Search Results (212)

Acute Respiratory Distress Syndrome (ARDS) is a severe complication of acute lung injury (ALI) characterized by acute hypoxemic respiratory failure and diffuse alveolar damage, with a high mortality rate and a current lack of treatments beyond supportive care. Its complex pathophysiology involves immune cell activation, pro-inflammatory cytokine release, and disruption of the alveolar–capillary barrier, leading to pulmonary edema and fibrosis. This review explores the potential of small interfering RNA (siRNA) therapy as a novel pathogenetic treatment for ARDS. The mechanism of RNA interference is described, highlighting its high specificity for silencing target genes. The paper then evaluates various animal models used in ARDS preclinical research, noting the advantages of large animals (pigs) for their physiological similarity to humans and the suitability of rodents for studying long-term fibrotic stages. Finally, the review summarizes promising in vivo studies where siRNA-mediated knockdown of several genes (e.g., TIMP1, BTK, LCN2, HDAC7, CCL2, NOX4, TNFα and TLR4) significantly reduced inflammation, improved lung histology, and increased survival. The collective evidence underscores siRNA’s considerable potential for developing targeted therapies against ARDS, moving beyond symptomatic care to address the root molecular mechanisms of the disease. Full article

Background: High-fat diet (HFD) consumption is commonly linked to low-grade brain inflammation and increased risk of neurodegeneration. However, in our previous research, HFD exposure for up to 24 weeks did not increase pro-inflammatory cytokine expression or impair learning and spatial memory. To further investigate neuroimmune responses, we examined microglial activation at the transcriptional level. Methods: Male C57BL/6J mice were fed either a normal diet (ND) or HFD for 4, 12, or 24 weeks. Bulk RNA sequencing was performed across four brain regions (cerebellum, hippocampus, hypothalamus, cortex) to assess region-specific transcriptional responses. Results: HFD induced region- and time-dependent transcriptional changes. In the hypothalamus, 0/11/37 differentially expressed genes (DEGs; p-value < 0.05; fold change > 1.5) were detected at 4, 12, and 24 weeks, respectively. In the hippocampus, 2/41/42 DEGS were observed; in the cortex, 1/3/68 DEGS; and in the cerebellum, 27/0/0 DEGS at the respective time points, indicating minimal cerebellar involvement beyond the early time point. Across all conditions, three genes (Lcn2, Ch25h, Gimap9) were consistently regulated. Several DEGs were linked to microglial activation and inflammatory signaling. In the manuscript, we discuss 33 biologically relevant DEGs in detail. Transcriptomic signatures and pathway enrichment analyses suggest potential engagement of NF-κB-related pathways, although this interpretation remains indirect. Conclusions: These findings demonstrate that HFD selectively alters brain homeostasis by inducing region-specific transcriptional changes associated with microglial activation and inflammatory processes. While NF-κB-related pathways emerged as recurrent candidates, direct mechanistic validation is required. Full article

Background/Objectives: Laparoscopic surgery has become the pre-eminent surgical approach for performing general surgical and gynecological operations, but it can lead to musculoskeletal disorder in surgeons. This study aimed to investigate the musculoskeletal demands of completing four core laparoscopic skills tasks amongst Obstetrics and Gynecology (O&G) and General Surgery (GS) trainees, recognizing that differences between specialties may create different ergonomic and muscular demands. Methods: Ten O&G and ten GS trainees both performed the same four tasks to evaluate their core laparoscopic skills whilst using electromyography (EMG) to assess the physical demand of each task in the trainee groups as a percent of maximum voluntary contraction. Results: O&G trainees had significantly higher muscle activity when completing a hand–eye coordination (HEC) task (167.9 ± 63.8 vs. 92.5 ± 31.3%, p = 0.019), bimanual coordination (BMC) task (205.6 ± 80.7 vs. 106.9 ± 47.0%, p = 0.017), and suturing (267.7 ± 121.6 vs. 122.2 ± 33.0%, p = 0.016) task in the right trapezius and deltoid muscle groups compared to GS trainees. No difference was observed between trainee groups in the laparoscopic camera navigation (LCN) task (p = 0.438). Conclusions: There appears to be increased muscular activity in O&G compared to GS trainees during the same simulated laparoscopic tasks. The findings should inform training policy around the optimization of ergonomics to minimize the risk of musculoskeletal disorder. Full article

