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Chemistry & Biodiversity Jun 2024G-quadruplex DNA sequences present in the promoter and telomere regions of the genomic sequence are considered therapeutic targets for the treatment of cancer. Curcumin,...
G-quadruplex DNA sequences present in the promoter and telomere regions of the genomic sequence are considered therapeutic targets for the treatment of cancer. Curcumin, derived from Curcuma longa, has been known as a quadruplex binder and has a potential role in the apoptosis of cancer cells. Here, we have reported the Schiff base ligand of curcumin synthesized through the condensation of the amino acid L-tryptophan and the knoevenagel derivative of curcumin (4-nitrobenzylidene curcumin (NBC)) as a potential G-quadruplex binder. Thus, spectroscopic and biophysical studies reveal a higher binding affinity of the ligand Sb-NBC towards the promoter and telomere G-quadruplex sequence as compared to the parent NBC. The ligand Sb-NBC highly stabilizes the parallel and hybrid G-quadruplex topologies to 10.5 0C- 6.4 0C. Interestingly, the ligands also exhibit selective cytotoxicity toward cancer cells over normal cells. Taken together, this work provides evidence of the possibility of applying curcumin Schiff base in cancer therapy to regulate oncogene expression in cancer cells.
PubMed: 38946104
DOI: 10.1002/cbdv.202400797 -
Journal of Nutritional Science and... 2024Excessive immune response and inflammation are associated with an increased risk of various diseases. In particular, excessive myeloperoxidase (MPO) activity in... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Excessive immune response and inflammation are associated with an increased risk of various diseases. In particular, excessive myeloperoxidase (MPO) activity in neutrophils causes inflammatory reactions and lifestyle-related diseases. Adlay has a long history of being used as a traditional Chinese medicine. Polyphenols present in adlay seeds are expected to have the effect of suppressing excessive immune and inflammatory responses. Here, we conducted a randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the suppressing effects of adlay seeds extract on excessive immune responses. One hundred and twenty adults participated in the study and they were equally divided into an adlay tea intake group and a placebo group. MPO activity was significantly elevated in the placebo group after 8-wk ingestion, while no significant change was observed in the adlay group. Vascular endothelial functions improved in the adlay group, especially in subjects over 40 y old. These results indicate that adlay tea intake may suppress an excessive immune and inflammatory responses, and improve arterial stiffness. Since caffeic acid, p-coumaric acid, and ferulic acid detected in adlay tea are known to inhibit MPO activity, these polyphenols may be the major functional molecules. Collectively, adlay tea is considered to have a preventative effect against lifestyle-related diseases through improving vascular endothelial function by effects to maintain immune homeostasis of the contained polyphenols. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000032263).
Topics: Humans; Double-Blind Method; Male; Female; Adult; Tea; Homeostasis; Middle Aged; Endothelium, Vascular; Polyphenols; Peroxidase; Seeds; Plant Extracts; Inflammation; Caffeic Acids; Medicine, Chinese Traditional
PubMed: 38945894
DOI: 10.3177/jnsv.70.280 -
Food Research International (Ottawa,... Aug 2024Although the industrial production of butanol has been carried out for decades by bacteria of the Clostridium species, recent studies have shown the use of the yeast...
Although the industrial production of butanol has been carried out for decades by bacteria of the Clostridium species, recent studies have shown the use of the yeast Saccharomyces cerevisiae as a promising alternative. While the production of n-butanol by this yeast is still very far from its tolerability (up to 2% butanol), the improvement in the tolerance can lead to an increase in butanol production. The aim of the present work was to evaluate the adaptive capacity of the laboratory strain X2180-1B and the Brazilian ethanol-producing strain CAT-1 when submitted to two strategies of adaptive laboratory Evolution (ALE) in butanol. The strains were submitted, in parallel, to ALE with successive passages or with UV irradiation, using 1% butanol as selection pressure. Despite initially showing greater tolerance to butanol, the CAT-1 strain did not show great improvements after being submitted to ALE. Already the laboratory strain X2180-1B showed an incredible increase in butanol tolerance, starting from a condition of inability to grow in 1% butanol, to the capacity to grow in this same condition. With emphasis on the X2180_n100#28 isolated colony that presented the highest maximum specific growth rate among all isolated colonies, we believe that this colony has good potential to be used as a model yeast for understanding the mechanisms that involve tolerance to alcohols and other inhibitory compounds.
Topics: Saccharomyces cerevisiae; Butanols; Fermentation; Ethanol; 1-Butanol; Ultraviolet Rays; Adaptation, Physiological
PubMed: 38945626
DOI: 10.1016/j.foodres.2024.114637 -
Neurobiology of Disease Jun 2024The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel...
