Galectin-3 Expression Research Articles

Relationship Between Tim-3 and Galectin-9 Expression Levels, Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of Colorectal Cancer

Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer. A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients. The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05). Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

Abstract P20: Anti-CD123 CAR NK cells and cam161533 Trispecific Killer Engager have synergistic activity against Acute Myeloid Leukemia

Abstract P20: Anti-CD123 CAR NK cells and cam161533 Trispecific Killer Engager have synergistic activity against Acute Myeloid Leukemia

Galectin-3 levels in children with cystic fibrosis.

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006). Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: • Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: • Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. • Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

Sirtuin 2 Exerts Regulatory Functions on Radiation-Induced Myocardial Fibrosis in Mice by Mediating H3K27 Acetylation of Galectin-3 Promoter.

Sirtuin 2 (SIRT2) and galectin-3 have been shown to protect the heart against fibrosis. However, their impacts on radiation-induced myocardial fibrosis (RIMF) remain to be elucidated. To deepen this understanding, the current study sought to explore the effects of SIRT2 and galectin-3 on RIMF and the underlying mechanisms. Galectin-3 knockout mice were obtained, and a radiation-induced heart damage (RIHD) mouse model was induced by local radiation exposure to the heart. Lentivirus transfection was then performed, and heart function, fibrosis of heart tissues, and levels of SIRT2, galectin-3, and fibrosis-related markers collagen type-I/-III and matrix metalloproteinase (MMP)2/MMP9 were respectively assessed by echocardiography, hematoxylin-eosin and Masson staining, reverse transcription-quantitative polymerase chain reaction, Western blot, and immunofluorescence staining. Additionally, Western blot and chromatin immunoprecipitation were used to test H3K27 acetylation levels and the binding of H3K27ac to galectin-3, respectively. After radiation exposure, heart tissues from the galectin-3 knockout mice had a smaller fibrotic area compared to normal mice, with reduced expression levels of collagen type-I/-III and MMP2/MMP9. SIRT2 was down-regulated and galectin-3 was up-regulated after RIHD treatment. The histone deacetylase inhibitor sirtinol promoted galectin-3 expression and H3K27 acetylation in a time-dependent manner, and increased H3K27ac enrichment in the galectin-3 promoter. Overexpression of SIRT2 down-regulated H3K27ac, collagen type-I/-III, and MMP2/MMP9 expression levels, and reduced the fibrotic area in mouse heart tissues. However, these effects were reversed by the additional overexpression of galectin-3. SIRT2 facilitates deacetylation of H3K27 to inhibit galectin-3 transcription, thus ameliorating RIMF in mice.

Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant cancer with a poor prognosis. Galectins (Gal) have been the subject of intensive research, but the comparative prognostic value of each Gal type is not yet understood. Therefore, a literature search for evaluating galectins as prognostic biomarkers in HNSCC was conducted. The relationship between Gal expression in HNSCC with HPV and TP53 mutational status was assessed using the UALCAN database. The impact of these biomarkers on prognosis was analyzed using ToPP and CPPA web tools. The expression of galectins in the tumor microenvironment and the impact on prognosis depending on the cancer immune subtype were analyzed using single-cell RNA sequencing. Gal-1 and Gal-3BP were shown to be promising biomarkers with a triple function for the prediction of HPV and TP53 mutational status, stratification of the HNSCC prognosis, and prediction of the response to treatment. In addition, these two galectins have been shown to be most influenced by the tumor microenvironment of HNSCC. Gal-1 and Gal-3BP are the most promising galectins in HNSCC. Furthermore, this study highlights the need for further studies to evaluate galectins in HNSCC and clarify the role of individual Gals in the patient's stratification.

Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions.

In overactive human osteoclasts, we previously identified an alternative splicing event in LGALS8, encoding galectin-8, resulting in decreased expression of the long isoform. Galectin-8, which modulates cell-matrix interactions and functions intracellularly as a danger recognition receptor, has never been associated with osteoclast biology. In human osteoclasts, inhibition of galectin-8 expression revealed its roles in bone resorption, osteoclast nuclearity, and mTORC1 signaling regulation. Galectin-8 isoform-specific inhibition asserted a predominant role for the short isoform in bone resorption. Moreover, a liquid chromatography with tandem mass spectrometry (LC-MS/MS) proteomic analysis of galectin-8 isoforms performed in HEK293T cells identified 22 proteins shared by both isoforms. Meanwhile, nine interacting partners were specific for the short isoform, and none were unique to the long isoform. Interactors specific for the galectin-8 short isoform included cell adhesion proteins and lysosomal proteins. We confirmed the interactions of galectin-8 with CLCN3, CLCN7, LAMP1, and LAMP2, all known to localize to secretory vesicles, in human osteoclasts. Altogether, our study reveals direct roles of galectin-8 in osteoclast activity, mostly attributable to the short isoform.

