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Biomolecules & Biomedicine Jun 2024Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate...
Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate glycolysis, was studied for its effects on liver fibrosis and its underlying mechanism. Results showed that QE effectively improved liver injury and fibrosis caused by carbon tetrachloride (CCl4). This was supported by evidence of improved pathological features and reduced levels of serum markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), hyaluronic acid (HA), laminin (LN), and procollagen type III. QE also decreased lactate production and downregulated the expression of glycolysis-related enzymes - pyruvate kinase M2 (PKM2), phosphofructokinase platelet (PFKP), and hexokinase 2 (HK2) - at both the mRNA and protein levels. In liver sinusoidal endothelial cells (LSECs), QE reduced the expression and activity of these enzymes, resulting in reduced glucose consumption, ATP production, and lactate generation. Further analysis revealed that QE inhibited the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and suppressed neutrophil recruitment. Overall, QE showed promising therapeutic potential for liver fibrosis by targeting LSEC glycolysis and reducing neutrophil infiltration.
PubMed: 38943679
DOI: 10.17305/bb.2024.10530 -
The Plant Cell Jun 2024The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene...
The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.
PubMed: 38943676
DOI: 10.1093/plcell/koae195 -
Journal of Burn Care & Research :... Jun 2024Finding a perfect epidermal transplant remains a holy grail of burn surgery. The epidermis is a site of stem cells that allows for the epithelial regeneration. The use...
Finding a perfect epidermal transplant remains a holy grail of burn surgery. The epidermis is a site of stem cells that allows for the epithelial regeneration. The use of CEA for the treatment of major burns was first reported in 1981. CEA requires specialized skills; thus, reports from different burn-centers have shown mixed results. Comparing our modern data with past data shows how this field has advanced while maintaining institutional control. We performed a retrospective analysis of all patients admitted between 01/01/1988-12/31/2021 for massive burns that were managed with CEA. Patients were divided into pre-defined groups: G1(early-era)=1988-1999, G2(pre-modern-era)=2000-2010, and G3(modern-era)=2011-2021. We compared demographics, %TBSA, presence of inhalation-injury, LOS, complications, and mortality. We treated 52 patients with CEA during the study period. In the modern-era, we found 11 patients; in the pre-modern-era, 10; and in the early-era, 31. Injury characteristics, including %TBSA and the presence of inhalation-injury, were not significantly different between the groups. We observed lower mortality rates in G1 and G3 (G1:20% vs. G2:42% vs. G3:27%, p<0.05), although the predicted mortality was not significantly different between the groups (G1:50% vs. G2:47% vs. G3:49%, NS). Patients in G1 also had a shorter hospital LOS, in days, (G1:90 vs. G2:127 vs. G3:205, p<0.05). Finally, the surface-area grafted per patient was the highest in G2 (G1:2,000cm2 vs. G2:4,187cm2 vs. G3:4,090cm2, p<0.01). CEA has not gained popularity despite proven positive outcomes. Our retrospective analysis showed that CEA should be considered as a treatment option for patients with large burns, given proper training and infrastructure.
PubMed: 38943557
DOI: 10.1093/jbcr/irae132 -
Otolaryngology--head and Neck Surgery :... Jun 2024Our study aims to assess if decreasing bottle cap size was associated with more ingestions and injuries nationally. STUDY DESIGN: Retrospective chart review.
OBJECTIVE
Our study aims to assess if decreasing bottle cap size was associated with more ingestions and injuries nationally. STUDY DESIGN: Retrospective chart review.
SETTING
The National Electronic Injury Surveillance System (NEISS) database.
METHODS
The NEISS was queried for bottle cap ingestions in children 0 to 18 years old between 2002 and 2021. Demographic factors including age, race, and sex of the patient were recorded. The location where the ingestion took place and the disposition of the patient were also analyzed. Data were excluded if the narrative did not specify the ingestion of a cap of a drinking bottle.
RESULTS
A total of 415 bottle cap ingestion injuries were identified, for a national estimate of 11,683 injuries. The mean age at the time of ingestion was 10.3 ± 5.2 years and the majority of the injuries occurred in males (N = 9129, 78.4%). 46.4% (N = 5398) were Caucasian, 17.6% (N = 2046) were Black or African American, and 2.7% (N = 311) were Hispanic. 55.0% (N = 6405) of injuries occurred at an unknown location, 41.4% (N = 4781) occurred at home, and 2.8% (N = 326) occurred at school. 82.3% (N = 9584) of patients were treated in the emergency department and released, 6.9% (N = 808) were treated and admitted, 6.7% (N = 783) were treated and transferred, and 0.9% (N = 110) were held for observation. From 2002 (N = 6) to 2021 (N = 2291), there was a statistically significant increase in bottle cap ingestions (P < .001).
