DigitalUM :: Browsing by browse.metadata.contributordepartment "Departamento de Biologia Celular e Histiologia"

Browsing by browse.metadata.contributordepartment "Departamento de Biologia Celular e Histiologia"

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Open Access
Adaptive changes in the visual cortex after photoreceptor degeneration in retinitis pigmentosa
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Martinez Galan, Juan R.; Caminos, Elena; Departamento de Biologia Celular e Histiologia
Retinitis pigmentosa (RP) is a group of hereditary disorders that cause progressive retinal degeneration, affecting the rods and, subsequently, the cones, which results in progressive vision loss. RP is genetically heterogeneous and is inherited in an autosomal dominant, autosomal recessive, X-linked, or sporadic non-Mendelian manner. The recent advance-ments in repairing damaged retinas highlight the necessity of understanding the impact of photoreceptor degeneration on the visual cortex. This is because functional vision may not be adequately restored if this region is significantly impaired prior to treatment. In the present review, we have analyzed the rodent models of RP that have been most frequently used and the physiological and morphological changes occurring in both humans and rodents with this disorder. Following visually evoked stimulation, the processing of visual information in the primary visual cortex (V1) of individuals with RP is altered due to modifications in the transduction of the signal originating in the degenerated retina. Moreover, alterations in the intrinsic electro-physiological properties of cortical neurons and neural circuits have also been documented. Finally, several neurochemical and/or morphological changes are observed in synaptic structures associated with pyramidal neurons and in select inhibitory interneurons. Nevertheless, despite the physiological and morphologi-cal changes that have been described, the impact of RP on the visual cortex does not inevitably result in irreversible damage, as the alterations do not appear to be particularly severe. Brain plasticity is more restricted in adults; however, remodeling of the visual cortex in mice and humans is possible, which encourages further work on therapies capable of partially restoring the lost visual function.
Open Access
Biomechanical and histological analyses of a multilayer stent in a swine model of suprarenal aortic aneurysm
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Tobita, Allana Maryel; Strazzi, Anna Paula Weinhardt Baptista; Portugal, Maria Fernanda Cassino; Wolosker, Nelson; Aun, Ricardo; Monteiro, Frederico de Lima Jacy; Vieira da Silva, Luiz; Sincos, Igor Rafael; Departamento de Biologia Celular e Histiologia
Objectives. To analyze and compare, in an animal model, the treatment of thoracoabdominal aneurysms with multilayer stents and its hemodynamic effects through the biomechanical and histological analysis of the aortic wall in contact with the stent. Methods. Large White pigs were randomized into two groups: Stent (n=6) and Control (n=5, non-stent). All animals were subjected to the creation of a suprarenal aneurysm with a bovine pericardial patch. In the Stent group, a multilayer stent was implanted immediately after aneurysm formation. After four weeks, all animals were subjected to angiographic assessment and intravascular ultrasound, and the stent was explanted before euthanasia for histological and biomechanical analyses. Results. At histological analysis, the groups did not differ significantly in maximum thickness of the intima (p=0.526), media (p=0.129), or adventitia (p=0.662). Thrombus formation was observed in 100% of the animals on the intima and media layers of the stented aorta vs. none in the Control group (p=0.048). At biomechanical analysis, no statistical differences were observed in aortic wall elasticity (p=0.158), strength (p=0.360), or thickness (p=0.323). Conclusion. We identified thrombosis of the aneurysmal sac through the presence of thrombi on the intima of the aorta in 100% of the animals in the Stent group; as for the biomechanical analysis, this study showed no statistical differences in vessel wall thickness, strength, and elasticity between
Open Access
Cocaine abuse and its impact on the thymus and spleen
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Aki, Toshihiko; Unuma, Kana; Departamento de Biologia Celular e Histiologia
Cocaine is a psychostimulant abused worldwide. Its pharmacotoxicological properties are derived mainly from its impact on the neurotransmission of sympathomimetic nerves. Cocaine enhances and prolongs the neurotransmission of monoamines, such as dopamine, serotonin, and adrenaline, which are responsible not only for cocaine’s euphoric effects, but also its cardiovascular toxicity. In addition to these effects on central as well as peripheral nerves, immunosuppression is also implicated in cocaine toxicity. The thymus and spleen are lymphoid organs that are essential in lymphocyte maturation and erythrocyte homeostasis. Reductions in thymus and spleen size, which are observed under both physiological and pathological conditions, are known as thymic involution and splenic contraction, respectively. These phenomena are also observed in experimental animal models of binge cocaine abuse. In this brief review, we describe the mechanisms of cocaine toxicity, thymic involution, and splenic contraction, followed by discussions about the possible role of the latter two phenomena in cocaine intoxication.
