ABSTRACT
BACKGROUND: Gastric electrical stimulation (GES) is used for patients with drug-refractory gastroparesis (Gp) symptoms. Approximately two-thirds of patients with Gp symptoms are either overweight or obese. We aimed to assess symptoms and nutritional status pre-GES and post-GES placement in a large sample of drug-refractory Gp patients. METHODS: We conducted a chart review of 282 patients with drug-refractory Gp who received temporary followed by permanent GES at an academic medical center. Gastrointestinal symptoms were collected by a traditional standardized PRO (0-4, 0 being asymptomatic and 4 being worst symptoms), baseline nutritional status by BMI plus subjective global assessment (SGA score A, B, C, for mild, moderate, and severe nutritional deficits), ability to tolerate diet, enteral tube access, and parenteral therapy were assessed at baseline and after permanent GES placement. RESULTS: Comparing baseline with permanent, GES was found to significantly improve upper GI symptoms in all quartiles. Of the 282 patients with baseline body mass index (BMI) information, 112 (40%) patients were severely malnourished at baseline, of which 36 (32%) patients' nutritional status improved after GES. Among all patients, 76 (68%) patients' nutritional status remained unchanged. Many patients with high BMI were malnourished by SGA. CONCLUSION: We conclude that symptomatic patients of different BMIs showed improvement in their GI symptoms irrespective of baseline nutritional status. Severely malnourished patients were found to have an improvement in their nutritional status after GES therapy. We conclude that BMI, even if high, is not by itself a contraindication for GES therapy for symptomatic patients.
Subject(s)
Electric Stimulation Therapy , Gastrointestinal Diseases , Gastroparesis , Humans , Nutrition Assessment , Gastroparesis/diagnosis , Gastroparesis/therapy , Gastrointestinal Diseases/therapy , Nutritional Status , Electric Stimulation , Treatment Outcome , Gastric EmptyingABSTRACT
Oxaliplatin (OXA) resistance remains the major obstacle to the successful chemotherapy of colorectal cancer (CRC). As a self-protection mechanism, autophagy may contribute to tumor drug resistance, therefore autophagy suppression could be regarded as a possible treatment option in chemotherapy. Cancer cells, especially drug-resistant tumor cells, increase their demand for specific amino acids by expanding exogenous supply and up-regulating de novo synthesis, to meet the needs for excessive proliferation. Therefore, it is possible to inhibit cancer cell proliferation through pharmacologically blocking the entry of amino acid into cancer cells. SLC6A14 (ATB0,+) is an essential amino acid transporter, that is often abnormally up-regulated in most cancer cells. Herein, in this study, we designed oxaliplatin/berbamine-coloaded, ATB0,+-targeted nanoparticles ((O + B)@Trp-NPs) to therapeutically target SLC6A14 (ATB0,+) and inhibit cancer proliferation. The (O + B)@Trp-NPs utilize the surface-modified tryptophan to achieve SLC6A14-targeted delivery of Berbamine (BBM), a compound that is found in a number of plants used in traditional Chinese medicine, which could suppress autolysosome formation though impairing autophagosome-lysosome fusion. We verified the feasibility of this strategy to overcome the OXA resistance during colorectal cancer treatment. The (O + B)@Trp-NPs significantly inhibited the proliferation and decreased the drug resistance of resistant colorectal cancer cells. In vivo, (O + B)@Trp-NPs greatly suppressed the tumor growth in tumor-bearing mice, which is consistent with the in vitro data. This research offers a unique and promising chemotherapeutic treatment for colorectal cancer.
Subject(s)
Colorectal Neoplasms , Nanoparticles , Animals , Mice , Oxaliplatin/pharmacology , Drug Resistance, Neoplasm , Autophagy , Colorectal Neoplasms/drug therapy , Cell Line, TumorABSTRACT
Compared with the commonly used technique of freeze-drying, spray drying has lower energy costs. However, spray drying also has a fatal disadvantage: a lower survival rate. In this study, the survival of bacteria in a spray-drying tower decreased as the water content was reduced. The water content of 21.10% was the critical point for spray drying Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) sp1.1 based on sampling in the tower. Based on the relationship between the moisture content of spray drying and the survival rate, the water content of 21.10% was also the critical point for the change in the survival rate during spray drying. Proteomic analysis was used to investigate the reasons for L. bulgaricus sp1.1 inactivation during and after spray drying. Gene Ontology (GO) enrichment revealed that differentially expressed proteins were mainly associated with the cell membrane and transport. In particular, proteins related to metal ion transport included those involved in the transport of potassium, calcium and magnesium ions. The protein-protein interaction (PPI) network revealed that Ca++/Mg++ adenosine triphosphatase (ATPase) may be a key protein. Ca++/Mg++ ATPase activity decreased substantially during spray drying (p < 0.05). Supplementation with Ca++ and Mg++ significantly increased the expression of ATPase-related genes and enzyme activity (p < 0.05). The Ca++/Mg++ ATPase activity of L. bulgaricus sp1.1 was enhanced by increasing the intracellular Ca++ or Mg++ concentration, thus increasing the survival of spray-dried LAB. Bacterial survival rates were increased to 43.06% with the addition of Ca++ and to 42.64% with the addition of Mg++, respectively. Ca++/Mg++ ATPase may be the key to the damage observed in spray-dried bacteria. Furthermore, the addition of Ca++ or Mg++ also reduced bacterial injury during spray drying by enhancing the activity of Ca++/Mg++ ATPase.
