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2.
Clin Transl Med ; 14(5): e1705, 2024 May.
Article in English | MEDLINE | ID: mdl-38797935

ABSTRACT

Ribosomal RNA (rRNA) modifications, essential components of ribosome structure and function, significantly impact cellular proteomics and cancer biology. These chemical modifications transcend structural roles, critically shaping ribosome functionality and influencing cellular protein profiles. In this review, the mechanisms by which rRNA modifications regulate both rRNA functions and broader cellular physiological processes are critically discussed. Importantly, by altering the translational output, rRNA modifications can shift the cellular equilibrium towards oncogenesis, thus playing a key role in cancer development and progression. Moreover, a special focus is placed on the functions of mitochondrial rRNA modifications and their aberrant expression in cancer, an area with profound implications yet largely uncharted. Dysregulation in these modifications can lead to metabolic dysfunction and apoptosis resistance, hallmark traits of cancer cells. Furthermore, the current challenges and future perspectives in targeting rRNA modifications are highlighted as a therapeutic approach for cancer treatment. In conclusion, rRNA modifications represent a frontier in cancer research, offering novel insights and therapeutic possibilities. Understanding and harnessing these modifications can pave the way for breakthroughs in cancer treatment, potentially transforming the approach to combating this complex disease.


Subject(s)
Neoplasms , RNA, Ribosomal , Ribosomes , Humans , Neoplasms/genetics , Neoplasms/drug therapy , Neoplasms/metabolism , RNA, Ribosomal/metabolism , RNA, Ribosomal/genetics , Ribosomes/metabolism , Ribosomes/genetics , RNA Processing, Post-Transcriptional/genetics
3.
J Asian Nat Prod Res ; : 1-10, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753580

ABSTRACT

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.

4.
Zool Res ; 45(3): 617-632, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38766745

ABSTRACT

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.


Subject(s)
Adrenal Glands , Steroids , Animals , Adrenal Glands/metabolism , Humans , Steroids/biosynthesis , Steroids/metabolism , Transcriptome , Mice , Tupaiidae , Female , Multiomics
5.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2512-2521, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812155

ABSTRACT

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P<0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P<0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P<0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P<0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.


Subject(s)
Drugs, Chinese Herbal , Ointments , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/drug therapy , Drugs, Chinese Herbal/administration & dosage , Male , Middle Aged , Female , Double-Blind Method , Aged , Treatment Outcome , Adult , Pain/drug therapy , Pain/etiology
6.
Article in English | MEDLINE | ID: mdl-38814596

ABSTRACT

Background: Infectious bone defect refers to severe bone tissue damage caused by skeletal infection, often resulting in impaired skeletal function and intense inflammatory responses. Treating infectious bone defects is a challenging task, as conventional treatment methods often fail to completely eliminate the infection focus and may easily lead to inflammatory responses in the bone defect area. Objective: To examine the impacts of bone transport (BT) in conjunction with drug-loaded calcium sulfate (DLCS) on the expression of inflammatory factors and vascular endothelial growth factor (VEGF) in rats with infectious bone defects. Methods: A total of 40 rats were randomly allocated to 4 groups-the sham, model, BT, and BT + DLCS groups-with 10 rats in each group. Interleukin 10 (IL-10), tumor necrosis factor (TNF), nuclear factor-κB (NF-κB), insulinlike growth factor 1 (IGF 1), and recombinant human basic fibroblast growth factor (rhbFGF) concentrations in serum were measured using enzyme-linked immunosorbent assay. In bone tissue, histopathological changes in defective bone were assessed through hematoxylin-eosin staining, CD34 expression was examined by immunohistochemistry, and VEGF expression was examined by Western blot. Results: In comparison with the sham group, the model group had significant increases in serum IL-10, TNF, and NF-κB concentrations as well as notable decreases in IGF-1 and rhbFGF serum concentrations and CD34 and VEGF expression in the bone tissue (P < .05). In contrast to the model group, both the BT and BT + DLCS groups had significant reductions in serum concentrations of IL-10, TNF, and NF-κB. Additionally, the BT and BT + DLCS groups had significant increases in serum concentrations of IGF-1 and rhbFGF as well as expression of CD34 and VEGF in the bone tissue (P < .05). The BT + DLCS group had significantly lower serum concentrations of IL-10, TNF, and NF-κB compared with the BT group. Furthermore, the BT + DLCS group had significantly elevated serum concentrations of IGF-1 and rhbFGF as well as increased expression of CD34 and VEGF in the bone tissue compared with the BT group (P < .05). Conclusion: The promotion of infected bone defect healing in rats through the combination of BT and DLCS may be attributed to the suppression of inflammatory responses and the elevation of VEGF expression to facilitate vascular regeneration.

7.
bioRxiv ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38746392

ABSTRACT

Genomic surveillance is crucial for identifying at-risk populations for targeted malaria control and elimination. Identity-by-descent (IBD) is being used in Plasmodium population genomics to estimate genetic relatedness, effective population size (Ne), population structure, and positive selection. However, a comprehensive evaluation of IBD segment detection tools is lacking for species with high rates of recombination. Here, we employ genetic simulations reflecting P. falciparum's high recombination rate and decreasing Ne to benchmark IBD callers, including probabilistic (hmmIBD, isoRelate), identity-by-state-based (hap-IBD, phased IBD) and others (Refined IBD), using genealogy-based true IBD and downstream inference of population characteristics. Our findings reveal that low marker density per genetic unit, related to high recombination rates relative to mutation rates, significantly affects the quality of detected IBD segments. Most IBD callers suffer from high false negative rates, which can be improved with parameter optimization. Optimized parameters allow for more accurate capture of selection signals and population structure, but hmmIBD is unique in providing less biased estimates of Ne. Empirical data subsampled from the MalariaGEN Pf7 database, representing different transmission settings, confirmed these patterns. We conclude that the detection of IBD in high-recombining species requires context-specific evaluation and parameter optimization and recommend that hmmIBD be used for quality-sensitive analysis, such as estimation of Ne in these species.

8.
Chem Commun (Camb) ; 60(42): 5546-5549, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38700121

ABSTRACT

Airborne nanoplastics can enter alveolar cells and trigger intracellular oxidative stress primarily. Herein, taking advantage of the high electrochemical resolution of SiC@Pt nanoelectrodes, we achieved the quantitative discrimination of the major ROS/RNS within A549 cells, disclosed the sources of their precursors, and observed that the NO (RNS precursor) level significantly increased, whereas O2˙- (ROS precursor) remained relatively stable during the nanoplastics exposure. This establishes that iNOS or mitochondrion-targeted treatment may be a preventive or therapeutic strategy for nanoplastic-induced lung injury.


Subject(s)
Electrochemical Techniques , Reactive Nitrogen Species , Reactive Oxygen Species , Humans , Reactive Oxygen Species/metabolism , A549 Cells , Reactive Nitrogen Species/metabolism , Oxidative Stress/drug effects , Electrodes
9.
J Phys Chem Lett ; 15(22): 5854-5861, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38804436

ABSTRACT

Tin oxide (SnO2) as electron transportation layer (ETL) has demonstrated remarkable performance applied in perovskite solar cells but still accommodated a host of defects such as oxygen vacancies, uncoordinated Sn4+ , and absorbed hydroxyl groups. Here, we use inorganic sodium thiosulfate Na2S2O3 to modify SnO2 nanoparticles in a bulk blending manner. Strong interaction between Na2S2O3 and SnO2 occurs, as reflected from the elemental chemical state change. The interaction has endowed the SnO2 film with better uniformity, increased conductivity, and more matched energy level with perovskite. Moreover, the modified SnO2 film as a substrate could promote the crystallization of perovskite by suppressing unreacted residual PbI2. The trap density from perovskite bulk to the SnO2 film across their interface has been effectively reduced, thus inhibiting the nonradiative recombination and promoting the transportation and extraction of charge carriers. Finally, the solar cell based on modified SnO2 has achieved a champion efficiency of 25.2%, demonstrating the effectiveness and potential of sulfur-containing molecules on optimizing the SnO2 property.

10.
Front Psychol ; 15: 1352878, 2024.
Article in English | MEDLINE | ID: mdl-38746915

ABSTRACT

Background: The Barthel Index (BI) is used to standardize the grading of assessments for clinical needs, insurance support, and long-term care resource allocation in China. However, its psychometric properties among nursing home residents remain unclear. Therefore, this study aims to assess and modify the psychometric properties of BI in nursing home residents. Methods: A total of 1,402 individuals undergoing evaluation in a nursing home facility in China were included in this study from November 2021 to November 2022. Correlations between items were examined to identify the potential multicollinearity concerns. The unidimensional item response theory (IRT) was used to validate and modify the single structure of BI. Furthermore, the logistic regression/IRT hybrid DIF detection method was conducted to assess differential item functioning (DIF) between the dementia group and the normal group. Results: The pairing of items 5 ("bowl control") and 6 ("bladder control") revealed a local dependence issue, leading to their consolidation. Items 56 (bowel and bladder control) and 9 (mobility) both displayed poor fit indices and underwent category collapsing. Through the application of the generalized partial credit model, the adjusted scale displayed better fit indices, demonstrating a robust discriminative power (DC >1.5) and orderly thresholds. Furthermore, non-uniform DIF was identified in item 2 (bathing) between the dementia group and the normal group. Conclusion: The modified BI demonstrated favorable psychometric properties and proved to be suitable for evaluating nursing home residents experiencing moderate functional impairment, which may provide a precise evaluation for long-term care resource allocation. Future studies could explore integrating supplementary measurements, such as objective indices, to assess a broader spectrum of functional statuses to potentially enhance the limited precision width observed in BI.

