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Nature Communications Jun 2024Phage predation is generally assumed to reduce microbial proliferation while not contributing to the spread of antibiotic resistance. However, this assumption does not...
Phage predation is generally assumed to reduce microbial proliferation while not contributing to the spread of antibiotic resistance. However, this assumption does not consider the effect of phage predation on the spatial organization of different microbial populations. Here, we show that phage predation can increase the spread of plasmid-encoded antibiotic resistance during surface-associated microbial growth by reshaping spatial organization. Using two strains of the bacterium Escherichia coli, we demonstrate that phage predation slows the spatial segregation of the strains during growth. This increases the number of cell-cell contacts and the extent of conjugation-mediated plasmid transfer between them. The underlying mechanism is that phage predation shifts the location of fastest growth from the biomass periphery to the interior where cells are densely packed and aligned closer to parallel with each other. This creates straighter interfaces between the strains that are less likely to merge together during growth, consequently slowing the spatial segregation of the strains and enhancing plasmid transfer between them. Our results have implications for the design and application of phage therapy and reveal a mechanism for how microbial functions that are deleterious to human and environmental health can proliferate in the absence of positive selection.
Topics: Plasmids; Escherichia coli; Bacteriophages; Drug Resistance, Bacterial; Anti-Bacterial Agents; Conjugation, Genetic
PubMed: 38926498
DOI: 10.1038/s41467-024-49840-7 -
Ecotoxicology and Environmental Safety Jun 2024Evidence linking nitrogen dioxide (NO) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This...
BACKGROUND
Evidence linking nitrogen dioxide (NO) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This study seeks to quantify mortality risk, excess deaths, and loss of life expectancy (LLE) associated with long-term exposure to NO among elderly individuals in China.
METHODS
A nationwide dynamic cohort of 20352 respondents ≥65 years old were enrolled from the China Longitudinal Health and Longevity Survey during 2005-2018. Residential exposures to NO and co-pollutants were assessed by well-validated spatiotemporal prediction models. A Cox regression model with time-dependent covariates was utilized to quantify the association of all-cause mortality with NO exposure, controlling for confounders such as demographics, lifestyle, health status, and ambient temperature. NO-attributable deaths and LLE were evaluated for the years 2010 and 2020 based on the pooled NO-mortality relation derived from multi-national cohort investigations. Decomposition analyses were conducted to dissociate net shift in NO-related deaths between 2010 and 2020 into four primary contributing factors.
RESULTS
A total of 14313 deaths were recorded during follow-up of approximately 100 hundred person-years (median 3.6 years). We observed an approximately linear relationship (nonlinear P = 0.882) of NO exposure with all-cause death across a broad range from 6.6 to 95.7 μg/m. Every 10-μg/m rise in yearly average NO concentration was linked to a hazard ratio (HR) of 1.045 (95% confidence interval [CI]: 1.031-1.059). In the updated meta-analysis of this study and 9 existing cohorts, we estimated a pooled HR of 1.043 (95% CI: 1.023-1.063) for each 10-μg/m growth in NO. Reaching a 10 -μg/m counterfactual target of NO concentration in China could avoid 0.33 (95% empirical CI: 0.19-0.49) million premature deaths and an LLE of 0.40 (95% empirical CI: 0.23-0.59) years in 2010, which greatly dropped to 0.24 (95% empirical CI: 0.14-0.36) million deaths and 0.21 (95% empirical CI: 0.12-0.31) years of LLE in 2020. The net fall in NO-attributable deaths (-26.8%) between 2010 and 2020 was primarily driven by the declines in both NO concentration (-41.6%) and mortality rate (-27.1%) under population growth (+41.0%) and age structure transition (+0.9%).
CONCLUSIONS
Our findings provide national evidence for increased risk of premature death and loss of life expectancy attributed to later-life NO exposure among the elderly in China. In an accelerated aging society, strengthened clean air actions should be formulated to minimize the health burden and regional inequality in NO-attributable mortality.
PubMed: 38925032
DOI: 10.1016/j.ecoenv.2024.116627 -
Endokrynologia Polska Jun 2024Beyond growth acceleration, growth hormone (GH) therapy improves body composition of GH-deficient (GHD) children due to the interaction of GH with lipid and carbohydrate...
