Search Results (683)

Aronia melanocarpa is rich in anthocyanins, compounds with significant medicinal and industrial value, making it an attractive species for enhanced production. Compared with fruits or intact plants, callus tissue offers a uniform, controllable in vitro system that is particularly suitable for dissecting regulatory mechanisms under defined environmental conditions. Although light quality is known to influence anthocyanin biosynthesis, its specific regulatory mechanisms in A. melanocarpa remain unclear. In this study, callus tissues were cultured under six light regimes: full-spectrum LED, blue:red (5:1), red:blue (5:1), red:blue:white (1:1:1), red:white (5:1), and pure blue light. Anthocyanin content was quantified using the pH differential method, and the results showed that the blue:red (5:1) treatment produced the highest accumulation, reaching 14.06 mg/100 g. Transcriptome sequencing was then performed to compare the gene expression profiles between calli cultured under blue:red (5:1) light and those maintained in darkness. A total of 10,547 differentially expressed genes (DEGs) were identified, including 6134 upregulated and 4413 downregulated genes. Functional enrichment analysis indicated that these DEGs were mainly involved in anthocyanin biosynthesis and transport. Importantly, key structural genes such as PAL, C4H, 4CL, CHS, ANS, UFGT, and GST were significantly upregulated under blue:red (5:1) light, as further validated by qRT-PCR. Overall, our findings demonstrate that a blue:red (5:1) light ratio enhances anthocyanin accumulation by promoting the expression of biosynthetic and transport-related genes. This study not only provides new transcriptomic insights into the light-mediated regulation of secondary metabolism in A. melanocarpa callus, but also establishes a foundation for optimizing in vitro culture systems for sustainable anthocyanin production. Full article

Introduction: Tumors of the lateral skull base, particularly those arising from the external auditory canal and peri-retroauricular regions, present considerable surgical and reconstructive difficulties due to their intricate anatomy and aggressive nature. The anterolateral thigh (ALT) free flap offers a viable reconstruction option, enhancing oncological radicality while minimizing morbidity. Materials and Methods: A retrospective analysis was conducted on five cases of malignant tumors involving the external auditory canal and adjacent soft tissues, treated at a tertiary center from March 2023 to March 2025. All patients underwent radical resection, which included lateral or subtotal temporal bone resection, along with parotidectomy and neck dissection when necessary. Reconstruction was performed using myocutaneous anterolateral thigh free flaps. The study evaluated clinical outcomes, complications, and esthetic results. Results: The ALT flap was used in all cases without major postoperative complications. Two patients received adjuvant radiotherapy; one did not start treatment due to early recurrence. At follow-up, three patients were disease-free, while two had died from unrelated causes. Esthetic and functional outcomes were satisfactory in all patients. Conclusions: The ALT free flap is a universal and reliable option for the reconstruction of complex lateral skull base defects, especially in patients following the radical removal of tumors of the external auditory canal and peri-retroauricular areas. It offers excellent tissue coverage, facilitates adjuvant treatment, and has a low complication rate. While our experience supports its use in aggressive oncological resection, larger studies are needed to confirm these findings. Level of evidence: 4. Full article

Innervation is ubiquitous in diseased tissues, including cancer. Increasing evidence suggests that innervation not only plays a direct role in cancer pain, but is also closely related to disease progression, including cancer growth, metastasis, and drug resistance. At the molecular level, tumor-associated nerves can interact with cancer cells and the tumor microenvironment through neurotrophic factors, thereby promoting tumor occurrence and development, and represent a potential intervention for solid tumors with nerve enrichment. By dissecting the transcriptome dynamics of cancer-associated neurons with single cell resolution, numbers of novel therapeutic targets for tumor denervation have been uncovered, including a novel phenomenon—Macrophage to Neuron-like cell Transition (MNT). This review systematically summarizes the latest research findings of tumor denervation, from molecular mechanisms to the innovative denervation strategies, paving the way for novel, safe, and effective cancer treatments in the clinic. Full article

The process of dissection is essential to the study of anatomy, with the variety of colours, shapes, patterns and textures revealing the distinctive features of each anatomical system, but it can also be misleading, because while the body’s constituent ‘parts’ have traditionally been classified according to their appearance, assumed functions and perceived importance, this basic information can be interpreted in different ways. Living organisms are intrinsically indeterminate, which implies that the conclusions arrived at through the study of anatomy are not necessarily congruent with the anatomical reality, and the abstract classifications of the connective tissues (CTs) are a case in point. This paper highlights a seventeenth-century interpretation of CT anatomy that was pushed aside as the musculoskeletal duality assumed functional dominance and relegated the fascial tissues to mere ancillary roles. In other words, an architectural framework of tensioned fibrous tissues that encompasses a complex body-wide heterarchy of space-filling compartments under compression and reasserts the structural significance of the soft CTs. The problems with orthodox classifications are then discussed alongside a mechano-structural role for the ‘loose’ fibrillar network: a closed-chain kinematic system that guides changes in the relative positions of adjacent compartments and refutes the notion of fascial ‘layers’. Full article

Background: Cervical artery dissection (CAD) is a leading cause of acute ischemic stroke among young and middle-aged patients. Currently, the growing availability of high-resolution magnetic resonance imaging (MRI), particularly fat-saturated T1-weighted black-blood SPACE sequences, allows the non-invasive, rapid, and reliable diagnosis of multiple arterial dissections. Methods: We reported our experience from two tertiary stroke centers of patients diagnosed with spontaneous multiple cervical artery dissections, detected with high-resolution MRI, during a three-year period (2022–2025). Results: Among 95 consecutive patients with CAD, 11 patients (mean age: 48 ± 9 years, 6 (55%) females) were diagnosed with multiple symptomatic or asymptomatic CADs, whereas in 84 patients (mean age: 49 ± 11 years, 32 (38%) females) a single CAD was detected. In all patients, high-resolution MRI and MR-angiography were performed, whereas digital subtraction angiography (DSA) with simultaneous evaluation of renal arteries was conducted in nine patients. A history of trauma or chiropractic manipulations, intense physical exercise prior to symptom onset, recent influenza-like illness, and recent childbirth in a young female patient were reported as predisposing risk factors. Cervicocranial pain, cerebral infarctions leading to focal neurological signs, and Horner’s syndrome were among the most commonly documented symptoms. Characteristic findings in the high-resolution 3D T1 SPACE sequence were detected in all patients. Fibromuscular dysplasia and Eagle syndrome were detected in four patients and one patient, respectively. Eight patients were treated with antiplatelets, whereas three patients received anticoagulation with low-molecular-weight heparin. There was only one case of stroke recurrence during a mean follow-up period of 9 ± 4 months. Conclusions: This case series highlights the utility of specific high-resolution MRI sequences as a very promising method for detecting multiple CADs in young patients. The systematic use of these sequences could enhance the sensitivity of detecting multiple cervical CADs, affecting also the thorough investigation for underlying connective tissue vasculopathies, stratifying the risk for first-ever or recurrent ischemic stroke, and influencing acute reperfusion and secondary prevention therapeutic strategies. Full article

Diffuse large B-cell lymphoma (DLBCL) is a molecular and clinical heterogenous entity, and, over the past 30 years, many efforts have been made in trying to dissect this diverseness and identify biomarkers capable of efficiently stratifying DLBCL patients and spotting the ones showing a worse clinical outcome. Despite the achievement in this research field, only a few biomarkers have been validated and introduced in a clinical setting. Among those, approximately 5–15% of DLBCL cases harbor MYC gene translocations, often involving immunoglobulin genes as a translocation partner, and concomitant point mutations, correlating with a poor response to standard therapies. However, given the difficulty in detecting these abnormalities requiring specialized techniques and high-quality specimens, the use of metabolomics (i.e., the study of small metabolites in body fluids and tissues) can offer a useful alternative for the identification of high-risk DLBCL patients. Amino acids (AAs) are metabolites essential in the process of tumorigenesis and can increase immune escape and drug resistance. Therefore, we review the use of metabolomics to improve the diagnosis and prognosis in DLBCL patients in relation to the MYC role in the regulation of amino acid metabolism, as these metabolites may be used as potential biomarkers in a clinical environment. Full article

Purpose: Cadaveric dissection is a cornerstone of neurosurgical education, providing trainees with a realistic 3D understanding of anatomy and a safe environment to practice surgical approaches. A preservation technique was developed that merges the advantages of fresh-frozen and embalmed cadavers, maintaining tissue realism while enhancing durability. This approach preserves flexibility and natural color, improves anatomical detail, and creates a safe, long-lasting model ideal for neurosurgical training. Methods: Four specimens were thawed, cannulated, and irrigated before implementing a protocol consisting of low concentration formaldehyde with glycerol and ethanol for extended preservation. The specimens were prepared for both neurosurgery training and educational purposes, and their condition was evaluated with a semi-quantitative scale. Each specimen was evaluated independently by two raters, blinded to the time-point, using a semi-quantitative scale anchored to predefined criteria (0–3 per domain). Inter-rater reliability was calculated using the intraclass correlation coefficient (ICC [2,k]) for continuous scores and Cohen’s κ for categorical agreement. Results: Over nine years of intermittent use, the specimens remained in good condition: tissues retained sufficient softness for dissection, injected vessels stayed vivid in color, and no foul odor or microbial growth was observed. The evaluation employed a semi-quantitative scale, with results ranging from 11/14 to 14/14. The mean values demonstrate stable tissue quality over time, with only minor variations in color and perfusion. The inter-rater reliability was high (ICC = 0.91; κ = 0.88). Conclusions: The preservation method leverages the strengths of both fresh-frozen and embalmed models. The results suggest feasibility of long-term reuse, although further quantitative validation is needed. Full article

Background/Objectives: The neuromuscular junction (NMJ) is the area where peripheral nerves communicate with muscle tissue. Muscle injury can occur as part of an acute degenerative process at the NMJ. This study aims to investigate the remodeling of the NMJ after a muscle injury in an experimental model. Methods: We used sixty male Wistar rats divided into five groups: a control group (C) and four muscle injury groups (MI) at different time points: 0 h, 24 h, 48 h, and 7 d after injury. We subjected the right hind limb to muscle injury and dissected the gastrocnemius muscles for analysis. We employed light microscopy to examine cell nuclei and the connective tissue, immunostaining to identify and measure the pre- and postsynaptic regions as well as calcium channels (P/Q), and real-time PCR to assess the gene expression of NRG1 and Agrin. Results: Our findings revealed an accumulation of nuclei and connective tissue in the acute injury groups (0 to 48 h). The morpho-quantitative analyses showed that the presynaptic structures and calcium channels underwent similar remodeling due to their morpho-functional relationship. Meanwhile, the postsynaptic receptors were significantly affected by the degenerative and inflammatory processes. These results can be linked to increased expression of NRG1 and Agrin in the acute injury groups. Conclusions: In conclusion, the synaptic regions displayed substantial adaptations within the first 48 h, with the presynaptic region recovering rapidly and the postsynaptic region recovering slowly. This relationship suggests that significant increases in Agrin and NRG1 play a crucial role in maintaining the integrity of these structures. Full article

The azygos lobe (AL), an additional lung lobe most commonly found in the right apical lung region, is a rare anatomical variant present in approximately 1% of the population. It is embryological in origin and may form if the azygos vein fails to migrate medially over the lung. While it is normally clinically silent, it can have surgical and clinical implications. An AL can be the source of infection or disease, such as squamous cell carcinoma, and can also compress the upper lobe and lead to obstruction, infarction, and necrotic tissue. Additionally, it can present as an unforeseen surgical obstacle, specifically during a thoracotomy, and can be mistaken for a thoracic mass on radiographic imaging, potentially leading to unnecessary interventions. In this case report, a 38-year-old male donor with a history of Ogilvie’s syndrome, multiple traumatic brain injuries (TBIs), and chronic respiratory failure presented with an AL during routine donor dissection. The cause of death was listed as prostate cancer, hypertension, atrial fibrillation, and type II diabetes mellitus. The AL, located on the posterior apical surface of the right lung, measured 5 cm in width and 8 cm in length. The left lung showed signs of atrophy and discoloration, possibly the result of pollution exposure or smoking earlier in life. In this article, we describe the incidence, historical classification, embryology, and physiology associated with an AL and its clinical implication for this donor. Full article

Background: Centrosome amplification, a hallmark of cell cycle dysregulation, drives carcinogenesis through aneuploidy induction and invasive phenotype acquisition. In pancreatic adenocarcinoma—a malignancy characterized by profound genomic instability—the molecular circuitry of centrosome amplification remains enigmatic. Critical gaps persist in understanding its spatiotemporal dynamics in tumor microenvironment remodeling and therapy resistance. Methods: This study integrated centrosome amplification-related genes from TCGA and Genecards, established a prognostic risk model through univariate Cox regression–LASSO penalized Cox regression–multivariate Cox regression analyses, and validated it using GEO datasets. Single-cell sequencing analyses dissected transcriptional heterogeneity and intercellular communication networks, while spatially resolved transcriptomics unveiled spatiotemporal expression patterns and molecular regulatory mechanisms of core genes. With further experimental validation via PCR analysis of patient-derived tissue samples confirming key gene expression patterns. Results: This study identified 23 centrosome amplification-related prognostic genes in pancreatic adenocarcinoma, establishing IFI27, KIF20A, KLK10, SPINK7, and TOP2A as highly specific diagnostic and prognostic biomarkers. The constructed signature was established as an independent prognostic indicator correlating with aggressive clinicopathological characteristics and chemoresistance. Mechanistically linked to enhanced DNA repair capacity and accelerated cell cycle progression, also synergizes with KRAS mutational profiles. Tumor microenvironment analysis revealed significant associations with immunosuppressive. Single-cell resolution demonstrated cellular specificity of IFI27/KLK10 in ductal epithelial cells and fibroblasts, with intercellular communication networks exhibiting multidimensional regulatory features. Spatially resolved transcriptomics delineated tumor-region-specific expression patterns of core genes. While PCR validation on matched tumor/normal tissues confirmed significant differential expression of IFI27, KIF20A, KLK10, and TOP2A. Conclusions: This study deciphers the multidimensional clinic–molecular network orchestrated by centrosome amplification in PDAC, revealing its dual-pathogenic mechanism in fueling tumor aggressiveness through coordinated induction of genomic instability and immunosuppressive microenvironment reprogramming. These findings establish a translational framework for developing centrosome dynamics-based prognostic stratification and molecularly targeted therapeutic strategies. Full article

