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1.
Eur J Med Chem ; 270: 116356, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38579621

RESUMO

The heat shock protein 90 kDa (Hsp90) molecular chaperone machinery is responsible for the folding and activation of hundreds of important clients such as kinases, steroid hormone receptors, transcription factors, etc. This process is dynamically regulated in an ATP-dependent manner by Hsp90 co-chaperones including a group of tetratricopeptide (TPR) motif proteins that bind to the C-terminus of Hsp90. Among these TPR containing co-chaperones, FK506-binding protein 51 kDa (FKBP51) is reported to play an important role in stress-related pathologies, psychiatric disorders, Alzheimer's disease, and cancer, making FKBP51-Hsp90 interaction a potential therapeutic target. In this study, we report identification of potent and selective inhibitors of FKBP51-Hsp90 protein-protein interaction using a structure-based virtual screening approach. Upon in vitro evaluation, the identified hits show a considerable degree of selectivity towards FKBP51 over other TPR proteins, particularly for highly homologous FKBP52. Tyr355 of FKBP51 emerged as an important contributor to inhibitor's specificity. Additionally, we demonstrate the impact of these inhibitors on cellular energy metabolism, and neurite outgrowth, which are subjects of FKBP51 regulation. Overall, the results from this study highlight a novel pharmacological approach towards regulation of FKBP51 function and more generally, Hsp90 function via its interaction with TPR co-chaperones.


Assuntos
Proteínas de Choque Térmico HSP90 , Proteínas de Ligação a Tacrolimo , Humanos , Ligação Proteica , Proteínas de Ligação a Tacrolimo/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Chaperonas Moleculares , Fatores de Transcrição/metabolismo
2.
J Transl Med ; 22(1): 252, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459493

RESUMO

BACKGROUND: Albuminuria, the presence of excess of protein in urine, is a well-known risk factor for early kidney damage among diabetic/prediabetic patients. There is a complex interaction between physical activity (PA) and albuminuria. However, the relationship of specific-domain PA and albuminuria remained obscure. METHODS: Albuminuria was defined as urinary albumin/creatinine ratio (ACR) > 30 mg/g. PA was self-reported by participants and classified into transportation-related PA (TPA), occupation-related PA (OPA), and leisure-time PA (LTPA). Weighted logistic regression was conducted to compute the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate the dose-response of PA domains with the risk of albuminuria. RESULTS: A total of 6739 diabetic/prediabetic patients (mean age: 56.52 ± 0.29 years) were enrolled in our study, including 3181 (47.20%) females and 3558 (52.80%) males. Of them, 1578 (23.42%) were identified with albuminuria, and 5161(76.58%) were without albuminuria. Diabetic/prediabetic patients who adhered the PA guidelines for total PA had a 22% decreased risk of albuminuria (OR = 0.78, 95%CI 0.64-0.95), and those met the PA guidelines for LTPA had a 28% decreased of albuminuria (OR = 0.72, 95%CI 0.57-0.92). However, OPA and TPA were both not associated with decreased risk of albuminuria. RCS showed linear relationship between the risk of albuminuria with LTPA. CONCLUSIONS: Meeting the PA guideline for LTPA, but not OPA and TPA, was inversely related to the risk of albuminuria among diabetic/prediabetic patients. Additionally, achieving more than 300 min/week of LTPA conferred the positive effects in reducing albuminuria among diabetic/prediabetic patients.


Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Albuminúria/complicações , Exercício Físico/fisiologia
3.
Future Oncol ; 20(7): 381-392, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456312

RESUMO

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to play a diagnostic and predictive role in gestational trophoblastic disease. However, the conclusions are still ambiguous. This meta-analysis aimed to evaluate the combined predictive value of NLR and PLR in the malignant progression of gestational trophoblastic disease. Method: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and China Biomedical Literature Database were searched for the relevant literature published up to 1 October 2022. Study selection and data extraction were performed independently by two reviewers. All analyses were performed using Revman, MetaDisc and STATA software. Results: A total of 858 patients from five studies were included in this meta-analysis. The pooled sensitivity and specificity of NLR were 0.8 (95% CI: 0.71-0.88) and 0.73 (95% CI: 0.69-0.76), respectively, and the area under curve of the summary receiver operating curve was 0.81. The pooled sensitivity and specificity of PLR were 0.87 (95% CI: 0.75-0.95) and 0.49 (95% CI: 0.44-0.54), respectively, and the area under curve of the summary receiver operating curve was 0.88. I2 statistic and Deek's funnel plot showed no heterogeneity and publication bias. Conclusion: NLR can accurately predict the progression from hydatidiform mole to gestational trophoblastic neoplasia and is a promising biomarker in further follow-up.


