Among 28 early confirmed cases of Covid-19 in South Korea, diagnosis was delayed in 11 patients because of subclinical symptoms and diverse initial manifestations. Covid-19 was diagnosed by ...surveillance testing in 3 patients who were asymptomatic.
Matrix metalloproteinases (MMPs) are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are also involved in the inflammatory response by ...regulating the pro-inflammatory cytokines TNF-α and IL-1β. Dysregulation in the inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases. Therefore, numerous studies have been conducted to understand the role of MMPs in disease pathogenesis. MMPs are involved in the pathogenesis of infectious diseases through a dysregulation of the activity and expression of MMPs. In this review, we discuss the role of MMPs in infectious diseases and inflammatory responses. Furthermore, we present the potential of MMPs as therapeutic targets in infectious diseases.
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•AuNSs@Ag@AAO substrates were prepared for microplastic detection in water.•Nanosized Raman substrates sensitively detected submicrometer-sized particles.•Numerical analysis supported ...strong electromagnetic enhancements of AuNSs@Ag.•A 0.4 μm polystyrene sample could be quantified with a detection limit of ∼0.005 %.•Enhanced Raman spectroscopy provided a fast detection of nanosized plastics.
We prepared novel Raman substrates for the sensitive detection of submicron-sized plastic spheres in water. Anisotropic nanostar dimer-embedded nanopore substrates were prepared for the efficient identification of submicron-sized plastic spheres by providing internal hot spots of electromagnetic field enhancements at the tips of nanoparticles. Silver-coated gold nanostars (AuNSs@Ag) were inserted into anodized aluminum oxide (AAO) nanopores for enhanced microplastic (MP) detection. We found that surface-enhanced Raman scattering (SERS) substrates of AuNSs@Ag@AAO yielded stronger signals at the same weight percentages for polystyrene MP particles with diameters as small as 0.4 μm, whereas such behaviors could not be observed for larger MPs (diameters of 0.8 μm, 2.3 μm, and 4.8 μm). The detection limit of the submicrometer-sized 0.4 μm in our Raman measurements were estimated to be 0.005% (∼0.05 mg/g =50 ppm) along with a fast detection time of only a few min without any sample pretreatments. Our nano-sized dimensional matching substrates may provide a useful tool for the application of SERS substrates for submicrometer MP pollutants in water.
Radiotherapy or accidental exposure to high-dose radiation can cause severe damage to healthy organs. The gastrointestinal (GI) tract is a radiation-sensitive organ of the body. The intestinal ...barrier is the first line of defense in the GI tract, and consists of mucus secreted by goblet cells and a monolayer of epithelium. Intestinal stem cells (ISCs) help in barrier maintenance and intestinal function after injury by regulating efficient regeneration of the epithelium. The Wnt/β-catenin pathway plays a critical role in maintaining the intestinal epithelium and regulates ISC self-renewal. Metformin is the most widely used antidiabetic drug in clinical practice, and its anti-inflammatory, antioxidative, and antiapoptotic effects have also been widely studied. In this study, we investigated whether metformin alleviated radiation-induced enteropathy by focusing on its role in protecting the epithelial barrier. We found that metformin alleviated radiation-induced enteropathy, with increased villi length and crypt numbers, and restored the intestinal barrier function in the irradiated intestine. In a radiation-induced enteropathy mouse model, metformin treatment increased tight-junction expression in the epithelium and inhibited bacterial translocation to mesenteric lymph nodes. Metformin increased the number of ISCs from radiation toxicity and enhanced epithelial repair by activating Wnt/β-catenin signaling. These data suggested that metformin may be a potential therapeutic agent for radiation-induced enteropathy.
•Epidemiologic features of the second and third waves of the coronavirus disease 2019 (COVID-19) pandemic in South Korea were compared.•Strengthening of social distancing policies was delayed in the ...third wave compared with the second wave.•The third wave persisted longer than the second wave, and had a higher case fatality rate.•Early public health intervention is important to control the COVID-19 pandemic.
