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1.
Adv Sci (Weinh) ; : e2402804, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38953462

RÉSUMÉ

Understanding the regulation of normal erythroid development will help to develop new potential therapeutic strategies for disorders of the erythroid lineage. Cellular repressor of E1A-stimulated genes 1 (CREG1) is a glycoprotein that has been implicated in the regulation of tissue homeostasis. However, its role in erythropoiesis remains largely undefined. In this study, it is found that CREG1 expression increases progressively during erythroid differentiation. In zebrafish, creg1 mRNA is preferentially expressed within the intermediate cell mass (ICM)/peripheral blood island (PBI) region where primitive erythropoiesis occurs. Loss of creg1 leads to anemia caused by defective erythroid differentiation and excessive apoptosis of erythroid progenitors. Mechanistically, creg1 deficiency results in reduced activation of TGF-ß/Smad2 signaling pathway. Treatment with an agonist of the Smad2 pathway (IDE2) could significantly restore the defective erythroid development in creg1-/- mutants. Further, Klf1, identified as a key target gene downstream of the TGF-ß/Smad2 signaling pathway, is involved in creg1 deficiency-induced aberrant erythropoiesis. Thus, this study reveals a previously unrecognized role for Creg1 as a critical regulator of erythropoiesis, mediated at least in part by the TGF-ß/Smad2-Klf1 axis. This finding may contribute to the understanding of normal erythropoiesis and the pathogenesis of erythroid disorders.

2.
Intensive Care Med Exp ; 12(1): 58, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38954280

RÉSUMÉ

BACKGROUND: Treatment and prevention of intracranial hypertension (IH) to minimize secondary brain injury are central to the neurocritical care management of traumatic brain injury (TBI). Predicting the onset of IH in advance allows for a more aggressive prophylactic treatment. This study aimed to develop random forest (RF) models for predicting IH events in TBI patients. METHODS: We analyzed prospectively collected data from patients admitted to the intensive care unit with invasive intracranial pressure (ICP) monitoring. Patients with persistent ICP > 22 mmHg in the early postoperative period (first 6 h) were excluded to focus on IH events that had not yet occurred. ICP-related data from the initial 6 h were used to extract linear (ICP, cerebral perfusion pressure, pressure reactivity index, and cerebrospinal fluid compensatory reserve index) and nonlinear features (complexity of ICP and cerebral perfusion pressure). IH was defined as ICP > 22 mmHg for > 5 min, and severe IH (SIH) as ICP > 22 mmHg for > 1 h during the subsequent ICP monitoring period. RF models were then developed using baseline characteristics (age, sex, and initial Glasgow Coma Scale score) along with linear and nonlinear features. Fivefold cross-validation was performed to avoid overfitting. RESULTS: The study included 69 patients. Forty-three patients (62.3%) experienced an IH event, of whom 30 (43%) progressed to SIH. The median time to IH events was 9.83 h, and to SIH events, it was 11.22 h. The RF model showed acceptable performance in predicting IH with an area under the curve (AUC) of 0.76 and excellent performance in predicting SIH (AUC = 0.84). Cross-validation analysis confirmed the stability of the results. CONCLUSIONS: The presented RF model can forecast subsequent IH events, particularly severe ones, in TBI patients using ICP data from the early postoperative period. It provides researchers and clinicians with a potentially predictive pathway and framework that could help triage patients requiring more intensive neurological treatment at an early stage.

3.
Org Lett ; 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38975861

RÉSUMÉ

Presented herein is the exploration of a novel non-covalent anion-carbonyl (X-···C═O) interaction using aromatic imides as receptors and halides as lone pair donors. Combined theoretical calculations and experimental methods including 13C NMR, IR, and crystallographic analyses were performed to provide the physical origin and experimental evidence of anion-carbonyl interactions. The EDA analysis (energy decomposition analysis) based on DFT calculation indicates that electrostatic terms are the dominant contributions for the binding energy while electron delocalization also significantly contributes alongside the electrostatic attraction. Orbital interaction (n → π*) involving the delocalization of halide lone pairs on the carbonyl antibonding orbitals was visualized with NBO (Natural Bond Orbital) analysis. 13C NMR and IR spectra demonstrated upfield chemical shifts and red-shift frequency of hosts upon the addition of halides, reflecting the effect of orbital overlap between the halide lone pairs and π* of carbonyl (n → π* contribution). The anion-carbonyl interactions were directly revealed by X-ray structural analysis of anion and benzene triimide complexes.

