Multifunctional Au Modified Ti3C2-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy.

Ti3C2-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a multifunctional nanoplatform based on Ti3C2-MXene-Au nanocomposites, which combines photothermal properties and peroxidase-like activity, accomplishing synergistic photothermal therapy (PTT) and enzyme dynamic therapy (EDT) accompanied by photoacoustic (PA) and thermal dual-mode imaging in vivo. Furthermore, PTT induces immunogenic cell death, and EDT promotes cell apoptosis, facilitating dendritic cell (DC) maturation and T cell infiltration into the tumor. On this basis, the antibody OX40 (αOX40) was utilized to further contribute immune therapy for reversing the immunosuppressive tumor microenvironment by activating CD4+ and CD8+ T cells. In summary, a triune of PTT/EDT/antitumor immune therapy is achieved by combining Ti3C2-MXene-Au nanocomposites and αOX40, which possesses several strong features of good biocompatibility, NIR-controlled targeting, significant cancer cell killing, and satisfactory biosafety in vitro and in vivo. Our work might highlight the promising application of MXene-based nanoplatforms for cancer therapy.

Screening and Identification of a Novel Anti-Siglec-15 Human Antibody 3F1 and Relevant Antitumor Activity.

Sialic acid-binding Ig-like lectin-15 is an important immunosuppressive molecule considered to be a key target in next-generation tumor immunotherapy. In this study, we screened 22 high-affinity antibodies that specifically recognize human Siglec-15 by using a large human phage antibody library, and five representative sequences were selected for further study. The results showed the binding activity of five antibodies to Siglec-15 (EC50 ranged from 0.02368 µg/mL to 0.07949 µg/mL), and in two Siglec-15-overexpressed cell lines, three antibodies had the strongest binding activity, so the two clones were discarded for further study. Subsequently, the affinity of three antibodies were measured by bio-layer interferometry technology (5-9 × 10E-09M). As the reported ligands of Siglec-15, the binding activity of Siglec-15 and sialyl-Tn, cluster of differentiation 44, myelin-associated glycoprotein, and leucine-rich repeat-containing protein 4C can be blocked by three of the antibodies. Among these, 3F1 had a competitive advantage. Then, the antibody 3F1 showed an obvious antibody-dependent cell-mediated cytotoxicity effect (EC50 was 0.85 µg/mL). Further, antibody 3F1 can reverse the inhibitory effect of Siglec-15 on lymphocyte proliferation (especially CD4+T and CD8+T) and cytokine release Interferon-γ. Given the above results, 3F1 was selected as a candidate for the in vivo pharmacodynamics study. In the tumor model of Balb/c Nude mice, 3F1 (10 mg/kg) showed certain antitumor effects [tumor growth inhibition (TGI) was 31.5%], while the combination of 3F1 (5 mg/kg) and Erbitux (5 mg/kg) showed significant antitumor effects (TGI was 48.7%) compared with the PBS group. In conclusion, novel human antibody 3F1 has antitumor activity and is expected to be an innovative candidate drug targeting Siglec-15 for tumor immunotherapy. SIGNIFICANCE STATEMENT: Siglec-15 is considered as an important target in the next generation of tumor immunotherapy. 3F1 is expected to be the most promising potential candidate for targeting Siglec-15 for cancer treatment and could provide a reference for the development of antitumor drugs.

Peer Support as an Ideal Solution for Racial/Ethnic Disparities in Colorectal Cancer Screening: Evidence from a Systematic Review and Meta-analysis.

BACKGROUND: Low implementation of colorectal cancer screening in ethnic minorities is the main reason for racial and ethnic disparities in colorectal cancer morbidity and mortality. Peer support is widely used for promoting health care in ethnic minorities. However, whether it improves their acceptance to undergo the screening remains controversial. OBJECTIVE: We performed a meta-analysis of the currently available studies to further explore its effectiveness. DATA SOURCES: This meta-analysis was undertaken using PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO for randomized controlled trials. STUDY SELECTION: We included studies that compared peer support interventions among ethnic minorities versus other interventions to promote uptake of colorectal cancer screening. RESULTS: Thirteen studies comprising 8090 participants met the eligibility criteria. Peer support intervention can increase colorectal cancer screening implementation and raise awareness and intention to undergo the screening in ethnic minorities more significantly than fecal occult blood test outreach, print, and usual care. Subgroup analysis showed that peer support intervention achieved great results in Asian Americans and intervention of peer counseling. LIMITATIONS: The results of subgroup analysis had substantial heterogeneity, which may decrease the precision of our estimates. CONCLUSIONS: Peer support can significantly improve the awareness about and the intention for receiving colorectal cancer screening in ethnic minorities and is an ideal choice for promoting the screening among ethnic minorities, particularly in a diverse community. Peer support intervention is recommended to promote the implementation of screening in Asian Americans. Peer counseling is worth promoting; however, church-based peer counseling programs require enhanced management to maintain their fidelity.

