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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1091-1101, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621916

RESUMO

This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.


Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Humanos , Idoso , Reprodutibilidade dos Testes , Pneumonia/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Tosse/induzido quimicamente
2.
Stem Cells Dev ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623785

RESUMO

The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation, decreased ossification, and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. Additionally, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues.This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development, and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which Provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.

3.
Br J Haematol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632670

RESUMO

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

4.
Biomed Opt Express ; 15(4): 2451-2465, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38633098

RESUMO

Label-free detection of intracellular substances for living cancer cells remains a significant hurdle in cancer pathogenesis research. Although the sensitivity of light polarization to intracellular substances has been validated, current studies are predominantly focused on tissue lesions, thus label-free detection of substances within individual living cancer cells is still a challenge. The main difficulty is to find specific detection methods along with corresponding characteristic parameters. With refractive index as an endogenous marker of substances, this study proposes a detection method of intracellular refractive index distribution (IRID) for label-free living colon cancer (LoVo) cells. Utilizing the circular depolarization decay model (CDDM) to calculate the degree of circular polarization (DOCP) modulated by the cell allows for the derivation of the IRID on the focal plane. Experiments on LoVo cells demonstrated the refractive index of single cell can be accurately and precisely measured, with precision of 10-3 refractive index units (RIU). Additionally, chromatin content during the interphases (G1, S, G2) of cell cycle was recorded at 56.5%, 64.4%, and 71.5%, respectively. A significantly finer IRID can be obtained compared to the phase measurement method. This method is promising in providing a dynamic label-free intracellular substances detection method in cancer pathogenesis studies.

5.
Front Physiol ; 15: 1331693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606008

RESUMO

This study investigated whether exercise could improve the reduced HRV in an environment of high altitude. A total of 97 young, healthy male lowlanders living at 3,680 m for >1 year were recruited. They were randomized into four groups, of which three performed-low-, moderate-, and high-intensity (LI, MI, HI) aerobic exercise for 4 weeks, respectively. The remaining was the control group (CG) receiving no intervention. For HI, compared to other groups, heart rate (p = 0.002) was significantly decreased, while standard deviation of RR intervals (p < 0.001), SD2 of Poincaré plot (p = 0.046) and the number of successive RR interval pairs that differ by > 50 ms divided by total number of RR (p = 0.032), were significantly increased after intervention. For MI, significantly increase of trigonometric interpolation in NN interval (p = 0.016) was observed after exercise. Further, a decrease in systolic blood pressure (SBP) after high-intensity exercise was found significantly associated with an increase in SD2 (r = - 0.428, p = 0.042). These results indicated that there was a dose effect of different intensities of aerobic exercise on the HRV of acclimatized lowlanders. Moderate and high-intensity aerobic exercise would change the status of the autonomic nervous system (ANS) and decrease the blood pressure of acclimatized lowlanders exposed to high altitude.

7.
J Nutr Biochem ; : 109648, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631512

RESUMO

Insulin resistance (IR) is a global health challenge, often initiated by dysfunctional adipose tissue. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) may have different effects on IR, but the mechanisms are unknown. This study aims to evaluate the protective effect of EPA and DHA against IR in a high-fat diet (HFD) mice model and investigate whether EPA and DHA alter IR modulate the G-protein-poupled receptor 120/peroxisome proliferator-activated receptor γ (GPR120/PPARγ) pathway in macrophages and adipocytes, which may affect IR in adipocytes. The findings of this study show that 4% DHA had a better effect in improving IR and reducing inflammatory cytokines in adipose tissue of mice. Additionally, in the cell experiment, the use of AH7614 (a GPR120 antagonist) inhibited the glucose consumption increase and the increasable expression of PPARγ and insulin signaling molecules mediated by DHA in adipocytes. Furthermore, GW9662 (a PPARγ antagonist) hindered the upregulation of glucose consumption and insulin signaling molecule expression induced by EPA and DHA in adipocytes. DHA exhibited significant effects in reducing the number of migrated cells and inflammation. The compounds AH7614 and GW9662 hindered the suppressive effects of EPA and DHA on macrophage-induced IR in adipocytes. These findings suggest that DHA has a stronger potential in improving IR in adipocytes through the GPR120/PPARγ pathway in macrophages, when compared to EPA.