4.
Cell Death Dis ; 15(7): 485, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38971772

RÉSUMÉ

The discovery of novel oncotargets for glioma is of immense significance. We here explored the expression patterns, biological functions, and underlying mechanisms associated with ORC6 (origin recognition complex 6) in glioma. Through the bioinformatics analyses, we found a significant increase in ORC6 expression within human glioma tissues, correlating with poorer overall survival, higher tumor grade, and wild-type isocitrate dehydrogenase status. Additionally, ORC6 overexpression is detected in glioma tissues obtained from locally-treated patients and across various primary/established glioma cells. Further bioinformatics scrutiny revealed that genes co-expressed with ORC6 are enriched in multiple signaling cascades linked to cancer. In primary and immortalized (A172) glioma cells, depleting ORC6 using specific shRNA or Cas9-sgRNA knockout (KO) significantly decreased cell viability and proliferation, disrupted cell cycle progression and mobility, and triggered apoptosis. Conversely, enhancing ORC6 expression via a lentiviral construct augmented malignant behaviors in human glioma cells. ORC6 emerged as a crucial regulator for the expression of key oncogenic genes, including Cyclin A2, Cyclin B2, and DNA topoisomerase II (TOP2A), within glioma cells. Silencing or KO of ORC6 reduced the mRNA and protein levels of these genes, while overexpression of ORC6 increased their expression in primary glioma cells. Bioinformatics analyses further identified RBPJ as a potential transcription factor of ORC6. RBPJ shRNA decreased ORC6 expression in primary glioma cells, while its overexpression increased it. Additionally, significantly enhanced binding between the RBPJ protein and the proposed ORC6 promoter region was detected in glioma tissues and cells. In vivo experiments demonstrated a significant reduction in the growth of patient-derived glioma xenografts in the mouse brain subsequent to ORC6 KO. ORC6 depletion, inhibited proliferation, decreased expression of Cyclin A2/B2/TOP2A, and increased apoptosis were detected within these ORC6 KO intracranial glioma xenografts. Altogether, RBPJ-driven ORC6 overexpression promotes glioma cell growth, underscoring its significance as a promising therapeutic target.


Sujet(s)
Prolifération cellulaire , Régulation de l'expression des gènes tumoraux , Gliome , Complexe ORC , Humains , Gliome/génétique , Gliome/anatomopathologie , Gliome/métabolisme , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Animaux , Complexe ORC/métabolisme , Complexe ORC/génétique , Tumeurs du cerveau/génétique , Tumeurs du cerveau/anatomopathologie , Tumeurs du cerveau/métabolisme , Souris nude , Souris , Apoptose/génétique , Cycline A2/métabolisme , Cycline A2/génétique , ADN topoisomérases de type II/métabolisme , ADN topoisomérases de type II/génétique , Cycline B2/métabolisme , Cycline B2/génétique , Mouvement cellulaire/génétique , Mâle
5.
Mol Cancer ; 23(1): 139, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38970106

RÉSUMÉ

BACKGROUND: Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. METHODS: The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. RESULTS: We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. CONCLUSIONS: Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.


