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1.
Mol Biomed ; 5(1): 13, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616230

RESUMO

Compared with those in adenocarcinoma, PIK3CA mutations are more common in squamous cell carcinoma (SCC), which arises from stratified squamous epithelia that are usually exposed to adverse environmental factors. Although hotspot mutations in exons 9 and 20 of PIK3CA, including E542K, E545K, H1047L and H1047R, are frequently encountered in the clinic, their clinicopathological meaning remains to be determined in the context of SCC. Considering that few reviews on PIK3CA mutations in SCC are available in the literature, we undertook this review to shed light on the clinical significance of PIK3CA mutations, mainly regarding the implications and ramifications of PIK3CA mutations in malignant cell behavior, prognosis, relapse or recurrence and chemo- or radioresistance of SCC. It should be noted that only those studies regarding SCC in which PIK3CA was mutated were cherry-picked, which fell within the scope of this review. However, the role of mutated PIK3CA in adenocarcinoma has not been discussed. In addition, mutations occurring in other main members of the PI3K-AKT-mTOR signaling pathway other than PIK3CA were also excluded.

2.
J Pharm Pharmacol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624082

RESUMO

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.

3.
Neuroimage Clin ; 42: 103603, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38588618

RESUMO

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38613763

RESUMO

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI - 0.658 ~ - 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction.

5.
J Agric Food Chem ; 72(15): 8840-8848, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38570314

RESUMO

A series of new 4-amino-3,5-dicholo-6-(5-aryl-substituted-1H-pyrazol-1-yl)-2-picolinic acid compounds were designed and prepared to discover herbicidal molecules. The inhibitory activities of all new compounds against the root growth ofArabidopsis thaliana were assayed. On the whole, the new synthesized compounds displayed good inhibition effects and had excellent herbicidal activities on root growth of weed at 500 µM. Importantly, a selection of compounds demonstrated comparable herbicidal properties to picloram. At the dosage of 250 g/ha, most of the compounds showed a 100% postemergence herbicidal activity to control Chenopodium album and Amaranthus retroflexus. Using compound V-2, the mechanism of action was investigated based on a phenotype study using AFB5-deficient Arabidopsis thaliana. It was found that the novel 6-pyrazolyl-2-picolinic acids were auxinic compounds. In addition, it was proposed that V-2 may be an immune activator due to its upregulation of defense genes and the increased content of jasmonic acid.


Assuntos
Arabidopsis , Herbicidas , Herbicidas/farmacologia , Relação Estrutura-Atividade , Ácidos Picolínicos/farmacologia , Arabidopsis/genética
6.
Adv Sci (Weinh) ; : e2308384, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634607

RESUMO

Cell-specific transcriptional regulatory networks (TRNs) play vital roles in plant development and response to environmental stresses. However, traditional single-cell mono-omics techniques are unable to directly capture the relationships and dynamics between different layers of molecular information within the same cells. While advanced algorithm facilitates merging scRNA-seq and scATAC-seq datasets, accurate data integration remains a challenge, particularly when investigating cell-type-specific TRNs. By examining gene expression and chromatin accessibility simultaneously in 16,670 Arabidopsis root tip nuclei, the TRNs are reconstructed that govern root tip development under osmotic stress. In contrast to commonly used computational integration at cell-type level, 12,968 peak-to-gene linkage is captured at the bona fide single-cell level and construct TRNs at an unprecedented resolution. Furthermore, the unprecedented datasets allow to more accurately reconstruct the coordinated changes of gene expression and chromatin states during cellular state transition. During root tip development, chromatin accessibility of initial cells precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for subsequent differentiation steps. Pseudo-time trajectory analysis reveal that osmotic stress can shift the functional differentiation of trichoblast. Candidate stress-related gene-linked cis-regulatory elements (gl-cCREs) as well as potential target genes are also identified, and uncovered large cellular heterogeneity under osmotic stress.

