Revistas y Congresos

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Esta comunidad la componen las revistas editadas por la UM y Actas, Jornadas y Congresos organizados por la misma.

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Open Access
1,25-Dihydroxyvitamin D3 mitigates high glucose-induced oxidative stress, inflammation, and extracellular matrix accumulation in glomerular mesangial cells via the ROS/TXNIP/NLRP3 pathway
(2026) Bo Chen; Chunjiang Zhang; Lin Jia; Xingyu Yao; Gang Liu; Qingyue Meng; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
ackground. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is a physiologically active form of vitamin D. Our study investigated the renoprotective functions of 1,25(OH)2D3 in diabetic nephropathy (DN) progression and its underlying mechanism targeting the ROS/TXNIP/NLRP3 inflammasome pathway. Methods. DN was induced in Wistar rats via high-fat diet (4 weeks) and streptozotocin injection (30 mg/kg, i.p.); hyperglycemic rats were randomized into DN and DN + 1,25(OH)2D3 (16 μg/kg, 12 weeks) groups. Rat mesangial HBZY-1 cells were maintained under normal glucose (5.5 mM), high glucose (25 mM), high glucose plus 1,25(OH)2D3 (1-50 nM), or high glucose plus N acetylcysteine (NAC, 10 mM). Cell viability was assessed by the CCK-8 assay. Oxidative stress parameters (ROS via DCFH-DA fluorescence, MDA content, SOD activity) and pyroptosis markers (LDH release, PI/Hoechst 33342 nuclear staining) were quantified. Renal histopathology was performed using PAS and Masson trichrome staining. Biochemical analyses included serum creatinine, urea nitrogen, and 24h urinary protein quantification. Molecular profiling encompassed ELISA (IL-1β, IL-6, TNF-α, IL-18, fibronectin, collagen IV), RT-qPCR (NOX2, NOX4, NLRP3, ASC), western blotting (TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, collagen IV, fibronectin, laminin), and TXNIP immunofluorescence. Results. 1,25(OH)2D3 significantly attenuated high glucose-induced pathological alterations in HBZY-1 cells, including ROS overproduction, TXNIP upregulation, NLRP3 inflammasome activation, oxidative stress, inflammation, extracellular matrix (ECM) deposition, and pyroptotic cell death. Consistently, 1,25(OH)2D3 suppressed ROS/TXNIP/ NLRP3/caspase-1 signaling, ameliorated renal dysfunction, and mitigated histopathological damage in DN rats. Conclusion. 1,25(OH)2D3 confers renoprotection in DN by inhibiting the ROS/TXNIP/NLRP3 inflamma some axis, thereby suppressing oxidative stress, inflammatory cytokine production, ECM accumulation, and pyroptotic cell death in glomerular mesangial cells and renal tissues.
Open Access
A clinicopathological study of eight cases presenting a biphasic structure: A distinct variant of pulmonary carcinoma
(2026) Qiuyao Li; Jiwei Ma; Kun Yang; Xiaoyan Lin; Huifeng Jiang; Yali Xu; Lin Song; Yu Zhang; Xiaoqian Liu; Zheng Mou; Wenjing Su; Hongyu Wang; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Biphasic structures, which are composed of outer basal cells and inner glandular cells, are frequently indicative of salivary gland-type tumors or benign lesions, such as bronchial adenoma, within the lung. However, the occurrence of a biphasic structure in lung cancer is rarely reported and can lead to significant challenges and confusion in diagnosis, particularly in biopsy specimens. In our study, we collected eight lung epithelial tumors that presented with a distinct biphasic structure component and examined their clinicopathological characteristics. Histological examination revealed that the biphasic structure component, often intermingled with conventional squamous cell carcinoma or adeno carcinoma, was defined by basal cells encircling the glandular epithelium. Immunohistochemical analysis demonstrated a distinctive peripheral p40 staining pattern in the biphasic structure component. Genetic analysis identified driver mutations in seven out of eight patients, which are typically associated with conventional pulmonary adenocarcinomas, including EGFR L858R, EGFR 19-del, EGFR 20-ins, and KRAS mutations. The presence of biphasic structure components in these cases confirms a genuine form of lung cancer, likely representing a variant of lung adenocarcinoma. This study's findings enhance the understanding of lung cancer's morphological diversity and caution against prematurely dismissing the malignancy potential of pulmonary epithelial lesions based solely on the presence of basal cells, especially with biopsy specimens.