Sujet(s)
5-Méthyl-cytosine , Protéines du cycle cellulaire , Régulation de l'expression des gènes tumoraux , Protéines et peptides de signalisation intracellulaire , ARN messager , Radiotolérance , Tumeurs du col de l'utérus , Tumeurs du col de l'utérus/génétique , Tumeurs du col de l'utérus/métabolisme , Tumeurs du col de l'utérus/radiothérapie , Tumeurs du col de l'utérus/anatomopathologie , Humains , Femelle , Radiotolérance/génétique , 5-Méthyl-cytosine/métabolisme , 5-Méthyl-cytosine/analogues et dérivés , Protéines du cycle cellulaire/génétique , Protéines du cycle cellulaire/métabolisme , Protéines et peptides de signalisation intracellulaire/génétique , Protéines et peptides de signalisation intracellulaire/métabolisme , Animaux , Souris , ARN messager/génétique , ARN messager/métabolisme , Lignée cellulaire tumorale , Pronostic , Tests d'activité antitumorale sur modèle de xénogreffe , Methyltransferases/génétique , Methyltransferases/métabolisme
6.
J Orthop Surg Res ; 19(1): 374, 2024 Jun 24.
Article de Anglais | MEDLINE | ID: mdl-38915048

RÉSUMÉ

BACKGROUND: The coronavirus disease 2019 (COVID-19) rapidly spreads worldwide and causes more suffering. The relation about the aggravation of inguinal pain and COVID-19 was unclear in patients with total hip arthroplasty (THA). This study aimed to evaluate the risk of groin pain aggravation in short-term THA patients after COVID-19. METHODS: Between 2020 and 2022, 129 patients with THA who were affected COVID-19 were enrolled. A short-standardized questionnaire was administered during follow-up to inquire about the aggravation of groin ache before and after SARS-COV-2 affection. Furthermore, we evaluated the potential association between the presence of increased pain and various factors, including age, gender, body mass index, diagnosis, and length of hospital stay. RESULTS: The case-crossover study revealed an increased risk of inguinal soreness aggravation when comparing 8 weeks after COVID-19 with 12 weeks before COVID-19 (Relative risk [RR], 9.5; 95% Confidence intervals [CI], 2.259-39.954). For COVID-19 positive patients, multivariate analysis showed length of stay was an independent factor significantly associated with increased risk of aggravation of groin pain (Odds ratio [OR], 1.26; 95%CI, 1.03-1.55, p = 0.027). CONCLUSION: This study confirms the association between COVID-19 and the exacerbation of soreness in the groin region in THA patients and extended length of stay is a possible contributing factor. This study expands the current literature by investigating the risk of aggravation of inguinal pain in patients with THA after COVID-19, providing valuable insights into postoperative outcomes in this specific population. Trial registration This retrospective study was approved by the Institutional Review Board of Shanghai general hospital (No.2023-264).


Sujet(s)
Arthroplastie prothétique de hanche , COVID-19 , Études croisées , Aine , Humains , COVID-19/complications , COVID-19/épidémiologie , Arthroplastie prothétique de hanche/effets indésirables , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Douleur postopératoire/étiologie , Douleur postopératoire/épidémiologie , Durée du séjour , Facteurs temps , Adulte , Sujet âgé de 80 ans ou plus , Facteurs de risque
7.
ACS Appl Mater Interfaces ; 16(25): 32481-32489, 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38875075

RÉSUMÉ

Rational control of the supramolecular aggregation of π-conjugated molecules plays an important role in determining their optoelectronic properties and applications. Here, we report a systematic study of the factors, including solvent polarity, concentration, and surfactants, that affect the aggregation behavior of a brominated hydroazaheptacene tetraimide (HATI) and its thiophene-substituted derivative, Th-HATI, as near-infrared fluorophores, in both nonpolar and polar solvents. The thermal stability of the aggregates is also studied by monitoring their optical absorption against temperature change. Our results indicate that the aggregation of HATI is highly sensitive to the solvent polarity. Moreover, the average aggregation number of HATI inside the colloidal nanoparticles formed in aqueous media can be controlled by surfactants. The substitution of the bromo groups in HATI by thiophene units induces a slight blue shift of the optical absorption, enhanced crystallinity, distinct aggregation behavior in both nonpolar and polar solvents, and improved thermal stability. The multifacet understanding of the supramolecular aggregation of these systems may offer insight for other π-conjugated molecular chromophores with various optoelectronic properties and applications.

