Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks. OBJECTIVE: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial. METHODS: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose. RESULTS: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL. CONCLUSIONS: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Whole genome sequence data of a marine bacterium, Marinobacter adhaerens PBVC038, associated with toxic harmful algal bloom.

Marinobacter adhaerens (PBVC038) was isolated from a harmful algal bloom event caused by the toxic dinoflagellate Pyrodinium bahamense var. compressum (P. bahamense) in Sepanggar Bay, Sabah, Malaysia, in December 2012. Blooms of P. bahamense are frequently linked to paralytic shellfish poisoning, resulting in morbidity and mortality. Prior experimental evidence has implicated the role of symbiotic bacteria in bloom dynamics and the synthesis of biotoxins. The draft genome sequence data of a harmful algal bloom-associated bacterium, Marinobacter adhaerens PBVC038 is presented here. The genome is made up of 21 contigs with an estimated 4,246,508 bases in genome size and a GC content of 57.19%. The raw data files can be retrieved from the National Center for Biotechnology Information (NCBI) under the Bioproject number PRJNA320140. The assessment of bacterial communities associated with harmful algal bloom should be studied more extensively as more data is needed to ascertain the functions of these associated bacteria during a bloom event.

Association between fat mass and obesity-related variant and osteoarthritis risk: Integrated meta-analysis with bioinformatics.

Objective: The association of fat mass and obesity-related (FTO) gene with osteoarthritis (OA) risk has been investigated in multiple genome-wide association studies but showed inconsistent results. Our study aimed to assess FTO expression in different OA sequencing datasets and to meta-analyze whether FTO polymorphism was associated with the risk of osteoarthritis. Method: Gene expression profiles were obtained from ArrayExpress, Gene Expression Omnibus (GEO), and BioProject databases. Three electronic databases including PubMed and EMBASE were systematically retrieved to identify articles exploring the association between FTO polymorphisms and OA risk published before September 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to perform the result. Stata software was utilized to conduct analyses on predetermined ethnicity and gender subgroups and sensitivity. Results: FTO gene was differentially expressed in the datasets from the UK. This systematic review and meta-analysis encompasses eight studies that revealed a significant association between FTO polymorphisms and OA risk [OR 1.07, 95% CI (1.03, 1.11), P < 0.001] in the overall population. In subgroup analysis, a marked association was observed in European Caucasian [OR 1.08, 95% CI (1.04-1.12), P < 0.001] and North American Caucasian with the Asian subgroups [OR 0.98, 95% CI (0.83-1. 6), P = 0.83] as an exception. Among the studies, four of them demonstrated attenuation in their OA risk after body mass index (BMI) adjustment in Caucasian populations. Conclusion: FTO significant differential expression was associated with the increased risk of OA in Caucasian populations. Nevertheless, the causality between FTO polymorphisms and OA risk remains largely elusive. Hence, further studies with larger sample size are necessary to validate whether FTO gene polymorphism contributes to OA susceptibility.

Chemical-Empowered Human Adipose-Derived Stem Cells with Lower Immunogenicity and Enhanced Pro-angiogenic Ability Promote Fast Tissue Regeneration.

Mesenchymal stem cells (MSCs) have been widely used as functional components in tissue engineering. However, the immunogenicity and limited pro-angiogenic efficacy of MSCs greatly limited their pro-regenerative ability in allogenic treatment. Herein, utilizing a chemically defined cocktail in the culture system, including cytokines, small molecules, structural protein, and other essential components, we generated the immunoprivileged and pro-angiogenic cells (IACs) derived from human adipose tissues. Conventional adipose-derived MSCs (cADSCs) were used as a control in all the experiments. IACs show typical MSC properties with enhanced stemness capacity and a robust safety profile. IACs induce a significantly milder immune response of allogenic peripheral blood mononuclear cells in an H3K27me3-HLA axis-dependent manner. IACs, through superior paracrine effects, further promote nitric oxide production, anti-apoptotic ability, and the tube formation of human vein endothelial cells. Embedded in a photo-reactive hydrogel (Gel) termed as GelMA/HA-NB/LAP for tissue engineering treatment, IACs promote faster tissue regeneration in a xenogeneic full-thickness skin defect model, eliciting a milder immune response and enhanced blood vessel formation in IACs-treated defect areas. Together with its excellent pro-regenerative potential and robust safety, our findings suggest that IACs may be a promising candidate for clinically relevant stem cell and tissue engineering therapeutics.

Designing Electrochemical Biosensing Platforms Using Layered Carbon-Stabilized Porous Silicon Nanostructures.

Porous silicon (pSi) is an established porous material that offers ample opportunities for biosensor design thanks to its tunable structure, versatile surface chemistry, and large surface area. Nonetheless, its potential for electrochemical sensing is relatively unexplored. This study investigates layered carbon-stabilized pSi nanostructures with site-specific functionalities as an electrochemical biosensor. A double-layer nanostructure combining a top hydrophilic layer of thermally carbonized pSi (TCpSi) and a bottom hydrophobic layer of thermally hydrocarbonized pSi (THCpSi) is prepared. The modified layers are formed in a stepwise process, involving first an electrochemical anodization step to generate a porous layer with precisely defined pore morphological features, followed by deposition of a thin thermally carbonized coating on the pore walls via temperature-controlled acetylene decomposition. The second layer is then generated beneath the first by following the same two-step process, but the acetylene decomposition conditions are adjusted to deposit a thermally hydrocarbonized coating. The double-layer platform features excellent electrochemical properties such as fast electron-transfer kinetics, which underpin the performance of a TCpSi-THCpSi voltammetric DNA sensor. The biosensor targets a 28-nucleotide single-stranded DNA sequence with a detection limit of 0.4 pM, two orders of magnitude lower than the values reported to date by any other pSi-based electrochemical DNA sensor.

