Urinary matrix metalloproteinase-7 is a sensitive biomarker to evaluate renal tubular injury in patients with minimal change disease and focal segmental glomerulosclerosis.

Objective: To explore the advantages of urinary matrix metalloproteinase-7 (MMP-7) in evaluating renal tubular injury in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients compared with urinary cystatin C (CysC) and retinol-binding protein (RBP). Methods: Serum and urine samples were collected from 20 healthy volunteers, and 40 MCD and 20 FSGS patients. Serum and urinary MMP-7 levels were measured by enzyme-linked immunosorbent assay. Urinary total protein, CysC and RBP levels were measured by automatic specific protein analyzer and compared with urinary creatinine level for calibration. The renal tissue serial sections were stained by MMP-7 immunohistochemistry and periodic acid-Schiff. Results: Under light microscopy, MMP-7 granular weak positive expression was showed sporadically in the cytoplasm of a few renal tubular epithelial cells without obvious morphological changes in MCD patients, and MMP-7-positive expression was observed in the cytoplasm of some renal tubular epithelial cells in FSGS patients. There was no significant difference in serum MMP-7 level among the three groups. Compared with the control group, the urinary MMP-7 level in MCD patients was higher, but urinary CysC and RBP levels were not increased significantly. Compared with the control group and MCD patients, urinary MMP-7, CysC and RBP levels in FSGS patients were upregulated significantly. Conclusions: Urinary MMP-7 could not only evaluate the mild renal tubular epithelial cells injury in MCD patients with massive proteinuria, but also evaluate the continuous renal tubular epithelial cells injury in FSGS patients.

Efficacy of pericapsular nerve group block vs. fascia iliaca compartment block for Hip surgeries: A systematic review and meta-analysis.

Objective: The review aimed to compare outcomes of pericapsular nerve group block (PENG) vs. fascia iliaca compartment block (FICB) for patients undergoing hip surgeries. Methods: Randomized controlled trials (RCTs) published in the databases of PubMed, CENTRAL, Embase, and Web of Science comparing PENG vs. FICB for pain control after hip surgeries were included in the review. Results: Six RCTs were included. 133 patients received PENG block and were compared with 125 patients receiving FICB. Our analysis showed no difference in 6 h (MD: -0.19 95% CI: -1.18, 0.79 I 2 = 97% p = 0.70), 12 h (MD: 0.04 95% CI: -0.44, 0.52 I 2 = 72% p = 0.88) and 24 h (MD: 0.09 95% CI: -1.03, 1.21 I 2 = 97% p = 0.87) pain scores between PENG and FICB groups. Pooled analysis showed that mean opioid consumption in morphine equivalents was significantly less with PENG as compared to FICB (MD: -8.63 95% CI: -14.45, -2.82 I 2 = 84% p = 0.004). Meta-analysis of three RCTs showed no variation in the risk of postoperative nausea and vomiting in the two groups. The quality of evidence on GRADE was mostly moderate. Conclusion: Moderate quality of evidence suggests that PENG may result in better analgesia than FICB in patients undergoing hip surgeries. Data on motor-sparing ability and complications are scarce to draw conclusions. Further large-scale and high-quality RCTs should be conducted to supplement current findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022350342.

17beta-estradiol alleviates contusion-induced skeletal muscle injury by decreasing oxidative stress via SIRT1/PGC-1α/Nrf2 pathway.

