Generation of Human Epidermis-Derived Mesenchymal Stem Cell-like Pluripotent Cells and their reprogramming in mouse chimeras

Stem cells can be derived from the embryo (embryonic stem cells, ESCs), from adult tissues (adult stem cells, ASCs), and by induction of fibroblasts (induced pluripotent stem cells, iPSs). Ethical problems, immunological rejection, and difficulties in obtaining human tissues limit the use of ESCs in clinical medicine. Induced pluripotent stem cells are difficult to maintain in vitro and carry a greater risk of tumor formation. Furthermore, the complexity of maintenance and propagation is especially difficult in the clinic. Adult stem cells can be isolated from several adult tissues and present the possibility of self-transplantation for the clinical treatment of a variety of human diseases. Recently, several ASCs have been successfully isolated and cultured in vitro, including hematopoietic stem cells (HSCs) , mesenchymal stem cells (MSCs), epidermis stem cells, neural stem cells (NSCs), adipose-derived stem cells (ADSCs), islet stem cells, and germ line stem cells. Human mesenchymal stem cells originate mainly from bone marrow, cord blood, and placenta, but epidermis-derived MSCs have not yet been isolated. We isolated small spindle-shaped cells with strong proliferative potential during the culture of human epidermis cells and designed a medium to isolate and propagate these cells. They resembled MSCs morphologically and demonstrated pluripotency in vivo; thus, we defined these cells as human epidermis-derived mesenchymal stem cell-like pluripotent cells (hEMSCPCs). These hEMSCPCs present a possible new cell resource for tissue engineering and regenerative medicine

The impact of long-term exercise intervention on heart rate variability indices: a systematic meta-analysis

BackgroundHeart rate variability (HRV) is a critical indicator for assessing autonomic nervous system (ANS) function and is closely associated with both cardiovascular and psychological health. Although previous studies have demonstrated that exercise interventions can improve HRV, their effects vary considerably depending on exercise type, intervention characteristics, and individual differences. This meta-analysis aims to evaluate the impact of long-term exercise interventions on HRV and to explore potential factors that influence these effects.MethodsA systematic search was conducted in PubMed, Cochrane Library, EBSCO, CINAHL, Web of Science, and Embase up to November 20, 2024, to identify randomized controlled trials (RCTs) examining the effects of long-term exercise interventions on HRV. Studies involving short-term interventions, non-original research, or incomplete data were excluded. Two researchers independently performed data extraction and quality assessment. In total, 34 studies involving 1,434 participants were included.ResultsLong-term exercise interventions significantly reduced the LF/HF ratio (P < 0.05). Subgroup analyses indicated that the intervention effects were more pronounced in populations with existing health conditions and in interventions lasting ≥8 weeks. Aerobic training and resistance training demonstrated significant benefits.ConclusionLong-term exercise interventions significantly reduce the LF/HF ratio and improve ANS balance. These effects, however, are influenced by individual health status, intervention design, and control group conditions. The high heterogeneity among the included studies and limited data on certain intervention characteristics warrant cautious interpretation of the findings. Future research should focus on conducting more high-quality RCTs to validate these results.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, PROSPERO CRD42024541380

Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Zhanrong Li,1,* Xianghua Wu,1,* Jingguo Li,2 Lin Yao,1 Limei Sun,1 Yingying Shi,1 Wenxin Zhang,1 Jianxian Lin,1 Dan Liang,1 Yongping Li1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China*These authors contributed equally to this workBackground: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs) on retinoblastoma and to investigate the potential mechanisms involved.Methods: Celastrol-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-κB p65, and phospo-NF-κB p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma.Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an IC50 of 17.733 µg/mL (celastrol-loading content: 7.36%) after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-κB p65, and phospo-NF-κB p65 proteins decreased after exposure to CNPs 54.4 µg/mL for 48 hours. Additionally, the Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not significantly altered. CNPs inhibit the growth of retinoblastoma and induce apoptosis in retinoblastoma cells in mice.Conclusion: CNPs inhibit the growth of retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells, which may be related to the increased Bax/Bcl-2 ratio and the inhibition of NF-κB. CNPs may represent a potential alternative treatment for retinoblastoma.Keywords: apoptosis, SO-Rb 50 cells, poly(ethylene glycol)-block-poly(ε-caprolactone), nanopolymeric micelles, celastrol nanoparticles&nbsp

The Core Competencies in Emergency Management and Areas in Demand for Improvement in Community Public Health Emergency Responders amid COVID-19 Pandemic

BackgroundUnder the conditions of regular containment of COVID-19 epidemic, the levels of core competencies in emergency management of community public health emergency responders are directly associated with the effectiveness of management of public health emergencies. However, there are few studies on core competencies in emergency management of public health emergencies and areas in demand for improvement in community public health emergency responders.ObjectiveTo examine the core competencies in emergency management of COVID-19 pandemic, and associated factors as well as areas in demand for improvement within community public health emergency responders from Zhejiang Province.MethodsUsing the Core Response Competence Index System for Infectious Disease Emergencies among Medical Staff as a reference, we developed a questionnaire consisting of three parts: demographic and COVID-19 containment status, Core Competencies for Emergency Management of Public Health Emergencies (CCEMPHE) , and areas in demand for improvement, and used it to conduct an online survey with 749 community public health emergency responders selected from six counties (districts) of Zhejiang using stratified cluster sampling in September 2020.ResultsThe survey achieved a response rate of 93.3% (699/749) . The average score of CCEMPHE for the respondents was (118.38±27.60) , with a scoring rate of 62.3%. The scoring rates of three dimensions of the CCEMPHE from high to low were prevention ability (66.4%) , preparedness ability (63.7%) and rescue ability (62.0%) . Multiple linear regression analysis showed that education background (b=4.55) , physical quality for emergency work (b=9.26) , experiences of participating in developing emergency plan/technical proposal (b=6.43) , attending emergency training (b=6.35) , field epidemiology training (b=4.62) , on-site emergency disposal experience (b=5.32) , the number of theoretical trainings related to COVID-19 (b=4.29) , and the number of COVID-19 containment projects involved in (b=1.16) , were associated with the core competencies in emergency management of COVID-19 pandemic in community public health emergency responders (P<0.05) . In terms of areas in demand for improvement, the knowledge related to health emergency response and management (4.09±0.86) was in highest demand, on-site guidance (4.17±0.84) was the most popular training form and short-term training (3.93±0.92) was the most suitable training method.ConclusionThe community public health emergency responders in Zhejiang Province had lower intermediate CCEMPHE, and a high demand for improvement. To improve the core competencies in emergency management of infectious disease emergencies of community public health emergency responders, it is suggested to health administrators to strengthen practice trainings for these responders based on their needs, especially on-site practice trainings, with a focus on practical skill training

Characteristics and Evolutionary Analysis of Photosynthetic Gene Clusters on Extrachromosomal Replicons: from Streamlined Plasmids to Chromids.

