BACKGROUND:Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss. Evidence links gut-brain axis dysfunction and metabolic disturbances to AD. Although cannabidiol (CBD) has neuroprotective effects, its use is limited by poor bioavailability and brain delivery. METHODS:Arginylglycylaspartic acid (RGD)-functionalized, CBD-loaded lipid nanoparticles (CBD/LNP-RGD) were developed to enhance targeted delivery across the blood-brain barrier (BBB) via integrin αvβ3-mediated transcytosis. Cellular uptake and BBB permeability were evaluated in vitro. Anti-inflammatory and antioxidant effects were assessed in Aβ/LPS-induced models. In vivo efficacy was examined using cognitive-behavioral tests, including the novel object recognition and the Morris water maze. Metabolic parameters, histopathology, synaptic protein expression, and gut barrier integrity were also evaluated. RESULTS:CBD/LNP-RGD demonstrated a 3-fold increase in cellular uptake and a 65% enhancement in BBB transport compared to non-targeted formulations. Treatment significantly reduced pro-inflammatory cytokines (i.e., IL-6 and TNF-α, p < 0.001) and intracellular reactive oxygen species (p < 0.001). In vivo, CBD/LNP-RGD improved cognitive performance comparable to Donepezil (p < 0.001). Additionally, it normalized glycemic control, insulin resistance, and triglyceride levels without hepatic or renal toxicity. At the tissue level, CBD/LNP-RGD reduced Aβ and tau pathology, restored short-chain fatty acids, preserved hippocampal neuronal integrity, and upregulated synaptophysin and PSD-95 proteins. Enhanced intestinal barrier function was evidenced by increased expression of tight junction proteins ZO-1 and occludin. CONCLUSIONS:CBD/LNP-RGD represents a multifunctional nanotherapeutic platform that improves brain delivery and exerts neuroprotective, anti-inflammatory, antioxidant, and metabolic regulatory effects. Its ability to modulate both central pathology and the gut-brain axis highlights its potential as a disease-modifying strategy for Alzheimer's disease.
Japanese encephalitis virus (JEV) is an arbovirus which is the most common virus in the genus Orthoflavivirus that causes significant viral encephalitis with a high fatality rate and is distributed throughout Asian countries. JEV infection induces brain tissue disease characterized by neuronal death. We previously demonstrated that JEV elevates the formation of an N-terminal truncated version of BAX (p18 BAX), triggering mitochondria-mediated apoptosis. However, the mechanisms by which virus-host interactions induce the generation of p18 BAX during JEV infection are unclear. The present study aims to investigate the underlying mechanism by which JEV-induced cell apoptosis is mediated by the activation of calpain-induced proteolytic cleavage of BAX. Calpeptin, a calpain inhibitor, was used to evaluate the effect on calpain activity, cell viability, and apoptotic molecules expression in JEV-infected neuroblastoma SH-SY5Y cells. Our data showed that JEV infection resulted in the activation of the calpain-mediated apoptosis pathway, as evidenced by increased calpain activation and p18 BAX generation. The translocation of p18 BAX to the mitochondria results in cytochrome c release and increased of caspase-3 activity, resulting in an increase of cleaved PARP expression, which induced neuronal apoptosis. Inhibiting calpain activity by calpeptin attenuated all these effects. Our results reveal that JEV induces neuronal cell apoptosis by activating calpain-mediated cleavage of BAX. These findings provide a novel insight into JEV-caused encephalitis and suggest that calpain inhibition may represent a potential therapeutic strategy.
