Amyloid β (Aβ) accumulation in the brains of patients with Alzheimer's disease (AD) contributes to cognitive impairment and neuronal damage. Urolithin A (UA), a gut microbiota-derived metabolite of ellagic acid, has been reported to cross the blood-brain barrier to exert anti-inflammatory and anti-oxidation effects in the brain. However, the molecular mechanisms of UA in AD were still unclear. This study aims to explore the neuroprotective effect and mechanism of UA on APP/PS1 mice and Aβ-injured N2a and PC12 cells.

This study aimed to investigate whether cancer-associated fibroblast (CAF)-derived chemokine C-C motif ligand 5 (CCL5) promotes breast cancer (BC) cell metastasis by enhancing aerobic glycolysis via upregulation of IP3R.

Cholinergic neurons in the basal forebrain cholinergic nuclei (BFCN) and neostriatum (CPu) play key roles in learning, attention, and motor control. The loss of cholinergic neurons causes major neurodegenerative diseases such as Alzheimer's disease. This study aimed to elucidate the molecular diversity of choline acetyltransferase immunoreactive (ChAT-ir) neurons in these brain regions. We performed immunohistochemistry to determine the co-expression of ChAT-ir neurons with two neuropeptides, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK), as well as three calcium-binding proteins, such as calbindin, calretinin, and parvalbumin, in the adult mouse brain. The results showed that ChAT, calbindin, CGRP and CCK were strongly expressed in the BFCN, including medial septal nucleus (MS), nucleus of vertical limb and horizontal limb of the diagonal band of Broca (VDB and HDB), substantia innominata basal part (SIB), and in the caudate putamen (CPu). CGRP and CCK showed a high immunoreactive co-expression with ChAT, especially in the HDB and CPu. Calbindin immunoreactivity was widely present and coincided with ChAT in the VDB, HDB, and CPu. However, calretinin immunoreactivity showed a selective co-expression with ChAT in the VDB, SIB, and CPu. Although parvalbumin immunoreactivity was observed throughout the BFCN and CPu, but there was no co-expression between ChAT and parvalbumin. The neurochemical diversity of ChAT-ir neurons in the BFCN and neostriatum suggests the specialized functions of cholinergic neurons across different circuits, especially by modulating CGRP, CCK, or calbindin. These results could provide new insight into cholinergic modulation throughout the BFCN and striatum.

Skeletal muscle, which accounts for nearly 40 % of total body mass, serves as the primary effector organ for locomotion, metabolism, and thermoregulation. Skeletal muscle atrophy, a common condition associated with aging, disease, and disability, significantly compromises patients' quality of life. This review focuses on the occurrence and progression of skeletal muscle atrophy. Forkhead box protein O1 (FoxO1) is a key regulatory factor that mediates pathological mechanisms through multidimensional molecular networks. It influences skeletal muscle metabolism via post-translational modifications (PTMs), dysregulated autophagy, an imbalanced inflammatory microenvironment, and the regulation of satellite cell function. Therapeutic strategies targeting FoxO1, such as resveratrol-induced SIRT1 activation and miR-486 mimics, have shown promising results in preclinical models. This review highlights the central role of FoxO1 in molecular pathways, proposes a potential framework for addressing muscle atrophy, and offers new insights into the treatment of sarcopenia and related diseases.