The effects of a galectin-3 inhibitor on bladder pain syndrome in mice with cyclophosphamide-induced cystitis.

To explore the effect of blocking galectin-3 in the bladder pain syndrome associated with interstitial cystitis. A galectin-3 inhibitor was used to treat mice with cyclophosphamide-induced cystitis. The expression of galectin-3 in bladder tissues and urine was examined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Suprapubic-pelvic pain, bladder voiding, bladder pain-like nociceptive behavior, and referred hyperalgesia were assessed. The weights of the bladders were also measured, and inflammatory cell infiltration and inflammatory cytokine levels were examined by histopathological evaluation. The inflammatory cytokines interleukin 1β (IL-1β), nerve growth factor (NGF), IL-6, and tumor necrosis factor α (TNF-α) were measured by ELISA. Increases in galectin-3 levels, inflammation, bladder weight, and bladder pain-related symptoms were observed in bladders with cyclophosphamide-induced cystitis. Administration of the galectin-3 inhibitor significantly mitigated bladder pain-related symptoms and inflammatory response. In response to the 500 μM dose of the galectin-3 inhibitor, nociceptive behaviors, nociceptive score, and bladder-to-body weight ratios were reduced by 65.1%, 65.3%, and 40.3%, respectively, while 500 μM Gal-3 inhibitor increased pelvic pain threshold by 86.7%. Moreover, galectin-3 inhibitor treatment inhibited the inflammation. Compared to untreated CYP-induced mice, there were significant changes in the levels of IL-1β (41.72 ± 2.05 vs. 18.91 ± 2.26 pg/mg tissues), NGF (9.64 ± 0.38 vs. 1.88 ± 0.05 pg/mg tissues), IL-6 (42.67 + 1.51 vs. 21.26 + 2.78 pg/mg tissues, and TNF-α (22.02 ± 1.08 vs. 10.70 ± 0.80 pg/mg tissues) in response to the highest dose of the Gal-3 inhibitor subgroup (500 μM), and 500 μM Gal-3 inhibitor reduced mast cell infiltration ratios by 71.8%. The galectin-3 inhibitor relieved pelvic pain, urinary symptoms, and bladder inflammation in mice with cyclophosphamide-induced cystitis. Thus, galectin-3 inhibitors may be novel agents in interstitial cystitis treatment.

The Effect of Nordic Walking on the Galectin 3 and Some New Metabolic Markers in Elderly Men with Osteosarcopenic Obesity

Background: Sarcopenia is the age-related progressive loss of muscle mass and strength. The main symptom of the condition is muscle weakness. Objectives: The aim of the present study was to determine the effect of 12 weeks of Nordic walking on the expression of the cardiovascular biomarker galectin 3 gene and some new metabolic markers in elderly men with osteosarcopenic obesity. Methods: Twenty elderly men with a Mean age of 60 to 80 years, who had osteosarcopenic obesity with a body mass index (equal to and above 30) and body fat percentage (equal to and above 30) participated in this research and they were randomly divided into 2 Nordic walking training groups and a control group (10 people in each group). The Nordic walking training program was implemented for 12 weeks and 3 days a week. The intensity of the exercises in each session was 50 to 75% of the maximum heart rate and the duration of each exercise session was 60 minutes. Results: 12 weeks of Nordic walking exercises caused a significant decrease in the circulating levels of galectin-3 (P = 0.001) and a decrease in the TyG-BMI index (P = 0.001) in the subjects. But there was no significant effect on the atherogenic index of plasma (AIP) (P = 0.265) and TyG (P = 0.126) and TyG-BMI (P = 0.347) indices of the subjects. Conclusions: Nordic walking exercise plays an important role in reducing cardiovascular risks by reducing galectin 3 biomarker and atherogenic plasma index (AIP).

