The associations between peak O2 consumption and leptin in 10‐ to 12‐year‐old boys

The aim of this study was to assess the associations of circulating levels of leptin with the peak O₂ consumption (VO_2peak) in 10 ‐ to 12‐year‐old boys of different BMI selected by Cole et al. (BMJ, 320,2000,1–6): total group (n = 248), normal (n = 190), overweight (n = 34) and obese (n = 24). We hypothesized that there is a close relationship in overweight and obese subgroups of boys with relative VO_{2peak kg}^?1(ml min^?1 kg^?1) and leptin. Most of the subjects were Tanner stage 2. Peak O₂ consumption was measured directly using an increasing incremental protocol until volitional exhaustion on an electronically braked cycle ergometer. The expired gas was sampled continuously breadth‐by‐breadth mode for the measurement of oxygen consumption (MetaMax, Germany). Blood samples were obtained after an overnight fast from an antecubital vein for leptin measurements. Peak O₂ consumption (l min^?1) was higher or lower (ml min^?1 kg^?1) in overweight and obese groups, compared with normal BMI group. Leptin was higher in overweight and obese groups, compared with normal BMI group. Peak O₂ consumption (l min^?1) correlated significantly with leptin only in total group (n = 248, r   =   0·196). Contrary, relative VO_2peak kg^?1 correlated significantly and negatively with leptin. The relationship was highest on the total group (r   =  ?0·674). We can conclude that leptin first of all correlated negatively with relative peak O₂ consumption. Absolute VO_2peak correlated with leptin only in total group.     

Cerebrospinal fluid neuron‐specific enolase in non‐selected patients

The degree to which cerebrospinal fluid (CSF) neuron‐specific enolase (NSE) contributes to the diagnosis and prognosis of disorders of the central nervous system (CNS) or peripheral nervous system (PNS) is still under debate. The aim of the study was thus to assess the validity of CSF‐NSE levels in the diagnostic work‐up of these conditions. The study consecutively included 106 adult patients who had undergone a diagnostic spinal tap or myelography during the diagnostic work‐up for various CNS or PNS disorders. Thirty‐five of these patients (16 F, 19 M, aged 24–88 years) without indication of a CNS disorder and with normal routine CSF investigations served as controls. The remaining 71 patients (31 F, 40 M, aged 28–87 years) constituted the disease group. CSF‐NSE was independent of sex and age. The upper reference limit of CSF‐NSE was 0.01536?ng/L. CSF‐NSE was elevated in 13 of the 71 patients (18%): 6 with metabolic myopathy, 4 with polyneuropathy and 3 with hepatic encephalopathy, multiple sclerosis and paraspasticity, respectively. Only 6 of the 13 patients (46%) showed CNS involvement. The study shows that CSF‐NSE is elevated in only one‐fifth of unselected patients who consecutively undergo a spinal tap. CSF‐NSE is elevated most frequently in patients with metabolic myopathy and polyneuropathy, even in cases without CNS abnormalities.     

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Abstract

Objectives: Chest pain is a common reason for accessing an emergency department (ED) and a frequent cause of outpatient physician visits. Whether patients referred for cardiac stress testing from these referral sources differ in clinically significant ways is unknown, and is thus the purpose of this investigation. Methods: This study prospectively assessed 301 patients presenting to Virginia Commonwealth University Medical Center with symptoms suggestive of myocardial ischemia. All subjects underwent nuclear stress testing as a part of their assessment. Results: Patients referred from the ED were more likely to be African American and outpatients were more likely to be Caucasian. Outpatients were older than those referred from the ED. Patients referred from the ED were less likely to have a diagnosis of hypertension, dyslipidemia, or diabetes, but were more likely to smoke. The exercise response was similar, with a few exceptions. There were no differences in the frequency of equivocal or positive nuclear stress test results based on referral source. Conclusions: The results of the present study indicate that several characteristics of patients undergoing outpatient nuclear stress testing differ according to referral source. Future research should be directed toward developing effective strategies to reduce ED utilization and increasing outpatient management.     

有氧运动对青少年临界高血压患者血压的影响

目的：探讨有氧运动对青少年临界高血压患者血压的影响。方法将50例青少年临界高血压患者按护士为其制定的运动处方进行规律运动,分别记录干预前后患者的降压效果。结果干预后患者降压效果较干预前有显著性意义(P<0.01)。结论有氧运动可促进血压的降低,有利于患者生存质量提高,同时具有可操作性与实用性,值得在社区护理中推广应用。     

Cancer metabolic reprogramming： importance,main features,and potentials for precise targeted anti-cancer therapies

Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.     

PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer

Background:

Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.

Methods:

Quantitative real-time PCR was used to assess the expression of PKM2 in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy. PKM2 mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.

Results:

In the training set, high PKM2 mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months vs 6.4, P=0.006), overall survival (OS; 10.1 vs 17.0 months, P=0.01) and disease control rate (DCR; 57.7% vs 74.3% P=0.021) compared to patients with low PKM2 levels. In the validation set, high PKM2 mRNA levels were also associated with deceased PFS (3.7 vs 5.9 months, P=0.006), OS (8.3 vs 16.8 months, P=0.003) and DCR (57.7% vs 70.9% P=0.049) compared to those with low PKM2 mRNA levels. There was no correlation between the PKM2 mRNA levels and the PFS (5.6 vs 5.9, P=0.43) or the OS (9.8 vs 10.1, P=0.51) in the control group. Multivariate analysis revealed high PKM2 mRNA expression as an independent predictive factor for the poor patients'' outcome.

