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MBio Dec 2023A peptidoglycan cell wall is an essential component of almost all bacterial cell envelopes, which determines cell shape and prevents osmotic rupture. Antibiotics that...
A peptidoglycan cell wall is an essential component of almost all bacterial cell envelopes, which determines cell shape and prevents osmotic rupture. Antibiotics that interfere with peptidoglycan synthesis have been one of the most important treatments for bacterial infections. Peptidoglycan must also be hydrolyzed to incorporate new material for cell growth and division and to help accommodate important envelope-spanning systems. However, the enzymes that hydrolyze peptidoglycan must be carefully controlled to prevent autolysis. Exactly how this control is achieved is poorly understood in most cases but is a highly active area of current research. Identifying hydrolase control mechanisms has the potential to provide new targets for therapeutic intervention. The work here reports the important discovery of a novel inhibitor/anti-inhibitor system that controls the activity of a cell wall hydrolase in the human pathogen , which also affects resistance to an antibiotic used in the clinic.
PubMed: 38047649
DOI: 10.1128/mbio.02022-23 -
Journal of Bacteriology Dec 2023is unusual in that the bacteria release larger amounts of cell wall material as they grow as compared to related bacteria, and the released cell wall fragments induce...
is unusual in that the bacteria release larger amounts of cell wall material as they grow as compared to related bacteria, and the released cell wall fragments induce inflammation that leads to tissue damage in infected people. The study of MltG revealed the importance of this enzyme for controlling cell wall growth, cell wall fragment production, and bacterial cell size and suggests a role for MltG in a cell wall synthesis and degradation complex. The increased antibiotic sensitivities of mutants suggest that an antimicrobial drug inhibiting MltG would be useful in combination therapy to restore the sensitivity of the bacteria to cell wall targeting antibiotics to which the bacteria are currently resistant.
Topics: Humans; Neisseria gonorrhoeae; Peptidoglycan; Mutation; Anti-Bacterial Agents; Cell Wall
PubMed: 38038461
DOI: 10.1128/jb.00277-23 -
Journal of Oral and Maxillofacial... 2023According to Codex Alimentarius, 'Honey is the natural sweet substance, produced by honeybees from the nectar of plants or from secretions of living parts of plants, or... (Review)
Review
According to Codex Alimentarius, 'Honey is the natural sweet substance, produced by honeybees from the nectar of plants or from secretions of living parts of plants, or excretions of plant-sucking insects on the living parts of plants, which the bees collect, transform by combining with specific substances of their own, deposit, dehydrate, store and leave in honeycombs to ripen and mature'. It can also penetrate deep into the tissue and can prevent autolysis and putrefaction. This paper highlights the usefulness of honey as an embalming agent.
PubMed: 38033935
DOI: 10.4103/jomfp.jomfp_42_23 -
Acta Biochimica Polonica Nov 2023Previously, the direct interactions of Bβ26-42 fibrin residues with prothrombin were demonstrated. It was also shown that forming prothrombin complexes with E- or...
Previously, the direct interactions of Bβ26-42 fibrin residues with prothrombin were demonstrated. It was also shown that forming prothrombin complexes with E- or DDE-fragments causes non-enzymatic prothrombin activation. The direct measuring of the prothrombin level in the blood plasma of patients with acute myocardial infarction (AMI) allowed us to find a situation where such an activation can occur in vivo. Blood coagulation parameters in the blood plasma of patients with AMI were measured at 2 hours, three days, and seven days after the thrombolysis by streptokinase accompanied with intravenous administration of anticoagulants: unfractionated high molecular weight heparin (HMWH) and low-molecular-weight heparin (LMWH). The prothrombin level in the blood plasma of patients with AMI was normal before thrombolytic therapy and substantially decreased after streptokinase administration. This effect was prominent in the case of concomitant anticoagulant therapy with LMWH and was not observed when HMWH was applied. It can be explained by the fact that LMWH preferentially inhibits factor Xa, while the HMWH is an effective inhibitor of both factor Xa and thrombin. This observation suggested that the prothrombin level decrease was caused by the thrombin-like activity and possible autolysis of prothrombin by thrombin. Also, thrombolytic therapy with streptokinase caused the accumulation of fibrin degradation products (FDPs), some of which were able to bind prothrombin. The dramatic decrease of prothrombin level in the blood plasma of patients with AMI during thrombolysis allowed us to conclude the non-enzymatic prothrombin activation with the following autolysis of prothrombin that contributes to the pathology.
Topics: Humans; Prothrombin; Heparin, Low-Molecular-Weight; Thrombin; Factor Xa; Myocardial Infarction; Heparin; Streptokinase; Thrombolytic Therapy; Anticoagulants
PubMed: 38011253
DOI: 10.18388/abp.2020_6962 -
Medicina (Kaunas, Lithuania) Nov 2023: One's quality of life depends on overall health, and in particular, oral health, which has been and continues to become a public health issue through frequent...