Open Access
Contribution of the dopaminergic system in toxoplasmic encephalitis neuroimmunopathogenesis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Anteplıoğlu, Tuğçe; Dincel, Gungor Cagdas; Alçiğir, Mehmet Eray; Türkmen, Merve Bışkın; Yapic, Tilbe Su; Kul, Oguz; Al Olayan, Ebtsam; Alshahrani, Mohammad Y.; El Ashram, Saeed; Departamento de Biologia Celular e Histiologia
Toxoplasma gondii (T. gondii), a parasitic intracellular protozoan, can establish a chronic infection in the host brain and cause significant neuropathology. The current study aimed to determine the role of Tyrosine Hydroxylase (TH), Dopamine Receptor D1 (D1R), Nuclear Receptor Related-1 (Nurr1), and Dopamine Transporter (DAT) expression in the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) at 15, 30, 45, and 60 days after infection with T. gondii. Additionally, the study investigated whether there was a correlation between the markers on these critical days, which had yet to be explored. The results showed that TH expression in brain tissue of BALB/c mice was significantly increased in all infected groups compared with healthy controls (p<0.05). However, other striking findings of the study were that D1R, DAT, and Nurr1 expression were significantly decreased in all infected groups compared with healthy controls, in contrast to TH expression (p<0.05). Study findings regarding behavioral changes in chronic T. gondii-infected laboratory animals and humans with TE provide important evidence of the relationship between neuropsychiatric diseases and T. gondii infection. By elucidating the pathogenesis of the disease in detail, treatment protocols that consider these coordinated changes in expression that vary from day to day can be developed.
Open Access
Cytoskeleton proteins, the structural basis of T-lymphocyte and TEC restructure during rapid thymus regeneration
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wen, Xunuo; Gao, Jianli; Departamento de Biologia Celular e Histiologia
Thymus regeneration is the main way for humans to combat immune degeneration and immunosenescence. The interesting cycle of thymus degeneration and regeneration achieves the renewal of adaptive immunity, which is crucial for reconstructing cellular immunity. Rapid thymic regeneration is the main renewal mode after various acute stress-induced thymic involutions, such as radiation, immunosuppressants, and starvation. The cytoskeleton is a key regulator of immune response by affecting the structure and function of immune cells. Our team has conducted years of research on rapid thymic regeneration and found that some types of cytoskeletal proteins, such as F-actin/G-actin, the Thymosin β family, ERM (Ezrin/Radixin/ Moesin), and WAVE2, play a critical role in the spatial development of thymic epithelial cells (TECs), and finally regulate the regeneration of the thymus by modulating the skeleton of TECs and T lymphocytes. Here, we summarize the current understanding of cytoskeleton proteins and cell restructure of TECs or T lymphocytes and its relationship with the regeneration of the thymus.
Open Access
DNMT1 silencing induces KIR2DL1/2/3 expression via methylation to alleviate graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhang, Ping; Yu, Shuling; Yan, Xiao; Zhu, Huiling; Sheng, Lixia; Zhang, Yi; Yang, Shujun; Ouyang, Guifang; Departamento de Biologia Celular e Histiologia
Natural killer (NK) cells are the promoters in graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), while demethylation can regulate NK cell function. We explored the mechanism of demethylation regulating NK cell function to affect GVHD after allo-HSCT. BALB/c mice were transfused with C57BL/6 mouse-derived NK and bone marrow cells to establish GVHD models, followed by isolation and in vitro expansion of NK cells. NK cell purity, cytokine levels, proliferation, and cytokine-producing NK cell levels were measured via flow cytometry. KIR2DL1/2/3 methylation was tested by Methylation-specific polymerase chain reaction (MSP), with determination of mouse survival and GVHD scores. KIR2DL1/2/3 and DNMT1 expression was detected through qRT-PCR and/or western blot. Methylation levels were upregulated and KIR2DL1/2/3 expression was downregulated in GVHD mouse model-derived NK cells following IL-2 stimulation. DNMT1 silencing promoted KIR2DL1/2/3 expression, proliferation, and the secretion of Granzyme, Perforin, and Interferon-γ (IFN-γ) in C57BL/6 mouse-derived NK cells. DNMT1 silencing also enhanced mouse survival, reduced GVHD scores, promoted KIR2DL1/2/3 expression on the NK cell surface, and increased the secretion of Granzyme, Perforin, IFN-γ, and the number of cytokine-producing NK cells in the spleen, liver, and lung tissues of the models. Collectively, DNMT1 silencing induced KIR2DL1/2/3 expression in NK cells through reducing methylation to alleviate GVHD after allo-HSCT
Open Access
Effects of combustible cigarettes and electronic nicotine delivery systems on the regenerative properties of mesenchymal stem cells derived from periodontal ligament (PDL-MSCs)
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Kastratovic, Nikolina; Milosevic Djordjevic, Olivera; Harrell, Carl Randall; Djonov, Valentin; Volarevic, Vladislav; Departamento de Biologia Celular e Histiologia