Time-course analysis of liver and serum galectin-3 in acute liver injury after alpha-galactosylceramide injection.

Galectin-3 is a beta-galactoside-binding lectin that plays important roles in diverse physiological functions, such as cell proliferation, apoptosis, and mRNA splicing. This protein is expressed on inflammatory cells and acts as a local inflammatory mediator. Recently, galectin-3 has been detected in several diseases, such as chronic liver, heart, and kidney diseases, diabetes, viral infection, autoimmune and neurodegenerative diseases, and tumors, and its role as a biomarker has attracted attention. Alpha-galactosylceramide is an artificially synthesized sphingolipid that can induce acute liver injury via the natural killer T pathway. However, the pathophysiological roles and kinetics of galectin-3 in acute liver injury are not fully understood. This study aimed to elucidate the expression and time course of galectin-3 in liver tissues during acute liver injury following alpha-galactosylceramide injection. Animals were histologically examined on days 1, 2, 4, and 7 after intraperitoneal injection of alpha-galactosylceramide, and the expressions of galectin-3 and ionized calcium-binding adaptor molecule 1 were analyzed. Notably, galectin-3 formed characteristic cluster foci, particularly on day 2 after injection. Cluster formation was not observed in chronic liver disease. Simultaneously, ionized calcium-binding adaptor molecule 1-positive cells were observed in the cluster foci. Serum galectin-3 levels increased on day 2 of treatment and correlated well with the number of galectin-3-positive cell clusters in the liver. Moreover, galectin-3 expression was an important mediator of the early phase of liver injury after alpha-galactosylceramide injection. These results suggest that serum galectin-3 may be a biomarker for the early diagnosis of acute liver injury and that clusters of galectin-3-positive cells may be a specific finding in acute liver injury.

Sex-dependent expression of galectin-1, a cardioprotective β-galactoside-binding lectin, in human calcific aortic stenosis.

We aimed to analyze sex-related differences in galectin-1 (Gal-1), a β-galactoside-binding lectin, in aortic stenosis (AS) and its association with the inflammatory and fibrocalcific progression of AS. Gal-1 was determined in serum and aortic valves (AVs) from control and AS donors by western blot and immunohistochemistry. Differences were validated by ELISA and qPCR in AS samples. Invitro experiments were conducted in primary cultured valve interstitial cells (VICs). Serum Gal-1 was not different neither between control and AS nor between men and women. There was no association between circulating and valvular Gal-1 levels. The expression of Gal-1 in stenotic AVs was higher in men than women, even after adjusting for confounding factors, and was associated with inflammation, oxidative stress, extracellular matrix remodeling, fibrosis, and osteogenesis. Gal-1 (LGALS1) mRNA was enhanced within fibrocalcific areas of stenotic AVs, especially in men. Secretion of Gal-1 was up-regulated over a time course of 2, 4, and 8 days in men's calcifying VICs, only peaking at day 4 in women's VICs. Invitro, Gal-1 was associated with similar mechanisms to those in our clinical cohort. β-estradiol significantly up-regulated the activity of an LGALS1 promoter vector and the secretion of Gal-1, only in women's VICs. Supplementation with rGal-1 prevented the effects elicited by calcific challenge including the metabolic shift to glycolysis. In conclusion, Gal-1 is up-regulated in stenotic AVs and VICs from men in association with inflammation, oxidative stress, matrix remodeling, and osteogenesis. Estrogens can regulate Gal-1 expression with potential implications in post-menopause women. Exogenous rGal-1 can diminish calcific phenotypes in both women and men.

Bacterial surface display of human lectins in Escherichia coli.

Lectin-glycan interactions sustain fundamental biological processes involved in development and disease. Owing to their unique sugar-binding properties, lectins have great potential in glycobiology and biomedicine. However, their relatively low affinities and broad specificities pose a significant challenge when used as analytical reagents. New approaches for expression and engineering of lectins are in demand to overcome current limitations. Herein, we report the application of bacterial display for the expression of human galectin-3 and mannose-binding lectin in Escherichia coli. The analysis of the cell surface expression and binding activity of the surface-displayed lectins, including point and deletion mutants, in combination with molecular dynamics simulation, demonstrate the robustness and suitability of this approach. Furthermore, the display of functional mannose-binding lectin in the bacterial surface proved the feasibility of this method for disulfide bond-containing lectins. This work establishes for the first time bacterial display as an efficient means for the expression and engineering of human lectins, thereby increasing the available toolbox for glycobiology research.