The Impact of the Addition of Vitamins on a Silicone Lining Material to the Oral Mucosa Tissue-Evaluation of the Biocompatibility, Hydrolytic Stability and Histopathological Effect.
: One's quality of life depends on overall health, and in particular, oral health, which has been and continues to become a public health issue through frequent manifestations in various forms, from simple oral stomatitis (inflammations of the oral cavity) to the complicated oral health pathologies requiring medical interventions and treatments (caries, pulp necrosis and periodontitis). The aim of this study focused on the preparation and evaluation of vitamins (vitamin A, B1 and B6) incorporated into several silicone-based lining materials as a new alternative to therapeutically loaded materials designed as oral cavity lining materials in prosthodontics. : Silicone-based liners containing vitamins were prepared by mixing them in solution and becoming crosslinked, and then they were characterized using Fourier-transform infrared (FT-IR) spectroscopy to confirm the incorporation of the vitamins into the silicone network; scanning electron microscopy (SEM) to evidence the morphology of the liner materials; dynamic vapor sorption (DVS) to evaluate their internal hydrophobicity, swelling in environments similar to biological fluids and mechanical test to demonstrate tensile strength; MTT to confirm their biocompatibility on normal cell cultures (fibroblast) and mucoadhesivity; and histopathological tests on porcine oral mucosa to highlight their potential utility as soft lining materials with improved efficiency. : FT-IR analysis confirmed the structural peculiarities of the prepared lining materials and the successful incorporation of vitamins into the silicone matrix. The surface roughness of the materials was lower than 0.2 μm, while in cross-section, the lining materials showed a compact morphology. It was found that the presence of vitamins induced a decrease in the main mechanical parameters (strength and elongation at break, Young's modulus) and hydrophobicity, which varied from one vitamin to another. A swelling degree higher than 8% was found in PBS 6.8 (artificial saliva) and water. Hydrolytic stability studies in an artificial saliva medium showed the release of low concentrations of silicone and vitamin fragments in the first 24 h, which increased the swelling behavior of the materials, diffusion and solubility of the vitamins. The microscopic images of fibroblast cells incubated with vitamin liners revealed very good biocompatibility. Also, the silicone liners incorporating the vitamins showed good mucoadhesive properties. The appearance of some pathological disorders with autolysis processes was more pronounced in the case of vitamin A liners. : The addition of the vitamins was shown to have a beneficial effect that was mainly manifested as increased biocompatibility, hydrolytic stability and mucoadhesiveness with the mucosa of the oral cavity and less of an effect on the mechanical strength. The obtained lining materials showed good resistance in simulated biological media but caused a pronounced autolysis phenomenon, as revealed by histopathological examination, showing that these materials may have broad implications in the treatment of oral diseases.
Topics: Animals; Swine; Silicone Elastomers; Denture Liners; Vitamins; Vitamin A; Mouth Mucosa; Quality of Life; Saliva, Artificial; Spectroscopy, Fourier Transform Infrared; Materials Testing; Vitamin K
PubMed: 38003985
DOI: 10.3390/medicina59111936 -
International Journal of Molecular... Nov 2023The thermostable protease TTHA0724 derived from HB8 is an ideal industrial washing enzyme due to its thermophilic characteristics; although it can be expressed in via...
The thermostable protease TTHA0724 derived from HB8 is an ideal industrial washing enzyme due to its thermophilic characteristics; although it can be expressed in via pET-22b, high yields are difficult to achieve, leading to frequent autolysis of the host. This paper details the development of a signal peptide library in the expression system of and the optimization of signal peptides for enhanced extracellular expression of TTHA0724. When was used as the host and the optimized signal peptide was used, the expression level of TTHA0724 was 16.7 times higher compared with . as an expression host does not change the characteristics of TTHA0724. The potential application fields of TTHA0724 are studied. TTHA0724 can be used as a detergent additive at 60 °C, which can sterilize and eliminate mites while thoroughly cleaning protein stains. Soybean meal enzymatic hydrolysis with TTHA0724 at a high temperature produced a higher content of antioxidant peptides. These results indicate that TTHA0724 has great potential for industrial applications.
Topics: Bacillus subtilis; Serine Proteases; Protein Sorting Signals; Escherichia coli; Serine Endopeptidases
PubMed: 37958933
DOI: 10.3390/ijms242115950 -
Food Chemistry Mar 2024This study investigated the effects of aerobic and anaerobic growth and proteolytic enzymes on the amino acid content of yeast hydrolysates in relation to taste and...
This study investigated the effects of aerobic and anaerobic growth and proteolytic enzymes on the amino acid content of yeast hydrolysates in relation to taste and nutrition. Saccharomyces cerevisiae ATCC5574 was grown under fed-batch aerobic or batch anaerobic conditions. Intracellular glutamic acid (Glu) concentrations were 18-fold higher in aerobic yeast. Hydrolysis with papain and alkaline protease released more amino acids (AA) than simple autolysis or hydrolysis with bromelain, most significantly when applied to aerobic yeast (∼2-fold increase). Autolysates and bromelain hydrolysates from aerobic yeast had low levels of bitter and essential AAs, with high levels of umami Glu. Papain and alkaline protease hydrolysates of aerobic yeast had high levels of umami, bitter and essential AAs. Autolysates/hydrolysates from anaerobic yeast had moderate, high, and low levels of bitter, essential and umami AAs. Selection of both yeast growth conditions and hydrolysis enzyme can manipulate the free AA profile and yield of hydrolysates.
Topics: Peptide Hydrolases; Bromelains; Saccharomyces cerevisiae; Amino Acids; Taste; Papain; Hydrolysis; Glutamic Acid; Protein Hydrolysates
PubMed: 37939420
DOI: 10.1016/j.foodchem.2023.137906 -
World Journal of Clinical Cases Sep 2023Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis, leading to cardiac arrest, are rare. To...
BACKGROUND
Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis, leading to cardiac arrest, are rare. To date, no specific treatment method for autolysis or surgical amputation or guidelines for determining the level of amputation have been established.
CASE SUMMARY
In this case report, we describe a treatment method that effectively preserved the function of fingers by surgical treatment under local anesthesia with a minimum operative time, while also preserving finger length to the maximum possible extent.
CONCLUSION
Our approach may contribute to improved postoperative quality of life by preserving finger length.
PubMed: 37900227
DOI: 10.12998/wjcc.v11.i27.6640 -
Molecules and Cells Nov 2023Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, and chronic infections. Additionally, the... (Review)
Review
Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, and chronic infections. Additionally, the decline in autophagic activity contributes to tissue and organ dysfunction and aging-related diseases. Several factors, such as down-regulation of autophagy components and activators, oxidative damage, microinflammation, and impaired autophagy flux, are linked to autophagy decline. An autophagy flux impairment (AFI) has been implicated in neurological disorders and in certain other pathological conditions. Here, to enhance our understanding of AFI, we conducted a comprehensive literature review of findings derived from two well-studied cellular stress models: glucose deprivation and replicative senescence. Glucose deprivation is a condition in which cells heavily rely on oxidative phosphorylation for ATP generation. Autophagy is activated, but its flux is hindered at the autolysis step, primarily due to an impairment of lysosomal acidity. Cells undergoing replicative senescence also experience AFI, which is also known to be caused by lysosomal acidity failure. Both glucose deprivation and replicative senescence elevate levels of reactive oxygen species (ROS), affecting lysosomal acidification. Mitochondrial alterations play a crucial role in elevating ROS generation and reducing lysosomal acidity, highlighting their association with autophagy dysfunction and disease conditions. This paper delves into the underlying molecular and cellular pathways of AFI in glucose-deprived cells, providing insights into potential strategies for managing AFI that is driven by lysosomal acidity failure. Furthermore, the investigation on the roles of mitochondrial dysfunction sheds light on the potential effectiveness of modulating mitochondrial function to overcome AFI, offering new possibilities for therapeutic interventions.
Topics: Humans; Mitophagy; Reactive Oxygen Species; Glucose; Autophagy; Lysosomes; Hydrogen-Ion Concentration
PubMed: 37867391
DOI: 10.14348/molcells.2023.0121 -
American Journal of Translational... 2023Although the main action of human hepatitis B immunoglobulin (HBIG) is to neutralize hepatitis B virus surface antigen (HBsAg) in serum, HBIG is known to be localized in...
BACKGROUND AND AIMS
Although the main action of human hepatitis B immunoglobulin (HBIG) is to neutralize hepatitis B virus surface antigen (HBsAg) in serum, HBIG is known to be localized in the cell. However, the effect of intracellularly located HBIG is poorly understood because of the low purity of conventional plasma-derived HBIG (cHBIG). We attempted to elucidate the mechanism of action of internalized HBIG using recombinant HBIG (lenvervimab).
METHODS
We used HBsAg producing cell lines, non-HBsAg cell lines and human HBsAg-producing hepatocytes. The autophagosome lysis pathway-related proteins Rab5, calnexin, giantin, and Rab7 were used to localize HBsAg and anti-HBs-IgG in the cytoplasm using Western blotting and confocal microscopy.
RESULTS
Intracellular anti-HBs-IgG (lenvervimab and cHBIG) transported via Fc receptor-mediated endocytosis increased the number of autophagosomes. However, there was no change in autolysis. HBsAg and anti-HBs-IgG co-localized in the multivesicular body and precipitated in the cytoplasm. HBsAg secretion into culture medium decreased after lenvervimab treatment. Simultaneously, the amount of cellular HBsAg increased in the cell lines but decreased in human hepatocytes. Furthermore, intracellular lenvervimab is not easily removed from HBsAg cell lines.
CONCLUSIONS
Lenvervimab decreases HBsAg secretion, and HBsAg antibody precipitation in the multivesicular body may play an important role.
PubMed: 37854220
DOI: No ID Found