CONCLUSION
Plastic bottle cap ingestions have increased in children over the last 20 years, coincident with the change to smaller bottle caps.
PubMed: 38943452
DOI: 10.1002/ohn.876 -
Journal of Alzheimer's Disease : JAD Jun 2024Disease-modifying therapies (DMT) for Alzheimer's disease (AD) are highly longed-for. In this quest, anti-amyloid therapies take center stage supported by genetic facts... (Review)
Review
Disease-modifying therapies (DMT) for Alzheimer's disease (AD) are highly longed-for. In this quest, anti-amyloid therapies take center stage supported by genetic facts that highlight an imbalance between production and clearance of amyloid-β peptide (Aβ) in AD patients. Indeed, evidence from basic research, human genetic and biomarker studies, suggests the accumulation of Aβ as a driver of AD pathogenesis and progression. The aspartic protease β-site AβPP cleaving enzyme (BACE1) is the initiator for Aβ production. Underpinning a critical role for BACE1 in AD pathophysiology are the elevated BACE1 concentration and activity observed in the brain and body fluids of AD patients. Therefore, BACE1 is a prime drug target for reducing Aβ levels in early AD. Small-molecule BACE1 inhibitors have been extensively developed for the last 20 years. However, clinical trials with these molecules have been discontinued for futility or safety reasons. Most of the observed adverse side effects were due to other aspartic proteases cross-inhibition, including the homologue BACE2, and to mechanism-based toxicity since BACE1 has substrates with important roles for synaptic plasticity and synaptic homeostasis besides amyloid-β protein precursor (AβPP). Despite these setbacks, BACE1 persists as a well-validated therapeutic target for which a specific inhibitor with high substrate selectivity may yet to be found. In this review we provide an overview of the evolution in BACE1 inhibitors design pinpointing the molecules that reached advanced phases of clinical trials and the liabilities that precluded adequate trial effects. Finally, we ponder on the challenges that anti-amyloid therapies must overcome to achieve clinical success.
PubMed: 38943390
DOI: 10.3233/JAD-240146 -
Journal of Forensic Sciences Jun 2024Automobile paint chips are a crucial piece of trace evidence for forensic investigators. This is because automotive paints are composed of multiple layers, including the...
Automobile paint chips are a crucial piece of trace evidence for forensic investigators. This is because automotive paints are composed of multiple layers, including the primer, basecoat, and clearcoat, each of which has its own chemical composition that can vary by vehicle make, model, year, and manufacturing plant. Thus, Fourier-transform infrared (FTIR) spectral databases for automobile paint systems have been established to aid law enforcement in, for example, narrowing search parameters for a suspect's vehicle. Recently, car manufacturers have implemented primers on plastic substrates that are much thinner (~5 μm) than those on metal substrates, making it more difficult to manually separate for analyses. Here, we evaluated FTIR microspectroscopy (μ-FTIR) and optical photothermal infrared spectroscopy (O-PTIR) to chemically image cross sections of paint chips without manually separating the layers. For μ-FTIR, transmission and transflection modes provided the highest quality spectra compared to reflection and μ-ATR analyses. Point analysis was preferable to chemical imaging, as peaks were identified in the point (MCT) detector's lower spectral range that was below the imaging (FPA) detector's cutoff, such as those associated with titanium dioxide. Reduced spectral range can lead to a similar issue in O-PTIR analyses depending on instrument configuration. However, its complementary Raman spectra showed strong titanium dioxide peaks, providing an alternate means of identification. Both techniques are likely to become more relevant as they are non-destructive and avoid manual separation of the layers. O-PTIR is particularly well-suited for analysis of the thin primer layer due to its superior spatial resolution.
