A novel web-based risk calculator for predicting surgical site infection in HIV-positive facture patients: a multicenter cohort study in China.

Background: Surgical site infection (SSI) is a common complication in HIV-positive fracture patients undergoing surgery, leading to increased morbidity, mortality, and healthcare costs. Accurate prediction of SSI risk can help guide clinical decision-making and improve patient outcomes. However, there is a lack of user-friendly, Web-based calculator for predicting SSI risk in this patient population. Objective: This study aimed to develop and validate a novel web-based risk calculator for predicting SSI in HIV-positive fracture patients undergoing surgery in China. Method: A multicenter retrospective cohort study was conducted using data from HIV-positive fracture patients who underwent surgery in three tertiary hospitals in China between May 2011 and September 2023. We used patients from Beijing Ditan Hospital as the training cohort and patients from Chengdu Public Health and Changsha First Hospital as the external validation cohort. Univariate, multivariate logistic regression analyses and SVM-RFE were performed to identify independent risk factors for SSIs. A web-based calculator was developed using the identified risk factors and validated using an external validation cohort. The performance of the nomogram was evaluated using the area under the receiver operating characteristic (AUC) curves, calibration plots, and decision curve analysis (DCA). Results: A total of 338 HIV-positive patients were included in the study, with 216 patients in the training cohort and 122 patients in the validation cohort. The overall SSI incidence was 10.7%. The web-based risk calculator (https://sydtliubo.shinyapps.io/DynNom_for_SSI/) incorporated six risk factors: HBV/HCV co-infection, HIV RNA load, CD4+ T-cell count, Neu and Lym level. The nomogram demonstrated good discrimination, with an AUC of 0.890 in the training cohort and 0.853 in the validation cohort. The calibration plot showed good agreement between predicted and observed SSI probabilities. The DCA indicated that the nomogram had clinical utility across a wide range of threshold probabilities. Conclusion: Our study developed and validated a novel web-based risk calculator for predicting SSI risk in HIV-positive fracture patients undergoing surgery in China. The nomogram demonstrated good discrimination, calibration, and clinical utility, and can serve as a valuable tool for risk stratification and clinical decision-making in this patient population. Future studies should focus on integrating this nomogram into hospital information systems for real-time risk assessment and management.

CRISPLD1 promotes gastric cancer progression by regulating the Ca2+/PI3K-AKT signaling pathway.

Gastric cancer (GC) is a malignant tumor with poor prognosis. Studies have shown that cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is associated with tumor progression. However, its role in GC is unclear. The present study aimed to determine the pathogenic mechanism of CRISPLD1 in GC. Analysis of public databases revealed high mRNA expression of CRISPLD1 in GC, which was associated with poor prognosis. Additionally, CRISPLD1 expression levels showed significant correlations with T stage, overall survival events, and stage. Knockdown of CRISPLD1 reduced cell proliferation, invasion, and migration. Furthermore, CRISPLD1 knockdown decreased intracellular calcium levels in GC cells and inhibited the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Treatment with an AKT activator reversed the inhibitory effect of CRISPLD1 knockdown on GC cell migration and invasion. Our findings suggest that CRISPLD1 promotes tumor cell progression in GC by mediating intracellular calcium levels and activating the PI3K-AKT pathway, highlighting CRISPLD1 as a potential therapeutic target for GC.

Multifunctional DNA-Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction.

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.

Antibacterial and DNA-Based Hydrogels In Situ Block TNF-α to Promote Diabetic Alveolar Bone Rebuilding.

Alveolar bone injury under diabetic conditions can severely impede many oral disease treatments. Rebuilding diabetic alveolar bone in clinics is currently challenging due to persistent infection and inflammatory response. Here, an antibacterial DNA-based hydrogel named Agantigel is developed by integrating silver nanoclusters (AgNCs) and tumor necrosis factor-alpha (TNF-α) antibody into DNA hydrogel to promote diabetic alveolar bone regeneration. Agantigel can effectively inhibit bacterial growth through AgNCs while exhibiting negligible cytotoxicity in vitro. The sustained release of TNF-α antibody from Agantigel effectively blocks TNF-α and promotes M2 polarization of macrophages, ultimately accelerating diabetic alveolar bone regeneration in vivo. After 21 days of treatment, Agantigel significantly accelerates the defect healing rate of diabetic alveolar bone up to 82.58 ± 8.58% and improves trabecular architectures compared to free TNF-α (42.52 ± 15.85%). The results imply that DNA hydrogels are potential bio-scaffolds helping the sustained release of multidrug for treating DABI or other oral diseases.

