Recent Advances in Fluorescent Probes for G-quadruplex DNAs / RNAs.

Guanine-quadruplexes (G4s) are high-level structures formed by the folding of guaninerich nucleic acid sequences. G4s play important roles in various physiological processes, such as gene transcription, replication, recombination, and maintenance of chromosomal stability. Specific and sensitive monitoring of G4s lays the foundation for further understanding the structure, content, distribution, and function of G4s in organisms, which is important for the treatment and diagnosis of diseases. Moreover, visualization of G4s will provide new ideas for developing antitumor strategies targeting G4s. The design and development of G4-specific ligands are challenging due to the subtle differences in the structure of G4s. This review focuses on the progress of research on G4 fluorescent probes and their binding mechanisms to G4s. Finally, the challenges and future prospects for better detection and targeting of G4s in different organisms are discussed. This paper provides ideas for the development of novel G4 fluorescent probes.

Mechanism of Peptide Self-assembly and Its Study in Biomedicine.

The development of peptide-based materials is one of the most challenging aspects of biomaterials research in recent years. The assembly of peptides is mainly controlled by forces such as hydrogen bonding, hydrophobic interaction, electrostatic interaction, and π-π accumulation. Peptides have unique advantages such as simple structure, easy synthesis, good biocompatibility, non-toxicity, easy modification, etc. These factors make peptides turn into ideal biomedical materials, and they have a broad application prospect in biomedical materials, and thus have received wide attention. In this review, the mechanism and classification of peptide self-assembly and its applications in biomedicine and hydrogels were introduced.

Mechanisms and influencing factors of peptide hydrogel formation and biomedicine applications of hydrogels.

Self-assembled peptide-based hydrogels have shown great potential in bio-related applications due to their porous structure, strong mechanical stability, high biocompatibility, and easy functionalization. Herein, the structure and characteristics of hydrogels and the mechanism of action of several regular secondary structures during gelation are investigated. The factors influencing the formation of peptide hydrogels, especially the pH responsiveness and salt ion induction are analyzed and summarized. Finally, the biomedical applications of peptide hydrogels, such as bone tissue engineering, cell culture, antigen presentation, antibacterial materials, and drug delivery are reviewed.

Synthesis and mechanism of action of new purine derivatives against triple negative breast cancer.

Triple negative breast cancer (TNBC) is considered to be the most difficult subtype of breast cancer to treat because of its extremely prone to metastasis and the lack of targeted therapy drugs. New purine derivatives were synthesized and evaluated in a series of kinases and cell lines. The most active compounds 3g and 3j were selected based on their antiproliferative activities, then their pharmaceutical activity and mechanism in MDA-MB-231 cells were analyzed. The results in vitro indicated that compounds 3g and 3j can induce MDA-MB-231 cells apoptosis, and inhibit its migration and angiogenesis through influencing protein expression such as Bcl-2, Bax, Bcl-xl, P38, MMP2, MMP9, AKT and EGFR. In vivo results indicate that compounds 3g and 3j can inhibit tumor growth and metastasis and reduce the expression of Ki67 and CD31 protein in TNBC xenograft models. These findings not only broaden our understanding of the anti-TNBC effects and mechanisms of compounds 3g and 3j, but also provide new ideas and reference directions for the treatment of TNBC.

Recent advances in the development of inhibitors targeting KRAS-G12C and its related pathways.

The RAS gene, also known as the mouse sarcoma virus, includes three genes (KRAS, HRAS, and NRAS) that are associated with human tumors. Among them, KRAS has the highest incidence of mutations in cancer, accounting for around 80% of cases. At the molecular level, the RAS gene plays a regulatory role in transcription and translation, while at the cellular level, it affects cell proliferation and migration, making it crucial for cancer development. In 2021, the FDA approved AMG510, the first direct inhibitor targeting the KRAS-G12C mutation, which has shown tumor regression, prolonged survival, and low off-target activity. However, with the increase of drug resistance, a single inhibitor is no longer sufficient to achieve the desired effect on tumors. Therefore, a large number of other highly efficient inhibitors are being developed at different stages. This article provides an overview of the mechanism of action targeting KRAS-G12C in the KRASGTP-KRASGDP cycle pathway, as well as the structure-activity relationship, structure optimization, and biological activity effects of inhibitors that target the upstream and downstream pathways, or combination therapy.

The predictive value of CD4, CD8, and C-reactive protein in the prognosis of schistosomal and non-schistosomal colorectal cancer.

BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China and occasional outbreaks occur in Europe in recent years. The relationship between inflammation caused by Schistosoma japonicum and colorectal cancer (CRC) is still obscure, and the inflammation based prognostic systems of schistosomal colorectal (SCRC) has rarely been reported. AIM: To explore the different roles of tumor infiltrating lymphocytes (TILs) and C-reactive protein (CRP) in SCRC and in Non-schistosomal CRC (NSCRC), providing a possible predictive system to evaluate outcomes and to improve the risk stratification for CRC patients, especially for CRC patients with schistosomiasis. METHODS: Three hundred fifty-one CRC tumors were evaluated for density of CD4 + , CD8 + T cells and CRP in intratumoral and stromal compartments by immunohistochemical using tissue microarray. RESULTS: There were no association between TILs and CRP and schistosomiasis. Multivariate analysis identified stromal CD4 (sCD4) (p = 0.038), intratumoral CD8 (iCD8) (p = 0.003), schistosomiasis (p = 0.045) as independent prognostic factors for overall survival (OS) in the whole cohort; and sCD4 (p = 0.006) and iCD8 (p = 0.020) were independent prognostic factors for OS in the NSCRC and SCRC set, respectively. Besides, we found that there were no differences of TILs and CRP, which were distributed in different areas of tumor tissue, between CRC patients with and without schistosomiasis. CONCLUSION: The results remind us that different subtypes of TILs have distinguished biological behavior and prognosis value in the immune microenvironment of NSCRC and SCRC patients. Meanwhile, the findings require us to stratify patients with schistosomiasis and this might facilitate patient counseling and management.

Association between serum iron, blood lead, cadmium, mercury, selenium, manganese and low cognitive performance in old adults from National Health and Nutrition Examination Survey (NHANES): a cross-sectional study.

Cognitive decline is a public health problem for the world's ageing population. This study was to evaluate the relationships between serum Fe, blood Pb, Cd, Hg, Se and Mn and cognitive decline in elderly Americans. Data of this cross-sectional study were extracted from the National Health and Nutritional Examination Survey (NHANES 2011-2014). Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency and Digit Symbol Substitution Test (DSST) tests. Weighted univariable and multivariate logistic regression analyses were used to assess the associations between six trace elements and low cognitive performance. Subgroup analyses based on diabetes and hypertension history were further assessed the associations. A total of 2002 adults over 60 years old were included. After adjusting covariates, elevated serum Fe levels were associated with the decreased risk of low cognitive performance, especially in the elderly without diabetes history and with hypertension history. High blood Cd levels were associated with the high odds of low cognitive performance in old adults with diabetes and hypertension history. Elevated blood Mn levels were connected with low cognitive performance in old hypertensive people. High blood Pb levels were related to the high odds of low cognitive performance, especially in the elderly without diabetes and hypertension history. High blood Se levels were linked to the decreased risk of low cognitive performance in all the elderly. Appropriate Fe, Se supplementation and Fe-, Se-rich foods intake, while reducing exposure to Pb, Cd and Mn may be beneficial for cognitive function in the elderly.

Spectroscopic studies on noncovalent binding of nicotinamide-modified BRCA1 (856-871) analogs to calf thymus DNA.

Various peptide drugs have entered the market with the development of molecular biology. Peptide drugs are used for treat diseases such as diabetes, breast cancer, and HIV infection. In this study, three nicotinamide-modified peptides were synthesized by modifying the N-terminus of BRCA1 (856-871, Y856R, K862Y, R866W) peptide with three nicotinic acid derivatives using solid-phase peptide synthesis. The results of calf thymus DNA (ctDNA) binding activity indicated that binding constants of BRCA1 (856-871, Y856R, K862Y, R866W) (P0) and three nicotinamide-modified peptides (P1, P2, and P3) to ctDNA were 1.89 × 103, 2.97 × 104, 7.61 × 104, and 8.09 × 104 L·mol-1, respectively. The binding affinity of the modified peptides was superior to that of BRCA1 (856-871, Y856R, K862Y, R866W). ΔHθ < 0 and ΔSθ < 0 indicated that van der Waals force and hydrogen bond contributed most to peptide-ctDNA binding. Results obtained by Circular dichroism (CD) indicated that peptide binding interaction led to conformational changes in ctDNA. Ultraviolet-visible (UV) spectroscopy, ethidium bromide (EB) competition experiments, DNA melting experiments, and viscosity measurements verified that peptides interacted with ctDNA via groove binding. Ionic strength experiments manifested that electrostatic binding was also involved in peptide-ctDNA binding.

Comparison of the prognostic value of stromal tumor-infiltrating lymphocytes and CD3 + T cells between schistosomal and non-schistosomal colorectal cancer.

AIM: To compare the prognostic value of tumor-infiltrating lymphocytes (TILs) and CD3 + cells and CD20 + cells between schistosomal colorectal cancer (SCRC) and non-schistosomal CRC (NSCRC). BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China, and occasional outbreaks occur in Europe recently. The role of immune cells in the immune microenvironment of SCRC and NSCRC is remaining obscure, and the inflammation-based prognostic systems of SCRC has rarely been reported. METHODS: HE-stained sections of 349 colorectal cancer (CRC) tumors, which were completely resected, were evaluated for density of TILs. Meanwhile, we evaluated CD3 + T lymphocytes and CD20 + B lymphocytes by immunochemistry. The relationship of these infiltrating immune cells with clinicopathological features, including schistosomiasis, and clinical outcomes was evaluated, and the prognostic roles of TILs in SCRC and NSCRC were explored. RESULTS: Except for age (P < 0.0001), there were no significant differences between NSCRC and SCRC patients in clinicopathological features (P > 0.05). Beside, the positive expression pattern of sTILs, iTILs, CD3, and CD20 between NSCRC and SCRC patients was also similar (P > 0.05). In the whole cohort, sTILs and CD3 were defined as independent prognostic factors (P = 0.031 and P = 0.003, respectively). CD3 was an independent prognostic factor both in the NSCRC and SCRC set (P = 0.026 and P = 0.045, respectively). Higher sTILs, CD3, and CD20 were correlated with less aggressive tumor characteristics in the whole cohort and in subgroups. CONCLUSION: Although CD3 was an independent prognostic factor for both NSCRC and SCRC set, there were no significant differences between SCRC and NSCRC patients in sTILs, CD3, CD20, and in other clinicopathological features.

Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke.

Our previous study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes (hNSC-Exo) in ischemic stroke. Here, we loaded brain-derived neurotrophic factor (BDNF) into exosomes derived from NSCs to construct engineered exosomes (BDNF-hNSC-Exo) and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo. In a model of H2O2-induced oxidative stress in NSCs, BDNF-hNSC-Exo markedly enhanced cell survival. In a rat middle cerebral artery occlusion model, BDNF-hNSC-Exo not only inhibited the activation of microglia, but also promoted the differentiation of endogenous NSCs into neurons. These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stroke. Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.

Synapsin 1 Ameliorates Cognitive Impairment and Neuroinflammation in Rats with Alzheimer's Disease: An Experimental and Bioinformatics Study.

BACKGROUND: Alzheimer's disease (AD) is a persistent neuropathological injury that manifests via neuronal/synaptic death, age spot development, tau hyperphosphorylation, neuroinflammation, and apoptosis. Synapsin 1 (SYN1), a neuronal phosphoprotein, is believed to be responsible for the pathology of AD. OBJECTIVE: This study aimed to elucidate the exact role of SYN1 in ameliorating AD and its potential regulatory mechanisms. METHODS: The AD dataset GSE48350 was downloaded from the GEO database, and SYN1 was focused on differential expression analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. After establishing an AD rat model, they were treated with RNAi lentivirus to trigger SYN1 overexpression. The amelioration of SYN1 in AD-associated behavior was validated using multiple experiments (water maze test and object recognition test). SYN1's repairing effect on the important factors in AD was confirmed by detecting the concentration of inflammatory factors (interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α), neurotransmitters (acetylcholine (ACh), dopamine (DA), and 5-hydroxytryptophan (5-HT)) and markers of oxidative stress (glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS)). Molecular biology experiments (qRT-PCR and western blot) were performed to examine AD-related signaling pathways after SYN1 overexpression. RESULTS: Differential expression analysis yielded a total of 545 differentially expressed genes, of which four were upregulated and 541 were downregulated. The enriched pathways were basically focused on synaptic functions, and the analysis of the protein- protein interaction network focused on the key genes in SYN1. SYN1 significantly improved the spatial learning and memory abilities of AD rats. This enhancement was reflected in the reduced escape latency of the rats in the water maze, the significantly extended dwell time in the third quadrant, and the increased number of crossings. Furthermore, the results of the object recognition test revealed reduced time for rats to explore familiar and new objects. After SYN1 overexpression, the cAMP signaling pathway was activated, the phosphorylation levels of the CREB and PKA proteins were elevated, and the secretion of neurotransmitters such as ACh, DA, and 5-HT was promoted. Furthermore, oxidative stress was suppressed, as supported by decreased levels of MDA and ROS. Regarding inflammatory factors, the levels of IL-6, IL-1ß, and TNF-α were significantly reduced in AD rats with SYN1 overexpression. CONCLUSION: SYN1 overexpression improves cognitive function and promotes the release of various neurotransmitters in AD rats by inhibiting oxidative stress and inflammatory responses through cAMP signaling pathway activation. These findings may provide a theoretical basis for the targeted diagnosis and treatment of AD.

Preparation and Properties of Egg White Dual Cross-Linked Hydrogel with Potential Application for Bone Tissue Engineering.

In this study, an egg white dual cross-linked hydrogel was developed based on the principle that the external stimulus can denature proteins and cause them to aggregate, forming hydrogel. The sodium hydroxide was used to induce gelation of the egg white protein, subsequently introducing calcium ions to cross-link with protein chains, thereby producing a dual cross-linked hydrogel. The characteristics of the dual cross-linked hydrogels-including the secondary structure, stability, microstructure, swelling performance, texture properties, and biosafety-were investigated to determine the effects of calcium ion on the egg white hydrogel (EWG) and evaluate the potential application in the field of tissue engineering. Results showed that calcium ions could change the ß-sheet content of the protein in EWG after soaking it in different concentrations of CaCl2 solution, leading to changes in the hydrogen bonds and the secondary structure of polypeptide chains. It was confirmed that calcium ions promoted the secondary cross-linking of the protein chain, which facilitated polypeptide folding and aggregation, resulting in enhanced stability of the egg white dual cross-linked hydrogel. Furthermore, the swelling capacity of the EWG decreased with increasing concentration of calcium ions, and the texture properties including hardness, cohesiveness and springiness of the hydrogels were improved. In addition, the calcium cross-linked EWG hydrogels exhibited biocompatibility and cell-surface adhesion in vitro. Hence, this work develops a versatile strategy to fabricate dual cross-linked protein hydrogel with biosafety and cell-surface adhesion, and both the strategy and calcium-egg white cross-linked hydrogels have potential for use in bone tissue engineering.

YAFAF-Based Hydrogel: Characterization, Mechanism, and Factors Influencing Micro-organization.

The YAFAF-based hydrogel was a three-dimensional network cross-linked by grooved fiber bundles. The fiber bundles were formed by entanglement of fibrils with a diameter of 2 nm, and the surface of the fibrils also presented grooves. Spectroscopic analysis revealed that the main secondary structures were ß-sheets and ß-turns, which led to the grooved feature of fibrils. In comparison of the nuclear magnetic resonance spectra of peptide solutions at 313 and 277 K, the nuclear Overhauser effects can be clearly observed, indicating that hydrogen-bondings and π-π stacking interactions play important roles in self-assembly. The micro-organization of the self-assemblies was affected by the ratio of solvents (xA) remarkably. Unexpectedly, xA of 0.05 produced hollow spherical aggregates. The result of these investigations on the mechanism and organization of the YAFAF-based hydrogel can contribute to the development of strategies using hydrogels in the food industry.

Natural 8-C-ascorbyl-(-)-epigallocatechin as antidiabetic agent: α-glucosidase and PTP-1B signaling pathway dual regulators.

α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) signaling pathway dual regulators decrease postprandial blood glucose levels and improve insulin sensitivity, making it a new treatment strategy for type 2 diabetes. This study examined in vitro antidiabetic activities of 8-C-ascorbyl-(-)-epigallocatechin (AE), found in oolong tea. AE inhibited α-glucosidase (IC50 = 142.8 µM) with activity higher than that of acarbose (IC50 = 250.2 µM). AE significantly promoted glucose-consumption and activated the insulin signaling pathway through enhancing the protein levels of p-GSK3ß and p-Akt and inhibiting the expression of PTP1B, along with slightly inhibitory activity against PTP1B. Docking analysis showed AE inhibited α-glucosidase activity via binding to the catalytic site through hydrogen bonds and Pi-Pi interactions, as well as a good shape match to the active pocket. In addition, AE could relieve oxidative damage and possessed good antioxidant capacity. Taken together, the results of this study indicate that AE exhibits antidiabetic activity in vitro, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12).

INTRODUCTION: Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50-50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation. METHODS AND ANALYSIS: The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization. ETHICS AND DISSEMINATION: This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.

Design, synthesis and properties of peptide inhibitors based on BRCA1856-871.

Overexpression of RAD51 protein was found to increase drug resistance in breast cancer cells. Breast cancer susceptibility gene 1 (BRCA1) protein can specifically bind to RAD51 protein and regulate the expression level of RAD51 protein. Based on previous studies, eight modified peptides were obtained by modifying the N-terminus of the key peptide segment 856-871 of BRCA1 with nicotinic acid (NA) and its derivatives. The interaction of BRCA1856-871 and modified peptides with the RAD51158-180 target peptide was investigated by fluorescence and circular dichroism spectroscopies. The results showed that the binding ability of 2-TFM-NA-PP to RAD51158-180 was significantly enhanced. BRCA1856-871 and modified peptides were studied by in vitro cell experiments. The results showed that the antitumor activity of 5-TFM-NA-PP was significantly enhanced compared with BRCA1856-871.

In vitro and in vivo evaluation of DC-targeting PLGA nanoparticles encapsulating heparanase CD4+ and CD8+ T-cell epitopes for cancer immunotherapy.

Heparanase has been identified as a universal tumor-associated antigen, but heparanase epitope peptides are difficult to recognize. Therefore, it is necessary to explore novel strategies to ensure efficient delivery to antigen-presenting cells. Here, we established a novel immunotherapy model targeting antigens to dendritic cell (DC) receptors using a combination of heparanase CD4+ and CD8+ T-cell epitope peptides to achieve an efficient cytotoxic T-cell response, which was associated with strong activation of DCs. First, pegylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate a combined heparanase CD4+ and CD8+ T-cell epitope alone or in combination with Toll-like receptor 3 and 7 ligands as a model antigen to enhance immunogenicity. The ligands were then targeted to DC cell-surface molecules using a DEC-205 antibody. The binding and internalization of these PLGA NPs and the activation of DCs, the T-cell response and the tumor-killing effect were assessed. The results showed that PLGA NPs encapsulating epitope peptides (mHpa399 + mHpa519) could be targeted to and internalized by DCs more efficiently, stimulating higher levels of IL-12 production, T-cell proliferation and IFN-γ production by T cells in vitro. Moreover, vaccination with DEC-205-targeted PLGA NPs encapsulating combined epitope peptides exhibited higher tumor-killing efficacy both in vitro and in vivo. In conclusion, delivery of PLGA NP vaccines targeting DEC-205 based on heparanase CD4+ and CD8+ T-cell epitopes are suitable immunogens for antitumor immunotherapy and have promising potential for clinical applications.

Radiotherapy-Related Neurologic Complications in Patients with Nasopharyngeal Carcinoma: A Multicenter Epidemiologic Study in Southern China.

BACKGROUND: We aim at describing the incidence, potential predisposing factors, and progression of major radiotherapy-related neurologic complications (RRNC) in nasopharyngeal carcinoma (NPC)-endemic regions, especially southern China. METHODS: We performed a multicenter longitudinal retrospective study with clinical follow-ups in 22,302 patients with post-radiotherapy NPC between January 2003 and June 2017 covering three major residential areas. Epidemiology, potential predisposing/protective factors, clinicopathologic progression, and survival conditions of each RRNC were separately recorded and analyzed on the basis of their related clinical, radiologic, and laboratory parameters. RESULTS: 949 new cases of RRNCs occurred among the 22,302 patients with post-radiotherapy NPC during 101,714 person years' follow-up, which is equal to an incidence density rate of 9.3 new cases per 1000 person year. Radiation-induced cranial nerve palsy showed the highest incidence (2.68%, 597/22,302) with the earliest onset (median latency, 4.45 years) as well. Patients benefited from intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in both overall survival (median survival 13.2 years for IMRT vs. 8.3 years for CRT) and RRNC-free survival (except for epilepsy and cranial nerve palsy). Causes of death varied substantially between patients with or without RRNCs. CONCLUSIONS: Our study indicates a non-negligible incidence of RRNC spectrum in southern China in the past ten years. IMRT is one of the most significant protectors against development and progression of RRNCs. IMPACT: Our findings support the hypothesis that patients with NPC with preexisting predispositions would receive long-term benefits from IMRT and other dose-related modulations (like hyperfractionation and dose conformation).

Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer.

BACKGROUND: The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported. METHODS: Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells. RESULTS: In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045). CONCLUSIONS: The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

Effect of differential hypoxia-related gene expression on glioblastoma.

OBJECTIVE: Glioblastoma (GB) is a refractory malignancy with a high rate of recurrence and treatment resistance. Hypoxia-related genes are promising prognostic indicators for GB, so we herein developed a reliable hypoxia-related gene risk scoring model to predict the prognosis of patients with GB. METHOD: Gene expression profiles and corresponding clinicopathological features of patients with GB were obtained from the Cancer Genome Atlas (TCGA; n = 160) and Gene Expression Omnibus (GEO) GSE7696 (n = 80) databases. Univariate and multivariate Cox regression analyses of differentially expressed hypoxia-related genes were performed using R 3.5.1 software. RESULT: Fourteen prognosis-related genes were identified and used to construct a risk signature. Patients with high-risk scores had significantly lower overall survival (OS) than those with low-risk scores. The median risk score was used as a critical value and for OS prediction in an independent external verification GSE7696 cohort. Risk score was not significantly affected by clinical-related factors. We also developed a prediction nomogram based on the TCGA training set to predict survival rates, and included six independent prognostic parameters in the TCGA prediction model. CONCLUSION: We determined a reliable hypoxia-related gene risk scoring model for predicting the prognosis of patients with GB.