CpG methylation signature predicts prognosis in breast cancer.

PURPOSE: DNA methylation can be used as prognostic biomarkers in various types of cancers. We aimed to identify a CpG methylation pattern for breast cancer. METHODS: In this study, using the microarray data from the cancer genome atlas (TCGA) and gene expression omnibus (GEO), we profiled DNA methylation between 97 healthy control samples and 786 breast cancer samples in a training cohort (from TCGA, n = 883) to build a gene classifier using a penalized regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (from GEO, n = 72). RESULTS: A total of 1777 differentially methylated CpGs corresponding to 1777 different methylated genes (DMGs) between breast cancer and control were chosen for this study. Subsequently, 16 CpGs were generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter overall survival (hazard ratio [HR], 4.674; 95% CI 2.918 to 7.487; P = 1.678e-12) than patients with low-risk scores. The prognostic accuracy was also validated in the validation cohorts. Furthermore, among patients with low-risk scores in the combined training and validation cohorts, the patients with the age > 60 years compared with the patients with the age < 60 years were associated with improved overall survival (HR 2.088, 95% CI 1.348 to 3.235; p = 7.575e-04) in patients with a high-risk score but not in patients with low-risk score (HR 1.246, 95% CI 0.515 to 3.011; p = 0.625). The patients treated with radiotherapy compared with the patients without radiotherapy were associated with improved overall survival (HR 0.418, 95% CI 0.249 to 0.703; p = 6.991e-04) in patients with a high-risk score but not in patients with low-risk score (HR 2.092, 95% CI 0.574 to 7.629; p = 0.253). For the patients with recurrence and the patients without recurrence both groups were all associated with improved overall survival (HR 7.475, 95% CI 4.333 to 12.901; p = 6.991e-04) in patients with a high-risk score and in patients with low-risk score (HR 14.33, 95% CI 4.265 to 48.17; p = 4.883e-13). CONCLUSION: The 16 CpG-based signature is useful as a biomarker in predicting prognosis for patients with breast cancer.

Peer support interventions for breast cancer patients: a systematic review.

PURPOSE: Due to the clear efficacy of peer support as a means of improving emotional well-being and healthy behaviors in a highly cost-effective manner, this program is widely used. Controversy remains, however, with regard to its efficacy in breast cancer patients. Given the heterogeneity of peer support interventions, this review aimed to categorize, assess, and synthesize the existing evidence from randomized controlled trials (RCTs) to clarify the effects of different types of peer support on breast cancer patients. METHODS: We searched Pubmed, EMBase, CENTRAL, CINAHL, PsychINFO, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data for English and Chinese language RCTs. The Cochrane Collaboration 'risk of bias' tool for systematic reviews was used to assess the methodological quality of each RCT. RESULTS: Of the 1494 studies screened, 15 studies met eligibility criteria for inclusion, comprising 1695 breast cancer patients. Overall, there were more positive effects than invalid or negative effects across peer interventions, with notable exceptions: unmoderated and unstructured group peer support interventions as well as Internet-based models without peer training had no effect or adverse effects on proximal and distal outcomes. However, adding other peer roles to the peer support structure or using one-on-one models could significantly improve the patients' negative emotions. Peer education showed promising effects on stress management, quality of life, and healthy behaviors. CONCLUSIONS: This systematic review found that different types of peer support have different effects on outcomes for breast cancer patients. Web-based group peer support without peer training must be avoided or used with caution in the future. Peer education is recommended for breast cancer patient support models, given its excellent results and cost-effectiveness.

Characterization of the Stroke-Induced Changes in the Variability and Complexity of Handgrip Force.

