nicotine (NC001) / Neurocea, Neuraltus - LARVOL DELTA

Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development. (PubMed, Genes (Basel)) - "Further dissection of RNA-Seq during fetal brain development and within cerebral organoids showed an association of ODC1 expression with cell proliferation of neural progenitor cells, suggesting gain-of-function variants with neural over-proliferation and loss-of-function variants with neural depletion. The linkage from the expression data of ODC1 in early neural progenitor proliferation to phenotypes of neurodevelopmental delay and to the connection of polyamine metabolites in brain function establish ODC1 as a bona fide neurodevelopmental disorder gene."

Journal • Alopecia • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Mood Disorders • Oncology • Psychiatry • Rare Diseases • Schizophrenia • ODC1

Optimized HSP90 mediated fluorescent probes for cancer-specific bioimaging. (PubMed, J Mater Chem B) - "Herein, a highly efficient tumor-targeting fluorescent probe (NP-001), which is integrated with 4-hydroxy-1,8-naphthalimide and NVP-AUY922, for tumor imaging has been established...NP-002, a resorcinol-blocked probe which prevented binding with an amino acid residue of the HSP90 ATP binding pocket, was also synthesized as a control...Moreover, pharmacokinetic studies and histological analysis also indicated that NP-001 had a relatively longer retention time and showed no major organ-related toxicities. Overall, these encouraging data suggest that NP-001 is a promising new candidate for the early diagnosis of metastatic disease as well as targeted tumor imaging."

Journal • Oncology • HSP90AA1

Mutations causing Lopes-Maciel-Rodan Syndrome are huntingtin hypomorphs. (PubMed, Hum Mol Genet) - "The NM_002111.8: c.4469 + 1G > A splice donor variant results in aberrant (exon 34) splicing and severely reduced mRNA, whereas, surprisingly, the NM_002111.8: c.8157 T > A NP_002102.4: Phe2719Leu missense variant results in abnormally rapid turnover of the Leu2719 huntingtin protein. Thus, while rare and subject to an as yet unknown loss-of-function intolerance at the population level, bona fide HTT loss-of-function variants can be transmitted by normal individuals leading to severe consequences in compound heterozygotes due to huntingtin deficiency."

Journal • CNS Disorders • Developmental Disorders • Huntington's Disease • Movement Disorders • Psychiatry

The Translational Switch of MYC Protein Aliases in Myeloma Tumor Cells (ASH 2019) - "Previous studies have determined that the translations can be alternatively initiated from an in-frame CUG (Leucine) codon to generate NP_002458 alias or at a downstream canonical cap-dependent AUG (Methionine) codon to generate P01106 alias...We are currently examining the precise amino acid sequences on both N-terminal and C-terminal ends of MYC aliases to study the regulatory mechanisms of the translational switching. This may indicate a novel anti-cancer strategy to cease cancer proliferation by deliberately inducing alternative translation of the antagonistic alias of an oncogene, and eventually overcome cooperation of the chromosomal rearrangements and dysregulated oncogene transcriptions in progressive cancer cells."

Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • MYC • TP53

Effect of NP002, a centrally acting cholinergic agent, in reducing dyskinesia, freezing of gait, and falls in patients with Parkinsons disease (AAN 2018) - "NP002, a novel direct cholinergic agonist, improved two relatively refractory symptoms of PD: falls and FOG, while probably reducing LIDs."

Clinical • CNS Disorders • Parkinson's Disease

Environmental exposure and effects on health of children from a tobacco-producing region. (PubMed) - Environ Sci Pollut Res Int - "Biomarkers of exposure to the following xenobiotics were assessed: pesticides, nicotine, toxic elements, and organic solvents. The increased Cr levels were associated with decreased lymphocytes and increased basophils. Our findings demonstrate that children environmentally exposed to xenobiotics in rural area may present early kidney dysfunction, hematological alterations, as well as lipid and protein damages, associated with co-exposure to different xenobiotics involved in tobacco cultivation."

Biomarker • Journal • Biosimilar • Renal Disease

Chronic FAAH inhibition during nicotine abstinence alters habenular CB1 receptor activity and precipitates depressive-like behaviors. (PubMed) - Neuropharmacology - "No FAAH inhibition-induced alterations were observed in animals that had a previous history of saline self-administration. Taken together, our results suggest that chronic FAAH inhibition prevents the homeostatic adaptations of habenular CB1 receptor function that are necessary for the recovery from nicotine dependence."

Journal • Biosimilar

Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke. (PubMed) - Regul Toxicol Pharmacol - "Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F."

Journal • Biosimilar • Immunology

Process development for cigarette butts recycling into cellulose pulp. (PubMed) - Waste Manag - "During the process, a dark liquor is generated, which was found to contain lignin, carbonyls, metals, nicotine and specific tobacco nitrosamines. The dark liquor presented a high chemical oxygen demand (COD; 29,986mg/L), which was partially removed by precipitation (20%), chitosan coagulation (66%) and ozonation (45.8%). As the remaining COD was still high, we proposed reusing the clarified effluent in alkaline pulping, which seemed to be the easiest and most efficient procedure with the lowest cost."

