2-Butoxytetrahydrofuran, Isolated from Holothuria scabra, Attenuates Aggregative and Oxidative Properties of α-Synuclein and Alleviates Its Toxicity in a Transgenic Caenorhabditis elegans Model of Parkinson's Disease.

Aggregative α-synuclein and incurring oxidative stress are pivotal cascading events, leading to dopaminergic (DAergic) neuronal loss and contributing to clinical manifestations of Parkinson's disease (PD). Our previous study demonstrated that 2-butoxytetrahydrofuran (2-BTHF), isolated from Holothuria scabra (H. scabra), could inhibit amyloid-ß aggregation and its ensuing toxicity, which leads to Alzheimer's disease. In the present study, we found that 2-BTHF also attenuated the aggregative and oxidative activities of α-synuclein and lessened its toxicity in a transgenic Caenorhabditis elegans (C. elegans) PD model. Such worms treated with 100 µM of 2-BTHF showed substantial reductions in α-synuclein accumulation and DAergic neurodegeneration. Mechanistically, 2-BTHF, at this concentration, significantly decreased aggregation of monomeric α-synuclein and restored locomotion and dopamine-dependent behaviors. Molecular docking exhibited potential bindings of 2-BTHF to HSF-1 and DAF-16 transcription factors. Additionally, 2-BTHF significantly increased the mRNA transcripts of genes encoding proteins involved in proteostasis, including the molecular chaperones hsp-16.2 and hsp-16.49, the ubiquitination/SUMOylation-related ubc-9 gene, and the autophagy-related genes atg-7 and lgg-1. Transcriptomic profiling revealed an additional mechanism of 2-BTHF in α-synuclein-expressing worms, which showed upregulation of PPAR signaling cascades that mediated fatty acid metabolism. 2-BTHF significantly restored lipid deposition, upregulated the fat-7 gene, and enhanced gcs-1-mediated glutathione synthesis in the C. elegans PD model. Taken together, this study demonstrated that 2-BTHF could abrogate aggregative and oxidative properties of α-synuclein and attenuate its toxicity, thus providing a possible therapeutic application for the treatment of α-synuclein-induced PD.

Extracts of tropical green seaweed Caulerpa lentillifera reduce hepatic lipid accumulation by modulating lipid metabolism molecules in HepG2 cells.

Seaweed has attracted attention as a bioactive source for preventing different chronic diseases, including liver injury and non-alcoholic fatty liver disease, the leading cause of liver-related mortality. Caulerpa lentillifera is characterized as tropical edible seaweed, currently being investigated for health benefits of its extracts and bioactive substances. This study examined the effects of C. lentillifera extract in ethyl acetate fraction (CLEA) on controlling lipid accumulation and lipid metabolism in HepG2 cells induced with oleic acid through the in vitro hepatic steatosis model. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that CLEA contained diverse organic compounds, including hydrocarbons, amino acids, and carboxylic acids. Docked conformation of dl-2-phenyltryptophane and benzoic acid, two major bioactive CLEA components, showed high affinity binding to SIRT1 and AMPK as target molecules of lipid metabolism. CLEA reduced lipid accumulation and intracellular triglyceride levels in HepG2 cells stimulated with oleic acid. The effect of CLEA on regulating expression of lipid metabolism-related molecules was investigated by qPCR and immunoblotting. CLEA promoted expression of the SIRT1 gene in oleic acid-treated HepG2 cells. CLEA also reduced expression levels of SREBF1, FAS, and ACC genes, which might be related to activation of AMPK signaling in lipid-accumulated HepG2 cells. These findings suggest that CLEA contains bioactive compounds potentially reducing triglyceride accumulation in lipid-accumulated HepG2 hepatocytes by controlling lipid metabolism molecules.

Biosynthesis of Cry5B-Loaded Sulfur Nanoparticles using Arthrobotrys oligospora Filtrate: Effects on Nematicidal Activity, Thermal Stability, and Pathogenicity against Caenorhabditis elegans.