7.
Front Endocrinol (Lausanne) ; 15: 1368088, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590826

RESUMO

Background: There is no doubt that both Hashimoto thyroiditis and Graves' disease are autoimmune thyroid diseases (AITDs), but the relationship between anti-nuclear antibody (ANA) and AITDs is poorly studied. The association between thyroid autoantibody levels and ANA positivity was evaluated to assess the role of ANA in AITDs. Methods: We conducted an analysis using data from 1,149,893 patients registered at our hospital and 53,021 patients registered in the National Health and Nutrition Examination Survey databases. We focused on patients with data for thyroid peroxidase antibody (TPOAb)/ANA, TPOAb/immunoglobulin G (IgG), thyroid-stimulating hormone (TSH) receptor antibody (TRAb)/ANA, TRAb/IgG, TSH/ANA, or TSH/IgG. Results: ANA positivity rates were 12.88% and 21.22% in TPOAb/ANA and TSH/ANA patients, respectively. In TPOAb/IgG and TSH/IgG data, high IgG levels (≥15 g/L) were detected in 2.23% and 4.06% of patients, respectively. There were significant differences in ANA positivity rates and high IgG proportions among patients with different TPOAb and TSH levels. TPOAb level was correlated with ANA positivity rate and high IgG proportion, and TSH level was correlated with ANA positivity rate. Regression analysis showed positive correlations between TPOAb levels and ANA positivity risk or high IgG risk, TSH levels and high IgG risk, and elevated TSH and ANA positivity risk. Of patients with TRAb/ANA data, 35.99% were ANA-positive, and 13.93% had TRAb levels ≥1.75IU/L; 18.96% of patients with TRAb/IgG data had high IgG levels, and 16.51% had TRAb levels ≥1.75IU/L. ANA positivity rate and high IgG proportion were not significantly different among different TRAb levels. TRAb levels, ANA positivity risk and high IgG risk were not correlated. Conclusion: ANA positivity and high IgG are related to Hashimoto thyroiditis but not Graves' disease, which implies distinct pathophysiological mechanisms underlying the AITDs.


Assuntos
Doença de Graves , Doença de Hashimoto , Humanos , Inquéritos Nutricionais , Autoanticorpos , Doença de Graves/diagnóstico , Receptores da Tireotropina , Imunoglobulina G , Tireotropina
8.
J Diabetes Investig ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593274

RESUMO

AIMS/INTRODUCTION: Our aim was to investigate the optimal fasting glucose (FPG) range in Chinese older adults with type 2 diabetes, and to clarify whether the optimal range varies according to the control of risk factors. MATERIALS AND METHODS: The baseline survey for the cohort study began in 2018, with follow up ending in 2022. Our study enrolled 59,030 older diabetes patients with no history of cardiovascular disease (CVD). Participants were divided into nine groups based on their baseline glycemic status. The association between FPG and the risk of adverse outcomes was mainly estimated by multivariate Cox proportional risk models and restricted spline analysis. RESULTS: During the 4-year follow-up period, a total of 5,637 deaths and 4,904 CVD events occurred. The associations of FPG with mortality and CVD events showed J-shaped curves. Among all-cause deaths, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.50 (95% confidence interval [CI] 1.31-1.71) and 1.84 (95% CI 1.67-2.02). Among CVD, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.31 (95% CI 1.13-1.53) and 1.71 (95% CI 1.54-1.89), respectively. The optimal FPG ranges of all-cause mortality and CVD were 5.50-7.50 and 4.50-7.50 mmol/L, respectively. For participants with at least two risk factors, the optimal FPG levels were higher than those with fewer risk factors. CONCLUSIONS: In older Chinese diabetes patients, the FPG ranges related to the minimum death and CVD event rates were 5.50-7.50 and 4.50-7.50 mmol/L, respectively. Patients with more cardiovascular risk factors had higher optimal blood glucose ranges than those with fewer risk factors.