Introduction: The variability and complexity of handgrip forces in various modulations were investigated to identify post-stroke changes in force modulation, and extend our understanding of stroke-induced deficits. Methods: Eleven post-stroke subjects and ten age-matched controls performed voluntary grip force control tasks (power-grip tasks) at three contraction levels, and stationary dynamometer holding tasks (stationary holding tasks). Variability and complexity were described with root mean square jerk (RMS-jerk) and fuzzy approximate entropy (fApEn), respectively. Force magnitude, Fugl-Meyer upper extremity assessment and Wolf motor function test were also evaluated. Results: Comparing the affected side with the controls, fApEn was significantly decreased and RMS-jerk increased across the three levels in power-grip tasks, and fApEn was significantly decreased in stationary holding tasks. There were significant strong correlations between RMS-jerk and clinical scales in power-grip tasks. Discussion: Abnormal neuromuscular control, altered mechanical properties, and atrophic motoneurons could be the main causes of the differences in complexity and variability in post-stroke subjects.

Progress in the treatment of advanced gastric cancer.

Gastric cancer is one of the most common malignant tumors in the digestive system. Surgery is currently considered to be the only radical treatment. As surgical techniques improve and progress is made in traditional radiotherapy, chemotherapy, and the implementation of neoadjuvant therapy, the 5-year survival rate of early gastric cancer can reach >95%. However, the low rate of early diagnosis means that most patients have advanced-stage disease at diagnosis and so the best surgical window is missed. Therefore, the main treatment for advanced gastric cancer is the combination of neoadjuvant chemoradiotherapy, molecular-targeted therapy, and immunotherapy. In this article, we summarize several common methods used to treat advanced gastric cancer and discuss the progress made in the treatment of gastric cancer in detail. Only clinical practice and clinical research will allow us to prolong the survival time of patients and allow the patients to truly benefit by paying attention to the individual patient characteristics, drug choice, and developing a reasonable and comprehensive treatment plan.

Emerging Roles of Graphitic Carbon Nitride-based Materials in Biomedical Applications.

Graphite carbon nitride (g-C3N4) is a two-dimensional conjugated polymer with a unique energy band structure similar to graphene. Due to its outstanding analytical advantages, such as relatively small band gap (2.7 eV), low-cost synthesis, high thermal stability, excellent photocatalytic ability, and good biocompatibility, g-C3N4 has attracted the interest of researchers and industry, especially in the medical field. This paper summarizes the latest research on g-C3N4-based composites in various biomedical applications, including therapy, diagnostic imaging, biosensors, antibacterial, and wearable devices. In addition, the application prospects and possible challenges of g-C3N4 in nanomedicine are also discussed in detail. This review is expected to inspire emerging biomedical applications based on g-C3N4.

Association of clinical outcomes and the predictive value of T lymphocyte subsets within colorectal cancer patients.

Introduction: Tumor immunity is a hot topic in tumor research today, and human immunity is closely related to tumor progression. T lymphocyte is an important component of human immune system, and the changes in their subsets may influence the progression of colorectal cancer (CRC) to some extent. This clinical study systematically describes and analyzes the association of CD4+ and CD8+ T-lymphocyte content and CD4+/CD8+ T-lymphocyte ratio with CRC differentiation, clinical pathological stage, Ki67 expression, T-stage, N-stage, carcinoembryonic antigen (CEA) content, nerve and vascular infiltration, and other clinical features, as well as preoperative and postoperative trends. Furthermore, a predictive model is constructed to evaluate the predictive value of T-lymphocyte subsets for CRC clinical features. Methods: Strict inclusion and exclusion criterion were formulated to screen patients, preoperative and postoperative flow cytometry and postoperative pathology reports from standard laparoscopic surgery were assessed. PASS and SPSS software, R packages were invoked to calculate and analyze. Results: We found that a high CD4+ T-lymphocyte content in peripheral blood and a high CD4+/CD8+ ratio were associated with better tumor differentiation, an earlier clinical pathological stage, lower Ki67 expression, shallower tumor infiltration, a smaller number of lymph node metastases, a lower CEA content, and a lower likelihood of nerve or vascular infiltration (P < 0.05). However, a high CD8+ T-lymphocyte content indicated an unpromising clinical profile. After effective surgical treatment, the CD4+ T-lymphocyte content and CD4+/CD8+ ratio increased significantly (P < 0.05), while the CD8+ T-lymphocyte content decreased significantly (P < 0.05). Further, we comprehensively compared the merits of CD4+ T-lymphocyte content, CD8+ T-lymphocyte content, and CD4+/CD8+ ratio in predicting the clinical features of CRC. We then combined the CD4+ and CD8+ T-lymphocyte content to build models and predict major clinical characteristics. We compared these models with the CD4+/CD8+ ratio to explore their advantages and disadvantages in predicting the clinical features of CRC. Discussion: Our results provide a theoretical basis for the future screening of effective markers in reflecting and predicting the progression of CRC. Changes in T lymphocyte subsets affect the progression of CRC to a certain extent, while their changes also reflect variations in the human immune system.

High-affinity decoy protein, nFD164, with an inactive Fc region as a potential therapeutic drug targeting CD47.

CD47, as an innate immune checkpoint molecule, is an important target of cancer immunotherapy. We previously reported that a high-affinity SIRPα variant FD164 fused with IgG1 subtype Fc showed a better antitumor effect than wild-type SIRPα in an immunodeficient tumor-bearing model. However, CD47 is widely expressed in blood cells, and the drugs targeting CD47 may cause potential hematological toxicity. Herein, we modified the FD164 molecule by Fc mutation (N297A) to inactivate the Fc-related effector function and named it nFD164. Moreover, we further studied the potential of nFD164 as a candidate drug targeting CD47, including the stability, in vitro activity, antitumor activity of single or combined drugs in vivo, and hematological toxicity in humanized CD47/SIRPα transgenic mouse model. The results show that nFD164 maintains strong binding activity to CD47 on tumor cells, but has weak binding activity with red blood cells or white blood cells, and nFD164 has good drug stability under accelerated conditions (high temperature, bright light and freeze-thaw cycles). More importantly, in the immunodeficient or humanized CD47/SIRPα transgenic mice bearing tumor model, the combination of nFD164 and anti-CD20 antibody or anti-mPD-1 antibody had a synergistic antitumor effect. Especially in transgenic mouse models, nFD164 combined with anti-mPD-1 significantly enhanced tumor suppressive activity compared with anti-mPD-1 (P < 0.01) or nFD164 (P < 0.01) as a single drug and had fewer hematology-related side effects than FD164 or Hu5F9-G4. When these factors are taken together, nFD164 is a promising high-affinity CD47-targeting drug candidate with better stability, potential antitumor activity, and improved safety profile.

The effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture on chemotherapy-induced peripheral neuropathy (CIPN). Methods: We searched for relevant randomized controlled trials (RCTs) in PubMed, Cochrane Library, and Embase databases from their inception to 1 April 2022. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Brief Pain Inventory-Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), Numerical Rating Scale (NRS), and adverse events were the outcome measures. All studies had at least one of these outcome measures. Mean differences (MDs) with 95% confidence intervals (CIs) were assessed in the meta-analysis using the RevMan 5.3 software. Results: Five studies were included in the analysis. The results showed that acupuncture and placebo acupuncture were not significantly different in reducing chemotherapy-induced neurotoxicity and functional disability (random-effects estimates; MD: 4.30; 95% CI: -0.85~9.45; P = 0.10; I2 = 74%). Acupuncture was better than placebo acupuncture in reducing pain severity and pain interference with patients' daily function (fixed-effect estimates; MD: -1.14; 95% CI: 1.87 to -0.42; P = 0.002; I2 = 13%). Acupuncture was not significantly different from placebo acupuncture in relieving CIPN symptoms (MD: -0.81; 95% CI: -2.02 to 0.40, P = 0.19). Acupuncture improved quality of life better than placebo acupuncture (MD: 10.10; 95% CI: 12.34 to 17.86, P = 0.01). No severe adverse events were recorded in all five studies. Conclusion: This meta-analysis suggests that acupuncture may be more effective and safer in reducing pain severity and pain interference with patients' daily function than placebo acupuncture. Additionally, acupuncture may improve the quality of life of patients with CIPN. However, large sample size studies are needed to confirm this conclusion. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324930, identifier: CRD42022324930.

Study on the file management method of data storage system for airborne radar.

In order to solve the problem that the air-to-ground data transfer rate is much lower than the radar data rate, the onboard system is commonly used for storing the airborne radar data. However, there are two main problems in the data storage using the traditional file management method. The first is that the frequent data updating of the file allocation table (FAT) and the file directory table (FDT) cause a high frequency of address jumps among the discontinuous areas, which leads to a long response time. The second is that the updating frequencies of the FAT, the FDT and the data region are seriously inconsistent, which results in uneven wear of the three areas. To solve these two problems, a file management method, which optimizes the data writing in the three areas of the FAT, the FDT and the data region, is proposed in this study. An actual measurement is carried out on a data storage system of the airborne radar using the proposed file management method. The result shows that the proposed method significantly reduces the updating frequency of FAT and FDT, and achieves the wear levelling of file area and data region.