Journal • Biosimilar

Optimization of Carbon Nanotube Membranes by Electrochemical Oxidation for Remotely Programmable Transdermal Nicotine Replacement Therapy (AAPS 2016) - " Electrochemical oxidation is an effective method to open the blocked pores of CNT in order to achieve therapeutically useful nicotine fluxes and also reduce batch to batch variations. These blue-tooth enabled CNT membrane devices along with smart phone app based interventions for behavioral support are highly promising for smoking cessation therapy."

Biosimilar

Ibogaine - structure, influence on human body, clinical relevance (PubMed) - Pol Merkur Lekarski - "Other effects include reduction or complete disappearance of absitnence symptoms visible in people addicted to the nicotine, alcohol, methamphetamine, cocaine or opioids, what has been scientifically proven after the tests on animals and small groups of people. There is more hope with synthetic derivatives of ibogaine, which although are less toxic still keep their anti-addiction properties. The aim is to collect the available knowledge related to the structure and effects on human body of alkaloid Tabernanthe iboga and consider the possibility of commercial medical use."

Journal • Review • Biosimilar • Ophthalmology

Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction: A Multifactorial Perspective. (PubMed) - Front Psychiatry - "However, pre-existing cognitive and mood disorders may also influence the development and maintenance of nicotine dependence, by biasing nicotine-induced alterations in information processing and associative learning, decision-making, and inhibitory control. Here, we discuss the potential forms of contribution of cognitive and affective deficits to nicotine addiction-related processes, by reviewing major clinical and preclinical studies investigating either the procognitive and therapeutic action of nicotine or the putative primary role of cognitive and emotional impairments in addiction-like features."

Journal • Review • Biosimilar • CNS Disorders • Multiple Sclerosis • Schizophrenia

Medical swab touch spray-mass spectrometry for newborn screening of nicotine and cotinine in meconium. (PubMed) - J Mass Spectrom - "These results provided that medical swab TS-MS would be useful for newborn screening of nicotine and cotinine in meconium with high reproducibility, speed, sensitivity, and specificity. The use of disposable medical swabs involves no sample preparation and no chromatographic separation, significantly reducing the cost and time required for screening of a large number of clinical sample."

Journal • Biosimilar • Multiple Sclerosis

Long-term e-cigarette use and smoking cessation: a longitudinal study with US population. (PubMed) - Tob Control - "Short-term e-cigarette use was not associated with a lower rate of smoking cessation. Long-term use of e-cigarettes was associated with a higher rate of quitting smoking."

Journal • Biosimilar

Nicotine-induced structural plasticity in mesencephalic dopaminergic neurons is mediated by dopamine D3 receptors and Akt-mTORC1 signalling (Mol Pharmacol) - PMID: 23543412; "...exposure to nicotine in utero (5 mg/kg/day for 5 days) resulted in increased soma area of DAergic neurons of newborn mice, effects not observed in D3KO mice...nicotine-induced structural plasticity in mesencephalic dopaminergic neurons involves α4β2 nAChRs together with dopamine D3R-mediated recruitment of ERK/Akt-mTORC1 signaling."

Preclinical • Parkinson's Disease

MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH PATTERNS AND NEWBORN SIZE. (PubMed) - J Biosoc Sci - "The association patterns between maternal height and pre-pregnancy weight status with fetal growth patterns (p<0.001), as well as newborn size (p<0.001), were independent of maternal age, nicotine consumption and fetal sex. In general, taller and heavier women gave birth to larger infants. This association between maternal size and fetal growth patterns was detectable from the first trimester onwards."

Journal • Biosimilar

Immunomodulatory effects of nicotine on interleukin 1β activated human astrocytes and the role of cyclooxygenase 2 in the underlying mechanism. (PubMed) - J Neuroinflammation - "Activation of the cholinergic system through α7nAChR agonists has been known to suppress inflammation both in the CNS and periphery. In the CNS, earlier experimental data shows that cholinergic activation through nicotine inhibits microglial activation and proinflammatory cytokine release. Here, we report similar anti-inflammatory effects of cholinergic activation on human astrocytes, at least partly mediated through the COX-2 pathway. These results confirm the potential for cholinergic neuroprotection, which is looked upon as a promising therapy for neuroinflammation as well as neurodegenerative diseases and stroke. Our data implicates an important role for the prostaglandin system in cholinergic regulatory effects."

Journal • Biosimilar • Immunology

Clinical and Ultrastructural Studies of Gelatinous Drop-Like Corneal Dystrophy (GDLD) of a Patient with TACSTD2 Gene Mutation. (PubMed, J Ophthalmol) - "A homozygous c.355T > A mutation in exon 1 of the TACSTD2 (M1S1) gene was detected, and alteration of the amino acid (p.Cysl19Ser in NCBI entry NP_002344.2) was observed. In our patient with GDLD, a "c.355T > A" mutation in exon 1 of TACSTD2 was detected and believed to be responsible for the alteration of the amino acid leading to the formation of the amyloid deposits. The deposits caused the ultrastructural degeneration of epithelium, Bowman's layer, stroma, and keratocytes of the GDLD cornea."

Clinical • Journal