Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR⁺) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR⁺ neurons directly regulate the mPFC-NAcShell circuit via GABA_A receptors. Thus, the MOR⁺ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Animals ; Nucleus Accumbens/drug effects* ; Prefrontal Cortex/drug effects* ; Nicotine/pharmacology* ; Receptors, Opioid, mu/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Tobacco Use Disorder/metabolism* ; Neurons/drug effects* ; Neural Pathways/drug effects*

Cell Differentiation ; Nicotine/pharmacology* ; Osteogenesis/physiology* ; Periodontal Ligament ; Stem Cells

Blakeslea trispora is a natural source of carotenoids, including β-carotene and lycopene, which have industrial applications. Therefore, classical selective breeding techniques have been applied to generate strains with increased productivity, and microencapsulated β-carotene preparation has been used in food industry (Li et al., 2019). In B. trispora, lycopene is synthesized via the mevalonate pathway (Venkateshwaran et al., 2015). Lycopene cyclase, which is one of the key enzymes in this pathway, is a bifunctional enzyme that can catalyze the cyclization of lycopene to produce β-carotene and exhibit phytoene synthase activity (He et al., 2017).
Citric Acid Cycle ; Fermentation ; Gas Chromatography-Mass Spectrometry/methods* ; Lycopene/metabolism* ; Mucorales/metabolism* ; Nicotine/pharmacology* ; beta Carotene/biosynthesis*

OBJECTIVETo explore the effect of nicotine on the autophagy level of human periodontal ligament cells (hPDLCs).

METHODSPeriodontal tissues collected from premolars for orthodontic treatment reasons were used to culture hPDLCs. Western blot analysis was performed to test the most optimal time and concentration of nicotine on the autophagy level of the hPDLCs. Transmission electron microscope and immunofluorescence observation were carried out to detect the form of autophagosomes and expression of autophagy related protein LC3 in hPDLCs under this optimal condition.

RESULTSProtein expression of LC3Ⅱ was up regulated with the 12 h nicotine stimulating. Besides that, the up regulation of the protein expression of LC3Ⅱ was concentration dependent and nicotine with a concentration of 1×10⁻⁵ mol·L⁻¹ was the most optimal condition. Transmission electron microscope and immunofluorescence observations indicated that nicotine would activate the autophagy level of hPDLCs by increasing the number of autophagosomes and up regulating the expression of autophagy related protein LC3.

CONCLUSIONSNicotine could increase autophagy level of hPDLCs, thus affecting the occurrence and development of smoking related periodontitis.

Autophagy ; Blotting, Western ; Cell Culture Techniques ; Cells, Cultured ; Humans ; Microtubule-Associated Proteins ; Nicotine ; pharmacology ; Nicotinic Agonists ; pharmacology ; Periodontal Ligament ; Periodontitis ; Up-Regulation

A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Amyloid beta-Peptides ; antagonists & inhibitors ; metabolism ; Binding Sites ; Butyrylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Nicotine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology

Streptococcus mutans is a common Gram-positive bacterium and plays a significant role in dental caries. Tobacco and/or nicotine have documented effects on S. mutans growth and colonization. Sortase A is used by many Gram-positive bacteria, including S. mutans, to facilitate the insertion of certain cell surface proteins, containing an LPXTGX motif such as antigen I/II. This study examined the effect of nicotine on the function of sortase A to control the physiology and growth of S. mutans using wild-type S. mutans NG8, and its isogenic sortase-defective and -complemented strains. Briefly, the strains were treated with increasing amounts of nicotine in planktonic growth, biofilm metabolism, and sucrose-induced and saliva-induced antigen I/II-dependent biofilm formation assays. The strains exhibited no significant differences with different concentrations of nicotine in planktonic growth assays. However, they had significantly increased (P≤0.05) biofilm metabolic activity (2- to 3-fold increase) as the concentration of nicotine increased. Furthermore, the sortase-defective strain was more sensitive metabolically to nicotine than the wild-type or sortase-complemented strains. All strains had significantly increased sucrose-induced biofilm formation (2- to 3-fold increase) as a result of increasing concentrations of nicotine. However, the sortase-defective strain was not able to make as much sucrose- and saliva-induced biofilm as the wild-type NG8 did with increasing nicotine concentrations. These results indicated that nicotine increased metabolic activity and sucrose-induced biofilm formation. The saliva-induced biofilm formation assay and qPCR data suggested that antigen I/II was upregulated with nicotine but biofilm was not able to be formed as much as wild-type NG8 without functional sortase A.
Amino Acid Motifs ; Aminoacyltransferases ; drug effects ; genetics ; Antigens, Bacterial ; drug effects ; Bacterial Adhesion ; drug effects ; Bacterial Proteins ; drug effects ; genetics ; Biofilms ; drug effects ; Cysteine Endopeptidases ; drug effects ; genetics ; Dose-Response Relationship, Drug ; Humans ; Mutation ; genetics ; Nicotine ; administration & dosage ; pharmacology ; Peptidoglycan ; drug effects ; genetics ; Saliva ; physiology ; Streptococcus mutans ; drug effects ; enzymology ; growth & development ; Sucrose ; pharmacology

OBJECTIVEThe present study was to explore signaling mechanisms underlying nicotine-induced inhibition of large-conductance calcium-activated potassium channels (BK(Ca)).

METHODS8 week male Wistar rats were divided randomly into saline group and nicotine group and received respectively injection with saline or nicotine (Sigma, Shanghai, China) at 2 mg/(kg x d) for 21 days. Coronary vascular smooth muscle cells were dissociated enzymatically. Dissociated smooth muscle cells were interfered with CPT-cAMP (100 micromol/L) or forskolin (10 micromol/L). The signal channel open dwell-time (To), close dwell-time (Tc) and open probability (Po) were recorded.

RESULTSCPT-cAMP or forskolin significantly prolonged To, shorten Tc and increased Po in saline group (P < 0.01). But in nicotine group To, Tc and Po did not been changed.

CONCLUSIONThis phenomenon may serve as a physiological mechanism that nicotine inhibits BK(Ca) channel activity to increase via cAMP/PKA-dependent pathway.

Animals ; Arteries ; cytology ; drug effects ; metabolism ; Coronary Vessels ; cytology ; drug effects ; metabolism ; Large-Conductance Calcium-Activated Potassium Channels ; metabolism ; Male ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Nicotine ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Signal Transduction

OBJECTIVETo observe the role of magnesium sulfate in vascular calcification, to explore the role and the mechanism of magnesium sulfate in vascular calcification.

METHODSThe vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN) in SD rats. To estimate the extent of calcification by Von Kossa staining, calcium content and alkaline phosphatase activity, osteopontin (OPN) mRNA were determined by using semi-quantitative reverse-transcription polymerase chain reaction.The malondialdehyde (MDA) and nitric oxide (NO) content and activities of superoxide dismutase(SOD) were measured by biochemistry.

RESULTSA strong positive staining of black/brown areas among the elastic fibers of the medial layer in calcified aorta by Von Kossa staining, calcium content and ALP activity in calcified arteries increased by 3.9-and 3.4-fold as compared with the controls. The expression of OPN mRNA was up-regulated by 40% (P < 0.01). The lipid peroxidation products MDA in vascular were increased 2.0-fold (P < 0.01). The NO content and SOD activity were greatly decreased by 64% and 72% (P < 0.01), respectively, compared with controls. However, calcium content and ALP activity in VDN plus magnesium sulfate group were lower than those in VDN group. Low and high dosage magnesium sulfate obviously relieved degree of calcification in the cardiovascular tissues in a dosage-dependent manner (P < 0.01).

CONCLUSIONMagnesium sulfate plays a role in the pathogenesis of vascular calcification by reducing vascular calcification and decreasing vascular injury.

Animals ; Cholecalciferol ; adverse effects ; Magnesium ; pharmacology ; Male ; Nicotine ; adverse effects ; Osteopontin ; metabolism ; RNA, Messenger ; genetics ; Rats ; Vascular Calcification ; chemically induced ; pathology

OBJECTIVETo review the current evidence that links smoking to obstructive sleep apnea (OSA) and to discuss some potential mechanisms proposed for these links.

DATA SOURCESWe searched PubMed and Medline to identify studies investigating the interaction between smoking and OSA.

STUDY SELECTIONArticles regarding the relationship between smoking and OSA were selected. Studies considered smoking as a confounding factor were excluded.

RESULTSThe association of smoking and OSA has been confirmed in several studies. The effects of smoking on the pathophysiology of OSA may include smoking-induced upper airway inflammation, stimulant effects of nicotine on upper airway muscles, and a "rebound effect" due to nightly short-term nicotine withdrawal, or all of the above. In addition, the coexistence of OSA and smoking may have more widespread implications for cardiovascular dysfunction in patients with OSA. Finally, OSA might be responsible for the addiction to nicotine.

CONCLUSIONSSmoking may act as a risk factor for OSA and join with OSA in a common pathway to increase the risk of systematic injury. OSA, in turn, may be a predisposing factor for smoking. Thus, smoking cessation is recommended when considering treatment for OSA, and treating OSA may be a necessary precondition for successful smoking cessation.

Asthma ; epidemiology ; etiology ; Bronchi ; drug effects ; Humans ; Nicotine ; pharmacology ; Risk Factors ; Sleep ; physiology ; Sleep Apnea, Obstructive ; epidemiology ; etiology ; Smoking ; adverse effects ; Tobacco Use Disorder ; epidemiology ; etiology

Human amylin (hAmylin) is co-released with insulin from pancreatic B-cells and the actions of this peptide on its target tissues maintain the cell excitability and glucose homeostasis. Inappropriate control of hAmylin secretion may result in human disease, particularly Alzheimer's disease (AD). It's unknown that which kind of receptor is activated by human amylin, leading to the neurotoxicity in neurons of brain. Nicotinic acetylcholine receptors (nAChRs) are known to play a critical role in a variety of nervous diseases. In the present study, we sought to determine the inter-relationships between these two receptors by examining the actions of hAmylin and nicotine on whole-cell currents and membrane potential in basal forebrain neurons. Whole cell patch-clamp recordings were performed on enzymatically dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. The results showed that either hAmylin or nicotine individually caused a dose-dependent (1 nmol/L-20 µmol/L) membrane depolarization and an increase in firing frequency of DBB neurons. Application of AC253, an amylin receptor antagonist, blocked the excitatory effects of not only hAmylin but also nicotine; dihydro-β-erythroidine (DHβE), a nAChR antagonist, also blocked the effects of nicotine and hAmylin. These electrophysiological results suggest that hAmylin receptor and nAChRs on DBB neurons are coupled and may function in a co-operative manner to influence the excitability of DBB neurons. This finding is important for us to understand the cause and mechanisms of AD.
Animals ; Brain ; metabolism ; physiology ; Diagonal Band of Broca ; metabolism ; physiology ; Humans ; Islet Amyloid Polypeptide ; pharmacology ; Male ; Neurons ; metabolism ; physiology ; Nicotine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Islet Amyloid Polypeptide ; physiology ; Receptors, Nicotinic ; physiology