9.
Lupus Sci Med ; 11(1)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599669

RESUMO

OBJECTIVE: Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN). METHODS: This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression. RESULTS: Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280). CONCLUSION: Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Nefrite Lúpica/complicações , Inflamação , Progressão da Doença
10.
bioRxiv ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38562850

RESUMO

The dmPFC plays a dual role in modulating drug seeking and fear-related behaviors. Learned associations between cues and drug seeking are encoded by a specific ensemble of neurons. This study explored the stability of a dmPFC cocaine seeking ensemble over two weeks and its influence on persistent cocaine seeking and fear memory retrieval. In the first series of experiments, we trained TetTag mice in cocaine self-administration and tagged strongly activated neurons with EGFP during the initial day 7 cocaine seeking session. Subsequently, a follow-up seeking test was conducted two weeks later to examine ensemble reactivation between two seeking sessions via c-Fos immunostaining. In the second series of experiments, we co-injected viruses expressing TRE-cre and a cre-dependent inhibitory PSAM-GlyR into the dmPFC of male and female c-fos -tTA mice to enable "tagging" of cocaine seeking ensemble or cued fear ensemble neurons with an inhibitory chemogenetic receptors. Then we investigated their contribution to subsequent cocaine seeking and fear recall during inhibition of the tagged ensemble by administering uPSEM792s (0.3 mg/kg), a selective ligand for PSAM-GlyR. In both sexes, there was a positive association between the persistence of cocaine seeking and the proportion of reactivated EGFP+ neurons within the dmPFC. More importantly, inhibition of the cocaine seeking ensemble suppressed cocaine seeking, but not recall of fear memory, while inhibition of the fear ensemble reduced conditioned freezing but not cocaine seeking. The results demonstrate that cocaine and fear recall ensembles in the dmPFC are stable, but largely exclusive from one another.

11.
Opt Express ; 32(7): 12636-12644, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571081

RESUMO

Organic photodetectors (OPDs) have attracted increasing attention in the future wearable sensing and real-time health monitoring, due to their intrinsic features including the mechanical flexibility, low-cost processing and cooling-free operations; while their performances are lagging as the results of inferior carrier mobility and small exciton diffusion coefficient of organic molecules. Graphene exhibits the great photoresponse with wide spectral bandwidth and high response speed. However, weak light absorption and the absence of a gain mechanism have limited its photoresponsivity. Here, we report a sensitive organic/inorganic phototransistor with fast response speed by coupling PTCDA organic single crystal with the monolayer graphene. The long range exciton diffusion in highly ordered π-conjugated molecules, efficient exciton dissociation and charge transfer at the PTCDA/graphene heterointerfaces, and the high mobility of graphene enable a high responsivity (8 × 104A/W), short response time (220 µs) and excellent specific detectivity (>1011 Jones), which is higher than the level of commercial on-chip device. This interfacial photogating effect is verified by the high-resolution spatial photocurrent mapping experiment. In addition, the high sensitivity to polarization is clear and the ultrahigh photoconductive gain enables a near-infrared (NIR) response for 980 and 1550 nm. Finally, high-speed visible and NIR imaging applications are successfully demonstrated. This work suggests that high quality organic single crystal/graphene is a promising platform for future high performance optoelectronic systems and imaging applications.