Background: Xuebijing Injection (XBJ), a plant-derived traditional Chinese medicine administered as an injection, is widely used in clinical practice to treat various acute critical illnesses including severe acute pancreatitis (SAP). The mechanisms by which XBJ alleviates SAP remain elusive. Methods: Active components of XBJ were identified using UPLC-QTOF/MS. A mouse SAP model was established by intraperitoneal injections of cerulein (50 μg/kg/h × 7) followed by lipopolysaccharide (10 mg/kg). XBJ of 2.5, 5, and 10 mL/kg was co-administered twice after induction of SAP. The protective effects of XBJ on pancreatic acinar cells were further investigated in vitro. An integrated analysis of transcriptomic data from human and mouse blood, as well as mouse lung, combined with network pharmacology were employed to delineate the therapeutic mechanisms of XBJ on SAP, followed by pancreatic immunoblotting and proteomics validation. Results: Component analysis revealed 9 active ingredients of XBJ. XBJ at 10 mL/kg had the best effect and consistently decreased pancreatic, lung, and circulatory pro-inflammatory indices. XBJ dose-dependently reduced necrotic cell death activation. Transcriptomics, proteomics and network pharmacology analyses identified 14 key targets, with IL-17-related signaling pathways being the most significant. Experimental validation further confirmed that XBJ significantly reduced serum levels of key IL-17-related inflammatory cytokines (such as IL-17, IL-1β, IL-6, and TNF-α) and downregulated the mRNA expression of related inflammatory factors in pancreatic tissue. Virtual docking and surface plasmon resonance demonstrate that hydroxysafflor yellow A had the highest binding affinity with MMP-9, MAPK14, and LCN2. Crucially, subsequent pancreatic immunoblotting and proteomics analyses did not confirm significant direct modulation of these targets at the protein level within pancreatic tissue. Conclusions: XBJ attenuates SAP severity by quelling pro-inflammatory mediators, an effect chiefly attributed to modulating systemic IL-17–related signaling rather than direct pancreatic intervention. Full article

Neutropenia is a common complication in oncology patients receiving chemotherapy, and rapid regeneration of functional neutrophils is critical for effective management. Bletilla striata polysaccharide (BSP) has shown therapeutic potential, but its mechanisms and molecular targets remain unclear. Here, we demonstrate that BSP accelerates the recovery of white blood cells, particularly neutrophils, in a chemotherapy-induced neutropenia (CIN) mouse model with cyclophosphamide (CY). The regenerated neutrophils retained phagocytic activity against bacteria, and BSP treatment significantly reduced mortality in the endotoxin-induced mouse death model. Furthermore, BSP enhanced the repopulation of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and promoted cell-cycle entry, resulting in increased frequencies of long-term hematopoietic stem cells (LT-HSCs), multipotent progenitors 2 (MPP2), and MPP3/4 subsets. Both in vitro colony formation and in vivo competitive transplantation assays confirmed that BSP reshapes hematopoietic reconstitution and corrects aberrant myeloid differentiation. PCR array analysis of HSPCs indicated that this process is mediated by C/EBPε and its downstream genes (LTF, LCN2, and ELANE). Consistently, BSP failed to support myeloid reconstitution following C/EBPε knockdown in vitro. In a C/EBPε knockout mouse model, HSPCs repopulation and regeneration were impaired, and BSP failed to promote neutrophil recovery after CY challenge or the mobilization of MPP2 and MPP3/4 subsets. The regulatory effects of BSP on C/EBPε target genes were also abolished. In conclusion, our findings identify C/EBPε as a key mediator of BSP activity, driving HSPCs repopulation and restoring hematopoietic function. These results highlight BSP as a potential therapeutic strategy for chemotherapy-induced neutropenia. Full article

Olfactory perception depends on soluble proteins in the perireceptor environment that support odorant transport, mucosal protection, and tissue homeostasis. In insects, odorant-binding proteins (OBPs) in the sensillum lymph are indispensable for odor detection, whereas in humans the indispensability of OBPs (OBP2A/2B) remains unclear because they are inconsistently detected in nasal mucus. Consequently, it remains unclear whether other soluble proteins compensate for this function or how they contribute to odorant processing and signal transmission within the olfactory mucus. Accumulating evidence indicates that OBP-like lipocalins (LCN1, LCN2, LCN15) and apolipoprotein D, together with bactericidal/permeability-increasing (BPI)-fold proteins, act as major mediators of odorant solubilization, antimicrobial defense, oxidative stress regulation, and extracellular matrix (ECM) remodeling. Alterations in those proteins and ECM organization are linked to idiopathic and age-related smell loss, chronic rhinosinusitis, and neurodegenerative disorders, underscoring their broad relevance at the interface of chemosensation, mucosal defense, and brain health. Major unresolved issues include the functional indispensability of human OBPs, the receptor-specific contributions of OBP-like proteins, and the mechanistic relationships linking olfactory proteome remodeling, sensory signaling, and disease progression. This review provides an integrative overview of structural and mechanistic insights, highlights current controversies, and proposes future research directions, including receptor–protein mapping, integrated structural–functional studies, structural–functional analysis of OBP–ECM networks, and clinical validation of OBP-related biomarkers. Full article

Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) are major neurodegenerative disorders that share certain pathological features but differ in their genetic etiology and clinical presentation. Their potential molecular intersections remain incompletely understood. In this research, we conducted a comparative transcriptomic analysis using postmortem brain RNA-seq datasets from AD (GSE53697), PD (GSE68719), and HD (GSE64810) to identify shared and disease-specific transcriptional signatures. Differentially expressed genes (DEGs) were determined and functionally characterized through Gene Ontology (GO) enrichment. Protein–protein interaction (PPI) networks were generated using STRING and visualized in Cytoscape to identify central hub genes, followed by gene–disease and drug-interaction analyses to assess functional and therapeutic relevance. Ten DEGs were found to overlap among the three disorders, exhibiting variable directions of regulation across diseases. Enrichment analysis indicated convergence on immune- and inflammation-related biological processes. Key hub genes, including MMP9, LCN2, CXCL2, CCL2, S100A8, and S100A9, were identified as central nodes within the PPI network. Although the overlap in DEGs was limited, the findings suggest that neuroinflammatory signaling represents a shared molecular theme across AD, PD, and HD, warranting further validation in independent cohorts. Full article

Cardio-kidney-metabolic (CKM) syndrome represents an integrated clinical and molecular continuum encompassing metabolic dysfunction, cardiovascular disease and chronic kidney disease. This multidimensional disorder arises from interdependent biological pathways that extend beyond conventional risk factors. Emerging evidence highlights a group of adipokines and vascular modulators—including retinol-binding protein 4 (RBP4), lipocalin 2 (LCN2), apolipoprotein M (ApoM), Klotho and matrix Gla protein (MGP)—emerging molecular modulators with potential involvement in CKM pathophysiology. Pro-inflammatory adipokines such as RBP4 and LCN2 contribute to insulin resistance, oxidative stress and endothelial dysfunction. In contrast, protective molecules including ApoM and Klotho preserve nitric oxide bioavailability, lipid metabolism and antioxidant defense. MGP modulates vascular calcification and adipose remodeling, with its inactive form (dp-ucMGP) linked to vascular stiffness and renal decline. The combined dysregulation of these molecules sustains cycles of inflammation, oxidative stress and tissue remodeling that drive CKM progression. Collectively, current data support their dual role as biomarkers and therapeutic targets. Nonetheless, clinical translation remains limited, emphasizing the need for standardized assays, longitudinal validation, and integrative multimarker approaches within precision medicine frameworks for CKM syndrome. Full article

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder with high mortality and long-term disability. It is more prevalent in women than men, but most preclinical research has been performed in male animals. Upregulation of lipocalin-2 (Lcn2), an acute-phase protein involved in iron homeostasis and neuroinflammation, has been implicated in hemorrhagic brain injury in male animals. The purpose of this study was to examine whether genetic deletion of Lcn2 also reduces early brain injury after SAH in female mice. Adult female wild-type (WT) and Lcn2 knockout (KO) mice were subjected to endovascular perforation to induce SAH. Lcn2 expression was assessed by immunohistochemistry and Western blotting, while brain injury was evaluated using MRI T2 lesion measurement, blood–brain barrier (BBB) permeability assays, Fluoro-Jade C staining, and Garcia’s neurological scoring. We found that Lcn2 expression was upregulated in multiple brain regions after SAH, particularly in astrocytes. Compared with WT mice, Lcn2 KO mice exhibited significantly reduced oxidative stress, attenuated ferritin induction, smaller T2 lesions, decreased BBB leakage, reduced neuronal degeneration, and improved neurological recovery over 7 days. These findings identify Lcn2 as a critical mediator of early brain injury after SAH in female mice. These results further support targeting Lcn2 as a therapeutic strategy to reduce brain damage and improve outcomes in SAH patients. Full article

Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic molecules. However, several studies have shown that aberrant LCN2 expression is associated with poor prognosis in various malignancies, including breast cancer, which is the most common cancer in women worldwide and can be classified into four molecular subtypes. Among these, TNBC represents a disproportionately aggressive subtype characterized by poor prognosis and high metastatic potential. Although LCN2 has been extensively studied in breast cancer overall, its specific role in TNBC progression and metastasis is only beginning to be understood. Recent evidence suggests that LCN2 contributes to several tumor-promoting processes such as angiogenesis, therapy resistance and modulation of the tumor microenvironment. Moreover, LCN2 appears to influence organ-specific metastasis, particularly to the lung and brain, while its role in liver and bone dissemination remains unclear. Collectively, current data identify LCN2 as a critical mediator of TNBC progression and highlight its potential as a prognostic factor and modulator of disease progression. This review aims to summarize insights from both in vitro and in vivo studies, with particular focus on the role of LCN2 in the metastatic cascade, while also addressing existing research gaps and critically evaluating the current findings. Full article

The conventional OLSR protocol faces substantial challenges in highly dynamic and interference-intensive UAV environments, including high mobility, frequent topology changes, and insufficient adaptability to electromagnetic interference. This paper proposes a cross-layer improved OLSR protocol, OLSR-LCN, that integrates three evaluation metrics—link lifetime (LL), channel interference index (CII), and node load (NL)—to enhance communication stability and network performance. The proposed protocol extends the OLSR control message structure and employs enhanced MPR selection and routing path computation algorithms. LL prediction enables proactive selection of stable communication paths, while the CII helps avoid heavily interfered nodes during MPR selection. Additionally, the NL metric facilitates load balancing and prevents premature node failure due to resource exhaustion. Simulation results demonstrate that across different UAV flight speeds and network scales, OLSR-LCN protocol consistently outperforms both the OLSR and the position-based OLSR in terms of end-to-end delay, packet loss rate, and network efficiency. The cross-layer optimization approach effectively addresses frequent link disruptions, interference, and load imbalance in dynamic environments, providing a robust solution for reliable communication in complex FANETs. Full article

Background/Objectives: For surgical candidates with metastatic renal cell carcinoma with a tumor thrombus (mRCC-TT), surgery is cytoreductive nephrectomy with tumor thrombectomy (CN-TT). This is carried out through an open (OCN-TT), laparoscopic (LCN-TT), or robotic (RCN-TT) approach. The purpose of this study was to compare survival outcomes to CN-TT by operative approach. Methods: This was a retrospective analysis of all patients with a diagnosis of mRCC-TT, who underwent CN-TT from a multi-institutional database from 1999–2024. Metastatic locations were qualified as either lung, bone, brain, liver, retroperitoneum, adrenal, paraaortic nodes, or other nodes. Progression was defined as radiographic evidence of recurrence or metastasis not seen on imaging prior to CN-TT. Progression locations were all metastatic locales previously noted plus the nephrectomy bed. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were calculated. Comparisons were performed between OCN-TT, LCN-TT, and RCN-TT. Results: A total of 131 patients were included in the analysis (97 OCN-TT, 25 LCN-TT, and 9 RCN-TT). The TT level was not different (p-value > 0.05) by approach (p-value > 0.05). Preoperative tumor size, final pathologic tumor subtype, and postoperative tumor size were equivalent between the three surgical approaches (p-value > 0.05). Rates of progression were equivalent as were all locations of disease progression in the study (p-value > 0.05). Median OS was 1.6 years in OCN-TT, 1.5 years in LCN-TT, and 2.5 years in RCN-TT (p-value = 0.42). Median CSS was 2.1 years in OCN-TT, 3 years in LCN-TT, and 2.5 years in RCN-TT (p-value = 0.86). PFS was 0.8 years in OCN-TT, 1.2 years in LCN-TT, and 1.2 years in RNC-TT (p-value = 0.76). Conclusions: The operative approach does not affect survival outcomes for CN-TT. Surgeon comfort and patient preference should weigh heavily in operative decision making. Full article

IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis, with heterogeneous clinical outcomes. Conventional prognostic factors, such as proteinuria, eGFR, and Oxford histologic classification, have poor sensitivity and specificity. Recently, transcriptomic profiling has been employed to provide insights into the molecular definition of IgAN and facilitate patient stratification in those at risk of disease progression. In this review, we summarize our current understanding of IgAN derived from bulk RNA sequencing, single-cell transcriptomics, spatial transcriptomics, and gene expression profiling to elucidate the molecular characteristics of IgAN. Bulk transcriptomics of glomerular and tubulointerstitial compartments highlighted consistently upregulated genes (e.g., CCL2, CXCL10, LCN2, HAVCR1, COL1A1) and altered pathways (e.g., NF-κB, TGF-β, JAK/STAT, and complement) that are associated with clinical decline. Single-cell and single-nucleus RNA-sequencing has also identified the value of pathogenic cell types and regulatory networks in mesangial cells, tubular epithelium, and immune infiltrates. Furthermore, noninvasive transcriptomic signatures developed from urine and blood may represent useful real-time surrogates of tissue activity. With the advent of integrated analyses and machine learning approaches, personalized risk models that outperform traditional metrics are now available. While challenges remain, particularly related to standardization, cohort size, and clinical deployment, transcriptomics is likely to revolutionize IgAN by providing early risk predictions and precision therapeutics. Unlike prior reviews, our work provides an integrative synthesis across bulk, single-cell, spatial, and noninvasive transcriptomics, linking molecular signatures directly to clinical translation in risk stratification and precision therapeutics. Full article

This study investigated the protective effect of fermented milk by Lacticaseibacillus rhamnosus D1 in a murine model of Typhoid fever, focusing on cytokines, antimicrobial peptides and microbiota modulation. BALB/c mice were pre-treated with milk fermented by L. rhamnosus D1 prior to Salmonella Typhimurium challenge. Outcomes assessed included survival, weight change, bacterial translocation, mRNA expression of cytokines and antimicrobial peptides, in addition to gut microbiota modulation. Mice receiving fermented milk exhibited higher survival rates, reduced bacterial translocation and attenuated weight loss compared to controls. mRNA expression analyses revealed that L. rhamnosus D1 pre-treatment suppressed the expression of pro-inflammatory cytokines (IFN-γ, IL-6 and IL-12) and upregulated anti-inflammatory cytokines (IL-5, IL-10 and TGF-β), as well as antimicrobial peptides (Reg3β, Reg3γ and Lcn2). Furthermore, we observed that the consumption of fermented milk changed the gut microbiota of infected mice, not only by modulating the existing taxa, but also by facilitating the emergence of unique, potentially beneficial microbial lineages, such as Muribaculum, Roseburia, Intestinimonas, Bdellovibrio and Facklamia. These findings indicate that L. rhamnosus D1 protected mice against S. Typhimurium infection through immunomodulatory and microbiota-mediated mechanisms, changing mucosal immunity and strengthening the intestinal barrier by modulating gut microbiota and immune responses, in addition to promoting host antimicrobial defenses. Full article

Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with subtypes ranging from patchy alopecia (AAP) to alopecia totalis and universalis (AT/AU). The aim of this research is to investigate molecular features across AA severity by performing an integrated analysis of scalp transcriptomic datasets (GSE148346, GSE68801, GSE45512, GSE111061) and matched serum proteomic data from GSE148346. Differential expression analysis indicated that, relative to normal scalp, non-lesional AA tissue shows early immune activation—including Type 1 (C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CD8a molecule (CD8A), C-C motif chemokine ligand 5 (CCL5)) and Type 2 (CCL13, CCL18) signatures—together with reduced expression of hair-follicle structural genes (keratin 32(KRT32)–35, homeobox C13 (HOXC13)) (FDR < 0.05, |fold change| > 1.5). Lesional AAP and AT/AU scalp showed stronger pro-inflammatory upregulation and greater loss of keratins and keratin-associated proteins (KRT81, KRT83, desmoglein 4 (DSG4), KRTAP12/15) compared with non-lesional scalp (FDR < 0.05, |fold change| > 1.5). Ferroptosis-associated genes (cAMP responsive element binding protein 5 (CREB5), solute carrier family 40 member 1 (SLC40A1), (lipocalin 2) LCN2, SLC7A11) and IRS (inner root sheath) differentiation genes (KRT25, KRT27, KRT28, KRT71–KRT75, KRT81, KRT83, KRT85–86, trichohyalin (TCHH)) were consistently repressed across subtypes, with the strongest reductions in AT/AU lesions versus AAP lesions, suggesting that oxidative-stress pathways and follicular structural integrity may contribute to subtype-specific pathology. Pathway analysis of lesional versus non-lesional scalp highlighted enrichment of IFN-α/γ, cytotoxic, and IL-15 signaling. Serum proteomic profiling, contrasting AA vs. healthy controls, corroborated scalp findings, revealing parallel alterations in immune-related proteins (CXCL9–CXCL10, CD163, interleukin-16 (IL16)) and structural markers (angiopoietin 1 (ANGPT1), decorin (DCN), chitinase-3-like protein 1 (CHI3L1)) across AA subtypes. Together, these data offer an integrated view of immune, oxidative, and structural changes in AA and found ferroptosis-related and IRS genes, along with immune signatures, as potential molecular indicators to support future studies on disease subtypes and therapeutic strategies. Full article