Introduction. Periodontal ligament-derived mesenchymal stem cells (PDL-MSCs) are promising cells with crucial roles in maintaining and repairing periodontal tissue. However, their regenerative capacity can be influenced by various factors, including cigarette smoke and electronic nicotine delivery system (ENDS) aerosols. Smoking and vaping can impair their regenerative potential, and even though ENDS are perceived as safer tobacco products, there is a lack of evidence to guarantee this assumption. Material and methods. Changes in the viability and proliferation of PDL-MSCs will be investigated after smoke and aerosol generation and cell exposure. In addition, the effects of smoke and aerosols on the immunomodulatory capacity of PDL-MSCs co-cultured with T lymphocytes will be further determined via the evaluation of cytokine profiles and flow cytometry analysis of T-cell phenotypes. Results. Combustible cigarettes (CCs) induced more severe impairment in the viability and proliferation of PDL-MSCs compared with ENDS. Also, CCs promoted a proinflammatory immune response that could cause tissue damage to progress. On the other hand, ENDS had the potential to generate an immunosuppressive response that would prevent further cell decay. Discussion. The regenerative capacity of PDL-MSCs decreased after treatment with both cigarette smoke and ENDS-aerosols. Even though the results demonstrate less severe effects with ENDS, further research is essential to evaluate their safety and impact on the capacity of PDL-MSCs to prevent and restore oral injuries caused by chronic exposure to aerosols
Open Access
Evaluation of the impact of Momordica charantia on the testis of cisplatin-treated albino rats: Biochemical, histopathological, and ultrastructural study
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Shalaby, Fatma Mohsen; Elrefaie, Amany Omar; Abd, Kandil; Attia, El Hai; Departamento de Biologia Celular e Histiologia
Cisplatin is an antineoplastic drug that exhibits toxicity dependent on dosage and has adverse reproductive effects. Momordica charantia (Bitter melon) is a natural vegetable plant; its active ingredients possess antioxidant, apoptotic, antiproliferative, hypoglycemic, and other therapeutic properties. This study evaluates the effect of the administration of bitter melon extract, cisplatin, and cisplatin/bitter melon cotreatment on liver and kidney functions, serum and testicular oxidative status, testis histology, and sperm parameters. Adult male Wistar rats were randomly divided into four groups: Group I (Control) received normal saline, Group II received oral bitter melon extract (300 mg/kg), Group III received cisplatin (2.5 mg/kg), and Group IV received the same doses of cisplatin and bitter melon, for six successive weeks, daily. Our results showed that bitter melon extract stimulates antioxidant enzymes and has anti-lipid peroxidation properties through the significantly increased plasma levels of glutathione and significantly decreased testicular malondialdehyde. The cisplatin-treated group showed oxidative stress indicated by the significant decrease of catalase, glutathione, and superoxide dismutase levels and a significant increase in malondialdehyde levels in both serum and testis compared with the control group. In the cisplatin/bitter melon-cotreated group, there was a significant increase in superoxide dismutase and a significant decrease in malondialdehyde in both serum and testis compared with cisplatin-treated rats. The bitter melon alone or with cisplatin cotreatment resulted in reduced gonadosomatic index, sperm count, motility, and viability. These results were confirmed by histopathological examinations, apoptosis assay using flow cytometry, and immunohistochemical staining for proliferating cell nuclear antigen. In conclusion, the administration of bitter melon extract alone or in combination with cisplatin led to testicular structure disturbances and showed an anti-spermatogenic effect. These findings are likely due to a combination of inhibited cellular proliferation, increased cell death, minor decrease in testosterone levels, and localized oxidative stress that outweigh the antioxidant benefits of bitter melon extract.
Open Access
Ex vivo applications of porcine ocular surface tissues: Advancing eye research and alternatives to animal studies
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Diebold, Yolanda; García Posada, Laura; Departamento de Biologia Celular e Histiologia
The use of tissues of porcine origin has gained significant momentum in the scientific community due to their anatomical and physiological resemblance to human tissues. This review provides a comprehensive overview of the key biological features of porcine ocular structures, including the cornea, conjunctiva, and associated tissues, in comparison to their human counterparts. Additionally, this review outlined the ex vivo applications of these tissues in the study of different biological processes and the simulation of pathological conditions. By high-lighting the potential of porcine ocular surface tissues as cost-effective, ethically appropriate, and reliable models, this review underscores their value in advancing eye and vision research.