The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4.

PURPOSE: Breast cancer (BC) is the most frequent malignant tumor in women worldwide with exceptionally high morbidity. The RNA-binding protein MEX3A plays a crucial role in genesis and progression of multiple cancers. We attempted to explore its clinicopathological and functional significance in BC in which MEX3A is expressed. METHODS: The expression of MEX3A detected by RT-qPCR and correlated the results with clinicopathological variables in 53 BC patients. MEX3A and IGFBP4 profile data of BC patients were downloaded from TCGA and GEO database. Kaplan-Meier (KM) analysis was used to estimate the survival rate of BC patients. Western Blot, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MEX3A and IGFBP4 in BC cell proliferation, invasion and cell cycle in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of BC cells after MEX3A knockdown. The interactions among MEX3A and IGFBP4 were measured by RNA pull-down and RNA immunoprecipitation. RESULTS: The expression of MEX3A was upregulated in BC tissues compared to adjacent tissues and high expression of MEX3A was associated with poor prognosis. Subsequent in vitro studies demonstrated that MEX3A knockdown inhibited BC cells proliferation and migration, as well as xenograft tumor growth in vivo. The expression of IGFBP4 was significantly negatively correlated with MEX3A in BC tissues. Mechanistic investigation showed that MEX3A binds to IGFBP4 mRNA in BC cells, decreasing IGFBP4 mRNA levels, which further activated the PI3K/AKT and other downstream signaling pathways implicated cell cycle progression and cell migration. CONCLUSION: Our results indicate that MEX3A plays a prominent oncogenic role in BC tumorigenesis and progression by targeting IGFBP4 mRNA and activating PI3K/AKT signaling, which can be used as a novel therapeutic target for BC.

Annexin A9 promotes cell proliferation by regulating the Wnt signaling pathway in colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Expression of Annexin A9 (ANXA9), a member of the annexin A family, is upregulated in CRC. However, the molecular role of ANXA9 in CRC remains unknown. In the present study, we aimed to investigate the function of ANXA9 and to elucidate the mechanisms underlying its regulation in CRC. In this study, mRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and GEPIA database, respectively. Kaplan-Meier analysis was used to analyze the survival rates. LinkedOmics and Metascape databases were used to explore the potential mechanisms of regulation of ANXA9 and to identify genes co-expressed with ANXA9. Finally, in vitro experiments were used to evaluate the function of ANXA9 and explore potential mechanisms. We found that ANXA9 expression was significantly elevated in CRC tissue and cells. High ANXA9 expression was associated with shorter overall survival, poorer disease specific survival, as well as with patient age, clinical stage, M stage, and OS events in CRC. Knockdown of ANXA9 inhibited cell proliferation, invasion, migratory potential, and cell cycle arrest. Mechanistically, functional analysis revealed that genes co-expressed with ANXA9 were mainly enriched in the Wnt signaling pathway. ANXA9 deletion suppressed cell proliferation via the Wnt signaling pathway, while Wnt activation reversed the effects of ANXA9. In conclusion, ANXA9 may promote CRC progression by regulating the Wnt signaling pathway and may be a potential diagnostic biomarker in the clinical management of CRC.

Function of stem cells in radiation-induced damage.