ABSTRACT
Characterization of the melatonin (MLT) biosynthesis pathway in plants is still limited. Additionally, a metabolomic analysis of MLT biosynthesis in plants is still a challenge due to analyte structural and chemical diversity, low analyte abundances, and plant matrix complexities. Herein, a sensitive liquid chromatography-mass spectrometry (LC-MS) method enabling the simultaneous determination of seven plant MLT biosynthetic metabolites was developed. In the proposed strategy, the targeted metabolites, which included tryptophan (Trp), tryptamine (TAM), 5-hydroxytryptophan (5HTP), serotonin (5HT), N-acetylserotonin (NAS), 5-methoxytryptamine (5MT), and MLT, were purified from plant extracts using a one-step dispersive solid-phase extraction (DSPE). The samples were then chemically labeled with dansyl chloride (DNS-Cl), followed by analysis using LC-MS. The limit of detection (LOD) values ranged from 0.03 to 1.36 pg/mL and presented a 22- to 469-fold decrease when compared to the unlabeled metabolites. Due to the high sensitivity of the proposed method, the consumption of plant materials was reduced to 10 mg FW. Ultimately, the established method was utilized to examine the distributions of MLT and its intermediates in rice shoots and roots with or without cadmium (Cd) stress. The results suggested that under normal condition, MLT may also be generated via a Trp/TAM/5HT/5MT/MLT path (Pathway II) in addition to the previously reported Trp/TAM/5HT/NAS/MLT path (Pathway I), although Pathway I was shown to be dominant. During Cd stress, MLT was also shown to be produced through these two pathways, with Pathway II shown to be dominant in rice shoots and roots.
Subject(s)
Chromatography, Liquid/methods , Mass Spectrometry/methods , Melatonin/metabolism , 5-Hydroxytryptophan/metabolism , 5-Methoxytryptamine/metabolism , Serotonin/metabolism , Tryptamines/metabolism , Tryptophan/metabolismABSTRACT
Most fish species possess duplicate leptin genes (LEP). Mandarin fish (Siniperca chuatsi) leptin A gene (sLEP-A) have been cloned in the previous study. In the present study, we cloned and characterized leptin B gene (sLEP-B) in mandarin fish, including a 471bp open reading frame (ORF) encoding a 158-amino acid protein. The three-dimensional (3D) structural model of sLEP-B protein showed a highly conserved of tertiary structure similar to that of other vertebrates. Genomic sequencing results indicated that sLEP-B possessed only one intron. This is the first report of the loss of an intron in LEP-B in Perciformes. The different distribution patterns of sLEPs suggest different physiological roles of these two genes. The presence of HNF3ß, a liver-enriched transcription factor, only in sLEP-A indicated abundant expression and metabolic function of sLEP-A in the liver. In an in vivo experiment, the expressions of brain sLEP-A and sLEP-B were observed to increase after a meal. During the short-term fasting, the expressions of sLEPs in mandarin fish brain were decreased significantly. A persistent and significant increase in hepatic sLEP-A expression supported a relationship between leptin and food intake in mandarin fish. These results suggest that sLEP-A plays an important role in the regulation of energy homeostasis in this carnivorous fish, and sLEP-B is probably a specialized gene responsible for the central nervous system (CNS) control of energy regulation.
Subject(s)
Fasting , Fishes/genetics , Leptin/genetics , Postprandial Period , Amino Acid Sequence , Animals , Base Sequence , DNA, Complementary , Leptin/chemistry , Molecular Sequence Data , Sequence Homology, Amino AcidABSTRACT
A highly sensitive method was developed for the detection of phytochelatins (PCs) in rice by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (IL-LC-ESI-MS/MS) analysis. A pair of isotope-labeling reagents [ω-bromoacetonylquinolinium bromide (BQB) and BQB-d(7)] were used to label PCs in plant sample and standard PCs, respectively, and then combined prior to LC/MS analysis. The heavy labeled standards were used as the internal standards for quantitation to minimize the matrix and ion suppression effects in MS analysis. In addition, the ionization efficiency of PCs was greatly enhanced through the introduction of a permanent charged moiety of quaternary ammonium of BQB into PCs. The detection sensitivities of PCs upon BQB labeling improved by 14-750-fold, and therefore, PCs can be quantitated using only 5 mg of plant tissue. Furthermore, under cadmium (Cd) stress, we found that the contents of PCs in rice dramatically increased with the increased concentrations and treatment time of Cd. It was worth noting that PC5 was first identified and quantitated in rice tissues under Cd stress in the current study. Taken together, this IL-LC-ESI-MS/MS method demonstrated to be a promising strategy in detection of PCs in plants with high sensitivity and reliability.
Subject(s)
Chromatography, High Pressure Liquid/methods , Oryza/chemistry , Phytochelatins/chemistry , Plant Extracts/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Isotope Labeling , Molecular StructureABSTRACT
OBJECTIVE: To study the effects of Naoan tablets on brain hemodynamics and cerebral microcirculation of soft membrane. METHOD: Cerebral blood stream flux, resistance of blood vessels, blood pressure and heart rate were used as observation indexes in hemodynamics experiment. Artery caliber and the number of capillaries with recovered blood stream were used as observation indexes in microcirculation experiment. RESULT: Naoan tablets at dose of 0.5 g x kg(-1) and 1.0 g x kg(-1) could enhance cerebral blood stream flux, decrease resistance of blood vessels, and reduce blood pressure. While no effects on heart rate. Naoan tablet at dose of 0.7 g x kg(-1) and 2.1 g x kg(-1) could increase the number of capillaries with recovered blood stream and enlarge the artery caliber of soft membrane in rats. CONCLUSION: Naoan tablets can improve the indexes of hemodynamics and cerebral microcirculation of soft membrane.