Time-dependent diffusion MRI-based microstructural mapping for differentiating high-grade serous ovarian cancer from serous borderline ovarian tumor.

PURPOSE: To investigate the value of microstructural characteristics derived from time-dependent diffusion MRI in distinguishing high-grade serous ovarian cancer (HGSOC) from serous borderline ovarian tumor (SBOT) and the associations of immunohistochemical markers with microstructural features. METHODS: Totally 34 HGSOC and 12 SBOT cases who received preoperative pelvic MRI were retrospectively included in this study. Two radiologists delineated the tumors to obtain the regions of interest (ROIs). Time-dependent diffusion MRI signals were fitted by the IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) model, to extract microstructural parameters, including fraction of the intracellular component (fin), cell diameter (d), cellularity and extracellular diffusivity (Dex). Apparent diffusion coefficient (ADC) values were obtained from standard diffusion-weighted imaging (DWI). The parameters of HGSOCs and SBOTs were compared, and the diagnostic performance was evaluated. The associations of microstructural indexes with immunopathological parameters were assessed, including Ki-67, P53, Pax-8, ER and PR. RESULTS: In this study, fin, cellularity, Dex and ADC had good diagnostic performance levels in differentiating HGSOC from SBOT, with AUCs of 0.936, 0.909, 0.902 and 0.914, respectively. There were no significant differences in diagnostic performance among these parameters. Spearman analysis revealed in the HGSOC group, cellularity had a significant positive correlation with P53 expression (P = 0.028, r = 0.389) and Dex had a significant positive correlation with Pax-8 expression (P = 0.018, r = 0.415). ICC showed excellent agreement for all parameters. CONCLUSION: Time-dependent diffusion MRI had value in evaluating the microstructures of HGSOC and SBOT and could discriminate between these tumors.

The Efficacy of Recombinant Human Type III Collagen in the Treatment of Atrophic Scars and Its Impact on p38 MAPK Signaling Pathway Proteins.

Objective: To investigate the effects of recombinant human type III collagen on atrophic scars and its impact on the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. Methods: A total of 94 patients with atrophic scars admitted to our hospital from March 2020 to October 2022 were selected as subjects and evenly divided into a control group and an observation group. The control group (n = 47) received carbon dioxide fractional laser treatment, while the observation group (n = 47) was treated with recombinant human type III collagen dressings in addition to the laser treatment. Clinical efficacy, scar conditions, skin physiological parameters, serum levels of p38MAPK pathway-related proteins, and inflammatory markers were compared between the two groups. Results: The overall effective rate in the observation group was 95.74%, significantly higher than 74.47% in the control group (P < .05). Before treatment, there was no significant difference in Vancouver Scar Scale (VSS) scores, stratum corneum hydration, and transepidermal water loss between the two groups (P > .05). After treatment, the VSS score in the observation group was significantly lower than in the control group (P < .05). Similarly, prior to treatment, there were no significant differences in serum levels of mitogen-activated protein kinase 1 (MEK1), mitogen-activated protein kinase 2 (MEK2), extracellular signal-regulated kinase 1 (ERK1), and extracellular signal-regulated kinase 2 (ERK2), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) between the two groups (P > .05). After treatment, levels of MEK1, MEK2, ERK1, ERK2, IL-10, and TNF-α in the observation group were significantly lower than those in the control group (P < .05). Conclusion: Recombinant human type III collagen significantly improves the treatment of atrophic scars, effectively ameliorating scar conditions and skin physiology. It also regulates the p38MAPK signaling pathway and reduces inflammation.

Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: a systematic review and Bayesian network meta-analysis.

Background: Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable. This systematic review aimed to compare the therapeutic effects and safety of JAK inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, and interleukin (IL) inhibitors in patients with AS. Methods: We retrieved literature from various databases including Web of Science, Cochrane, Embase, PubMed, China National Knowledge Infrastructure, Weipu Journal Database, SinoMed, and WanFang Data up to February 1, 2023, and evaluated the quality of the included RCTs using the Cochrane risk-of-bias tool. R 4.1.3, STATA 15.1 were employed for network meta-analyses. Results: We identified 48 eligible articles including 8,937 patients. Ten articles were rated as "low risk", 5 as "high risk", and the others as "some concerns". In terms of efficacy, IL-17, IL-6, and JAK inhibitors were compared with TNF-α inhibitors in ASAS20 (RR =0.81, 95% CI: 0.66-0.98; RR =0.57, 95% CI: 0.35-0.95; RR =0.77, 95% CI: 0.60-0.99). IL-6 inhibitors were compared with TNF-α inhibitors in ASAS5/6 (RR =0.39, 95% CI: 0.16-0.98). IL-23, JAK inhibitors were compared with TNF-α inhibitors in BASDAI50 (RR =0.35, 95% CI: 0.20-0.60; RR =0.70, 95% CI: 0.49-0.98). IL-17 inhibitors were compared with IL-23 and IL-6 inhibitors in BASFI (MD =-1.05, 95% CI: -1.65--0.51; MD =-1.46, 95% CI: -2.02--0.97). In terms of safety, IL-6 inhibitors were compared with JAK, TNF-α inhibitors in AEs (RR =1.38, 95% CI: 1.06-1.88; RR =1.30, 95% CI: 1.01-1.70). Conclusions: TNF-α inhibitors are significantly superior to both IL and JAK inhibitors, and may be the preferable option to deal with the rapid progression of AS and severe functional limitations. IL-17 inhibitors may better improve the BASDAI50 response compared with JAK, IL-23, and TNF-α inhibitors. The efficacy and safety of IL-6 inhibitors are inferior to other types of drugs, indicating the low efficacy and high risk of IL-6 inhibitors.