Screening of gene markers related to the prognosis of metastatic skin cutaneous melanoma based on Logit regression and survival analysis.

BACKGROUND: Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis. METHODS: We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs. RESULTS: Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected. CONCLUSION: The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.

Identification of an MiRNA-mRNA Regulatory Network in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the fourth most prevalent cancer in the world. However, the molecular mechanism underlying CRC is largely unknown. OBJECTIVE: To explore the pathogenic mechanism of CRC and to facilitate better diagnosis and treatment of this disease. METHODS: Differentially expressed miRNAs (DEMs) and genes (DEGs) in CRC vs. Control samples from the miRNA expression data in GSE115513 and the miRNA and mRNA expression data in the TCGA-COAD dataset were screened, followed by the construction of the miRNAmRNA regulatory network. Functional and pathway enrichment analysis, protein-protein interaction (PPI) analysis, and survival analysis were then performed for these DEGs and DEMs. RESULTS: We identified 64 DEMs from the GSE115513 dataset and 265 DEMs and 2218 DEGs from the TCGA-COAD dataset. miR-27a-3p was a hub DEM with the highest degree in the miRNA-mRNA network, while GRIN2B and PCDH10 were hub DEGs targeted by multiple miRNAs, including miR-27a-3p. SNAP25 and GRIN2B were also hub DEGs with the highest degree of interactions in the PPI network. These DEMs and DEGs were significantly enriched in multiple KEGG pathways, including proteoglycans expression and cAMP signaling pathway in cancer. Finally, seven DEGs, including FJX1 Dsc2, and hsa-miR-375, were revealed to be correlated with CRC prognosis. CONCLUSION: Aberrant expressions of genes and miRNAs were involved in the pathogenesis of CRC, probably by regulating proteoglycans expression and cAMP signaling. miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 were identified as potential targets for understanding the pathogenic mechanism of CRC. In addition, FJX1, Dsc2 and hsa-miR-375 were identified as potential predictive markers for CRC prognosis.

Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine.

BACKGROUND: siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells. MATERIALS AND METHODS: The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays. RESULTS: The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%. CONCLUSION: FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.

EIF4E regulates STEAP1 expression in peritoneal metastasis.

Gastric cancer is the most prominent form of malignancy in China, and the high mortality associated with it is mostly due to peritoneal metastasis. We have previously elucidated that the RNA-binding protein poly r(C) binding protein 1 (PCBP1) and miR-3978 function as repressors of peritoneal metastasis, partially by downregulation of six-transmembrane epithelial antigen of the prostate 1 (STEAP1). We now show that STEAP1 is regulated at the level of cap-dependent translation initiation by phosphorylated eIF4E. Chemically inhibiting phosphorylation of eIF4E or genetic ablation of phosphorylated eIF4E inhibit translational upregulation of STEAP1 in the peritoneal metastasis mimicking cell line MKN45 in comparison to the normal mesothelial cell line HMrSV5. Thus phosphorylation of eIF4E is required for peritoneal metastasis of gastric cancer via translational control of STEAP1. Chemical inhibitors targeting phosphorylation of eIF4E or its interaction with the translation initiation complex thus might prove effective in treating patients with peritoneal metastasis.

Intestinal Bacteria Encapsulated by Biomaterials Enhance Immunotherapy.

The human intestine contains thousands of bacterial species essential for optimal health. Aside from their pathogenic effects, these bacteria have been associated with the efficacy of various treatments of diseases. Due to their impact on many human diseases, intestinal bacteria are receiving increasing research attention, and recent studies on intestinal bacteria and their effects on treatments has yielded valuable results. Particularly, intestinal bacteria can affect responses to numerous forms of immunotherapy, especially cancer therapy. With the development of precision medicine, understanding the factors that influence intestinal bacteria and how they can be regulated to enhance immunotherapy effects will improve the application prospects of intestinal bacteria therapy. Further, biomaterials employed for the convenient and efficient delivery of intestinal bacteria to the body have also become a research hotspot. In this review, we discuss the recent findings on the regulatory role of intestinal bacteria in immunotherapy, focusing on immune cells they regulate. We also summarize biomaterials used for their delivery.