Open Access
A low nuclear-to-cytoplasmic ratio of VDR expression is an independent prognostic marker in breast cancer
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Schubert Charlotte; Vilsmaier Theresa; Batz Falk; Cavaillès Vincent; Sixou Sophie; Kolben Thomas; Meister Sarah; Buschmann Christina; Hagemann Friederike; Biología Celular e Histología
The aim of this retrospective study was to analyze the prognostic value of cytoplasmic versus nuclear expression of the vitamin D receptor (VDR) in breast cancer (BC) tissue samples and to relate the results to clinicopathological parameters. VDR expression was assessed in 319 primary breast cancer patients using the Remmele and Stegner immunoreactive scoring (IRS) system. Follow-up data were obtained from the Munich Cancer Registry. The correlation with overall survival (OS) and disease-free survival (DFS) was calculated using univariate and multivariate analyses. Correlation analysis revealed a correlation between nuclear VDR expression and improved outcomes for both OS (p=0.004) and DFS (p=0.001). Conversely, cytoplasmic VDR expression was significantly associated with a shorter OS (p=0.003) and DFS (p<0.001). Additionally, both cytoplasmic and nuclear VDR expression were found to be independent markers of DFS (p<0.001; p=0.021) when examined alongside clinicopathological parameters. Moreover, nuclear VDR expression was positively associated with lower lymph node invasion (pN; p=0.01). For triple-negative patients, cytoplasmic VDR expression was found to have a significant inverse correlation with DFS (p<0.001). Lastly, the ratio of VDR nuclear/cytoplasmic was identified as an auxiliary independent marker of DFS and OS. These findings strongly indicate that the subcellular localization of VDR is crucial in determining BC prognosis. The expression of nuclear VDR appears to have a protective effect, while cytoplasmic VDR is associated with a more aggressive disease course. The data may help identify subgroups of patients with high-risk BC, possibly leading to specific options for targeted tumor therapy
Open Access
A redefinition of prognosis: Invasive carcinoma with metastasis originating from microglandular adenosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Xiaochun Fei; Dan Chen; Biología Celular e Histología
Aim. To investigate the clinicopathological features, immunophenotype, diagnosis, and prognosis of invasive carcinoma originating from microglandular adenosis. Methods. Two cases of invasive carcinoma originating from microadenosis were analyzed in the Department of Pathology of the Ruijin Hospital affiliated with the Medical College of Shanghai Jiaotong University. Histopathological morphology, immuno-histochemical staining, and prognosis were observed. Results. (1) Histopathological morphology: microscopically, the tumor showed small clusters and nests of infiltrative growth; a few areas showed tubules, and some eosinophilic secretions were observed in the lumen. (2) Immunohistochemistry and molecular genetics: Case 1 was partly positive for S-100, positive for SOX-10, and negative for ER, PR, and HER2 (2+). The result of HER2 gene amplification was negative. Breast and liver tissue lesions in Case 2 were positive for S-100 and SOX-10 but negative for ER and HER2. PR was positive in the liver lesions but showed moderate to strong expression in approximately 80% of the staining. Myoepithelial markers (p63 and calponin) showed loss of myoepithelium around the nests of invasive cancers. TP53 (R213Ter) showed somatic gene variations, and no exon amplification or deletion was detected in BRCA1/2. Conclusion. Invasive carcinoma originating from microadenosis has the same immunophenotype as microadenosis, and its prognosis is difficult to determine.
