Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 206
Filtrer
2.
Elife ; 122024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38900028

RÉSUMÉ

The long-trunked elephantids underwent a significant evolutionary stage characterized by an exceptionally elongated mandible. The initial elongation and subsequent regression of the long mandible, along with its co-evolution with the trunk, present an intriguing issue that remains incompletely understood. Through comparative functional and eco-morphological investigations, as well as feeding preference analysis, we reconstructed the feeding behavior of major groups of longirostrine elephantiforms. In the Platybelodon clade, the rapid evolutionary changes observed in the narial region, strongly correlated with mandible and tusk characteristics, suggest a crucial evolutionary transition where feeding function shifted from the mandible to the trunk, allowing proboscideans to expand their niches to more open regions. This functional shift further resulted in elephantids relying solely on their trunks for feeding. Our research provides insights into how unique environmental pressures shape the extreme evolution of organs, particularly in large mammals that developed various peculiar adaptations during the late Cenozoic global cooling trends.


The elephant's trunk is one of the most efficient food-gathering organs in the animal kingdom. From large branches to thin blades of grass, it can coil around and bring many types of vegetation to the animals' strong, short mandibles. This versatility allows elephants to thrive in a range of environments, including grasslands. Trunks are not the only spectacular feature to emerge in Proboscideans, the family of which elephants are the only surviving group. During the early and middle Miocene (between 23 to 11.6 million years ago), many of these species had dramatically elongated lower jaws; how and why this trait emerged then disappeared is poorly understood. The role that lengthened mandibles and trunks played during feeding also remains unclear. To address these questions, Li et al. focused on Platybelodon, Choerolophodon and Gomphotherium, which belong to three Proboscidean families that roamed Northern China between 17 and 15 million years ago. Each had elongated lower jaws, but with strikingly distinct lengths and morphologies. Chemical analyses on enamel samples helped determine which habitat the families occupied, while mathematical modelling revealed how their mandibles tackled different types of plants. Trunk shape was assessed via analyses of the nasal region. The results suggest that Choerolophodon had mandibles better suited for processing branches and a short, 'primitive' trunk. Gomphotherium sported a versatile jaw that could handle both grass and trees, as well as a rather 'elephant-like' trunk. The jaw of Platybelodon seemed well-adapted to cut grass, and remarkable bone structures point towards a long, strong and flexible trunk. While modern elephants fully depend on their trunks to eat, morphological constraints suggest that, in these species, the appendage only served to assist feeding (e.g., by pressing down on branches). All families shared an environment that included grasslands and forests, but analyses suggest that, for a period, Choerolophodon favored relatively closed habitats while Platybelodon spread into grasslands and Gomphotherium navigated both landscapes. This suggests that the evolution of long, strong and flexible trunks is tightly associated with grazing. About 14 million years ago, a global cooling event led to grasslands expanding worldwide. The fossil record shows the mandibles of Proboscideans starting to shorten after this period, including in the descendants of Gomphotherium that would give rise to modern elephants. The work by Li et al. sheds light onto these evolutionary processes, and the environmental pressures which helped shape the trunk.


Sujet(s)
Évolution biologique , Éléphants , Comportement alimentaire , Mandibule , Animaux , Mandibule/anatomie et histologie , Mandibule/physiologie , Comportement alimentaire/physiologie , Éléphants/physiologie , Éléphants/anatomie et histologie , Fossiles , Phylogenèse
3.
Reprod Health ; 21(1): 86, 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38886725

