functions. Recent studies have shown that many endogenous circRNAs have sponge function to absorb microRNAs (miRNA). They can regulate target gene messenger RNA expression and play important roles in many biological processes. However, expression profile and function of circRNAs in human tongue squamous cell carcinoma (TSCC) have not been reported. High-throughput sequencing was performed to identify and annotate from three TSCC tissues and adjacent tissues. A separate set (n = 20) of human TSCCs and corresponding adjacent tissues were subjected to reverse-transcription polymerase chain reaction (RT-PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA-miRNA network analysis were also performed to predict the function of circRNA in TSCC. A total of 12 156 circRNAs were identified and annotated, most of the circRNAs were novel ( n = 6231) and exonic (62.09%). Statistical analysis revealed 322 differentially expressed (DE) circRNAs. RT-PCR results showed that circRNA expression in TSCC was higher than that in adjacent tissues. GO functional analysis, KEGG pathway analysis, and circRNA-miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain extent. The current study is the first to systematically characterize and annotate circRNA expression in TSCC, the majority were novel circRNAs. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor-relevant miRNAs, indicating that circRNAs might be promoted development and progression of TSCC.

Laparoscopic adrenalectomy for adrenal tumors.

Objective. To evaluate the indication and the clinical value of laparoscopic adrenalectomy of different types of adrenal tumor. Methods. From 2009 to 2014, a total of 110 patients were diagnosed with adrenal benign tumor by CT scan and we performed laparoscopic adrenalectomy. The laparoscopic approach has been the procedure of choice for surgery of benign adrenal tumors, and the upper limit of tumor size was thought to be 6 cm. Results. 109 of 110 cases were successful; only one was converted to open surgery due to bleeding. The average operating time and intraoperative blood loss of pheochromocytoma were significantly more than the benign tumors (P < 0.05). After 3 months of follow-up, the preoperative symptoms were relieved and there was no recurrence. Conclusions. Laparoscopic adrenalectomy has the advantages of minimal invasion, less blood loss, fewer complications, quicker recovery, and shorter hospital stay. The full preparation before operation can decrease the average operating time and intraoperative blood loss of pheochromocytomas. Laparoscopic adrenalectomy should be considered as the first choice treatment for the resection of adrenal benign tumor.

Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells.

Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24-48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3-1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells.

The imbalanced expression of adenosine receptors in an epilepsy model corrected using targeted mesenchymal stem cell transplantation.

Adenosine inhibits epileptic episodes by interacting with G-protein-coupled receptors. This study examined the mechanism by which the inhibitory effect of adenosine becomes impaired during epileptogenesis. Dynamic changes in adenosine A1 receptors (A1Rs) and A2a receptors (A2aRs) were investigated in a kindling model of epilepsy. RT-PCR, Western blotting, and immunofluorescence results indicated that expression of A1Rs was increased in the hippocampus 24 h after kindling, but progressively decreased 1 and 6 months after kindling. Opposite changes were seen in the expression of A2aRs. This bidirectional change resulted in an imbalance between A1Rs and A2aRs and dysregulation of the adenosine system. Autologous mesenchymal stem cell (MSC) transplantation was used to correct this disorder and avoid side effects of systematic adenosine therapy. Paramagnetic iron oxide particles were used to mark and track the MSCs in vivo using MRI. The results indicated that the transplanted cells migrated along the callosum and settled at the ependymal layer. The MSCs displayed a relatively long survival time, at least 3 months. The improved AR expression and EEG findings suggested that MSC transplantation was a potentially effective means of treating refractory epilepsy.

[Establishment of BGC-823/WTX-EGFP gastric cancer cell line stably expressing Wilms tumor gene on X chromosome].

OBJECTIVE: To establish the BGC-823/WTX-EGFP gastric cancer cell line with stable expression of Wilms tumor gene on the X chromosome (MTX) for functional analysis of WTX gene. METHODS: The full-length WTX cDNA was amplified from human embryonic kidney 293FT cells and cloned into the pEGFP-N1 vector containing the reporter gene of green fluorescence protein. The recombinant pEGFP-WTX expression vector, after digestion by restriction enzyme to identify the size of target gene fragment, was transfected into 293FT cells and the expression of fluorescent reporter gene was observed under fluorescence microscope. pEGFP-WTX vector was transfected into human gastric cancer BGC-823 cell line to establish BGC-823/WTX-EGFP cell line stably expressing WTX. Quantitative RT-PCR and immunocytochemical staining were used to detect the expression of WTX in both BGC-823/WTX-EGFP and control BGC-823 cells. RESULTS: The recombinant pEGFP-WTX plasmid was successfully constructed and verified by PCR and sequencing. The mRNA and protein expressions of MTX were significantly increased in BGC-823/WTX-EGFP cells as compared with those in the control cells. CONCLUSION: The full-length WTX expression vector (pEGFP-WTX) and BGC-823/WTX-EGFP gastric cancer cell line have been successfully established to facilitate further functional study of WTX gene.

Surgical treatment for 11 cases of penile verrucous carcinoma.

Penile verrucous carcinoma is a rare, well-differentiated and low-grade tumor. The surgeons are deficiently aware about the biological behavior and the clinicopathological characteristic of this disease, which raises difficulties during the treatment. In our present study, the clinical and pathological data of 11 patients with penile verrucous carcinoma, aged between 49 to 85 years was retrospectively analyzed. The tumors exhibited exophytic, papillary, caulifower-like or verrucose lesions of great dimensions measuring between 2 to 10 cm on the penises. The tumors were located at glans in 6 cases, invaded the coronoid sulcus in 4 cases and invaded the shaft of the penis in 1 case. Eight cases underwent partial penectomy, while the other 3 were treated with local excision. The diagnosis of penile verrucous carcinoma was confirmed by histopathologic examination of the specimens with the negative surgical margins in all the cases. Within the period of 12 to 60 months of follow-up, all the patients were disease-free with no case of recurrence and metastasis. The novel knowledge and experience of the treatment of penile verrucous carcinoma will be a useful clinical guide for surgeons in the future.

Retroperitoneal laparoscopic dismembered Anderson-Hynes pyeloplasty in treatment of ureteropelvic junction obstruction (report of 150 cases).

OBJECTIVES: To assess the feasibility and efficacy of retroperitoneal laparoscopic dismembered Anderson-Hynes pyeloplasty in the treatment of ureteropelvic junction obstruction (UPJO). METHODS: Between August 2003 and June 2007, retroperitoneal laparoscopic dismembered Anderson-Hynes pyeloplasty was performed in 150 patients diagnosed with UPJO. All patients were assessed preoperatively by imaging examinations (ultrasonography, computerized tomography, and intravenous or retrograde urography) and isotope diuretic renography. Additionally, of the 150 cases, 16 patients with renal calculi underwent concomitant pyelolithotomy. RESULTS: All surgeries were successful. No conversion to open surgery was observed. The average operating time, blood loss, and postoperative hospital stay was 105 minutes (range 95-190), 35 mL (range 20-80), and 7.4 days (range 6-12), respectively. A crossing vessel was encountered in 70 (46.7%) patients. Concomitant renal calculi were successfully removed in 11 patients. Two cases presented with urinary leakage that disappeared on the 11th and 12th postoperative day, respectively. Success rate was 98% at a mean follow-up of 16 months (range 12-24). CONCLUSIONS: Retroperitoneal laparoscopic pyeloplasty provides a minimal invasive treatment modality with low morbidity, short hospital stay, and quick postoperative recovery for patients with UPJO. In experienced hands, laparoscopic pyeloplasty is an effective alternative treatment for UPJO.