12.
Appl Opt ; 63(8): 1947-1951, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568633

RESUMO

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

13.
Brain Pathol ; : e13261, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602336

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

14.
Oncol Lett ; 27(5): 224, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38586212

RESUMO

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have transformed the treatment paradigm for patients with ALK-positive non-small cell lung cancer (NSCLC). Yet the differential efficacy between alectinib and crizotinib in treating patients with NSCLC and central nervous system (CNS) metastases has been insufficiently studied. A retrospective analysis was conducted of clinical outcomes of patients with ALK-positive NSCLC and CNS metastases treated at the Shandong Cancer Centre. Based on their initial ALK-TKI treatment, patients were categorised into either the crizotinib group or the alectinib group. Efficacy, progression-free survival (PFS), intracranial PFS and overall survival (OS) were evaluated. A total of 46 eligible patients were enrolled in the present study: 33 patients received crizotinib and 13 patients received alectinib. The median OS of the entire group was 66.8 months (95% CI: 48.5-85.1). Compared with the patients in the crizotinib group, the patients in the alectinib group showed a significant improvement in both median (m)PFS (27.5 vs. 9.5 months; P=0.003) and intracranial mPFS (36.0 vs. 10.8 months; P<0.001). However, there was no significant difference in OS between the alectinib and crizotinib groups (not reached vs. 58.7 months; P=0.149). Furthermore, there were no significant differences between patients receiving TKI combined with radiotherapy (RT) vs. TKI alone with respect to mPFS (11.0 vs. 11.7 months, P=0.863) as well as intracranial mPFS (12.5 vs. 16.9 months, P=0.721). In the present study, alectinib exhibited superior efficacy to crizotinib for treating patients with ALK-positive NSCLC and CNS metastases, especially in terms of delaying disease progression and preventing CNS recurrence. Moreover, the results demonstrated that it might be beneficial to delay local RT for patients with ALK-positive NSCL and CNS metastases.

15.
Heliyon ; 10(7): e28608, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586331

RESUMO

Apoptosis is the primary cause of cell death in the differentiation of Adipose-derived stromal cells (ADSCs) into neurons. However, the relationship between endoplasmic reticulum stress (ERS) and death receptor-mediated apoptosis in ADSC-induced neuronal differentiation is not clear. ADSCs were isolated and induced to differentiate into neurons using ß-mercaptoethanol. The expression of neuron-specific enolase (NSE), GRP94, CHOP, Fas/FasL, TNFR1/TNF-α, DR5/TRAIL, Caspase8, and Caspase3 in ADSCs was examined using immunocytochemistry and Western blotting before induction, during pre-induction, and after induction. Transmission electron microscopy (TEM) was used to observe changes in the morphology of the endoplasmic reticulum (ER), and the MTT assay was employed to measure cell viability in the uninduced and induced groups. Additionally, the number of apoptotic cells during the induction process was measured using flow cytometry with Annexin V/PI. With increasing induction time, the positive expression rates of CHOP, Fas/FasL, Caspase8, Caspase-3, and NSE gradually increased, while the positive expression rate of GRP94 decreased. TNFR1/TNF-α and DR5/TRAIL peaked at 5 h post-induction and then decreased at 8 h. TEM revealed swelling and expansion of the ER, vacuolar changes, and degranulation in cells. The MTT assay showed a gradual decrease in the absorbance of surviving cells in all groups. Flow cytometry indicated an increasing rate of apoptosis in cells. Therefore, ERS in the normal culture and growth of ADSCs, manifesting as enhanced unfolded protein response (UPR), maintains the normal survival of ADSCs. However, in the process of ADSC-induced differentiation into neurons, ERS and death receptor-mediated apoptosis are significant causes of cell death.

16.
Biomol Biomed ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581717

RESUMO

Cyclin B1 (CCNB1) encodes a regulatory protein essential for the regulation of cell mitosis, particularly in controlling the G2/M transition phase of the cell cycle. Current research has implicated CCNB1 in the progression of various types of cancer, including gastric cancer, breast cancer, and non-small cell lung cancer. In this study, we conducted a pan-cancer analysis of CCNB1 to investigate its prognostic significance and immunological aspects. Our comprehensive investigation covered a wide range of analyses, including gene expression, promoter methylation, genetic alterations, immune infiltration, immune regulators, and enrichment studies. We utilized multiple databases and tools for this purpose, such as The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, the Human Protein Atlas (HPA), the University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), the Gene Expression Profiling Interactive Analysis (GEPIA), the DNA Methylation Interactive Visualization Database (DNMIVD), the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Sangerbox, and cBioPortal. Data analyses were executed using GraphPad Prism software, R software, and various online tools. Our findings demonstrated a significant increase in CCNB1 expression across 28 cancer types. Elevated CCNB1 expression correlated with decreased overall survival (OS) in 11 cancer types and disease-free survival (DFS) in 12 cancer types. Additionally, DNA promoter methylation levels were significantly decreased in 14 cancer types. Furthermore, the study verified a significant association between CCNB1 expression and immune infiltration, immune modulators, microsatellite instability (MSI), and tumor mutational burden (TMB). Enrichment analysis indicated that CCNB1 is involved in multiple cellular pathways. Collectively, our results suggested that CCNB1 has the potential to serve as a valuable prognostic biomarker and may be a promising target for immunotherapy in various cancer types.