Yin Yang 1 (YY1) is a multifunctional transcription factor implicated in gene regulation, cell proliferation, and survival. While its role in breast cancer (BC) has been explored, its prognostic significance remains controversial. In this study, we evaluated nuclear YY1 expression in 276 BC tissue samples using immunohistochemistry (IHC), tissue microarrays (TMAs), and digital pathology (DP). Nuclear staining was quantified using Aperio ImageScope software, focusing on tumor regions to avoid confounding from stromal or non-tumor tissues. This selective and standardized approach enabled precise quantification of YY1 expression. Our results show elevated median YY1 expression in tumor vs. normal matched tissues (p < 0.001). The optimal cutoff for medium-intensity nuclear YY1 expression in tumor areas for overall survival (OS) was established by a receiver operating characteristic (ROC) curve (AUC = 0.718, 95% CI: 0.587–0.849, p = 0.008). In contrast, ROC curves showed no prognostic impact (AUC and p-value) for YY1 quantification in whole spots (tumor + normal). As a categorical variable, high YY1 expression was correlated with more aggressive BC features, including tumor size > 3 cm (57.7% vs. 44.2% p = 0.037), the triple-negative breast cancer (TNBC) molecular subtype (27.3% vs. 13.9% p = 0.026), and advanced prognostic stage (III) (31.8% vs. 16.7% p = 0.003), while as a continuous variable, YY1 was associated with higher histological (p = 0.003) and nuclear grades (p = 0.022). High YY1 expression was significantly associated with a reduced OS of BC patients, as shown by Kaplan–Meier curves (HR = 2.227, p = 0.002). Since YY1 was significantly enriched in TNBC, we evaluated its prognostic resolution in this subgroup. But, probably due to the small number of patients within this subset, our results were not statistically significant (HR = 1.317, 95% CI: 0.510–3.405, p = 0.566). Next, we performed multivariate Cox regression, confirming YY1 as an independent prognostic factor for overall survival (HR = 1.927, 95% CI: 1.144–3.247, p = 0.014). In order to improve prognostic value, we constructed a mathematical model derived from the multivariate Cox regression results, including YYI, AJCC prognostic stage (STA), and axillary lymph node dissection (ALN), with the following equation: h(t) = h₀(t) × exp (0.695 × YY1 + 1.103 × STA − 0.503 × ALN). ROC analysis of this model showed a better AUC of 0.915, similar sensitivity (83.3%), and much higher specificity (92%). Bioinformatic analysis of public datasets supported these findings in BC, showing YY1 overexpression in multiple cancer types and its association with poor outcomes in BC. These results suggest that YY1 may play a role in tumor progression and serve as a valuable prognostic biomarker in BC. DP combined with molecular data enhanced biomarker accuracy, supporting clinical applications of YY1 in routine diagnostics and personalized therapy. Additionally, developing a combined score based on the modeling of multiple prognostic factors significantly enhanced survival predictions, representing a practical tool for risk stratification and the guidance of therapeutic decisions. Full article

The field of oncology has been extensively studied to design more effective and efficient treatments. This review explores the advanced techniques that are transforming our comprehension of cancer and its constituents. Specifically, it highlights the signaling pathways that drive tumor progression, angiogenesis, and resistance to therapy, as well as the modern approaches used to identify and characterize these pathways within the tumor microenvironment (TME). Key pathways discussed in this review include vascular endothelial growth factor (VEGF), programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and various extracellular matrix (ECM) pathways. Conventional methods of diagnosis have yielded sufficient knowledge but have failed to reveal the heterogeneity that exists within the TME, resulting in gaps in our understanding of the cellular interaction and spatial dynamics. Single-cell sequencing (SCS) and spatial transcriptomics (ST) are effective tools that can enable the dissection of the TME with the resolution capacity of a single cell. SCS allows the capture of the unique genetic and transcriptomic profiles of individual cells along with rare cell types and new therapeutic targets. ST complements this by providing a spatial map of gene expression, showing the gene expression profiles within the tumor tissue at specific sites with good accuracy. By mapping gene expression patterns at a single cell level and correlating them with the spatial locations, researchers can uncover the intricate networks and microenvironmental influences that contribute to tumor heterogeneity. Full article

The stomach epithelium is a highly dynamic tissue that undergoes continuous self-renewal and responds robustly to injury through tightly regulated repair processes. Organoids have emerged as powerful tools for modelling gastrointestinal biology. This review focuses on the capacity of gastric organoids to model epithelial homeostasis, injury and repair in the stomach. We examine how organoid systems recapitulate key features of in vivo gastric architecture and stem cell dynamics, enabling detailed interrogation of lineage specification, proliferative hierarchies and regional identity. Gastric organoids have proven particularly useful for studying how environmental factors, such as Helicobacter pylori infection or inflammatory cytokines, disrupt epithelial equilibrium and drive metaplastic transformation. Furthermore, we discuss the emerging use of injury-mimicking conditions, co-cultures and bioengineered platforms to model regeneration and inflammatory responses in vitro. While organoids offer unparalleled accessibility and experimental manipulation, they remain limited by the absence of critical niche components such as immune, stromal and neural elements. Nevertheless, advances in multi-cellular and spatially resolved organoid models are closing this gap, making them increasingly relevant for disease modelling and regenerative medicine. Overall, gastric organoids represent a transformative approach to dissecting the cellular and molecular underpinnings of stomach homeostasis and repair. Full article

