Lymphatic vessels in patients with crescentic glomerulonephritis: association with renal pathology and prognosis.

BACKGROUND: Various immune cells, including T cells, B cells, macrophages, and neutrophils contribute to the development of crescentic glomerulonephritis. Previous animal studies have suggested that lymphangiogenesis is involved in the migration of inflammatory cells and the activation of adaptive immunity. However, the extent of the association between lymphatic vessels and crescentic glomerulonephritis severity and prognosis remains unknown. METHODS AND RESULTS: In this study, we assessed lymphatic vessel density in 71 patients with crescentic glomerulonephritis who underwent renal biopsies between June 2017 and June 2022. By immunohistochemistry and immunofluorescence, we identified increased lymphatic vessel density in the kidneys of patients with crescentic glomerulonephritis compared to controls. Lymphatic vessels were categorized as total, periglomerular, and interstitial. Spearman's rank correlation analysis showed a positive correlation between total and periglomerular lymphatic vessel density and glomerular crescent proportion. High lymphatic vessel density (total and periglomerular) correlated with declining kidney function, increased proteinuria, and severe glomerular and interstitial pathology. Interstitial lymphatic vessel density had minimal relationship with renal lesions. After a median duration of 13 months of follow-up, higher total and periglomerular lymphatic vessel density was associated with poorer prognosis. Transcriptomic analysis revealed increased immune cell activation and migration in crescentic glomerulonephritis patients compared to healthy controls. Periglomerular lymphatic vessels might play a significant role in immune cell infiltration and renal injury. CONCLUSION: Elevated lymphatic vessel density in patients with crescentic glomerulonephritis is associated with poor prognosis and may serve as a predictive factor for adverse outcomes in these patients.

Identification of driver genes in lupus nephritis based on comprehensive bioinformatics and machine learning.

Background: Lupus nephritis (LN) is a common and severe glomerulonephritis that often occurs as an organ manifestation of systemic lupus erythematosus (SLE). However, the complex pathological mechanisms associated with LN have hindered the progress of targeted therapies. Methods: We analyzed glomerular tissues from 133 patients with LN and 51 normal controls using data obtained from the GEO database. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key gene modules. The least absolute shrinkage and selection operator (LASSO) and random forest were used to identify hub genes. We also analyzed immune cell infiltration using CIBERSORT. Additionally, we investigated the relationships between hub genes and clinicopathological features, as well as examined the distribution and expression of hub genes in the kidney. Results: A total of 270 DEGs were identified in LN. Using weighted gene co-expression network analysis (WGCNA), we clustered these DEGs into 14 modules. Among them, the turquoise module displayed a significant correlation with LN (cor=0.88, p<0.0001). Machine learning techniques identified four hub genes, namely CD53 (AUC=0.995), TGFBI (AUC=0.997), MS4A6A (AUC=0.994), and HERC6 (AUC=0.999), which are involved in inflammation response and immune activation. CIBERSORT analysis suggested that these hub genes may contribute to immune cell infiltration. Furthermore, these hub genes exhibited strong correlations with the classification, renal function, and proteinuria of LN. Interestingly, the highest hub gene expression score was observed in macrophages. Conclusion: CD53, TGFBI, MS4A6A, and HERC6 have emerged as promising candidate driver genes for LN. These hub genes hold the potential to offer valuable insights into the molecular diagnosis and treatment of LN.

Current status of research on endophytes of traditional Tibetan medicinal plant and their metabolites.

The Qinghai-Tibet Plateau, known as the "Third Pole of the World," has a rich variety of medicinal plants that play an important role in the field of medicine due to its unique geographical environment. However, due to the limited resources of Tibetan medicinal plants and the fragility of the ecological environment of the Qinghai-Tibet Plateau, more and more Tibetan medicinal plants are on the verge of extinction. As a reservoir of biologically active metabolites, endophytes of medicinal plants produce a large number of compounds with potential applications in modern medicine (including antibacterial, immunosuppressive, antiviral, and anticancer) and are expected to be substitutes for Tibetan medicinal plants. This paper reviews 12 Tibetan medicinal plants from the Qinghai-Tibet Plateau, highlighting the diversity of their endophytes, the diversity of their metabolites and their applications. The results show that the endophytes of Tibetan medicinal plants are remarkably diverse, and the efficacy of their metabolites involves various aspects, such as antioxidant, anti-disease and anti-parasitic. In addition, conservation measures for the resources of Tibetan medicinal plants are summarised to provide a reference for an in-depth understanding of the endophytes of Tibetan medicinal plants and to stimulate the scientific community to bioprospect for the endophytes of Tibetan medicinal plants, as well as to provide ideas for their rational exploitation.

High Renal Mast Cell Density Is Associated with Poor Prognosis in Patients with Immunoglobulin A Nephropathy.

INTRODUCTION: This observational cohort study evaluated the prognostic value of mast cells in the pathogenesis and progression of IgA nephropathy. METHODS: A total of 76 adult IgAN patients were enrolled into this study from Jan 2007 and June 2010. Immunohistochemistry and immunofluorescence were used to identify tryptase-positive mast cells in renal biopsy samples. Patients were classified into Tryptasehigh and Tryptaselow groups. Depending on an average of 96-month follow-up, the predictive value of tryptase-positive mast cells in IgAN progression was analyzed. RESULTS: Tryptase-positive mast cells were found frequently in IgAN kidneys while rarely observed in normal kidneys. We also found IgAN patients in Tryptasehigh group presented both severe clinical and pathological renal manifestations. Furthermore, Tryptasehigh group contained more interstitial macrophages and lymphocytes infiltration than Tryptaselow group. Higher tryptase-positive cells density is associated with poor prognosis in patients with IgAN. CONCLUSIONS: High renal mast cells density is associated with severe renal lesions and poor prognosis in patients with Immunoglobulin A nephropathy. High renal mast cells density might be used as a predictor of poor prognosis in patients with IgAN.

Stealth-like polysarcosine-modified nanoparticles with low dye doses and long blood circulation for efficient breast cancer pulmonary metastasis imaging.

Fluorescence imaging (FLI) in the near-infrared-II (NIR-II; 1000-1700 nm) window holds great potential for cancer metastasis imaging owing to its deep tissue penetration and a high signal-to-background ratio. However, currently reported organic NIR-II contrast agents generally present problems such as poor water solubility, low NIR-II fluorescence quantum yield (QY), short blood circulation half-life (t1/2), high injection doses, and undesirable tumor accumulation. In this study, an NIR-II small-molecule-based polymer (TQF-PSar) modified with four dense/hydrophilic polysarcosine (PSar) arms was prepared for efficient breast cancer pulmonary metastasis imaging. The NIR-II intensity of TQF-PSar (whose QY was calculated to be 1%) was 26.4-fold higher than that of the PEGylated nanoparticles (TQF-PEG NPs) at the same low dye dose (core TQF concentration: 2.5 µg mL-1). Moreover, owing to the ideal stealth character, TQF-PSar displayed a more prolonged blood circulation t1/2 (36.9 h) and better tumor accumulation capability than TQF-PEG NPs even at this low dye concentration. Finally, the successful use of TQF-PSar in noninvasive NIR-II FLI for breast cancer pulmonary metastasis was demonstrated in living mice.

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy.

AIMS: Glomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long-term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression. METHODS AND RESULTS: From June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3high group (34 patients) and a glomerular C3low group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow-up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3high group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3low group. Renal biopsies in the C3high group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-γ than those in the C3low group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end-stage renal disease. CONCLUSIONS: A high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long-term poor renal survival for IgAN patients.

Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy.

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has been challenged. Here, we fabricate iron oxide nanoparticle shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform. Iron oxide nanoparticles serve as both magnetic and photothermal agents. Once intravenously injected, NSMs can be magnetically guided to the tumor site. Ultrasound triggers the release of iron oxide nanoparticles, facilitating the penetration of nanoparticles deep into the tumor due to the cavitation effect of microbubbles. Thereafter, magnetic hyperthermia and photothermal therapy can be performed on the tumor for combinational cancer therapy, a solution for cancer resistance due to the tumor heterogeneity. In this protocol, the synthesis and characterization of NSMs including structural, chemical, magnetic and acoustic properties were performed. In addition, the anti-cancer efficacy by thermal therapy was investigated using in vitro cell cultures. The proposed delivery strategy and combination therapy holds great promise in cancer treatment to improve both delivery and anticancer efficacies.

Association between dense PAX1 promoter methylation and HPV16 infection in cervical squamous epithelial neoplasms of Xin Jiang Uyghur and Han women.

DNA methylation is an epigenetic alteration that may lead to carcinogenesis by silencing key tumor suppressor genes. Hypermethylation of the paired box gene 1 (PAX1) promoter is important in cervical cancer development. Here, PAX1 methylation levels were compared between Uyghur and Han patients with cervical lesions. Data on PAX1 methylation in different cervical lesions were obtained from the Gene Expression Omnibus (GEO) database, whereas data on survival and PAX1 mRNA expression in invasive cervical cancer (ICC) were retrieved from the Cancer Genome Atlas (TCGA) database. MassARRAY spectrometry was used to detect methylation of 19 CpG sites in the promoter region of PAX1, whereas gene mass spectrograms were drawn by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Human papillomavirus (HPV) 16 infection was detected by polymerase chain reaction. PAX1 methylation in high-grade squamous intraepithelial lesion (HSIL) and ICC was significantly higher than in normal tissues. PAX1 hypermethylation was associated with poor prognosis and reduced transcription. ICC-specific PAX1 promoter methylation involved distinct CpG sites in Uyghur and Han patients HPV16 infection in HSIL and ICC patient was significantly higher than in normal women (p < 0.05). Our study revealed a strong association between PAX1 methylation and the development of cervical cancer. Moreover, hypermethylation of distinct CpG sites may induce HSIL transformation into ICC in both Uyghur and Han patients. Our results suggest the existence of ethnic differences in the genetic susceptibility to cervical cancer. Finally, PAX1 methylation and HPV infection exhibited synergistic effects on cervical carcinogenesis.