Open Access
ADAMTS4 is expressed in different cells and tissues in leprosy skin lesions: A potential biomarker and therapeutic target for leprosy and its reactional phenomena
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Rafael Dantas Soares; Igor Bueno Garrido; Natália Silveira Virgili; Luciana Raquel Vincenzi Fachin; Patricia Sammarco Rosa; Ana Paula Fávaro Trombone; Andrea de Faria Fernandes Belone; Cleverson Teixeira Soares; Biología Celular e Histología
Introduction. A disintegrin and metallo-proteinase with thrombospondin motifs-4 (ADAMTS4), a metalloproteinase involved in extracellular matrix (ECM) degradation, is implicated in several pathological conditions. This study evaluated ADAMTS4 in leprosy skin lesions. Methods. In total, 519 skin samples were selected, including 20 healthy controls (HC) and 499 samples with leprosy skin lesions. Leprosy lesions were divided into tuberculoid range “T” (n=95), lepromatous range “L” (n=115), type 1 reaction (n=120), type 2 reaction (n=128), and lesions in regression (n=41). Following standardization with an anti-ADAMTS4 marker, all samples were subjected to immunohistochemistry (IHC). Marker expression in cells or tissues with moderate or intense staining intensity (2+ or 3+) was considered positive, and the absence of or weak expression (0 or 1+) was considered negative. Results. ADAMTS4 was expressed in several cells involved in the inflammatory processes of leprosy, particularly macrophages and fibroblasts, and in different skin tissues affected by leprosy lesions. Marker expression was remarkable in different tissues affected by leprosy lesions compared with the control group. Conclusion. ADAMTS4 expression in different leprosy lesions and their reaction phenomena suggest its contribution to disease progression and reactive inflammatory amplification, indicating ADAMTS4 as a potential biomarker and therapeutic target in leprosy.
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; Biología Celular e Histología
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
Advantages and limitations of 3,3',5,5'-tetramethylbenzidine for immunohistochemical staining
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Yu Chao; Liu Xiao; Zhao Peiyuan; Sun Zhidong; Song Yurong; Cao Yuan; Cheng Ming; Biología Celular e Histología
In this study, two chromogenic systems, horseradish peroxidase (HRP)-3,3’-diaminobenzidine (DAB) and HRP-3,3',5,5'-tetramethylbenzidine (TMB), were used to perform single-color and double-color immunohistochemical staining (sIHC and dIHC, respectively) on multiple antigens in four distinct tissue types. The chromogenic results of the HRP-TMB system exhibited a vibrant blue-green color, and the tissue localization and signal intensity were consistent with those of the HRP-DAB system. In addition, it demonstrated clear differentiation from the hematoxylin-stained nucleus, endogenous melanin, and brown chromogenic results of HRP-DAB. TMB staining in tissues that contain high endogenous pigment levels eliminates the need for melanin bleaching, thereby facilitating direct observation and potentially improving the detection speed and interpretation. TMB can also be used in combination with DAB for dIHC, thus allowing detection of the two markers on a single slide. However, the TMB staining results are not stable over the long term and require image storage using slide scanners, thereby limiting its application. Additionally, in dIHC, overlapping signals of the first marker may obscure the second marker, potentially leading to bias or false negatives. Therefore, careful consideration is required when designing dIHC detection systems. Based on the above, we propose that TMB is a valuable supplement to DAB for immunohistochemical staining and deserves further promotion and utilization. However, additional research is needed to improve the composition of TMB chromogenic reagents, prolong the longevity of staining results, and overcome current limitations
Open Access
AHSA1 promotes the progression of lung cancer by enhancing the expression of HSP90α
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Zifeng Jiang; Kun Gao; Min Wang; Biología Celular e Histología