Transcriptomic analysis reveals genetic factors regulating early steroid-induced osteonecrosis of the femoral head.

The present study aimed to explore the signaling pathways involved in development of early steroid-induced osteonecrosis of the femoral head (SONFH) and identify diagnostic biomarkers regulating peripheral blood in SONFH patients. We downloaded transcriptome data and identified differentially expressed genes (DEGs) using the R software. We used ClusterProfiler to perform enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and analyzed protein-protein interactions using the STRING database. Network X was used to visualize the networks in Python. A total of 584 DEGs were identified, of which 294 and 290 were upregulated and downregulated, respectively. Enrichment analysis showed that the DEGs were mainly involved in red blood cell differentiation, cell protein catabolism, gas transportation, activation of myeloid leukocytes, phagocytosis, and inflammatory response. Pathway analysis revealed that these DEGs were involved in regulation of mitophagy-animal, human T-cell leukemia virus-1 infection, Forkhead box O, phagocytosis, osteoclast differentiation, and cytokine-cytokine receptor interaction. Quantitative real-time polymerase chain reaction results were consistent with findings from protein-protein interaction network analysis. Several genes, including peroxiredoxin 2, haptoglobin, matrix metallopeptidase 8, formyl peptide receptor 2, and integrin subunit alpha X, promote SONFH occurrence by regulating the redox, inflammatory response, and osteoblast and osteoclast structure and function pathways. They may be important targets for designing approaches for early diagnosis and treatment of SONFH.

Emerging nanozyme-based multimodal synergistic therapies in combating bacterial infections.

Pathogenic infections have emerged as major threats to global public health. Multidrug resistance induced by the abuse of antibiotics makes the anti-infection therapies to be a global challenge. Thus, it is urgent to develop novel, efficient and biosafe antibiotic alternatives for future antibacterial therapy. Recently, nanozymes have emerged as promising antibiotic alternatives for combating bacterial infections. More significantly, the multimodal synergistic nanozyme-based antibacterial systems open novel disinfection pathways. In this review, we are mainly focusing on the recent research progress of nanozyme-based multimodal synergistic therapies to eliminate bacterial infections. Their antibacterial mechanism, the synergistic antibacterial systems are systematically summarized and discussed according to the combination of mechanisms and the purpose to improve their antibacterial efficiency, biosafety and specificity. Finanly, the current challenges and prospects of the multimodal synergistic antibacterial systems are proposed.

Immune Regulator Retinoic Acid-Inducible Gene I (RIG-I) in the Pathogenesis of Cardiovascular Disease.

Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor that contains two CARD domains, an RNA helicase domain, and a C-terminal domain. RIG-I initiates antiviral innate immunity by recognizing exogenous viral RNAs/DNAs. However, some studies have reported that RIG-I activation leads to damage in various organs and tissues in diverse circumstances. Recent studies have shown that RIG-I is involved in cancer, lupus nephritis, immunoglobulin A nephropathy, Crohn's disease, and atherosclerosis. These reports indicate that RIG-I not only participates in antiviral signaling pathways but also exerts an influence on non-viral infectious diseases. RIG-I is widely expressed in immune and non-immune cells including smooth muscle cells, endothelial cells, and cardiomyocytes. A succinct overview of RIG-I and its signaling pathways, with respect to the cardiovascular system, will aid in the development of novel therapeutics for cardiovascular diseases. In this review, we summarize the structure, activation, signaling pathways, and role of RIG-I in cardiovascular diseases.

An Au@NH2-MIL-125(Ti)-based multifunctional platform for colorimetric detections of biomolecules and Hg2.

In this report, a novel nanocomposite of highly dispersed Au nanoparticles deposited on NH2-MIL-125(Ti) was designed and proposed as a peroxidase-like mimic. Compared with individual Au nanoparticles and NH2-MIL-125(Ti), the peroxidase-like nanozyme exhibits enhanced peroxidase-like activity. Moreover, kinetic analysis reveals that the as-prepared nanozyme has lower Km values and stronger affinity towards both substrates than the natural horseradish peroxidase (HRP). The detection limits of the multifunctional platform for H2O2, cysteine and Hg2+ are down to 0.24 µM, 0.14 µM and 100 nM, respectively. This work provides rapid and sensitive colorimetric detection strategies for small biomolecules and Hg2+, which have great potential for application in biosensors and biotechnology.