Cry5B, a crystal protein produced by Bacillus thuringiensis (Bt), is a bionematicide with potent nematicidal activity against various plant-parasitic and free-living nematodes. This protein, however, is susceptible to destruction by ultraviolet light, proteolytic enzymes, and high temperatures. This study aims to produce Cry5B protein for bionematicidal use and improve its stability and nematicidal efficacy by loading it intoArthrobotrys oligospora-mediated sulfur nanoparticles (AO-SNPs). Based on the mortality assay, the Cry5B protein exhibited dose-dependent nematicidal activity against the model organismCaenorhabditis elegans. The nematicidal activity, thermal stability, and pathogenic effects of Cry5B-loaded AO-SNPs (Cry5B-SNPs) were compared to those of free Cry5B. After 3 h of exposure to heat at 60 °C, Cry5B-SNPs had greater nematicidal activity than free Cry5B protein, indicating the effective formulation of Cry5B-SNPs that could be used as an alternative to current nematicide delivery strategies.

Anti-Obesity Effects of Marine Macroalgae Extract Caulerpa lentillifera in a Caenorhabditis elegans Model.

Obesity is a multifactorial disease characterized by an excessive accumulation of fat, which in turn poses a significant risk to health. Bioactive compounds obtained from macroalgae have demonstrated their efficacy in combating obesity in various animal models. The green macroalgae Caulerpa lentillifera (CL) contains numerous active constituents. Hence, in the present study, we aimed to elucidate the beneficial anti-obesity effects of extracts derived from C. lentillifera using a Caenorhabditis elegans obesity model. The ethanol (CLET) and ethyl acetate (CLEA) extracts caused a significant decrease in fat consumption, reaching up to approximately 50-60%. Triglyceride levels in 50 mM glucose-fed worms were significantly reduced by approximately 200%. The GFP-labeled dhs-3, a marker for lipid droplets, exhibited a significant reduction in its level to approximately 30%. Furthermore, the level of intracellular ROS displayed a significant decrease of 18.26 to 23.91% in high-glucose-fed worms treated with CL extracts, while their lifespan remained unchanged. Additionally, the mRNA expression of genes associated with lipogenesis, such as sbp-1, showed a significant down-regulation following treatment with CL extracts. This finding was supported by a significant decrease (at 16.22-18.29%) in GFP-labeled sbp-1 gene expression. These results suggest that C. lentillifera extracts may facilitate a reduction in total fat accumulation induced by glucose through sbp-1 pathways. In summary, this study highlights the anti-obesity potential of compounds derived from C. lentillifera extracts in a C. elegans model of obesity, mediated by the suppression of lipogenesis pathways.

Ethanolic extract of Halymenia durvillei induced G2/M arrest and altered the levels of cell cycle regulatory proteins of MDA-MB-231 triple-negative breast cancer cells.

Background and purpose: The GC-MS analysis reported n-hexadecanoic acid or palmitic acid as a major component of the ethanolic extract of Halymenia durvillei (HDET). This compound shows cytotoxic effects against various human cancer cells. The present study investigated the effect of HDET on the viability and proliferation of MDA-MB-231, a triple-negative breast cancer (TNBC) cell line. Experimental approach: Cell proliferation and cell cycle analysis were determined by flow cytometry and cell cycle regulatory protein expression levels were then determined by Western blotting. The presence of reactive oxygen species (ROS) was evaluated by dichlorofluorescein, followed by analyzing changes in gene expression of antioxidant enzymes using a real-time polymerase chain reaction. Findings/Results: HDET dose-dependently reduced cell viability with the 50% inhibitory concentration (IC50) of 269.4 ± 31.2 µg/mL at 24 h. The cell proliferation assays showed increased succinimidyl ester fluorescent intensity after treatment with ≥ 100 µg/mL of HDET, indicating the inhibition of cell proliferation. Cell cycle analysis using propidium iodide staining showed an increased percentage of cells in the G2/M phase. HDET also decreased the levels of cell cycle regulatory proteins including cyclin D1 and increased the level of p21. HDET promoted oxidative stress by increasing ROS levels along with the reduction of catalase expression. However, HDET did not induce apoptosis and caspase activation in TNBC cells. Conclusion and implications: These findings suggest that HDET which is rich in palmitic acid may serve as a potential therapeutic agent to target TNBC via arrest cell cycle progression at the G2/M phase.

