Schistosome infection promotes osteoclast-mediated bone loss.

Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.

Glycyrrhizae radix et Rhizoma-Derived Carbon Dots and Their Effect on Menopause Syndrome in Ovariectomized Mice.

With the extension of the human life span and the increasing pressure of women's work and life, menopause syndrome (MPS) refers to a problem that puzzles almost all women worldwide. Hormone replacement treatment (HRT) can effectively mitigate the symptoms but can also exert adverse effects to a certain extent. Glycyrrhizae radix et rhizome (GRR) is commonly made into a charcoal processed product, termed GRR Carbonisatas (GRRC), for use in traditional Chinese medicine (TCM). GRRC is widely used to treat MPS and other gynecological diseases. In this study, GRRC was prepared through pyrolysis. Subsequently, GRR-derived carbon dots (GRR-CDs) were purified through dialysis and characterized using transmission electron microscopy, high-resolution transmission electron microscopy, Fourier-transform infrared, ultraviolet, fluorescence, X-ray photoelectron microscopy, and high-performance liquid chromatography. The effects of GRR-CDs on MPS were examined and confirmed using ovariectomized female mice models. The GRR-CDs ranged from 1.0 to 3.0 nm in diameter and with multiple surface chemical groups, as indicated by the results. GRR-CDs can elevate the estradiol (E2) level of healthy female mice. Moreover, GRR-CDs can alleviate MPS using the typical ovariectomized mice model, as confirmed by elevating the estradiol (E2) level and reducing the degree of follicle stimulating hormone (FSH) and luteinizing hormone (LH) and raising the degree of uterine atrophy. The results of this study suggested that GRR-CDs may be a potential clinical candidate for the treatment of MPS, which also provides a possibility for nanodrugs to treat hormonal diseases.

MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma.

BACKGROUND: The aberrant expression of E3 ubiquitin ligase Pellino-1 (PELI1) contributes to several human cancer development and progression. However, its expression patterns and functional importance in papillary thyroid cancer (PTC) remains unknown. METHODS: PELI1 expression profiles in PTC tissues were obtained and analyzed through the starBase v3.0 analysis. Real-time PCR, Immunohistochemical assays (IHC) and Western blot were used to investigate the mRNA and protein levels of PELI1 in PTC. The effects of PELI1 on PTC cell progression were evaluated through CCK-8, colony formation, Transwell, and Wound healing assay in vitro, and a PTC xenograft mouse model in vivo. The downstream target signal of PELI1 in PTC was analyzed by using Kyoto encyclopedia of genes and genomes (KEGG), and bioinformatics tools were used to identify potential miRNAs targeting PELI1. Human umbilical cord mesenchymal stem cells were modified by miR-30c-5p and the miR-30c-5p containing extracellular vesicles were collected (miR-30c-5p-EVs) by ultra-high-speed centrifugation method. Then, the effects of miR-30c-5p-EVs on PELI1 expression and PTC progression were evaluated both in vitro and in vivo. RESULTS: Both mRNA and protein expression of PELI1 were widely increased in PTC tissues, and overexpression of PELI1 was positively correlated with bigger tumor size and lymph node metastases. PELI1 promoted PTC cell proliferation and migration in vitro. While, PELI1 silencing significantly suppressed PTC growth in vivo accompanied with reduced expression of Ki-67 and matrix metallopeptidase 2 (MMP-2). Mechanistically, PI3K-AKT pathway was identified as the downstream target of PELI1, and mediated the functional influence of PELI1 in PTC cells. Moreover, we found that the expression of miR-30c-5p was inversely correlated with PELI1 in PTC samples and further confirmed that miR-30c-5p was a tumor-suppressive miRNA that directly targeted PELI1 to inhibit PTC cell proliferation and migration. Furthermore, we showed that miR-30c-5p-EVs could effectively downregulate PELI1 expression and suppress the PTC cell growth in vitro and in vivo. CONCLUSION: This study not only supported the first evidence that miR-30c-5p loss-induced PELI1 accumulation facilitated cell proliferation and migration by activating the PI3K-AKT pathway in PTC but also provided novel insights into PTC therapy based on miR-carrying-hUCMSC-EVs.

SJMHE1 protects against excessive iodine-induced pyroptosis in human thyroid follicular epithelial cells through a toll-like receptor 2-dependent pathway.

To elucidate the effect of Schistosoma japonicum peptide (SJMHE1) on pyroptosis in thyroid follicular epithelial cells (TFCs) induced by excessive iodine and the potential mechanism, the effects of SJMHE1 were investigated in NaI-treated Nthy-ori 3-1 cells; and the involvement of the ROS/MAPK/NF-κB signaling pathways in these effects was evaluated by employing CCK-8 assays, flow cytometry, ELISA, and Western blotting experiments. We found that SJMHE1 significantly reduced NLRP3, N-terminus of gasdermin D (GSDMD-N) and cleaved caspase-1 (C-caspase-1) expression, and decreased IL-1ß secretion in TFCs. SJMHE1 also markedly reduced reactive oxygen species (ROS) production, and decreased the phosphorylation levels of MAPK and NF-κB pathway members. Moreover, blocking of the Toll-like receptor 2 significantly impaired SJMHE1-mediated protection from excessive iodine-induced pyroptosis in TFCs. Therefore, our results suggested a protective role of SJMHE1 in excessive iodine-induced pyroptosis in TFCs, which might be attributed to its suppression for ROS/MAPK/NF-κB signaling pathway by binding of SJMHE1 with TLR2.

Down-regulation of long non-coding RNA MEG3 promotes Schwann cell proliferation and migration and repairs sciatic nerve injury in rats.

Peripheral nerve injury and regeneration are complex processes and involve multiple molecular and signalling components. However, the involvement of long non-coding RNA (lncRNA) in this process is not fully clarified. In this study, we evaluated the expression of the lncRNA maternally expressed gene 3 (MEG3) in rats after sciatic nerve transection and explored its potential mechanisms. The expression of lncRNA MEG3 was up-regulated following sciatic nerve injury and observed in Schwann cells (SCs). The down-regulation of lncRNA MEG3 in SCs enhanced the proliferation and migration of SCs via the PTEN/PI3K/AKT pathway. The silencing of lncRNA MEG3 promoted the migration of SCs and axon outgrowth in rats after sciatic nerve transection and facilitated rat nerve regeneration and functional recovery. Our findings indicated that lncRNA MEG3 may be involved in nerve injury and injured nerve regeneration in rats with sciatic nerve defects by regulating the proliferation and migration of SCs. This gene may provide a potential therapeutic target for improving peripheral nerve injury.

Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice.

Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthma. We previously identified SJMHE1, a small molecule peptide from the HSP60 protein of Schistosoma japonicum. SJMHE1 can inhibit delayed-type hypersensitivity and collagen-induced arthritis in mice. In the present study, we evaluated this peptide's potential intervention effect and mechanism on ovalbumin-induced asthma in mice. SJMHE1 treatment suppressed airway inflammation in allergic mice, decreased the infiltrating inflammatory cells in the lungs and bronchoalveolar lavage fluid, modulated the production of pro-inflammatory and anti-inflammatory cytokines in the splenocytes and lungs of allergic mice, reduced the percentage of Th2 cells and increased the proportion of Th1 and regulatory T cells (Tregs). At the same time, Foxp3 and T-bet expression increased, and GATA3 and RORγt decreased in the lungs of allergic mice. We proved that SJMHE1 can interrupt the development of asthma by diminishing airway inflammation in mice. The down-regulation of Th2 response and the up-regulation of Th1 and Tregs response may contribute to the protection induced by SJMHE1 in allergic mice. SJMHE1 can serve as a novel therapy for asthma and other allergic or inflammatory diseases.

Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats.

Peripheral nerve injury results in limited nerve regeneration and severe functional impairment. Mesenchymal stem cells (MSCs) are a remarkable tool for peripheral nerve regeneration. The involvement of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) in peripheral nerve regeneration, however, remains unknown. In this study, we evaluated functional recovery and nerve regeneration in rats that received hUCMSC-EV treatment after nerve transection. We observed that hUCMSC-EV treatment promoted the recovery of motor function and the regeneration of axons; increased the sciatic functional index; resulted in the generation of numerous axons and of several Schwann cells that surrounded individual axons; and attenuated the atrophy of the gastrocnemius muscle. hUCMSC-EVs aggregated to rat nerve defects, down-regulated interleukin (IL)-6 and IL-1ß, up-regulated IL-10 and modulated inflammation in the injured nerve. These effects likely contributed to the promotion of nerve regeneration. Our findings indicate that hUCMSC-EVs can improve functional recovery and nerve regeneration by providing a favourable microenvironment for nerve regeneration. Thus, hUCMSC-EVs have considerable potential for application in the treatment of peripheral nerve injury.

The IL-33-ST2-MyD88 axis promotes regulatory T cell proliferation in the murine liver.

Hepatic Foxp3+ Treg cells are crucial for maintaining local immune homeostasis in the liver. However, the environmental cues required for hepatic Treg cell homeostasis are unclear. In this study, we showed that the IL-33 receptor ST2 was preferentially expressed on Treg cells in the mouse liver, but it was more lowly expressed in the spleen, mesenteric lymph nodes, and blood. More importantly, we found that IL-33 promoted the proliferation of hepatic Treg cells through myeloid differentiation factor MyD88 signaling concomitant with increased cyclin-dependent kinase 4 and cyclin D1 expression. These results suggest that IL-33 is a potential tissue-specific factor controlling Treg cell homeostasis via increased Treg proliferation in the liver.

MDR1 gene polymorphism correlated with pathological characteristics and prognosis in patients with primary hepatocellular carcinoma receiving interventional therapy.

The aim of this study was to explore the relationship of multidrug resistance gene 1 (MDR1) C1236T and C3435T single nucleotides polymorphisms (SNPs) with hepatocellular carcinoma (HCC) pathological features and prognosis. A total of 143 patients with HCC were treated with transcatheter arterial chemoembolization. Moreover, 251 controls were included in the study. C1236T and C3435T single nucleotide polymorphisms (SNPs) were detected by PCR-RFLP. Association of C1236T and C3435T SNPs with HCC was analyzed subsequently. There was no significant difference in genotypes distribution between HCC group and control group (P>0.05), indicating comparability. Among patients with portal vein tumor thrombus, the CC+CT genotype of C1236T locus was significantly higher than that of TT genotype (P=0.031). The median progression-free survival after interventional therapy for patients with C3435T genotype T (TC+TT) and C genotype (CC) was 36 and 18 months, respectively. CC and TC+TT genotype patients with C1236T loci showed statistically significant differences in tumor size stratification (χ=4.006, P=0.045). When tumor diameter was less than 5 cm, 5-10 cm, and more than 10 cm, the mean survival time of C and T genotypes was decreased gradually. The logistic regression model suggested that lesion size, blood volume value, and permeability surface value were influential factors for response to chemoradiotherapy (all P<0.05). Univariate analysis showed that postoperative chemotherapy, portal vein tumor thrombus, and capsular invasion were correlated with overall survival in patients with HCC. Cox proportional hazard model showed that postoperative chemotherapy, capsule invasion, and portal vein tumor thrombus were independent factors of overall survival after interventional therapy in patients with HCC (all P<0.05). C1236T genotype may predict changes in pathological features of patients with HCC to a certain extent, and C3435T SNP can be used as one of the prognostic factors of HCC. Postoperative chemotherapy and portal vein tumor thrombus are independent factors of overall survival in patients with HCC.

SjHSP60 induces CD4+ CD25+ Foxp3+ Tregs via TLR4-Mal-drived production of TGF-ß in macrophages.

CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) play a pivotal role in limiting immunopathological damage to host organs after schistosome infection. Transforming growth factor-ß (TGF-ß) is an essential factor for the periphery conversion of CD4+ CD25- T cells into CD4+ CD25+ Foxp3+ Tregs by inducing the key transcription factor Foxp3. Antigen presenting cells (APCs), which highly express TGF-ß, are involved in parasite antigen-induced Treg conversion in peripheral. However, the mechanisms underlying high TGF-ß induction in APCs by parasite antigens remain to be clarified during schistosome infection. Here, we demonstrated that Schistosoma japonicum stress protein, heat shock protein 60 (SjHSP60), promoted TGF-ß production in macrophages (Mφ). Furthermore, we showed that activation of TLR4-Mal (MyD88 adaptor-like protein) signaling by SjHSP60 is necessary for induction of TGF-ß expression in Mφ, which subsequently promoted Treg induction. Our results not only demonstrate a novel mechanism of TGF-ß production in Mφ for inducing Tregs in mice with schistosomiasis, but also allude to the possibility of targeting parasite stress protein for potential therapeutics.

Inhibition of cytokine response to TLR stimulation and alleviation of collagen-induced arthritis in mice by Schistosoma japonicum peptide SJMHE1.

Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA). We show that SJMHE1 not only modulates the cytokine production of murine macrophage (MΦ) and dendritic cell but also affects cytokine production upon coculturing with allogeneic CD4+ T cell. SJMHE1 potently inhibits the cytokine response to TLR ligands lipopolysaccharide (LPS), CpG oligodeoxynucleotides (CpG) or resiquimod (R848) from mouse splenocytes, and human PBMCs stimulated by LPS. Furthermore, SJMHE1 suppressed clinical signs of CIA in mice and blocked joint erosion progression. This effect was mediated by downregulation of key cytokines involved in the pathogenesis of CIA, such as interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-17, and IL-22 and up-regulation of the inhibitory cytokine IL-10, Tgf-ß1 mRNA, and CD4+ CD25+ Foxp3+ Tregs. This study provides new evidence that the peptide from S. japonicum, which is the 'safe' selective generation of small molecule peptide that has evolved during host-parasite interactions, is of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

Upregulation of Long Non-Coding RNA PlncRNA-1 Promotes Metastasis and Induces Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

BACKGROUND/AIMS: PlncRNA-1 has been demonstrated to promote malignancy in various cancers. The present study aims to investigate the expression pattern, prognosis value and the function of PlncRNA-1 in human hepatocellular carcinoma (HCC). METHODS: The expression of PlncRNA-1 in 84 pairs of HCC and their matched normal tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of PlncRNA-1 expression and clinicopathological characteristics and prognosis were also analyzed. The biological role of PlncRNA-1 in cell proliferation, migration and invasion was examined in vitro and in vivo. RESULTS: The results showed that the level of PlncRNA-1 expression was significantly increased in HCC tissues and significantly correlated with tumor size, vascular invasion and advanced TNM stage. Moreover, patients with high levels of PlncRNA-1 expression had relatively poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that knockdown of PlncRNA-1 expression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) signaling. Animal model experiments confirmed the ability of PlncRNA-1 to promote tumor growth in vivo. CONCLUSIONS: Taken together, our findings suggest that PlncRNA-1 may serve as an oncogene in HCC progression and represent a valuable prognostic marker and potential therapeutic target for HCC.

C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1/2-mediated epithelial-mesenchymal transition.

C5a and its receptor, C5a receptor (C5aR), play critical roles in tumor progression. However, mechanisms of C5a-C5aR axis in hepatocellular carcinoma (HCC) cell invasiveness are not fully elucidated. In this study, we found that C5aR expression was highly expressed in HCC cell lines and tumor tissues, and associated with capsular invasion, tumor stage and some epithelial-mesenchymal transition (EMT)-related markers. Activation of C5aR by C5a promoted HCC cell invasion and migration, whereas depletion of C5aR expression significantly impaired C5a-stimulated invasion and migration. Furthermore, we found that C5aR induced EMT in HCC cells, through downregulation of E-cadherin and Claudin-1 expression, and upregulation of Snail expression. Finally, we demonstrated that C5aR stimulated activation of ERK1/2, and ERK1/2 pathway was involved in C5aR-mediated EMT, cell invasion and migration of HCC cells. Thus, our data suggest that C5aR stimulates cell invasion and migration via ERK1/2-mediated EMT in HCC cells, and implicate that blocking C5aR expression has therapeutic promise to inhibit HCC invasiveness.

IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2-ERK1/2 Pathway.

BACKGROUND: As a pro-inflammatory cytokine, IL-33 has been demonstrated to play an important role in tumor progression. It is reported that IL-33 is highly expressed in the serum and tumor tissues of patients with gastric cancer. However, the function of IL-33 in gastric cancer remains elusive. We here tried to elucidate the effects of IL-33 on gastric cancer cell invasion and migration. METHODS: Invasion assay and migration assay were performed to assess the effects of IL-33 on gastric cancer cell invasion and migration. ST2 receptor was silenced by siRNA, and ERK1/2 pathway was inhibited by U0126. Protein levels of MMP-3 and IL-6 in cell supernatant were measured by ELISA. RESULTS: IL-33 promoted the invasion and migration of gastric cancer cells, in a dose-dependent manner. Knockdown of the IL-33 receptor ST2 attenuated the IL-33-mediated invasion and migration. Furthermore, via ST2 receptor, IL-33 induced the activation of ERK1/2 and increased the secretion of MMP-3 and IL-6. In addition, blockage of ERK1/2 pathway resulted in inhibition of invasion and migration induced by IL-33, and downregulation of MMP-3 and IL-6 production. CONCLUSIONS: IL-33 promotes gastric cancer cell invasion and migration by stimulating the secretion of MMP-3 and IL-6 via ST2-ERK1/2 pathway. Thus, IL-33 may be a useful marker for the diagnosis and treatment of gastric cancer.

Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis.

The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3(+) CD4(+) IL-17(+) Th17 cells were significantly higher, and CD4(+) CD25(+) FOXP3(+) Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro-inflammatory cytokines, including IL-17, IL-6, IL-1ß, TNF-α and IL-22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR-21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up-regulated miR-21 expression from healthy controls, but down-regulated miR-21 expression from RA patients. Therefore, we speculate that miR-21 may be part of a negative feedback loop in the normal setting. However, miR-21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR-21 may thus serve as a novel regulator in T-cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.

An On-Treatment Decreased Trend of Serum IL-6 and IL-8 as Predictive Markers Quickly Reflects Short-Term Efficacy of PD-1 Blockade Immunochemotherapy in Patients with Advanced Gastric Cancer.

Objective: Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. Materials and Methods: The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-α, IL-1ß, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results: When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1ß, IL-2R, IL-10, IL-17, and TNF-α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. Conclusion: Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy.

hUCMSC-derived extracellular vesicles relieve cisplatin-induced granulosa cell apoptosis in mice by transferring anti-apoptotic miRNAs.

Premature ovarian insufficiency (POI) caused by chemotherapy is a common complication in female cancer survivors of childbearing age. Traditional methods including mesenchymal stem cell (MSC) transplant and hormone replacement therapy have limited clinical application due to their drawbacks, and more methods need to be developed. In the current study, the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) were investigated in a cisplatin (CDDP)-induced POI mouse model and a human granulosa cell (GC) line. The results showed that hUCMSC-EVs significantly attenuated body weight loss, ovarian weight loss, ovary atrophy, and follicle loss in moderate-dose (1.5 mg/kg) CDDP-induced POI mice, similar to the effects observed with hUCMSCs. We further discovered that the hUCMSC-EVs might inhibit CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic miRNA levels in GCs, thereby downregulating the mRNA levels of multiple pro-apoptotic genes. In general, our findings indicate that moderate-dose chemotherapy may be a better choice for clinical oncotherapy considering the effective rescue of oncotherapy-induced ovarian damage with hUCMSC-EVs. Additionally, multiple miRNAs in hUCMSC-EVs may potentially be used to inhibit chemotherapy-induced ovarian GC apoptosis, thereby restoring ovarian function and improving the life quality of female cancer patients.

PG I and PG II show unique value in diagnosing postoperative biochemical recurrence in patients with gastric cancer after total gastrectomy.

OBJECTIVE: To investigate the potential of group I pepsinogen (PG I) and group II pepsinogen (PG II) as diagnostic markers for recurrence in gastric cancer (GC) patients post-total gastrectomy. METHODS: Ninety-six patients who underwent total gastrectomy for GC between June 2022 and June 2023 were included in this study. Clinical data, serum samples, and ascites samples were collected. Patients were categorized based on recurrence status at the time of sample collection and the primary tumor site. PG I and PG II levels were determined using a chemiluminescent immunoassay, and their clinical utility following total gastrectomy for GC was evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: This study included 96 GC patients who underwent total gastrectomy, 55 of whom experienced postoperative recurrence (57.29%). The levels of serum PG I (27.86 (27.04, 30.97) vs. 26.05 (24.16, 27.09) ng/mL; P < 0.0001) and PG II (1.95 (1.23, 3.05) vs. 0.63 (0.47, 0.90) ng/mL; P < 0.0001) were significantly greater in the recurrent group compared to the non-recurrent group. The secretion of PG I and/or PG II by metastatic cancer cells correlated with the primary lesion site. When the cut-off value for serum PG I was 26.93 ng/mL, the area under the curve (AUC) for PG I was 0.77. When the cut-off value for serum PG II was 0.96 ng/mL, the AUC reached 0.90. The combined AUC was 0.97. CONCLUSION: These findings suggest that serum PG I and PG II are valuable biomarkers for identifying GC patients with biochemical recurrence post-total gastrectomy.

Carbon Dots Derived from Curcumae Radix and Their Heartprotective Effect.

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases. Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats. Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro. Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases.

Isolation and characterization of extracellular vesicle-like nanoparticles derived from migrasomes.

Migrasomes comprise a recently identified unique type of extracellular vesicle (EV) containing varying numbers of small vesicles. However, the final fate of these small vesicles is still unclear. Here, we report the discovery of EV-like migrasome-derived nanoparticles (MDNPs) that are produced by migrasomes releasing internal vesicles via self-rupture and through a process similar to cell plasma membrane budding. Our results demonstrate that MDNPs have a membrane structure with a typical round-shaped morphology and have the characteristic markers of migrasomes, but do not present the markers of EVs from the cell culture supernatant. More importantly, we also show that MDNPs are loaded with a large number of microRNAs different from those found in migrasomes and EVs. Our results provide evidence that migrasomes can produce EV-like nanoparticles. These findings have important implications for understanding the unknown biological functions of migrasomes.