Open Access
Exploring pathological targets and advancing pharmacotherapy in autism spectrum disorder: Contributions of glial cells and heavy metals
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Chatterjee, Dhrita; Maparu, Kousik; Singh, Shamsher; Departamento de Biologia Celular e Histiologia
Autism spectrum disorder (ASD) is a globally recognized neurodevelopmental condition characterized by repetitive and restrictive behavior, persistent deficits in social interaction and communication, mental disturbances, etc., affecting approximately 1 in 100 children worldwide. A combination of genetic and environmental factors is involved in the etiopathogenesis of the disease, but specific biomarkers have not yet been identified. Due to the lack of clinical evidence, fluctuations in symptoms, and difficulties in in-vitro and in-vivo modeling, developing medications for ASD is quite difficult. Although several drugs are used to treat autism, only risperidone and aripiprazole have received FDA approval in the United States. Epidemiological studies have suggested that maternal exposure to valproic acid (VPA), acetaminophen, propionic acid, and metals, such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg), may contribute to the development of various neurodevelopmental disorders. Pathological targets directly implicated in the disease include excitatory-inhibitory (E/A) imbalance, hyperserotonemia, GSK-3 inhibition, and Akt pathway activation. However, while a combination of pharmacotherapy, behavioral, and nutritional/dietary interventions has been found to be the most effective conventional therapy to date, many patients have chosen to implement particular dietary supplements for reducing ASD symptoms. In this review, we briefly describe various pathological targets and their roles in the pathophysiology of ASD and treatment strategies, including some future research directions.
Open Access
Expression and prognostic value of PIM-1 kinase in gliomas
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Li, Zelin; Wang, Hu; Wang, Guangxiu; Wang, Chen; Zhang, Anling; Mo, Lidong; Jia, Zhifan; Tong, Xiaoguang; Departamento de Biologia Celular e Histiologia
Objective. This study aimed to explore the correlation of PIM-1 with the clinicopathological features and prognosis of patients. Methods. The MTERF3 mRNA and protein expression levels in tissues were detected by western blot and immunohistochemistry. The expression and survival of PIM-1 in patients with glioma were analysed using the Gene Expression Profiling Interactive Analysis database, the Gene Expression Database of Normal and Tumor Tissues 2, and the Chinese Glioma Genome Atlas database. The relationship between PIM-1 expression and immune cells and chemokines was analysed using the Tumor Immune Estimation Resource Version 2.0 tool and the Tumor and Immune System Interactions Database. A Kaplan–Meier plot was used to estimate the correlation between PIM-1 expression and the survival of patients with glioma. Results. The expression of PIM-1 was upregulated in glioma and was positively correlated with tumour grade. The expression of PIM-1 was significantly inhibited on the second day after transfection (p<0.05), and the inhibition was most obvious on the sixth day (p<0.01). The results of the co-expression pattern of PIM-1 showed that the expression of 5,012 genes was positively correlated with PIM-1, while the expression of 3,651 genes was negatively correlated with PIM-1. Macrophages (p<0.001), myeloid dendritic cells (p<0.001), NK cells (p<0.001), CD4 T cells (p<0.001), cancer-associated fibroblasts (p<0.001), and neutrophils (p<0.001) were positively correlated with the expression of PIM-1 in low-grade glioma. Conclusion. PIM-1 is overexpressed in glioma and is related to the prognosis of glioblastoma multiforme, and PIM-1 may be a prognostic biomarker and therapeutic target for glioma.