To compare epidemiologic features of the second and third waves of the coronavirus disease 2019 (COVID-19) pandemic in South Korea.
Nationwide COVID-19 data were collected between 6 May and 30 December 2020. The degree of social activity was estimated using an Internet search trend analysis program for leisure-related keywords, including ‘eating-out’, ‘trip’ and ‘get directions’ (transportation). Demographics, transmission chains, case fatality rates, social activity levels and public health responses were compared between the second (13 August–18 September 2020) and third (4 November 2020–present) waves.
In comparison with the second wave, the third wave was characterized by delayed strengthening of social distancing policies (3 vs. 15 days), longer duration (36 vs. >56 days) and a higher case fatality rate (0.91% vs. 1.26%). There were significant differences in transmission chains between the second and third waves (P < 0.01). In comparison with the second wave, the proportion of local clusters (24.8% vs. 45.7%) was lower in the third wave, and personal contact transmission (38.5% vs. 25.9%) and unknown routes of transmission (23.5% vs. 20.8%) were higher in the third wave.
Early and timely interventions with strengthened social distancing policies should be implemented to suppress and control the COVID-19 pandemic effectively.
Intestinal organoids have recently emerged as an in vitro model relevant to the gut system owing to their recapitulation of the native intestinal epithelium with crypt–villus architecture. However, ...it is unclear whether intestinal organoids reflect the physiology of the in vivo stress response. Here, we systemically investigated the radiation response in organoids and animal models using mesenchymal stem cell‐conditioned medium (MSC‐CM), which contains secreted paracrine factors. Irradiated organoids exhibited sequential induction of viability loss and regrowth after irradiation (within 12 days), similar to the response of the native intestinal epithelium. Notably, treatment with MSC‐CM facilitated the reproliferation of intestinal stem cells (ISCs) and restoration of damaged crypt‐villus structures in both models. Furthermore, Wnt/Notch signaling pathways were commonly upregulated by MSC‐CM, but not radiation, and pharmacologically selective inhibition of Wnt or Notch signaling attenuated the enhanced recovery of irradiated organoids, with increases in ISCs, following MSC‐CM treatment. Interestingly, the expression of Wnt4, Wnt7a, and active β‐catenin was increased, but not notch family members, in MSC‐CM‐treated organoid after irradiation. Treatment of recombinant mouse Wnt4 and Wnt7a after irradiation improved to some extent intestinal epithelial regeneration both in vitro and in vivo. Overall, these results suggested that intestinal organoids recapitulated the physiological stress response of the intestinal epithelium in vivo. Thus, our findings provided important insights into the physiology of intestinal organoids and may contribute to the development of strategies to enhance the functional maturation of engineered organoids.
The extent to which in vitro intestinal organoids system recapitulate the physiology of in vivo stress response remains unclear. Kim and colleagues reported that intestinal organoids recapitulated the in vivo physiological response to radiation exhibiting specific responses to damage and regeneration. Moreover, the authors revealed that MSC‐CM‐activated Wnt4/7a signaling pathway partially improve the intestinal epithelial regeneration both in vitro and in vivo. These findings may contribute to the development of strategies to enhance the functional maturation of engineered organoids.
The activity of beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is elevated during aging and in sporadic Alzheimer's disease (AD), but the underlying mechanisms of this change are ...not well understood. p25/Cyclin-dependent kinase 5 (Cdk5) has been implicated in the pathogenesis of several neurodegenerative diseases, including AD. Here, we describe a potential mechanism by which BACE activity is increased in AD brains. First, we show that BACE1 is phosphorylated by the p25/Cdk5 complex at Thr252 and that this phosphorylation increases BACE1 activity. Then, we demonstrate that the level of phospho-BACE1 is increased in the brains of AD patients and in mammalian cells and transgenic mice that overexpress p25. Furthermore, the fraction of p25 prepared from iodixanol gradient centrifugation was unexpectedly protected by protease digestion, suggesting that p25/Cdk5-mediated BACE1 phosphorylation may occur in the lumen. These results reveal a link between p25 and BACE1 in AD brains and suggest that upregulated Cdk5 activation by p25 accelerates AD pathogenesis by enhancing BACE1 activity via phosphorylation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bone marrow-mesenchymal stem cell (BM-MSC) therapy improves the recovery of cardiac function after myocardial infarction (MI); however, the underlying molecular mechanisms are not completely ...understood. Recent studies have shown that microRNAs (miRNAs) modulate the pathophysiology of cardiovascular diseases. Here, we investigated the mechanisms underlying the effects of BM-MSC-derived paracrine factors and cardiac miRNAs on myocardial regeneration after MI. In our study, MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery. BM-MSCs transplanted in infarcted rats significantly downregulated the expression of miRNA-23a and miRNA-92a and inhibited apoptosis in the myocardium. An in vitro experiment showed that supernatant from BM-MSCs cultured under hypoxia contained higher levels of vascular endothelial growth factor (VEGF) than that from BM-MSCs under normoxia. In addition, inhibition of miRNA-23a and miRNA-92a reduced cardiac apoptosis. Moreover, the VEGF-containing BM-MSC supernatant inhibited miRNA-23a and miRNA-92a expression and reduced apoptotic signaling in cardiomyocytes under hypoxia. These effects were inhibited when the supernatant was treated with neutralizing antibodies against VEGF. Our results indicate that the paracrine factor, VEGF, derived from transplanted BM-MSCs, regulated the expression of miRNAs such as miRNA-23a and miRNA-92a and exerted anti-apoptotic effects in cardiomyocytes after MI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with coronavirus disease 2019 (COVID-19) can unknowingly spread the virus to several people during the early subclinical period.
We evaluated the viral dynamics in various body fluid ...specimens, such as nasopharyngeal swab, oropharyngeal swab, saliva, sputum, and urine specimens, of two patients with COVID-19 from hospital day 1 to 9. Additional samples of the saliva were taken at 1 hour, 2 hours, and 4 hours after using a chlorhexidine mouthwash. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was determined by real-time reverse transcriptase polymerase chain reaction (rRT-PCR).
SARS-CoV-2 was detected from all the five specimens of both patients by rRT-PCR. The viral load was the highest in the nasopharynx (patient 1 = 8.41 log
copies/mL; patient 2 = 7.49 log
copies/mL), but it was also remarkably high in the saliva (patient 1 = 6.63 log
copies/mL; patient 2 = 7.10 log
copies/mL). SARS-CoV-2 was detected up to hospital day 6 (illness day 9 for patient 2) from the saliva of both patients. The viral load in the saliva decreased transiently for 2 hours after using the chlorhexidine mouthwash.
SARS-CoV-2 viral load was consistently high in the saliva; it was relatively higher than that in the oropharynx during the early stage of COVID-19. Chlorhexidine mouthwash was effective in reducing the SARS-CoV-2 viral load in the saliva for a short-term period.
Advances in surface-enhanced Raman scattering (SERS) detection have helped to overcome the limitations of traditional
diagnostic methods, such as fluorescence and chemiluminescence, owing to its high ...sensitivity and multiplex detection capability. However, for the implementation of SERS detection technology in disease diagnosis, a SERS-based assay platform capable of analyzing clinical samples is essential. Moreover, infectious diseases like COVID-19 require the development of point-of-care (POC) diagnostic technologies that can rapidly and accurately determine infection status. As an effective assay platform, SERS-based bioassays utilize SERS nanotags labeled with protein or DNA receptors on Au or Ag nanoparticles, serving as highly sensitive optical probes. Additionally, a microdevice is necessary as an interface between the target biomolecules and SERS nanotags. This review aims to introduce various microdevices developed for SERS detection, available for POC diagnostics, including LFA strips, microfluidic chips, and microarray chips. Furthermore, the article presents research findings reported in the last 20 years for the SERS-based bioassay of various diseases, such as cancer, cardiovascular diseases, and infectious diseases. Finally, the prospects of SERS bioassays are discussed concerning the integration of SERS-based microdevices and portable Raman readers into POC systems, along with the utilization of artificial intelligence technology.
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