8.
Anal Methods ; 16(25): 4150-4159, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38864437

RÉSUMÉ

Vegetable oil and animal fat residues are common evidence in the cases of homicide, arson, theft, and other crimes. However, the lipid composition and content changes during aging on complex carriers remain unclear. Therefore, this study dynamically monitored the lipid composition and content changes during aging of 13 different types of vegetable oils and animal fats on five different carriers using the UPLC-Q-Exactive Orbitrap MS method. A total of 6 subclasses of 93 lipids including lysophosphatidylcholine (2 species), phosphatidylcholine (2 species), diglyceride (5 species), triglyceride (81 species), acylGlcCampesterol ester (2 species), and acylGlcSitosterol ester (1 species), were first identified in fresh vegetable oils and animal fats. By comparing the LC-MS/MS chromatograms of fresh vegetable oils and animal fats, it was found that there were significant differences between the chromatograms of vegetable oils and animal fats, but it was difficult to distinguish between the chromatograms of vegetable oils or animal fats. After aging at 60 °C for 200 days, there was a significant decrease in the content of diglyceride, triglyceride, acylGlcCampesterol ester, and acylGlcSitosterol ester, while the content of lysophosphatidylcholine and phosphatidylcholine initially increased and then decreased. Furthermore, statistical analysis of lipid differences between vegetable oils and animal fats was performed using cluster heat maps, volcanic maps, PCA, and OPLS-DA. On average, 33 significantly different lipids were screened (VIP > 1, p < 0.05), which could serve as potential biomarkers for distinguishing vegetable oils and animal fats. It was found that the potential biomarkers still existed during aging of vegetable oils and animal fats (100 and 200 days). This research provides important reference information for the identification of vegetable oil and animal fat residues in complex carriers at crime scenes.


Sujet(s)
Lipidomique , Huiles végétales , Huiles végétales/composition chimique , Huiles végétales/analyse , Animaux , Chromatographie en phase liquide à haute performance/méthodes , Lipidomique/méthodes , Lipides/analyse , Spectrométrie de masse en tandem/méthodes , Matières grasses/composition chimique , Matières grasses/analyse
9.
Dalton Trans ; 53(26): 10919-10927, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38888145

RÉSUMÉ

Electrochemical reduction of carbon dioxide (CO2) or carbon monoxide (CO) to valuable multi-carbon (C2+) products like acetate is a promising approach for a sustainable energy economy. However, it is still challenging to achieve high activity and selectivity for acetate production, especially in neutral electrolytes. Herein, a bioinspired hemin/Cu hybrid catalyst was developed to enhance the surface *CO coverage for highly efficient electroreduction of CO to acetate fuels. The hemin/Cu electrocatalyst exhibits a remarkable faradaic efficiency of 45.2% for CO-to-acetate electroreduction and a high acetate partial current density of 152.3 mA cm-2. Furthermore, the developed hybrid catalyst can operate stably at 200 mA cm-2 for 14.6 hours, producing concentrated acetate aqueous solutions (0.235 M, 2.1 wt%). The results of in situ Raman spectroscopy and theoretical calculations proved that the Fe-N4 structure of hemin could enhance the CO adsorption and enrich the local concentration of CO, thereby improving C-C coupling for acetate production. In addition, compared to the unmodified Cu catalysts, the Cu catalysts functionalized with cobalt phthalocyanine with a Co-N4 structure also exhibit improved acetate performance, proving the universality of this bioinspired molecule-enhanced strategy. This work paves a new way to designing bioinspired electrolysis systems for producing specific C2+ products from CO2 or CO electroreduction.