IgA nephropathy (IgAN) is a prevalent glomerular disease characterized by mesangial deposition of IgA1-containing immune complexes, yet its underlying molecular mechanisms remain incompletely understood. In this study, we integrated bioinformatics analyses of two public datasets (GSE104948 and GSE93798) to identify key differentially expressed genes (DEGs) associated with IgAN. Periostin (POSTN) emerged as a hub gene, exhibiting significant upregulation in IgAN samples and correlating with histopathological severity. Functional enrichment revealed that overlapping DEGs are involved in extracellular matrix organization, immune response, and signaling pathways relevant to renal pathology. Immunohistochemical and immunofluorescence analyses confirmed increased POSTN and decreased GPX4 expression in renal biopsies from IgAN patients, indicating enhanced ferroptosis. In vitro, IgA1 stimulation of human mesangial cells (HMCs) elevated POSTN expression and induced ferroptosis, evidenced by increased oxidative stress, mitochondrial damage, and reduced cell viability. Knockdown of POSTN ameliorated these effects by restoring glutathione levels and reducing lipid peroxidation, while POSTN overexpression exacerbated ferroptosis. Notably, treatment with the ferroptosis inhibitor ferrostatin-1 reversed POSTN-induced cellular damage. Our findings suggest that POSTN promotes IgAN progression by facilitating ferroptosis through GPX4 downregulation, highlighting a novel pathogenic mechanism. Targeting POSTN-mediated ferroptosis may provide promising therapeutic strategies for IgAN. This study advances our understanding of IgAN molecular pathology and offers potential biomarkers and intervention targets to improve patient outcomes.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of renal malignancy, associated with poor prognosis in advanced stages. Emerging evidence highlights the potential tumor-suppressive role of the anti-aging protein Klotho (KL) and its cofactor, fibroblast growth factor 23 (FGF23), both of which are implicated in phosphate metabolism and cellular homeostasis.

Psoriasis is a chronic,immune-mediated inflammatory skin disorder characterized by recurrent thick plaque. As an alarmin of inflammation, the importance of S100A8 and S100A9 have already been confirmed to be associated with the development of chronic inflammation in diseases. However, the precise mechanisms of S100A8 and S100A9 in psoriasis remain unclear. Therefore,the aim of this study was to elucidate the effects and underlying mechanisms of S100A8 and S100A9 in psoriasis. In this study, we found that both S100A8 and S100A9 were highly expressed in cells treated with M5-a cytokine mixture containing IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α-as well as in a mouse model of imiquimod (IMQ)-induced psoriasis. Meanwhile, S100A8 and S100A9 knockdown in normal human epidermal keratinocytes (NHEK) inhibited the proliferation of NHEK cells in psoriasis. To further investigate the effects of S100A8 and S100A9 on psoriatic inflammation, T cells were co-cultured with S100A8 and S100A9 knockdown NHEK cells, and S100A8 and S100A9 promoted the production of pro-inflammatory cytokines by T cells through activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. In particular, when the S100A8 and S100A9 inhibitor paquinimod was added to a mouse model of imiquimot-induced psoriasis, psoriatic dermatitis and inflammatory factors were reduced, and the expression of TLR4/NF-κB was also significantly reduced. In conclusion, this study illustrated that S100A8 and S100A9 participates in the pathogenesis of psoriasis by activating TLR4/NF-κB signaling pathways, thereby promoting psoriasis-associated skin inflammation, which suggested the potential role of S100A8 and S100A9 in the development of psoriasis and provided new insight into targeted therapies.

Triple-negative breast cancer (TNBC) poses considerable clinical challenges due to its aggressive nature, early metastasis, and limited treatment options. The simplified 2D models and the physiological differences in animal models often result in inconsistent responses to anticancer drugs. To tackle these challenges, three-dimensional (3D) in vitro bioengineered models that accurately replicate the in vivo tumor microenvironment (TME) have been developed, offering a more reliable platform for preclinical drug testing. Recent advancements in cell culture techniques have facilitated the creation of 3D models derived from patient tissues and tumors, which effectively mimic the native tissue environment and exhibit drug sensitivity and cytotoxicity behaviors similar to those observed in vivo. It is increasingly acknowledged that the extracellular matrix and cellular diversity within the TME significantly influence the fate of cancer cells. Consequently, strategies to explore drug resistance mechanisms must account for both microenvironmental factors and genetic mutations. This review examines 3D in vitro model systems that integrate microenvironmental influences to investigate drug resistance mechanisms in breast cancer. We discussed various bioengineered models, including spheroid-based, biomaterial-based (such as polymeric scaffolds and hydrogels), patient-derived xenograft (PDX), 3D bioprinting, and microfluidic chip-based models. Additionally, we discuss the relevance of these 3D models in understanding the effects of TME signals on drug response and resistance, as well as their potential for developing strategies to overcome drug resistance and optimize treatment regimens.

Blood transfusions play a critical role in breast cancer management, particularly in addressing perioperative blood loss and chemotherapy-induced anemia. However, emerging evidence suggests that transfusions may adversely affect oncologic outcomes by inducing transfusion-related immunomodulation (TRIM) and altering the tumor microenvironment (TME). TRIM suppresses cytotoxic immune responses, potentially facilitating tumor progression-especially in aggressive subtypes such as triple-negative breast cancer (TNBC) and HER2-positive cancers. Additionally, transfusions can paradoxically exacerbate tumor hypoxia by increasing blood viscosity and impairing microvascular perfusion, thereby reducing the effectiveness of chemotherapy, radiotherapy, and immunotherapy. This review examines the dual role of blood transfusions in breast cancer, emphasizing both their clinical benefits and potential risks. We analyze their impact on treatment resistance and tumor progression and discuss strategies to mitigate associated risks, including leukoreduction, erythropoiesis-stimulating agents (ESAs), intravenous iron supplementation, and blood conservation techniques. Furthermore, we highlight the importance of personalized transfusion approaches guided by tumor subtype, immune status, and relevant biomarkers such as tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and circulating tumor DNA (ctDNA). Future research should focus on optimizing transfusion timing, implementing biomarker-driven protocols, and developing immune-modulating interventions to counteract TRIM. A personalized, evidence-based transfusion strategy may ultimately enhance treatment efficacy and improve long-term outcomes in breast cancer care.

Hypoxia plays a crucial role in driving tumor progression by altering cellular signaling pathways. Lysophosphatidic acid (LPA) receptor signaling regulates malignant properties in cancer cells, including motility and chemoresistance. This study aimed to compare the cellular functions of gastric cancer AGS cells under cobalt chloride (CoCl)-induced hypoxia and true hypoxia (1 % O), with a focus on the role of LPA receptor signaling in mediating these responses. Treatment with CoCl (200 μM) elevated LPAR1 and LPAR3 expression while reducing LPAR2 expression, resulting in enhanced cell motility. CoCl also increased AGS cell viability in response to cisplatin (CDDP) in the presence of LPA. These effects were suppressed by LW6, an inhibitor of HIF-1α, indicating HIF-1α involvement. Furthermore, AGS cel motility and CDDP resistance were enhanced by AM966 (LPA antagonist), GRI-977143 (LPA agonist), and (2S)-OMPT (LPA agonist), suggesting that LPA and LPA promote, while LPA suppresses, these cellular functions under CoCl-induced hypoxia. In contrast, under 1 % O conditions, LPAR1 and LPAR3 expression levels were downregulated, while LPAR2 expression remained unchanged. AGS cells cultured at 1 % O showed increased motility but reduced viability in response to CDDP. LW6 further inhibited viability under these conditions. Our results demonstrate that LPA receptor signaling is differentially regulated under CoCl-induced and true hypoxia, contributing to distinct outcomes in cell motility and drug response. This suggests that LPA receptor signaling is a potential target for controlling hypoxia-induced malignant transformation in gastric cancer cells.