Open Access
Fortunellin attenuates sepsis-induced acute kidney injury by inhibiting inflammation and ferroptosis via the TLR4/NF-κB pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Tianzhi, Liu; Yanmin, Zhang; Liu, Xiujuan; Zuo, Zhigang; Departamento de Biologia Celular e Histiologia
Objective. To investigate the potential protective effect of fortunellin in sepsis-induced acute kidney injury (AKI) and its underlying mechanisms. Methods. Lipopolysaccharide (LPS)-treated human kidney proximal tubular epithelial (HK-2) cells were used as a cell model and sepsis-induced AKI was induced by cecal ligation and puncture (CLP) surgery in mice. Cell Counting Kit-8 (CCK8) assays and flow cytometry analysis were performed to examine the viability of HK-2 cells. Enzyme-linked immunosorbent assay (ELISA) was performed to investigate the content of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in vivo and in vitro. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and free iron (Fe2+) were measured as indicators of ferroptosis. The phosphorylation levels of Interleukin-1 Receptor-Associated Kinase 4 (p-IRAK4), p65 (p-65), and inhibitor of kappa B alpha (p-IκBα) were detected by western blot as an indication of nuclear factor kappa-B (NF-κB) pathway activation. Results. Our cell and animal experiments revealed that fortunellin exhibits significant anti-inflammatory and cytoprotective properties. Fortunellin counteracted LPS-induced cellular damage in HK-2 cells, enhancing cell survival and suppressing the secretion of pro-inflammatory cytokines. Additionally, fortunellin demonstrated potent antioxidant effects, reducing MDA and Fe2+ levels while increasing SOD activity and GSH content. The protective effect of fortunellin was further corroborated in the mouse model of sepsis-induced AKI. Notably, fortunellin suppressed activation of the TLR4/NF-κB pathway in the AKI model, as evidenced by decreased levels of p-p65 and p-IκBα proteins. Conclusion. Fortunellin ameliorates inflammation and oxidative stress in sepsis-induced AKI, possibly through the modulation of the TLR4/NF-κB pathway. These findings suggest fortunellin's potential as a therapeutic agent for sepsis-associated AKI.
Open Access
Gradual expression of MMP9 and MT1-MMP at the tumor-stroma interface in head and neck squamous cell carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Rusu, Stefan; Nuyens, Vincent; Rousseau, Alexandre; Lothaire, Philippe; Nagy, Nathalie; Boudjeltia, Karim Zouaoui; Uzureau, Pierrick; Departamento de Biologia Celular e Histiologia
Due to the late-stage diagnosis of head and neck squamous cell carcinoma (HNSCC), treatment remains a significant clinical challenge. The metallo-proteinases MMP-9 and MT1-MMP play a pivotal role in extracellular matrix remodeling, thereby facilitating tumor growth and metastasis. Tumor progression requires the degradation of the basement membrane. The principal components of this structure, namely collagen IV and laminin, are the main targets of both MMP-9 and MT1-MMP. However, they can also exert influence over the expression of these enzymes. Oxidative stress plays an instrumental role in tumor development, functioning as a key inducer of metalloproteinase expression. The present study investigates the distribution of MMP-9 and MT1-MMP within tumor nests and along the basement membrane, comparing these with the distributions of collagen IV, laminin-332, and the antioxidant MnSOD. Biopsies from 12 patients with HNSCC and poor prognostic factors were subjected to immuno-fluorescence analysis. MMP-9 and MT1-MMP were found to be predominantly present in tumor cells, with a significant decrease in expression from the periphery to the center of tumor nests. Co-localization studies with laminin-332 and collagen IV, revealed substantial overlap, in accordance with the role of MMPs in basal membrane degradation. The cellular expression of laminin-332 associated with MMP-9 expression suggests an intricate relationship between metalloproteinases and their targets. While the previously observed pattern of glutathione-producing enzyme was similar to the metalloproteinases pattern, MnSOD expression was homogeneously distributed within tumor nests. Our findings reveal various distribution patterns of oxidative stress regulators, suggesting a complicated interplay in the development of HNSCC
Open Access
Hsa_circ_0088036 promotes tumorigenesis and chemotherapy resistance in hepatocellular carcinoma via the miR-140-3p/KIF2A axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wang, Zhong; Wang, Lei; Yin, Guoqing; Li, Heng; Zhang, Rong; Feng, Yuan; Chang, Wen; Departamento de Biologia Celular e Histiologia