10.
Pestic Biochem Physiol ; 202: 105956, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38879338

RÉSUMÉ

Pepper southern blight, caused by Sclerotium rolfsii, is a devastating soil-borne disease resulting in significant loss to pepper, Capsicum annuum L. production. Here, we isolated an antagonistic bacterial strain XQ-29 with antifungal activity against S. rolfsii from rhizospheric soil of pepper. Combining the morphological and biochemical characteristics with the 16S rDNA sequencing, XQ-29 was identified as Streptomyces griseoaurantiacus. It exhibited an inhibition of 96.83% against S. rolfsii and displayed significant inhibitory effects on Botrytis cinerea, Phytophthora capsica and Rhizoctonia solani. Furthermore, XQ-29 significantly reduced the pepper southern blight by 100% and 70.42% during seedling and growth stages, respectively. The antifungal mechanism involved altering the mycelial morphology, disrupting cell wall and membrane integrity, accompanied by accumulation of reactive oxygen species and lipid peroxidation in S. rolfsii mycelia. Furthermore, XQ-29 promoted growth and stimulated resistance of pepper plants by increasing defense-related enzyme activities and upregulating defense-related genes. Correspondingly, XQ-29 harbors numerous functional biosynthesis gene clusters in its genome, including those for siderophores and melanin production. The metabolic constituents present in the ethyl acetate extracts, which exhibited an EC50 value of 85.48 ± 1.62 µg/mL, were identified using LC-MS. Overall, XQ-29 demonstrates significant potential as a biocontrol agent against southern blight disease.


Sujet(s)
Botrytis , Capsicum , Maladies des plantes , Rhizoctonia , Streptomyces , Maladies des plantes/microbiologie , Maladies des plantes/prévention et contrôle , Capsicum/microbiologie , Streptomyces/génétique , Streptomyces/physiologie , Botrytis/effets des médicaments et des substances chimiques , Botrytis/physiologie , Rhizoctonia/physiologie , Rhizoctonia/effets des médicaments et des substances chimiques , Basidiomycota/physiologie , Phytophthora/physiologie , Phytophthora/effets des médicaments et des substances chimiques , Agents de lutte biologique/pharmacologie , Antifongiques/pharmacologie
11.
Science ; 384(6700): 1100-1104, 2024 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-38843317

RÉSUMÉ

One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley-Queisser limit efficiency in solar energy harvest within p-n junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS2 ribbon arrays with defined chirality and coherent polarity through an atomic manufacturing strategy. The chirality of WS2 ribbon was defined by substrate couplings into tunable armchair, zigzag, and chiral species, and the polarity direction was determined by the ribbon-precursor interfacial energy along a coherent direction. A single armchair ribbon showed strong bulk photovoltaic effect and the further integration of ~1000 aligned ribbons with coherent polarity enabled upscaling of the photocurrent.

12.
J Thorac Dis ; 16(5): 3213-3227, 2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38883654

RÉSUMÉ

Background: Although immunotherapy has revolutionized the treatment landscape of lung cancer and improved the prognosis of this malignancy, many patients with lung cancer still are not able to benefit from it because of many different reasons. The expression of programmed death ligand-1 (PD-L1) in tumor cells has been approved for the prediction of immunotherapy efficacy; however, its clinical application has been limited by the invasiveness of PD-L1 determination and the heterogeneity of tumor cells. As a promising technology, radiomics has made significant progress in the diagnosis and treatment of lung cancer. Thus, we constructed a noninvasive predictive model which based on radiomics to predict the immunotherapy efficacy of lung caner patients. Methods: Data of 82 patients with stage IIIa/IVb NSCLC who received immunotherapy at the First Affiliated Hospital of Soochow University from December 2019 to January 2023 were retrospectively collected. These patients were followed up for durable clinical benefit (DCB), as defined by whether progression-free survival (PFS) reached 12 months. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen for the radiomic features in the training set, and a radiomics score (Rad-score) was calculated. The clinical baseline data were analyzed, and the peripheral blood inflammation indices were calculated. Univariate and multivariate analyses were performed to identify the applicable indices, which were combined with the Rad-score to create a comprehensive forecasting model (CFM) and nomograms. Internal validation was performed in the validation set. Results: Up to the last follow-up time, 48 of 82 patients had a PFS of more than 12 months. The area under the receiver operating characteristic (ROC) curve (AUC) of the Rad-score was 0.858 and 0.812, respectively, in the training set and validation set. A systemic immune-inflammation index (SII) score of <500.88 after two cycles of immunotherapy was a protective factor for PFS >12 months [odds ratio (OR) 0.054; P=0.003]. The CFM had an AUC of 0.930 and 0.922, respectively, in the training and validation sets. The calibration curves and decision curve analysis (DCA) demonstrated the reliability and clinical applicability of the model, respectively. Conclusions: The radiomics model performed well in predicting whether patients with locally advanced or metastatic NSCLC can achieve DCB after receiving immunotherapy. The CFM had good predictive performance and reliability.

