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Background: Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was shown to be dysregulated in several cancer types, but the role of DARS-AS1 in cervical cancer remains unclear. Methods: Immunofluorescence staining, flow cytometry and transwell invasion assays were used to determine proliferation, apoptosis and invasion in cervical cancer cells, respectively. The dual luciferase reporter system assay was performed to assess the interaction between DARS-AS1, miR-188-5p, and high mobility group box 1 (HMGB1) in cervical cancer cells. Results: Downregulation of DARS-AS1 markedly inhibited the proliferation and invasion of cervical cancer cells. Moreover, DARS-AS1 knockdown obviously induced the apoptosis of SiHa and HeLa cells. Meanwhile, luciferase reporter assay identified that miR-188-5p was the potential miRNA binding of DARS-AS1, and HMGB1 was the potential binding target of miR-188-5p. Mechanistic analysis indicated that downregulation of DARS-AS1 decreased the expression of HMGB1 by acting as a competitive “sponge” of miR-188-5p. Conclusion: In this study, we found that DARS-AS1 knockdown suppressed the growth of cervical cancer cells via downregulating HMGB1 via sponging miR-188-5p. Therefore, DARS-AS1 might serve as a potential target for the treatment of cervical cancer.

Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

Background Hypertrophic scars (HS) affect millions of people each year and require better treatment strategies. Bacterial extracellular vesicles (EVs) are advantaged by low cost and high yield which was commonly used in the treatment of diseases. Here, we investigated the therapeutic efficacy of EVs obtained from Lactobacillus druckerii in hypertrophic scar. In vitro, the effects of Lactobacillus druckerii -derived EVs (LDEVs) on Collagen I/III and α-SMA in fibroblasts obtained from HS. In vivo , a scleroderma mouse model was used to investigate the effects of LDEVs on fibrosis. The impact of LDEVs on excisional wound healing was explored. The different proteins between PBS and LDEVs treated fibroblasts derived from hypertrophic scar were studied by untargeted proteomic analysis. Results In vitro, LDEVs treatment significantly inhibited the expression of Collagen I/III and α-SMA and cell proliferation of fibroblasts derived from HS. In vivo, LDEVs withdrawn the hypertrophic scar formation in scleroderma mouse model and decreased the expression of α-SMA. LDEVs promoted the proliferation of skin cells, new blood vessel formation and wound healing in excisional wound healing mice model. Moreover, proteomics has shown that LDEVs inhibit hypertrophic scar fibrosis through multiple pathways. Conclusions Our results indicated that Lactobacillus druckerii -derived EVs has the potential application in the treatment of hypertrophic scars and any other fibrosis diseases. Graphical Abstract

Compared with traditional lubricants, polyol ester lubricants exhibit superior oxidative stability and have been widely applied in extreme operating conditions such as aviation engines. However, under high-temperature conditions, polyol esters are still susceptible to oxidation and therefore require the addition of antioxidants. N-phenyl-α-naphthylamine is an excellent high-temperature antioxidant used in polyol ester. However, a notable issue is that oil sludge may form when this antioxidant is used at high temperatures. Excessive sludge can lead to a series of problems such as oil circuit blockage, more severe mechanical wear, and poor heat dissipation performance. In this work, oil sludge formation from N-phenyl-α-naphthylamine was simulated via high-temperature oxidation experiments in a polyol ester base oil. The formed sludge was then characterized by various advanced techniques, such as FT-IR, GPC, TGA, MALDI-TOF MS, and XPS. The results showed that the oil sludge was mainly composed of derivatives of polyol esters and N-phenyl-α-naphthylamine, along with some metal components. Further analysis showed that polymerization reactions between antioxidant molecules are the key factors leading to sludge generation, and polycyclic aromatic compounds formed by polymerization are responsible for inducing sludge generation in polyol esters.

Cervical cancer significantly affects women’s health, while current preoperative imaging methods for predicting lymph node status are suboptimal. This study aims to evaluate the predictive value of CT attenuation (Hounsfield units) for lymph node metastasis (LNM) in cervical cancer patients and to develop a nomogram integrates clinical and imaging features to improve the accuracy of preoperative assessment. A retrospective analysis was conducted on 132 cervical cancer patients treated at the Second Affiliated Hospital of Dalian Medical University from January 2021 to August 2024. The cohort was divided into a training set (70%) and a validation set (30%) for constructing and evaluating the nomogram. CT attenuation was identified as robust predictors of LNM. Multivariate logistic regression showed that preoperative SCC levels, tumor histology, uterine corpus involvement, and lymphovascular space invasion were independent risk factors for LNM. The nomogram incorporating CT attenuation demonstrated excellent discrimination and calibration. This study presents a simple but robust nomogram that integrates clinical and imaging data to predict lymph node status in cervical cancer patients. The model exhibits high accuracy and reliability, highlighting the utility of CT imaging as a non-invasive preoperative tool for assessing LNM.

Background Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. Methods Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. Results Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. Conclusion NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Abstract Background: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. Methods: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. Results: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. Conclusions: 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30–40% of all non-Hodgkin lymphoma cases. Organs located DLBCL such as lymph node, stomach, gastrointestinal tract, or skin were reported. However, the adrenal gland DLBCL was not been well explored. We performed RNA sequencing of ten DLBCL samples from adrenal gland, integrated analyzed DLBCL RNA data from multiple organs, defined the new subtypes of adrenal gland DLBCL and explored their molecular signatures. The special expression pattern and microenvironment immunology scores of adrenal glands DLBCL were observed when compared with other organs. Natural killer T cells was predicted to significantly enrichment in adrenal gland DLBCL, canonical cancer pathways such as programmed death protein 1 signaling pathways, tumor necrosis factor signaling pathways and peptide antigen binding pathways were found to be correlated with adrenal gland DLBCL. Further analysis defined two distant adrenal gland DLBCL sub-type by RNA expression pattern. Our study revealed the special expression, defined the molecular subtype of adrenal gland DLBCL. These results expanded the organ related DLBCL data, provided the new knowledge of adrenal gland DLBCL expression profile.

Background Hypertrophic scars (HS) generally occur after injury to the deep layers of the dermis, resulting in functional deficiency for patients. Growing evidence has been identified that the supernatant of adipose tissue-derived stem cells (ADSCs) significantly ameliorates fibrosis of different tissues, but limited attention has been paid to its efficacy on attenuating skin fibrosis. In this study, we explored the effect and possible mechanism of ADSC-conditioned medium (ADSC-CM) on HS. Method Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of collagen I (Col1), collagen III (Col3), and α-smooth muscle actin (α-SMA) after fibroblasts and cultured HS tissues were stimulated with ADSC-CM and p38 inhibitor/activator. Immunofluorescence staining was performed to test the expression of α-SMA. Masson’s trichrome staining, hematoxylin and eosin (H&E) staining, and immunohistochemistry staining were carried out to assess the histological and pathological change of collagen in the BALB/c mouse excisional model. All data were analyzed by using SPSS17.0 software. Statistical analysis was performed by Student’s t tests . Results The in vitro and ex vivo study revealed ADSC-CM decreased the expression of Col1, Col3, and α-SMA. Together, thinner and orderly arranged collagen was manifested in HS tissues cultured with ADSC-CM. Dramatically, the assessed morphology showed an accelerated healing rate, less collagen deposition, and col1- and col3-positive cells in the ADSC-CM treated group. Importantly, the protein level of p-p38 was downregulated in a concentration-dependent manner in HS-derived fibroblasts with ADSC-CM treatment, which further decreased the expression of p-p38 after the application of its inhibitor, SB203580. SB203580 led to an obvious decline in the expression of Col1, Col3, and α-SMA in fibroblasts and cultured HS tissues and presented more ordered arrangement and thinner collagen fibers in BALB/c mice. Lastly, anisomycin, an agonist of p38, upregulated the expression of fibrotic proteins and revealed more disordered structure and denser collagen fibers. Conclusion This study demonstrated that ADSC-CM could decrease collagen deposition and scar formation in in vitro , ex vivo and in vivo experiments. The regulation of the p38/MAPK signaling pathway played an important role in the process. The application of ADSC-CM may provide a novel therapeutic strategy for HS treatment, and the anti-scarring effect can be achieved by inhibition of the p38/MAPK signaling pathway.

Background Diabetic nephropathy leads to renal fibrosis via excessive ECM accumulation. Current therapies lack specificity, highlighting the need to identify targets like SRPK1, whose role in diabetic kidney fibrosis remains unclear. Methods We investigated SRPK1’s function using a streptozotocin-induced diabetic nephropathy mice model and administered the selective SRPK1 inhibitor SRPIN340. Histological, biochemical, and molecular analyses were performed to assess ECM deposition, renal function, and fibrotic marker expression. Additionally, Western blotting and immunohistochemistry were utilized to explore the involvement of the NF-κB/NLRP3 signaling pathway. Results SRPK1 expression was significantly elevated in fibrotic kidneys, correlating with increased ECM components (collagen I/III, fibronectin) and reduced renal function. SRPIN340 treatment markedly alleviated ECM accumulation, improved glomerular filtration rate, and suppressed fibrotic markers (α-SMA, TGF-β). Mechanistically, SRPK1 activation promoted NF-κB/NLRP3 pathway activation, leading to inflammatory cytokine release (IL-1β, TNF-α) and fibrosis. Inhibition of SRPK1 via SRPIN340 abrogated these effects, suggesting a causal role for SRPK1 in fibrotic progression. Conclusion SRPK1 activates NF-κB/NLRP3 pathway, promoting ECM synthesis and inflammation in diabetic nephropathy; SRPIN340 reduces fibrosis, highlighting SRPK1 as a therapeutic target. Key messages What is already known about this topic? Diabetic nephropathy (DN) is one of the major complications of diabetes, with its core pathological feature being renal interstitial fibrosis. SRPK1 (serine/arginine protein kinase 1) has been confirmed to participate in the progression of diseases such as pulmonary fibrosis and hepatic fibrosis by regulating RNA splicing and signaling pathways. However, its specific role in renal fibrosis remains unclear. What this study adds? This study demonstrates that SRPIN340, as an SRPK1 inhibitor, effectively alleviates renal fibrosis in animal models, thereby providing experimental evidence for the clinical translation of SRPK1-targeted therapies. How this study might affect research, practice, or policy? This study advocates for prioritizing SRPK1-targeted inhibitors in the development of future therapeutic strategies for chronic kidney disease (CKD), while urging interdisciplinary collaboration that synergizes pharmacological research, bioinformatics analysis, and clinical resources to expedite the advancement of SRPK1-based therapeutics.