INTRODUCTION
Beyond growth acceleration, growth hormone (GH) therapy improves body composition of GH-deficient (GHD) children due to the interaction of GH with lipid and carbohydrate metabolism, possibly mediated by adipokines secreted by adipose tissue and ghrelin. To promote linear growth, it is essential to have normal phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for the increased renal phosphorus reabsorption observed during GH therapy. This study aimed to assess the impact of one-year GH therapy on body composition, adipokines, acylated/unacylated ghrelin (AG/UAG), and FGF23 in GHD children.
MATERIAL AND METHODS
A prospective observational study of 42 prepubertal, non-obese GHD children followed up in the first year of GH replacement therapy, investigating changes in adipokine profiles, AG/UAG, FGF23, and body composition. Data before therapy onset were compared with measurements obtained after 6 and 12 months of GH therapy.
RESULTS
All children with a mean age of 9.2 ± 2.6 years grew at an accelerated pace. Total body fat decreased significantly, while the lipid profile improved, and total bone mineral density (BMD) significantly increased over the 12 months of treatment. Leptin and UAG levels decreased significantly, whereas adiponectin and AG values increased. A significant increase in plasma FGF23 and insulin growth factor 1 (IGF1) was accompanied by increased serum phosphate. Changes in FGF23 concentration did not have an impact on BMD. The strong association of FGF23 with IGF1 and height standard deviation (SD) could reveal a role of FGF23 in linear growth. In regression analysis models, GH therapy influences the changes of leptin and adiponectin, but not ghrelin, independently of body composition - lean or fat mass.
CONCLUSIONS
GH replacement therapy improves body composition and adipokine profile in GHD children and directly impacts leptin and adiponectin concentrations independently of body composition. Also, GHD children have increased serum phosphate, correlated with upregulation rather than with suppression of FGF23, an unexpected observation given the phosphaturic role of FGF23. Further research is needed to identify the molecular mechanisms by which the GH/IGF1 axis influences adipokines secretion and plasma changes of FGF23.
PubMed: 38923900
DOI: 10.5603/ep.98923 -
Current Issues in Molecular Biology Jun 2024Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by...
Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision wound model in diabetic rats and a HaCaT cell model. The wounds were treated daily with topical clonidine. The results analyzed by ImageJ2 software show that the wounds of the rats that were treated with 15 ng/mL clonidine recovered faster, and the wound size was also significantly reduced compared to the control group. Western blot assays determined that clonidine induced an increase in the expression of vascular growth factors, namely, Ang-1, Ang-2, and VEGF. Moreover, clonidine demonstrated a rescuing effect on JAK2 within the JAK/STAT pathway by inhibiting SOCS3 expression, leading to decreased SOCS3 levels and increased expression of JAK2 and phospho-STAT3. Histopathological analysis revealed that clonidine promoted complete epithelial repair and minimized inflammation in skin tissue. Additionally, clonidine stimulated HaCaT cell proliferation in vitro and enhanced cellular energy levels in the presence of AGEs. In conclusion, clonidine promoted vascular growth and wound healing by stimulating the expression of cytokines that are beneficial for wound healing.
PubMed: 38921010
DOI: 10.3390/cimb46060339 -
Frontiers in Immunology 2024Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for...
BACKGROUND
Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression.
METHODS
CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.
RESULTS
Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.
CONCLUSIONS
Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.
Topics: Animals; Colorectal Neoplasms; Hepatectomy; Mice; Liver Neoplasms; Liver; Tumor Microenvironment; Disease Models, Animal; Humans; Mice, Inbred C57BL; Inflammation; Male
PubMed: 38919609
DOI: 10.3389/fimmu.2024.1388272 -
PloS One 2024Increases in near-surface ozone (O3) concentrations is a global environmental problem. High-concentration O3 induces stress in plants, which can lead to visible damage... (Meta-Analysis)
Meta-Analysis
Increases in near-surface ozone (O3) concentrations is a global environmental problem. High-concentration O3 induces stress in plants, which can lead to visible damage to plants, reduced photosynthesis, accelerated aging, inhibited growth, and can even plant death. However, its impact has not been comprehensively evaluated because of the response differences between individual plant species, environmental O3 concentration, and duration of O3 stress in plants. We used a meta-analysis approach based on 31 studies 343 observations) to examine the effects of elevated O3 on malondialdehyde (MDA), superoxide dismutase (SOD), and peroxidase (POD) activities in herbaceous plants. Globally, important as they constitute the majority of the world's food crops. We partitioned the variation in effect size found in the meta-analysis according to the presence of plant species (ornamental herb, rice, and wheat), O3 concentration, and duration of O3 stress in plants. Our results showed that the effects of elevated O3 on plant membrane lipid peroxidation depending on plant species, O3 concentration, and duration of O3 stress in plants. The wheat SOD and POD activity was significantly lower compared to the herbs and rice (P<0.01). The SOD activity of all herbaceous plants increased by 34.6%, 10.5%, and 26.3% for exposure times to elevated O3 environments of 1-12, 13-30, and 31-60 days, respectively. When the exposure time was more than 60 days, SOD activity did not increase but significantly decreased by 12.1%. However, the POD activity of herbaceous plants increased by 30.4%, 57.3%, 21.9% and 5.81%, respectively, when exposure time of herbaceous plants in elevated O3 environment was 1-12, 13-30, 31-60 and more than 60 days. Our meta-analysis revealed that (1) rice is more resistant to elevated O3 than wheat and ornamental herbs likely because of the higher activity of antioxidant components (e.g., POD) in the symplasts, (2) exposure to elevated O3 concentrations for >60 days, may result in antioxidant SOD lose its regulatory ability, and the antioxidant component POD in the symplast is mainly used to resist O3 damage, and (3) the important factors affected the activity of SOD and POD in plants were not consistent: the duration of O3 stress in plants was more important than plant species and O3 concentration for SOD activity. However, for POD activity, plant species was the most important factor.