Background. Lung cancer (LC) is a leading cause of malignancy-related morbidity and mortality worldwide. The activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1), one of the chaperones of heat shock protein 90 kDa (heat shock protein 90, HSP90), is involved in the maturation, stabilization, degradation, and function of oncogenic proteins. The aim of this study was to investigate the specific mechanism and role of AHSA1 in LC development. Methods. Expression of AHSA1 in LC was analyzed using The Cancer Genome Atlas (TCGA) database. AHSA1 expression in LC cells and tissues was assessed by qRT-PCR and western blotting. In addition, Kaplan-Meier plotter analysis and univariate and multivariate Cox analyses were used to evaluate the relationship between AHSA1 and clinicopathological variables and prognosis. The effects of AHSA1 on LC cell proliferation and migration were observed using cell counting kit-8, flow cytometry, wound healing, and Transwell assays. Target genes were predicted by bioinformatics and subsequently validated using a qRT-PCR assay. Results. AHSA1 exhibited significant upregulation in LC tissues and cell lines, with its elevated expression correlating with adverse prognostic outcomes in LC patients. Functional assays revealed that downregulation of AHSA1 markedly impedes the proliferation, migration, and invasion of LC cells. Conversely, overexpression of AHSA1 enhanced these malignant behaviors. Furthermore, bioinformatics analysis suggested a potential interaction between AHSA1 and HSP90α, which was also found to be highly expressed in LC cells, exhibiting a notable increase in expression levels following AHSA1 upregulation. Conclusions. AHSA1 is implicated in promoting the progression of LC by enhancing the malignant phenotype of cancer cells through the upregulation of HSP90α expression, which may underlie the association of AHSA1 expression with adverse clinicopathologic features in LC patients. These findings indicate that AHSA1 serves as a potential prognostic biomarker and represents a viable therapeutic target for LC
Open Access
Alteration in epithelium and stroma of post-INTACS cornea: Ultrastructure and 3D transmission electron tomography
(2026) Omar Kirat2; Adrian Smedowski; Aljohara Alkanaan; Fahad Almoqbel; Turki Almubrad; Saeed Akhtar; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
This study was conducted to investigate the ultrastructure of the epithelium and stroma of post INTACS corneas. INTACS were surgically inserted into the corneas of three patients to remodel the keratoconus shape. INTACS were inserted with the IntraLase femtosecond laser. Patients 1, 2, and 3 returned to the clinic 8, 6, and 9 years, respectively, after surgery due to their deteriorating vision. The lamellae above the INTACS were removed surgically and processed for light and electron microscopy. 2D and 3D digital images of lamellae, collagen fibrils (CFs), and proteoglycans (PGs) were captured by a bottom-mounted camera and analysed using iTEM software. The epithelium and stromal lamellae had degenerated. A large number of aggregates of microfilaments were present in the Bowman’s layer (BW) and throughout the stroma. In the stroma, just above the INTACS insertion, lamellae were completely disorganised and running randomly in the large electron-lucent spaces. The CF diameter was significantly smaller than in the normal cornea. 3D images showed microfibrils within the CF were less in the post-INTACS cornea than in the normal cornea. We believe that insertion of the INTACS disturbed the lamellar organisation and uniform distribution of CFs. This non-uniform CF distribution increased over time, resulting in vision impairment.
Open Access
Amygdalin improves ovarian function by inhibiting oxidative stress and inflammation in premature ovarian failure mice
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Jintao Han; Jianyuan Li; Jin Yao; Wenwei Jiang; Biología Celular e Histología
Background. Menstrual stoppage, follicular dysplasia, and hypergonadotropic hypoestrogenism in women under forty are among the symptoms of premature ovarian failure (POF). This study aimed to explore the role and mechanism of amygdalin on ovarian function in a POF mouse model. Methods. A POF mouse model was established via injection of D-galactose (D-gal), followed by amygdalin treatment. Histological staining of ovarian tissues was applied to determine follicular development and granulosa cell apoptosis. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) were measured in ovarian tissues. Enzyme-linked immunosorbent assay was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), anti-Müllerian hormone (AMH), and reactive oxygen species (ROS) in serum, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels in ovaries. Results. D-gal increased levels of FSH, LH, ROS, MDA, TNF-α, IL-1β, IL-6, Bax, atretic follicles, and granulosa cell apoptosis, and decreased P, E2, AMH, SOD, GSH-px, Bcl-2, and primordial, primary, secondary, and total follicles (p<0.01). Amygdalin with different concentrations reversed the effects of D-gal on mice (p<0.05). Conclusion. Amygdalin improved ovarian function in POF mice through inhibiting oxidative stress, inflammation, and granulosa cell apoptosis. These results suggested that amygdalin may be a potential antioxidant for POF treatment.