Background. Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. There are limited treatment options, particularly for chemotherapy-resistant HCC patients. Circular RNA hsa_circ_0088036 was associated with the development of bladder cancer and non-small cell lung cancer. However, whether it might be a potential therapeutic target for HCC remains elusive. Methods. Hsa_circ_0088036 expression was detected in HCC tumor tissues and cell lines using real-time PCR. The influences of hsa_circ_0088036 on proliferation and invasion as well as chemotherapy sensitivity in HCC cells were investigated by gain- and loss-of-function analyses. Associations among hsa_circ_0088036, miR-140-3p, and KIF2A were validated by real-time PCR, miRNA pull-down assay, dual-luciferase reporter assay, and western blot. Furthermore, a rescue experiment using KIF2A overexpression was performed to evaluate the regulatory mechanism of hsa_circ_0088036 in HCC cells. Additionally, the effect and mechanism of hsa_circ_0088036 were confirmed in a xenograft mouse model. Results. Hsa_circ_0088036 was highly expressed in HCC tissues and cells, with even higher expression in oxaliplatin-resistant cells. This expression was positively correlated with tumor size and TNM stage of the patients. Overexpression of hsa_circ_0088036 promoted the proliferation and invasion of HCC cells, while silencing mediated the opposite effects. Meanwhile, knockdown of hsa_circ_0088036 enhanced chemo-therapy sensitivity, including oxaliplatin, doxorubicin, and sorafenib, in HCC cells. Furthermore, hsa_circ_ 0088036 silencing inhibited tumor growth and increased oxaliplatin sensitivity in vivo. Mechanically, hsa_circ_0088036 functioned via the miR-140-3p/KIF2A axis with the activation of PI3K/Akt and Notch signaling pathways. Conclusions. Hsa_circ_0088036 promoted HCC tumorigenesis and chemotherapy resistance by activating the PI3K/Akt and Notch pathways through regulating miR-140-3p/KIF2A signaling. Thus, hsa_circ_0088036 may be a potential therapeutic target in chemotherapy-resistant HC
Open Access
Human equilibrative nucleoside transporter 1 and concentrative nucleoside transporter 1 in colorectal cancer: What do we know? A systematic review
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) McKenna, Matthew; Linganathan, Saranya; Li, Amber; Ruge, Fiona; Lane, Jane; Ye, Lin; Jiang, Wen; Hargest, Rachel; Departamento de Biologia Celular e Histiologia
Colorectal cancer (CRC) remains a major global health challenge despite advances in screening, diagnosis, and treatment. This systematic review examines the roles of Human Equilibrative Nucleoside Transporter 1 (hENT1) and Human Concentrative Nucleoside Transporter 1 (hCNT1) in CRC, focusing on their expression, regulation, and impact on chemo-therapeutic efficacy, particularly with nucleoside analogues like 5-fluorouracil (5-FU). We conducted a comprehensive literature search following PRISMA guidelines, yielding 29 studies that met our inclusion criteria. The review reveals variable expression of hENT1 and hCNT1 in CRC tissues compared with normal tissues, with implications for treatment response and development of resistance. Increased hENT1 expression is associated with poor outcomes and resistance to 5-FU, suggesting its potential as a biomarker for predicting treatment response. Conversely, hCNT1's role appears more complex, with its expression influencing the efficacy of other chemotherapeutic agents like gemcitabine and capecitabine. The review also highlights the lack of robust, standardised methods for assessing mRNA and protein levels, which complicates the interpretation of data and the establishment of these transporters as reliable clinical markers. Key findings include the potential therapeutic benefits of modulating hENT1 and hCNT1 expression to enhance drug efficacy and overcome resistance. The study underscores the need for further research using standardised and advanced methodologies, such as 3D cell culture assays, to better understand the mechanistic pathways and clinical implications of nucleoside transporter expression in CRC. Future research should aim to clarify the roles of hENT1 and hCNT1 in CRC and chemoresistance to develop targeted therapies and improve patient outcomes.
Open Access
Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Casanova Martín, Carlos; Liviu Boaru, Diego; Fraile Martínez, Oscar; García Montero, Cielo; Leon Oliva, Diego De; Castro Martinez, Patricia De; Gimeno Longas, Maria José; Buján, Julia; García Honduvilla, Natalio; Guijarro, Luis G; Gragera, Raquel; López González, Laura; Saez, Miguel A.; Ferrara Coppola, Connie; Baena Romero, Víctor; Diaz Pedrero, Raul; Alvarez Mon, Melchor; Toledo Lobo, M. Val; Ortega, Miguel A.; Departamento de Biologia Celular e Histiologia