RÉSUMÉ

BACKGROUND: To discuss the current status of reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies. METHODS: A convenient sampling method was used to enroll 188 patients with gynecologic malignancies in Nanjing Maternity and Child Health Care Hospital, Nanjing Drum Tower Hospital, General Hospital of Ningxia Medical University, and Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from September 2022 to April 2023. Patients were assessed using general information questionnaire, Reproductive Concerns After Cancer Scale (RCAC), Fear of Cancer Recurrence Inventory (FCRI) questionnaire, and Perceived Social Support-Family (PSS-FA) Scale. RESULTS: Among patients of childbearing age with gynecologic malignancies, the total RCAC score was (54.35 ± 7.52), indicating a moderate level of reproductive concerns. Patients scored (20.98 ± 4.51) on FCRI, implying a moderate level of fear of recurrence. The PSS-FA score was (9.57 ± 2.76), denoting a moderate level of family support. The total score and each dimensional score of RCAC were positively correlated with FCRI total score (P < 0.05), and negatively correlated with PSS-FA total score (P < 0.05). Fear of recurrence, family support level, number of children, educational background, treatment modality, and fertility intention were influencing factors for reproductive concerns in patients of childbearing age with gynecologic malignancies (all P < 0.05). CONCLUSION: The reproductive concerns, fear of recurrence and family support are all at moderate levels in patients of childbearing age with gynecologic malignancies, and reproductive concerns are positively correlated with fear of recurrence and negatively correlated with family support.


Sujet(s)
Soutien familial , Peur , Tumeurs de l'appareil génital féminin , Récidive tumorale locale , Adolescent , Adulte , Femelle , Humains , Adulte d'âge moyen , Jeune adulte , Chine/épidémiologie , Peur/psychologie , Tumeurs de l'appareil génital féminin/psychologie , Récidive tumorale locale/psychologie , Enquêtes et questionnaires
4.
Medicine (Baltimore) ; 103(26): e38733, 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38941386

RÉSUMÉ

BACKGROUND: Dyskinesia is one of the most common complications of stroke. Acupuncture therapy (AT) and mirror therapy (MT) are promising rehabilitation measures for the treatment of post-stroke dyskinesia. Although some studies suggested that AT and MT are effective and safe for dyskinesia, the effects, and safety remain uncertain due to lacking strong evidence. The purpose of this study is to investigate the efficacy and safety of AT combined with MT in the treatment of post-stroke dyskinesia. METHODS: We searched the following databases: PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network, WANFANG, and China Biomedical Literature Database, from inception to 1 January 2023 to identify eligible studies. Total effective rate, the Fugl-Meyer assessment scale (FMA) upper and lower limb scores, modified Barthel index scores, Berg balance scale, modified Ashworth scale, and adverse reactions were adopted as outcome indicators. The Grading of Recommendations Assessment Development and Evaluation system was used by 2 independent reviewers to assess the quality of evidence for the outcome indicators included in the study. The statistical analysis was conducted by RevMan V.5.4 software. RESULTS: A total of 24 randomized controlled studies included 2133 patients with post-stroke dyskinesia were included. The total effective rate of AT combined with MT was more advantageous in the treatment of post-stroke dyskinesia (relative risk = 1.31, 95% confidence interval [CI] [1.22-1.42], Z = 6.96, P < .0001). AT combined with MT was more advantageous for FMA upper limb score (mean difference [MD] = 6.67, 95% CI [5.21-8.13], Z = 8.97, P < .00001) and FMA lower limb score (MD = 3.72, 95% CI [2.81-4.63], Z = 7.98, P < .00001). Meta-analysis showed that AT combined with MT for post-stroke dyskinesia had a more advantageous modified Barthel index score (MD = 9.51, 95% CI [7.44-11.58], Z = 9.01, P < .00001). CONCLUSION: AT combined with MT is effective in improving motor function and daily living ability of patients, especially in improving muscle spasms. However, these results should be regarded with caution given the low quality of evidence for the evaluation results.


Sujet(s)
Thérapie par acupuncture , Dyskinésies , Accident vasculaire cérébral , Humains , Thérapie par acupuncture/méthodes , Accident vasculaire cérébral/complications , Dyskinésies/étiologie , Dyskinésies/thérapie , Réadaptation après un accident vasculaire cérébral/méthodes , Essais contrôlés randomisés comme sujet , Association thérapeutique , Résultat thérapeutique
5.
Biochem Pharmacol ; 226: 116372, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38885773

RÉSUMÉ

MicroRNA and mitofusin-2 (Mfn2) play an important role in the myocardial apoptosis induced by acute myocardial infarction (AMI). However, the target relationship and underlying mechanism associated with interorganelle interaction between endoplasmic reticulum (ER) and mitochondria under ischemic condition is not completely clear. MI-induced injury, Mfn2 expression, Mfn2-mediated mitochondrial function and ER stress, and target regulation by miRNA-15b (miR-15b) were evaluated by animal MI and cellular hypoxic models with advanced molecular techniques. The results confirmed that Mfn2 was down-regulated and miR-15b was up-regulated upon the target binding profile under ischemic/hypoxic condition. Our data showed that miR-15b caused cardiac apoptotic injury that was reversed by rAAV9-anti-miR-15b or AMO-15b. The damage effect of miR-15b on Mfn2 expression and mitochondrial function was observed and rescued by rAAV9-anti-miR-15b or AMO-15b. The targeted regulation of miR-15b on Mfn2 was verified by luciferase reporter and microRNA-masking. Importantly, miR-15b-mediated Mfn2 suppression activated PERK/CHOP pathway, by which leads to ER stress and mitochondrial dysfunction, and cardiac apoptosis eventually. In conclusion, our research, for the first time, revealed the missing molecular link in Mfn2 and apoptosis and elucidated that pro-apoptotic miR-15b plays crucial roles during the pathogenesis of AMI through down-regulation of Mfn2 and activation of PERK-mediated ER stress. These findings may provide an opportunity to develop new therapies for prophylaxis and treatment of ischemic heart disease.


Sujet(s)
dGTPases , microARN , microARN/génétique , microARN/métabolisme , Animaux , dGTPases/génétique , dGTPases/métabolisme , Mâle , eIF-2 Kinase/métabolisme , eIF-2 Kinase/génétique , eIF-2 Kinase/antagonistes et inhibiteurs , Transduction du signal/physiologie , Ischémie myocardique/métabolisme , Ischémie myocardique/génétique , Ischémie myocardique/anatomopathologie , Souris , Stress du réticulum endoplasmique/physiologie , Stress du réticulum endoplasmique/génétique , Apoptose , Souris de lignée C57BL
6.
Environ Monit Assess ; 196(6): 576, 2024 May 24.
Article de Anglais | MEDLINE | ID: mdl-38789652

RÉSUMÉ

Phosphorus pollution poses a significant challenge in addressing water contamination. The coagulant is one of the effective methods to remove phosphorus from wastewater. Abundant Al and Fe oxides in sludge residue make it have great potential to synthesize water treatment coagulants. However, the utilization of sludge residue for preparation of coagulant was seldom investigated. In this study, we fabricated a novel coagulant, polyaluminum ferric chloride (SM-PAC), using sludge residue as a raw material through acid leaching and polymerization processes. Characterization results confirm that the parameters of SM-PAC meet the specifications outlined in the national standard (GB/T 22627-2022). We investigated the effects of pH, dosage, initial phosphorus concentration, and contact time on the removal efficiency of SM-PAC. As anticipated, the prepared SM-PAC exhibited a significant efficacy in removing phosphorus, meeting the discharge standards set for municipal sewage. Furthermore, the adsorption kinetics analysis suggests that the predominant mode of phosphorus adsorption on SM-PAC is chemical adsorption. Furthermore, the SM-PAC was employed in the actual wastewater treatment plant and exhibited excellent efficiency in phosphorus removal. The utilization of SM-PAC can not only effectively address the issue of sludge disposal but also achieve the goal of "treating waste with waste." It is expected that the proposed method of reusing sludge residue as a resource can provide a sustainable way to synthesize a coagulant for phosphorus removal.