13.
Materials (Basel) ; 17(11)2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38894019

RÉSUMÉ

Microplastics (MPs) pose a profound environmental challenge, impacting ecosystems and human health through mechanisms such as bioaccumulation and ecosystem contamination. While traditional water treatment methods can partially remove microplastics, their limitations highlight the need for innovative green approaches like photodegradation to ensure more effective and sustainable removal. This review explores the potential of nanomaterial-enhanced photocatalysts in addressing this issue. Utilizing their unique properties like large surface area and tunable bandgap, nanomaterials significantly improve degradation efficiency. Different strategies for photocatalyst modification to improve photocatalytic performance are thoroughly summarized, with a particular emphasis on element doping and heterojunction construction. Furthermore, this review thoroughly summarizes the possible fundamental mechanisms driving the photodegradation of microplastics facilitated by nanomaterials, with a focus on processes like free radical formation and singlet oxygen oxidation. This review not only synthesizes critical findings from existing studies but also identifies gaps in the current research landscape, suggesting that further development of these photocatalytic techniques could lead to substantial advancements in environmental remediation practices. By delineating these novel approaches and their mechanisms, this work underscores the significant environmental implications and contributes to the ongoing development of sustainable solutions to mitigate microplastic pollution.

14.
Biol Reprod ; 2024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38900909

RÉSUMÉ

Cytoplasmic dynein participates in transport functions and is essential in spermatogenesis. KM23 belongs to the dynein light chain family. The TGFß signaling pathway is indispensable in spermatogenesis, and Smad2 is an important member of this pathway. We cloned PTKM23 and PTSMAD2 from Portunus trituberculatus and measured their expression during spermatogenesis. PTKM23 may be related to cell division, acrosome formation and nuclear remodeling, and PTSMAD2 may participate in regulating the expression of genes related to spermatogenesis. We assessed the localization of PTKM23 with PTDHC and α-Tubulin, and the results suggested that PTKM23 functions in intracellular transport during spermatogenesis. We knocked down PTKM23 in vivo, and the expression of p53, B-CATAENIN and CYCLIN B decreased significantly, further suggesting a role of PTKM23 in transport and cell division. The localization of PTDIC with α-Tubulin and that of PTSMAD2 with PTDHC changed after PTKM23 knockdown. We transfected PTKM23 and PTSMAD2 into HEK-293 T cells and verified their colocalization. These results indicate that PTKM23 is involved in the assembly of cytoplasmic dynein and microtubules during spermatogenesis and that PTKM23 mediates the participation of cytoplasmic dynein in the transport of PTSMAD2 during spermatogenesis. This study provides a theoretical molecular biological basis for the breeding of P. trituberculatus.

15.
Chem Biodivers ; : e202400934, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38898600

RÉSUMÉ

Ginseng saponins ( ginsenosides), bioactive compounds derived from ginseng, are widely used natural products with potent therapeutic properties in the management of various ailments, particularly tumors, cardiovascular and cerebrovascular diseases, and immune system disorders. Autophagy, a highly regulated and multistep process involving the breakdown of impaired organelles and macromolecules by autophagolysosomes and autophagy-related genes (ATGs), has gained increasing attention as a potential target for ginsenoside-mediated disease treatment. This review aims to provide a comprehensive overview of recent research advances in the understanding of autophagy-related signaling pathways and the role of ginsenoside-mediated autophagy regulation. By delving into the intricate autophagy signaling pathways underpinning the pharmacological properties of ginsenosides, we highlight their therapeutic potential in addressing various conditions. Our findings serve as a comprehensive reference for further investigation into the medicinal properties of ginseng or ginseng-related products.

16.
Behav Brain Res ; 471: 115097, 2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38878971

RÉSUMÉ

Neuroadaptive changes in the hippocampus underlie addictive-like behaviors in humans or animals chronically exposed to cocaine. miR-181a, which is widely expressed in the hippocampus, acts as a regulator for synaptic plasticity, while its role in drug reinstatement is unclear. In this study, we found that miR-181a regulates the reinstatement of cocaine conditioned place preference(CPP), and altered miR-181a expression changes the complexity of hippocampal neurons and the density and morphology of dendritic spines. By using a luciferase gene reporter, we found that miR-181a targets PRKAA1, an upstream molecule in the mTOR pathway. High miR-181a expression reduced the expression of the PRKAA1 mRNA and promoted mTOR activity and the reinstatement of cocaine CPP. These results indicate that miR-181a is involved in neuronal structural plasticity induced by reinstatement of cocaine CPP, possibly through the activation of the mTOR signaling pathway. This study provides new microRNA targets and a theoretical foundation for the prevention of cocaine-induced reinstatement.

17.
Chem Sci ; 15(22): 8311-8322, 2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38846391

RÉSUMÉ

Drug resistance in tumor cells remains a persistent clinical challenge in the pursuit of effective anticancer therapy. XIAP, a member of the inhibitor of apoptosis protein (IAP) family, suppresses apoptosis via its Baculovirus IAP Repeat (BIR) domains and is responsible for drug resistance in various human cancers. Therefore, XIAP has attracted significant attention as a potential therapeutic target. However, no XIAP inhibitor is available for clinical use to date. In this study, we surprisingly observed that arsenic trioxide (ATO) induced a rapid depletion of XIAP in different cancer cells. Mechanistic studies revealed that arsenic attacked the cysteine residues of BIR domains and directly bound to XIAP, resulting in the release of zinc ions from this protein. Arsenic-XIAP binding suppressed the normal anti-apoptosis functions of BIR domains, and led to the ubiquitination-dependent degradation of XIAP. Importantly, we further demonstrate that arsenic sensitized a variety of apoptosis-resistant cancer cells, including patient-derived colon cancer organoids, to the chemotherapy drug using cisplatin as a showcase. These findings suggest that targeting XIAP with ATO offers an attractive strategy for combating apoptosis-resistant cancers in clinical practice.

18.
Prep Biochem Biotechnol ; : 1-8, 2024 Jun 10.
Article de Anglais | MEDLINE | ID: mdl-38856714

RÉSUMÉ

To enhance the stability and light resistance of the yellow compounds in citrus pomace, our study successfully isolated and purified five compounds using ultrasonic-assisted extraction and column chromatography. The identified compounds include methyl linoleate, (2-ethyl)hexyl phthalate, 1,3-distearoyl-2-oleoylglycerol, 6,6-ditetradecyl-6,7-dihydroxazepin-2(3H)-one, and n-octadeca-17-enoic acid. The monomers extracted from fresh pomace, compounds 1 and 2, exhibit structural similarities to flavonoids and carotenoids. In contrast, the polymers isolated from fermented pomace, compounds 3, 4, and 5, share structural units with the fresh pomace compounds, indicating the transformation to stable polymeric forms. This suggests that the microbial fermentation process not only enhances the value of citrus pomace, but also provides a promising pathway for the synthesis of natural antioxidant yellow pigments with far-reaching theoretical and practical significance.

19.
Integr Med Res ; 13(2): 101045, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38831890

RÉSUMÉ

Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.

20.
Nat Commun ; 15(1): 5312, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38906856

RÉSUMÉ

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.


Sujet(s)
Exposition maternelle , Issue de la grossesse , Premier trimestre de grossesse , Naissance prématurée , Humains , Femelle , Grossesse , Chine/épidémiologie , Exposition maternelle/effets indésirables , Adulte , Naissance prématurée/épidémiologie , Études prospectives , Issue de la grossesse/épidémiologie , Dydrogestérone/effets indésirables , Progestérone , Cohorte de naissance , Nouveau-né , Avortement spontané/épidémiologie , Avortement spontané/induit chimiquement , Mortinatalité/épidémiologie , Nourrisson à faible poids de naissance , Études longitudinales , Incidence , Jeune adulte
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