12.
J Am Heart Assoc ; 13(10): e033455, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38761074

ABSTRACT

BACKGROUND: The health effects of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) might differ depending on compositional variations. Little is known about the joint effect of PM2.5 constituents on metabolic syndrome and cardiovascular disease (CVD). This study aims to evaluate the combined associations of PM2.5 components with CVD, identify the most detrimental constituent, and further quantify the mediation effect of metabolic syndrome. METHODS AND RESULTS: A total of 14 427 adults were included in a cohort study in Sichuan, China, and were followed to obtain the diagnosis of CVD until 2021. Metabolic syndrome was defined by the simultaneous occurrence of multiple metabolic disorders measured at baseline. The concentrations of PM2.5 chemical constituents within a 1-km2 grid were derived based on satellite- and ground-based detection methods. Cox proportional hazard models showed that black carbon, organic matter (OM), nitrate, ammonium, chloride, and sulfate were positively associated with CVD risks, with hazard ratios (HRs) ranging from 1.24 to 2.11 (all P<0.05). Quantile g-computation showed positive associations with 4 types of CVD risks (HRs ranging from 1.48 to 2.25, all P<0.05). OM and chloride had maximum weights for CVD risks. Causal mediation analysis showed that the positive association of OM with total CVD was mediated by metabolic syndrome, with a mediation proportion of 1.3% (all P<0.05). CONCLUSIONS: Long-term exposure to PM2.5 chemical constituents is positively associated with CVD risks. OM and chloride appear to play the most responsible role in the positive associations between PM2.5 and CVD. OM is probably associated with CVD through metabolic-related pathways.


Subject(s)
Cardiovascular Diseases , Metabolic Syndrome , Particulate Matter , Humans , Particulate Matter/adverse effects , Cardiovascular Diseases/epidemiology , Male , China/epidemiology , Female , Middle Aged , Metabolic Syndrome/epidemiology , Prospective Studies , Adult , Air Pollutants/adverse effects , Air Pollutants/analysis , Environmental Exposure/adverse effects , Risk Assessment , Aged , Time Factors , Particle Size , Risk Factors , Air Pollution/adverse effects
13.
World J Gastrointest Oncol ; 16(5): 2038-2059, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38764836

ABSTRACT

BACKGROUND: Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated. AIM: To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway. METHODS: Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays. RESULTS: The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. CONCLUSION: These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

14.
Biomed Environ Sci ; 37(2): 228-232, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38582987

ABSTRACT

As a reducing salt, sodium sulfite could deprive oxygen in solution, which could mimic hypoxic stress in Caenorhabditis elegans. In this study, the wild-type Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves. We also analyzed the growth curves of mutant strains (for arcA/B, soxR/S, fnr, and oxyR) related to E. coli hypoxic pathways to reveal roles of the related genes during hypoxia. The ultrastructure of hypoxia-inhibited bacteria were also observed using transmission electron microscopy. Sodium sulfite could maintain hypoxic condition of bacterial culture for 8 h with concentrations over 40 mmol/L. Complete ultrastructure of the bacteria indicated sodium sulfite did inhibit bacterial growth and division. Among the hypoxia genes, fnr and arcB played key roles in sodium sulfite-induced hypoxia. This study showed that sodium sulfite could be used as a novel hypoxia revulsant for bacterial cultures.


