The lipid droplet (LD) is a unique multi-functional organelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.
Animals ; Bacteria ; metabolism ; ultrastructure ; Biological Evolution ; Cholesterol Esters ; metabolism ; Humans ; Lipid Droplets ; chemistry ; metabolism ; ultrastructure ; Lipid Metabolism ; genetics ; Nucleic Acids ; metabolism ; Peptide Initiation Factors ; chemistry ; metabolism ; Protein Binding ; RNA-Binding Proteins ; chemistry ; metabolism ; Ribosome Subunits ; chemistry ; metabolism ; Triglycerides ; metabolism

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The finding that cellular microparticles (MPs) generated by injured cells profoundly impact on pathological courses of TBI has paved the way for new diagnostic and therapeutic strategies. MPs are subcellular fragments or organelles that serve as carriers of lipids, adhesive receptors, cytokines, nucleic acids, and tissue-degrading enzymes that are unique to the parental cells. Their sub-micron sizes allow MPs to travel to areas that parental cells are unable to reach to exercise diverse biological functions. In this review, we summarize recent developments in identifying a casual role of MPs in the pathologies of TBI and suggest that MPs serve as a new class of therapeutic targets for the prevention and treatment of TBI and associated systemic complications.
Animals ; Astrocytes ; metabolism ; pathology ; Biological Transport ; Blood Coagulation Factors ; genetics ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Injuries, Traumatic ; genetics ; metabolism ; pathology ; physiopathology ; Cell-Derived Microparticles ; chemistry ; metabolism ; pathology ; Cytokines ; blood ; genetics ; Disease Models, Animal ; Disseminated Intravascular Coagulation ; genetics ; metabolism ; pathology ; physiopathology ; Gene Expression Regulation ; Humans ; Microglia ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Signal Transduction

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
Action Potentials ; physiology ; Biomarkers ; metabolism ; Cell Culture Techniques ; Embryoid Bodies ; cytology ; metabolism ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Lateral Ventricles ; cytology ; growth & development ; metabolism ; Microcephaly ; genetics ; metabolism ; pathology ; Models, Biological ; Mutation ; Neocortex ; cytology ; growth & development ; metabolism ; Nerve Tissue Proteins ; deficiency ; genetics ; Neurogenesis ; genetics ; Neurons ; cytology ; metabolism ; Organoids ; cytology ; metabolism ; PAX6 Transcription Factor ; genetics ; metabolism ; Patch-Clamp Techniques ; SOXB1 Transcription Factors ; genetics ; metabolism ; Zonula Occludens-1 Protein ; genetics ; metabolism

OBJECTIVETo investigate the short- and long-term effects of Xuezhikang (XZK), an extract of cholestin, on proprotein convertase subtilisin/kexin type 9 (PCSK9) level.

METHODSThirty rats were randomly divided into three groups and were given saline, XZK 1,200 mg/kg or lovastatin 10 mg/kg respectively by daily gavage for 3 days (n=10 for each). Sixteen patients without previous lipid-lowering drug treatment for dyslipidemia received XZK 1,200 mg daily for 8 weeks. Fasting blood samples and liver tissue were collected at day 3 for rats, while the blood samples were obtained at baseline and week 8 from patients. The serum PCSK9 and lipid profile were measured. The expression of hepatic low density lipoprotein (LDL) receptor and sterol regulatory element binding protein 2 (SREBP-2) were measured by real time-PCR.

RESULTSPCSK9 levels in rats were significantly increased in the XZK and lovastatin groups (P=0.002, P=0.003 vs. control) at day 3, while no significant differences were found in the levels of lipid parameters. PCSK9 levels in patients increased by 34% (P=0.006 vs. baseline) accompanied by total cholesterol and LDL-cholesterol decreased by 22% and 28% P=0.001, P=0.002 vs. baseline). The hepatic mRNA levels of LDL-receptor and SREBP-2 were significantly increased in the XZK and lovastatin groups.

CONCLUSIONXZK has significant impact on PCSK9 in a short- and long-term manner in both rats and humans. Moreover, the data indicated that as lovastatin, XZK increased PCSK9 levels through SREBP-2 pathway.

