Nutritional therapy bridges the critical cut-off point for the closed-loop role of type 2 diabetes and bone homeostasis: A narrative review.

Currently, osteoporosis-related fractures become the most cutting-edge problem of diabetes-related complications. Rational diet is not only the basis of glycemic management in type 2 diabetes patients, but also the direction of diabetic bone health. This review highlights the importance of micronutrient supplementation (including calcium, magnesium, zinc, vitamin D, vitamin K, and vitamin C) for patients with T2DM, as well as describing the constructive intermediary role of gut flora between T2DM and bone through nutrients predominantly high in dietary fiber. In addition, it is recommended to combine the Mediterranean dietary pattern with other diversified management approaches to prevent OP. Therefore, this provides a theoretical basis for the potential role of islet ß-cells in promoting bone health.

[Effect of early pulmonary rehabilitation training on the prognosis of patients with acute respiratory distress syndrome after weaning of invasive mechanical ventilation in the intensive care unit].

OBJECTIVE: To investigate the effect of early pulmonary rehabilitation (PR) training on the improvement of respiratory function in patients with acute respiratory distress syndrome (ARDS) after weaning of invasive mechanical ventilation in the intensive care unit (ICU). METHODS: The retrospective cohort research method was used. The clinical information of adult patients with ARDS receiving invasive mechanical ventilation admitted to the ICU of Qingdao Municipal Hospital from January 2019 to March 2023 was collected. The patients were divided into a control group and an observation group according to off-line training program. The control group received traditional training after weaning, and the observation group received the early PR training after weaning. Other treatments and nursing were implemented according to the routine of the ICU. The scores of the short physical performance battery (SPPB) on day 3-day 6 of the weaning training, respiratory muscle strength, level of interleukin-6 (IL-6), number of aspirations of sputum after weaning, length of stay after weaning, rehospitalization rate within 6 months after discharge, and pulmonary function indicators at discharge and 3 months after discharge [peak expiratory flow (PEF), forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and vital capacity (VC)] of the two groups of patients were compared. The Kaplan-Meier survival curve was drawn to analyze the cumulative survival rate of patients 6 months after discharge. RESULTS: A total of 50 of which 25 cases received the traditional training after weaning, 25 cases received the early PR training after weaning. There was no significant difference in gender, age, acute physiology and chronic health evaluation II (APACHE II), oxygenation index upon admission, etiological diagnosis of ARDS upon admission, time of invasive ventilation, mode of invasive mechanical ventilation, pulmonary function indicators at discharge, and other baseline data of the two groups. The SPPB questionnaire scores and respiratory muscle strength in both groups were increased gradually with the extended offline training time, the serum level of IL-6 in both groups were descend gradually with the extended offline training time, especially in the observation group [SPPB questionnaire score in the observation group were 7.81±0.33, 8.72±0.53, 9.44±0.31, 10.57±0.50, while in the control group were 7.74±0.68, 8.73±0.37, 8.72±0.40, 9.33±0.26, effect of time: F = 192.532, P = 0.000, effect of intervention: F = 88.561, P = 0.000, interaction effect between intervention and time: F = 24.724, P = 0.000; respiratory muscle strength (mmHg, 1 mmHg≈0.133 kPa) in the observation group were 123.20±24.84, 137.00±26.47, 149.00±24.70, 155.40±29.37, while in the control group were 129.00±20.34, 126.00±24.01, 132.20±25.15, 138.60±36.67, effect of time: F = 5.926, P = 0.001, effect of intervention: F = 5.248, P = 0.031, interaction effect between intervention and time: F = 3.033, P = 0.043; serum level of IL-6 in the observation group were 80.05±6.81, 74.76±9.33, 63.66±10.19, 56.95±4.72, while in the control group were 80.18±7.21, 77.23±9.78, 71.79±10.40, 66.51±6.49, effect of time: F = 53.485, P = 0.000, effect of intervention: F = 22.942, P = 0.000, interaction effect between intervention and time: F = 3.266, P = 0.026]. Compared with the control group, the number of aspirations of sputum after weaning of patients in the observation group significantly decreased (number: 22.46±1.76 vs. 27.31±0.90), the length of ICU stay after weaning significantly became shorter (days: 6.93±0.95 vs. 8.52±2.21), and the rehospitalization rate within 6 months after discharge significantly decreased [20.00% (5/25) vs. 48.00% (12/25)]. There were significant differences. The pulmonary function indicators 3 months after discharge of two groups of patients significantly increased compared with those at discharge and those of the observation group were significantly higher than those of the control group [PEF (L/min): 430.20±95.18 vs. 370.00±108.44, FEV1/FVC ratio: 0.88±0.04 vs. 0.82±0.05, VC (L): 3.22±0.72 vs. 2.74±0.37, all P < 0.05]. The Kaplan-Meier survival curve showed that the cumulative survival rate of patients 6 months after discharge of patients in the observation group was significantly higher than that of patients in the control group [76.9% vs. 45.5%, hazard ratio (HR) = 0.344, P = 0.017]. CONCLUSIONS: Early PR training can significantly improve the respiratory function of patients with ARDS after weaning of invasive mechanical ventilation. Continuous active respiratory training after discharge can improve the respiratory function of patients and effectively decrease mortality.

Cafestol inhibits colon cancer cell proliferation and tumor growth in xenograft mice by activating LKB1/AMPK/ULK1-dependent autophagy.

Chemotherapy failure in colorectal cancer patients is the major cause of recurrence and poor prognosis. As a result, there is an urgent need to develop drugs that have a good chemotherapy effect while also being extremely safe. In this study, we found cafestol inhibited colon cancer growth and HCT116 proliferation in vivo and in vitro, and improved the composition of intestinal flora. Further metabolomic data showed that autophagy and AMPK pathways were involved in the process of cafestol's anti-colon cancer effects. The functional validation studies revealed that cafestol increased autophagy vesicles and LC3B-II levels. The autophagic flux induced by cafestol was prevented by using BafA1. The autophagy inhibitor 3-MA blocked the cafestol-induced increase in LC3B-II and cell proliferation inhibition. Then we found that cafestol induced the increased expressions of LKB1, AMPK, ULK1, p-LKB1, p-AMPK, and p-ULK1 proteins in vivo and in vitro. Using the siRNA targeted to the Lkb1 gene, the levels of AMPK, ULK1, and LC3B-II were suppressed under cafestol treatment. These results indicated that the effect of cafestol is through regulating LKB1/AMPK/ULK1 pathway-mediated autophagic death. Finally, a correlation matrix of the microbiome and autophagy-related proteins was conducted. We found that cafestol-induced autophagic protein expression was positively correlated with the beneficial intestinal bacteria (Muribaculaceae, Bacteroides, Prevotellacece, and Alloprevotella) and negatively correlated with the hazardous bacteria. Conclusions: This study found that cafestol inhibited colon cancer in vitro and in vivo by the mechanism that may be related to LKB1/AMPK/ULK1 pathway-mediated autophagic cell death and improved intestinal microenvironment.

Life's Essential 8, Life's Simple 7 and the odds of hyperuricaemia: results from the China Multi-Ethnic Cohort Study.

Objective: Life's Essential 8 (LE8) is a new comprehensive metric based on Life's Simple 7 (LS7). Few studies have investigated the association between LE8 and the odds of hyperuricaemia (HUA). This study examined the association between LE8, LS7 with odds of HUA. Methods: We cross-sectionally analysed data from the China Multi-Ethnic Cohort (CMEC) study. LE8 and LS7 were categorized as low, moderate and high. The CMEC provided an ideal and unique opportunity to characterize the association between LE8, LS7 and the odds of HUA. Results: Of the 89 823 participants, 14 562 (16.2%) had HUA. A high level of LE8 was associated with lower odds of HUA after full adjustment. The adjusted odds ratios (ORs) were 1 (reference), 0.70 (95% CI 0.67, 0.73) and 0.45 (0.42, 0.48) across low, moderate and high LE8 groups, respectively (Ptrend < 0.001). Similar results were observed in LS7 and HUA. The adjusted ORs were 1 (reference), 0.68 (95% CI 0.65, 0.71) and 0.46 (95% CI 0.43, 0.49) across low, moderate and high LS7 groups, respectively (Ptrend < 0.001). There were significant interactions between LE8 and age, gender, ethnicity and drinking habits on HUA. Receiver operating characteristics analysis showed that the area under the curve for LE8 and LS7 were similar (0.638 and 0.635, respectively). Conclusion: This study indicated a clearly inverse gradient association between the cardiovascular health metrics LE8 and LS7 and the odds of HUA.