Acidisoma sibiricum DSM 21000T, the type strain of an obligately aerobic, acidophilic, and psychrotolerant bacterium, was isolated from a Sphagnum-dominated peat bog in the Bakchar region of western Siberia, Russia. Here we report the complete genome sequence data of this type strain. Genomic DNA was sequenced using both Illumina NovaSeq X (paired-end, 2×150 bp) and PacBio Revio platforms. Hybrid assembly yielded a complete genome consisting of one chromosome (3,925,831 bp) and two plasmids, pAS1 (577,300 bp) and pAS2 (19,537 bp), with a total genome size of 4,522,668 bp and a sequencing coverage of 312×. The genome was found to be 98.97% complete with an estimated contamination of 2.25%. This is the first report of a complete genome sequence for the type strain of A. sibiricum. Digital DNA-DNA hybridisation (dDDH) analysis confirmed that DSM 21000 is genomically distinct from the closest described Acidisoma species tested, with the highest dDDH value of 25.0% with A. cellulosilyticum HW T5.17, well below the 70% species delineation threshold. Genome annotation by NCBI PGAP revealed 4,225 genes, including 4,127 protein-coding sequences. A complete set of polyhydroxyalkanoate (PHA) biosynthesis genes was also identified, consistent with the presence of intracellular poly-β-hydroxybutyrate granules previously reported for this species. Furthermore, a putative aerobic anoxygenic photosynthesis (AAP) gene cluster was identified on the chromosome, comprising genes encoding a type II photosynthetic reaction center, a light-harvesting antenna complex LH1, and a complete bacteriochlorophyll a biosynthesis pathway. All sequence data were deposited in the NCBI GenBank database under BioProject PRJNA1302119.
Inflammatory lung injury from a fever or sepsis can impair pulmonary function. While anti-inflammatory agents are commonly used, side effects could occur. Andrographolide (AGP) exhibits potent anti-inflammatory activity, making it a promising alternative treatment. Nevertheless, AGP has low solubility and absorption, and drug-delivery liposomes (Lip) improve site-specific targeting and controlled release. This study aimed to develop and evaluate the physicochemical properties, safety, and therapeutic efficacy of AGP-Lip through both in vitro and in vivo studies. The characteristics of AGP-Lip included an average size of 139.7 ± 2.00 nm, a polydispersity index of 0.16 ± 0.02, and a zeta potential of 34.5 ± 0.80 mV, with strong mucoadhesive properties. AGP-Lip exhibited no cytotoxicity in IMR-90 lung fibroblast cells while effectively reducing inflammation by decreasing nitric oxide production in RAW 264.7 murine macrophage cells exposed to lipopolysaccharide. In the animal study, adult male C57BL/6 mice received a single intraperitoneal dose of 100 μg/kg of tumor necrosis factor-α (TNF-α)-induced acute pulmonary systemic inflammation. Mice were randomly assigned to six groups (9 mice per group): control, PBS (negative control), Blank-Lip, AGP-Lip, dexamethasone (POS), and AGP-Lip+POS. All treatments (20 to 25 μL with AGP-Lip, AGP-Lip, and/or POS at 1 mg/kg) were administered via nasal delivery daily for 7 days. The vehicle-treated mice exhibited signs of sickness and systemic inflammation, including reduced body weight gain, hyperlocomotion, decreased exploratory activity, elevated total white blood cell counts, serum IL-6 and TNF-α, and upregulation of targeted mRNA expression of lung inflammatory markers. Histological analysis showed an increase in inflammatory scores, and secretory cells were also observed in the vehicle-treated group. AGP-Lip improved body weight and stress-related behaviors, restored mRNA expression levels of IFN-γ, IL-1α/β, IL-6, IL-10, NF-κBp65, and TNF-α, and alleviated mucus secretion in lung histological analysis. Notably, AGP-Lip effectively mitigated the detrimental effects compared to POS alone, showing significant differences in serum IL-6, lung inflammation-related gene expression (i.e., IFN-γ, IL-1α, NF-κBp50, and VEGF), and PAS staining relative to the combined treatment. These findings suggest that AGP-Lip could serve as a potential alternative treatment for acute respiratory infections, warranting further consideration for long-term administration and clinical trials.
This study further investigates the potential of gelatin-based hydrogel cross-linked with vanillin and ferric ion (GVF), combined with andrographolide (AGP) and silver nanoparticles (AgNPs), as an anti-infection biomaterial for wound dressing, aimed at exploring the mechanisms that attenuate inflammation, enhance wound healing rates, and address allergic skin irritation. AGP-AgNPs were evaluated for cytotoxicity in human adult epidermal keratinocytes (HEKa) and the murine macrophage cell line (RAW 264.7), as well as for nitric oxide (NO) production in response to lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells. Skin-wound specimens from male Wistar rats were histologically analyzed for epidermal thickness and inflammatory changes. The mRNA expression profiling of dermal growth factors was assessed using RT-qPCR, and skin irritation tests were conducted in female New Zealand rabbits. These AGP-AgNPs exhibited significantly lower toxicity in HEKa and no toxicity in RAW 264.7. Interestingly, AGP-AgNPs at specific concentrations produced NO in RAW 264.7 control cells but were more effective in reducing inflammatory NO levels in RAW 264.7 cells pretreated with lipopolysaccharides, suggesting that AGP-AgNP composites are safe and effectively diminish inflammation. Furthermore, a marked increase in epidermal thickness and a reduction in histological inflammatory cells at wound sites were observed in rats treated with AGP-AgNPs/GVF hydrogels over 21 days. Upregulation of dermal genes promoting wound healing, including collagen types I and III, epidermal growth factor, transforming growth factor-beta, fibronectin, and vascular endothelial growth factor, but not fibroblast growth factor, was observed in a time-dependent manner. These results suggest that the anti-inflammatory properties of GVF/AGP-AgNP hydrogels could promote epithelialization, enhance cellular proliferation, support extracellular matrix synthesis, and facilitate angiogenesis. Additionally, rabbit skin in contact with GVF/AGP-AgNP hydrogels consistently displayed reduced levels of erythema and edema, with no swelling, and a standardized scoring system yielded low primary dermal irritation indices for this hydrogel. These findings suggest that the novel GVF/AGP-AgNP hydrogels possess anti-inflammatory-like activity and can modulate dermal growth factors for wound healing. This leads to reduced dermal irritation, making the formulation potentially suitable for safe topical applications in skin and wound care. However, comprehensive human studies and clinical trials should be required in the future.
Multidrug-resistant Acinetobacter baumannii ABU3 was isolated from a tracheal suction specimen from a 76-year-old female patient in Thailand. The draft genome was sequenced using Illumina NextSeq 550. The genome comprised 95 contigs totaling 3826,273 base pairs with an N50 of 112,717 bp and GC content of 38.89. Digital DNA-DNA hybridisation with A. baumannii ATCC 19606T revealed 80.3 % similarity. MLST assigned the isolate to ST-164, whereas MLST of the core genome showed 99.0 % similarity to cgST-4302. Resistance gene analysis identified blaOXA-23, blaCARB variants, blaADC-25, and tet(39). Antimicrobial susceptibility testing showed resistance to carbapenems, fluoroquinolones, beta-lactam combinations, extended-spectrum cephalosporins, and penicillins, with sensitivity to aminoglycosides and folate pathway inhibitors. Two intact prophage regions (23.5 and 26.3 kb) were identified containing structural and functional components. Data are available at NCBI under BioProject PRJNA550309.