Penile cancer is an uncommon disease compared with other urological tumors and is more common in low- and middle-income countries. Risk factors include age, ethnicity, smoking, hygiene, and human papillomavirus infection. Although carcinoma of the penis can be cured in up to 80% of cases if detected early, late diagnosis drastically reduces survival rates, especially in metastatic cases. More than 95% of cases are squamous cell carcinomas, and the degree of cell differentiation is a key histopathological factor, distinguishing between poorly (P), moderately (M), and well-differentiated (W) carcinomas, with verrucous carcinoma (V) having the best prognosis due to its low metastatic capacity. This study analyses the differential expression of several biomarkers related to cell proliferation and cell cycle, inflammation, epigenetics, and autophagy (cell cycle (IRS-4, Ki-67, RB1, CDK4, cyclin D1, ERBB2, β-catenin, and MAGE-A), inflammation (COX2, NLRP3, and AIF-1), epigenetics (HAT-1) and autophagy (ULK-1 and ATG9A) in penile carcinoma according to the degree of differentiation. Immunohistochemical techniques were performed on 34 penile squamous cell carcinoma (PSCC) samples classified into subtype V (N=6), and groups P (N=9), M (N=9), and W (N=10). The findings suggest a differential expression of molecules according to the degree of cell differentiation, with a higher differential expression of molecules according to the degree of cell differentiation, suggesting that the proteins studied could have predictive value. The study highlights the complexity of PSCC and the need for future studies to explore translational applications and search for new biomarkers to improve clinical management and understanding of this disease
Open Access
Knockdown of TBRG4 suppresses the migration, invasion, and epithelial-to-mesenchymal transition of pancreatic cancer cells via TGF-β/smad3 signaling
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ye, Xiao; Zheng, Xiaolin; Zhu, Ling; Departamento de Biologia Celular e Histiologia
Introduction. Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, with a low five-year survival rate of less than 10%. Transforming growth factor β regulator 4 (TBRG4) is differentially expressed in PC tissues, but its specific functions and regulatory role in PC have not been clarified. Methods. TBRG4 mRNA expression in PC cells was measured by qRT-PCR. Protein levels of TBRG4, key markers related to the epithelial-mesenchymal transition (EMT) process, and factors related to the TGF-β/smad3 pathway were quantified by western blot. The migratory and invasive abilities of PC cells were evaluated by wound healing and Transwell assays, respectively. Spearman’s correlation analysis was performed to analyze the expression correlation between TBRG4 and TGF-β1 (or SMAD3). Xenograft mouse models were established to explore the in vivo role of TBRG4. Results. The mRNA and protein expression of TBRG4 were elevated in PC cells. TBRG4 knockdown repressed PC cell migration, invasion, and the EMT process. Moreover, TBRG4 activated TGF-β/smad3 signaling in PC cells and positively correlated with TGF-β1 (or SMAD3) expression in PC tissues based on bioinformatics analysis. Furthermore, SRI-011381 (an agonist of TGF-β1) counteracted the inhibitory influence of TBRG4 knockdown on PC cellular behaviors, and SB431542 (an inhibitor of the TGF-β type I receptor) treatment countervailed the promoting influence of TBRG4 overexpression on PC cell invasion, migration, and EMT. Results of in vivo assays verified that TBRG4 silencing inhibited tumorigenesis and TGF-β/smad3 signaling. Conclusion. The silencing of TBRG4 inhibits PC cell invasion, migration, EMT, and tumorigenesis by inactivating TGF-β/smad3 signaling.
Open Access
Melatonin inhibits the activation of microglia and cough sensitivity of guinea pigs exposed to PM2.5
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhang, Shu; Long, Li; Chai, Senlin; Lin, Mingtong; Lu, Hankun; Liu, Xuemei; He, Yaowei; Dong, Rong; Chen, Zhe; Departamento de Biologia Celular e Histiologia
Objective. The study aimed to examine the impact of melatonin on mitigating brain inflammation and cough sensitivity resulting from exposure to particulate matter 2.5 (PM2.5). Methods. Guinea pigs were randomly assigned to the blank control group, normal saline group, PM2.5 exposure group, and PM2.5 exposure + melatonin group. The PM2.5 exposure and PM2.5 exposure + melatonin groups were given intranasal instillations of PM2.5 suspension twice daily for 28 consecutive days. Starting on day 21, the PM2.5 exposure + melatonin group was treated with an intraperitoneal injection of melatonin at 10 pm. Cough sensitivity to citric acid, microglia activation, IL-1β and TNF-α levels in the airway and dorsal vagal complex (DVC), and ultrastructural changes in neurons within the DVC were assessed. Results. The PM2.5 exposure group exhibited a significantly higher cough count to citric acid challenge (29.1±5.7 coughs) compared with the PM2.5 exposure + melatonin group (18.8±4.1 coughs), normal saline group (8.4±2.1 coughs), and blank control group (7.7±1.8 coughs). In addition, cough latency was shorter in the PM2.5 exposure group (26.9±6.5 seconds) than in the PM2.5 exposure + melatonin group (36.6±12.4 seconds), normal saline group (43.4±14.7 seconds), and blank control group (47.0±13.0 seconds). The PM2.5 exposure + melatonin group showed significantly