Assuntos
Doença Trofoblástica Gestacional , Gravidez , Feminino , Humanos , Doença Trofoblástica Gestacional/diagnóstico , Sensibilidade e Especificidade , Biomarcadores , China
4.
Urol Oncol ; 42(5): 144-154, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38485644

RESUMO

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Adenocarcinoma/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Proliferação de Células
5.
Artigo em Inglês | MEDLINE | ID: mdl-38551438

RESUMO

Background: Deep vein thrombosis is a common complication after surgery, particularly in cancer patients, necessitating efficient diagnostic methods for timely intervention. Objective: This study aimed to investigate the potential of combining C-reactive protein (CRP) and interleukin-6 (IL-6) tests in diagnosing deep vein thrombosis (DVT) following endometrial cancer surgery. Methods: A cohort of 60 patients who developed DVT post-endometrial cancer surgery and were admitted to the First Hospital of Hebei Medical University between March 2018 and March 2022 constituted the DVT group. Additionally, 60 patients who underwent endometrial cancer surgery during the same period but did not develop DVT formed the non-DVT group. Serum levels of CRP and IL-6 were quantified and compared between the two groups using reliable laboratory techniques. Subsequently, the diagnostic accuracy of single-parameter testing (CRP or IL-6 alone) versus combined testing (CRP and IL-6) for postoperative DVT was assessed. Results: Analysis revealed significantly elevated levels of CRP and IL-6 in the serum of patients in the DVT group compared to those in the non-DVT group (P < .05). Furthermore, combined testing of CRP and IL-6 exhibited heightened sensitivity (0.85%), specificity (0.917%), and area under the curve (AUC) (0.952) compared to single-parameter testing alone, indicating its superiority in diagnosing postoperative DVT. Conclusions: The combination of CRP and IL-6 testing presents a promising diagnostic strategy for identifying postoperative DVT in endometrial cancer patients. Implementing this approach in clinical practice could facilitate early detection and prompt management of DVT, thereby potentially reducing associated morbidity and mortality.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38518150

RESUMO

Objective: Investigating the application effectiveness of using loop-mediated isothermal amplification (LAMP) on a microfluidic chip to detect the pathogens associated with ventilator-associated pneumonia (VAP). Methods: Eighty samples of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia (VAP) were collected at The First Hospital of Hebei Medical University from July 2022 to July 2023. The bacterial culture technique and the LAMP method were used to detect the nucleic acid of the pathogens in the patient samples. The positivity rates of bacterial culture and LAMP method in detecting VAP pathogens were analyzed. Results: A total of 80 specimens were examined, with 73 positive specimens detected using the LAMP method (positivity rate of 91.25%) and 60 positive specimens detected using bacterial culture (positivity rate of 75.00%). The LAMP method exhibited a higher number of positive detections compared to bacterial culture. Both methods showed a high level of concordance and were virtually identical in detecting methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Haemophilus influenzae, and Streptococcus pneumoniae. Conclusion: The LAMP method demonstrates significantly improved performance in the detection of pathogens for VAP, with a higher pathogen positivity rate compared to bacterial culture. This method holds promising prospects for clinical application.

7.
J Vis Exp ; (203)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38345257

RESUMO

Tumor antigen-specific CD8+ T cells from draining lymph nodes gain an accumulating importance in mounting anti-tumor immune response during tumorigenesis. However, in many cases, cancer cells form metastatic loci in lymph nodes before further metastasizing to distant organs. To what extent the local and systematic CD8+ T cell responses were influenced by LN metastasis remains obscure. To this end, we set up a murine LN metastasis model combined with a B16F10-GP melanoma cell line expressing the surrogate neoantigen derived from lymphocytic choriomeningitis virus (LCMV), glycoprotein (GP), and P14 transgenic mice harboring T cell receptors (TCRs) specific to GP-derived peptide GP33-41 presented by the class I major histocompatibility complex (MHC) molecule H-2Db. This protocol enables the study of antigen-specific CD8+ T cell responses during LN metastasis. In this protocol, C57BL/6J mice were subcutaneously implanted with B16F10-GP cells, followed by adoptive transfer with naive P14 cells. When the subcutaneous tumor grew to approximately 5 mm in diameter, the primary tumor was excised, and B16F10-GP cells were directly injected into the tumor draining lymph node (TdLN). Then, the dynamics of CD8+ T cells were monitored during the process of LN metastasis. Collectively, this model has provided an approach to precisely investigate the antigen-specific CD8+ T cell immune responses during LN metastasis.


Assuntos
Antígenos , Linfócitos T CD8-Positivos , Camundongos , Animais , Metástase Linfática , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Antígenos/metabolismo , Vírus da Coriomeningite Linfocítica , Glicoproteínas/metabolismo , Carcinogênese/metabolismo , Linfonodos
8.
Cell Commun Signal ; 22(1): 149, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402193

RESUMO

Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.


Assuntos
Apoptose , Imunidade Inata , Humanos , Piroptose , Inflamação , Citoplasma
9.
ACS Appl Mater Interfaces ; 16(8): 11013-11025, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38353218

RESUMO

Industrial robots are the main piece of equipment of intelligent manufacturing, and array-type tactile sensors are considered to be the core devices for their active sensing and understanding of the production environment. A great challenge for existing array-type tactile sensors is the wiring of sensing units in a limited area, the contradiction between a small number of sensing units and high resolution, and the deviation of the overall output pattern due to the difference in the performance of each sensing unit itself. Inspired by the human somatosensory processing hierarchy, we combine tactile sensors with artificial intelligence algorithms to simplify the sensor architecture while achieving tactile resolution capabilities far greater than the number of signal channels. The prepared 8-electrode carbon-based conductive network achieves high-precision identification of 32 regions with 97% classification accuracy assisted by a quadratic discriminant analysis algorithm. Notably, the output of the sensor remains unchanged after 13,000 cycles at 60 kPa, indicating its excellent durability performance. Moreover, the large-area skin-like continuous conductive network is simple to fabricate, cost-effective, and can be easily scaled up/down depending on the application. This work may address the increasing need for simple fabrication, rapid integration, and adaptable geometry tactile sensors for use in industrial robots.

10.
Acta Obstet Gynecol Scand ; 103(4): 636-644, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38282348

RESUMO

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) is a highly invasive tumor, mainly spreading to the lungs. However, lung metastasis in GTN is usually not considered as an adverse prognostic factor. Therefore, the aim of this study was to summarize the results of previous studies and evaluate the effects of lung metastasis on the treatment and prognosis of GTN. MATERIAL AND METHODS: The study was prospectively registered in PROSPERO (CRD42023372371). Electronic databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and China Biomedical Literature Database were used for a systematical search of relevant studies published up to November 21, 2022. The observational studies reporting the clinical outcomes of GTN patients with and without lung metastasis were selected. The incidences of resistance, relapse, and mortality of GTN patients were extracted and successively grouped based on the presence of lung metastasis. The pooled relative risks (RRs) and 95% confidence interval (95% CI) of the eligible studies were calculated. The qualities of included studies were assessed with the Newcastle-Ottawa Scale and the certainty of evidence was graded based on the GRADE. The meta-analysis was performed using Stata 12.0 and GradePro software. RESULTS: Five publications with 3629 GTN patients were included. The meta-analysis revealed that the GTN with lung metastasis was strongly correlated with first-line chemoresistance (pooled RR = 1.40, 95% CI: 1.22 to 1.61, p < 0.001), recurrence (pooled RR = 3.03, 95% CI: 1.21 to 7.62, p = 0.018), and disease-specific death (pooled RR = 22.11, 95% CI: 3.37 to 145.08, p = 0.001). Ethnicity was also an important factor and Caucasian GTN patients with lung metastasis showed a higher risk of recurrence as revealed by the subgroup analysis (pooled RR = 5.10, 95% CI: 2.38 to 10.94, p < 0.001). CONCLUSIONS: GTN patients with lung metastasis exhibited a higher risk of chemoresistance, relapse, and disease-specific death. Patients with lung metastasis among the Caucasian population had a higher risk of recurrence than Asian populations. Therefore, the presence of lung metastases might be considered as a high-risk factor for prognosis of GTN and deserves more attention in the choice of first-line chemotherapy regimens and follow-up.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Gravidez , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/patologia , Prognóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Fatores de Risco , Recidiva , Estudos Retrospectivos
11.
Mol Neurobiol ; 61(3): 1479-1494, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37726498