Subject(s)
Escherichia coli Proteins , Escherichia coli , Sulfites , Humans , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Bacterial Outer Membrane Proteins/genetics , Hypoxia , Gene Expression Regulation, Bacterial
15.
Small ; : e2401834, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623962

ABSTRACT

Different facets in perovskite crystals exhibit distinct atomic arrangements, influencing their electronic, physical, and chemical properties. Perovskite films incorporating tin oxide (SnO2) as the electron transport layer face challenges in facet regulation. This study reveals that tea saponin (TS), a natural compound serves as a SnO2 modifier, facilitates optimal growth of perovskite crystals on the (111) facet. The modification promotes preferential crystal orientation through hydrogen bond and Lewis coordination. TS forms a chelate with SnO2, resulting in a smoother film and n-type doping, leading to improved carrier extraction and reduced defects. The TS-modified perovskite solar cells achieve a champion efficiency of 24.2%, leveraging from an obvious enhancement of open-circuit voltage (Voc) of 1.18 V and fill factor (FF) of 82.8%. The devices also demonstrate enhanced humidity tolerance and storage stability, ensuring improved stability without encapsulation.

16.
Autophagy ; : 1-21, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38686804

ABSTRACT

Obesity is one of the most common metabolic diseases around the world, which is distinguished by the abnormal buildup of triglycerides within adipose cells. Recent research has revealed that autophagy regulates lipid mobilization to maintain energy balance. TIGAR (Trp53 induced glycolysis regulatory phosphatase) has been identified as a glycolysis inhibitor, whether it plays a role in the metabolism of lipids is unknown. Here, we found that TIGAR transgenic (TIGAR+/+) mice exhibited increased fat mass and trended to obesity phenotype. Non-target metabolomics showed that TIGAR caused the dysregulation of the metabolism profile. The quantitative transcriptome sequencing identified an increased levels of LRRK2 and RAB7B in the adipose tissue of TIGAR+/+ mice. It was confirmed in vitro that TIGAR overexpression increased the levels of LRRK2 by inhibiting polyubiquitination degradation, thereby suppressing macroautophagy and chaperone-mediated autophagy (CMA) while increasing lipid accumulation which were reversed by the LRRK2 inhibitor DNL201. Furthermore, TIGAR drove LRRK2 to interact with RAB7B for suppressing lysosomal degradation of lipid droplets, while the increased lipid droplets in adipocytes were blocked by the RAB7B inhibitor ML282. Additionally, fat-specific TIGAR knockdown of TIGAR+/+ mice alleviated the symptoms of obesity, and adipose tissues-targeting superiority DNL201 nano-emulsion counteracted the obesity phenotype in TIGAR+/+ mice. In summary, the current results indicated that TIGAR performed a vital function in the lipid metabolism through LRRK2-mediated negative regulation of macroautophagy and CMA in adipocyte. The findings suggest that TIGAR has the potential to serve as a viable therapeutic target for treating obesity and its associated metabolic dysfunction.

17.
Medicine (Baltimore) ; 103(17): e37898, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38669428

ABSTRACT

Nonischemic cardiomyopathy (NICM) is a major cause of advanced heart failure, and the morbidity and mortality associated with NICM are serious medical problems. However, the etiology of NICM is complex and the related mechanisms involved in its pathogenesis remain unclear. The microarray datasets GSE1869 and GSE9128 retrieved from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between NICM and normal samples. The co-expressed genes were identified using Venn diagrams. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene ontology enrichment were used to clarify biological functions and signaling pathways. Analysis of protein-protein interaction networks using Search Tool for the Retrieval of Interacting Genes/Proteins online to define the hub genes associated with NICM pathogenesis. A total of 297 DEGs were identified from GSE1869, 261 of which were upregulated genes and 36 were downregulated genes. A total of 360 DEGs were identified from GSE9128, 243 of which were upregulated genes and 117 were downregulated genes. In the 2 datasets, the screening identified 36 co-expressed DEGs. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis showed that DEGs were mainly enriched in pantothenate and CoA biosynthesis, beta-alanine metabolism, kinetochore, G-protein beta/gamma-subunit complex, and other related pathways. The PPI network analysis revealed that DUSP6, EGR1, ZEB2, and XPO1 are the 4 hub genes of interest in the 2 datasets. Bioinformatics analysis of hub genes and key signaling pathways is an effective way to elucidate the mechanisms involved in the development of NICM. The results will facilitate further studies on the pathogenesis and therapeutic targets of NICM.