Background/Objectives: Gastric cancer remains a leading cause of cancer-related mortality, with over 50% of cases diagnosed at a locally advanced or metastatic stage. High-quality surgical resection within the embryological mesogastric layer is critical for achieving optimal oncological outcomes but is often complicated by anatomical distortion in advanced tumors. This study aimed to develop and validate a system of topographic and anatomical navigation landmarks for embryologically guided laparoscopic gastrectomy, leveraging 3D modeling to enhance precision and safety. Methods: A single-center study was conducted, analyzing 78 patients undergoing emergency laparoscopic gastrectomy for locally advanced gastric cancer. Preoperative 3D models were generated from CT data annotations to map the stomach, tumor, vascular structures, and mesogastric adipose tissue. Thirty biomodels were used to refine dissection techniques. Surgical procedures adhered to embryological principles, with lymphadenectomy guided by predefined landmarks. Histopathological validation assessed resection margins and tumor infiltration in resected specimens. Statistical analysis compared outcomes between patients with and without 3D planning. Results: The 3D models demonstrated 100% concordance with intraoperative vascular anatomy. Radiologically dense adipose tissue, resected as potentially tumor-infiltrated, showed histopathological invasion in 74% of cases. R0 resection was achieved in 74.4% of patients. Operative time decreased from 300 to 250 min after technical optimization, with a 7.7% conversion rate (primarily due to vascular injury or tumor fixation). Postoperative mortality was 5.1%, attributed to comorbidities. Patients with 3D planning had significantly higher lymph node yields (p < 0.00001) and R0 rates (p = 0.045). Conclusions: The integration of embryologically based topographic landmarks and 3D navigation improves the safety and standardization of laparoscopic gastrectomy for locally advanced gastric cancer. This approach enhances oncological radicality, reduces operative time, and mitigates risks in anatomically distorted fields. Further validation in larger cohorts is warranted. Full article

The prevalence of hyperuricemia with elevated serum uric acid is increasing worldwide. However, the effects of high uric acid on diabetic patients with dyslipidemia and the mechanisms underlying these effects remain unexplored. This study aimed to develop a novel diabetic model of hyperuricemia and dyslipidemia in male hamsters to evaluate the effects of high uric acid on glucolipid metabolism, renal injury and the gut microbiota. Twelve healthy hamsters were randomly divided into two groups and fed with a normal diet and high-fat/cholesterol diet (HFCD), respectively. Twenty-four diabetic hamsters were randomly divided into four groups receiving a normal diet; HFCD; potassium oxonate (PO) treatment (intragastric PO at doses of 350 mg/kg and adenine at doses of 150 mg/kg with 5% fructose water); and PO treatment with HFCD, respectively. After 4 weeks, all animals were dissected for determining serum biochemical indicators, tissue antioxidant parameters, renal pathological changes, target gene expressions, fecal short-chain fatty acids content, and the gut microbiota composition. The results showed that a hamster model with hyperuricemia and dyslipidemia was successively established by the combination of PO treatment and HFCD, in which serum uric acid, glucose, triglyceride and total cholesterol levels reached 499.5 ± 61.96 μmol/L, 16.88 ± 2.81 mmol/L, 119.88 ± 27.14 mmol/L and 72.92 ± 16.62 mmol/L, respectively. PO treatment and HFCD had synergistic effects on increasing uric acid, urea nitrogen, creatinine levels, liver xanthine oxidase activity, plasminogen activator inhibitor-1 and transforming growth factor-β expressions, and the relative abundance of Lleibacterium (p < 0.05); in addition, they caused glomerular mesangial cells and matrix proliferation, protein casts and urate deposition. High uric acid was closely related to decreased antioxidant capacity; decreased renal vascular endothelial growth factor expression; increased acetic acid content; decreased butyric, propanoic, and isobutyric acid levels; decreased Firmicutes to Bacteroidetes ratios (p < 0.05); and altered epithelial integrity and structure of the gut microbiota in diabetic hamsters. The findings indicate that high uric acid affects the glucolipid metabolism, accelerates renal damage, and disrupts the balance of intestinal flora in diabetic animals, which provides a scientific basis for metabolic syndrome prevention and control in diabetes. Full article