Dataset of genome sequence, de novo assembly, and functional annotation of Ruegeria sp. (PBVC088), a marine bacterium associated with the toxin-producing harmful dinoflagellate, Pyrodinium bahamense var. compressum.

The dataset comprises a whole-genome sequence of Ruegeria sp. PBVC088, a symbiotic (Gram-negative) bacterium associated with Pyrodinium bahamense var. compressum, which has been associated with harmful algal blooms in the coastal waters of west Sabah, Malaysia. Harmful algal blooms contribute to economic losses for the aquaculture industry, as well as human illnesses and fatalities due to paralytic shellfish poisoning. Bacteria-algae dynamics have posited that the interaction is potentially responsible for the toxin production during a toxic harmful algal bloom event. Despite the expanding body of literature on the capabilities of these bacteria to metabolize, produce, and modify toxins autonomously, it has yet to be confirmed that these toxin-producing bacteria are capable of autonomous toxin synthesis. Saxitoxin, a paralytic shellfish poisoning toxin, is produced by a unique biosynthetic pathway, where the genetic basis for the saxitoxin production was first reported in the saxitoxin-producing cyanobacteria strain Cylindrospermopsis raciborskii T3 (NCBI accession no. DQ787200). The genes responsible for saxitoxin biosynthesis in dinoflagellates, have yet to be fully elucidated. The identification of cyanobacteria saxitoxin biosynthesis genes (sxt) may eventually lead to the identification of homologous genes within the dinoflagellates. Previous studies on the diversity of the bacterial communities associated with the same toxic P. bahamense harmful alga has been carried out by using both the culture-dependent 16S ribosomal RNA gene sequence analysis and culture-independent 16S metagenomic sequence analysis. This study extends the knowledge pertaining to the genomic aspect of an associated bacterium isolated from P. bahamense alga by adopting a whole genome sequencing approach. Here, we report the genome sequencing, de novo assembly, and annotation data of a bacterium, Ruegeria sp. PBVC088, associated with harmful alga P. bahamense, which can be referenced by researchers to identify the genes and pathways related to toxin biosynthesis from a much larger data set. The genome of Ruegeria sp. PBVC088 was sequenced using the Illumina MiSeq platform with 250 bp paired-end reads. The number of reads generated from the MiSeq sequencer was 1,135,484, with an estimated coverage of 100X. The estimated genome size for the marine bacterium was computed to be 5.78 Mb. Annotation of the genome predicted 5,689 gene sequences, which were assigned putative functions based on homology to existing protein sequences in public databases. In addition, annotation of genes related to saxitoxin biosynthesis pathway was also performed. Raw fastq reads and the final version of the genome assembly have been deposited in the National Center for Biotechnology Information (NCBI) (BioProject: PRJNA324753, WGS: LZNT00000000, SRA: SRR3646181). The genome data provided here are expected to better understand the genetic processes involved in saxitoxin biosynthesis in marine bacteria associated with dinoflagellates.

Genomic data of two Bacillus and two Pseudomonas strains isolated from the acid mine drainage site at Mamut Copper Mine, Ranau, Malaysia.

The genomic data of four bacteria strains isolated from the abandoned Mamut Copper Mine, an Acid Mine Drainage (AMD) site is presented in this report. Two of these strains belong to the genus Bacillus, while the other two belong to the genus Pseudomonas. The draft genome size of Pseudomonas sp. strain MCMY3 was 6,396,595 bp (GC: 63.3%), Bacillus sp. strain MCMY6 was 6,815,573 bp (GC: 35.2%), Bacillus sp. strain MCMY13 was 5,559,059 bp (GC: 35.5%) and Pseudomonas sp. strain MCMY15 was 7,381,777 bp (GC: 64.8%). These four genomes contained 493, 495, 495 and 579 annotated subsystems, respectively. The sequence data are available at GenBank sequence read archive with accessions numbers SRX7859406, SRX7859404, SRX7859405 and SRX7293032 for strains MCMY3, MCMY6, MCMY13 and MCMY15, respectively.

Adaptive Strategies of Bacillus thuringiensis Isolated from Acid Mine Drainage Site in Sabah, Malaysia.

The adaptive process in bacteria is driven by specific genetic elements which regulate phenotypic characteristics such as tolerance to high metal ion concentrations and the secretion of protective biofilms. Extreme environments such as those associated with heavy metal pollution and extremes of acidity offer opportunities to study the adaptive mechanisms of microorganisms. This study focused on the genome analysis of Bacillus thuringiensis (Bt MCMY1), a gram positive rod shaped bacterium isolated from an acid mine drainage site in Sabah, Malaysia by using a combination of Single Molecule Real Time DNA Sequencing, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The genome size of Bt MCMY1 was determined to be 5,458,152 bases which was encoded on a single chromosome. Analysis of the genome revealed genes associated with resistance to Copper, Mercury, Arsenic, Cobalt, Zinc, Cadmium and Aluminum. Evidence from SEM and FTIR indicated that the bacterial colonies form distinct films which bear the signature of polyhydroxyalkanoates (PHA) and this finding was supported by the genome data indicating the presence of a genetic pathway associated with the biosynthesis of PHAs. This is the first report of a Bacillus sp. isolated from an acid mine drainage site in Sabah, Malaysia and the genome sequence will provide insights into the manner in which B. thuringiensis adapts to acid mine drainage.