PURPOSE: This study aimed to investigate the role of 17ß-estradiol (E2) in the repair of contusion-induced myoinjury in mice and to identify the underlying molecular mechanisms. METHODS: In vivo, contusion protocol was performed for preparing mice myoinjury model, and Injection (i.p.) of 17ß-estradiol (E2) or estrogen receptor antagonist ICI 182,780, or ovariectomy (OVX), was used to alter estrogen level of animal models. In vitro, C2C12 myoblasts were treated with H2O2 (oxidative stress inducer), SIRT1 inhibitor EX527, or aromatase inhibitor anastrozole. Serum E2 level was assessed by enzyme-linked immunosorbent assay (ELISA). Muscle damage repair was evaluated by H&E staining and the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH). The oxidative stress was estimated by the levels of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Western blot was performed to measure the protein expressions of SIRT1, PGC-1α, Nrf2, and HO-1. RESULTS: We observed the elevated serum E2 levels and the upregulated oxidative stress in damaged muscle in female mice after contusion-induction. The E2 administration in vivo alleviated contusion-induced myoinjury in OVX mice by reducing CK and LDH activities, suppressing oxidative stress, and enhancing the expression levels of SIRT1, PGC-1α, Nrf2, and HO-1. These effects were inhibited by treatment with an ERα/ß antagonist. Moreover, EX527 or anastrozole treatment exacerbated H2O2-induced growth inhibition and oxidative stress, and expression downregulation of SIRT1, PGC-1α, Nrf2, and HO-1 in C2C12 cells in vitro. CONCLUSION: Our results suggest that E2 is a positive intervention factor for muscle repair followed contusion-induced myoinjury, through its effects on suppressing oxidative stress via activating the SIRT1/PGC-1α/Nrf2 pathway.

Four novel mutations identification in 17 beta-hydroxysteroid dehydrogenase-3 deficiency and our clinical experience: possible benefits of early treatment.

Introduction: Individuals with 17-beta-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) deficiency face a multitude of challenges, primarily concerning genital appearance, potential malignancy risks, and fertility issues. This study reports our findings from an investigation involving five individuals affected by 17ß-HSD3 deficiency, ranging in age from pre-adolescence to adolescence. Notably, we identified four previously unreported mutations in these subjects. Methods: Our study included a comprehensive evaluation to determine the potential occurrence of testicular tumors. The methods involved clinical examinations, genetic testing, hormone profiling, and patient history assessments. We closely monitored the progress of the study subjects throughout their treatment. Results: The results of this evaluation conclusively ruled out the presence of testicular tumors among our study subjects. Moreover, four of these individuals successfully underwent gender transition. Furthermore, we observed significant improvements in genital appearance following testosterone treatment, particularly among patients in the younger age groups who received appropriate treatment interventions. Discussion: These findings underscore the critical importance of early intervention in addressing concerns related to genital appearance, based on our extensive clinical experience and assessments. In summary, our study provides insights into the clinical aspects of 17ß-HSD3 deficiency, emphasizing the vital significance of early intervention in addressing genital appearance concerns. This recommendation is supported by our comprehensive clinical assessments and experience.

[Targeted binding of estradiol with ESR1 promotes proliferation of human chondrocytes in vitro by inhibiting activation of ERK signaling pathway].

OBJECTIVE: To investigate the effect of estradiol (E2)/estrogen receptor 1 (ESR1) on the proliferation of human chondrocytes in vitro and explore the molecular mechanism. METHODS: The Ad-Easy adenovirus packaging system was used to construct and package the ESR1-overexpressing adenovirus Ad-ESR1. Western blotting and qPCR were used to detect the expression of ESR1 protein and mRNA in human chondrocyte C28I2 cells. In the cells treated with different adenoviruses, the effects of E2 were tested on the expressions of proteins related with cell autophagy and apoptosis and the phosphorylation of ERK signaling pathway using Western blotting. Immunofluorescence assay was used to observe the intracellular autophagic flow, flow cytometry was performed to analyze the cell apoptosis rate and the cell cycle changes, and qPCR was used to detect the expressions of PCNA, cyclin B1 and cyclin D1 mRNAs. The inhibitory effect of the specific inhibitor of ERK on the expressions of autophagy- and apoptosis-related genes at both the protein and mRNA levels were detected using Western blotting and qPCR. RESULTS: Transfection with the recombinant adenovirus overexpressing ESR1 and E2 treatment of C28I2 cells significantly enhanced the expressions of autophagy-related proteins LC3, ATG7, promoted the colocalization of LC3 and LAMP1 in the cytoplasm, increased the expressions of the proliferation-related marker genes PCNA, cyclin B1 and cyclin D1, and supressed the expressions of cleaved caspase-3, caspase-12 and pERK. RNA interference of ESR1 obviously lowered the expression levels of autophagy-related proteins in C28I2 cells, causing also suppression of the autophagic flow, increments of the expressions of apoptosis-related proteins and pERK, and down-regulated the expressions of the proliferation marker genes. Blocking ERK activation with the ERK inhibitor obviously inhibited the effects of E2/ESR1 on autophagy, proliferationrelated gene expressions and cell apoptosis. CONCLUSIONS: The targeted binding of E2 with ESR1 promotes the proliferation of human chondrocytes in vitro possibly by inhibiting the activation of ERK signaling pathway to promote cell autophagy and induce cell apoptosis.