Sujet(s)
Phosphore , Recyclage , Eaux d'égout , Élimination des déchets liquides , Polluants chimiques de l'eau , Phosphore/analyse , Phosphore/composition chimique , Eaux d'égout/composition chimique , Élimination des déchets liquides/méthodes , Polluants chimiques de l'eau/analyse , Polluants chimiques de l'eau/composition chimique , Recyclage/méthodes , Adsorption , Composés du fer III/composition chimique , Eaux usées/composition chimique
7.
Leukemia ; 38(6): 1334-1341, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38714876

RÉSUMÉ

We investigated data from 180 consecutive patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) who were diagnosed according to the 2022 World Health Organization (WHO) classification of myeloid neoplasms to identify covariates associated with survival. At a median follow-up of 48 months (95% confidence interval [CI] 35-61 months), the median survival was 69 months (95% CI 59-79 months). Patients with bone marrow ring sideroblasts (RS) < 15% had shorter median overall survival (OS) than did those with bone marrow RS ≥ 15% (41 months [95% CI 32-50 months] versus 76 months [95% CI 59-93 months]; P < 0.001). According to the univariable analyses of OS, age ≥ 65 years (P < 0.001), hemoglobin concentration (Hb) < 80 g/L (P = 0.090), platelet count (PLT) ≥ 800 × 10E + 9/L (P = 0.087), bone marrow RS < 15% (P < 0.001), the Revised International Prognostic Scoring System (IPSS-R) cytogenetic category intermediate/poor/very poor (P = 0.005), SETBP1 mutation (P = 0.061) and SRSF2 mutation (P < 0.001) were associated with poor survival. Based on variables selected from univariable analyses, two separate survival prediction models, a clinical survival model, and a clinical-molecular survival model, were developed using multivariable analyses with the minimum value of the Akaike information criterion (AIC) to specifically predict outcomes in patients with MDS/MPN-SF3B1-T according to the 2022 WHO classification.


Sujet(s)
Mutation , Maladies myélodysplasiques-myéloprolifératives , Phosphoprotéines , Facteurs d'épissage des ARN , Thrombocytose , Humains , Facteurs d'épissage des ARN/génétique , Mâle , Femelle , Thrombocytose/génétique , Sujet âgé , Phosphoprotéines/génétique , Adulte d'âge moyen , Maladies myélodysplasiques-myéloprolifératives/génétique , Maladies myélodysplasiques-myéloprolifératives/mortalité , Maladies myélodysplasiques-myéloprolifératives/anatomopathologie , Pronostic , Sujet âgé de 80 ans ou plus , Adulte , Taux de survie , Études de suivi , Syndromes myélodysplasiques/génétique , Syndromes myélodysplasiques/mortalité , Syndromes myélodysplasiques/anatomopathologie , Facteurs d'épissage riches en sérine-arginine/génétique
8.
Environ Sci Pollut Res Int ; 31(23): 34446-34458, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38703318

RÉSUMÉ

Underground coal gasification (UCG) is a promising technology, but the groundwater pollution caused by UCG is a potential risk to the environment. The measured results of the stratum in the combustion cavity resulting from UCG had proven that the combustion cavity would be filled with some UCG residues and caving rocks when UCG was finished. The pollutants in underground water around the combustion cavity include organic pollutants, inorganic pollutants, and ammonia nitrogen, and one of the primary organic pollutants is phenol. The migration and diffusion characteristics of organic pollutants (taking phenol as a representative) in the groundwater of the combustion cavity were investigated by breakthrough experiments and numerical simulations. The results show that the hydraulic conductivity of the coarse UCG residues is much higher than that of fine residues, and the hydraulic conductivity of the UCG residues with the size of - 0.15 mm and 0.15-0.3 mm are 4.68 × 10-6 m/s and 1.91 × 10-4 m/s respectively. The dispersivity λ for the migration of organic pollutants will be influenced significantly by the size of UCG residues in fractures of the combustion cavity, while the distribution coefficient Kd will not. The dispersivity of organic pollutants in the fine UCG residues is more significant than that in the coarse residues, and the λ for the two kinds of residues are 3.868 cm and 1.765 cm, respectively. The shape of the migration path slightly affects the pollutant concentration distribution along the path, but the width of a path has a more pronounced influence on the concentration distribution. In this research, the influence was formulated by a new technical term, MPWIT, which is related to transverse dispersion. Specifically, while the transverse dispersion values account for 20% and 10% of the longitudinal dispersion, respectively, the corresponding MPWIT values are 39.48 mm and 33.96 mm.


Sujet(s)
Charbon , Nappe phréatique , Polluants chimiques de l'eau , Nappe phréatique/composition chimique , Polluants chimiques de l'eau/analyse , Surveillance de l'environnement
9.
Clin Nucl Med ; 49(8): 777-778, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38768090

RÉSUMÉ

ABSTRACT: We present a case of pulmonary inflammatory pseudotumor with elevated 68 Ga-FAPI activity. Our case suggested that pulmonary inflammatory pseudotumor should be considered in the differential diagnosis of cancer-like solitary pulmonary nodules with increased 68 Ga-FAPI uptake.


Sujet(s)
Granulome à plasmocytes du poumon , Humains , Granulome à plasmocytes du poumon/imagerie diagnostique , Radio-isotopes du gallium , Femelle , Mâle , Adulte d'âge moyen , Tomographie par émission de positons couplée à la tomodensitométrie , Tomodensitométrie
10.
Front Oncol ; 14: 1373286, 2024.
Article de Anglais | MEDLINE | ID: mdl-38779097

RÉSUMÉ

Purpose: This study aimed to investigate the characteristics of various pulmonary lesions as revealed by 68Ga-FAPI PET/CT and to determine the utility of 68Ga-FAPI PET/CT in distinguishing the nature of these pulmonary lesions. Methods: A retrospective analysis was conducted on 99 patients with pulmonary lesions, who were categorized into three distinct groups: primary lung tumors (G1), metastatic lung tumors (G2), and benign lesions (G3). Each participant underwent a 68Ga-FAPI PET/CT scan. Among these groups, variables such as the Tumor/Background Ratio (TBR), Maximum Standardized Uptake Value (SUVmax), and the true positive rate of the lesions were compared. Furthermore, the FAPI uptake in nodular-like pulmonary lesions (d<3cm) and those with irregular borders was evaluated across the groups. A correlation analysis sought to understand the relationship between FAPI uptake in primary and pulmonary metastatic lesions. Results: The study's participants were composed of 52 males and 47 females, with an average age of 56.8 ± 13.2 years. A higher uptake and detection rate for pulmonary lesions were exhibited by Group G1 compared to the other groups (SUVmax [G1 vs. G2 vs. G3: 9.1 ± 4.1 vs. 6.1 ± 4.1 vs. 5.3 ± 5.8], P<0.05; TBR [G1 vs. G2 vs. G3: 6.2 ± 2.4 vs. 4.1 ± 2.2 vs. 3.2 ± 2.7], P<0.01; true positive rate 95.1% vs. 88% vs. 75.6%]. In nodular-like lung lesions smaller than 3 cm, G1 showed a significantly higher FAPI uptake compared to G2 and G3 (SUVmax [G1 vs. G2 vs. G3: 8.8 ± 4.3 vs. 5.2 ± 3.2 vs. 4.9 ± 6.1], P<0.01; TBR [G1 vs. G2 vs. G3: 5.7 ± 2.7 vs. 3.7 ± 2.1 vs. 3.3 ± 4.4], P<0.05). Both G1 and G2 demonstrated significantly elevated FAPI agent activity in irregular-bordered pulmonary lesions when compared to G3 (SUVmax [G1 vs. G2 vs. G3: 10.9 ± 3.3 vs. 8.5 ± 2.7 vs. 4.6 ± 2.7], P<0.01; TBR [G1 vs. G2 vs. G3: 7.2 ± 2.1 vs. 6.4 ± 1.3 vs. 3.2 ± 2.4], P<0.01). A positive correlation was identified between the level of 68Ga-FAPI uptake in primary lesions and the uptake in pulmonary metastatic lesions within G2 (r=0.856, P<0.05). Conclusion: 68Ga-FAPI PET/CT imaging proves to be of significant value in the evaluation of pulmonary lesions, offering distinctive insights into their nature.