Open Access
Antagonism of GPR4 with NE 52-QQ57 alleviates gestational diabetes mellitus-induced placental insults mediated by inhibiting NF-κB
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Zongxu Qiao; Jinhui Feng; Yaning Wang; Xiaohui Zhao; Fang Li1; Biología Celular e Histología
Gestational diabetes mellitus (GDM) refers to a diabetic condition observed in pregnant women, significantly affecting both the health of the mother and the growth of the offspring. G protein-coupled receptor 4 (GPR4) is a receptor widely distributed across various tissues, but its role in GDM remains unclear. Our research aims to investigate the role of GPR4 in GDM and explore the potential therapeutic effects of its antagonist, NE 52-QQ57, in treating this condition. First, we found that GPR4 was expressed in placental tissues. Mice were divided into three groups: wild-type, db/+ pair-fed, and db/+ pair-fed + NE 52-QQ57. GPR4 expression was significantly higher in the db/+ pair-fed mice compared with wild-type mice. Markedly increased blood glucose and serum insulin levels were observed in GDM mice on gestational days (GD), accompanied by disrupted lipid profiles, all of which were significantly alleviated by NE 52-QQ57. Moreover, undesirable fetal outcomes, including increased fetal mortality, decreased fetal weight, reduced crown-rump length, and decreased placental weight, were observed in GDM mice, however, all were notably improved by NE 52-QQ57. Increased oxidative stress (OS) and the release of inflammatory cytokines were observed in GDM mice, but these were significantly reversed by NE 52-QQ57. Additionally, activated nuclear factor κ-B (NF-κB) signaling in placental tissues of GDM mice was significantly suppressed by NE 52-QQ57. Collectively, antagonism of GPR4 protected against GDM-induced placental damage in mice, confirming the critical role of GPR4 in the development of GDM.
Open Access
Assessing acute pancreatitis: A novel method combining live cell imaging with tissue damage evaluation
(Universidad de Murcia, Histología e Histopatología, 2025) Kovačič Polona; Skelin Klemen Maša; Paradiž Leitgeb Eva; Venglovecz Viktória; Kiss Lóránd; Mihalekné Fűr Gabriella; Stožer Andraž; Dolenšek Jurij; Biología Celular e Histología
Acute pancreatitis (AP) is a sudden inflammation of the exocrine part of the pancreas, resulting in self-digestion and destruction of exocrine tissue. The intricate relationship between exocrine and endocrine functions is pivotal, as damage to acinar cells can affect endocrine cell function and vice versa. However, our understanding of these interactions remains limited. An effective strategy for investigating pancreatic cells involves the utilization of live in-situ acute mouse pancreas tissue slice preparations, combined with noninvasive fluorescent calcium labeling of endocrine or exocrine cells, and subsequent analysis using confocal laser scanning microscopy. Nevertheless, this approach encounters inherent conflicts with conventional methodologies employed to histologically assess the severity of tissue damage due to AP in the model. Traditional methods involve fixing and staining tissue samples with hematoxylin and eosin, thereby precluding live-cell imaging. In this study, our objective was to introduce an innovative method utilizing a commercial fluorescence Live/Dead assay that enables calcium imaging and tissue damage assessment in the same sample. This approach was validated against the classical histological grading of AP severity, and we found a good correlation between the classical histological grading method and the in-situ approach employing the Live/Dead assay. The primary advantage of our novel approach lies in its capacity to enable timely and efficient live-cell imaging together with damage assessment in the same tissue, thereby enabling the study of functional consequences of structural damage at the cellular level and reducing the number of animals required for experimentation.
Open Access
Astragaloside IV suppression of chronic atrophic gastritis by upregulating PAR-1 in vitro and in vivo
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Duan Bensong; Bao Zhewei; Yang Jingya; Wang Zhenzhen; Li Aoxiang; Yang Jin; Lv Mengke; Zhang Haibin; Biología Celular e Histología
Background. Astragaloside IV (AS-IV) has demonstrated a protective effect against gastrointestinal tract injury induced by various factors. However, its potential mechanism against chronic atrophic gastritis (CAG) remains unknown. Purpose. The objective of the present study was to investigate the impact of AS-IV on CAG and elucidate its molecular mechanism. Methods. The mRNA and protein levels of protease-activated receptor-1 (PAR-1) and related proteins were assessed using reverse transcription-polymerase chain reaction and western blot analyses, respectively. In addition, the levels of inflammatory factors were measured via enzyme-linked immunosorbent assay in GES-1 cells following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The CAG model was established in rats induced with MNNG and concurrently treated with AS-IV for 10 weeks. Subsequently, serum samples were collected to assess the expression levels of proteins reflecting inflammatory markers. The gastric tissue sections were used for hematoxylin and eosin staining, immunohistochemical analysis, and the assessment of p-NF-κB p65 and PAR-1 signaling. Results. In-vitro experiments demonstrated that the mRNA levels of PAR-1 were upregulated following treatment with AS-IV and MNNG. Conversely, inhibition of PAR-1 expression reversed the therapeutic effects of AS-IV on MNNG-treated GES-1 cells, leading to increased expression of cyclooxygenase-2 and p-NF-κB p65. In addition, PAR-1 inhibition notably reversed MNNG-induced inflammatory factors, including IL increase. In-vivo experimental validation further confirmed that the upregulation of PAR-1 expression following treatment with AS-IV exerted a protective effect on the gastric mucosa of CAG rats. Conclusion. In conclusion, the findings of the present study suggested that AS-IV exhibited therapeutic efficacy against CAG induced by MNNG; its mechanism may be closely associated with the thrombin/PAR-1 signaling pathway. The present study provides a theoretical foundation for further exploration of the pharmacological effects of AS-IV on the treatment of human CAG
Open Access
Astrocyte heterogeneity and gliosis in Huntington’s disease: Histopathological insights into striatal and white matter pathology
(2026) Taylor Brown; Rocio Gomez-Pastor; Ross Pelzel; Biología Celular e Histología
Huntington’s disease (HD) is a devastating, autosomal dominant neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Among the major pathological hallmarks of HD are mutant huntingtin aggregation, white matter loss and reactive astrogliosis, which together contribute to neuronal dysfunction and death, particularly in the striatum and cortex. Recent studies in HD mouse models have identified a specialized astrocyte subtype that clusters around white matter bundles originating from the secondary cortex and passing through the striatum. While the functional role of these astrocytes remains unclear, they express Glial Fibrillary Acidic Protein (GFAP), a marker typically associated with both fibrous and reactive astrocytes. The discovery of this white matter-associated astrocyte subtype, along with other astrocytic subtypes differing between grey and white matter, underscores the complexity of glial responses in HD. Accurate identification and interpretation of these glial populations are crucial for understanding disease mechanisms and progression. Given the overlapping expression profiles of commonly used astrocyte markers like GFAP, the careful selection and application of both astrocyte and white matter markers in histopathological analyses are essential to advance our understanding of how glial cells contribute to HD pathology. In this review we discuss different histopathological approaches to assess the roles of glia in HD, emphasizing the need for standardized approaches and critical evaluation of marker specificity.
Open Access
Betulinic acid isolated from Betula platyphylla induces apoptosis and reduces the mTOR/PI3K/AKT signaling pathway in endometrial cancer cells
(2026) Ceren Oy; Mücahit Secme; Duygu Gok Yurtseven; Sema Serter Koçoğlu; Gözde Korkusuz Akçal; Biología Celular e Histología
Endometrial cancer is one of the most common gynecological cancers worldwide, and an average of 42,000 women die each year. Chemotherapy, radiotherapy, and surgery are among the treatments available for endometrial cancer. Currently, drugs used for chemotherapy have had limited success in increasing the cure rate. Betulinic acid, a lupane-type triterpene widely found in the plant kingdom, has attracted attention for cancer treatment in recent years due to its ability to inhibit tumor growth and induce cell apoptosis. The aim of this study is to investigate the mTOR pathway-mediated anticancer effects of betulinic acid in human endometrial cancer cells. The effect of betulinic acid on Ishikawa cell viability was determined by the CCK-8 method. Its effect on the expression of genes involved in apoptosis and the mTOR pathway was assessed by real-time PCR. The effect on protein expression in the mTOR pathway was evaluated with immunohistochemistry and western blot, and the effects on apoptosis via Annexin V. Betulinic acid reduced Ishikawa endometrial cancer cell proliferation. Betulinic acid administration caused a significant decrease in Bcl2 (p=0.008) expression and increased caspase-8 (p=0.001) expression in Ishikawa cells. The results of Annexin V supported the idea that betulinic acid administration triggered apoptosis in Ishikawa cells. The mean rate of apoptotic cells in the betulinic acid group was 22±3.23%, while it was 2.31±0.2% in the control group (p=0.02). Betulinic acid caused a significant decrease in the expression of AKT1 (p=0.0001) and a significant increase in the expression of RAPTOR (p=0.00002). Betulinic acid administration also significantly percentage of p-PI3K, p-AKT, and p-mTOR-positive cells in Ishikawa cells was 89.39±5.19%, 74.84%±5.07, and 82.02%±6.14, respectively, in the control group. In the betulinic acid group, these values were 49.12± 19.12% (p=0.002), 44.46±7.39% (p<0.001), and 53.70±8.94% (p<0.001), respectively. This study showed that betulinic acid decreased Ishikawa cell proliferation, triggered apoptosis, and decreased mTOR signaling; thus, betulinic acid may be a potential anticancer agent for the treatment of endometrial cancer. decreased protein expression in the mTOR pathway. The
Open Access
Bioartificial human corneas generated by tissue engineering. A historical and technical review
(2026) Pascual-Vicente Crespo; José-Manuel García; Maria-Carmen Sánchez-Quevedo; Antonio Campos; Miguel Alaminos; Biología Celular e Histología
Different types of bioartificial corneas have been generated by tissue engineering through combining cells, biomaterials, and bioactive molecules. Orthotypical corneal cells can be obtained from corneal biopsies, and include epithelial, stromal, and endothelial cells, whereas heterotypical cells are obtained from alternative cell sources with corneal differentiation potential, such as mesenchymal stem cells. In turn, two main types of biomaterials have been applied to corneal tissue engineering: those generated by the de-cellularization of natural tissues and biomaterials generated de novo using synthetic or natural biomaterials, especially collagen, fibrin, and agarose. Cells and biomaterials are combined with bioactive factors, inducing cell proliferation and differentiation. A review of previous studies revealed that most bioartificial corneas were not able to fulfill the complex requirements required for clinical translation, which include a thorough preclinical characterization, generation of the tissue as an advanced therapy medicinal product, a clinical research phase, and a final authorization by the European Medicines Agency or another competent regulatory agency. Most authorized products correspond to partial corneal substitutes consisting of one cell type associated or not with a scaffold, and only one product consisting of a human bioartificial cornea containing a fibrin-agarose scaffold and two corneal cell lineages (epithelial and stromal cells) called NANOULCOR was evaluated in patients in the context of an advanced therapy medicinal product. These findings confirm the existence of a bottleneck between basic and clinical research and suggest the need to implement novel clinical studies to develop new therapies that can improve the results of current corneal therapies.
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; Biología Celular e Histología
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
Brazilin attenuates kidney ischemia- reperfusion injury by regulating inflammation, oxidative stress, and mitochondrial dysfunction
(2026) Lulu Zhang; Fei Mu; Ying Yu; Chen Cui; Meng Tang; Kexin Sun; Yanping Yin; Jingwen Wang; Rui Gong; Jinyi Zhao; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
Brazilin, a natural homoisoflavonoid, is the primary bioactive ingredient derived from the bark and heartwood of Caesalpinia sappan L. It has been proven to exhibit multiple biological activities and therapeutic potential in chronic degenerative diseases, fibrotic disorders, inflammatory diseases, and cancers. However, whether it is involved in regulating the pathological process of acute kidney injury (AKI) is not fully understood. This study aimed to elucidate the role and key pharmacological molecular mechanisms of brazilin in AKI. Our data demonstrated that pretreatment with brazilin can significantly reduce the high expression of serum creatinine (Scr), blood urea nitrogen (BUN), and lipocalin-2 (LCN2) in mice exposed to ischemia/ reperfusion (I/R) and alleviate kidney histopathological damage. Meanwhile, pretreatment with brazilin can alleviate apoptosis, inflammation, and oxidative stress injury in the kidney tissue cells by partially inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory pathway or activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase‐1 (HO-1) antioxidant pathway. In vitro, pretreatment with brazilin significantly downregulated pro-apoptotic Bax and upregulated anti apoptotic Bcl-2 expression in human renal proximal tubular cells (HK-2) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Besides, it ameliorated mitochondrial dysfunction by enhancing mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively suppressed oxidative stress injury and NLRP3 inflammasome signaling pathway activation. In summary, brazilin exhibits significant protective effects against I/R-induced AKI by attenuating inflammation, oxidative stress and cell apoptosis, and mitochondrial damage. These findings suggest that brazilin holds promise as a potential therapeutic agent for AKI.