Combination Vaccines of Fasciola gigantica Saposin-like Protein-2 and Leucine Aminopeptidase.

Saposin-like protein-2 (SAP-2) and leucine aminopeptidase (LAP) are major proteins involved in the digestive process of Fasciola gigantica (Fg). Both SAP-2 and LAP are highly expressed in F. gigantica; therefore, they could be vaccine candidates for fasciolosis. The aims of this study are (1) to observe the tissue expression of F. gigantica SAP-2 (FgSAP-2) and F. gigantica LAP (FgLAP) in F. gigantica by indirect immunofluorescence technique under confocal microscopy and (2) to test the vaccine potentials of individual and combined recombinant (r) FgSAP-2 and rFgLAP against F. gigantica in Imprinting Control Region (ICR) mice (n = 10 per group). By indirect immunofluorescence-confocal microscopy, FgSAP-2 and FgLAP were localized in the caecal epithelium but at different sites: FgSAP-2 appeared in small granules that are distributed in the middle and lower parts of the cytoplasm of epithelial cells, while FgLAP appeared as a line or zone in the apical cytoplasm of caecal epithelial cells. For vaccine testing, the percent protection of combined rFgSAP-2 and rFgLAP vaccines against F. gigantica was at 80.7 to 81.4% when compared with aluminum hydroxide (alum) adjuvant and unimmunized controls, respectively. The levels of IgG1 and IgG2a in the sera were significantly increased in single and combine vaccinated groups compared with the control groups. Vaccinated mice showed reduced liver damage when compared with control groups. This study indicates that the combined rFgSAP-2 and rFgLAP vaccine had a higher vaccine potential than a single vaccine. These results support the further testing and application of this combined vaccine against F. gigantica infection in farmed livestock animals.

Ethyl Acetate Extract of Halymenia durvillei Induced Apoptosis, Autophagy, and Cell Cycle Arrest in Colorectal Cancer Cells.

Colorectal cancer is one of the most death-dealing cancers. However, conventional cancer treatments still have side effects. Therefore, novel chemotherapeutic agents with less side effects are still in search. A marine red seaweed, Halymenia durvillei, is recently interested in its anticancer effects. This study investigated the anticancer effect of ethyl acetate extract of H. durvillei (HDEA) on HT-29 colorectal cancer cells in association with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. HDEA-treated HT-29 and OUMS-36 cells were used for cell viability tests by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay. The effects of HDEA on apoptosis and cell cycle were evaluated. The nuclear morphology and mitochondrial membrane potential (ΔΨm) were observed by Hoechst 33342 and JC-1 staining, respectively. The gene expression of PI3K, AKT, and mTOR genes was evaluated using a real-time semiquantitative reverse transcription-polymerase chain reaction. The corresponding protein expressions were assessed by western blot analysis. The result revealed that the cell viability of treated HT-29 cells diminished while that of OUMS-36 cells was non-significant. By the down-regulation of cyclin-dependent ki-nase 4 and cyclin D1, HDEA-treated HT-29 cells were arrested in the G0/G1 phase. By the up-regulation of cleaved poly(adenosine diphosphate-ribose) polymerase, caspase-9, caspase-8, caspase-3, and Bax, HDEA-treated HT-29 cells underwent apoptosis, but suppressed Bcl-2, disrupted nuclear morphology and ΔΨm. Furthermore, treated HT-29 cells underwent autophagy by up-regulation of light chain 3-II and beclin-1. Lastly, HDEA suppressed the expression of PI3K, AKT, and mTOR. Therefore, HDEA exerts anticancer effects against HT-29 cells, confirmed by apoptosis, autophagy, and cell cycle arrest induction via regulation of the PI3K/AKT/mTOR signaling pathway.

Anti-Parkinson Effects of Holothuria leucospilota-Derived Palmitic Acid in Caenorhabditis elegans Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease which is still incurable. Sea cucumber-derived compounds have been reported to be promising candidate drugs for treating age-related neurological disorders. The present study evaluated the beneficial effects of the Holothuria leucospilota (H. leucospilota)-derived compound 3 isolated from ethyl acetate fraction (HLEA-P3) using Caenorhabditis elegans PD models. HLEA-P3 (1 to 50 µg/mL) restored the viability of dopaminergic neurons. Surprisingly, 5 and 25 µg/mL HLEA-P3 improved dopamine-dependent behaviors, reduced oxidative stress and prolonged lifespan of PD worms induced by neurotoxin 6-hydroxydopamine (6-OHDA). Additionally, HLEA-P3 (5 to 50 µg/mL) decreased α-synuclein aggregation. Particularly, 5 and 25 µg/mL HLEA-P3 improved locomotion, reduced lipid accumulation and extended lifespan of transgenic C. elegans strain NL5901. Gene expression analysis revealed that treatment with 5 and 25 µg/mL HLEA-P3 could upregulate the genes encoding antioxidant enzymes (gst-4, gst-10 and gcs-1) and autophagic mediators (bec-1 and atg-7) and downregulate the fatty acid desaturase gene (fat-5). These findings explained the molecular mechanism of HLEA-P3-mediated protection against PD-like pathologies. The chemical characterization elucidated that HLEA-P3 is palmitic acid. Taken together, these findings revealed the anti-Parkinson effects of H. leucospilota-derived palmitic acid in 6-OHDA induced- and α-synuclein-based models of PD which might be useful in nutritional therapy for treating PD.

Holothuria scabra extracts confer neuroprotective effect in C. elegans model of Alzheimer's disease by attenuating amyloid-ß aggregation and toxicity.

Background and aim: Alzheimer's disease (AD) is the most common aged-related neurodegenerative disorder that is associated with the toxic amyloid-ß (Aß) aggregation in the brain. While the efficacies of available drugs against AD are still limited, natural products have been shown to possess neuroprotective potential for prevention and therapy of AD. This study aimed to investigate the neuroprotective effects of H. scabra extracts against Aß aggregation and proteotoxicity in C. elegans model of Alzheimer's diseases. Experimental procedure: Whole bodies (WB) and body wall (BW) of H. scabra were extracted and fractionated into ethyl acetate (WBEA, BWEA), butanol (WBBU, BWBU), and ethanol (BWET). Then C. elegans AD models were treated with these fractions and investigated for Aß aggregation and polymerization, biochemical and behavioral changes, and level of oxidative stress, as well as lifespan extension. Results and conclusion: C. elegans AD model treated with H. scabra extracts, especially triterpene glycoside-rich ethyl acetate and butanol fractions, exhibited significant reduction of Aß deposition. These H. scabra extracts also attenuated the paralysis behavior and improved the neurological defects in chemotaxis caused by Aß aggregation. Immunoblot analysis revealed decreased level of Aß oligomeric forms and the increased level of Aß monomers after treatments with H. scabra extracts. In addition, H. scabra extracts reduced reactive oxygen species and increased the mean lifespan of the treated AD worms. In conclusion, this study demonstrated strong evidence of anti-Alzheimer effects by H. scabra extracts, implying that these extracts can potentially be applied as natural preventive and therapeutic agents for AD. Taxonomy classification by EVISE: Alzheimer's disease, Neurodegenerative disorder, Traditional medicine, Experimental model systems, Molecular biology.