Conclusions:

PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.     

Metabolic effect of TAp63α: enhanced glycolysis and pentose phosphate pathway,resulting in increased antioxidant defense

TAp63α is a member of the p53 family, which plays a central role in epithelial cancers. Recently, a role has emerged for p53 family members in cancer metabolic modulation.In order to assess whether TAp63α plays a role in cancer metabolism, we exploited p53-null osteosarcoma Tet-On Saos-2 cells, in which the expression of TAp63α was dependent on doxycycline supplementation to the medium. Metabolomics labeling experiments were performed by incubating the cells in ¹³C-glucose or ¹³C¹⁵N-glutamine-labeled culture media, as to monitor metabolic fluxes upon induced expression of TAp63α.Induced expression of TAp63α resulted in cell cycle arrest at the G1 phase. From a metabolic standpoint, expression of Tap63α promoted glycolysis and the pentose phosphate pathway, which was uncoupled from nucleotide biosynthesis, albeit prevented oxidative stress in the form of oxidized glutathione. Double ¹³C-glucose and ¹³C¹⁵N-glutamine metabolic labeling confirmed that induced expression of TAp63α corresponded to a decreased flux of pyruvate to the Krebs cycle and decreased utilization of glutamine for catabolic purposes in the TCA cycle. Results were not conclusive in relation to anabolic utilization of labeled glutamine, since it is unclear to what extent the observed minor TAp63α-dependent increases of glutamine-derived labeling in palmitate could be tied to increased rates of reductive carboxylation and de novo synthesis of fatty acids. Finally, bioinformatics elaborations highlighted a link between patient survival rates and the co-expression of p63 and rate limiting enzymes of the pentose phosphate pathway, G6PD and PGD.     

甲基转移酶样因子3 通过调控GLUT4-mTORC1 轴影响食管鳞状细胞 癌细胞的糖酵解及增殖

目的：探讨甲基转移酶样因子3（METTL3）在食管鳞状细胞癌（ESCC）组织和细胞中的表达水平及其对ESCC 细胞糖 酵解和增殖能力的影响和潜在的分子机制。方法：基于TCGA 数据库分析METTL3 在ESCC 细胞中的表达及可能的富集通路。 收集2021 年1 月至2021 年6 月间在北川医学院附属医院外科手术切除的34 例ESCC 组织及相应癌旁组织,采用免疫组化法验证 ESCC 组织中METTL3 的表达。采用CCK-8 法和平板克隆形成实验检测干扰METTL3 后ESCC 细胞增殖能力的变化,利用比色 法检测干扰METTL3 后ESCC 细胞总RNA 中m6A 的表达水平,采用甲基化RNA 免疫沉淀定量PCR（MeRIP-qPCR）检测METTL3 对葡萄糖转运蛋白4（GLUT4）基因mRNA 的m6A 修饰水平的影响,采用WB 和qPCR 等技术探索METTL3 参与ESCC 细胞糖酵解 的生物学机制。结果：METTL3 在ESCC 组织以及细胞中均呈高表达（均P<0.001）。干扰METTL3 表达后,ESCC 细胞的增殖能 力明显减弱、细胞内总RNA 的m6A 修饰水平显著降低（均P<0.001）。此外,干扰METTL3 可显著抑制KYSE150 和TE-1 细胞中 GLUT4 基因mRNA 的m6A 修饰水平（均P<0.01）,并通过下调GLUT4 的表达抑制葡萄糖的摄取以及乳酸的释放（均P<0.01）,最 终下调mTORC1 通路活性并抑制ESCC 细胞的增殖;在干扰METTL3 的ESCC 细胞同时联合运用mTORC1 通路抑制剂显示有协 同的抗癌作用。结论：METTL3 介导的m6A 修饰通过调控GLUT4-mTORC1 信号轴影响ESCC 细胞的糖酵解及增殖。     

BCAT1 knockdown-mediated suppression of melanoma cell proliferation and migration is associated with reduced oxidative phosphorylation

Malignant melanoma has a high mutational rate. As a result, resistance to current therapies is common. Consequently, there is an unmet medical need to develop novel therapies. Recent data suggest that branched-chain amino acid transaminase 1 (BCAT1) is overexpressed in multiple cancers, and such overexpressed BCAT1 is necessary for individual cancer progression. Therefore, BCAT1 appears to be a good target in cancer treatment. Additionally, because its expression in healthy tissues is highly restricted in adults and is limited to the brain, ovary, and placenta, BCAT1 is especially an ideal target in cancer therapies. Currently, the function of BCAT1 in malignant melanoma has not been demonstrated. Therefore, we investigated the role of BCAT1 in the proliferation and migration of malignant melanomas using human samples and mouse malignant B16 melanoma cell line. Our data showed that BCAT1 was overexpressed in malignant melanoma tissues both in humans and mice. Besides, BCAT1 knockdown suppressed melanoma cell proliferation and migration, which was associated with reduced oxidative phosphorylation. Collectively, our data indicate that BCAT1 is a promising therapeutic target for the treatment of malignant melanomas.