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3-dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.

The Role of Galectin3, Tubulinβ, and Maspin in Promoting Tumor Budding in Colorectal Carcinoma and Their Clinical Implications.

Colorectal cancer (CRC) is a leading cause of death worldwide. Despite the advances in surgical and therapeutic management, tumor metastases and poor prognosis are still major problems. Tumor budding is a relevant prognostic factor in CRC, and it can predict tumor metastasis. Galectin3 is responsible for the development and progression of many cancers through the regulation of cell-cell/cell-matrix interactions and tumor cell invasion. Tubulin is a microtubule protein, and maspin is a serine protease inhibitor; both induce tumor cell invasion through the stimulation of epithelial-mesenchymal transition. This study aims to evaluate the relationship between the expression of galecin3, tubulinβ, and maspin in CRC and clinicopathological features, including tumor budding, their prognostic roles, and clinical implications using immunohistochemistry. Galectin3, tubulinβ, and maspin were detected in tumor cells in 95%, 65%, and 87.5% of cases and in stromal cells in 28.8%, 40%, and 0% of cases. High expression of galectin3 and tubulinβ expression either in tumor cells or stroma was significantly associated with aggressive tumor features such as lymph node metastasis, lymphovascular invasion, tumor budding, and advanced tumor stage. The nucleocytoplasmic expression of maspin in tumor cells showed a significant association with deeper tumor invasion, lymph node metastasis, tumor budding, and advanced tumor stage. Significant associations were found between high galectin3 tumor cell expression and nucleocytoplasmic maspin and shorter survival. High expression of galectin3, tubulinβ, and nucleocytoplasmic maspin were significantly associated with aggressive tumor features such as tumor invasion, metastasis, high tumor budding, and short survival in CRC. They could be used as biomarkers for tumor budding and tumor aggressiveness in CRC and may be considered for future target therapy.

Knockdown of the Shwachman-Diamond syndrome gene, SBDS, induces galectin-1 expression and impairs cell growth.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The depletion of SBDS protein by RNA interference has been shown to cause inhibition of cell proliferation in several cell lines. However, the precise mechanism by which the loss of SBDS leads to inhibition of cell growth remains unknown. To evaluate the impaired growth of SBDS-knockdown cells, we analyzed Epstein-Barr virus-transformed lymphoblast cells (LCLs) derived from two patients with SDS (c. 183_184TA > CT and c. 258 + 2T > C). After 3days of culture, the growth of LCL-SDS cell lines was considerably less than that of control donor cells. By annealing control primer-based GeneFishing PCR screening, we found that galectin-1 (Gal-1) mRNA expression was elevated in LCL-SDS cells. Western blot analysis showed that the level of Gal-1 protein expression was also increased in LCL-SDS cells as well as in SBDS-knockdown 32Dcl3 murine myeloid cells. We confirmed that recombinant Gal-1 inhibited the proliferation of both LCL-control and LCL-SDS cells and induced apoptosis (as determined by annexin V-positive staining). These results suggest that the overexpression of Gal-1 contributes to abnormal cell growth in SBDS-deficient cells.

Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.

Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality-of-life including the ability to communicate and breathe. Treatment was traditionally limited to serial ablative procedures in the O.R. with possible local adjuvant therapy, but new systemic therapies, such as Vascular endothelial growth factor (VEGF) inhibitors, are showing significant promise. This study aims to determine whether rationale exists for combination therapeutic approaches using VEGF inhibitors and/or immune checkpoint blockade. Using fresh specimens from the O.R., we performed flow cytometry on papilloma, normal adjacent tissue, and blood. Papilloma and surrounding tissue were examined for expression of PD-L1, PD-L2, Galectin-9, VEGFR2, and VEGFR3. CD8+ and CD4+ T cells were assayed for expression of PD-1, TIGIT, LAG3, and TIM3. Our data shows that papilloma tissue exhibits significantly higher levels of PD-L1 and PD-L2 compared to adjacent tissue. Elevated levels of the VEGF receptor VEGFR3 were also observed in papilloma tissue. When examining T cells within the papilloma, elevated PD-1 and TIGIT expression was observed on CD8+ T cells, while levels of PD-1, TIGIT, and TIM3 were elevated on CD4+ T cells compared to PBMCs. Heterogenous marker expression was observed between individuals. Our analysis shows that RRP tissue shows elevated levels of multiple immune check point targets and VEGFR3, with varied patterns unique to each papilloma patient. Some of these immune checkpoint markers already have novel immunotherapies available or in development, providing molecular rationale to offer these systemic treatments to selected patients affected by RRP alongside VEGF inhibitors. Laryngoscope, 134:2819-2825, 2024.

ARID1A deficiency promotes progression and potentiates therapeutic antitumour immunity in hepatitis B virus-related hepatocellular carcinoma.

Exploring predictive biomarkers and therapeutic strategies of ICBs has become an urgent need in clinical practice. Increasing evidence has shown that ARID1A deficiency might play a critical role in sculpting tumor environments in various tumors and might be used as pan-cancer biomarkers for immunotherapy outcomes. The current study aims to explored the immune-modulating role of ARID1A deficiency in Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC) and its potential immunotherapeutic implications. In the current study, we performed a comprehensive analysis using bioinformatics approaches and pre-clinical experiments to evaluate the ARID1A regulatory role on the biological behavior, and immune landscape of Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC). A total of 425 HBV-related hepatocellular carcinoma patients from TCGA-LIHC, AMC and CHCC-HBV cohort were enrolled in bioinformatics analysis.Immunohistochemical staining of HBV-HCC specimens and ARID1A deficiency cellular models were used to validate the results of the analysis. Our results have shown that ARID1A deficiency promoted tumor proliferation and metastasis. More importantly, ARID1A deficiency in HBV-HCC was associated with the higher TMB, elevated immune activity, and up-regulated expression of immune checkpoint proteins, especially TIM-3 in HBV-HCC. Further, the expression of Galectin-9, which is the ligand of TIM-3, was elevated in the ARID1A knockout HBV positive cell line. To conclude, we have shown that the ARID1A deficiency was correlated with more active immune signatures and higher expression of immune checkpoints in HBV-HCC. Additionally, the present study provides insights to explore the possibility of the predictive role of ARID1A in HBV-HCC patients responsive to immunotherapy.

Differential immunohistochemical expression of Galectin-1 and Galectin-3 in renal cell carcinoma

Background Renal cell carcinoma (RCC) is a heterogeneous cancer with many histological and molecular subtypes. Many new potential diagnostic, prognostic, and predictive biomarkers are still emerging. RCC treatment approaches are plentiful, including surgical resection, ablation, and active surveillance as well as immunotherapy. However, many cases are nonresponsive to such modalities and others experience recurrence or metastatic disease. Accordingly, the research work nowadays is concerned with looking for new targeted therapy biomarkers to treat RCC. Galectin-1 and Galectin-3 are the proposed biomarkers for this issue. Aim and methods This work aims to review the expression of Galectin-1 and Galectin-3 immune markers among the main histological subtypes of RCC and their correlation with clinicopathological parameters. To carry out this work, 60 cases of RCC were included in this study: 36 clear RCC, 16 papillary RCC I and II, and eight cases chromophobe RCC. Results Galectin-1 was highly expressed in 42 out of 60 cases, while Galectin-3 was highly expressed in only 13 cases. There was a statistically significant association between Galectin-1 and Galectin-3 expression and the histological subtype being expressed more in chromophobe subtype rather than others. There was a statistically significant inverse association between Galectin-1 expression and lymphovascular invasion as well as Galectin-3 expression and tumor necrosis and hemorrhage. There was no statistically significant association between Galectin-1 and 3 and the remaining clinicopathological parameters. Conclusion Galectin-1 and Galectin-3 could be used as potential diagnostic markers for chromophobe RCC as they are highly expressed in this subtype in comparison to others and can be used as targeted biomarkers for RCC therapy in the future. Galectin-3 has an anti-necrotic role and this could lead to chemotherapy resistance.