Cross-Sectional Area of the Tibial Nerve in Diabetic Peripheral Neuropathy Patients: A Systematic Review and Meta-Analysis of Ultrasonography Studies.

Background: There is a link between diabetic peripheral neuropathy (DPN) progression and the increase in the cross-sectional area (CSA) of the tibial nerve at the ankle. Nevertheless, no prior meta-analysis has been conducted to evaluate its usefulness for the diagnosis of DPN. Methods: We searched Google Scholar, Scopus, and PubMed for potential studies. Studies had to report tibial nerve CSA at the ankle and diabetes status (DM, DPN, or healthy) to be included. A random-effect meta-analysis was applied to calculate pooled tibial nerve CSA and mean differences across the groups. Subgroup and correlational analyses were conducted to study the potential covariates. Results: The analysis of 3295 subjects revealed that tibial nerve CSA was 13.39 mm2 (CI: 10.94−15.85) in DM patients and 15.12 mm2 (CI: 11.76−18.48) in DPN patients. The CSA was 1.93 mm2 (CI: 0.92−2.95, I2 = 98.69%, p < 0.01) larger than DPN-free diabetic patients. The diagnostic criteria of DPN and age were also identified as potential moderators of tibial nerve CSA. Conclusions: Although tibial nerve CSA at the ankle was significantly larger in the DPN patients, its clinical usefulness is limited by the overlap between groups and the inconsistency in the criteria used to diagnose DPN.

Neuroprotective effects of a medium chain fatty acid, decanoic acid, isolated from H. leucospilota against Parkinsonism in C. elegans PD model.

Sea cucumbers are marine organism that have long been used for food and traditional medicine in Asian countries. Recently, we have shown that ethyl acetate fraction (HLEA) of the crude extract of the black sea cucumber, Holothuria leucospilota, could alleviate Parkinsonism in Caenorhabditis elegans PD models. In this study, we found that the effective neuroprotective activity is attributed to HLEA-P1 compound chemically isolated and identified in H. leucospilota ethyl acetate. We reported here that HLEA-P1 could attenuate DAergic neurodegeneration, improve DAergic-dependent behaviors, reduce oxidative stress in 6-OHDA-induced C. elegans. In addition, HLEA-P1 reduced α-synuclein aggregation, improved behavior deficit and recovered lipid deposition in transgenic C. elegans overexpressing α-synuclein. We also found that HLEA-P1 activates nuclear localization of DAF-16 transcription factor of insulin/IGF-1 signaling (IIS) pathway. Treatment with 25 µg/ml of HLEA-P1 upregulated transcriptional activity of DAF-16 target genes including anti-oxidant genes (such as sod-3) and small heat shock proteins (such as hsp16.1, hsp16.2, and hsp12.6) in 6-OHDA-induced worms. In α-synuclein-overexpressed C. elegans strain, treatment with 5 µg/ml of HLEA-P1 significantly activated mRNA expression of sod-3 and hsp16.2. Chemical analysis demonstrated that HLEA-P1 compound is decanoic acid/capric acid. Taken together, our findings revealed that decanoic acid isolated from H. leucospilota exerts anti-Parkinson effect in C. elegans PD models by partly modulating IIS/DAF-16 pathway.

2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways.