reduced IL-1β (105.3±14.3 pg/ml) and TNF-α levels (113.0±23.5 pg/ml) in the DVC, as well as in the bronchoalveolar lavage fluid (IL-1β: 24.92±5.14 pg/ml, TNF-α: 12.72±3.99 pg/ml) compared with the PM2.5 exposure group (in the DVC: IL-1β: 132.7±17.6 pg/ml, TNF-α: 143.8±30.4 pg/ml; in the bronchoalveolar lavage fluid: IL-1β: 34.0±5.3 pg/ml; TNF-α: 15.8±0.8 pg/ml). Microglia in the DVC were less activated in the PM2.5 exposure + melatonin group (25.1±5.4) than in the PM2.5 exposure group (54.6±9.9). Furthermore, the PM2.5 exposure group exhibited an impaired blood-brain barrier in the DVC, which tended to alleviate the PM2.5 exposure + melatonin group. Conclusions. Exposure to PM2.5 induces airway inflammation, central facilitation, and heightened cough sensitivity in guinea pigs. Melatonin significantly inhibits microglia activation and reduces airway and DVC inflammation, which might contribute to attenuated cough hypersensit
Open Access
Modulation of the malignant behavior of tongue squamous cell carcinoma cells by matrix metallopeptidase 25 through the NF-κB pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Bai, Shuang; Sun, Shao Kang; Xu, Zhen-Qi; Yan, Ying-Bin; Departamento de Biologia Celular e Histiologia
Objective. Accumulating evidence has implicated matrix metalloproteinases (MMPs) in the progression of human cancers. Matrix metallopeptidase 25 (MMP25) is a membrane-type MMP whose role in tumorigenesis and cancer development is not well understood. Here, we investigated the functions of MMP25 in tongue squamous cell carcinoma (TSCC). Methods. Gene expression was measured using real-time PCR and western blot. CCK-8 and Transwell assays were used to determine the proliferation, migration, and invasion of TSCC cells. An NK cell co-culture experiment was performed to evaluate the killing of TSCC cells by NK cells. Results. MMP25 had higher expression levels in TSCC tissues than in adjacent non-cancerous tissues. MMP25-overexpressing and MMP25-silenced TSCC cell lines were established by lentiviral transduction. Overexpression of MMP25 promoted proliferation, migration, and invasion of TSCC cells, whereas knockdown of MMP25 had opposite effects. MMP25 modulated the levels of proliferation- and apoptosis-related proteins (PCNA, cyclin D, cyclin B1, p27, and cleaved caspase 3 and 9) and upregulated two invasion-related MMPs (mature MMP2 and MMP9). Additionally, MMP25 promoted tumor growth of TSCC cells in athymic nude mice. Notably, MMP25 upregulated PD-L1 in TSCC cells, attenuated NK cell killing of TSCC cells, and inhibited the secretion of anti-tumor cytokines (TNF-α and IFN-γ). Furthermore, MMP25 promoted the nuclear translocation of NF-κB p65, suggesting that activation of NF-κB signaling may mediate the pro-tumor functions of MMP25 in TSCC. Conclusion. This study revealed a novel role for MMP25 in TSCC, highlighting the potential of MMP25 as a therapeutic target in TSCC.
Open Access
Paeonol regulates glycolytic metabolism by downregulating BACH1 to ameliorate stemness, angiogenesis, and EMT in SiHa cervical cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Sheng, Shaoqin; Xu, Jing; Hu, Danhong; Qian, Weiwei; Xu, Xiangqian; He, Jing; Departamento de Biologia Celular e Histiologia
As a common reproductive malignancy of the female reproductive system, cervical cancer has increasingly become a public health concern. Paeonol, which is a natural phenolic monomer, has been found to possess substantial anticancer effects in some human cancers. The present study was conceived to explore the role and mechanism of paeonol in cervical cancer. Initially, the cytotoxicity of paeonol on immortalized H8 cervical epithelial cells and the proliferation of SiHa cervical cancer cells with paeonol treatment were detected using the CCK-8 assay. Cell stemness was assessed with the spheroid formation assay while western blot was applied for the measurement of proteins associated with cell stemness. The tube formation assay was used to detect the angiogenesis of human umbilical vein endothelial cells (HUVECs) and western blot was used to estimate the expression of EMT- and angiogenesis-related proteins. The extra-cellular acidification rate (ECAR) and oxygen consumption rate (OCR) of cells were appraised via a Seahorse XFe24 Flux Analyzer. Lactate production, glucose consumption, and ATP levels were evaluated with corresponding assay kits. Western blot was applied for the evaluation of GLUT1 and HK2. The mRNA and protein expression of BACH1 before and after transfection were detected using RT-qPCR and western blot. The luciferase reporter assay was used to detect the activities of GLUT1 and HK2 promoters. In this study, we found that paeonol inhibited cell proliferation, cell stemness, EMT progress, angiogenesis, and glycolysis in cervical cancer via downregulating BACH1. In summary, paeonol impeded the progression of cervical cancer by regulating glycolytic metabolism through the inhibition of BACH1.