8.
Mol Ther ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38584391

RESUMO

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38597290

RESUMO

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor ß1 (siTGF-ß1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-ß1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-ß1, delivered by ASNPs, significantly silenced the expression of TGF-ß1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-ß1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

11.
J Orthop Surg Res ; 19(1): 227, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581052

RESUMO

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the standard procedure for the treatment of cervical spinal stenosis (CSS), but complications such as adjacent segment degeneration can seriously affect the long-term efficacy. Currently, posterior endoscopic surgery has been increasingly used in the clinical treatment of CSS. The aim of this study was to compare the clinical outcomes of single-segment CSS patients who underwent full endoscopic laminotomy decompression or ACDF. METHODS: 138 CSS patients who met the inclusion criteria from June 2018 to August 2020 were retrospectively analyzed and divided into endoscopic and ACDF groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the groups. Then, perioperative data were recorded and clinical outcomes were compared, including functional scores and imaging data. Functional scores included Visual Analog Scale of Arms (A-VAS) and Neck pain (N-VAS), Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), and imaging data included Disc Height Index (DHI), Cervical range of motion (ROM), and Ratio of grey scale (RVG). RESULTS: After PSM, 84 patients were included in the study and followed for 24-30 months. The endoscopic group was significantly superior to the ACDF group in terms of operative time, intraoperative blood loss, incision length, and hospital stay (P < 0.001). Postoperative N-VAS, A-VAS, JOA, and NDI were significantly improved in both groups compared with the preoperative period (P < 0.001), and the endoscopic group showed better improvement at 7 days postoperatively (P < 0.05). The ROM changes of adjacent segments were significantly larger in the ACDF group at 12 months postoperatively and at the last follow-up (P < 0.05). The RVG of adjacent segments showed a decreasing trend, and the decrease was more marked in the ACDF group at last follow-up (P < 0.05). According to the modified MacNab criteria, the excellent and good rates in the endoscopic group and ACDF group were 90.48% and 88.10%, respectively, with no statistically significant difference (P > 0.05). CONCLUSION: Full endoscopic laminotomy decompression is demonstrated to be an efficacious alternative technique to traditional ACDF for the treatment of single-segment CSS, with the advantages of less trauma, faster recovery, and less impact on cervical spine kinematics and adjacent segmental degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Fusão Vertebral , Estenose Espinal , Humanos , Estudos Retrospectivos , Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/cirurgia , Laminectomia , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Resultado do Tratamento , Seguimentos , Pontuação de Propensão , Fusão Vertebral/métodos , Discotomia/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Descompressão
13.
Int J Surg ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573115
14.
Neurol Res ; : 1-11, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602308

RESUMO

OBJECTIVE: To investigate the correlation between gender differences in plasma lipoprotein phospholipase A2 (Lp-PLA2) levels and the risk of recurrent stroke in patients with acute ischaemic stroke in China. METHODS: We conducted a prospective follow-up study that included baselineLp-PLA2 levels and NIH Stroke Scale (NIHSS) scores in patients with ischaemic stroke upon admission. The diagnostic efficacy of the baseline Lp-PLA2 level for stroke recurrence was evaluated. And Kaplan‒Meier method was used to analyse the difference in the risk of recurrent stroke between these two groups among males and females. A paired t test was used to analyse the difference in Lp-PLA2 levels in male and female patients after follow-up. RESULTS: Baseline plasma Lp-PLA2 was higher in men and women with recurrent stroke than in those without recurrent stroke. The correlation between baseline Lp-PLA2 and neurological impairment was higher in female than male stroke patients (R = 0.338 and 0.253, respectively). Although weakly correlated with neurological impairment, baseline Lp-PLA2 was more effective in predicting recurrent stroke (AUC = 0.705 in men, 0.788 in women). A Cox model was used to compare the risk of stroke between the high- and low-Lp-PLA2 groups (OR = 3.98 in men, 2.61 in women). According to the follow-up time of 6 months as the node, Lp-PLA2 will give different risk indicators. CONCLUSION: Elevated plasma Lp-PLA2 is an independent risk factor for recurrent ischaemic stroke but is not strongly associated with the degree of cerebral damage. The predictive value of baseline Lp-PLA2 for stroke recurrence risk was higher in females than in males.