Topics: Superoxide Dismutase; Antioxidants; Ozone; Malondialdehyde; Lipid Peroxidation; Plants; Oxidative Stress; Oxidoreductases; Oryza; Peroxidase
PubMed: 38917096
DOI: 10.1371/journal.pone.0305688 -
Cureus May 2024Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard...
Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard conservative therapies include rest and activity modification, physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cold/heat therapy, and corticosteroid injections. Ongoing research and anecdotal evidence support using platelet-rich plasma (PRP) for supraspinatus/rotator cuff tears. Platelet releasate is obtained from PRP via the activation of platelets, subsequently releasing bioactive substances. Activation can be achieved through various methods, some of which include the addition of calcium chloride, thrombin, or exposure to low-level lasers. Platelet releasate has the potential to assist in the healing of tears by releasing growth factors that facilitate muscle and tendon repair. This case presentation discusses the outcomes of platelet releasate paired with extracorporeal shock wave therapy (ESWT) for the treatment of a partial-thickness supraspinatus tear in an 18-year-old male baseball athlete. After exploring conservative treatment options, the patient opted for a single platelet releasate injection along with a four-part series with ESWT. Four weeks post-procedure, the patient reported a 25% improvement. He was able to fully return to play for the entire baseball season. Although the effectiveness of platelet releasate is still a topic of debate and further investigation, this case demonstrates how platelet releasate shows promising results in accelerating the treatment recovery for a partial supraspinatus tear. Further investigation and research could support the benefit of this procedure for accelerated recovery of injuries compared to PRP.
PubMed: 38915987
DOI: 10.7759/cureus.61057 -
Epigenetics Dec 2024Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the...
Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the functions and related regulatory mechanisms of circCTNNB1 in lung cancer remain largely indistinct. The mRNA and protein expression levels were examined through real-time polymerase chain reaction (RT-qPCR) and western blot. The cell proliferation was tested through CCK-8 assay. The cell migration and invasion were confirmed through Transwell assays. The cell senescence was evaluated through SA-β-gal assay. The binding ability between miR-186-5p and circCTNNB1 (or YY1) was verified through luciferase reporter and RIP assays. In this study, the higher expression of circCTNNB1 was discovered in lung cancer tissues and cell lines and resulted in poor prognosis. In addition, circCTNNB1 facilitated lung cancer cell proliferation, migration, invasion, and suppressed cell senescence. Knockdown of circCTNNB1 retarded the Wnt pathway. Mechanism-related experiments revealed that circCTNNB1 combined with miR-186-5p to target YY1. Through rescue assays, YY1 overexpression could rescue decreased cell proliferation, migration, invasion, increased cell senescence, and retarded Wnt pathway mediated by circCTNNB1 suppression. Furthermore, YY1 acts as a transcription factor that can transcriptionally activate circCTNNB1 to form YY1/circCTNNB1/miR-186-5p/YY1 positive loop. Through in vivo assays, circCTNNB1 accelerated tumour growth in vivo. All findings revealed that a positive loop YY1/circCTNNB1/miR-186-5p/YY1 aggravated lung cancer progression by modulating the Wnt pathway.