Targeted cancer imaging and photothermal therapy via monosaccharide-imprinted gold nanorods.

Plasmonic nanomaterials have been widely used for photothermal therapy (PTT) of cancer, but their recognition specificity remains challenging. We prepared monosaccharide-imprinted gold nanorods (AuNRs) for targeted cancer PTT, using sialic acid (SA) as a representative monosaccharide. The SA-imprinted AuNRs exhibited good specificity, enabling the killing of cancer cells without damaging healthy cells.

Probing Low-Copy-Number Proteins in a Single Living Cell.

Single-cell analysis techniques are essential for understanding the microheterogeneity and functions of cells. Low-copy-number proteins play important roles in cell functioning, but their measurement in single cells remains challenging. Herein, we report an approach, called plasmonic immunosandwich assay (PISA), for probing low-copy-number proteins in single cells. This approach combined in vivo immunoaffinity extraction and plasmon-enhanced Raman scattering (PERS). Target proteins were specifically extracted from the cells by microprobes modified with monoclonal antibody or molecularly-imprinted polymer (MIP), followed by labeling with Raman-active nanotags. The PERS detection, with Raman intensity enhanced by 9 orders of magnitude, provided ultrasensitive detection at the single-molecule level. Using this approach, we found that alkaline phosphatase and survivin were expressed in distinct levels in cancer and normal cells, and that extended culture passage resulted in reduced expression of survivin. We further developed acupuncture needle-based PISA for probing low-copy-number proteins in living bodies.

Targeting and Imaging of Cancer Cells via Monosaccharide-Imprinted Fluorescent Nanoparticles.

The recognition of cancer cells is a key for cancer diagnosis and therapy, but the specificity highly relies on the use of biorecognition molecules particularly antibodies. Because biorecognition molecules suffer from some apparent disadvantages, such as hard to prepare and poor storage stability, novel alternatives that can overcome these disadvantages are highly important. Here we present monosaccharide-imprinted fluorescent nanoparticles (NPs) for targeting and imaging of cancer cells. The molecularly imprinted polymer (MIP) probe was fluorescein isothiocyanate (FITC) doped silica NPs with a shell imprinted with sialic acid, fucose or mannose as the template. The monosaccharide-imprinted NPs exhibited high specificity toward the target monosaccharides. As the template monosaccharides used are over-expressed on cancer cells, these monosaccharide-imprinted NPs allowed for specific targeting cancer cells over normal cells. Fluorescence imaging of human hepatoma carcinoma cells (HepG-2) over normal hepatic cells (L-02) and mammary cancer cells (MCF-7) over normal mammary epithelial cells (MCF-10A) by these NPs was demonstrated. As the imprinting approach employed herein is generally applicable and highly efficient, monosaccharide-imprinted NPs can be promising probes for targeting cancer cells.

Surface-enhanced Raman scattering imaging of cancer cells and tissues via sialic acid-imprinted nanotags.

Molecularly imprinted nanoparticles were prepared as surface-enhanced Raman scattering tags for the selective imaging of cancer cells and tissues against normal cells and tissues relying on the use of sialic acid-templated imprinting to recognize cancer cells, which are over-expressed with sialic acid at the surface.