The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel App knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.
PubMed: 38945496
DOI: 10.1016/j.nbd.2024.106584 -
Contemporary Clinical Trials Jun 2024Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by...
BACKGROUND
Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure.
METHODS
This is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation.
CONCLUSION
The Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.
PubMed: 38945293
DOI: 10.1016/j.cct.2024.107614 -
Environmental Pollution (Barking, Essex... Jun 2024Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the...
Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p<0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage Ⅲ/silicosis stage Ⅰ groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.
PubMed: 38945194
DOI: 10.1016/j.envpol.2024.124469 -
Medical Physics Jun 2024Automatic segmentation of vertebrae in spinal x-ray images is crucial for clinical diagnosis, case analysis, and surgical planning of spinal lesions.
BACKGROUND
Automatic segmentation of vertebrae in spinal x-ray images is crucial for clinical diagnosis, case analysis, and surgical planning of spinal lesions.
PURPOSE
However, due to the inherent characteristics of x-ray images, including low contrast, high noise, and uneven grey scale, it remains a critical and challenging problem in computer-aided spine image analysis and disease diagnosis applications.
METHODS
In this paper, a Multiscale Feature Enhancement Network (MFENet), is proposed for segmenting whole spinal x-ray images, to aid doctors in diagnosing spinal-related diseases. To enhance feature extraction, the network incorporates a Dual-branch Feature Extraction Module (DFEM) and a Semantic Aggregation Module (SAM). The DFEM has a parallel dual-branch structure. The upper branch utilizes multiscale convolutional kernels to extract features from images. Employing convolutional kernels of different sizes helps capture details and structural information at different scales. The lower branch incorporates attention mechanisms to further optimize feature representation. By modeling the feature maps spatially and across channels, the network becomes more focused on key feature regions and suppresses task-irrelevant information. The SAM leverages contextual semantic information to compensate for details lost during pooling and convolution operations. It integrates high-level feature information from different scales to reduce segmentation result discontinuity. In addition, a hybrid loss function is employed to enhance the network's feature extraction capability.
RESULTS
In this study, we conducted a multitude of experiments utilizing dataset provided by the Spine Surgery Department of Henan Provincial People's Hospital. The experimental results indicate that our proposed MFENet demonstrates superior segmentation performance in spinal segmentation on x-ray images compared to other advanced methods, achieving 92.61 ± 0.431 for MIoU, 92.42 ± 0.329 for DSC, and 99.51 ± 0.037 for Global_accuracy.
CONCLUSIONS
Our model is able to more effectively learn and extract global contextual semantic information, significantly improving spinal segmentation performance, further aiding doctors in analyzing patient conditions.
PubMed: 38944886
DOI: 10.1002/mp.17278 -
Journal of Minimally Invasive Gynecology Jun 2024Endometrial biopsy (EB) is one of the most common gynecologic procedures. Office-based EB has replaced procedures involving general/loco-regional anesthesia and cervical...
OBJECTIVE
Endometrial biopsy (EB) is one of the most common gynecologic procedures. Office-based EB has replaced procedures involving general/loco-regional anesthesia and cervical dilatation, performed in the operating room[1,2,3]. The Grasp Biopsy seems to be the most appropriate EB technique for reproductive aged women[1,2,4]. Recently, the Visual D&C performed with hysteroscopic tissue removal devices has shown to be a valid alternative[5]. However, it is often difficult to obtain ad adequate specimen in peri/post-menopausal women with hypo/atrophic endometrium[2]. Our aim is to show a novel hysteroscopic EB technique called "Rail Biopsy" which requires widespread and cheap instruments.
SETTING
Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero-Universitaria di Bologna" Bologna, Italy.
PARTICIPANTS
women referred to our center for hysteroscopic endometrial biopsy.
INTERVENTIONS
We performed the "Rail Biopsy" technique with a 5.0 mm Continuous Flow Operative Hysteroscope with a 30° Lens and a 5Fr operative channel. We identify the endometrial target area (ETA) and we create a first track cutting through the endometrium in a caudo-cranial direction using cold scissors. We repeat the procedure creating a second parallel track, thus completing our "rail" and isolating a wide ETA. Then, in caudo-cranial direction, we cut through the stromal layer beneath the ETA. With a 5Fr cold grasping forceps, we clench the cranial edge of the ETA and we remove it from the uterine cavity. A high-quality specimen, even in case of hypo/atrophic endometrium or focal sessile lesions, can be obtained with this technique. The crucial aspect of the "Rail Biopsy" indeed is cutting through the stromal tissue, while the endometrium is minimally touched, avoiding thermal damage deriving from electrosurgery. The instruments required are widespread and cheap. Moreover, this technique can be performed on any wall of the uterus, under vision and, in the majority of patients, in an office-setting without cervical dilatation or general/loco-regional anesthesia, making it an attractive alternative to hysteroscopy performed in the operating room setting. Further studies comparing "Rail Biopsy" to other EB techniques are needed.