Topics: YY1 Transcription Factor; Humans; MicroRNAs; Lung Neoplasms; Wnt Signaling Pathway; Cell Proliferation; Animals; Cell Line, Tumor; RNA, Circular; Cell Movement; Mice; Gene Expression Regulation, Neoplastic; Mice, Nude; Male; Disease Progression; Female; A549 Cells
PubMed: 38913848
DOI: 10.1080/15592294.2024.2369006 -
JCI Insight May 2024Patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic disease due to mutations of the PKD1 or PKD2 gene, show signs of complement activation in...
Patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic disease due to mutations of the PKD1 or PKD2 gene, show signs of complement activation in the urine and cystic fluid, but their pathogenic role in cystogenesis is unclear. We tested the causal relationship between complement activation and cyst growth using a Pkd1KO renal tubular cell line and newly generated conditional Pkd1-/- C3-/- mice. Pkd1-deficient tubular cells have increased expression of complement-related genes (C3, C5, CfB, C3ar, and C5ar1), while the gene and protein expression of complement regulators DAF, CD59, and Crry is decreased. Pkd1-/- C3-/- mice are unable to fully activate the complement cascade and are characterized by a significantly slower kidney cystogenesis, preserved renal function, and reduced intrarenal inflammation compared with Pkd1-/- C3+/+ controls. Transgenic expression of the cytoplasmic C-terminal tail of Pkd1 in Pkd1KO cells lowered C5ar1 expression, restored Daf levels, and reduced cell proliferation. Consistently, both DAF overexpression and pharmacological inhibition of C5aR1 (but not C3aR) reduced Pkd1KO cell proliferation. In conclusion, the loss of Pkd1 promotes unleashed activation of locally produced complement by downregulating DAF expression in renal tubular cells. Increased C5a formation and C5aR1 activation in tubular cells promotes cyst growth, offering a new therapeutic target.
Topics: Animals; Polycystic Kidney, Autosomal Dominant; Mice; CD55 Antigens; Complement C3; Mice, Knockout; Receptor, Anaphylatoxin C5a; Disease Models, Animal; Complement Activation; TRPP Cation Channels; Humans; Cell Proliferation; Male; Cell Line; Receptors, Complement 3b
PubMed: 38912583
DOI: 10.1172/jci.insight.175220 -
PhytoKeys 2024Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group...
Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica. Following the recent re-circumscription of 15 Caesalpinioideae genera as presented in Advances in Legume Systematics 14, Part 1, and using as a basis a phylogenomic analysis of 997 nuclear gene sequences for 420 species and all but five of the genera currently recognised in the subfamily, we present a new higher-level classification for the subfamily. The new classification of Caesalpinioideae comprises eleven tribes, all of which are either new, reinstated or re-circumscribed at this rank: Caesalpinieae Rchb. (27 genera / ca. 223 species), Campsiandreae LPWG (2 / 5-22), Cassieae Bronn (7 / 695), Ceratonieae Rchb. (4 / 6), Dimorphandreae Benth. (4 / 35), Erythrophleeae LPWG (2 /13), Gleditsieae Nakai (3 / 20), Mimoseae Bronn (100 / ca. 3510), Pterogyneae LPWG (1 / 1), Schizolobieae Nakai (8 / 42-43), Sclerolobieae Benth. & Hook. f. (5 / ca. 113). Although many of these lineages have been recognised and named in the past, either as tribes or informal generic groups, their circumscriptions have varied widely and changed over the past decades, such that all the tribes described here differ in generic membership from those previously recognised. Importantly, the approximately 3500 species and 100 genera of the former subfamily Mimosoideae are now placed in the reinstated, but newly circumscribed, tribe Mimoseae. Because of the large size and ecological importance of the tribe, we also provide a clade-based classification system for Mimoseae that includes 17 named lower-level clades. Fourteen of the 100 Mimoseae genera remain unplaced in these lower-level clades: eight are resolved in two grades and six are phylogenetically isolated monogeneric lineages. In addition to the new classification, we provide a key to genera, morphological descriptions and notes for all 163 genera, all tribes, and all named clades. The diversity of growth forms, foliage, flowers and fruits are illustrated for all genera, and for each genus we also provide a distribution map, based on quality-controlled herbarium specimen localities. A glossary for specialised terms used in legume morphology is provided. This new phylogenetically based classification of Caesalpinioideae provides a solid system for communication and a framework for downstream analyses of biogeography, trait evolution and diversification, as well as for taxonomic revision of still understudied genera.
PubMed: 38912426
DOI: 10.3897/phytokeys.240.101716