Extracts from a sea cucumber, Holothuria scabra, have been shown to exhibit various pharmacological properties including anti-oxidation, anti-aging, anti-cancer, and anti-neurodegeneration. Furthermore, certain purified compounds from H. scabra displayed neuroprotective effects against Parkinson's and Alzheimer's diseases. Therefore, in the present study, we further examined the anti-aging activity of purified H. scabra compounds in a Caenorhabditis elegans model. Five compounds were isolated from ethyl acetate and butanol fractions of the body wall of H. scabra and characterized as diterpene glycosides (holothuria A and B), palmitic acid, bis (2-ethylhexyl) phthalate (DEHP), and 2-butoxytetrahydrofuran (2-BTHF). Longevity assays revealed that 2-BTHF and palmitic acid could significantly extend lifespan of wild type C. elegans. Moreover, 2-BTHF and palmitic acid were able to enhance resistance to paraquat-induced oxidative stress and thermal stress. By testing the compounds' effects on longevity pathways, it was shown that 2-BTHF and palmitic acid could not extend lifespans of daf-16, age-1, sir-2.1, jnk-1, and skn-1 mutant worms, indicating that these compounds exerted their actions through these genes in extending the lifespan of C. elegans. These compounds induced DAF-16::GFP nuclear translocation and upregulated the expressions of daf-16, hsp-16.2, sod-3 mRNA and SOD-3::GFP. Moreover, they also elevated protein and mRNA expressions of GST-4, which is a downstream target of the SKN-1 transcription factor. Taken together, the study demonstrated the anti-aging activities of 2-BTHF and palmitic acid from H. scabra were mediated via DAF-16/FOXO insulin/IGF and SKN-1/NRF2 signaling pathways.

Ethyl Acetate Extract of Marine Algae, Halymenia durvillei, Provides Photoprotection against UV-Exposure in L929 and HaCaT Cells.

Halymenia durvillei is a red alga distributed along the coasts of Southeast Asian countries including Thailand. Previous studies have shown that an ethyl acetate fraction of H. durvillei (HDEA), containing major compounds including n-hexadecanoic acid, 2-butyl-5-hexyloctahydro-1H-indene, 3-(hydroxyacetyl) indole and indole-3-carboxylic acid, possesses high antioxidant and anti-lung cancer activities. The present study demonstrated that HDEA could protect mouse skin fibroblasts (L929) and human immortalized keratinocytes (HaCaT) against photoaging due to ultraviolet A and B (UVA and UVB) by reducing intracellular reactive oxygen species (ROS) and expressions of matrix metalloproteinases (MMP1 and MMP3), as well as increasing Nrf2 nuclear translocation, upregulations of mRNA transcripts of antioxidant enzymes, including superoxide dismutase (SOD), heme oxygenase (HMOX) and glutathione S-transferase pi1 (GSTP1), and procollagen synthesis. The results indicate that HDEA has the potential to protect skin cells from UV irradiation through the activation of the Nrf2 pathway, which leads to decreasing intracellular ROS and MMP production, along with the restoration of skin collagen.

MINERVA: A CubeSat for demonstrating DNA damage mitigation against space radiation in C. elegans by using genetic modification.

The ideas of deep-space human exploration, interplanetary travel, and space civilizations are becoming a reality. However, numerous hindrances remain standing in the way of accomplishing these feats, one of which is space ionizing radiation. Space ionizing radiation has become the most hazardous health risk for long-term human space exploration, as it can induce chromosomal damage and epigenetic changes. The Minerva mission aims to demonstrate cutting-edge technology to inhibit DNA damage against deep-space radiation exposure by using genetic modification. The concept of the experiment is to transform a creature with radiation intolerance into a transgenic organism that is radiation-tolerant. In this mission, Caenorhabditis elegans (C. elegans) will be genetically engineered with a protein-coding gene associated with DNA damage protection called damage suppressor (Dsup). Dsup is a nucleosome-binding protein from the tardigrade Ramazzottius varieornatus that has a unique ability to prevent DNA damage. This paper describes the feasibility of Minerva CubeSat, which will venture out to cis-lunar orbit with a biosensor payload capable of sustaining and culturing C. elegans under space environment conditions for 4 months. The mission will set in motion a paradigm shift corresponding to future space medicines and how they will be developed in the future, introducing a platform suitable for future experiments in the fields of space biology. Ultimately, the paramount objective of Minerva will be to test the limits of genetic engineering and incorporate it into the arduous journey of human perseverance to overcome the boundaries of space exploration-a vital step in making Mars colonization safe.