Chronic stress induces mood disturbances, disrupts gut barrier function, and promotes low-grade systemic inflammation. This study assessed the therapeutic effects of atomoxetine (ATX), escitalopram (ESC), cannabidiol (CBD), and CBD-loaded lipid nanoparticles (CBD/LNP) in male rats exposed to repeated restraint stress. Stressed rats exhibited a 2.03-fold increase in interleukin-6 and a 1.89-fold increase in TNF-α, a 1.20-fold decrease in brain-derived neurotrophic factor, a 1.36-fold decrease in osteocalcin, accompanied by alterations in gut metabolites, particularly short-chain fatty acids (SCFAs; from 155.3 to 94.83 μmol/L), polyamines (from 273.6 to 192.4 μmol/L), and bile acids (BAs; from 21.19 to 14.53 μmol/L), compared with the control group. Protein analysis revealed gut barrier disruption and microglial/macrophage activation, accompanied by reduced synaptic plasticity. ATX improved gut permeability and reduced glial activation but did not restore osteocalcin. ESC provided neuroimmune benefits with limited and BA gut restoration and modulated the gut–brain axis and improved anxiety-like behaviors, partly by altering gut microbiota and metabolites. CBD and CBD/LNP treatment restored intestinal barrier function, as indicated by intestinal permeability in the range of 1.15–1.61-fold. These treatments also normalized bile acids (1.0–1.38-fold) and osteocalcin (1.0–1.28-fold) and significantly reduced glial activation (0.63–1.12-fold) as opposed to the non-treated stressed group. All treatments were found to be effective in correcting SCFA and polyamine levels. Histological analysis confirmed that CBD/LNP, ATX, and ESC ameliorated tissue alterations. These findings highlight CBD/LNP as a promising intervention for stress-induced gut–brain–bone axis disruption, supporting its potential as a therapeutic alternative through modulation of microbiota-driven gut–brain communication in stress-associated disorders.
Bacillus subtilis AMFE023/7, a Gram-positive bacterium with aciditolerans and halotolerant properties, was isolated from Pla Ra, a traditional fermented fish product popular in Thai cuisine. The sample was obtained from a local morning market in Amnat Charoen, Thailand. The complete genome was assembled through the integration of complementary sequencing platforms, specifically Illumina and PacBio. The genome spans 4132,147 base pairs with a GC content of 43.87 %. Comparison with the reference strain B. subtilis ATCC 6051T using digital DNA-DNA hybridisation confirmed the identity of the isolate with 89.3 % similarity. The genome analysis revealed gene clusters responsible for producing potentially useful compounds such as kanosamine and bacilysin, which have antimicrobial properties. This genome sequence provides valuable data for researchers studying microbial communities in fermented foods, those conducting comparative genomics, and scientists searching for new bioactive compounds. The complete genome sequence data has been made publicly available through NCBI under BioProject accession number PRJNA1253417.
Vision is a highly rhythmic function adapted to daily changes in light intensity. Rhythms disruption is known to compromise retinal health and visual function. This study investigates expression patterns of cone proteins over the 24-h daily cycle in order to understand the molecular bases of cone cyclic physiology. Cones were isolated by vibratome-sectioning from Nrl knockout mice at four time points across the 24-h LD (Light-Dark) cycle and protein extracts were quantified by label-free LC-MS/MS. The resulting protein data was then submitted to MetaCycle analysis to identify proteins with rhythmic expression patterns and associated functions. Cyclic profiles were further validated by SWATH-MS analysis. A total of 1208 proteins were identified. Rhythmic expression patterns were found for 319 proteins, categorized into four clusters based on intensity variation. SWATH-MS analysis validated the approach. Functional enrichment analysis revealed proteins critical for photoreceptor function, including those involved in phototransduction, oxidative phosphorylation, RNA processing, proteostasis, transport, synaptic function and cilia biogenesis. These findings provide a unique dataset of rhythmic cone proteins, potentially crucial for elucidating cone cell physiology and visual function. This knowledge can empower future research on preventing and treating vision impairment.
This study aimed to improve the delivery efficacy of andrographolide (Andro) by encapsulating it in nanostructured lipid carriers (NLCs) and to evaluate its effectiveness in reducing systemic inflammation. These AndroNLCs exhibited homogeneity with a particle size of 131.40 ± 1.30 nm and approximately 89% encapsulation efficiency. AndroNLCs potentially enhanced oral efficacy by improving gastrointestinal stability, with reduced toxicity and inflammation in SH-SY5Y neuroblastoma cells. Inflammation was induced in sexually active C57BL/6 male mice with five intraperitoneal doses of 63 µg/kg TNF-alpha every three days. This was accompanied by daily oral administration of 10 mg/kg AndroNLCs, venlafaxine, or 1 mg/kg dexamethasone for 14 days. Mice with TNF-alpha-induced inflammation showed sickness signs and abnormal behaviors, assessed via physical changes, anxiety and depression tests (i.e., open field, elevated-T maze, tail suspension, and forced swimming), and biochemical assays. These changes included weight loss and compensatory responses to inflammation, as indicated by increased immune- and stress-modulated organ weights, elevated serum corticosterone levels, altered liver function markers, and higher levels of hippocampal IL-6 and TNF-alpha. Furthermore, histological analysis showed pyknotic cells, reduced layer thickness, and decreased hippocampal cell survival. Conversely, AndroNLCs significantly improved stress- and inflammation-related markers, alleviated behavioral abnormalities, reduced liver toxicity, and restored hippocampal morphology, showing effects greater than Andro alone and comparable to traditional treatments. These findings suggest that AndroNLCs have therapeutic effects on neuroinflammation but may risk contributing to mood disorders.
The Streptomyces genus is a remarkable source of bioactive compounds in the pharmaceutical repertoire of nature. Here, we present the first complete genome sequence of Streptomyces boninensis TBRC 7755 assembled using a hybrid sequencing approach combining Illumina and PacBio technologies. The genome comprises a high-quality 9.6-Mb linear chromosome, exhibiting exceptionally high completeness and minimal contamination. Phylogenomic analysis and genomic relatedness metrics of S. coryli A7024 provide reliable reference data for comparative genomic studies. The genome architecture revealed 8543 protein-coding genes complemented by a diverse RNA repertoire comprising 15 rRNAs, 60 tRNAs, and 3 ncRNAs. Genome mining identified biosynthetic gene clusters encoding potentially bioactive compounds, including the iron-chelating siderophore desferrioxamine, antineoplastic peptide chaxapeptin, and antimicrobial griseobactin. These computational predictions require experimental validation to confirm bioactivity. This genomic blueprint serves two purposes: (1) providing reference data for bacterial taxonomy and (2) illuminating pathways for the discovery of potential bioactive compounds.
Haloferax volcanii is an extreme halophile belonging to the Haloferacaceae family that thrives in hypersaline environments. This study presents the complete genome sequence of the H. volcanii strain PC0224 isolated from a Thai solar saltern. Genomic data will enhance our understanding of circadian rhythm mechanisms and their evolutionary significance in extremophilic archaea. The H. volcanii PC0224 genome comprises four circular sequences containing 3,773,977 bp and 66.16
This study presents the development and evaluation of Centella Asiatica (CA)-loaded transfersomes (CANP) as a novel nanocarrier for transdermal delivery. CANP were prepared using an oil-in-water emulsion method, producing nanoparticles with a size of 135.22 ± 4.80 nm, a polydispersity index of 0.22 ± 0.01, and a zeta potential of -26.13 ± 0.58 mV. Stability tests confirmed consistent physicochemical properties under various storage conditions, with encapsulation efficiencies above 68% for madecassoside and 89% for asiaticoside. Ex vivo permeation studies using porcine skin showed significantly improved skin penetration compared to liposomes and niosomes, attributed to the high deformability index (1.31 ± 0.21 mg/cm2). In vitro cytotoxicity assays indicated cell viability above 80% across concentrations. Functionally, CANP reduced nitric oxide production in LPS-stimulated RAW 264.7 cells, demonstrating superior anti-inflammatory effects over native CA. CANP also promoted fibroblast proliferation and collagen production by 91.9% and 213.3% at days 7 and 14, respectively, exceeding vitamin C. Wound healing assays confirmed enhanced fibroblast migration and closure rates similar to fibroblast growth factor. In vivo, CANP hydrogels accelerated healing, with early fibroblast activity and collagen deposition between days 7-14, supporting epithelial regeneration over 21 days. Compared to controls, they more effectively reduced inflammation and increased dermal growth factor expression. These findings support CANP as a promising transdermal nanocarrier with enhanced skin penetration, anti-inflammatory activity, and regenerative potential. Encapsulating CA into transfersomes boosts its therapeutic efficacy, making it a strong candidate for advanced dermal applications.
Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.
Diabetic Parkinson’s disease (DP) is a progressive neurodegenerative disease with metabolic syndrome that is increasing worldwide. Emerging research suggests that cannabidiol (CBD) is a neuropharmacological compound that acts against this disease, especially CBD in nano-formulation. The safety of cannabidiol lipid nanoparticles (CBD-LNP) was evaluated by assessing in vitro cytotoxicity in neurons and therapeutic outcomes in a DP animal model, including metabolic parameters and histopathology. CBD-LNPs were fabricated by using a microfluidization technique and showed significantly lower cytotoxicity than the natural form of CBD. The DP rats were induced by streptozotocin followed by a 4-week injection of MPTP with a high-fat diet. Rats were treated orally with a vehicle, CBD, CBD-LNP, or levodopa for 4 weeks daily. As a result, vehicle-treated rats exhibited metabolic abnormalities, decreased striatal dopamine levels, and motor and memory deficits. CBD-LNP demonstrated reduced lipid profiles, enhanced insulin secretion, and restored dopamine levels compared to CBD in the natural form. CBD-LNP also had comparable efficacy to levodopa in ameliorating motor deficits and memory impairment in behavior tests. Interestingly, CBD-LNP presented migration of damaged neuronal cells in the hippocampus more than levodopa. These findings suggest that CBD-LNP holds promise as an intervention addressing both metabolic and neurodegenerative aspects of DP, offering a potential therapeutic strategy.
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes high mortality rates in humans and it is the most clinically important and common cause of viral encephalitis in Asia. To date, there is no specific treatment for JEV infection. Melatonin, a neurotropic hormone, is reported to be effective in combating various bacterial and viral infections. However, the effects of melatonin on JEV infection have not yet been studied. The investigation tested the antiviral effects of melatonin against JEV infection and elucidated the possible molecular mechanisms of inhibition. Melatonin inhibited the viral production in JEV-infected SH-SY5Y cells in a time- and dose-dependent manner. Time-of-addition assays demonstrated a potent inhibitory effect of melatonin at the post-entry stage of viral replication. Molecular docking analysis revealed that melatonin negatively affected viral replication by interfering with physiological function and/or enzymatic activity of both JEV nonstructural 3 (NS3) and NS5 protein, suggesting a possible underlying mechanism of JEV replication inhibition. Moreover, treatment with melatonin reduced neuronal apoptosis and inhibited neuroinflammation induced by JEV infection. The present findings reveal a new property of melatonin as a potential molecule for the further development of anti-JEV agents and treatment of JEV infection.
Oral calcium and calcium plus vitamin D supplements are commonly prescribed to several groups of patients, e.g., osteoporosis, fracture, and calcium deficiency. Adequate and steady extracellular calcium levels are essential for neuronal activity, whereas certain forms of calcium supplement (e.g., CaCO3) probably interfere with memory function. However, it was unclear whether a long-term use of ionized calcium (calcium chloride in drinking water ad libitum), vitamin D supplement (oral gavage) or the combination of both affected anxiety and memory, the latter of which was probably dependent on the hippocampal neurogenesis. Here, we aimed to determine the effects of calcium and/or vitamin D supplement on the anxiety- and memory-related behaviors and the expression of doublecortin (DCX), an indirect proxy indicator of hippocampal neurogenesis. Eight-week-old male Wistar rats were divided into 4 groups, i.e., control, calcium chloride-, 400 UI/kg vitamin D3-, and calcium chloride plus vitamin D-treated groups. After 4 weeks of treatment, anxiety-, exploration- and recognition memory-related behaviors were evaluated by elevated pulse-maze (EPM), open field test (OFT), and novel object recognition (NOR), respectively. The hippocampi were investigated for the expression of DCX protein by Western blot analysis. We found that oral calcium supplement increased exploratory behavior as evaluated by OFT and the recognition index in NOR test without any effect on anxiety behavior in EPM. On the other hand, vitamin D supplement was found to reduce anxiety-like behaviors. Significant upregulation of DCX protein expression was observed in the hippocampus of both calcium- and vitamin D-treated rats, suggesting their positive effects on neurogenesis. In conclusion, oral calcium and vitamin D supplements positively affected exploratory, anxiety-like behaviors and/or memory in male rats. Thus, they potentially benefit on mood and memory in osteoporotic patients beyond bone metabolism.