11.
PLoS One ; 19(5): e0301468, 2024.
Article de Anglais | MEDLINE | ID: mdl-38718090

RÉSUMÉ

BACKGROUND: Aphasia is one of the most common complications of stroke. Mirror therapy (MT) is promising rehabilitation measure for the treatment of post-stroke aphasia. Although some studies suggested that MT is effective and safe for aphasia, the effects and safety remain uncertain due to lacking strong evidence, such as the relevant systematic review and meta- analysis. METHODS: This study will search PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network (CNKI), WANFANG, China Biomedical Literature Database (CBM), from inception to 1th May 2023 to identify any eligible study. No language or date of publication shall be limited. We will only include randomised controlled trials of MT in the Treatment of poststroke aphasia. Two investigators will work separately on the study selection, data extraction, and study quality assessment. The western aphasia battery (WAB) and aphasia quotient (AQ) will be included as the main outcomes. Boston diagnostic aphasia examination method (BDAE), Chinese standard aphasia examination (CRRCAE) will be included as the secondary outcomes. The statistical analysis will be conducted by RevMan V.5.4 software. The risk of bias of included studies will be assessed by the Cochrane 'Risk of bias' tool. The quality of proof of the results will be evaluated by using the Grading of Recommendations Assessment, Development and Evaluation guidelines. RESULTS: The finding will be presented in a journal or related conferences. CONCLUSION: This study will provide a basis for whether mirror therapy (MT) is effective and safe in the treatment of post-stroke aphasia. TRIAL REGISTRATION: Systematic review registration INPLASY registration number: INPLASY 202340054.


Sujet(s)
Aphasie , Méta-analyse comme sujet , Réadaptation après un accident vasculaire cérébral , Accident vasculaire cérébral , Revues systématiques comme sujet , Humains , Aphasie/étiologie , Aphasie/rééducation et réadaptation , Aphasie/thérapie , Accident vasculaire cérébral/complications , Réadaptation après un accident vasculaire cérébral/méthodes , Résultat thérapeutique , Essais contrôlés randomisés comme sujet
13.
Cell Death Dis ; 15(4): 282, 2024 Apr 20.
Article de Anglais | MEDLINE | ID: mdl-38643215

RÉSUMÉ

FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.


Sujet(s)
Adénocarcinome pulmonaire , Tumeurs du poumon , Humains , Animaux , Souris , Protéines proto-oncogènes c-akt/métabolisme , Phosphatidylinositol 3-kinases/métabolisme , Protéomique , Prolifération cellulaire , Adénocarcinome pulmonaire/anatomopathologie , Tumeurs du poumon/anatomopathologie , Sérine-thréonine kinases TOR/métabolisme , Lignée cellulaire tumorale , Mouvement cellulaire , Régulation de l'expression des gènes tumoraux , Protéines du muscle/métabolisme , SKP cullin F-box protein ligases/métabolisme , Phosphohydrolase PTEN/génétique , Phosphohydrolase PTEN/métabolisme
14.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1007-1016, 2024 Feb.
Article de Chinois | MEDLINE | ID: mdl-38621908

RÉSUMÉ

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.