Open Access
C6orf15 expression in thyroid tumors: A promising diagnostic biomarker for the classic variant of papillary thyroid carcinoma
(2026) Pengju Zhang; Jiaxin Chai; Jiandong Wang; Pengfei Huang; Xudong Gu; Aobo Xu; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Although C6orf15 is highly expressed in certain human cancers, its expression pattern in papillary tumors remains unclear. In this study, we investigated C6orf15 expression in papillary tumors and assessed its potential as a diagnostic biomarker for histopathological evaluation and fine-needle aspiration cytology (FNAC). We collected a total of 87 formalin-fixed and paraffin embedded (FFPE) thyroid tissue specimens that included: 10 cases with Hashimoto's thyroiditis (HT), 11 with follicular adenomas (FAs), two with non-invasive follicular thyroid neoplasms with papillary-like nuclear feature (NIFTP), six with follicular thyroid carcinomas (FTCs), three with invasive encapsulated follicular variant of papillary thyroid carcinomas (IEFVPTCs), three with medullary thyroid carcinomas (MTCs), and 52 with papillary thyroid carcinomas (PTCs). Additionally, 33 FNAC samples from thyroid nodules were analyzed, comprising three samples of FA, five atypia of undetermined significance (AUS), and 25 cases of PTC. Immunohistochemical (IHC) staining was performed to assess C6orf15 expression in thyroid tumor tissues and FNAC samples. We conducted BRAF V600E mutation analysis via Sanger sequencing and IHC and discerned that C6orf15 expression was absent in normal follicular epithelial cells, FA, NIFTP, TFC, and MTC. The positivity rates for C6orf15 in FFPE samples were as follows: 66.7% for IEFVPTC, 86.5% for PTC, and 60.0% for AUS. In FNAC samples, the positivity rate was 80.0% for PTC. A significant positive correlation was observed between C6orf15 expression and the BRAF V600E mutation in PTC tissues (p<0.001), but no such association was found in FNAC samples (p=0.230). C6orf15 exhibited high expression levels in the majority of IEFVPTC (66.7%), PTC tissues (86.5%), and FNAC samples (80.0%). These findings suggest that C6orf15 constitutes a promising diagnostic biomarker for the classic variant of PTC and is applicable to histo pathological assessment and FNAC-based diagnosis.
Open Access
Calycosin accelerates wound healing in diabetic rats by alleviating oxidative stress and promoting angiogenesis
(2026) Min Lu; Lifen Xue; Mi Zhou; Meifeng Zhang; Huifeng Zhu; Wei Lu; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
Background. Angiogenesis is a physiological process of diabetic wound healing. Although calycosin has been reported to exert protective effects on diabetic nephropathy, its role and mechanisms in diabetic wound healing remain unclear. This study investigates the effects of calycosin on wound healing and angiogenesis, and the role of the Nrf2/HO-1 pathway in mitigating oxidative stress in diabetic rats. Methods. In vivo, type 2 diabetes (T2DM) in Sprague-Dawley (SD) rats was induced by a high-fat diet for six weeks combined with a single intraperitoneal injection of 45 mg/kg streptozotocin (STZ). The anesthetized diabetic rats underwent a full skin excision on the back and were then treated with calycosin for two weeks to evaluate the protective effect of calycosin on oxidative stress associated with the Nrf2/HO-1 pathway in diabetic wound rats. In vitro, damage to Human Umbilical Vein Vascular Endothelial Cells (HUVECs) was induced by high glucose, and then treated with calycosin or combined with Nrf2 agonist to evaluate whether calycosin affects cell activity and inhibits oxidative damage via the Nrf2/HO-1 pathway. Results. Our results indicate that calycosin promotes angiogenesis by activating the Nrf2/HO-1 signaling pathway and upregulating downstream antioxidant genes, thereby accelerating wound healing. In vitro studies have also shown that Nrf2/HO-1 signaling activation can enhance the promoting effect of calycosin on cell activity and the inhibitory effect on oxidative stress in HUVECs induced by high glucose. Conclusion. Our results show that calycosin can accelerate wound healing by promoting angiogenesis and inhibiting oxidative stress mediated by the Nrf2/HO 1 pathway, which provides a theoretical basis for the treatment of refractory diabetic wounds.