The study of oligodendrocyte precursor cells (OPCs) in both physiological and pathological contexts is challenging due to their capacity for self-renewal. This research aimed to examine the effects of OPC depletion on neurons. Tamoxifen-inducible Sox10/iCreER; netrin-1 (NTN-1 cKO) mice were used to inactivate NTN-1 in Sox10 oligodendroglia at varying tamoxifen doses. The impact of Necrostatin-1s (Nec-1s) and cytarabine on neuronal degeneration was evaluated, along with a comparison of the effects of tamoxifen dissolved in different plant oils on lineage tracing in Sox10/iCreER; tdTomato mice, as well as on neuronal degeneration in NTN-1 cKO mice. Our findings showed that administering 3 mg of tamoxifen per NTN-1 cKO mouse triggered necroptosis and apoptosis in Sox10 cells. Notably, a higher dose of 6 mg of tamoxifen resulted in the degeneration of cortical neurons, which was accompanied by astrogliosis, amyloidosis, and a reduction in microglia. Immunostaining and RNAscope analysis indicated that it was Cre recombinase, rather than Cre mRNA, that was transferred to neurons. Nec-1s and cytarabine successfully prevented cortical neuron degeneration, though through distinct mechanisms. Furthermore, administering tamoxifen dissolved in vitamin E-rich wheat germ oil reduced Cre transfer in both Sox10/iCreER; tdTomato mice and NTN-1 cKO mice, significantly preventing cortical neurons from being labeled with tdTomato and protecting them from degeneration. These results suggest that, under pathological conditions, Cre recombinase can transfer from oligodendroglia to neurons, a process triggered by neuronal stress. This highlights the need for careful consideration in using Cre-loxP lineage tracing and gene-editing methods involving oligodendrocyte lineage cells and neurons.

AARS1 is a newly reported lactyl-transferase that plays vital roles in tumorigenesis and innate immune response. However, the function of AARS1-mediated lactylation in osteoblast differentiation is still unclear. Here, we found that silencing of AARS1 impaired the ALP activity and formation of mineralized nodules during osteoblast differentiation. Additionally, our findings demonstrated that AARS1 catalyzed lactylation of Osterix (Osx), a crucial transcription factor involved in the differentiation process of osteoblast cells. Lactylation of Osx increased its binding to target genes and promoted the interaction between Osx and WDR5, facilitating H3K4 tri-methylation on downstream target genes. This in turn enhanced the expression of Osx target genes and osteoblast differentiation. In summary, our study revealed a novel role of AARS1-mediated Osx lactylation during osteoblast differentiation.

Calcipotriol is a well-established treatment for psoriasis and other dermatological conditions. This study aimed to investigate whether calcipotriol exerts its therapeutic effects through ferroptosis and to elucidate its underlying molecular mechanisms using bioinformatics and cellular experiments. Differentially expressed genes (DEGs) and their functional enrichment were analyzed in psoriatic skin lesions using bioinformatics. A lipopolysaccharide (LPS)-induced HaCaT cell model was established to simulate psoriatic inflammation. The effects of calcipotriol at various concentrations and time points on HaCaT cell proliferation, apoptosis, and expression of key markers were assessed. Additionally, ferrostatin-1 (a ferroptosis inhibitor) and RSL3 (a ferroptosis inducer) were used to evaluate ferroptosis-related changes, including cell proliferation, apoptosis, reactive oxygen species (ROS) levels, glutathione (GSH) content (via ELISA), and protein expression of GPX4 and Ki-67 (via Western blot). Bioinformatics analysis revealed significant differential expression of ferroptosis-related genes, such as GPX4 and SLC7A11, in psoriatic lesions. Calcipotriol treatment inhibited HaCaT cell proliferation in a dose- and time-dependent manner, elevated ROS levels, and reduced GSH, GPX4, and Ki-67 expression. These effects were reversed by ferrostatin-1, which restored antioxidant defenses and cell viability. Conversely, RSL3 increased ROS levels and partially negated the protective effects of ferrostatin-1. These findings suggest that calcipotriol regulates ferroptosis-related gene expression and inhibits keratinocyte proliferation through induction of oxidative stress and ferroptosis, offering new insights into its mechanism of action in psoriasis treatment.

