Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcom...Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes.Recent insights into the mechanism of native bone repair highlight a robust path dependence.Organoid-based bottom-up developmental engineering mimics this pathdependence to design personalized living implants scaffold-free,with in-build outcome predictability.Yet,adequate(noninvasive)quality metrics of engineered tissues are lacking.Moreover,insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants.Here,male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition,transcriptome,and secreted proteome signatures to directly link in vivo outcomes to quality metrics.As a result,donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone,through either a hypertrophic cartilage or a fibrocartilaginous template.The followed pathway was determined early,as a biological sexdependent activation of distinct progenitor populations.Independent of donor or biological sex,a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling,mineralization,and attraction of vasculature.Hence,the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering.展开更多
Helicobacter pylori performs the unique action of assimilating exogenous non-esterified cholesterol into its cell membrane. This bacterium aggressively incorporates non-esterified cholesterol into the membrane, induce...Helicobacter pylori performs the unique action of assimilating exogenous non-esterified cholesterol into its cell membrane. This bacterium aggressively incorporates non-esterified cholesterol into the membrane, induces its glucosylation, and uses both non-esterified cholesterol and glucosylated cholesterols as membrane lipid compositions. The reason for this assimilation of non-esterified cholesterol into the cell membrane of H. pylori has eluded investigators for many years. Recent hypotheses posit that the sterol-uptake and sterol-glucosylation contribute to the survival of H. pylori cells in different ways. The incorporation of the non-esterified cholesterol into the cell membrane fortifies the resistance of H. pylori against the antibacterial actions of phosphatidylcholines, antibiotics, and bile salts. In parallel, the glucosylation of the non-esterified cholesterol incorporated into the cell membrane serves H. pylori in two ways. First, it helps the bacterium evade host immune responses, such as phagocytosis by macrophages and activation of antigen-specific T cells. Second, it detoxifies sterols fatal to the bacterium via a novel action of sterol glucosylation recently described in another report from our group. The reluctance of H. pylori to absorb esterified cholesterol remains unexplained. A recent study by our group has demonstrated that the phosphatidylethanolamine (PE) in the outer membrane of H. pylori serves as a steroid-binding lipid the incorporation of non-esterified cholesterol into the membrane. We have also discovered that the myristic acid (C14:0) molecule attached to the PE of this bacterium plays an important role in the selective binding of non-esterified cholesterol but not esterified cholesterol.展开更多
<strong>Introduction: </strong>Urinary tract infection represents more than 40% of all nosocomial infections of which 80% are attributed to the use of an indwelling urinary catheter. Although the device is...<strong>Introduction: </strong>Urinary tract infection represents more than 40% of all nosocomial infections of which 80% are attributed to the use of an indwelling urinary catheter. Although the device is useful medically to treat urinary retention and incontinence, its uses have also been associated with infections such as catheter-associated urinary tract infections. <strong>Objectives:</strong> To evaluate catheter-associated urinary tract infection in terms of its prevalence, pathogens causing the infection and the resistance pattern to some commonly used antibiotics. <strong>Methods: </strong>Urine and biofilm specimen were collected from 105 catheterized patients. Bacteria pathogens were identified based on colony morphology, Gram staining and other biochemical reactions. Kirby-Bauer disc diffusion method was employed to determine the antibiotic resistance pattern of the isolated pathogens. <strong>Results: </strong>The study recorded a 74.29% prevalence of catheter-associated urinary tract infection among the rarely symptomatic patients. <em>Escherichia coli</em> were significantly isolated (p < 0.000) in both samples compared to Klebsiella pneumoniae and <em>Staphylococcus aureus</em>. Most isolated pathogens from both samples were resistant to ciprofloxacin with the biofilm pathogens being highly resistant than the urine pathogens. K. pneumoniae from both samples showed higher resistance levels to antibiotics than <em>E. coli</em> and <em>S. aureus</em>. <strong>Conclusion:</strong> Ciprofloxacin, a commonly used antibiotic by catheterized patients turn out to be less effective against the pathogens. The use of ciprofloxacin in catheter-associated urinary tract infection treatment should therefore be given a second thought.展开更多
Local Ghanaian beverages such as Sobolo and Lamugin, play a significant cultural, economic, and medicinal role in the daily lives of the population. These traditional drinks are produced using locally sourced ingredie...Local Ghanaian beverages such as Sobolo and Lamugin, play a significant cultural, economic, and medicinal role in the daily lives of the population. These traditional drinks are produced using locally sourced ingredients, making them both affordable and accessible. The COVID-19 pandemic further heightened the economic importance of these beverages, as demand surged due to their perceived immune-boosting properties. However, the production of these beverages often occurs in non-sterile environments with minimal regulatory oversight, leading to concerns about microbial contamination. This study aimed to evaluate the microbial quality of Sobolo and Lamugin sold at selected street markets in the Greater Accra region of Ghana. Samples were collected from various vendors and analyzed for bacterial and fungal pathogens using standard microbiological techniques. The results revealed significant microbial contamination in many samples, with bacteria such as Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae detected at levels exceeding safe limits. These findings raise serious public health concerns, as the consumption of contaminated beverages could lead to gastrointestinal infections and other health issues. This highlights the urgent need for stricter regulations and improved hygiene practices in the production of local beverages to ensure their safety for consumers. Implementing better regulatory frameworks, regular inspections, and public awareness campaigns could help mitigate the risks associated with these popular drinks, ensuring they remain a safe and cherished part of Ghana’s cultural heritage.展开更多
Escherichia coli and other Proteobacteria are augmented and several other bacteria are diminished in Crohn’s (CD) disease patients’ intestine. This imbalance in bacterial species composition—termed dysbiosis—seems...Escherichia coli and other Proteobacteria are augmented and several other bacteria are diminished in Crohn’s (CD) disease patients’ intestine. This imbalance in bacterial species composition—termed dysbiosis—seems to be determinant of CD manifestation. Since a great part of intestinal bacteria are not cultivable, detection of CD dysbiosis is accomplished by molecular tools, involving sequences analysis of the 16SrRNA gene (16SrDNA) present in the patient’s clinical samples, which can be done by sequencing or electrophoresis in denaturing gels of 16SrDNA amplicons. By analyzing, by temperature gradient gel electrophoresis (TGGE) and next generation sequencing of 16SV6-V8rDNA amplicons present in gram negative cultures from four distinct clinical samples of a control subject and a CD patient, this study demonstrates that both techniques were able to detect E. coli overgrowth and reduction in species richness in CD and that TGGE can discriminate sequences collectively labeled as “unclassified” in 16SrDNA databases. Although TGGE per se does not identify the sequences, the discriminatory power that it confers represents valuable accessory information to next generation DNA sequencing (NGS), and as such must be used as a NGS complementary tool.展开更多
In a recent study published in Science,Koenig et al.1 reported on rationally engineered biparatopic nanobodies targeting the receptor-binding domain(RBD)of the spike protein that not only efficiently neutralize SARS-C...In a recent study published in Science,Koenig et al.1 reported on rationally engineered biparatopic nanobodies targeting the receptor-binding domain(RBD)of the spike protein that not only efficiently neutralize SARS-CoV-2,but additionally suppress mutational escape.Population growth,increased travel and climate change foster epidemic and pandemic threats by(re)emerging viruses.展开更多
基金financed by the Hercules Foundation(project AKUL/13/47)funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 874837+2 种基金supported by the Flemish Government(department of Economy,Science and Innovation)through the Regenerative Medicine Crossing Borders(http://www.regmedxb.com)initiativeImages were recorded on a Zeiss LSM 780-SP Mai Tai HP DS(Cell and Tissue Imaging Cluster(CIC),Supported by Hercules AKUL/11/37 and FWO G.0929.15 to Pieter Vanden Berghe,University of Leuvensupported by Interne Fondsen KU Leuven/Internal Funds KU Leuven grant numbers C24M/22/058.
文摘Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes.Recent insights into the mechanism of native bone repair highlight a robust path dependence.Organoid-based bottom-up developmental engineering mimics this pathdependence to design personalized living implants scaffold-free,with in-build outcome predictability.Yet,adequate(noninvasive)quality metrics of engineered tissues are lacking.Moreover,insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants.Here,male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition,transcriptome,and secreted proteome signatures to directly link in vivo outcomes to quality metrics.As a result,donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone,through either a hypertrophic cartilage or a fibrocartilaginous template.The followed pathway was determined early,as a biological sexdependent activation of distinct progenitor populations.Independent of donor or biological sex,a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling,mineralization,and attraction of vasculature.Hence,the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering.
文摘Helicobacter pylori performs the unique action of assimilating exogenous non-esterified cholesterol into its cell membrane. This bacterium aggressively incorporates non-esterified cholesterol into the membrane, induces its glucosylation, and uses both non-esterified cholesterol and glucosylated cholesterols as membrane lipid compositions. The reason for this assimilation of non-esterified cholesterol into the cell membrane of H. pylori has eluded investigators for many years. Recent hypotheses posit that the sterol-uptake and sterol-glucosylation contribute to the survival of H. pylori cells in different ways. The incorporation of the non-esterified cholesterol into the cell membrane fortifies the resistance of H. pylori against the antibacterial actions of phosphatidylcholines, antibiotics, and bile salts. In parallel, the glucosylation of the non-esterified cholesterol incorporated into the cell membrane serves H. pylori in two ways. First, it helps the bacterium evade host immune responses, such as phagocytosis by macrophages and activation of antigen-specific T cells. Second, it detoxifies sterols fatal to the bacterium via a novel action of sterol glucosylation recently described in another report from our group. The reluctance of H. pylori to absorb esterified cholesterol remains unexplained. A recent study by our group has demonstrated that the phosphatidylethanolamine (PE) in the outer membrane of H. pylori serves as a steroid-binding lipid the incorporation of non-esterified cholesterol into the membrane. We have also discovered that the myristic acid (C14:0) molecule attached to the PE of this bacterium plays an important role in the selective binding of non-esterified cholesterol but not esterified cholesterol.
文摘<strong>Introduction: </strong>Urinary tract infection represents more than 40% of all nosocomial infections of which 80% are attributed to the use of an indwelling urinary catheter. Although the device is useful medically to treat urinary retention and incontinence, its uses have also been associated with infections such as catheter-associated urinary tract infections. <strong>Objectives:</strong> To evaluate catheter-associated urinary tract infection in terms of its prevalence, pathogens causing the infection and the resistance pattern to some commonly used antibiotics. <strong>Methods: </strong>Urine and biofilm specimen were collected from 105 catheterized patients. Bacteria pathogens were identified based on colony morphology, Gram staining and other biochemical reactions. Kirby-Bauer disc diffusion method was employed to determine the antibiotic resistance pattern of the isolated pathogens. <strong>Results: </strong>The study recorded a 74.29% prevalence of catheter-associated urinary tract infection among the rarely symptomatic patients. <em>Escherichia coli</em> were significantly isolated (p < 0.000) in both samples compared to Klebsiella pneumoniae and <em>Staphylococcus aureus</em>. Most isolated pathogens from both samples were resistant to ciprofloxacin with the biofilm pathogens being highly resistant than the urine pathogens. K. pneumoniae from both samples showed higher resistance levels to antibiotics than <em>E. coli</em> and <em>S. aureus</em>. <strong>Conclusion:</strong> Ciprofloxacin, a commonly used antibiotic by catheterized patients turn out to be less effective against the pathogens. The use of ciprofloxacin in catheter-associated urinary tract infection treatment should therefore be given a second thought.
文摘Local Ghanaian beverages such as Sobolo and Lamugin, play a significant cultural, economic, and medicinal role in the daily lives of the population. These traditional drinks are produced using locally sourced ingredients, making them both affordable and accessible. The COVID-19 pandemic further heightened the economic importance of these beverages, as demand surged due to their perceived immune-boosting properties. However, the production of these beverages often occurs in non-sterile environments with minimal regulatory oversight, leading to concerns about microbial contamination. This study aimed to evaluate the microbial quality of Sobolo and Lamugin sold at selected street markets in the Greater Accra region of Ghana. Samples were collected from various vendors and analyzed for bacterial and fungal pathogens using standard microbiological techniques. The results revealed significant microbial contamination in many samples, with bacteria such as Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae detected at levels exceeding safe limits. These findings raise serious public health concerns, as the consumption of contaminated beverages could lead to gastrointestinal infections and other health issues. This highlights the urgent need for stricter regulations and improved hygiene practices in the production of local beverages to ensure their safety for consumers. Implementing better regulatory frameworks, regular inspections, and public awareness campaigns could help mitigate the risks associated with these popular drinks, ensuring they remain a safe and cherished part of Ghana’s cultural heritage.
文摘Escherichia coli and other Proteobacteria are augmented and several other bacteria are diminished in Crohn’s (CD) disease patients’ intestine. This imbalance in bacterial species composition—termed dysbiosis—seems to be determinant of CD manifestation. Since a great part of intestinal bacteria are not cultivable, detection of CD dysbiosis is accomplished by molecular tools, involving sequences analysis of the 16SrRNA gene (16SrDNA) present in the patient’s clinical samples, which can be done by sequencing or electrophoresis in denaturing gels of 16SrDNA amplicons. By analyzing, by temperature gradient gel electrophoresis (TGGE) and next generation sequencing of 16SV6-V8rDNA amplicons present in gram negative cultures from four distinct clinical samples of a control subject and a CD patient, this study demonstrates that both techniques were able to detect E. coli overgrowth and reduction in species richness in CD and that TGGE can discriminate sequences collectively labeled as “unclassified” in 16SrDNA databases. Although TGGE per se does not identify the sequences, the discriminatory power that it confers represents valuable accessory information to next generation DNA sequencing (NGS), and as such must be used as a NGS complementary tool.
文摘In a recent study published in Science,Koenig et al.1 reported on rationally engineered biparatopic nanobodies targeting the receptor-binding domain(RBD)of the spike protein that not only efficiently neutralize SARS-CoV-2,but additionally suppress mutational escape.Population growth,increased travel and climate change foster epidemic and pandemic threats by(re)emerging viruses.