Aberrantly Methylated and Expressed Genes as Prognostic Epigenetic Biomarkers for Colon Cancer.

This study aimed to identify prognostic epigenetic biomarkers for colon cancer (CC). Methylation and mRNA expression in CC samples with clinical characteristics that corresponded to those in The Cancer Genome Atlas were analyzed. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were screened between matched tumor and nontumor tissues. Among the 415 DEGs and DMGs that significantly correlated between cytosine-phosphate-guanine (CpG) methylation and gene expression, unc-5 netrin receptor C (UNC5C), solute carrier family 35 member F (SLC35F)1, Ly6/Neurotoxin (LYNX)1, stathmin (STMN)2, slit guidance ligand (SLIT)3, cell adhesion molecule L1 like (CHL1), CAP-Gly domain containing linker protein family member 4 (CLIP4), transmembrane protein (TMEM) 255A, granzyme B (GZMB), and brain expressed X-Linked (BEX)1 were promising epigenetic biomarkers. Prediction was more accurate when models were based on the expression and/or methylation of GZMB rather than clinical stage. Comparisons of tissues with high or low GZMB expression significantly associated the DEGs with natural killer-mediated cytotoxicity, cytokine-cytokine receptor interactions, and chemokine signaling pathways. From among the 10 epigenetic biomarkers, GZMB might serve as a tumor suppressor and function in several immune-related pathways in CC. Prognostic models based on GZMB expression and/or methylation would be significant for patients with CC.

MicroRNA-143 suppresses the proliferation and metastasis of human gastric cancer cells via modulation of STAT3 expression.

Accumulating evidences suggest that miRNAs may prove essential therapeutic targets for the treatment of cancer. Herein, the role and therapeutic implications of miRNA-143 was investigated in gastric cancer. The results revealed miRNA-143 to be aberrantly downregulated in gastric cancer cell lines. Ectopic expression of miRNA-143 resulted in a significant (P<0.05) inhibition of AGS gastric cancer cell proliferation suggestive of the tumor suppressive role of miRNA-143. The inhibition of AGS cell proliferation was mainly via activation of apoptotic cell death as evident from the AO/EB and annexin V/PI staining. Additionally, miR-143 overexpression also caused a significant (P<0.05) decline in the migration and invasion of AGS cells. TargetScan analysis and the dual luciferase assay revealed STAT3 to be the potential target of miRNA-143 in AGS cells. Analysis of STAT3 expression in gastric cancer cell lines showed upto 3.5 fold upregulation of STAT3. However, miRNA-143 overexpression resulted in considerable downregulation of STAT3 expression. Silencing of STAT3 also resulted in the inhibition of cell proliferation, migration and invasion of the AGS cells. Moreover, overexpression of STAT3 could nullify the tumor suppressive effects of miRNA-143 in AGS cells. Taken together, miRNA-143 has a tumor suppressive role in gastric cancer and may prove essential in gastric cancer treatment.

Long non-coding RNA OIP5-AS1 promotes the growth of gastric cancer through the miR-367-3p/HMGA2 axis.

Increasing evidence shows that aberrant lncRNAs expression contributes to the progression of gastric cancer (GC). The role of the novel lncRNA OIP5-AS1 and its underlying mechanisms in the growth of GC is largely unknown. Here we demonstrate for the first time that OIP5-AS1 expression was up-regulated in GC tissues and cell lines, which significantly correlated with unfavorable clinical characteristics and shorter survival. The results of in vitro and in vivo gain- and loss-of-function experiments indicate that OIP5-AS1 promoted cell proliferation and colony formation while inhibiting apoptosis of GC cells. OIP5-AS1 functioned as an endogenous sponge for miR-367-3p in GC cells. Restoration of miR-367-3p expression abolished the biological effects of OIP5-AS1 on GC cells. Moreover, we show that HMGA2 was a downstream target of miR-367-3p and mediated the effects of OIP5-AS1 on GC cells. OIP5-AS1 regulated the activities of the PI3K/AKT and Wnt/ß-catenin pathways through HMGA2. In conclusion, OIP5-AS1 functions as an oncogenic lncRNA that promotes the progression of GC and may serve as a therapeutic target for managing GC.