16.
Pediatr Res ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575694

RESUMO

BACKGROUND: Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days. METHODS: Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.4 F who underwent an ED evaluation with blood and urine cultures. Models to predict IBI were developed and validated respectively using a random 80/20 dataset split, including 10-fold cross-validation. We used precision recall curves as the classification metric. RESULTS: Of 4411 eligible infants with a mean age of 37 days, 29% had characteristics that would likely have excluded them from existing risk stratification protocols. There were 196 patients with IBI (4.4%), including 43 (1.0%) with bacterial meningitis. Analytic approaches varied in performance characteristics (precision recall range 0.04-0.29, area under the curve range 0.5-0.84), with the XGBoost model demonstrating the best performance (0.29, 0.84). The five most important variables were serum white blood count, maximum temperature, absolute neutrophil count, absolute band count, and age in days. CONCLUSION: A machine learning model (XGBoost) demonstrated the best performance in predicting a rare outcome among febrile infants, including those excluded from existing algorithms. IMPACT: Several models for the risk stratification of febrile infants have been developed. There is a need for a preferred comprehensive model free from limitations and algorithm exclusions that accurately predicts IBIs. This is the first study to derive an all-inclusive predictive model for febrile infants aged 7-60 days in a community ED sample with IBI as a primary outcome. This machine learning model demonstrates potential for clinical utility in predicting IBI.

17.
MAbs ; 16(1): 2303781, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38475982

RESUMO

Early identification of antibody candidates with drug-like properties is essential for simplifying the development of safe and effective antibody therapeutics. For subcutaneous administration, it is important to identify candidates with low self-association to enable their formulation at high concentration while maintaining low viscosity, opalescence, and aggregation. Here, we report an interpretable machine learning model for predicting antibody (IgG1) variants with low viscosity using only the sequences of their variable (Fv) regions. Our model was trained on antibody viscosity data (>100 mg/mL mAb concentration) obtained at a common formulation pH (pH 5.2), and it identifies three key Fv features of antibodies linked to viscosity, namely their isoelectric points, hydrophobic patch sizes, and numbers of negatively charged patches. Of the three features, most predicted antibodies at risk for high viscosity, including antibodies with diverse antibody germlines in our study (79 mAbs) as well as clinical-stage IgG1s (94 mAbs), are those with low Fv isoelectric points (Fv pIs < 6.3). Our model identifies viscous antibodies with relatively high accuracy not only in our training and test sets, but also for previously reported data. Importantly, we show that the interpretable nature of the model enables the design of mutations that significantly reduce antibody viscosity, which we confirmed experimentally. We expect that this approach can be readily integrated into the drug development process to reduce the need for experimental viscosity screening and improve the identification of antibody candidates with drug-like properties.


Assuntos
Anticorpos Monoclonais , Imunoglobulina G , Anticorpos Monoclonais/química , Viscosidade , Imunoglobulina G/química , Mutação , Ponto Isoelétrico
18.
Artigo em Inglês | MEDLINE | ID: mdl-38498783

RESUMO

PURPOSE: To explore the contribution of paired-related homeobox 1-positive cells to the implant-induced osseointegration process in adult alveolar bone and the potential underlying mechanisms. MATERIALS AND METHODS: Cre recombinase-induced lineage tracing and cell ablation were conducted in a murine dental implant model. Scratch and transwell assays were used to assess MC3T3-E1 cell migration after paired-related homeobox 1 overexpression. Single-cell RNA sequencing were applied to identify potential genes involved in pairedrelated homeobox 1-positive cells-driven osteogenesis. RESULTS: Paired-related homeobox 1- positive cells were observed to accumulate in the peri-implant area in a time-dependent manner. The number of these cells were found to reach its maximum on day 14. Osseointegration in mice were noticeably impaired after ablation of paired-related homeobox 1-positive cells. Further, it was discovered that paired-related homeobox 1 promotes MC3T3- E1 cell migration, a process which is indispensable for sound healing of peri-implant tissue. Finally, Semaphorin 3C was detected exclusively and abundantly expressed by paired-related homeobox 1-positive cells. Knockdown of semaphorin 3C in paired-related homeobox 1- positive cells significantly weakened their osteogenic potential. CONCLUSION: Our data suggest that paired-related homeobox 1-positive cells contribute to the osseointegration process under stress stimulation and semaphorin 3C may play a critical role in paired-related homeobox 1- positive cell-driven osteogenesis. Paired-related homeobox 1 could significantly promote MC3T3-E1 cell migration.

19.
Oral Dis ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501171

RESUMO

OBJECTIVE: This study investigates the DP7-C/miR-26a complex as a stable entity resulting from the combination of miR-26a with the immunomodulatory peptide DP7-C. Our focus is on utilizing DP7-C loaded with miR-26a to modulate the immune microenvironment in bone and facilitate osteogenesis. METHODS: The DP7-C/miR-26a complex was characterized through transmission electron microscopy, agarose electrophoresis, and nanoparticle size potentiometer analysis. Transfection efficiency and cytotoxicity of DP7-C were assessed using flow cytometry and the CCK-8 assay. We validated the effects of DP7-C/miR-26a on bone marrow mesenchymal stem cells (BMSCs) and macrophages RAW 264.7 through gene expression and protein synthesis assays. A comprehensive evaluation of appositional bone formation involved micro-CT imaging, histologic analysis, and immunohistochemical staining. RESULTS: DP7-C/miR-26a, a nanoscale, and low-toxic cationic complex, demonstrated the ability to enter BMSCs and RAW 264.7 via distinct pathways. The treatment with DP7-C/miR-26a significantly increased the synthesis of multiple osteogenesis-related factors in BMSCs, facilitating calcium nodule formation in vitro. Furthermore, DP7-C/miR-26a promoted M1 macrophage polarization toward M2 while suppressing the release of inflammatory factors. Coculture studies corroborated these findings, indicating significant repair of rat skull defects following treatment with DP7-C/miR-26a. CONCLUSION: The DP7-C/miR-26a system offers a safer, more efficient, and feasible technical means for treating bone defects.

20.
bioRxiv ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38496556

RESUMO

Potential systemic factors contributing to aging-associated breast cancer (BC) remain elusive. Here, we reveal that the polyploid giant cells (PGCs) that contain more than two sets of genomes prevailing in aging and cancerous tissues constitute 5-10% of healthy female bone marrow mesenchymal stromal cells (fBMSCs). The PGCs can repair DNA damage and stimulate neighboring cells for clonal expansion. However, dying PGCs in advanced-senescent fBMSCs can form "spikings" which are then separated into membraned mtDNA-containing vesicles (Senescent PGC-Spiking Bodies; SPSBs). SPSB-phagocytosed macrophages accelerate aging with diminished clearance on BC cells and protumor M2 polarization. SPSB-carried mitochondrial OXPHOS components are enriched in BC of elder patients and associated with poor prognosis. SPSB-incorporated breast epithelial cells develop aggressive characteristics and PGCs resembling the polyploid giant cancer cells (PGCCs) in clonogenic BC cells and cancer tissues. These findings highlight an aging BMSC-induced BC risk mediated by SPSB-induced macrophage dysfunction and epithelial cell precancerous transition. SIGNIFICANCE: Mechanisms underlying aging-associated cancer risk remain unelucidated. This work demonstrates that polyploid giant cells (PGCs) in bone marrow mesenchymal stromal cells (BMSCs) from healthy female bone marrow donors can boost neighboring cell proliferation for clonal expansion. However, the dying-senescent PGCs in the advanced-senescent fBMSCs can form "spikings" which are separated into mitochondrial DNA (mtDNA)-containing spiking bodies (senescent PGC-spiking bodies; SPSBs). The SPSBs promote macrophage aging and breast epithelial cell protumorigenic transition and form polyploid giant cancer cells. These results demonstrate a new form of ghost message from dying-senescent BMSCs, that may serve as a systemic factor contributing to aging-associated immunosuppression and breast cancer risk.

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