PURPOSE: The aim of this review is to discuss previous studies on the function of stem cells in radiation-induced damage, and the factors affecting these processes, in the hope of improving our understanding of the different stem cells and the communication networks surrounding them. This is essential for the development of effective stem cell-based therapies to regenerate or replace normal tissues damaged by radiation. CONCLUSION: In salivary glands, senescence-associated cytokines and inflammation-associated cells have a greater effect on stem cells. In the intestinal glands, Paneth cells strongly affect stem cell-mediated tissue regeneration after radiation treatment. In the pancreas, ß-cells as well as protein C receptor positive (Procr) cells are expected to be key cells in the treatment of diabetes. In the bone marrow, a variety of cytokines such as CXC-chemokine ligand 12 (CXCL12) and stem cell factor (SCF), contribute to the functional recovery of hematopoietic stem cells after irradiation.

Sini Decoction Inhibits Tumor Progression and Enhances the Anti-Tumor Immune Response in a Murine Model of Colon Cancer.

BACKGROUND: Sini decoction (SND) is a widely used Traditional Chinese Medicine (TCM). The reports of SND application in colorectal cancer (CRC) is limited. OBJECTIVE: The objective of this study is to investigate the anti-tumor activity of SND in the treatmeant of CRC. METHODS: SND was analyzed using high-performance liquid chromatography. A CRC metastasis model was established using murine CT-26 cells. Whole-body fluorescence imaging was used to observe CRC liver metastasis. Liver morphology was determined using hematoxylin-eosin staining. Cytokine mRNA expression (interleukin-2 (IL-2), interleukin-10 (IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor beta (TNF-ß)) were determined using real-time reverse transcription polymerase chain reaction. Spectral flow cytometry was used to detect mouse tumor immune subgroups. Databases were used to find potential target genes of SND. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify potential signaling pathways of target genes. RESULTS: SND suppressed CRC liver metastasis and alleviated liver injury in vivo. After SND treatment, IL-2 and IFN-γ were upregulated, whereas IL-10 and TGF-ß were downregulated. Moreover, CD3+, CD8+T cells, natural killer T cells, and macrophages increased significantly after SND treatment, while CD4+CD25+T cells decreased significantly. Importantly, increasing the aconite concentration had a better anti-tumor effect. Fifty-50 compounds in SND were screened, and 611 potential target genes were identified. Functional analyses showed that the genes were associated with the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and HIF-1 signaling pathway. CONCLUSION: SND exerts anti-tumor activity by inhibiting tumor progression and enhancing antitumor immunity in mice, suggesting its application to prevent and treat CRC.

Temporal metabolic trajectory analyzed by LC-MS/MS based targeted metabolomics in acute pancreatitis pathogenesis and Chaiqin Chengqi decoction therapy.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of pancreas that lacks effective specific drugs as well as gold standard laboratory tests for diagnosis and severity assessment. Chaiqin chengqi decoction (CQCQD) has been proven to alleviate the severity and mortality of AP, but its underlying mechanisms remain incompletely understood. PURPOSE: To investigate the correlation between metabolic trajectories of the serum and pancreas, the metabolic pathways with respect to the onset and progression of AP, and investigate the effect of CQCQD in modulating the dysregulated pancreatic metabolism of AP. METHODS: Serum and pancreas samples from cerulein-induced AP mice were collected for pathology, biochemical index assessment, LC-MS/MS based metabolomics and functional validation over the course of 1 - 24 h. The temporal trends of pancreatic and serum metabolites in AP were analyzed using Mfuzz clustering algorithm, and their associations were revealed by Pearson correlation analysis. The metabolic trajectories and pathways across multi-timepoints were analyzed by univariate and multivariate statistical analyses, and the AP-related metabolic pathways were further screened by metabolite correlation and network interaction analyses. Finally, the changes in metabolite levels and metabolic trajectory after CQCQD therapy were identified, and the altered expression of related metabolic enzymes was verified by RT-qPCR, western blotting, and immunohistochemistry. RESULTS: Amino acid metabolism was significantly altered in the pancreas and serum of AP, but with different trends. The unsynchronized "open" and "closed" metabolic trajectories in pancreas and serumrevealed that metabolic processes occur earlier in peripheral rather than local tissue, with the most obvious changes occuring at 12 h in the pancreas which were also consistent with the inflammation score results. Several amino acid intermediates showed strong positive correlation between serum and pancreas, and therein serum cystathionine was positively correlated to 33 pancreatic metabolites. In particular, the correlations between the levels of pancreatic cystathionine and methionine, serine, and glutathione (GSH) emphasized the importance of trans-sulfuration to GSH metabolism for AP progression. CQCQD treatment reversed the metabolic trajectory of the pancreas, and also restored the levels of cystathionine and glutathione synthase. CONCLUSION: Our results have defined a unique time-course metabolic trajectory for AP progression in both the serum and pancreas; it has also revealed a key role of CQCQD in reversing AP-associated metabolic alterations, thus providing new metabolic targets for the treatment and prognosis of AP.

LncRNA LIMT (LINC01089) contributes to sorafenib chemoresistance via regulation of miR-665 and epithelial to mesenchymal transition in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide and HCC patients often develop drug resisitene. Long non-coding RNAs (LncRNAs) are closely related to cell cycle, growth, development, differentiation, and apoptosis. Abnormally expressed lncRNAs have been proved to mediate drug resistance in tumor cells. However, the effect of LIMT on drug resistance has not been explored in HCC. In this study, we explored the effect of long non-coding RNA LIMT on drug resistance and its underlying mechanism in hepatocellular carcinoma (HCC). Our results showed that LncRNA LINC01089 (LIMT) expression is downregulated in 78.57% (44/56) of 56 HCC tumor tissue samples. LIMT expression is also downregulated in HCC cells compared with that in normal liver LO2 cells. Inhibition of LIMT increases the resistance to sorafenib and promotes cell invasion via regulation of epithelial to mesenchymal transition (EMT) in HCC. StarBase V3.0 was used to predict the potential binding site of miR-665 in . Furthermore, miR-665 participates in sorafenib resistance and also regulates the level of EMT-related proteins in HCC cells. A rescue experiment demonstrated that silencing of eliminats the inhibitory effect of the miR-665 inhibitor on sorafenib resistance in HCC cells. Taken together, our findings revealed that downregulation of LIMT increases the resistance of HCC to sorafenib via miR-665 and EMT. Therefore, LIMT, which serves as a therapeutically effective target, will provide new hope for the treatment of HCC.

LncRNA-HOTAIR activates autophagy and promotes the imatinib resistance of gastrointestinal stromal tumor cells through a mechanism involving the miR-130a/ATG2B pathway.

Gastrointestinal stromal tumors (GISTs) are common neoplasms of the gastrointestinal tract that can be treated successfully using C-kit target therapy and surgery; however, imatinib chemoresistance is a major barrier to success in therapy. The present study aimed to discover alternative pathways in imatinib-resistant GISTs. Long noncoding RNAs (lncRNAs) are newly discovered regulators of chemoresistance. Previously, we showed that the lncRNA HOTAIR was upregulated in recurrent GISTs. In this study, we analyzed differentially expressed lncRNAs after imatinib treatment and found that HOTAIR displayed the largest increase. The distribution of HOTAIR in GISTs was shifted from nucleus to cytoplasm after imatinib treatments. The expression of HOTAIR was validated as related to drug sensitivity through Cell Counting Kit-8 assays. Moreover, HOTAIR was associated strongly with cell autophagy and regulated drug sensitivity via autophagy. Mechanistically, HOTAIR correlated negatively with miRNA-130a in GISTs. The downregulation of miRNA-130a reversed HOTAIR-small interfering RNA-induced suppression of autophagy and imatinib sensitivity. We identified autophagy-related protein 2 homolog B (ATG2B) as a downstream target of miR-130a and HOTAIR. ATG2B downregulation reversed the effect of pEX-3-HOTAIR/miR-130a inhibitor on imatinib sensitivity. Finally, HOTAIR was shown to influence the autophagy and imatinib sensitivity of GIST cells in mouse tumor models. Our results suggested that HOTAIR targets the ATG2B inhibitor miR-130a to upregulate the level of cell autophagy so that promotes the imatinib resistance in GISTs.

MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer.

BACKGROUND: Cisplatin is widely used as a first-line treatment for non-small cell lung cancer (NSCLC), but chemoresistance remains a major clinical obstacle for efficient use. As a microRNA, miR-223 was reported to promote the doxorubicin resistance of NSCLC. However, whether miR-223 is also involved in cisplatin resistance of NSCLC and the mechanism miR-223 involved in drug resistance is unclear. Accumulated evidence has shown that abnormal autophagy is associated with tumor chemoresistance. The study aimed to study the role of miR-223 on cisplatin sensitivity in NSCLC and uncover the potential mechanisms. METHODS: NSCLC cells transfected with mimic or inhibitor for miR-223 was assayed for chemoresistance in vitro. MiR-223 expression was assessed by quantitative real-time PCR (qRT-PCR). Western blot were used to study the expression level of F-box/WD repeat-containing protein 7 (FBXW7) and autophagy-related protein. The effect of miR-223 on cisplatin sensitivity was examined by using CCK-8, EdU assays and Autophagic flux assay. Luciferase assays, EdU assays and small interfering RNA were performed to identify the targets of miR-223 and the mechanism by which it promotes treatment resistance. Xenograft models were established to investigate the effect of mir-223 on cisplatin sensitivity. RESULTS: In the present study, we found that the level of miR-223 was significantly positively correlated with cisplatin resistance. MiR-223 overexpression made NSCLC cells resistant to cisplatin treatment. We further found that autophagy mediated miR-223-mediated cisplatin resistance in NSCLC cells. Further mechanistic research demonstrated that miR-223 directly targeted FBXW7. The overexpression of miR-223 could inhibit the level of FBXW7 protein expression, thus promoting autophagy and making NSCLC cells resistant to cisplatin. Finally, we confirmed the increased effect of cisplatin sensitivity by miR-223 Antagomir in xenograft models of NSCLC. CONCLUSIONS: Our results demonstrate that miR-223 could enhance autophagy by targeting FBXW7 in NSCLC cells. Inhibition of autophagy by miR-223 knockdown provides a novel treatment strategy to alleviate cisplatin resistance in NSCLC.

Characterization of N-linked intact glycopeptide signatures of plasma IgGs from patients with prostate carcinoma and benign prostatic hyperplasia for diagnosis pre-stratification.

The discovery of novel non-invasive biomarkers for discriminating between prostate carcinoma (PCa) patients and benign prostatic hyperplasia (BPH) patients is necessary to reduce the burden of biopsies, avoid overdiagnosis and improve quality of life. Previous studies suggest that abnormal glycosylation of immunoglobulin gamma molecules (IgGs) is strongly associated with immunological diseases and prostate diseases. Hence, characterizing N-linked intact glycopeptides of IgGs that correspond to the N-glycan structure with specific site information might enable a better understanding of the molecular pathogenesis and discovery of novel signatures in preoperative discrimination of BPH from PCa. In this study, we profiled N-linked intact glycopeptides of purified IgGs from 51 PCa patients and 45 BPH patients by our developed N-glycoproteomic method using hydrophilic interaction liquid chromatography enrichment coupled with high resolution LC-MS/MS. The quantitative analysis of the N-linked intact glycopeptides using pGlyco 2.0 and MaxQuant software provided quantitative information on plasma IgG subclass-specific and site-specific N-glycosylation. As a result, we found four aberrantly expressed N-linked intact glycopeptides across different IgG subclasses. In particular, the N-glycopeptide IgG2-GP09 (EEQFNSTFR (H5N5S1)) was dramatically elevated in plasma from PCa patients, compared with that in BPH patients (PCa/BPH ratio = 5.74, p = 0.001). Additionally, the variations in these N-linked intact glycopeptide abundances were not caused by the changes in the IgG concentrations. Furthermore, IgG2-GP09 displayed a more powerful prediction capability (auROC = 0.702) for distinguishing PCa from BPH than the clinical index t-PSA (auROC = 0.681) when used alone or in combination with other indicators (auROC = 0.853). In conclusion, these abnormally expressed N-linked intact glycopeptides have potential for non-invasive monitoring and pre-stratification of prostate diseases.

Chimeric peptide supramolecular nanoparticles for plectin-1 targeted miRNA-9 delivery in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis. Insights into the roles of MicroRNAs (miRNAs) in diseases, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Methods: Here, we employed a novel chimeric peptide supramolecular nanoparticle delivery system for plectin-1 (PL-1)-targeted PDAC-specific miR-9 delivery in vitro and in pancreatic cancer patient-derived xenograft (PDX) model. RT-PCR and immunohistochemistry (IHC) were conducted to detect the expression pattern of eIF5A2. mRFP-GFP-LC3 fluorescence microscopy and Western blot were carried out to determine autophagy. Luciferase reporter assays were performed to elucidate the regulatory role of miR-9/eIF5A2 axis. Results: PL-1/miR-9 nanocomplexes dramatically improve the anticancer effect of doxorubicin through downregulating eIF5A2 expression to inhibit autophagy and induce apoptosis in PDAC therapy in vivo. Mechanistically, miR-9 directly targets the eIF5A2 transcript by binding to its 3'-untranslated region (3'-UTR) to reduce the expression levels and the secreted protein of eIF5A2 in PDAC cells. Conclusion: PL-1/miR-9 nanoparticles can be used as a novel promising anti-cancer strategy with tumor targeting and miR-9/eIF5A2 may serve as a new potential therapeutic target for future synergic therapy against human PDAC.

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer.

Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS). Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome. Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5-CD28- group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H- and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed.

Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tumor Effects Of Paclitaxel-Loaded PLGA Nanoparticles For Colorectal Cancer Treatment.

BACKGROUND: Nanoparticles exhibit great promise for improving the solubility and tissue-specific distribution of chemotherapeutic agents; however, the passive and highly variable enhanced permeability and retention (EPR) effects observed in tumors frequently leads to insufficient delivery of nanodrugs into tumors. The tumor-penetrating peptide iRGD can actively enhance tumor-selective delivery of nanoparticles into tumors by binding to integrin and interacting with tissue-penetrating receptor neuropilin-1. MATERIALS AND METHODS: To improve colorectal cancer treatment, in this study, we prepared a paclitaxel (PTX)-loaded PLGA nanoparticle (PLGA-PTX) and evaluated its tumor-targeting and antitumor activity by co-administration with iRGD. RESULTS: Compared to free PTX, encapsulated PTX retained preferential cytotoxicity toward various colorectal cancer cells while effectively sparing healthy cells. PLGA-PTX treatment resulted in cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of cancer cell migration and invasion. PLGA-PTX combined with iRGD displayed little enhancement of cytotoxicity in vitro. Despite this, iRGD receptors integrin and neuropilin-1 were found to be primarily overexpressed on abundant tumor vessels in mice bearing colorectal tumors. Consequently, co-administration of nanoparticles with iRGD promoted the selective delivery of nanoparticles into tumor tissues in vivo. Additionally, the combined regimen enhanced the antitumor effects compared to those of each individual reagent. CONCLUSION: Our findings suggest that PLGA nanoparticles combined with the iRGD peptide provide a promising drug delivery strategy for facilitating active drug accumulation into tumors, given that iRGD receptors are overexpressed on tumor vessels. This co-administration system lacking covalent conjugation provides a more convenient means to combine various therapeutic agents with iRGD to achieve personalized nanotherapy.

Transanal endoscopic microsurgery for radical resection of sigmoid cancer.

PURPOSE: This study aimed to investigate the efficacy and safety of transanal endoscopic microsurgery for radical resection of sigmoid cancer. METHODS: 91 patients with sigmoid cancer who underwent sigmoid cancer resection were divided to the Control Group (43 patients who underwent conventional laparoscopic surgery and pathological specimens were taken through the abdomen) and the Study Group (48 patients who were subjected to transanal endoscopic microsurgery and pathological specimens were taken through the anus). Comparisons were made about the operation time and the amount of surgical bleeding of the two groups, as well as the postoperative exhaust time and postoperative visual analogue score (VAS) of the two groups. Also, factors like the complications, postoperative hospitalization time, additional analgesic treatment, and treatment efficacy of patients within the first month after the surgery were compared between the two groups. Finally, a 3-year follow up for patients was performed to record the 3-year recurrence rates. RESULTS: The operation time and the amount of surgical bleeding of the Study Group were significantly lower than those of the Control Group (p<0.05); the 3-year recurrence rate of the Study Group was lower than that of the Control Group. On the contrary, the 3-year survival rate of the Study Group was significantly higher than that of the Control Group (p<0.05). CONCLUSION: The application of transanal endoscopic microsurgery for radical resection of sigmoid cancer is worthy of clinical promotion despite its high technical requirements for the surgeon and certain degree of promotion difficulty, since it boasts high effective rate, low rate of complications, and the contribution for decreased recurrence rate and improved survival. Key words: anal endoscopic microsurgery, sigmoid cancer, effectiveness, safety analysis.

MiR-204 inhibits hepatocellular cancer drug resistance and metastasis through targeting NUAK1.

Liver cancer is a leading cause of cancer-related deaths globally. Tumor response rate of liver cancer patients towards systemic chemotherapy is low and chemoresistance can easily develop. Identifying novel molecules that can repress drug resistance and metastasis of liver cancer will facilitate the development of new therapeutic strategies. The aim of this study is to determine the roles of NUAK1 and miR-204 in the drug resistance and metastasis of liver cancer and to reveal their relationship. We found that NUAK1 was increased in the tumor of primary liver cancer. Knockdown of NUAK1 significantly inhibited cell growth and migration. Moreover, NUAK1 was the direct downstream target of miR-204, and there was clinical relevance between miR-204 down-regulation and NUAK1 up-regulation in liver cancer. Furthermore, we found that miR-204 increased drug sensitivity by down-regulating NUAK1 expression. Based on these results, we identified miR-204 as a tumor suppressor by inhibiting NUAK1 expression in liver cancer, indicating both miR-204 and NUAK1 may act as promising targets for liver cancer therapy.

MicroRNA-212 suppresses nonsmall lung cancer invasion and migration by regulating ubiquitin-specific protease-9.

MicroRNAs (miRNAs) play crucial roles in various biological processes, including migration, proliferation, differentiation, cell cycling, and apoptosis. Epithelial-mesenchymal transition (EMT) has been shown to be related to the capability of migration and invasion in many tumor cells. In this study, we used wound-healing assay and transwell invasion to analysis the capability of migration and invasion in non-small-cell lung carcinoma (NSCLC), respectively. The expression of ubiquitin-specific protease-9-X-linked (USP9X) and miR-212 messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction and Western blot analysis was used to determine the E-cadherin and vimentin expression. Our results showed that miR-212 mimic inhibited cell migration and invasion, while miR-212 inhibitor increased cell migration and invasion. There was no significant difference between WP1130 and miR-212 mimic combined with WP1130 groups. Moreover, WP1130 inhibited the capability of the migration and invasion of NSCLC cells. Western blot analysis displayed that miR-212 mimic upregulated E-cadherin expression and downregulated vimentin expression, while miR-212 inhibitor downregulated E-cadherin and upregulated vimentin expression. These data showed that miR-212 regulated NSCLC cell invasion and migration by regulating USP9X expression. Taken together, these findings indicated that miR-212 regulated NSCLC cells migration and invasion through targeting USP9X involved in EMT.

USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy.

Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key regulators in cancer chemo-resistance. The present study aimed to investigate the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines and a mouse xenograft model. We found that the expression of USP9X in pancreatic cancer cells was positively correlated with gemcitabine resistance, and that inhibition of USP9X by WP1130 sensitized pancreatic cancer cells to gemcitabine. Gemcitabine induced autophagy, and blocking autophagy with chloroquine improved sensitivity to gemcitabine. We also found that WP1130 inhibited gemcitabine-induced autophagy, and blocking autophagy abolished the sensitization effect of WP1130 on gemcitabine in pancreatic cancer cells. Finally, combined gemcitabine and WP1130 treatment enhanced the anti-tumor effect of gemcitabine by suppressing autophagy in vivo. Taken together, these results demonstrate that inhibition of USP9X sensitized pancreatic cancer cells to gemcitabine by inhibiting autophagy, which provides a novel insight into gemcitabine resistance in pancreatic cancer.