CONCLUSION
We showed a novel approach for hysteroscopic EB that may be particularly useful in patients with hypo/atrophic endometrium, easy to learn and with low costs.
PubMed: 38944338
DOI: 10.1016/j.jmig.2024.06.013 -
Free Radical Biology & Medicine Jun 2024Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the...
Reactive oxygen species in skeletal muscle injury, fatigue, regeneration and ageing: In memory of John Faulkner The role of zinc and matrix metalloproteinases in myofibrillar protein degradation in critical illness myopathy.
Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the activation of matrix metalloproteinases (MMPs) in skeletal muscle exposed to the intensive care unit (ICU) condition (immobilization and mechanical ventilation). ICU patients exposed to 12 days ICU condition were followed longitudinally with six repeated muscle biopsies while they showed a progressive preferential myosin loss, i.e., the hallmark of Critical Illness Myopathy (CIM), in parallel with the activation of Zn-transporters. In this study, we have revisited the expression of Zn-transporters and the activation of MMPs in clinical as well as in experimental studies using an established ICU model. MMPs are a group Zn-dependent endopeptidases which do not only target and cleave extracellular proteins but also intracellular proteins including multiple sarcomeric proteins. MMP-9 is of specific interest since the hallmark of CIM, the preferential myosin loss, has also been reported in dilated cardiomyopathy and coupled to MMP-9 activation. Transcriptional activation of Zn-transporters was observed in both clinical and experimental studies as well as the activation of MMPs, in particular MMP-9, in various limb and respiratory muscles in response to long-term exposure to the ICU condition. The activation of Zn-transporters was paralleled by increased Zn levels in skeletal muscle which in turn showed a negative linear correlation with the preferential myosin loss associated with CIM, offering a potential intervention strategy. Thus, activation of Zn-transporters, increased intramuscular Zn levels, and activation of the Zn-dependent MMPs are forwarded as a probable mechanism involved in CIM pathophysiology. These effects were confirmed in different rat strains subjected to a model of CIM and exacerbated by old age. This is of specific interest since old age and muscle wasting are the two factors most strongly associated with ICU mortality.
PubMed: 38944212
DOI: 10.1016/j.freeradbiomed.2024.06.022 -
The Journal of Biological Chemistry Jun 2024Shy (side chain hydratase) and Sal (side chain aldolase), are involved in successive reactions in the pathway of bile acid side chain catabolism in Proteobacteria....
Shy (side chain hydratase) and Sal (side chain aldolase), are involved in successive reactions in the pathway of bile acid side chain catabolism in Proteobacteria. Untagged Shy co-purified with His-tagged Sal indicating that the two enzymes form a complex. Shy contains a MaoC and a DUF35 domain. When co-expressed with Sal, the DUF35 domain but not the MaoC domain of Shy was observed to co-purify with Sal, indicating Sal interacts with Shy through its DUF35 domain. The MaoC domain of Shy (Shy) remained catalytically viable and could hydrate cholyl-enoyl-CoA with similar catalytic efficiency as in the Shy-Sal complex. Sal expressed with the DUF35 domain of Shy (Sal-Shy) was similarly competent for the retroaldol cleavage of cholyl-3-OH-CoA. Shy showed a preference for C side chain bile acid substrates, exhibiting low activity towards C side chain substrates. The Shy structure was determined by X-ray crystallography, showing a hot dog fold with a short central helix surrounded by a twisted anti-parallel β-sheet. Modeling and mutagenesis studies suggest that the bile acid substrate occupies the large open cleft formed by the truncated central helix and repositioning of the active site housing. Shy therefore contains two substrate binding sites per homodimer, making it distinct from previously characterized MaoC steroid hydratases that are (pseudo)-heterodimers with one substrate binding site per dimer. The characterization of Shy provides insight into how MaoC family hydratases have adapted to accommodate large polycyclic substrates that can facilitate future engineering of these enzymes to produce novel steroid pharmaceuticals.
PubMed: 38944126
DOI: 10.1016/j.jbc.2024.107509