Associations between residential greenness and the predicted 10-year risk for atherosclerosis cardiovascular disease among Chinese adults.

BACKGROUND: Exposure to build environments, especially residential greenness, offers benefits to reduce the development of atherosclerotic cardiovascular diseases (ASCVD). The 10-year ASCVD risk is a useful indicator for long-term ASCVD risk, but the evidence on the association and potential pathway of residential greenness in mitigating its development remains unclear. OBJECTIVES: This study aimed to investigate the associations between residential greenness and the 10-year predicted ASCVD risks, and potentially mediation effect on this association by air pollution, body mass index (BMI) and physical activity (PA). METHODS: The baseline of the China Multi-Ethnic Cohort (CMEC) study, enrolling 99,556 adults during 2018-2019, was used in this cross-sectional study. The participants' 10-year ASCVD risks were predicted as low-, moderate-, and high-risk groups, based on the six risk factors: age, smoking, hypertension, low-density lipoprotein cholesterol (LDL-C), high high-density lipoprotein cholesterol (HDL-C), and high total cholesterol (TC). The 3-year mean value within the circular buffer of 500 m and 1000 m of Enhanced Vegetation Index (EVI500m and EVI1000m) were used to assess greenness exposure. Multiple logistic regression was used to evaluate the association between residential greenness and the 10-year ASCVD risks. Stratified analyses by sex, age and smoking status were performed to identify susceptible populations. Causal mediation analysis was used to explore the mediation effects of air pollution, BMI and PA. RESULTS: A total of 75,975 participants were included, of which 17.9 % (n = 13,614) and 5.6 % (n = 4253) had the moderate and high 10-year ASCVD risks, respectively. Compared to the low-risk group, each interquartile increase in EVI500m and EVI1000m reduced the ASCVD risk of the moderate-risk group by 4 % (OR = 0.96 [0.94, 0.98]) and 4 % (OR = 0.96 [0.94, 0.98]), respectively; and reduced the risk of the high-risk group by 8 % (OR = 0.92 [0.90, 0.96]) and 7 % (OR = 0.93 [0.90, 0.97]), respectively. However, the increased greenness did not affect the ASCVD risk of the high-risk group when compared to the moderate-risk group. Effects of residential greenness on the ASCVD risk were stronger in women than in men (p < 0.05), and were not observed in those aged ≥55. PA and BMI partially mediated the association between greenness and the 10-year ASCVD risk. CONCLUSIONS: ASCVD prevention strategies should be tailored to maximize the effectiveness within the groups with different ASCVD risks, better at early stages when the ASCVD risk is low.

Does awareness of diabetic status increase risk of depressive or anxious symptoms? Findings from the China Multi-Ethnic cohort (CMEC) study.

INTRODUCTION: People with diabetes mellitus (DM) have increased risk of depressive symptoms (DS) or anxious symptoms (AS). This study explores whether awareness of DM will contribute to prevalence of DS or AS. METHODS: The baseline data including 81,717 adults from Southwest China was analyzed. DS and AS were assessed using PHQ-2 and GAD-2. Exposures were defined as 1) having self-reported physician diagnosis of diabetes (self-reported DM), 2) no prior diagnosis of diabetes but meeting diagnostic criteria (newly diagnosed DM), 3) having self-reported physician diagnosis or meeting criteria of non-diabetic diseases (non-diabetic patients), 4) healthy participants. Generalized linear mixed models were used to assess impact of presence and awareness of DM on DS or AS, adjusting for regional and individual related factors. RESULTS: The prevalence of DS in self-reported DM, newly diagnosed DM, non-diabetic patient and healthy participants was 7.08 %, 4.30 %, 5.37 % and 3.17 %. The prevalence of AS was 7.80 %, 5.77 %, 6.37 % and 3.91 %. After adjusting for related factors, compared with healthy participants, self-reported DM and non-diabetic patients were associated with DS [AORDS, self-reported = 1.443(1.218,1.710), AORDS, nondiabetic patients = 1.265(1.143,1.400)], while the association between newly diagnosed DM and DS was not statistically significant. The associations between self-reported DM, newly diagnosed DM, non-diabetic patients and AS were all statistically significant. LIMITATIONS: DS and AS were assessed through self-report and may suffer recall or information bias. CONCLUSIONS: The association between awareness of diabetes and DS/AS suggests to pay attention to distinguish between self-reported and newly diagnosed DM and screening for DS and AS in diabetic population.