RESUMO

FK506-binding protein 51 kDa (FKBP51), encoded by Fkbp5 gene, gained considerable attention as an important regulator of several aspects of human biology including stress response, metabolic dysfunction, inflammation, and age-dependent neurodegeneration. Its catalytic peptidyl-prolyl isomerase (PPIase) activity is mediated by the N-terminal FK506-binding (FK1) domain, whereas the C-terminal tetratricopeptide motif (TPR) domain is responsible for FKBP51 interaction with molecular chaperone heat shock protein 90 (Hsp90). To understand FKBP51-related biology, several mouse models have been created. These include Fkbp5 complete and conditional knockouts, overexpression, and humanized models. To dissect the role of FKBP51-Hsp90 interaction in FKBP51 biology, we have created an interaction-deficient mouse (Fkbp5TPRmut) by introducing two-point mutations in the TPR domain of FKBP51. FKBP51-Hsp90 interaction-deficient mice are viable, fertile and show Mendelian inheritance. Intracellular association of FKBP51 with Hsp90 is significantly reduced in homozygous mutants compared to wild-type animals. No behavioral differences between genotypes were seen at 2 months of age, however, sex-dependent differences were detected in Y-maze and fear conditioning tests at the age of 12 months. Moreover, we have found a significant reduction in plasma levels of corticosterone and adrenocorticotropic hormone in Fkbp5TPRmut mice after acute stress. In contrast to Fkbp5 knockout mice, females of Fkbp5TPRmut showed increased body weight gain under high-fat diet treatment. Our data confirm the importance of FKBP51-Hsp90 interactions for stress-related endocrine signaling. Also, Fkbp5TPRmut mice can serve as a useful in vivo tool to discriminate between Hsp90-dependent and independent functions of FKBP51.


Assuntos
Dieta Hiperlipídica , Caracteres Sexuais , Animais , Feminino , Humanos , Lactente , Masculino , Camundongos , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo
12.
J Clin Pathol ; 77(5): 358-362, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38123348

RESUMO

We report a case of a middle-aged woman with a rapidly growing abdominal mass that was diagnosed as myxoid pleomorphic liposarcoma, a recently recognised, rare and aggressive subtype of liposarcoma. The tumour exhibits a combination of histological features from both myxoid liposarcoma and pleomorphic liposarcoma. Genetic analysis revealed mutations in TP53 and RB1, along with widespread loss of heterozygosity. However, no DDIT3 gene translocation or MDM2/CDK4 gene amplification was detected. These genetic characteristics can be used to distinguish this type of liposarcoma from others. Two unusual gene fusion/rearrangements, CREB5::TERT fusion and ETV1::LFNG rearrangement, were identified. The patient underwent complete removal of the tumour without the use of radiotherapy or chemotherapy. No recurrence was observed during the follow-up period of 18 months.


Assuntos
Lipossarcoma Mixoide , Lipossarcoma , Pessoa de Meia-Idade , Feminino , Adulto , Humanos , Lipossarcoma/genética , Lipossarcoma/patologia , Lipossarcoma Mixoide/genética , Lipossarcoma Mixoide/patologia , Mutação , Amplificação de Genes , Rearranjo Gênico , Translocação Genética
13.
Clin Chim Acta ; 553: 117730, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38141936

RESUMO

BACKGROUND AND AIMS: Metagenomic next-generation sequencing (mNGS) provided promising supports to rapid pathogen diagnosis. However, summary of scientific application strategy based on clinical practice study is still necessary for enhancing clinical benefits. MATERIALS AND METHODS: We conducted a retrospective analysis of 775 samples from patients with suspected infectious diseases (IDs). Based on final diagnosis, diagnostic performance, clinical relevance and clinical impact of mNGS among various clinical settings were assessed, and influencing factors were deeply explored. RESULTS: 84.26 % tests were clinically relevant; sample, but not sequencing, was the influencing factor. 40.77 % tests contributed to positive clinical impact, while 0.13 % and 59.10 % to negative and no impact respectively. mNGS utility in patients with IDs, definite infection site, BALF and CSF contributed to higher positive impacts. Days of empirical treatment before sampling ≤ 5 in ICU and ≤ 2 or between 11 and 20 in non-ICU, and reporting in 2 days brought about higher clinical benefit rates. Characteristic pathogen spectrum between ICU and non-ICU cases were revealed. CONCLUSIONS: Our findings highlighted clinical benefits from mNGS varied among different clinical settings, and elucidated choices on patients, samples, sampling and reporting time were four key factors. Rational strategy should be concerned to promote scientific application of mNGS and better improve clinical value.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
J Clin Pathol ; 77(2): 73-76, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38124011

RESUMO

The V-set and transmembrane domain containing 2A (VSTM2A) gene is located on chromosome 7. In the physiological state, VSTM2A regulates preadipocyte cell differentiation. VSTM2A is highly expressed in normal human brain tissue and minimally expressed in other normal tissues. Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a distinct renal tumour subtype with signature chromosomal copy number alterations and an indolent outcome in the majority of cases. VSTM2A overexpression is highly enriched in this renal cancer subtype and has been shown to have potential diagnostic value in distinguishing MTSCC from renal tumours with overlapping histological appearances.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Neoplasias Renais/patologia , Carcinoma de Células Renais/patologia , Rim/patologia , Diferenciação Celular , Adenocarcinoma Mucinoso/patologia
15.
Environ Sci Pollut Res Int ; 30(53): 113674-113687, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37851266

RESUMO

The rapid development of the Internet has significantly impacted various socio-economic activities. Using Chinese Industrial Enterprise database and Industrial Enterprise Pollution database, this research examines the impact and mechanisms of Internet development on CO2 emissions. The key findings are as follows: (1) Internet development has substantially reduced the CO2 intensity of enterprises, and this conclusion remains robust even after performing a series of robustness analyses. (2) The major mechanisms responsible for the reduction in CO2 emissions are productivity improvement, technological innovation, and energy structure adjustment. (3) The analysis of heterogeneity reveals that the effect of Internet development on CO2 reduction is more pronounced in coastal areas, areas with a high share of secondary industry, low-carbon industries, clean industries, small-scale enterprises, and export enterprises. This study provides empirical evidence supporting China's "Internet+" strategy and its progress towards achieving the "Carbon Peaking and Carbon Neutrality Goals."


Assuntos
Dióxido de Carbono , Carbono , Carbono/análise , Dióxido de Carbono/análise , Desenvolvimento Econômico , Poluição Ambiental , China
16.
Cell Mol Immunol ; 20(10): 1216-1231, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37644165

RESUMO

Although DNA mutation drives stem cell aging, how mutation-accumulated stem cells obtain clonal advantage during aging remains poorly understood. Here, using a mouse model of irradiation-induced premature aging and middle-aged mice, we show that DNA mutation accumulation in hematopoietic stem cells (HSCs) during aging upregulates their surface expression of major histocompatibility complex class II (MHCII). MHCII upregulation increases the chance for recognition by bone marrow (BM)-resident regulatory T cells (Tregs), resulting in their clonal expansion and accumulation in the HSC niche. On the basis of the establishment of connexin 43 (Cx43)-mediated gap junctions, BM Tregs transfer cyclic adenosine monophosphate (cAMP) to aged HSCs to diminish apoptotic priming and promote their survival via activation of protein kinase A (PKA) signaling. Importantly, targeting the HSC-Treg interaction or depleting Tregs effectively prevents the premature/physiological aging of HSCs. These findings show that aged HSCs use an active self-protective mechanism by entrapping local Tregs to construct a prosurvival niche and obtain a clonal advantage.


Assuntos
Células-Tronco Hematopoéticas , Linfócitos T Reguladores , Medula Óssea , Senescência Celular , DNA/metabolismo
17.
Brain Inj ; 37(11): 1235-1244, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37515578

RESUMO

OBJECTIVE: This study aims to explore the function of circRIMS in cerebral ischemia/reperfusion (CIR) and its regulatory mechanism. METHOD: The expression of the circRIMS was examined in GEO chip data and validated by qRT-PCR analysis. A middle cerebral artery occlusion/repression (MCAO/R) model was developed using C57BL/6J mice. Starbase and circinteractome were employed to identify the target miRNA and mRNA. The result was confirmed by dual-luciferase reporter assay, and biotinylated RNA-pulldown assay. The cell viability and apoptosis were confirmed through CCK-8 and flow cytometry assay. RESULTS: This study revealed that circRIMS expression was upregulated in MCAO mice model and OGD/RX-simulated cell model. Knockdown circRIMS demonstrated the functional of circRIMS in increasing cell viability, reducing apoptosis, LDH activity and inflammatory factors secretion in OGD/RX-simulated CIR injury in vitro. Additionally, miR-96-5p was identified as a target of circRIMS, while the STAT1 gene is a downstream gene of miR-96-5p, and JAK was also considered to be a downstream gene of the JAK-STAT pathway. Furthermore, inhibition of miR-96-5p or overexpression of STAT1 promoted the progression of CIR injury by elevating apoptosis, reducing cell viability, and increasing the secretion of inflammatory cytokines. CONCLUSION: CircRIMS contributes to the progression of CIR injury via regulating miR-96-5p/JAK/STAT1 axis.


Assuntos
Isquemia Encefálica , MicroRNAs , Traumatismo por Reperfusão , Camundongos , Animais , Regulação da Expressão Gênica , Janus Quinases/genética , Janus Quinases/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Isquemia Encefálica/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Glucose
18.
Molecules ; 28(10)2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37241821

RESUMO

The recycling of spent lithium-ion batteries (LIBs) has attracted great attention, mainly because of its significant impact on resource recycling and environmental protection. Currently, the processes involved in recovering valuable metals from spent LIBs have shown remarkable progress, but little attention has been paid to the effective separation of spent cathode and anode materials. Significantly, it not only can reduce the difficulty in the subsequent processing of spent cathode materials, but also contribute to the recovery of graphite. Considering the difference in their chemical properties on the surface, flotation is an effective method to separate materials, owing to its low-cost and eco-friendly characteristics. In this paper, the chemical principles of flotation separation for spent cathodes and materials from spent LIBs is summarized first. Then, the research progress in flotation separation of various spent cathode materials (LiCoO2, LiNixCoyMnzO2, and LiFePO4) and graphite is summarized. Given this, the work is expected to offer the significant reviews and insights about the flotation separation for high-value recycling of spent LIBs.

20.
Mar Pollut Bull ; 192: 114978, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37209659

RESUMO

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) are commonly found in the environment as components of brominated flame retardants. Due to their potential impact on human health and wildlife, it is imperative to closely monitor and manage their levels in the environment. This study investigated the spatial distribution, sources, and ecological risks of PBDEs and HBCDs in Jiaozhou Bay (JZB), a large bay situated on the eastern coast of China. The results showed that PBDE concentrations ranged from not detected (ND) to 7.93 ng/L in the water and ND to 65.76 ng/g in the sediment, while HBCD concentrations ranged from ND to 0.31 ng/L in the water and ND to 16.63 ng/g in the sediment. Furthermore, we observed significantly higher concentrations of PBDEs and HBCDs in the inner JZB compared to the outer JZB. Our source apportionment analysis showed that PBDEs primarily originated from the production and debromination of BDE-209, as well as the emission of commercial PeBDEs, whereas HBCDs in sediments mostly stemmed from anthropogenic activities and river input. Finally, our eco-logical risk assessment highlighted the need for continuous monitoring of PBDEs in JZB sediments. Overall, our study aims to provide valuable assistance for the environmental management of the JZB bay area, which is characterized by a complex net-work of rivers and a thriving economy.


Assuntos
Monitoramento Ambiental , Éteres Difenil Halogenados , Humanos , Éteres Difenil Halogenados/análise , Monitoramento Ambiental/métodos , China , Água/análise
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