The basement membrane is a specialized extracellular matrix network that orchestrates fundamental cellular processes in many organs. In the lung, this dynamic scaffold provides compositionally encoded instructions that direct epithelial differentiation, regulate injury responses, and modulate disease progression. Despite its fundamental importance, the basement membrane remains an understudied aspect of lung biology, with its precise composition, spatial organization, and biomechanical properties in health and disease poorly defined. This review synthesizes current understanding of lung epithelial basement membrane composition and function with emphasis on how this matrix layer supports lung development, injury repair, and cancer progression. We highlight evidence that basement membrane components are not merely structural supports but active regulators of cellular phenotype and discuss how this conceptual shift opens new therapeutic strategies in lung cancer.

Study on chronic toxicity, metabolic profiles and potential mechanisms of Aristolochiae Fructus in rats.

Function diagrams focus on physiological concepts rather than associated structures and can serve as elaboration tools and mnemonic aids. A function diagram prototype of the gastrointestinal system was recently described (Wilson TE, Barrett KE. Adv Physiol Educ 45: 264-268, 2021). In this article, a functional diagram of the glomerulus, nephron, urinary system, and bladder is proposed. Colloquially named "Nessie the Nephron" to loosely capture the looping structure and elusive understanding of renal blood flow, glomerular filtration, and epithelial transport for the student, not to mention the nearly mythical countercurrent multiplier. "Navigating the Lochs" references Nessie's possible habitat and more importantly the movement and storage of the modified ultrafiltrate from the nephron. The primary analogies that form the structure of this function diagram are Rain Barrel, Soaker Hose, and Hose Nozzle (afferent and efferent blood flow and filtration pressure); Water Purification System (glomerular filtration barrier forming multiple step filtration process involving the capillary, basement membrane, and podocytes); Mixed Recycling Machine (proximal tubule individual, co-, and bulk transport); Desiccator and Briner (thin descending limb removal of water and thin/thick ascending limb removal of salt); Conveyor Belt Picker (distal nephron selective ion transport); and Concentrator (collecting duct water and urea transport). The primary analogies that elaborate Navigating the Lochs are Aqueduct and Cistern System (fluid movement and collection); and Pressure Gauge, Syringe Bulb, and Two-Valve Plumbing (bladder storage and micturition). Complementing these analogies is the rich potential for inclusion of clinical and comparative applications and examples to link previous knowledge and strengthen memories for future retrieval.NEW & NOTEWORTHY Function diagrams put the focus on physiology and physiological concepts rather than the associated anatomy and can serve as elaboration tools and mnemonic aids. The function diagram of the nephron can provide analogies for glomerular filtration, bulk and selective epithelial transport, and overall ability to create concentrated or dilute urine. The function diagram of the urinary system and bladder can provide analogies for moving and storing urine and finally micturition.

Invasive breast carcinoma with a DCIS-like growth pattern: Clinicopathological features and diagnostic pitfalls.

Diagnostic and prognostic value of LAMB2 in sepsis patients admitted to the intensive care unit.

Comprehensive analysis of Fraser syndrome 1 as a potential biomarker and therapeutic target in hepatocellular carcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, due to its aggressive invasiveness and resistance to therapy. The dense, stiff extracellular matrix, composed primarily of collagen I and basement membrane components such as collagen IV and laminin, acts as a mechanical barrier that constrains PDAC invasion. We investigated whether the actin-related protein (Arp) 2/3 complex, a key actin nucleator, is essential for PDAC cells to overcome extracellular matrix stiffness and facilitate migration. CRISPR/Cas9 knockout of the Arpc4 gene in murine PDAC cell lines derived from KrasG12D-driven transgenic mice resulted in substantially downregulated all Arp2/3 complex members. Inactivation of Arp2/3 significantly impaired PDAC cell migration, disrupted branched tubular structure formation in collagen I, and inhibited invasive front formation in organoid culture together with tumor-associated macrophages and fibroblasts. Mechanistically, β1 integrin signaling emerged as a key regulator of Arp2/3-dependent migration through collagen-rich matrices. Clinically, elevated expression of Arp2/3 complex components correlates with poor patient survival and basal-like differentiation subtypes, underscoring its role in disease progression. This study identifies the Arp2/3 complex and β1 integrin signaling as critical mediators of PDAC invasiveness and suggests them as potential therapeutic targets for mitigating PDAC progression.

Nanotherapy targeting liver sinusoidal endothelial cells in liver fibrosis.

The mechanism of isosmotic water reabsorption in the kidney proximal tubule, with a focus on the interaction between the lateral Na+/K+-ATPase, apical water pathways mediated by AQP1 and SGLT1, and paracellular water flow through Claudin-2. A mathematical model of proximal tubular transport was used to compute coupled ion, solute, and water fluxes. The model included apical ENaC and a full electrogenic Na+/K+-ATPase formulation that incorporated its electromotive force, Epump, as a thermodynamic constraint linked to ATP hydrolysis at the pump site. Published cellular cation concentrations indicate metabolic stress in excised tubules, providing biophysical rationale for interpreting enhanced NHE3 activity and proton secretion in isolated proximal tubules as consequences of reduced ΔGATP, while modeling apical Na+ entry under non-stressed conditions by ENaC. Active Na+ transport generated a slightly hyperosmotic and hyperbaric lateral intercellular space, driving fluid efflux across the interspace basement membrane. Without ion recirculation, the absorbed fluid remained hyperosmotic. Isosmotic reabsorption therefore required ion recirculation between serosal fluid and the lateral intercellular space. SGLT1-mediated glucose uptake redistributed water flow between AQP1, SGLT1 and the paracellular pathway, whereas total water reabsorption remained closely linked to active Na+ transport, consistent with experiments. Proximal tubular water reabsorption is not explained by passive osmotic equilibration alone, but emerges from thermodynamic coupling between active Na+ transport, water permeability pathways, and regulated ion recirculation. The proximal tubule therefore functions as an ATP-consuming epithelial fluid pump that maintains isosmotic reabsorption by using additional metabolic energy to convert initially hyperosmotic absorbate intoisosmotic reabsorbed fluid.

Male fertility is declining globally, prompting efforts to identify contributing dietary factors. Wheat, a major staple worldwide, provides caloric and protein value but also contains anti-nutritional components such as wheat germ agglutinin (WGA), which has been implicated in oxidative stress and infertility. This study investigated the effects of common wheat lectin on male reproductive parameters in prepubertal Sprague-Dawley (SD) rats. Forty-five prepubertal SD rats (40-50 g; 30 days old) were randomized into three treatment durations (2, 5, and 10 weeks), each subdivided into three groups: control, pure wheat lectin (250 mg/kg), and common wheat lectin extract (250 mg/kg). Treatments were administered orally once daily. At each time point, testicular histology, sperm quality, reproductive hormones, and oxidative stress markers were assessed. Rats treated with wheat lectin showed significant reductions (p < 0.05) in testicular antioxidants (SOD, CAT, GSH) and testosterone (serum and intratesticular), alongside elevated malondialdehyde (MDA) and reproductive hormones (LH, FSH, prolactin). Sperm concentration, motility, and morphology were significantly impaired. Histological analysis revealed notable damage to the seminiferous germinal epithelium, expansion of the interstitial compartment consistent with edema, and basement membrane disintegration. Chronic exposure to wheat-derived lectins, may adversely influence male reproductive biology in this prepubertal rat model. The findings suggest a potential association between lectin exposure and testicular dysfunction, possibly mediated by alterations in hormone regulation and oxidative stress. These results should be interpreted cautiously and warrant further investigation to clarify their relevance to human reproductive health.

Introduction. Chemotherapy is one of the main methods of treating common/metastatic forms of malignant diseases. A commonly used chemotherapy drug is Cisplatin, a significant side effect of which is a toxic effect on organs with high proliferative potential, including the testicles, which can lead to severe disorders of spermatogenesis, androgen deficiency and infertility. The aim of the study. To study the possibility of preventing Cisplatin gonadotoxicity using Cellex therapy, which refers to drugs containing products of stem cell secretion. Materials and methods. Experiments were conducted on 45 male mongrel rats: Series 1 – intraperitoneal cisplatin administration at a dose of 5 mg/ kg, Series 2 – cisplatin administration at a dose of 7 mg/ kg, Series 3 – cisplatin administration at a dose of 5 mg/ kg during therapy with Cellex (0.1 mg/ kg intramuscularly daily for 10 days), 4 series – the introduction of Cisplatin at a dose of 7 mg / kg with Cellex therapy as in 3 series. After 3, 7, and 14 days, the concentration of testosterone in the blood was determined, and after 14 days, the testicles were removed, followed by their histological and morphometric examination. Results. In the 1st and 2nd series, the development of testicular hypoplasia with a decrease in their mass by 15% was revealed with pronounced disorders of spermatogenesis, manifested in a decrease in the diameter and cross-sectional area of the seminal tubules, layers of the germinal epithelium and the number of Sertoli cells per 100 mcm of the basement membrane. At the same time, in the 2nd series, the appearance of destroyed tubules and groups of tubules completely devoid of epithelial lining was revealed. In the 3rd and 4th series, the histological picture approached normal, although the morphometric parameters still did not reach normal values. In group 4, the proportion of destroyed and emptied tubules was significantly less than in group 2. The level of testosterone in the blood of rats decreased starting from day 3 in group 1 and on day 1 in group 2 and remained significantly reduced until the end of the follow-up, whereas in groups 3 and 4 it remained within normal limits at all times. Conclusion. Cellex therapy can significantly reduce the toxic effect of Cisplatin on the testicle, while maintaining active spermatogenesis and testosterone synthesis. Keywords: chemotherapy, cisplatin, spermatogenesis disorder, testosterone, cell therapy, cellex.

Basement membranes (BMs) are dynamic extracellular matrices whose remodelling controls tissue morphogenesis, regeneration and malignant progression. This review examines how a shared protease- and extracellular matrix (ECM)-based machinery reshapes laminin- and collagen IV-rich BMs during development and wound repair, and how the altered levels, localisation and regulation of these components drive cancer invasion. In development, patterned BM thinning, perforation and stiffening driven by MMPs, MT-MMPs, ADAMTS proteases and nonproteolytic regulators generate gradients that guide branching, tissue elongation and axis formation. In cutaneous wound healing, many of the same proteases (including MMP-1, MMP-9, MT1-MMP, stromelysins, serine proteases and cathepsins) act in transient, spatially restricted patterns so that keratinocytes remodel a provisional matrix at the wound edge and then rebuild a mature dermal-epidermal BM. By contrast, in carcinomas, invadopodia enriched in MT1-MMP, MMP-2, MMP-9 and related proteases concentrate pericellular proteolysis to perforate BMs, while collagen IV 'escape tracks' and laminin-derived cryptic fragments promote proliferation, survival, epithelial-mesenchymal transition and angiogenesis. Finally, we highlight emerging therapeutic strategies, including isoform- and site-selective protease inhibitors and protease-responsive or protease-modulating biomaterials, that seek to locally rebalance this protease-ECM programme to restore BM integrity in chronic wounds and limit invasive growth in cancer.

Renal cell carcinoma (RCC) associated with BRCA2 mutation is an extremely rare but increasingly recognized tumor type with characteristic but variable morphological features and aggressive behavior. We report a new case of high‑grade RCC harboring a somatic BRCA2 mutation in a 69‑year‑old male presenting with painless gross hematuria. The tumor exhibited a complex admixture of solid papillary/alveolar, cribriform, and tubulocystic architectures with prominent eosinophilic nucleoli. A biphasic pattern was observed, with central nests of more bland clear cells forming rosette‑like structures around hyaline basement membrane material, a finding reminiscent of TFEB‑altered RCC. Immunohistochemically, the tumor showed a nonspecific immunophenotype with expression of PAX8, CD10, and vimentin, while other RCC‑associated markers were negative. SMARCB1/INI1, SDHB, and FH expression were retained. Targeted next‑generation sequencing confirmed a somatic BRCA2 truncating mutation and absence of alterations in VHL, MET, TSC1/2/MTOR, SDHx, FH, or MiTF genes. A review of all five previously reported BRCA2‑associated RCCs revealed that all six reported cases (including ours) shared certain features: mixed papillary and solid architecture, high‑grade cytology with prominent nucleoli, and absence of other RCC‑defining molecular drivers. Our case not only reinforces the previously reported features but also expands the morphological spectrum of BRCA2‑associated RCC, providing further evidence that this may represent a distinct subtype of RCC.