Plasma Fatty Acids, Not Dietary Fatty Acids, Associated with Obesity in Four Ethnic Minority Groups Unique to Southwest China: A Cross-Sectional Study.

Background: Dietary fatty acids (DFAs) and plasma fatty acids (PFAs) are linked to obesity. However, whether this association exists among ethnic minorities remains lacking. The present cross-sectional study was designed to investigate the correlation between DFAs, PFAs and obesity in four ethnic minority groups to Southwest China. Methods: A total of 166 obese people, and 166 normal-BMI subjects matched based on their age-, sex-, and ethnicity- were recruited from four different ethnic minority groups. DFAs were obtained through food frequency questionnaires. PFAs were assayed by GC/MS method. Binary and multiple regression analyses were performed to evaluate the correlation among DFAs, PFAs and obesity. Canonical correlation analysis (CCA) was conducted to assess the relationship between DFAs and PFAs. Results: FAs were found to be highest in the Naxi people and lowest in the Hani people. Multiple logistic regression analysis revealed that plasma C16:0 (OR = 1.310; 95% CI, 1.028-1.669) in the Hani people; plasma C20:3 n-6 (OR = 6.250; 95% CI, 1.224-31.927) and dietary C20:1 (OR = 9.231; 95% CI, 1.253-68.016) in the Wa people; plasma C18:0 (OR = 0.788; 95% CI, 0.681-0.912) in the Naxi people were seen to be independent predictive factors for obesity. CCA showed that DFAs were positively correlated with PFAs in the Naxi (r: 0.676; P < 0.05) and Bulang people (r: 0.897; P < 0.05), but there was no correlation in the Hani and Wa people. Conclusion: In this study, PFAs but not DFAs were independently associated with obesity, and different among the four ethnic minorities.

Association of Sedentary Behavior and Physical Activity With Hyperuricemia and Sex Differences: Results From the China Multi-Ethnic Cohort Study.

OBJECTIVE: To determine the association of physical activity (PA) and sedentary time (ST; leisure and total ST), commuting mode with hyperuricemia in a multiethnic Chinese population, and to analyze the difference between sexes. METHODS: Baseline data were analyzed from 22,094 participants from the China Multi-Ethnic Cohort study in the Yunnan region, China. PA and sedentary behavior were assessed through questionnaires. Hyperuricemia was defined as serum urate > 7.0 mg/dL among men and > 6.0 mg/dL among women. A restricted cubic spline (RCS) was created to model the possible nonlinear relationship of PA and ST with hyperuricemia. Logistic regression was used to estimate the odds ratio (OR) and 95% CI. RESULTS: Hyperuricemia prevalence in the observed population was 15.5% (men 25.5%, women 10.7%). Compared to those with light PA, participants with moderate-to-vigorous PA had lower odds of hyperuricemia (adjusted ORs were 0.85 [95% CI 0.77-0.94] and 0.88 [95% CI 0.79-0.97]). However, RCS showed a U-shaped nonlinear relationship between PA and hyperuricemia, and a linear relationship between hyperuricemia prevalence and increasing ST. Total ST ≥ 4 hours/day increased the risk of hyperuricemia in women but not in men. Mode of transportation revealed that sedentary behavior increased the risk of hyperuricemia, but there were inconsistent results based on sex. CONCLUSION: Moderate PA may be more beneficial in reducing the risk of hyperuricemia. Reducing ST may have a greater effect on preventing hyperuricemia in females than in males.

Exposure to air pollution is associated with an increased risk of metabolic dysfunction-associated fatty liver disease.