Sujet(s)
Protéine HMGB1 , Ligusticum , Arthrose , Humains , Rats , Animaux , Facteur de transcription NF-kappa B/génétique , Facteur de transcription NF-kappa B/métabolisme , Chondrocytes , Caspase-3/métabolisme , Protéine Bax/métabolisme , Cyclooxygenase 2/génétique , Cyclooxygenase 2/métabolisme , Interleukine-1 bêta/génétique , Interleukine-1 bêta/métabolisme , Protéine HMGB1/génétique , Protéine HMGB1/métabolisme , Protéine HMGB1/pharmacologie , Dinoprostone , Facteur de différenciation myéloïde-88/métabolisme , Récepteur de type Toll-4/génétique , Récepteur de type Toll-4/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , Transduction du signal , Inflammation/métabolisme , Arthrose/traitement médicamenteux , Arthrose/génétique , Apoptose , ARN messager/métabolisme
15.
EJHaem ; 5(2): 333-345, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38633121

RÉSUMÉ

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

16.
J Mol Biol ; 436(10): 168559, 2024 May 15.
Article de Anglais | MEDLINE | ID: mdl-38580077

RÉSUMÉ

Upstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one of the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, or microproteins, encoded by uORFs were rarely studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functional microprotein (SLC35A4-MP) because of its conserved amino acid sequence. Through a series of biochemical and cellular experiments, we find that the 103-amino acid SLC35A4-MP is a single-pass transmembrane inner mitochondrial membrane (IMM) microprotein. The IMM contains the protein machinery crucial for cellular respiration and ATP generation, and loss of function studies with SLC35A4-MP significantly diminish maximal cellular respiration, indicating a vital role for this microprotein in cellular metabolism. The findings add SLC35A4-MP to the growing list of functional microproteins and, more generally, indicate that uORFs that encode conserved microproteins are an untapped reservoir of functional microproteins.


Sujet(s)
Membranes mitochondriales , Protéines mitochondriales , Transporteurs de nucléotides , Cadres ouverts de lecture , Humains , Régions 5' non traduites/génétique , Séquence d'acides aminés , Mitochondries/métabolisme , Mitochondries/génétique , Membranes mitochondriales/métabolisme , Protéines mitochondriales/métabolisme , Protéines mitochondriales/génétique , Cadres ouverts de lecture/génétique , Biosynthèse des protéines , ARN messager/génétique , ARN messager/métabolisme , Transporteurs de nucléotides/génétique , Transporteurs de nucléotides/métabolisme , Cellules HEK293
17.
Front Immunol ; 15: 1321406, 2024.
Article de Anglais | MEDLINE | ID: mdl-38469318

RÉSUMÉ

Background: The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has made significant contributions to fighting the epidemic in the past three years. However, the rapid development and application raised concerns about its safety in reproductive health, especially after several studies had observed a decrease in semen parameters following two doses of mRNA SARS-CoV-2 vaccination. Thus, it is necessary to comprehensively evaluate the effect of inactivated SARS-CoV-2 vaccine on male fertility. Methods: A retrospective cohort study was conducted in the Center for Reproductive Medicine of the Affiliated Hospital of Jining Medical University between July 2021 and March 2023. A total of 409 men with different vaccination status and no history of SARS-CoV-2 infection were included in this study. Their sex hormone levels and semen parameters were evaluated and compared separately. Results: The levels of FSH and PRL in one-dose vaccinated group were higher than other groups, while there were no significant changes in other sex hormone levels between the control and inactivated SARS-CoV-2 vaccinated groups. Most semen parameters such as volume, sperm concentration, total sperm count, progressive motility and normal forms were similar before and after vaccination with any single dose or combination of doses (all P > 0.05). Nevertheless, the total motility was significantly decreased after receiving the 1 + 2 doses of vaccine compared to before vaccination (46.90 ± 2.40% vs. 58.62 ± 2.51%; P = 0.001). Fortunately, this parameter was still within the normal range. Conclusion: Our study demonstrated that any single dose or different combined doses of inactivated SARS-CoV-2 vaccination was not detrimental to male fertility. This information could reassure men who want to conceive after vaccination and be incorporated into future fertility recommendations.