Comparative analysis of galectin-1, galectin-3, and galectin-8 signatures in normal and choriocarcinoma trophoblast cell lines

Galectins are found in the placenta during both normal and pathological conditions. Specifically, galectins -1, -3, and -8 have been identified in extravillous trophoblast cells, with galectins -1, and -3 playing notable roles in trophoblast cell function. Altered expression profiles of galectins are linked to various cancers. This study explores the expression and localization of galectins -1, -3, and - 8 in a normal extravillous HTR-8/SVneo cell line and two choriocarcinoma cell lines, JAR and JEG-3. Expression levels of these galectins at both mRNA and protein levels were evaluated using PCR, qPCR, and Western blotting, while their cellular localization and distribution were assessed through immunocytochemistry, subcellular fractionation, and Western blotting. Galectins -1, -3, and -8 were expressed at lower levels in JAR and JEG-3 cells compared to HTR-8/SVneo cells. Additionally, different splice variants of galectin-8 were detected across all cell lines. Galectin-1 was predominantly localized at the plasma membrane. Notable differences in galectin-3 localization and distribution were observed between HTR-8/SVneo cells and choriocarcinoma cells. These findings highlight variations in the expression, staining patterns, and subcellular distribution of galectins -1, -3, and -8, suggesting their potential involvement in the pathology of choriocarcinoma.

Liraglutide improves adipose tissue remodeling and mitochondrial dynamics in a visceral obesity model induced by a high-fat diet

Central obesity is characterized by visceral adipose tissue (VAT) expansion, considered one of the main risk factors for metabolic complications. In recent years, new drugs have been studied for obesity treatment. Liraglutide (LGT), a GLP-1 agonist, decreases body weight, however, several mechanisms of action on VAT are still unknown. Aimto study the effect of LGT on factors associated with VAT remodeling and mitochondrial dynamics in mice fed a high-fat diet (HFD). MethodsC57BL/6 mice were divided into Control (C) and HFD. After 15 weeks of feeding, each group was subdivided according to LGT administration for 5 weeks: C, C + LGT, HFD, and HFD + LGT. In epididymal AT (EAT) we evaluated histological and mitochondrial characteristics, vascularity, gelatinase activity (MMPs), and galectin-3 expression. ResultsHFD presented larger adipocytes (p < 0.05), and lower vascular density and MMP-9 activity (p < 0.01) than C, while a major number of smaller adipocytes (p < 0.05) and an increase in vascularity (p < 0.001) and MMP-9 activity (p < 0.01) was observed in HFD + LGT. Collagen content was higher (p < 0.05) in EAT from HFD and decreased in HFD + LGT. In C, C + LGT, and HFD + LGT, mitochondria were predominantly tubular-shaped while in HFD mitochondria were mostly spherical (p < 0.001). ConclusionLGT positively influences VAT behavior by modulating gelatinase activity, enhancing vascularization, and improving adipocyte histological characteristics. Additionally, LGT improves mitochondrial dynamics, a process that would favor VAT functionality.

Angiotensin-II type 2 receptor-mediated renoprotection is independent of receptor Mas in obese Zucker rats fed high-sodium diet.

The consumption of a high-sodium diet (HSD) is injurious and known to elevate blood pressure (BP), especially in obesity. Acute infusion studies depict a functional interdependency between angiotensin-II type 2 receptor (AT2R) and receptor Mas (MasR). Hence, we hypothesize that the subacute blockade of MasR should reverse AT2R-mediated renoprotection in obese Zucker rats (OZRs). Male OZRs were fed an HSD (for 14days) and treated with the AT2R agonist C21 (100ng/min) without or with a MasR antagonist A779 (1,000ng/min). The indices of oxidative stress, proteinuria, kidney injury, and BP were measured before and after, along with the terminal measurements of an array of inflammatory and kidney injury markers. The HSD significantly decreased the estimated glomerular filtration rate and urinary osmolality and increased thirst, diuresis, natriuresis, kaliuresis, plasma creatinine, urinary excretion of H2O2, proteinuria, renal expression and urinary excretion of kidney injury markers (NGAL and KIM-1), and BP indexes. The HSD feeding showed early changes in the renal expression of CRP, ICAM-1, and galectin-1. The C21 treatment prevented these pathological changes. The MasR antagonist A779 attenuated C21-mediated effects on the urinary excretion and renal expression of NGAL and oxidative stress in the absence of inflammation and BP changes. Overall, we conclude that the subacute functional interactions between AT2R and MasR are weak or transient and that the beneficial effects of AT2R activation are independent of the MasR blockade in the kidney of male obese rats fed an HSD.