BACKGROUND & AIMS: Accumulating animal studies have demonstrated the harmful contribution of ambient air pollution (AP) to metabolic dysfunction-associated fatty liver disease (MAFLD), but corresponding epidemiological evidence is limited. We examined the associations between long-term AP exposure and MAFLD prevalence in a Chinese population. METHODS: We conducted a cross-sectional study of 90,086 participants recruited in China from 2018 to 2019. MAFLD was assessed based on radiologically diagnosed hepatic steatosis and the presence of overweight/obese status, diabetes mellitus, or metabolic dysregulation. Residence-specific levels of air pollutants, including particulate matter with aerodynamic diameters of ≤1 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2), were estimated by validated spatiotemporal models. We used logistic regression models to examine the AP-MAFLD associations and further evaluated potential effect modifications by demographics, lifestyle, central obesity, and diabetes status. RESULTS: Increased exposure levels to all 4 air pollutants were significantly associated with increased odds of MAFLD, with odds ratios (ORs) of 1.13 (95% CI 1.10-1.17), 1.29 (1.25-1.34), 1.11 (1.09-1.14), and 1.15 (1.12-1.17) for each 10 µg/m3 increase in PM1, PM2.5, PM10, and NO2, respectively. Further stratified analyses revealed that individuals who are male, alcohol drinkers, and current and previous smokers, those who consume a high-fat diet, and those with central obesity experience more significant adverse effects from AP exposure than other individuals. CONCLUSIONS: This study provides evidence that long-term exposure to ambient PM1, PM2.5, PM10, and NO2 may increase the odds of MAFLD in the real world. These effects may be exacerbated by unhealthy lifestyle habits and central obesity. LAY SUMMARY: We conducted an epidemiological study on the potential effect of ambient air pollution on the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in approximately 90 thousand adults in China. We found that long-term exposure to ambient air pollution may increase the odds of MAFLD, especially in individuals who are male, smokers, and alcohol drinkers, those who consume a high-fat diet, and those with central obesity.

Metabolic expression profiling stratifies diffuse lower-grade glioma into three distinct tumour subtypes.

BACKGROUND: Lower-grade gliomas (LGGs) show highly metabolic heterogeneity and adaptability. To develop effective therapeutic strategies targeting metabolic processes, it is necessary to identify metabolic differences and define metabolic subtypes. Here, we aimed to develop a classification system based on metabolic gene expression profile in LGGs. METHODS: The metabolic gene profile of 402 diffuse LGGs from the Cancer Genome Atlas (TCGA) was used for consensus clustering to determine robust clusters of patients, and the reproducibility of the classification system was evaluated in three Chinese Glioma Genome Atlas (CGGA) cohorts. Then, the metadata set for clinical characteristics, immune infiltration, metabolic signatures and somatic alterations was integrated to characterise the features of each subtype. RESULTS: We successfully identified and validated three highly distinct metabolic subtypes in LGGs. M2 subtype with upregulated carbohydrate, nucleotide and vitamin metabolism correlated with worse prognosis, whereas M1 subtype with upregulated lipid metabolism and immune infiltration showed better outcome. M3 subtype was associated with low metabolic activities and displayed good prognosis. Three metabolic subtypes correlated with diverse somatic alterations. Finally, we developed and validated a metabolic signature with better performance of prognosis prediction. CONCLUSIONS: Our study provides a new classification based on metabolic gene profile and highlights the metabolic heterogeneity within LGGs.

A potentially effective drug for patients with recurrent glioma: sermorelin.

BACKGROUND: Treatment insensitivity is the main cause of glioma. This study was designed to screen out effective drugs for recurrent gliomas based on the transcriptomics data. METHODS: A total of 1,018 glioma patients with transcriptome sequencing data and clinical data were included in this study. There were 325 patients in the discovery cohort, including 229 primary patients and 92 recurrent patients. There were 693 patients in the validation cohort, including 422 primary patients and 271 relapsed patients. Drug Resistant Scores (DRS) of 4,865 drugs of each patient were used for screening. The analysis and drawing in this study were mainly based on R language. RESULTS: After high-throughput drug screening, we found that recurrent glioma patients were most sensitive to sermorelin. Further analysis revealed that sermorelin was suitable for recurrent patients with high grade, IDH-wildtype and 1p/19q non-codeletion status. GO and KEGG analyses found that sermorelin may inhibit tumor cell proliferation by cell cycle blocking. Moreover, sermorelin was also related to the immune system process and negatively regulated immune checkpoints and M0 macrophages. Lastly, the Kaplan-Meier method showed the patient's benefit from sermorelin was independent of postoperative adjuvant treatment. CONCLUSIONS: Recurrent glioma patients are sensitive to sermorelin and it makes effect through glioma cells proliferation inhibiting and immune response enhancing.

Daytime Napping Duration Is Positively Associated With Risk of Hyperuricemia in a Chinese Population.

CONTEXT: Loss of sleep or disturbance of sleep-wake cycles has been related to metabolic impairments. However, few studies have investigated the association between daily sleep duration and hyperuricemia. OBJECTIVE: We investigated daily sleep duration (daytime napping and nocturnal sleep) with hyperuricemia risk. METHODS: We cross-sectionally analyzed data from the China Multi-Ethnic Cohort (CMEC), Yunnan region. A total of 22 038 participants aged 30 to 79 years were recruited in 2018. Hyperuricemia was defined as serum uric acid (SUA) above 7.0 mg/dL in men and above 6.0 mg/dL in women. Outcomes were associations between daily sleep duration and hyperuricemia. RESULTS: We found that the longest daytime napping duration was associated with a higher risk of hyperuricemia in the crude model (odds ratio [OR] [95% CI], 2.22 [1.88-2.61], P < .001) and in a multivariable adjustment model (OR, 1.69; 95% CI, 1.41-2.01, P < .001) after adjusting for demographic, sleep habits, and metabolic risk factors. The association was moderately attenuated with additionally adjusted for serum creatinine (OR, 1.54; 95% CI, 1.28-1.86, P < .001). Longer daytime napping duration was also related to higher risk of hyperuricemia combined with metabolic syndrome (MetS). Respondents in the group with daytime napping duration greater than or equal to 90 minutes presented with a higher risk of hyperuricemia combined with MetS (OR, 1.39; 95% CI, 1.06-1.79; P < .001) in the fully adjusted model. We did not observe any relation between nocturnal sleep duration and risk of hyperuricemia in the study. CONCLUSION: Longer daytime napping duration (but not nocturnal sleep duration) was independently associated with risk of hyperuricemia in a Chinese population.

A novel DNA repair-related nomogram predicts survival in low-grade gliomas.

AIMS: We aimed to create a tumor recurrent-based prediction model to predict recurrence and survival in patients with low-grade glioma. METHODS: This study enrolled 291 patients (188 in the training group and 103 in the validation group) with clinicopathological information and transcriptome sequencing data. LASSO-COX algorithm was applied to shrink predictive factor size and build a predictive recurrent signature. GO, KEGG, and GSVA analyses were performed for function annotations of the recurrent signature. The calibration curves and C-Index were assessed to evaluate the nomogram's performance. RESULTS: This study found that DNA repair functions of tumor cells were significantly enriched in recurrent low-grade gliomas. A predictive recurrent signature, built by the LASSO-COX algorithm, was significantly associated with overall survival and progression-free survival in low-grade gliomas. Moreover, function annotations analysis of the predictive recurrent signature exhibited that the signature was associated with DNA repair functions. The nomogram, combining the predictive recurrent signature and clinical prognostic predictors, showed powerful prognostic ability in the training and validation groups. CONCLUSION: An individualized prediction model was created to predict 1-, 2-, 3-, 5-, and 10-year survival and recurrent rate of patients with low-grade glioma, which may serve as a potential tool to guide postoperative individualized care.

Uronic acid metabolic process-related gene expression-based signature predicts overall survival of glioma.

Glioma is the most common and malignant cancer of the central nervous system, and the prognosis is poor. Metabolic reprogramming is a common phenomenon that plays an important role in tumor progression including gliomas. Searching the representative process among numerous metabolic processes to evaluate the prognosis aside from the glycolytic pathway may be of great significance. A novel prediction signature was constructed in the present study based on gene expression. A total of 1027 glioma samples with clinical and RNA-seq data were used in the present study. Lasso-Cox, gene set variation analysis, Kaplan-Meier survival curve analysis, Cox regression, receiver operating characteristic curve, and elastic net were performed for constructing and verifying predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. This signature was found to be stable in prognostic prediction in the Chinese Glioma Genome Atlas Network and the Cancer Genome Atlas databases. The possible mechanism was also explored, revealing that the aforementioned signature was closely related to DNA replication and ATP binding. In summary, a prognosis prediction signature for patients with glioma based on five genes was constructed and showed great potential for clinical application.

Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma.

Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical data as well as single-cell sequencing data from 6 glioma patients from publicly available databases. Gene set variation analysis and gene ontology analysis were performed to reveal the biological function of GLRX. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by t-distributed stochastic neighbor embedding analysis. The prognostic value of GLRX in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. GLRX was found to be highly enriched in gliomas of higher grades with wild-type IDH, without 1p/19q co-deletion, and with a methylated MGMT promoter. Moreover, GLRX could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of GLRX was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with GLRX being specifically expressed in M0 macrophages. GLRX is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that GLRX is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, GLRX-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.

A novel methylation signature predicts radiotherapy sensitivity in glioma.

Glioblastoma (GBM) is the most common and malignant cancer of the central nervous system, and radiotherapy is widely applied in GBM treatment; however, the sensitivity to radiotherapy varies in different patients. To solve this clinical dilemma, a radiosensitivity prediction signature was constructed in the present study based on genomic methylation. In total, 1044 primary GBM samples with clinical and methylation microarray data were involved in this study. LASSO-COX, GSVA, Kaplan-Meier survival curve analysis, and COX regression were performed for the construction and verification of predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. Via the integration analysis of methylation and the survival data of primary GBM, a novel prognostic and radiosensitivity prediction signature was constructed. This signature was found to be stable in prognosis prediction in the TCGA and CGGA databases. The possible mechanism was also explored, and it was found that this signature is closely related to DNA repair functions. Most importantly, this signature could predict whether GBM patients could benefit from radiotherapy. In summary, a radiosensitivity prediction signature for GBM patients based on five methylated probes was constructed, and presents great potential for clinical application.

Single-Cell RNA-Sequencing Shift in the Interaction Pattern Between Glioma Stem Cells and Immune Cells During Tumorigenesis.

Glioblastoma is one of the most common neoplasms in the central nervous system characterized by limited immune response and unlimited expansion capability. Cancer stem cells (GSCs), a small fraction of the tumor cells, possess a pivotal regulation capability in the tumor microenvironment with a superior proliferation ability. We aimed to reveal the interaction between glioma stem cells (GSCs) and immune cells during tumorigenesis. Single-cell sequencing data from seven surgical specimens of glioblastoma patients and patient-derived GSCs cocultured with peripheral leukocytes were used for the analysis. Cell grouping and trajectory analysis were performed using Seurat and Monocle 3 packages in R software. The gene set of Cancer Genome Anatomy Project was used to define different cell types. Cells with the ability of proliferation and differentiation in glioblastoma tissue were defined as GSCs, which had a similar expression pattern to that in the GSCs in vitro. Astrocytes in glioblastoma were mainly derived from differentiated GSCs, while oligodendrocytes were most likely to be derived from different precursor cells. No remarkable evolutionary trajectory was observed among the subgroups of T cells in glioblastoma. The immune checkpoint interaction between GSCs and immune cells was changed from stimulatory to inhibitory during tumorigenesis. The patient-derived GSCs system is an ideal model for GSC research. The above research revealed that the interaction pattern between GSC glioma stem cells and immune cells during tumorigenesis provides a theoretical basis for GSC glioma stem cell-targeted immunotherapy.

RPP30, a transcriptional regulator, is a potential pathogenic factor in glioblastoma.

BACKGROUND: Old age has been demonstrated to be a risk factor for GBM, but the underlying biological mechanism is still unclear. We designed this study intending to determine a mechanistic explanation for the link between age and pathogenesis in GBM. RESULTS: The expression of RPP30, an independent prognostic factor in GBM, was negatively correlated with age in both tumor and non-tumor brain samples. However, the post-transcriptional modifications carried out by RPP30 were different in primary GBM and non-tumor brain samples. RPP30 affected protein expression of cancer pathways by performing RNA modifications. Further, we found that RPP30 was related to drug metabolism pathways important in GBM. The decreased expression of RPP30 in older patients might be a pathogenic factor for GBM. CONCLUSION: This study revealed the role of RPP30 in gliomagenesis and provided the theoretical foundation for targeted therapy. METHODS: In total, 616 primary GBM samples and 41 non-tumor brain samples were enrolled in this study. Transcriptome data and clinical information were obtained from the CGGA, TCGA, and GSE53890 databases. Gene Set Variation Analysis and Gene Ontology analyses were the primary analytical methods used in this study. All statistical analyses were performed using R.