Anatomical variants identified on chest computed tomography of 1000+ COVID-19 patients from an open-access dataset.

Chest computed tomography (CT) has been the preferred imaging modality during the pandemic owing to its sensitivity in detecting COVID-19 infections. Recently, a large number of COVID-19 imaging datasets have been deposited in public databases, leading to rapid advances in COVID-19 research. However, the application of these datasets beyond COVID-19-related research has been little explored. The authors believe that they could be used in anatomical research to elucidate the link between anatomy and disease and to study disease-related alterations to normal anatomy. Therefore, the present study was designed to investigate the prevalence of six well-known anatomical variants in the thorax using open-access CT images obtained from over 1000 Iranian COVID-19 patients aged between 6 and 89 years (60.9% male and 39.1% female). In brief, we found that the azygos lobe, tracheal bronchus, and cardiac bronchus were present in 0.8%, 0.2%, and 0% of the patients, respectively. Variations of the sternum, including sternal foramen, episternal ossicles, and sternalis muscle, were observed in 9.6%, 2.9%, and 1.5%, respectively. We believe anatomists could benefit from using open-access datasets as raw materials for research because these datasets are freely accessible and are abundant, though further research is needed to evaluate the uses of other datasets from different body regions and imaging modalities. Radiologists should also be aware of these common anatomical variants when examining lung CTs, especially since the use of this imaging modality has increased during the pandemic.

The decreasing prevalence of the thyroid ima artery: A systematic review and machine learning assisted meta-analysis.

INTRODUCTION: Thyroid ima artery is a variant artery found on the anterior surface of the trachea. The aim of this meta-analysis was to obtain pooled prevalence data of the thyroid ima artery and discuss its clinical importance especially for tracheostomy. METHODS: A systematic literature search was performed through five electronic databases until May 2021. A set of inclusion and exclusion criteria based on AQUA guidelines were used to select relevant studies. Meta-analysis, subgroup analyses, meta-regression, and tests for publication bias were performed. Factors that influence the prevalence of the thyroid ima artery were detected using simple and interpretable machine learning (linear regression and K means). RESULTS: Thirty-six studies with a total of 4335 subjects met the inclusion criteria. The prevalence of the thyroid ima artery was 3.8% (95% CI: 0.027-0.049, I2=56.2%). Machine learning identified age, region and year of publication as potential covariates. Subgroup analysis showed that the prevalence of the thyroid ima artery was 4.5 times higher in fetuses (14.8%) than adults (3.3%) (z=-6.76, p<0.01). There was a significant negative correlation between the adult prevalence of the thyroid ima artery and the year of publication (Pearson's r=-0.354, p=0.040) thereby suggesting a decline in thyroid ima artery prevalence over time. This artery, if present, may originate from the brachiocephalic trunk (74%), right common carotid artery (9.6%), arch of aorta (7.7%), right internal thoracic artery (4.8%), left common carotid artery (1.9%) and left internal thoracic artery (1.9%). CONCLUSION: In addition to evidence-based synthesis of the thyroid ima artery, this study is the first ever study to report the decreasing prevalence over time of a human body structure in the postnatal life. Knowledge of the thyroid ima artery is of vital importance for surgeons to avoid accidental hemorrhage during tracheostomy.

Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in C. elegans Model of Parkinson's Disease.

Parkinson's disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from Cucumaria frondosa and ginsenoside Rg3 (Rg3) from Panax notoginseng in C. elegans PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in C. elegans. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, egl-1 and ced-3, and upregulation of sod-3 and cat-2. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including ubh-4, hsf-1, hsp-16.1 and hsp-16.2. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced C. elegans model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.

Diterpene glycosides from Holothuria scabra exert the α-synuclein degradation and neuroprotection against α-synuclein-Mediated neurodegeneration in C. elegans model.