Subject(s)
Cardiomyopathies , Computational Biology , Protein Interaction Maps , Cardiomyopathies/genetics , Humans , Computational Biology/methods , Protein Interaction Maps/genetics , Gene Expression Profiling/methods , Gene Regulatory Networks , Signal Transduction/genetics , Gene Ontology , Databases, Genetic
18.
Theranostics ; 14(6): 2345-2366, 2024.
Article in English | MEDLINE | ID: mdl-38646645

ABSTRACT

Rationale: Primordial follicles are limited in number and cannot be regenerated, dormant primordial follicles cannot be reversed once they enter a growth state. Therefore, the length of the female reproductive lifespan depends on the orderly progression and selective activation of primordial follicles, the mechanism of which remains unclear. Methods: We used human ovarian cortical biopsy specimens, granulosa cells from diminished ovarian reserve (DOR) patients, Hdac6-overexpressing transgenic mouse model, and RNA sequencing to analyze the crucial roles of histone deacetylase 6 (HDAC6) in fertility preservation and primordial follicle activation. Results: In the present study, we found that HDAC6 was highly expressed in most dormant primordial follicles. The HDAC6 expression was reduced accompanying reproductive senescence in human and mouse ovaries. Overexpression of Hdac6 delayed the rate of primordial follicle activation, thereby prolonging the mouse reproductive lifespan. Short-term inhibition of HDAC6 promoted primordial follicle activation and follicular development in humans and mice. Mechanism studies revealed that HDAC6 directly interacted with NGF, reducing acetylation modification of NGF and thereby accelerating its ubiquitination degradation. Consequently, the reduced NGF protein level maintained the dormancy of primordial follicles. Conclusions: The physiological significance of the high expression of HDAC6 in most primordial follicles is to reduce NGF expression and prevent primordial follicle activation to maintain female fertility. Reduced HDAC6 expression increases NGF expression in primordial follicles, activating their development and contributing to reproduction. Our study provides a clinical reference value for fertility preservation.


Subject(s)
Histone Deacetylase 6 , Mice, Transgenic , Nerve Growth Factor , Ovarian Follicle , Ubiquitination , Animals , Female , Humans , Mice , Acetylation , Granulosa Cells/metabolism , Histone Deacetylase 6/metabolism , Histone Deacetylase 6/genetics , Nerve Growth Factor/metabolism , Ovarian Follicle/metabolism
19.
Int J Biol Macromol ; 268(Pt 1): 131781, 2024 May.
Article in English | MEDLINE | ID: mdl-38657924

ABSTRACT

Alternative splicing is a crucial regulator in stem cell biology, intricately influencing the functions of various biological macromolecules, particularly pre-mRNAs and the resultant protein isoforms. This regulatory mechanism is vital in determining stem cell pluripotency, differentiation, and proliferation. Alternative splicing's role in allowing single genes to produce multiple protein isoforms facilitates the proteomic diversity that is essential for stem cells' functional complexity. This review delves into the critical impact of alternative splicing on cellular functions, focusing on its interaction with key macromolecules and how this affects cellular behavior. We critically examine how alternative splicing modulates the function and stability of pre-mRNAs, leading to diverse protein expressions that govern stem cell characteristics, including pluripotency, self-renewal, survival, proliferation, differentiation, aging, migration, somatic reprogramming, and genomic stability. Furthermore, the review discusses the therapeutic potential of targeting alternative splicing-related pathways in disease treatment, particularly focusing on the modulation of RNA and protein interactions. We address the challenges and future prospects in this field, underscoring the need for further exploration to unravel the complex interplay between alternative splicing, RNA, proteins, and stem cell behaviors, which is crucial for advancing our understanding and therapeutic approaches in regenerative medicine and disease treatment.


Subject(s)
Alternative Splicing , RNA Precursors , Stem Cells , Humans , RNA Precursors/genetics , RNA Precursors/metabolism , Animals , Stem Cells/metabolism , Stem Cells/cytology , Cell Differentiation/genetics
20.
Nanoscale ; 16(18): 8759-8777, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38619821

ABSTRACT

Cancer, the leading global cause of mortality, poses a formidable challenge for treatment. The effectiveness of cancer therapies, ranging from chemotherapy to immunotherapy, relies on the precise delivery of therapeutic agents to tumor tissues. Nanobiohybrids, resulting from the fusion of bacteria with nanomaterials, constitute a promising delivery system. Nanobiohybrids offer several advantages, including the ability to target tumors, genetic engineering capabilities, programmed product creation, and the potential for multimodal treatment. Recent advances in targeted tumor treatments have leveraged bacteria-based nanobiohybrids. Here, we outline the progress in cancer treatment using nanobiohybrids. Our focus is particularly on various therapeutic approaches within the context of nanobiohybrid systems, where bacteria are integrated with nanomaterials to combat cancer. It has been demonstrated that bacteria-based nanobiohybrids present a robust and effective method for tumor theranostics.


Subject(s)
Bacteria , Neoplasms , Neoplasms/therapy , Humans , Bacteria/metabolism , Animals , Drug Delivery Systems , Theranostic Nanomedicine , Immunotherapy , Nanostructures/chemistry , Nanostructures/therapeutic use
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