Research to date has provided novel insights into lactate's positive role in multiple brain functions and several brain diseases. Although notable controversies and discrepancies remain, the neurobiological role and the metabolic mechanisms of brain lactate have now been described. A theoretical framework on the relevance between lactate and brain function and brain diseases is presented. This review begins with the source and route of lactate formation in the brain and food; goes on to uncover the regulatory effect of lactate on brain function; and progresses to gathering the application and concentration variation of lactate in several brain diseases (diabetic encephalopathy, Alzheimer's disease, stroke, traumatic brain injury, and epilepsy) treatment. Finally, the dual role of lactate in the brain is discussed. This review highlights the biological effect of lactate, especially L-lactate, in brain function and disease studies and amplifies our understanding of past research.
We performed a phase II trial of docetaxel in combination with capecitabine to evaluate the antitumor response, toxicity, and survival in pre-treated patients with advanced esophageal squamous cell carcinoma. Patients with advanced esophageal squamous cell carcinoma who had failed first-line chemotherapy with cisplatin and 5-fluorouracil were enrolled in this study. Treatment consisted of oral capecitabine (825 mg/m(2) twice daily on days 1-14) plus 1-h intravenous docetaxel (60 mg/m(2) on day 1) every 3 weeks for up to 6 cycles. Between June 2008 and August 2011, thirty eligible patients with a median age of 58 years (range 38-68 years) were enrolled. Patients received a median of three cycles of treatment (range 1-6). The median follow-up was 15.4 months (range 1.0-31.5 months). Intent-to-treat efficacy analysis demonstrated an overall response rate of 23.3% (0 complete response and 7 partial response) and stable disease of 43.4 % (n = 13). The median time to progression was 3.0 months (95% CI 1.9-4.1 months). The median survival was 8.3 months (95% CI 6.8-9.8 months). Severe adverse events (grade 3/4) reported were as follows: neutropenia (33.3%, n = 10, including febrile neutropenia 6.7%, n = 2), anemia (16.7%, n = 5), thrombocytopenia (10 %, n = 3), hand-foot syndrome (13.3%, n = 4), and fatigue (10%, n = 3). Docetaxel plus capecitabine had a manageable adverse event profile and promising activity in advance esophageal squamous cell carcinoma as a second-line treatment.
The brain prefrontal control system is critical to successful recovery from substance use disorders, and the prefrontal cortex (PFC) regulates striatal reward-related processes. Substance-dependent individuals exhibit an increased response to drug rewards and decreased response to natural, nondrug rewards. Short-term aerobic exercise can ameliorate craving and inhibitory deficits in methamphetamine users, but the effect of exercise on food reward is unknown. This study used functional near-infrared spectroscopy (fNIRS) to measure the effects of moderate- and high-intensity short-term aerobic exercise on prefrontal activity related to food images and recorded the subjective feelings of appetite in methamphetamine-dependent users. In total, 56 men who met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for methamphetamine dependence, with a mean (SD) body mass index of 24.7 (3.5) kg/m2 and age of 30.2 (5.1) years, were randomly assigned to one of two exercise groups: moderate intensity (n = 28; 65%–75% of maximum heart rate) and high intensity (n = 28; 76%–85% of heart rate maximum). Each group also performed a resting control session for 35 min 1 week before or after the exercise, in a counterbalanced order. Mean oxygenated hemoglobin concentration changes in the PFC when viewing visual food cues were assessed by fNIRS, and subjective feelings of appetite were self-rated using visual analog scales after moderate- or high-intensity aerobic exercise and after the resting control session. A continuous-wave NIRS device was used to obtain functional data: eight sources and seven detectors were placed on the scalp covering the PFC, resulting in 20 channels per participant. We found that moderate-intensity aerobic exercise significantly increased both, the activation of the left orbitofrontal cortex (OFC) to images of high-calorie food (P = 0.02) and subjective sensations of hunger (F(1,54) = 7.16, P = 0.01). To our knowledge, this study provides the first evidence that moderate-intensity aerobic exercise increases OFC activity associated with high-calorie food images and stimulates appetite in methamphetamine-dependent individuals. These changes suggest that exercise may reestablish the food reward pathway hijacked by drugs and restore sensitivity to natural rewards. This evidence may contribute to the development of specific exercise programs for populations with methamphetamine dependence.
Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has gained increased attention in the metabolic characterization of human biofluids. However, the stability and reproducibility of nanoparticle-based substrates remain two of the biggest challenges in high-salt environments. Here, by controlling the extent of Coulomb repulsion of 26 nm positively charged AuNPs, a homogeneous layer of covalently bonded AuNPs on a coverslip with tunable interparticle distances down to 16 nm has been successfully fabricated to analyze small biomolecules in human serum. Compared with the self-assembled AuNP array, the covalently bonded AuNP array showed superior performances on stability, reproducibility, and sensitivity in high-salt environments. The stable attachment of AuNPs maintained a detection reproducibility with a RSD less than 12% and enabled the reusability of the array for 10 experiments without significant signal deterioration (<15%) and carryover effects. Moreover, the closely positioned AuNPs allowed the coupling of photoinduced plasmons to generate an enhanced electric field, which promotes the generation of excited electrons to facilitate the desorption/ionization processes instead of the heat dissipation, thus enhancing the detection sensitivity with detection limits down to the femtomole level. Combined with machine learning methods, the AuNP array has been successfully applied to discover seven biomarkers for differentiating early-stage lung cancer patients from healthy controls. It is anticipated that this simple approach of developing robust AuNP arrays can also be extended to other types of NP arrays for wider applications of SALDI-MS technology.
The present study investigated the treatment and survival outcomes of patients with synchronous primary esophageal squamous cell carcinoma and gastric adenocarcinoma. The medical records of 10,783 patients with primary esophageal squamous cancer treated at our institution between 1995 and 2012 were retrospectively reviewed. Overall survival (OS) rates were calculated using the Kaplan–Meier method. The incidence was 0.38% (41/10,783). Of these 41 patients, 26 underwent curative surgery, ten received palliative chemotherapy or radiotherapy, and five received no treatment. The median OS of the surgery, palliative-therapy, and treatment-free groups was 17.1, 9.0, and 3.8 months, respectively. The 1-, 3-, 5-, and 10-year OS rates for the surgery group were 77%, 45%, 33%, and 19%, respectively. No significant differences in median OS were observed between the surgery group and the historical cohort of isolated esophageal cancer (n = 186) (17.1 vs. 21.0 months, P = 0.061) or isolated gastric cancer (n = 51) (17.1 vs. 28.9 months, P = 0.875), or between the palliative-therapy group and its corresponding historical cohort (n = 30) (9.0 vs. 8.3 months, P = 0.862). The survival outcomes of patients with synchronous primary esophageal squamous and gastric cancers were not worse than those of patients with isolated esophageal cancer or isolated gastric cancer.
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