ETHNOPHARMACOLOGICAL RELEVANCE: Holothuria (Metriatyla) scabra Jaeger (H. scabra), sea cucumber, is the marine organism that has been used as traditional food and medicine to gain the health benefits since ancient time. Although our recent studies have shown that crude extracts from H. scabra exhibited neuroprotective effects against Parkinson's disease (PD), the underlying mechanisms and bioactive compounds are still unknown. AIM OF THE STUDY: In the present study, we examined the efficacy of purified compounds from H. scabra and their underlying mechanism on α-synuclein degradation and neuroprotection against α-synuclein-mediated neurodegeneration in a transgenic Caenorhabditis elegans PD model. MATERIAL AND METHODS: The H. scabra compounds (HSEA-P1 and P2) were purified and examined for their toxicity and optimal dose-range by food-clearance and lifespan assays. The α-synuclein degradation and neuroprotection against α-synuclein-mediated neurodegeneration were determined using transgenic C. elegans model, Punc-54::α-syn and Pdat-1:: α-syn; Pdat-1::GFP, respectively, and then further investigated by determining the behavioral assays including locomotion rate, basal slowing rate, ethanol avoidance, and area-restricted searching. The underlying mechanisms related to autophagy were clarified by quantitative PCR and RNAi experiments. RESULTS: Our results showed that HSEA-P1 and HSEA-P2 significantly diminished α-synuclein accumulation, improved motility deficits, and recovered the shortened lifespan. Moreover, HSEA-P1 and HSEA-P2 significantly protected dopaminergic neurons from α-synuclein toxicity and alleviated dopamine-associated behavioral deficits, i.e., basal slowing, ethanol avoidance, and area-restricted searching. HSEA-P1 and HSEA-P2 also up-regulated autophagy-related genes, including beclin-1/bec-1, lc-3/lgg-1, and atg-7/atg-7. RNA interference (RNAi) of these genes in transgenic α-synuclein worms confirmed that lc-3/lgg-1 and atg-7/atg-7 were required for α-synuclein degradation and DAergic neuroprotection activities of HSEA-P1 and HSEA-P2. NMR and mass spectrometry analysis revealed that the HSEA-P1 and HSEA-P2 contained diterpene glycosides. CONCLUSION: These findings indicate that diterpene glycosides extracted from H. scabra decreases α-synuclein accumulation and protects α-synuclein-mediated DAergic neuronal loss and its toxicities via lgg-1 and atg-7.

The prevalence of the azygos lobe: A meta-analysis of 1,033,083 subjects.

The azygos lobe (AL) is an accessory lobe of the right lung with prevalence between 0.4 and 1.2%. The aim of the present review is to provide a better estimate of the frequency of the AL and to examine its relationships with other variables such as population, diagnostic methods, and co-occurring illnesses. Studies published between 1899 and October 2020 were searched through three electronic databases; Google Scholar, PubMed, and JSTOR. Titles, abstracts, and full texts of the retrieved entries were screened to determine their appropriateness for inclusion. A total of 88 studies relating to 1,033,083 subjects met the inclusion criteria. A random-effects meta-analysis yielded an overall prevalence of 0.30% (95% CI: 0.0024-0.0035, I2  = 97.9%). Linear regression and subgroup analysis revealed a negative correlation (ρ = -0.540, p <0.001) between AL prevalence and sample size; studies with smaller sample sizes had higher prevalences. The AL prevalence in individuals with congenital pulmonary defects, 5.2% (95% CI: 0.0018-0.0086, I2  = 0%), was 17 times higher than the overall prevalence (z = 6.65, p <0.001), suggesting associations with other abnormalities and possibly a genetic predisposition. In addition to an evidence-based synthesis of AL prevalence, this study demonstrates publication bias and small-study effects in the anatomy literature. Awareness of the AL is crucial for radiologists when they interpret unusual radiological findings and for surgeons when they operate in the region.