17.
Gigascience ; 132024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38626722

RESUMO

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.


Assuntos
Genoma , Cromossomos Sexuais , Cromossomos Sexuais/genética , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
18.
Oral Dis ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622872

RESUMO

OBJECTIVES: Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5-HydroxyTryptamine, 5-HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5-HT on the modulation of orofacial pain. SUBJECTS AND METHODS: An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5-HT on the modulation of orofacial pain. RESULTS: In this review, we concisely review how 5-HT mediates orofacial pain, how 5-HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain. CONCLUSIONS: 5-HT plays a key role in the modulation of orofacial pain, implying that 5-HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.

19.
Front Psychol ; 15: 1335548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566953

RESUMO

Previous studies have a lack of meta-analytic studies comparing the trait (personality) envy, social comparison envy, and love-envy, and the understanding of the similarities and differences in the neural mechanisms behind them is relatively unclear. A meta-analysis of activation likelihood estimates was conducted using 13 functional magnetic resonance imaging studies. Studies first used single meta-analyses to identify brain activation areas for the three envy types. Further, joint and comparative analyses were followed to assess the common and unique neural activities among the three envy types. A single meta-analysis showed that the critical brain regions activated by trait (personality) envy included the inferior frontal gyrus, cingulate gyrus, middle frontal gyrus, lentiform nucleus and so on. The critical brain regions activated by social comparison envy included the middle frontal gyrus, inferior frontal gyrus, medial frontal gyrus, precuneus and so on. The critical brain regions activated by love-envy included the inferior frontal gyrus, superior frontal gyrus, cingulate gyrus, insula and so on. In terms of the mechanisms that generate the three types of envy, each of them is unique when it comes to the perception of stimuli in a context; in terms of the emotion regulation mechanisms of envy, the three types of envy share very similar neural mechanisms. Both their generation and regulation mechanisms are largely consistent with the cognitive control model of emotion regulation. The results of the joint analysis showed that the brain areas co-activated by trait (personality) envy and social comparison envy were frontal sub-Gyral, inferior parietal lobule, inferior frontal gyrus, precuneus and so on; the brain areas co-activated by trait (personality) envy and love-envy were extra-nuclear lobule, lentiform nucleus, paracentral lobule, cingulate gyrus and so on; the brain regions that are co-activated by social comparison envy and love-envy are anterior cingulate gyrus, insula, supramarginal gyrus, inferior frontal gyrus and so on. The results of the comparative analysis showed no activation clusters in the comparisons of the three types of envy.

20.
Mol Cytogenet ; 17(1): 7, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570848

RESUMO

BACKGROUND: Premature ovarian insufficiency (POI) is a clinical condition characterized by ovarian dysfunction in women under 40. The etiology of most POI cases remains unidentified and is believed to be multifactorial, including factors such as autoimmunity, metabolism, infection, and genetics. POI exhibits significant genetic heterogeneity, and it can result from chromosomal abnormalities and monogenic defects. CASE PRESENTATION: The study participant, a 33-year-old woman, presented with a history of irregular menstruation that commenced two years ago, progressing to prolonged menstrual episodes and eventual cessation. The participant exhibits a rearrangement of the X chromosome, characterized by heterozygosity duplication on the long arm and heterozygosity deletion on the short arm by whole exome sequencing(WES) combined with cell chromosome detection. CONCLUSIONS: This study expands the spectrum of mutations associated with POI resulting from X chromosomal abnormalities. WES-Copy number variation analysis, in conjunction with chromosome karyotype analysis and other detection techniques, can provide a more comprehensive understanding of the genetic landscape underlying complex single or multi-system diseases.

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