Animals ; Biological Products ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Proprotein Convertase 9 ; blood ; Rats, Sprague-Dawley ; Receptors, LDL ; genetics ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; genetics ; metabolism ; Time Factors

The heterochronic genes regulate cell proliferation and switch development stage transitions. Heterochronic genes might also play important roles in regulating the development of silkworm, but very few of their expression profiles, functions and their relationship with microRNAs are available so far. Firstly, in this work, the primers for cloning Bmlin-41 were designed based on the homologous sequence of known Drosophila melanogaster lin-41, which was used as the query to blast against SilkDB. The obtained full CDS (2 166 bp) of Bmlin-41 encodes 721 amino acids and contains B-box and NHL domains. Then, the spatiotemporal expression patterns of Bmlin-41 were characterized by RT-PCR, quantitative real time PCR as well as our lab's previous silkworm genome microarray data. Bmlin-41 was increasingly expressed from embryonic to adult stage. In diverse tissues of day-3 fifth instar, Bmlin-41 showed the highest accumulation in ovary, secondly in testis and midgut, but very low expression was observed in other tissues. Finally, 3'UTR of Bmlin-41 1 434 bp was cloned by rapid-amplification of cDNA ends (3'RACE) and was predicted to bare two binding sites of bmo-let-7 by using online RNAhybrid. To verify the binding effect, 3'UTR was cloned into psi-CHECK-2 vector and submitted to dual luciferase assay in the S2 cells in vitro. The dual luciferase assay demonstrated that Bmlin-41 was down-regulated by bmo-let-7 mimics and upregulated by bmo-let-7 antagomir, thus confirming the Bmlin-41 is negatively regulated by bmo-let-7. Our work might help further study on the roles of Bmlin-41 and bmo-let-7 and their regulation relationship involved in controlling metamorphosis of silkworm.
3' Untranslated Regions ; Animals ; Bombyx ; Cloning, Molecular ; DNA, Complementary ; Down-Regulation ; Drosophila melanogaster ; Gene Expression Regulation ; Insect Proteins ; genetics ; metabolism ; Metamorphosis, Biological ; MicroRNAs ; metabolism ; Transcription Factors ; genetics ; metabolism

BACKGROUND/AIMS: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evaluated in previous studies. METHODS: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components. RESULTS: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of criteria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to > or = 3 (p for trend < 0.001). CONCLUSIONS: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.
Adult ; Asymptomatic Diseases ; Biological Markers/blood ; Calcium/*analysis ; Coronary Angiography/methods ; Coronary Artery Disease/blood/*epidemiology/radiography ; Coronary Vessels/*chemistry/radiography ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Syndrome X/blood/diagnosis/*epidemiology ; Middle Aged ; Multidetector Computed Tomography ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Prevalence ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; Vascular Calcification/blood/*epidemiology/metabolism/radiography

Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.
Autonomic Nervous System/physiopathology ; Biological Markers/blood ; Blood Glucose/*drug effects/metabolism ; Diabetes Mellitus, Type 2/blood/complications/diagnosis/*drug therapy/physiopathology ; Health Knowledge, Attitudes, Practice ; Humans ; Hypoglycemia/blood/chemically induced/epidemiology/physiopathology/*prevention & control ; Hypoglycemic Agents/*adverse effects ; Incidence ; Patient Education as Topic ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors

To study the protective effect of Danqi Piantan capsule ( DPC) and its antelope horn substitution (DPCAS) on the cerebral ischemia, in order to preliminary study the possibility of replacing antelope horn with artificial bezoar. In this study, the left middle cerebral artery occlusion (MCAO) was adopted. Totally 150 SD rats were randomly divided into 5 groups: the sham operation group, the model group, the Danqi Piantan capsule (DPC) group (0.246 g x kg(-1) x d(-1)), the Danqi Piantan capsule without antelope horn (DPCRA) group (0.246 g x kg(-1) x d(-1)), the Danqi Piantan capsule without antelope horn and with double artificial bezoar (DPCDB) group (0.246 g x kg(-1) x d(-1)). The MCAO model was prepared 1 h later after the administration on the 5th day. At 24 h after the operation, the inner canthus blood was collected to determine the serum superoxide dismutase (SOD) activity and the endothelin (ET) content. At 72 h after the operation, the cerebral infarct size and the cerebral index were determined by TTC-staining. The fluorescent quantitative PCR method was used to detect brain Bcl-2, Caspase-3, IL-1β, P-selectin, E-selectin, ICAM-1 mRNA expressions. The mmunohistochemical method was used to detect ICAM-1, IL-1β, TNF-α, IL-6 expressions in ischemic penumbra. According to the results, compared with the model group, DPCDB and DPC groups showed almost consistent results, indicating both of the two group can significantly improved cerebral infarction index and cerebral index (P < 0.05), increase the serum SOD activity (P < 0.05), decrease the serum ET level and Caspase-3 expression, IL-1β, P-selectin, E-selectin, ICAM-1 mRNA expressions in brain tissues (P < 0.05) and expressions of ICAM-1, IL-1,6, TNF-α, IL-6 positive cells in ischemic penumbra (P < 0.05) and increase the Bcl-2 expression (P < 0.05). The DPCRA group showed much lower impacts on indexes than DPCDB and DPC groups. This suggests that DPCDB and DPC reveal similar efficacies and antelope horn in Danqi Piantan capsule can be substitutes by artificial bezoar.
Animals ; Antelopes ; Bile ; chemistry ; Biological Factors ; administration & dosage ; chemical synthesis ; chemistry ; Brain ; drug effects ; metabolism ; Caspase 3 ; genetics ; metabolism ; Drug Compounding ; Horns ; chemistry ; Humans ; Infarction, Middle Cerebral Artery ; drug therapy ; genetics ; metabolism ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Interleukin-1beta ; genetics ; metabolism ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; genetics ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

To investigate cytotoxic secondary metabolites of Micrococcus sp. R21, an actinomycete isolated from a deep-sea sediment (-6 310 m; 142 degrees 19. 9' E, 10 degrees 54. 6' N) of the Western Pacific Ocean, column chromatography was introduced over silica gel, ODS, and Sephadex LH-20. As a result, eight compounds were obtained. By mainly detailed analysis of the NMR data, their structures were elucidated as cyclo(4-hydroxy-L-Pro-L-leu) (1), cyclo(L-Pro-L-Gly) (2), cyclo( L-Pro-L-Ala) (3), cyclo( D-Pro-L-Leu) (4), N-β-acetyltryptamine (5), 2-hydroxybenzoic acid (6), and phenylacetic acid (7). Compound 1 exhibited weak cytotoxic activity against RAW264. 7 cells with IC50 value of 9.1 μmol x L(-1).
Animals ; Biological Factors ; chemistry ; isolation & purification ; metabolism ; pharmacology ; Cell Survival ; drug effects ; Macrophages ; cytology ; drug effects ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Mice ; Micrococcus ; chemistry ; genetics ; isolation & purification ; metabolism ; Molecular Structure ; Phylogeny ; RAW 264.7 Cells ; Seawater ; microbiology ; Secondary Metabolism

Endophytic fungi Penicillium dangeardii, isolated from Lysidice rhodostegia Hance root, was fermented and the secondary metabolites were studied. By means of Sephadex LH-20 column chromatography, ODS column chromatography and PHPLC over the fermented culture, 5 compounds were isolated. By using ESI-MS and NMR, the structures of the compounds were determined as N-[9-(β- D-ribofuranosyl)-9H-purin-6-yl]-L-aspartic acid (1), 3-caffeoylquinic acid (2), 4-caffeoylquinic acid (3), and 5-caffeoylquinic acid (4), 3-hydroxy-benzoic acid-4-O-β-D-glucopyranoside (5).
Biological Factors ; chemistry ; isolation & purification ; metabolism ; Endophytes ; chemistry ; metabolism ; Fabaceae ; microbiology ; Fermentation ; Molecular Structure ; Penicillium ; chemistry ; metabolism ; Secondary Metabolism