Sujet(s)
COVID-19 , Sperme , Humains , Mâle , Vaccins contre la COVID-19 , SARS-CoV-2 , Études rétrospectives , COVID-19/prévention et contrôle , Spermatozoïdes , Vaccination , Hormones sexuelles stéroïdiennes
18.
Sex Health ; 212024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38538087

RÉSUMÉ

Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.


Sujet(s)
COVID-19 , Humains , Mâle , COVID-19/prévention et contrôle , SARS-CoV-2 , Angiotensin-converting enzyme 2 , Peptidyl-Dipeptidase A , Fécondité , Hormones sexuelles stéroïdiennes , Vaccination
19.
Anticancer Drugs ; 35(5): 426-432, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38386015

RÉSUMÉ

The aim of this study was to investigate the utility of serum soluble B7-H3 (sB7-H3) as a diagnostic marker for early-stage nonsmall cell lung cancer (NSCLC) and its potential for evaluating the prognosis of patients with advanced-stage NSCLC. In this study, an ELISA was employed to detect the expression levels of sB7-H3 in a cohort of patients diagnosed with NSCLC ( n = 122) and a control group ( n = 42) during the same observation period. Comparative analyses were conducted to ascertain the variations in sB7-H3 concentrations between the NSCLC cohort and the healthy control group, as well as across pathological types and the presence and absence of lymph node metastasis. (1) The concentration of sB7-H3 in patients diagnosed with NSCLC exhibited a statistically significant increase compared to that observed in the healthy control group ( P < 0.05). Elevated expression levels of sB7-H3 demonstrated a significant correlation with pathological type, lymph node metastasis, tumor, node and metastasis stage and programmed cell death ligand (PD-L1) expression ( P < 0.05). (2) The diagnostic utility of sB7-H3 for the diagnosis of NSCLC and the heightened expression of PD-L1 demonstrated high levels of sensitivity and specificity. (3) Elevated levels of sB7-H3 emerged as an independent risk factor impacting the overall survival of patients diagnosed with advanced NSCLC. The findings of this study suggest that sB7-H3 holds promise as a diagnostic tool for early-stage NSCLC. The elevated expression of sB7-H3 appears to serve as a reliable indicator for assessing the prognosis of patients diagnosed with advanced NSCLC.


Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/diagnostic , Pronostic , Antigène CD274 , Tumeurs du poumon/diagnostic , Métastase lymphatique , Antigènes B7/métabolisme , Facteurs de transcription
20.
Small ; 20(30): e2310196, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38377307

RÉSUMÉ

"Perovskite / Carbon" interface has remained a key bottleneck for the hole-conductor-free perovskite solar cells based on carbon-electrode (CPSCs), due to problems like loose physics contact, defects, energy mismatch, poor chemical coupling, etc. A previous study shows that octylammonium iodide (OAI) blending in carbon paste induced a kind of "in-situ healing" effect for "perovskite / carbon" interface, and improved power conversion efficiency from ≈13% to >19%. Here the beneath mechanism is further explored by careful examination of the interaction between OAI molecule and carbon black (CB) nanoparticles. It comes to show that, the famous "CB adsorption" plays a key role during the "healing" processes. Due to CB adsorption behavior, the mass ratio between OAI and CB influences much on the healing effect. By suitably adjusting the mass ratio between OAI and CB, and increasing the light harvest of perovskite, an efficiency of 19.41% is achieved for the hole-conductor-free CPSCs. Device efficiency and the charge-extraction and recombination process are tracked with the storage period, continuous improvement appears for devices assembled by relatively higher CB mass. A kind of "slow-release effect" is revealed during the OAI-induced "in-situ healing" process, which is caused by the famous "CB adsorption" behavior.

SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE