The rapid evolution and spread of multidrug resistance among bacterial pathogens has significantly outpaced the development of new antibiotics, underscoring the urgent need for alternative therapies. Antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy have emerged as promising treatments. Antimicrobial photodynamic therapy relies on the interaction between light and a photosensitizer to produce reactive oxygen species, which are highly cytotoxic to microorganisms, leading to their destruction without fostering resistance. Antimicrobial sonodynamic therapy, a novel variation, substitutes ultrasound for light to activate the sonosensitizers, expanding the therapeutic reach. To increase the efficiency of antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy, the combination of these two methods, known as antimicrobial photo-sonodynamic therapy, is currently being explored and considered a promising approach. Recent advances, particularly in the application of nanomaterials, have further enhanced the efficacy of these therapies. Nanosensitizers, due to their improved reactive oxygen species generation and targeted delivery, offer significant advantages in overcoming the limitations of conventional sensitizers. These breakthroughs provide new avenues for treating bacterial infections, especially multidrug-resistant strains and biofilm-associated infections. Continued research, including comprehensive clinical studies, is crucial to optimizing nanomaterial-based antimicrobial photo-sonodynamic therapy for clinical use, ensuring their effectiveness in real-world applications.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Bacteria drug effects   MeSH
• Bacterial Infections * drug therapy   microbiology   therapy   MeSH
• Biofilms drug effects   MeSH
• Photochemotherapy * methods   MeSH
• Photosensitizing Agents * pharmacology   MeSH
• Humans MeSH
• Nanoparticles chemistry   MeSH
• Nanostructures chemistry   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Ultrasonic Therapy MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

A university textbook that focuses on pathobiochemistry of metabolic disorders.

• MeSH
• Biochemistry MeSH
• Metabolic Diseases MeSH
• Pathology MeSH

• Conspectus
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• biochemie
• patologie
• NML Publication type
• učebnice vysokých škol

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

• MeSH
• Femoral Artery * MeSH
• Adult MeSH
• Ischemia prevention & control   etiology   MeSH
• Catheterization methods   MeSH
• Extremities blood supply   MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * methods   MeSH
• Perfusion methods   MeSH
• Catheterization, Peripheral methods   adverse effects   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

In humans and many animals, a trade-off between a sufficiently high concentration of erythrocytes (hematocrit) to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. The optimal value lies between the extreme cases of pure blood plasma, which cannot practically transport any oxygen, and 100% hematocrit, which would imply very slow blood flow or none at all. As oxygen delivery to tissues is the main task of the cardiovascular system, it is reasonable to expect that maximum oxygen delivery has been achieved during evolution. Optimal hematocrit theory, based on this optimality principle, has been successful in predicting hematocrit values of about 0.3-0.5, which are indeed observed in the systemic circulation of humans and many animal species. Similarly, the theory can explain why a hematocrit higher than normal, ranging from 0.5 to 0.7, can promote better exertional performance. Here, we present a review of theoretical approaches to the calculation of the optimal hematocrit value under different conditions and discuss them in a broad physiological context. Several physiological and medical implications are outlined, for example, in view of blood doping, temperature adaptation, dehydration, and life at high altitudes.

• MeSH
• Erythrocytes physiology   metabolism   MeSH
• Hematocrit methods   MeSH
• Oxygen * blood   metabolism   MeSH
• Humans MeSH
• Models, Cardiovascular MeSH
• Blood Viscosity physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of OXPHOS during quiescence, beyond ATP production, is not well understood. Using mouse models of inducible OXPHOS deficiency in all cell types or specifically in the vascular endothelium that negligibly relies on OXPHOS-derived ATP, we show that selectively during quiescence OXPHOS provides oxidative stress resistance by supporting macroautophagy/autophagy. Mechanistically, OXPHOS constitutively generates low levels of endogenous ROS that induce autophagy via attenuation of ATG4B activity, which provides protection from ROS insult. Physiologically, the OXPHOS-autophagy system (i) protects healthy tissue from toxicity of ROS-based anticancer therapy, and (ii) provides ROS resistance in the endothelium, ameliorating systemic LPS-induced inflammation as well as inflammatory bowel disease. Hence, cells acquired mitochondria during evolution to profit from oxidative metabolism, but also built in an autophagy-based ROS-induced protective mechanism to guard against oxidative stress associated with OXPHOS function during quiescence.Abbreviations: AMPK: AMP-activated protein kinase; AOX: alternative oxidase; Baf A: bafilomycin A1; CI, respiratory complexes I; DCF-DA: 2',7'-dichlordihydrofluorescein diacetate; DHE: dihydroethidium; DSS: dextran sodium sulfate; ΔΨmi: mitochondrial inner membrane potential; EdU: 5-ethynyl-2'-deoxyuridine; ETC: electron transport chain; FA: formaldehyde; HUVEC; human umbilical cord endothelial cells; IBD: inflammatory bowel disease; LC3B: microtubule associated protein 1 light chain 3 beta; LPS: lipopolysaccharide; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; mtDNA: mitochondrial DNA; NAC: N-acetyl cysteine; OXPHOS: oxidative phosphorylation; PCs: proliferating cells; PE: phosphatidylethanolamine; PEITC: phenethyl isothiocyanate; QCs: quiescent cells; ROS: reactive oxygen species; PLA2: phospholipase A2, WB: western blot.

• MeSH
• Adenosine Triphosphate metabolism   MeSH
• Autophagy * MeSH
• Cysteine metabolism   MeSH
• Dextrans metabolism   MeSH
• Respiration MeSH
• Endothelial Cells metabolism   MeSH
• Fibroblasts metabolism   MeSH
• Formaldehyde metabolism   MeSH
• Phosphatidylethanolamines metabolism   MeSH
• Inflammatory Bowel Diseases * metabolism   MeSH
• Isothiocyanates MeSH
• Humans MeSH
• Lipopolysaccharides metabolism   MeSH
• DNA, Mitochondrial metabolism   MeSH
• Mitochondria metabolism   MeSH
• Mechanistic Target of Rapamycin Complex 1 metabolism   MeSH
• Mice MeSH
• AMP-Activated Protein Kinases metabolism   MeSH
• Microtubule-Associated Proteins metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Sirolimus MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

In humans and higher animals, a trade-off between sufficiently high erythrocyte concentrations to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. Optimal hematocrit theory has been successful in predicting hematocrit (HCT) values of about 0.3-0.5, in very good agreement with the normal values observed for humans and many animal species. However, according to those calculations, the optimal value should be independent of the mechanical load of the body. This is in contradiction to the exertional increase in HCT observed in some animals called natural blood dopers and to the illegal practice of blood boosting in high-performance sports. Here, we present a novel calculation to predict the optimal HCT value under the constraint of constant cardiac power and compare it to the optimal value obtained for constant driving pressure. We show that the optimal HCT under constant power ranges from 0.5 to 0.7, in agreement with observed values in natural blood dopers at exertion. We use this result to explain the tendency to better exertional performance at an increased HCT.

• MeSH
• Hematocrit * MeSH
• Humans MeSH
• Models, Cardiovascular * MeSH
• Athletic Performance MeSH
• Heart physiology   MeSH
• Physical Exertion MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Mitochondrie jsou součástí téměř všech eukaryotických buněk. Jejich funkcí je produkce a uvolňování energie k potřebám buňky, zajišťují beta oxidaci, podílejí se na syntéze steroidů, slouží k produkci tepla netřesovou termoregulací či ke skladování vápníkových iontů. Účastní se také apoptózy buňky a regulace membránového potenciálu. Energetická produkce mitochondrií ovlivňuje proliferaci buněk, změny genové exprese a tvorbu reaktivních forem kyslíku (ROS). Mitochondriální DNA (mtDNA) je uložená v matrix této organely a dědí se výhradně maternálně, proto je vhodným nástrojem pro zkoumání evoluce lidské populace, objasnění evolučních vztahů a také pro mapování migrace v průběhu historie. Genové mutace v jaderné DNA nebo mtDNA negativně ovlivňují mitochondriální aktivitu. V jejich důsledku vznikají různá mitochondriální onemocnění, která se vyznačují specifickým typem dědičnosti a různorodými klinickými projevy. Jejich vznik se nejčastěji vysvětluje teorií mitochondriálního stárnutí. Na kvalitu mitochondrií negativně působí mimo jiné některé vlivy prostředí, zejména záření. Příznivý vliv na mitochondrie má především zdravý životní styl, včetně stravy bohaté na vitaminy, fytonutrienty a antioxidanty.

Mitochondria are part of almost all eukaryotic cells. Their function is to produce and release energy for the needs of the cell, provide beta-oxidation, participate in the synthesis of steroids, serve for heat production through non-shaking thermoregulation or for calcium ions storage. They are also involved in the cell apoptosis and membrane potential regulation. Mitochondrial energy production affects cell proliferation, changes in gene expression, and the formation of reactive oxygen species (ROS). Mitochondrial DNA (mtDNA) is located in the matrix of mitochondria and is inherited exclusively maternally. Hence it is a suitable tool for studying the evolution of the human population, for elucidating evolutionary relationships, and for mapping the migration throughout history. Gene mutations in nuclear DNA or mtDNA negatively impact the mitochondrial activity. As a result, various mitochondrial diseases arise, which are characterized by a specific type of heredity and various clinical manifestations. Their origin has most often been explained by the theory of mitochondrial aging. The quality of mitochondria is negatively affected, among other, by environmental effects, mainly radiation. Most of all they benefit from healthy lifestyle including diets rich in vitamins, phytonutrients, and antioxidants.

• MeSH
• Apoptosis MeSH
• Humans MeSH
• DNA, Mitochondrial MeSH
• Mitochondrial Diseases MeSH
• Mitochondria * physiology   genetics   transplantation   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Catalase is one of the most abundant enzymes on Earth. It decomposes hydrogen peroxide, thus protecting cells from dangerous reactive oxygen species. The catalase-encoding gene is conspicuously absent from the genome of most representatives of the family Trypanosomatidae. Here, we expressed this protein from the Leishmania mexicana Β-TUBULIN locus using a novel bicistronic expression system, which relies on the 2A peptide of Teschovirus A. We demonstrated that catalase-expressing parasites are severely compromised in their ability to develop in insects, to be transmitted and to infect mice, and to cause clinical manifestation in their mammalian host. Taken together, our data support the hypothesis that the presence of catalase is not compatible with the dixenous life cycle of Leishmania, resulting in loss of this gene from the genome during the evolution of these parasites.

• MeSH
• Virulence Factors genetics   metabolism   MeSH
• Catalase genetics   metabolism   MeSH
• Cells, Cultured MeSH
• Leishmania mexicana genetics   growth & development   pathogenicity   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Protozoan Proteins genetics   MeSH
• Psychodidae parasitology   MeSH
• Life Cycle Stages genetics   MeSH
• Teschovirus genetics   MeSH
• Virulence MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Receptor adenylate cyclases (RACs) on the surface of trypanosomatids are important players in the host-parasite interface. They detect still unidentified environmental signals that affect the parasites' responses to host immune challenge, coordination of social motility, and regulation of cell division. A lesser known class of oxygen-sensing adenylate cyclases (OACs) related to RACs has been lost in trypanosomes and expanded mostly in Leishmania species and related insect-dwelling trypanosomatids. In this work, we have undertaken a large-scale phylogenetic analysis of both classes of adenylate cyclases (ACs) in trypanosomatids and the free-living Bodo saltans. We observe that the expanded RAC repertoire in trypanosomatids with a two-host life cycle is not only associated with an extracellular lifestyle within the vertebrate host, but also with a complex path through the insect vector involving several life cycle stages. In Trypanosoma brucei, RACs are split into two major clades, which significantly differ in their expression profiles in the mammalian host and the insect vector. RACs of the closely related Trypanosoma congolense are intermingled within these two clades, supporting early RAC diversification. Subspecies of T. brucei that have lost the capacity to infect insects exhibit high numbers of pseudogenized RACs, suggesting many of these proteins have become redundant upon the acquisition of a single-host life cycle. OACs appear to be an innovation occurring after the expansion of RACs in trypanosomatids. Endosymbiont-harboring trypanosomatids exhibit a diversification of OACs, whereas these proteins are pseudogenized in Leishmania subgenus Viannia. This analysis sheds light on how ACs have evolved to allow diverse trypanosomatids to occupy multifarious niches and assume various lifestyles.

• MeSH
• Adenylyl Cyclases genetics   MeSH
• Gene Duplication MeSH
• Phylogeny * MeSH
• Genome, Protozoan MeSH
• Host-Pathogen Interactions genetics   MeSH
• Evolution, Molecular * MeSH
• Trypanosomatina enzymology   genetics   MeSH
• Up-Regulation MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The atrial septum enables efficient oxygen transport by separating the systemic and pulmonary venous blood returning to the heart. Only in placental mammals will the atrial septum form by the coming-together of the septum primum and the septum secundum. In up to one of four placental mammals, this complex morphogenesis is incomplete and yields patent foramen ovale. The incidence of incomplete atrial septum is unknown for groups with the septum primum only, such as birds and reptiles. We found a low incidence of incomplete atrial septum in 11 species of bird (0% of specimens) and 13 species of reptiles (3% of specimens). In reptiles, there was a trabecular interface between the atrial septum and the atrial epicardium which was without a clear boundary between left and right atrial cavities. In developing reptiles (four squamates and one crocodylian), the septum primum initiated as a sheet that acquired perforations and the trabecular interface developed late. We conclude that atrial septation from the septum primum only results in a low incidence of incompleteness. In reptiles, the atrial septum and atrial wall develop a trabecular interface, but previous studies on atrial hemodynamics suggest this interface has a very limited capacity for shunting.

• MeSH
• Heart Septal Defects, Atrial epidemiology   etiology   MeSH
• Incidence MeSH
• Reptiles abnormalities   MeSH
• Birds abnormalities   MeSH
• Atrial Septum embryology   growth & development   pathology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH