Histology and histopathology最新文献

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent hepatic disorder with high morbidity and mortality. Licochalcone A (LiA) exhibits significant therapeutic efficacy in obesity through diverse pharmacological mechanisms. This study aimed to explore the efficacy and underlying mechanism of LiA in attenuating MASLD, which requires further investigation.

Methods: Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to establish a MASLD mouse model. The lipid level and liver function of mice were evaluated by the levels of TG, TC, ALT, and AST. H&E staining and Oil Red O staining were used to evaluate the pathological changes and lipid deposits in the liver. Lipid metabolism and PPARα/CPT1α signaling pathway-related genes were detected.

Results: LiA effectively reduced weight and improved glucose tolerance and insulin resistance in MASLD mice. LiA treatment significantly reduced lipid accumulation in HFD-induced mice. In addition, bioinformatics analysis, molecular docking, and cellular thermal shift assays further indicated that LiA alleviated MASLD by upregulating PPARα. Furthermore, the protective effect of LiA on lipid accumulation and hepatic steatosis was abolished by PPARα inhibitor (GW7461) pretreatment in MASLD mice.

Conclusion: This study demonstrated that LiA ameliorates the lipid metabolism disorder in MASLD mice by upregulating the PPARα/CPT1α signaling pathway.

Metabotropic GABA (GABA_B) receptors have modulatory functions on neuronal excitability and neurotransmitter release. To fulfil these functions, GABA_B receptors form macromolecular signaling complexes with G proteins, effectors, and other associated proteins. Here we investigated the postnatal development of GABA_B receptors (GABA_B1 and GABA_B2 subunits) in mouse brain, focusing on potential similarities in the spatial and temporal expression pattern of their associated proteins Ca_V2.1, Gα_o, Gβ5, and RGS7, using histoblots, immunofluorescence, and immunoelectron microscopic techniques. At all ages analyzed, histoblot showed that the six proteins were widely expressed in the brain, with mostly an overlapping pattern throughout postnatal development. In the hippocampus, immunoelectron microscopy and quantitative analysis of immunoparticles for GABA_B1, GABA_B2, Gα_o, Gβ5, and RGS7 revealed their progressive enrichment around excitatory synapses on dendritic spines of CA1 pyramidal cells toward P15. At presynaptic sites, GABA_B receptors colocalize with Ca_V2.1, Gα_o, Gβ5, and RGS7 in the active zone and extrasynaptic membranes of axon terminals, establishing synapses on dendritic spines of CA1 pyramidal cells. In the cerebellum, double immunofluorescence at P7 and P10 revealed the colocalization of GABA_B1 and Ca_V2.1 in the whole dendritic tree of developing Purkinje cells. Immunoelectron microscopy at P15 showed that GABA_B1, GABA_B2, Ca_V2.1, Gα_o, Gβ5, and RGS7 are distributed along the dendritic surface of Purkinje cells, enriched close to excitatory synapses in spines. Altogether, these data suggest that macromolecular complexes composed of GABA_B1/GABA_B2/Ca_V2.1/Gα_o/Gβ5/RGS7 are pre-assembled during key stages of postnatal development in hippocampal and cerebellar neurons.

Acute lung injury (ALI) is a frequent complication of sepsis that aggravates sepsis mortality and morbidity, which is tightly related to the inflammatory process. Oroxin B (OB), a flavonoid from Oroxylum indicum (L.) Vent, has exhibited anti-inflammatory properties in several illnesses. Nevertheless, it is still unclear how OB affects sepsis-induced ALI and how it works. RAW264.7 cells were challenged with lipopolysaccharide (LPS, 10 μg/mL), and mice received cecal ligation and puncture (CLP) to produce sepsis-evoked ALI in in vitro and in vivo models. The action of OB on sepsis-elicited ALI was probed through cell counting kit-8, pathological staining, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, and western blot. The results showed that OB improved pathological damage and pulmonary fibrosis in CLP-challenged mice. OB also reduced the concentration of MPO, the protein content in BALF, and macrophage and neutrophil numbers in BALF from CLP-challenged mice. Molecularly, OB decreased the levels of IL-1β, IL-6, TNF-α, CD86, and iNOS but increased the level of Arg1 and CD206 in both LPS-evoked RAW264.7 cells and CLP-treated mice. Mechanistically, OB downregulated the level of the TLR4/NF-κB axis in both LPS-challenged RAW264.7 cells and CLP-treated mice. Overexpression of TLR4 abrogated the effect of OB on the above-mentioned indicators in LPS-elicited RAW264.7 cells. Therefore, OB improved sepsis-elicited ALI by attenuating inflammation and promoting M2 macrophage polarization through the TLR4/NF-KB signaling pathway.

Interest in normal perivascular spaces (PVS) and their evolution to a pathogenic, remodeled enlarged perivascular spaces (EPVS) have increased in parallel with the recently described glymphatic system pathway (GS) during the past decade. EPVS on magnetic resonance images have been shown to be a biomarker for neurovascular, neuroinflammatory, and neurodegenerative diseases. Thus, the integrity of the PVS is absolutely essential for the proper function of the GS. The mechanisms involved in the evolution of PVS to EPVS are a hot topic in research and as we better understand the pericapillary venules and vein's role regarding the GS via higher resolution imaging some of the missing pieces of this puzzle will evolve. The GS is currently known to absolutely depend on the brain's existing PVS to provide a channel for the efflux of neurotoxic substances such as accumulated neurodegenerative misfolded proteins, proinflammatory cytokines/chemokines, leukocytes, and metabolic, proteolytic debris. The perivascular unit contains both the normal PVS and the pathologic remodeled EPVS and allows for a space to house incoming leukocytes to undergo excessive cellular crosstalk of leukocytes and the resident perivascular macrophage to result in neuroinflammation. Additionally, the polarized aquaporin 4 water channels are essential in waste and excess water removal by the GS.

Background: Septic patients are at high risk of acute lung injury (ALI). Luteoloside is a flavonoid isolated from natural herbs and has many beneficial effects. This study aimed to investigate the protective role of luteoloside in sepsis-induced ALI.

Methods: Sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Inflammation was induced by lipopolysaccharide (LPS) in MLE-12 cells. The survival rate over 12 days, histological changes in lung and heart, pulmonary edema, vascular leakage, hypoxemia, and inflammation were examined. Apoptosis was detected by TUNEL staining in vivo and flow cytometry in vitro. The levels of autophagy-related proteins, the AMPK/ULK1 pathway, and the NLRP3 inflammasome were evaluated by western blotting. Cell viability was estimated by MTT assays. LC3 expression was evaluated by immunofluorescence staining.

Results: Luteoloside attenuated lung and cardiac injury, pulmonary edema, vascular leakage, hypoxemia, and inflammation and improved the survival of septic mice. Luteoloside (20 mg/kg) had no toxic effect on the heart, liver, spleen, and kidney in normal mice. Luteoloside enhanced autophagy to inhibit apoptosis in vivo and in vitro, and autophagy induction was responsible for the protective effect of luteoloside. Luteoloside activated AMPK/ULK1 signaling to enhance autophagy. Luteoloside also inhibited the activation of the NLRP3 inflammasome in LPS-challenged MLE-12 cells.

Conclusion: Overall, luteoloside activates AMPK/ULK1 signaling to stimulate autophagy, thereby inhibiting apoptosis and alleviating sepsis-induced ALI.

Endolymphatic sac tumors (ELSTs) are rare, slow-growing neoplasms of the inner ear. Microscopically, they exhibit papillary-cystic and glandular histomorphology, closely resembling their primary differential diagnosis, choroid plexus papilloma (CPP). Through in-depth histological, immunohistochemical, and molecular analysis, we identified distinct characteristics of ELST that facilitate its identification and aid in differentiating it from CPP. Immunohistochemical staining that best discriminated between ELST and CPP included EMA, S-100 protein, EpCAM, cytokeratin, transthyretin, CD34, PTEN, PAX8, and YAP. In contrast to CPP, pan-cancer DNA panel next-generation sequencing frequently revealed pathogenic VHL gene alterations in ELST. In conclusion, comprehensive immunohistochemistry enhances the identification of this rare tumor type and helps prevent misdiagnosis. Furthermore, the detection of VHL gene alterations additionally supports the diagnosis of ELST.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with an incidence projected to rise significantly worldwide. While TNM staging remains the cornerstone of prognosis and treatment decisions, additional biomarkers are needed to enhance predictive accuracy and therapeutic targeting. Ferroptosis, an iron-dependent cell death pathway, has emerged as a key regulator of CRC progression and therapy resistance. Circadian rhythms, KLOTHO, and tumor suppressors, such as p53, CDKN1A (p21), and Rb, also play crucial roles in CRC biology. Integrating TNM staging with molecular markers and patient-specific variables offers a more precise, personalized approach to CRC management. In the present work, we analyze the histopathological expression of KLOTHO, ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian regulators (CLOCK, BMAL1, PER1, and PER2), and classical tumor suppressors (p53, p21, and Rb) in a cohort of 63 patients diagnosed with CRC. Besides, we have considered important clinical variables, like sex, age, and anatomical location, in our statistical analysis; correlation with the protein expression of these markers was also included for each stage (T1, T2, and T3). Our study reveals that advanced CRC stages (primarily T3) exhibit increased expression of ferroptosis markers (TFRC, ALOX5, ACSL4, and GPX4) and tumor suppressors (p53, p21, and Rb), alongside reduced histopathological detection of KLOTHO and circadian markers (BMAL1, CLOCK, PER1, and PER2) compared with earlier stages. Age, but not sex, influenced the expression of several markers. Tumor location also played a role, with right-sided CRCs showing significant stage-related differences in ferroptosis, tumor suppressor, and BMAL1, whereas left-sided tumors exhibited variations primarily in circadian markers (CLOCK, PER1, and PER2). Correlation analyses across tumor stages indicate dynamic shifts, with tumor suppressors maintaining positive associations with ferroptosis markers and anti-aging/circadian markers showing stage-dependent changes. Despite the inherent limitations of our study, these findings highlight the evolving biomarker landscape in CRC progression, although further research is needed to elucidate their clinical implications.

Hip osteoarthritis (HOA) is the most common hip joint disorder, accounting for approximately 27.9% of all cases of osteoarthritis (OA), often leading to total hip replacement (THR). In the last decades, femoroacetabular impingement (FAI) has been addressed as a significant etiological factor in the development of early-onset HOA, especially in young adults with non-dysplastic hips. FAI has been found to cause damage to all joint tissues, cartilage, labrum, and subchondral bone, thus underlining the importance of an early diagnosis and intervention to prevent progression to end-stage disease. This review aims to provide a comprehensive overview of the biochemical, morphological, and cellular alterations occurring in hip joint tissues in the presence of FAI. Understanding the early pathological changes is of crucial importance as they often precede radiographic signs of disease and may serve as valuable biomarkers for early detection and management of FAI and peri-arthritic conditions to delay or prevent the need for THR in younger populations.

Background: Stroke is a crucial cause of morbidity and mortality worldwide. The regulator of G protein signaling 14 (RGS14) plays important roles in mediating multiple signaling pathways and various pathophysiological processes. However, the function of RGS14 in cerebral ischemic reperfusion injury (CIRI) remains unknown.

Methods and results: In this study, the roles of RGS14 during CIRI were studied in terms of gain- and loss-of-function experiments. Using RT-PCR, western blot, and TCC, HE, TUNEL, immunofluorescence, immunohistochemical staining, etc., we found that RGS14 significantly improved CIRI by reducing inflammation and apoptosis in both a mouse model of transient middle cerebral artery occlusion (t/MCAO) and a primary neuronal model of oxygen-glucose deprivation/reperfusion (OGD/R). In addition, mechanism studies have shown that RGS14 acts by inhibiting the activation of the TAK1-JNK/p38 signaling pathway, which was further confirmed using the TAK1 inhibitor (iTAK1), 5Z-7-oxyzeaenol, during OGD/R treatment of AdshRGS14-infected primary neurons.

Conclusions: These findings imply that RGS14 is a novel negative regulator and may serve as a potential therapeutic target for CIRI.

The age-standardized point prevalence of global osteoarthritis (OA) has increased, and OA will not only lead to disability in patients but also to a greater psychological burden. In recent years, the focus of scientists on treating OA has turned to disease prevention and treatment of early OA. Previous studies have proved that WuFu Decoction (WFD) could protect chondrocytes, and the Chinese herbs in this prescription have shown anti-inflammatory effects. In this study, we built the OA rat model by the modified Hulth method, conducted research with WFD, and set D-Glucosamine sulfate as the positive control. It is proven that WFD improved the micromorphology and tissue damage of the knee joint, decreased the score of the Mankin and OARSI system, and inhibited the IL-1β, TNF-α, MMP-13, and CTX-1 levels in serum. Additionally, WFD treatment inhibited p-ERK1/2 levels and raised the mRNA and protein levels of TGF-β1, p-Smad2, p-Smad3, type II collagen (the gene is COL2A1), ALP, TRACP, and BMP7. Furthermore, TGF-β1 inhibitor (Decorin) reversed the improvement effect of WFD on OA, but ERK1/2 inhibitor (PD98059) promoted this improvement effect. Silencing TGFβR2 can reverse the protective effect of WFD on primary chondrocytes. It is suggested that WFD can improve OA and chondrocytes by regulating the TGF-β1/Smad and ERK1/2 pathways. This study also identified active ingredients, such as Fumaric acid, Glycyrrhizic acid, Albiflorin, and Isoliquiritigenin. It provides a basis for the clinical application of WFD and for the promotion and development of TCM.