Aerobic anoxygenic photoheterotrophic bacteria (AAPB) represent a bacteriochlorophyll a -containing functional group. Substantial evidence indicates that highly conserved photosynthetic gene clusters (PGCs) of AAPB can be transferred between species, genera, and even phyla. Furthermore, analysis of recently discovered PGCs carried by extrachromosomal replicons (exPGCs) suggests that extrachromosomal replicons (ECRs) play an important role in the transfer of PGCs. In this study, 13 Roseobacter clade genomes from seven genera that harbored exPGCs were used to analyze the characteristics and evolution of PGCs. The identification of plasmid-like and chromid-like ECRs among PGC-containing ECRs revealed two different functions: the spread of PGCs among strains and the maintenance of PGCs within genomes. Phylogenetic analyses indicated two independent origins of exPGCs, corresponding to PufC-containing and PufX-containing puf operons. Furthermore, the two different types of operons were observed within different strains of the same Tateyamaria and Jannaschia genera. The PufC-containing and PufX-containing operons were also differentially carried by chromosomes and ECRs in the strains, respectively, which provided clear evidence for ECR-mediated PGC transfer. Multiple recombination events of exPGCs were also observed, wherein the majority of exPGCs were inserted by replication modules at the same genomic positions. However, the exPGCs of the Jannaschia strains comprised superoperons without evidence of insertion and therefore likely represent an initial evolutionary stage where the PGC was translocated from chromosomes to ECRs without further combinations. Finally, a scenario of PGC gain and loss is proposed that specifically focuses on ECR-mediated exPGC transfer to explain the evolution and patchy distribution of AAPB within the Roseobacter clade. IMPORTANCE The evolution of photosynthesis was a significant event during the diversification of biological life. Aerobic anoxygenic photoheterotrophic bacteria (AAPB) share physiological characteristics with chemoheterotrophs and represent an important group associated with bacteriochlorophyll-dependent phototrophy in the environment. Here, characterization and evolutionary analyses were conducted for 13 bacterial strains that contained photosynthetic gene clusters (PGCs) carried by extrachromosomal replicons (ECRs) to shed light on the evolution of chlorophototrophy in bacteria. This report advances our understanding of the importance of ECRs in the transfer of PGCs within marine photoheterotrophic bacteria

Diagnostic and prognostic potential of the intra-tumoral microbiota profile in HPV-independent endocervical adenocarcinoma

BackgroundMicrobial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized.ObjectiveOur objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis.MethodsWe analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes.ResultsOur findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients.ConclusionThe study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome’s role in HPVI ECA

Intranasal methylene blue administration confers neuroprotection in rats subjected to exhaustive exercise training

IntroductionEmerging evidence suggests that exercise-induced fatigue negatively affects nervous system function, yet effective mitigation strategies are limited. This study aimed to determine whether intranasal methylene blue (MB) could prevent neurological deficits induced by exhaustive exercise in a rat model.MethodsWe utilized a rat exhaustive exercise training paradigm. Animal body weight was monitored, and a battery of behavioral tests was conducted to evaluate locomotor activity, anxiety-like behaviors, and spatial learning and memory. At the cellular level, we assessed neuron loss, apoptosis, synaptic proteins, myelin sheath, gliosis, and mitochondrial morphology in the hippocampal CA1 region and the striatum.ResultsRats subjected to exhaustive exercise exhibited reduced locomotor activity, increased anxiety-like behaviors, and impaired spatial memory. This was associated with significant neuron loss, activation of apoptotic pathways, loss of synaptic proteins and myelin sheath, gliosis, and compromised mitochondrial morphology in the hippocampus and striatum. Notably, intranasal MB treatment significantly rescued these neuronal damages and improved performance in behavioral tests.DiscussionOur findings demonstrate the neuroprotective effects of intranasal MB against exhaustive exercise-induced neurological deficits. This suggests that MB is a promising therapeutic agent for preventing the adverse neurological consequences of extreme physical exertion

Co-detection of azoxystrobin and thiabendazole fungicides in mold and mildew resistant wallboards and in children

The study measured the levels of azoxystrobin (AZ) and thiabendazole (TBZ) in wallboards and metabolite levels of these fungicides in children. The paper covering of wallboard samples contained a higher concentration of AZ and TBZ than the gypsum core, and similar amounts (w/w) of these two fungicides were present in the samples. These data suggest that commercial products containing a 1:1 (w/w) amount of AZ and TBZ, such as Sporgard® WB or Azo Tech„¢, were applied to the wallboard paper. This is the first detection of TBZ in mold-and-mildew resistant wallboards. The TBZ metabolite, 5OH-TBZ, was detected in 48% of urine samples collected from children aged 40-84 months, and was co-detected with AZ-acid, a common AZ metabolite, in 37.5% of the urine samples. The detection frequency of 5OH-TBZ was positively associated with the detection frequency of AZ-acid. These findings suggest that certain types of wallboards used in homes and commercial buildings may be a potential source of co-exposure to AZ and TBZ in humans