Abstract Objectives Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high rates of morbidity and mortality, largely because of its late diagnosis and metastatic potential. Lactate metabolism and protein lactylation are thought to play roles in NPC pathogenesis by modulating the tumor microenvironment and immune evasion. However, research specifically linking lactate-related mechanisms to NPC remains limited. This study aimed to identify lactate-associated biomarkers in NPC and explore their underlying mechanisms, with a particular focus on immune modulation and tumor progression. Methods To achieve these objectives, we utilized a bioinformatics approach in which publicly available gene expression datasets related to NPC were analysed. Differential expression analysis revealed differentially expressed genes (DEGs) between NPC and normal tissues. We performed weighted gene coexpression network analysis (WGCNA) to identify module genes significantly associated with NPC. Overlaps among DEGs, key module genes, and lactate-related genes (LRGs) were analysed to derive lactate-related differentially expressed genes (LR-DEGs). Machine learning algorithms can be used to predict potential biomarkers, and immune infiltration analysis can be used to examine the relationships between identified biomarkers and immune cell types, particularly M0 macrophages and B cells. Results A total of 1,058 DEGs were identified between the NPC and normal tissue groups. From this set, 372 key module genes associated with NPC were isolated. By intersecting the DEGs, key module genes, and lactate-related genes (LRGs), 17 lactate-related DEGs (LR-DEGs) were identified. Using three machine learning algorithms, this list was further refined, resulting in three primary lactate-related biomarkers: TPPP3, MUC4, and CLIC6. These biomarkers were significantly enriched in pathways related to "immune cell activation" and the "extracellular matrix environment." Additionally, M0 and B macrophages were found to be closely associated with these biomarkers, suggesting their involvement in shaping the NPC immune microenvironment. Conclusion In summary, this study identified TPPP3, MUC4, and CLIC6 as lactate-associated clinical modelling indicators linked to NPC. linked to NPC, providing a foundation for advancing diagnostic and therapeutic strategies for this malignancy.
Background and objective Ischaemic encephalopathy is a common cerebrovascular disease caused by insufficient blood supply to the cerebral vessels. The ischaemic encephalopathy is closely associated with the development of many chronic diseases such as obesity, hypertension and diabetes. Neurotrophic therapy has become the main therapeutic strategy for ischaemic encephalopathy. However, neurotrophic drugs only slightly recover the neurological function of patients, and their long-term efficacy is uncertain. Previous reports revealed that the active ingredients of natural medicines play important roles in the treatment of cerebral ischemia. In this study, we reviewed clearing herbs with anti-ischaemic encephalopathy functions using the data from quantitative statistical and network pharmacological exploration methods. We also discussed the different bioactive components and pharmacological effects of these herbs.
Abstract Background: Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury.Methods: BMSCs were isolated, cultured and identified by primary culture method. Exosomes derived from BMSCs were extracted by ultra-high speed centrifugation method. A testicular IRI model was established in male SD rats. Thirty healthy male SD rats were randomly divided into three groups. Group A: Sham group, group B: normal saline treatment group (I/R+NS), group C: BMSCs-derived exosomes (100 ug/mL) treatment group (I/R+ BMSCs-EXO). Finally take each side (left) of rat torsion by using optical microscope to detect testicular tissue pathology grade and fine structure of organization structure, adopt the method of biochemical determination of groups of testicular tissue MDA and NOS, SOD and CAT activity and T - AOC level.Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In animal model, Compared with the normal spermatogenic structure of testis in group A (Sham), the spermatogenic structure of testis in group B (I/R+NS) was obviously damaged to varying degrees, while the spermatogenic structure of testis in group C (I/R+ BMSCs-EXO) was improved to A certain extent (P<0.05). In the biochemical indexes of testis tissue, the contents of MDA and NOS in group B (I/R+NS) were significantly increased compared with group A (Sham), while the activities of SOD and CAT and T-AOC were decreased compared with group A (Sham) (P<0.05). In the exosome-treated group C (I/R+ BMSCs-EXO), compared with the normal saline treatment group B, The contents of MDA and NOS were decreased to a certain extent, while the activities of SOD and CAT and the level of T-AOC were increased (P<0.05).Conclusion: BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。
To explore the difference in rehabilitation effect between soft robot gloves and repetitive transcranial magnetic stimulation (rTMS) in patients with severe upper limb motor dysfunction after a stroke.A total of 69 post-stroke patients with severe upper limb dysfunction were randomly assigned to a repetitive transcranial magnetic group, a soft robotic glove group, and a conventional treatment group. The primary outcomes were the Fugl-Meyer Upper Extremity Assessment (FMA-UE) and the Modified Barthel Index (MBI). The secondary endpoints were the amplitude surface electromyogram of the extensor wrist muscle (sEMG) and the cerebral hemispheric resting motor threshold (RMT).The change of FMA-UE score in the soft robotic glove group was significantly better than that in the conventional treatment group (median difference: 2 points; 95% confidence interval [1, 3]; P < 0.05), but there was no significant difference compared with the repetitive transcranial magnetic stimulation group (median difference: 0 points; 95% confidence interval [-1, 2]; P [0.547] > 0.05). There was no significant difference in the change of MBI score between the soft robotic glove group and the conventional treatment and repetitive transcranial magnetic treatment groups [F = 2.458, P [0.093] > 0.05]. There was no significant difference in the change of sEMG score between the soft robotic glove group and the conventional treatment and repetitive transcranial magnetic treatment groups [H = 0.042, P [0.980] > 0.05]. Additionally, the change of RMT score in the soft robotic glove group was significantly inferior to that in the repetitive transcranial magnetic treatment group [difference: -1.09; 95% confidence interval [-2.048, 0.048]; P < 0.05], but there was no significant difference compared with the conventional treatment group [difference: 0.31 points; 95% confidence interval [-0.879, 0.358]; P [0.495] > 0.05].For patients with severe dyskinesia after a stroke, soft robotic gloves are as effective as repetitive transcranial magnetic stimulation and may be a good choice for home rehabilitation. In addition, conventional treatment combined with repetitive transcranial magnetic stimulation (rTMS) or a soft robotic glove produced better rehabilitation outcomes than conventional treatment alone.
Objective: To examine childhood body mass index (BMI), fasting glucose and insulin in relation to incident adult type-2 diabetes mellitus (T2DM). <p>Research Design and Methods: We used data from The International Childhood Cardiovascular Cohort Consortium. Data included childhood measurements (age 3-19) obtained during the 1970s-90s, a health questionnaire including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years, and a medical diagnosis registry (Finland). </p> <p>Results: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20-59 (mean 40.8) years, and 86% of them reported use of a confirmed anti-diabetic medication. BMI and glucose (age- and sex-standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to incrementally increased risk of T2DM beginning at age 30, beginning at cut points below the 95<sup>th</sup> percentile for BMI and below 100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. </p> <p>Conclusions: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy to apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.</p>
Objective: To examine childhood body mass index (BMI), fasting glucose and insulin in relation to incident adult type-2 diabetes mellitus (T2DM). <p>Research Design and Methods: We used data from The International Childhood Cardiovascular Cohort Consortium. Data included childhood measurements (age 3-19) obtained during the 1970s-90s, a health questionnaire including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years, and a medical diagnosis registry (Finland). </p> <p>Results: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20-59 (mean 40.8) years, and 86% of them reported use of a confirmed anti-diabetic medication. BMI and glucose (age- and sex-standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to incrementally increased risk of T2DM beginning at age 30, beginning at cut points below the 95<sup>th</sup> percentile for BMI and below 100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. </p> <p>Conclusions: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy to apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.</p>
Background ACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism–linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers. Methods The expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan–Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)–KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib. Results KIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan–Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells. Conclusion ACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.
Visit-to-visit variability of glycated hemoglobin (HbA1c) is a marker of long-term glycemic fluctuation, which has been related to increased risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM). The association between HbA1c variability and retinopathy in patients with T2DM, however, has been inconsistent in previous studies. In order to fully evaluate the above association, we conducted a meta-analysis. Observational studies related to the aim of the meta-analysis were identified by search of PubMed, Web of Science, and Embase databases. Studies with HbA1c variability evaluated as the standard deviation (SD) and/or the coefficients of variation (CV) of HbA1c were included. The results were analyzed using a random-effects model that incorporated potential heterogeneity between studies. Twelve observational studies involving 44 662 T2DM patients contributed to the meta-analysis. Overall, 5150 (11.5%) patients developed retinopathy. Pooled results showed that compared to patients with lower HbA1c variability, T2DM patients with higher HbA1c-SD (relative risk [RR]: 1.48, 95% confidence interval [CI]: 1.24 to 1.78, p<0.001, I2=34%) and higher HbA1c-CV (RR: 1.29, 95% CI: 1.05 to 1.59, p=0.02, I2=0%) were both associated with higher risk of DR. For studies with HbA1c-SD, the association was not significantly affected by study characteristics such as country, study design, mean age, disease duration, adjustment of mean HbA1c, or quality scores (p for subgroup difference all>0.05). In conclusion, higher HbA1c variability may be associated with an increased risk of retinopathy in patients with T2DM.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high rates of morbidity and mortality, largely because of its late diagnosis and metastatic potential. Lactate metabolism and protein lactylation are thought to play roles in NPC pathogenesis by modulating the tumor microenvironment and immune evasion. However, research specifically linking lactate-related mechanisms to NPC remains limited. This study aimed to identify lactate-associated biomarkers in NPC and explore their underlying mechanisms, with a particular focus on immune modulation and tumor progression. To achieve these objectives, we utilized a bioinformatics approach in which publicly available gene expression datasets related to NPC were analysed. Differential expression analysis revealed differentially expressed genes (DEGs) between NPC and normal tissues. We performed weighted gene coexpression network analysis (WGCNA) to identify module genes significantly associated with NPC. Overlaps among DEGs, key module genes and lactate-related genes (LRGs) were analysed to derive lactate-related differentially expressed genes (LR-DEGs). Machine learning algorithms can be used to predict potential biomarkers, and immune infiltration analysis can be used to examine the relationships between identified biomarkers and immune cell types, particularly M0 macrophages and B cells. A total of 1,058 DEGs were identified between the NPC and normal tissue groups. From this set, 372 key module genes associated with NPC were isolated. By intersecting the DEGs, key module genes and lactate-related genes (LRGs), 17 lactate-related DEGs (LR-DEGs) were identified. Using three machine learning algorithms, this list was further refined, resulting in three primary lactate-related biomarkers: TPPP3, MUC4 and CLIC6. These biomarkers were significantly enriched in pathways related to "immune cell activation" and the "extracellular matrix environment". Additionally, M0 and B macrophages were found to be closely associated with these biomarkers, suggesting their involvement in shaping the NPC immune microenvironment. In summary, this study identified TPPP3, MUC4 and CLIC6 as lactate-associated clinical modelling indicators linked to NPC, providing a foundation for advancing diagnostic and therapeutic strategies for this malignancy.
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