PubMed: 38943352
DOI: 10.1111/1556-4029.15575 -
Giornale Italiano Di Nefrologia :... Jun 2024The centralized preparation and distribution system of acidic concentrate represents a true innovation in hemodialysis, when compared to acid bags, in terms of... (Comparative Study)
Comparative Study
The centralized preparation and distribution system of acidic concentrate represents a true innovation in hemodialysis, when compared to acid bags, in terms of convenience and eco-sustainability. The aim of this study is to compare the use of traditional acid bags with the centralized distribution system of acidic concentrate, with particular attention to differences in terms of eco-sustainability and convenience. At the Nephrology Dialysis and Renal Transplantation Unit of the University Hospital of Modena was installed the Granumix system® (Fresenius Medical Care, Bad Homburg, Germany). Data collected before the introduction of the Granumix® system (including the used acid bags, boxes and pallets used for their packaging, liters of acid solution used and kilograms of waste generated from wood, plastic, cardboard and residual acid solution) were compared with those collected after the implementation of the Granumix® system. Factors such as material consumption, volume of waste generated, unused and wasted products, time required for dialysis session preparation and nurses' satisfaction were analyzed to document which system was more environmentally sustainable. Data collected in 2019 at our Dialysis Center showed a consumption of 30,000 acid bags, which generated over 20,000 kg of waste from wood, plastic and cardboard, and approximately 12,000 liters of residual acid solution to be disposed of, with a handling weight by operators reaching nearly 160,000 kg. The use of the centralized distribution system of acidic concentrate resulted in a significant reduction in waste generated (2,642 kg vs 13,617 kg), residual acid solution to be disposed of (2,351 liters vs 12,100 liters) and weights handled by operators (71,522 kg vs 158,117 kg). The acidic concentrate appears to be better suited to the sustainability challenge that dialysis must faces today, particularly due to the significant increase in the number of patients, which leads to a higher number of treatments and, therefore, a growing demand for eco-sustainable products.
Topics: Renal Dialysis; Humans; Italy; Acids; Hemodialysis Solutions; Conservation of Natural Resources
PubMed: 38943331
DOI: No ID Found -
Journal of Burn Care & Research :... Jun 2024
PubMed: 38943312
DOI: 10.1093/jbcr/irae125 -
Stem Cells and Development Jun 2024Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally...
Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally active VD3 improved adipose stem cell viability in ex vivo and in vivo fat grafting models. In this study, we evaluated the inactive form of VD3 (cholecalciferol) on adipose stromal cell (ASC) phenotype during hypoxia and the subsequent effect on human fat graft retention in the xenograft model. Lipoaspirate collected from six human donors was used for ex-vivo particle culture studies and isolated ASC studies. Adipose particles were treated with increasing doses of VD3 to determine impact on ASC survival. Expanded stromal cells were treated with VD3 during hypoxic culture and assessed for viability, apoptosis, mitochondrial activity, and nitric oxide release via caspase, DAF-FM, or TMRM. Finally, forty Nu/J mice receiving bilateral dorsal human lipoaspirate were treated thrice weekly with 1) Vehicle control, 2) 50ng calcitriol, 3) 50ng VD3, 4) 500ng VD3, and 5) 5000ng VD3 for 12 weeks, n=8 per group. Graft weight, volume, and architecture were analyzed. Adipose particles treated with dose escalating VD3 had significantly increased ASC viability compared to control (p<0.01). Under hypoxia, ASCs treated with 1nM VD3 had significantly greater viability than untreated and pre-treated cells (p<0.01, p<0.01) and significantly lower apoptosis-to-viability ratio (p<0.01). ASCs pre-treated with 1nM VD3 had significantly lower nitric oxide release (p<0.05) and lower mitochondrial polarization (p<0.05) compared to controls. In vivo results showed mice receiving 5000ng VD3 had significantly greater graft weight (p<0.05) and volume (p<0.05) after 12 weeks of treatment compared to controls. Grafts had enhanced neovascularization, intact adipocyte architecture, and absence of oil cysts. VD3 is an over-the-counter nutritional supplement with a known safety profile in humans. Our xenograft model suggests administering VD3 at the time of surgery may significantly improve fat graft retention.
PubMed: 38943277
DOI: 10.1089/scd.2024.0056 -
Cellular and Molecular Life Sciences :... Jun 2024Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes...
Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.
Topics: Humans; MicroRNAs; Cetuximab; Drug Resistance, Neoplasm; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Jumonji Domain-Containing Histone Demethylases; Argonaute Proteins; Animals; Mice; Cell Nucleus; Female; Mice, Nude
PubMed: 38943031
DOI: 10.1007/s00018-024-05324-x