Introduction: Stress disturbs the gut-brain axis and contributes to the development of mood disorders and memory impairment. Recent findings on the anti-stress effects of monoamine modulators have shown that the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine (Vlx) is more effective in stressed rodents. However, the effects of Vlx on microbiota and memory impairment-and stress-related behaviors are still unknown. Synbiotics (Syn), a mixture of probiotics and prebiotics, can modify the gut microbiome; however, the effects of anti-anxiety and anti-memory deficits are still not well understood. Therefore, this study proposed to compare the effectiveness of Vlx and Syn in the reduction of learned fear and memory impairment-like behaviors in an animal model of stress. Methods: Forty male adult Wistar rats were subjected to stress by immobilization in a restrainer for 2h per day and were administered 10mg/kg Vlx and/or 2g of Syn containing 1.0x1010 CFU probiotic strains and prebiotic oligosaccharides daily for 14 days. Learned fear, recognition memory and locomotor activity were evaluated by the elevated-T maze, novel objective recognition and open field tests. Blood samples and adrenal glands were collected to measure the circulating corticosterone levels and relative adrenal weights, which were used as markers of stress responses.Results: The immobilized-stressed rats showed hyperactivity in stress responses, as demonstrated by increased relative adrenal weights and serum corticosterone levels. Both Vlx and Syn reduced the increase in serum corticosterone levels in stressed rats. Furthermore, Vlx-and/or Syn-treated stressed rats had fewer learned fear-like behaviors and a higher discrimination index without any locomotor activity changes than vehicle-treated stressed rats.Conclusion: Syn supplementation had comparable effects to SNRIs in alleviating the risk of developing anxiety disorders and memory impairment in stressed individuals or psychiatric patients.
Morganella morganii WA01/MUTU is a heavy metal tolerant strain capable of producing silver nanoparticles (AgNPs) from AgNO3. Here we present the draft genome sequence of M. morganii WA01/MUTU isolated from a water sample collected in Nakhon Pathom province, Thailand. The draft genome was sequenced on the Illumina NextSeq 550 sequencer. The genome consisted of 34 contigs with a total size of 3,991,804 bp, an N50 value of 364,423 bp and a GC content of 50.93%. The digital DNA-DNA hybridisation (dDDH) between WA01/MUTU and Morganella morganii (NBRC 3848) was 83.9%, identifying the strain as Morganella morganii. The data presented here can be used in comparative genomics to identify gene clusters involved in AgNP biosynthesis and secondary metabolite production. The draft genome sequence data was deposited at NCBI under Bioproject accession number PRJNA493966.
Viral infections of the central nervous system (CNS) cause variable outcomes from acute to severe neurological sequelae with increased morbidity and mortality. Viral neuroinvasion directly or indirectly induces encephalitis via dysregulation of the immune response and contributes to the alteration of neuronal function and the degeneration of neuronal cells. This review provides an overview of the cellular and molecular mechanisms of virus-induced neurodegeneration. Neurotropic viral infections influence many aspects of neuronal dysfunction, including promoting chronic inflammation, inducing cellular oxidative stress, impairing mitophagy, encountering mitochondrial dynamics, enhancing metabolic rewiring, altering neurotransmitter systems, and inducing misfolded and aggregated pathological proteins associated with neurodegenerative diseases. These pathogenetic mechanisms create a multidimensional injury of the brain that leads to specific neuronal and brain dysfunction. The understanding of the molecular mechanisms underlying the neurophathogenesis associated with neurodegeneration of viral infection may emphasize the strategies for prevention, protection, and treatment of virus infection of the CNS.