Transthyretin amyloidosis (ATTR) is a degenerative disease affecting the heart and other organs. Transthyretin (TTR) aggregation is a driver of ATTR pathology, but the mechanism is poorly understood. We used proteomics and tissue clearing technology on wild-type (WT) human cardiac (WT/WT) and V122I human cardiac (V122I/WT) tissue to better understand TTR cardiomyopathy. Flash-frozen cardiac tissue slices from human subjects with end-stage WT-TTR cardiomyopathy, end-stage V122I TTR cardiomyopathy, and an age-matched control were used. Fibrils and tissue proteomes were extracted and assessed by bottom-up proteomics. Tissue clearing was performed using a lauryl sulfate-based lipid removal strategy. Slices were stained using indirect immunofluorescence against targets identified by proteomics. TTR deposits were imaged by antibody and AmyTracker 480 staining. Structures of ATTR fibrils were characterized using cryogenic electron microscopy. Proteomic analysis revealed high abundance of TTR, proteins associated with amyloid fibrils, as well as angiogenic, hemostatic, and complement cascade-associated proteins. Three-dimensional imaging revealed loss of normal microvascular architecture, regions of hypervascularization and hypovascularization, and microvascular obstruction by capillary thrombosis. ATTR fibrils adopted the spearhead fold and were decorated with collagen VI, an extracellular matrix component. Based on our imaging and proteomic data, we hypothesize that ATTR cardiomyopathy is a microangiopathy driven by capillary bed thromboinflammation and dysregulated angiogenic revascularization. In this model, increased capillary permeability exposes components of the vascular basement membrane to misfolded TTR. These components promote aggregation and stabilize amyloid fibrils. Congestion of the vascular basement membrane prevents appropriate revascularization, reducing cardiac exertional capacityover time, leading to heart failure.

Renal biopsy remains the gold standard for the diagnosis of kidney diseases, and specimen adequacy is essential for reliable histopathological evaluation. However, confirmation of glomerular yield in routine pathology workflows often relies on histological sections after staining, which may delay feedback when deeper sectioning is required. In this study, we investigated whether virtual staining applied to unstained renal biopsy sections could enable early assessment of glomerular adequacy. Unstained sections prepared under different mounting conditions were virtually transformed into H&E and special stains. The visibility of glomerular structures and the reliability of glomerular assessment were evaluated across multiple scanners. Optimized preparation of unstained sections enabled stable virtual staining with preserved morphological features. Virtual special stains enhanced the visualization of glomerular basement membranes and mesangial regions, allowing reliable identification of glomeruli on unstained tissue sections. This approach demonstrated robustness across different scanning systems, outperforming direct assessment on raw unstained images. Virtual staining of unstained renal biopsy sections provides a rapid and reagent-free strategy for early slide-level assessment of glomerular yield. By enabling feedback at the sectioning stage before routine staining, this method may improve efficiency and quality control in routine renal pathology workflows.

To evaluate kidney biopsy findings to clarify renal disease in patients after hematopoietic stem cell transplantation (HSCT) using unrelated umbilical cord blood transplantation (UCBT). We retrospectively examined 14 patients who underwent UCBT at Toranomon Hospital, Tokyo, Japan, from 2015 to 2023 and subsequently developed kidney injury requiring biopsy. At biopsy, median urinary protein was 0.57 g/day (IQR, 0.27-1.67), median serum creatinine was 1.97 mg/dL (IQR, 1.81-2.6), and median eGFR was 25.3 mL/min/1.73 m2 (IQR, 18.1-34.2). In 13 of 14 patients, mesangiolysis, glomerular basement membrane (GBM) duplication, and subendothelial widening without thrombi were observed-lesions defined as glomerular microangiopathy (GMA). Immunofluorescence and electron microscopy revealed no immune deposits typical of membranous nephropathy. Eleven patients showed distinctive arterial and arteriolar changes termed vascular microangiopathy. Nine exhibited severe interstitial fibrosis and tubular basement membrane duplication involving > 50% of the cortex. Human leukocyte antigen (HLA) incompatibility was found in 13 patients (92.9%) and ABO incompatibility in nine (64.2%). C4d positivity in glomeruli or peritubular capillaries was detected in 12 patients (85.7%). The coexistence of glomerular, vascular, and tubulointerstitial microangiopathic lesions was associated with mild proteinuria and renal dysfunction after UCBT. These findings suggest a chronic endothelial injury process distinct from classical thrombotic microangiopathy.

Accelerated basement membrane remodeling and serum matrix fragments as biomarkers of fibrosis in Alport syndrome.

Emerging experimental evidence shows that perivascular cells (PCs), referred to as pericytes lying within the basement membrane (BM) and surrounding endothelial cells (ECs) of microvasculatures, play multifarious roles in cancer metastasis. In the tumor microenvironment (TME), PC detachment and ablation from tumor microvessels obliterate the vascular integrity and the protective barrier of the vessel wall, leading to increased permeability for cancer cell intravasation. PCs retain mesenchymal stem cell (MSC) features and commit to differentiation into other stromal cells, including the pericyte-fibroblast transition (PFT) for promoting cancer metastasis. Activated PCs produce a myriad of growth factors, cytokines, and chemokines, which promote invasiveness and dissemination of cancer cells by altering tumor angiogenic, inflammatory, and immune microenvironment. Owing to their high lineage and phenotypic plasticity, PCs significantly constitute to the pre-metastatic niche formation in distal organs. This review provides an updated overview and mechanistic insights into each of PC-mediated critical processes of the metastatic cascade.

The Par complex regulates cell polarity in diverse animal cells, but how it is restricted to a specific membrane domain remains unclear. The tumor suppressor Lethal giant larvae (Lgl) is thought to inhibit Par complex membrane binding, yet in metaphase Drosophila neural stem cells (NSCs), Lgl is cytoplasmic while the Par complex is apically polarized, raising the question of how Lgl controls Par localization when it is not on the membrane. Using live imaging, we found that Lgl and atypical Protein Kinase C (aPKC) exhibit tightly coordinated, opposing membrane dynamics: aPKC displaces Lgl at mitotic entry, while Lgl displaces aPKC at mitotic exit. In Lgl-depleted NSCs, aPKC is not fully cleared from the membrane after mitosis, and this residual aPKC persists into the subsequent division, disrupting Miranda polarization. Apical aPKC recruitment still occurs, indicating that Lgl is not required for Par polarization per se, but rather for ensuring aPKC absence from the basal membrane before mitosis. These findings reveal a temporal mode of mutual antagonism between Lgl and the Par complex that may license proper asymmetric division.

Diabetic nephropathy (DN) is a major complication of diabetes. Swietenine (Swi), a natural compound derived from the fruit of Swietenia macrophylla, has shown beneficial effects in alleviating diabetic complications. However, its underlying mechanism for treating DN remains unclear. This study aimed to elucidate the therapeutic effects and molecular mechanisms of Swi against DN through invitro and invivo experiments. A model of streptozotocin/high-fat diet (STZ/HFD)-induced Sprague-Dawley (SD) rats was employed to evaluate the effects of Swi on improving DN renal fibrosis and enhancing autophagy invivo. Followed based on the results of proteomics, network pharmacology, and molecular docking, the potential mechanism of Swi in treating DN was predicted, and subsequently the cell model of high glucose induced human renal tubular epithelial cells (HK-2) was established invitro, and the potential mechanism of Swi's therapeutic effect was further validated through Western blot analysis, immunofluorescence, immunohistochemistry, and flow cytometry. After Swi treatment, levels of urinary protein, uric acid, creatinine, and urea nitrogen were significantly reduced in DN rats. Pathological improvements included decreased thickness of the tubular basement membrane, reduced PAS-positive deposits, less glycogen accumulation, and alleviated fibrosis. The number of autolysosomes increased significantly, especially with high-dose Swi. Immunofluorescence of renal tissue showed enhanced LC3B fluorescence intensity, suggesting restored autophagy levels. Western blot analysis revealed upregulation of LC3B and Beclin-1 and downregulation of p62 after Swi treatment. Immunohistochemistry indicated reduced expression of fibronectin (Fn) and collagen I (COI-I), indicating decreased extracellular matrix accumulation and renal injury. In high glucose-induced human renal tubular epithelial cells (HK-2), similar trends were observed. Swi treatment upregulated p-AMPK and p-ULK1 expression and downregulated p-mTOR. Overall, Swi significantly improved renal function and pathological damage in DN rats by activating the AMPK/mTOR/ULK1 signaling pathway, enhancing autophagy, reducing ROS production, and ameliorating mitochondrial injury, thereby delaying renal fibrosis progression. In conclusion, Swi exerts protective effects against DN by promoting autophagy and mitigating oxidative stress, suggesting its potential as a therapeutic agent for DN.