-
Journal of Extracellular Biology Feb 2024Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell...
Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in expression in the oxaliplatin-resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta-databases, RNA levels were continually detected in colorectal tissue arrays. Additionally, protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial-type marker CDH1 was suppressed in overexpression models, whereas the expression of the mesenchymal-type markers SNAI1 and SNAI2 increased. Notably, -induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that /AGR2 axis-mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.
PubMed: 38939899
DOI: 10.1002/jex2.141 -
Acta Medica Philippina 2024To determine the effect of the impacted position of the maxillary canine on the root resorption of the adjacent incisor using Cone-beam Computed Tomography (CBCT)...
OBJECTIVE
To determine the effect of the impacted position of the maxillary canine on the root resorption of the adjacent incisor using Cone-beam Computed Tomography (CBCT) imaging.
METHODS
This was an analytic quantitative study. The research sample determined CBCT images of treatment patients at the Orthodontic Specialist Policlinic in Dental Hospital of Airlangga University over a three-year period and secondary data taken from Pramita Laboratory. CBCT photos that met the inclusion criteria, including mesially impacted canine or close to central or lateral incisors with completely formed anatomy were then analyzed. Multiple linear regression was used to determine x-axis, y-axis, z-axis position of the impacted canine on the severity of root resorption of the adjacent incisor, and the effect of impacted canines on all axes simultaneously on the severity of root resorption of the adjacent incisors.
RESULTS
The position of the impacted canine in the x-axis and z-axis planes had a significant influence on the root resorption of the adjacent incisor. Meanwhile, impacted canine from the y-axis plane showed non-significant influence on the root resorption.
CONCLUSION
The position of the impacted canine when viewed in all planes of the tooth axis has a significant effect on the severity of root resorption of the adjacent incisor.
PubMed: 38939849
DOI: 10.47895/amp.vi0.4321 -
Current Developments in Nutrition Jun 2024This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central... (Review)
Review
This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central nervous system and the enteric nervous system. Phytochemicals, which are compounds derived from plants, have been shown to interact with the gut microbiota, immune system, and neurotransmitter systems, thereby influencing brain function. Phytochemicals such as polyphenols, carotenoids, flavonoids, and terpenoids have been identified as having potential therapeutic implications for various neurological disorders. The GBA plays a critical role in the development and progression of various neurological disorders, including Parkinson's disease, multiple sclerosis, depression, anxiety, and autism spectrum disorders. Dysbiosis, or an imbalance in gut microbiota composition, has been associated with a range of neurological disorders, suggesting that modulating the gut microbiota may have potential therapeutic implications for these conditions. Although these findings are promising, further research is needed to elucidate the optimal use of phytochemicals in neurological disorder treatment, as well as their potential interactions with other medications. The literature review search was conducted using predefined search terms such as phytochemicals, gut-brain axis, neurodegenerative, and Parkinson in PubMed, Embase, and the Cochrane library.
PubMed: 38939650
DOI: 10.1016/j.cdnut.2024.103785 -
Journal of Conservative Dentistry and... May 2024Seal the dentin of the pulp chamber during endodontic treatment to avoid interfering with the restorative treatment performed afterward.
CONTEXT
Seal the dentin of the pulp chamber during endodontic treatment to avoid interfering with the restorative treatment performed afterward.
AIMS
The aim was to evaluate the effect of three adhesive systems applied in different bonding strategies (etch-and-rinse, self-etch, and universal adhesive) and time-point application (immediately after the cavity access preparation or after endodontic obturation) on the hybrid layer formation and dentinal penetrability.
MATERIALS AND METHODS
Forty-eight sound molars were randomly distributed into six groups ( = 10) according to the adhesive system used: Forty-eight sound molars were randomly distributed into six groups ( = 10) according to the adhesive system used and the time-point application: Adper Scotchbond Multi-purpose (AS), Clearfil SE (CF) and Scotchbond Universal (SU) in strategy of immediate endodontic sealing (IES) or delayed endodontic sealing (DES). In IES-AS, IES-CF, and IES-SU groups, dentin sealing was performed immediately after the cavity access, while in DES-AS, DES-CF, and DES-SU, after root canal obturation. The specimens were sectioned in the long axis, in a buccal-lingual direction, and the dentinal penetrability of the adhesive systems was evaluated using confocal microscopy images. Hybrid layer formation was analyzed by scanning electron microscopy images.
STATISTICAL ANALYSIS USED
Dentinal penetrability data were analyzed with the ANOVA test and the Kruskal-Wallis test was performed for hybrid layer data (α = 0.05).
RESULTS
IES-CF showed the lowest dentinal penetrability ( < 0.05), while the other protocols were similar to each other ( > 0.05). No significant differences were found between groups regarding the hybrid layer formation ( > 0.05). Immediate and DES protocols do not influence the hybrid layer formation, regardless of the bond strategy used.
CONCLUSIONS
Sealing the pulp chamber dentin before endodontic treatment can improve the bond strength of the final restoration but the formation of the hybrid layer was not influenced by the bond strategy.
PubMed: 38939549
DOI: 10.4103/JCDE.JCDE_80_24 -
Journal of Extracellular Biology Jul 2023Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence...
Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence of BEVs ability to transmigrate across cellular barriers to elicit responses in other tissues, such as the central nervous system (CNS). Here we use a combination of single-, two- and three-cell culture systems to demonstrate the transmigration of derived BEVs (Bt-BEVs) across gut epithelium and blood brain barrier (BBB) endothelium, and their subsequent acquisition and downstream effects in neuronal cells. Bt-BEVs were shown to traffic to the CNS after intravenous administration to mice, and in multi-cell culture systems to transmigrate across gut epithelial and BBB endothelial cell barriers, where they were acquired by both microglia and immature neuronal cells. No significant activation/inflammatory effects were induced in non-differentiated neurons, in contrast to that observed in microglia cells, although this was notably less than that induced by lipopolysaccharide (LPS). Overall, our findings provide evidence for transmigration of Bt-BEVs across gut-epithelial and BBB endothelial cell barriers and , and their downstream responses in neural cells. This study sheds light onto how commensal bacteria-derived BEV transport across the gut-brain axis and can be exploited for the development of targeted drug delivery.
PubMed: 38939073
DOI: 10.1002/jex2.93 -
Research (Washington, D.C.) 2024Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse...
Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis. In summary, brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.
PubMed: 38939042
DOI: 10.34133/research.0400 -
JACC. Advances Mar 2024FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not...
BACKGROUND
FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not been reported.
OBJECTIVES
The purpose of this study was to determine factors associated with fetal aortic valvuloplasty (FAV) technical success (TS) and serious adverse events (SAEs).
METHODS
Retrospective, single-center, cohort analysis of attempted FAV from March 1, 2000, to December 31, 2020. The primary outcome was the TS of FAV, and the secondary outcome was the presence of an SAE.
RESULTS
A total of 165 FAVs were attempted in 163 patients with a median gestational age of 24.6 weeks (IQR: 22.9-27.1 weeks). FAV TS was 85% (141/165) and was higher in the 2010 to 2020 era (94% [85/90] vs 75% [56/75]; < 0.001). Pre-FAV echocardiographic left ventricle (LV) long axis dimension z-score >-0.10 ( < 0.001) and higher LV ejection fraction ( = 0.037) were independently associated with a higher odds of TS. There were 117 SAEs in 67 attempted FAVs (41%), 13 of which were fetal deaths (7.9%). By classification and regression tree analysis, gestational age <21 weeks or in older fetuses, a procedure time of ≥39.6 minutes was associated with higher SAE rate. In the multivariable logistic regression model correcting for gestational age, fetuses with an LV end-diastolic volume <4.09 mL had an age-adjusted OR of 4.71 (95% CI: 1.67-13.29; = 0.004) for experiencing an SAE.
CONCLUSIONS
TS of FAV has improved over time, and failure is associated with smaller fetal left heart sizes. SAEs are common and are associated with smaller left hearts and longer procedure times.
PubMed: 38938833
DOI: 10.1016/j.jacadv.2024.100835 -
Frontiers in Immunology 2024The comorbidity rate of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is high; nevertheless, the reasons behind this high rate remain unclear. Their...
BACKGROUND
The comorbidity rate of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is high; nevertheless, the reasons behind this high rate remain unclear. Their similar genetic makeup probably contributes to this comorbidity.
METHODS
Based on data obtained from the genome-wide association study of IBD and RA, we first assessed an overall genetic association by performing the linkage disequilibrium score regression (LDSC) analysis. Further, a local correlation analysis was performed by estimating the heritability in summary statistics. Next, the causality between the two diseases was analyzed by two-sample Mendelian randomization (MR). A genetic overlap was analyzed by the conditional/conjoint false discovery rate (cond/conjFDR) method.LDSC with specific expression of gene analysis was performed to identify related tissues between the two diseases. Finally, GWAS multi-trait analysis (MTAG) was also carried out.
RESULTS
IBD and RA are correlated at the genomic level, both overall and locally. The MR results suggested that IBD induced RA. We identified 20 shared loci between IBD and RA on the basis of a conjFDR of <0.01. Additionally, we identified two tissues, namely spleen and small intestine terminal ileum, which were commonly associated with both IBD and RA.
CONCLUSION
Herein, we proved the presence of a polygenic overlap between the genetic makeup of IBD and RA and provided new insights into the genetic architecture and mechanisms underlying the high comorbidity between these two diseases.
Topics: Arthritis, Rheumatoid; Humans; Genome-Wide Association Study; Inflammatory Bowel Diseases; Genetic Predisposition to Disease; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Mendelian Randomization Analysis; Comorbidity
PubMed: 38938570
DOI: 10.3389/fimmu.2024.1359857 -
Frontiers in Endocrinology 2024Endocannabinoids and their -acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy...
OBJECTIVE
Endocannabinoids and their -acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this cross-sectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth.
METHODS
Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated.
RESULTS
Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM- women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (β=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring.
CONCLUSION
The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM- women and was associated with GDM+ offspring growth at 2 months.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier (NCT04263675 and NCT02872402).
Topics: Humans; Endocannabinoids; Milk, Human; Female; Pregnancy; Diabetes, Gestational; Infant, Newborn; Adult; Cross-Sectional Studies; Male; Infant; Child Development
PubMed: 38938519
DOI: 10.3389/fendo.2024.1415630 -
Animal Bioscience Jun 2024Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the...
OBJECTIVE
Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.
METHODS
In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine CSO22 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine CSO22 (pVAX-asd) orally.
RESULTS
The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p < 0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and IGF-1 in the serum of goats (p < 0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology (GO) of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto Encyclopedia of Genes and Genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. DGKK, CYTB, DUSP1 and LRAT) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.
CONCLUSION
Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic-pituitary-liver axis.
PubMed: 38938026
DOI: 10.5713/ab.24.0121