Lymph node metastasis is a key determinant of the poor survival rate in patients with tongue squamous cell carcinoma (TSCC). Therefore, inhibiting lymph node metastasis is a primary strategy for TSCC treatment. Our previous research found that dihydroartemisinin (DHA) inhibited the migration in human tongue squamous carcinoma Cal-27 cells. However, the effect and mechanism of DHA on lymph node metastasis are unknown in TSCC.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by molecular mechanisms that promote tumor progression and therapeutic resistance. PANoptosis, an integrated programmed cell death pathway involving apoptosis, necroptosis, and pyroptosis, has emerged as a key regulator of tumorigenesis, yet its modulation in GC is poorly understood. This study aimed to investigate the role of heat shock protein beta-1 (HSPB1) in regulating PANoptosis and its impact on GC progression, hypothesizing that HSPB1 overexpression suppresses PANoptosis to enhance tumor malignancy. We employed an integrative approach combining bioinformatics analysis of GEO (GSE54129), TCGA, and GSE15460 datasets with experimental validations. HSPB1 expression was assessed in 40 paired GC and normal tissues and multiple GC cell lines (AGS, MKN-45, NCI-N87, HGC-27, SNU-1) via qPCR, Western blot, and immunohistochemistry. Functional roles were explored by overexpressing or silencing HSPB1 in NCI-N87 and AGS cells, followed by proliferation, colony formation, migration, and apoptosis assays. In vivo effects were evaluated using a nude mouse xenograft model with shHSPB1-transfected cells, analyzing tumor growth and PANoptosis markers (P-MLKL, RIPK3, Cleaved Caspase-1, NLRP3, Cleaved Caspase-3) via Western blot, IHC, and TUNEL assays. Bioinformatics revealed HSPB1 as a PANoptosis-related prognostic biomarker, with elevated expression in GC tissues correlating with poor survival. Experimental validation confirmed HSPB1 overexpression in GC tissues and cell lines. HSPB1 overexpression enhanced proliferation, invasion, and migration while suppressing apoptosis by downregulating PANoptosis markers. Conversely, HSPB1 silencing inhibited these oncogenic traits and activated PANoptosis, significantly reducing tumor growth in vivo, accompanied by upregulated PANoptosis-related proteins and increased apoptosis.HSPB1 promotes GC progression by inhibiting PANoptosis, thereby enhancing tumor survival and aggressiveness, whereas its silencing activates these cell death pathways to suppress tumorigenesis. These findings establish HSPB1 as a critical regulator of PANoptosis in GC and a potential therapeutic target, offering new avenues for overcoming resistance and improving patient outcomes.

Hepatocarcinogenesis is a complex, multistep process that begins with fatty liver, progresses to fibrosis, and ultimately leads to cancer. Numerous etiological factors contribute to this progression, highlighting the importance of developing animal models to facilitate both basic and translational research aimed at discovering new therapeutic strategies. Gankyrin is a key oncoprotein involved in the genetic regulation of liver pathology.

The mitochondrial permeability transition pore (mPTP) is a supramolecular entity in the inner mitochondrial membrane composed of various protein complexes, which is a critical component in maintaining mitochondrial function and cellular homeostasis. In this review, we provide a comprehensive summary of the current detection techniques for mPTP, including spectrophotometry, patch clamping, fluorescent probes, and flow cytometry, which have the potential to reveal the status of mPTP and its roles in degenerative diseases, inflammation, tumors and other diseases. Additionally, we discuss promising new methods to detect mPTP including enhancement in precision, high sensitivity, multi-parameter analysis, and technological integration. These advances highlight new possibilities of clinical diagnosis and treatment for mitochondria-related diseases.

Prostate cancer (PCa) stands as one of the primary contributors to cancer-related mortality among men globally. It is reported that USP22 functions as an oncogene, while PNMA5 exhibits a significant pro-metastatic effect. This research investigation centered on examining the interplay between USP22 and PNMA5 and their collaborative role in enhancing PCa progression.