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Medicina (Kaunas, Lithuania) May 2024For a large benign lesion within the maxillary sinus, such as an antral pseudocyst, maxillary sinus floor augmentation is more commonly performed using a two-stage...
For a large benign lesion within the maxillary sinus, such as an antral pseudocyst, maxillary sinus floor augmentation is more commonly performed using a two-stage approach. This involves first removing the lesion, and then, re-entry following several months of healing. In this case series, we described the "one-bony-window" approach, which is a technical surgical modification of the previous one-stage approach, for simultaneous cyst removal and maxillary sinus floor augmentation. Four patients with large maxillary antral pseudocysts were included. The "one-bony-window" approach involves the preparation of a large window opening of approximately 15 mm × 20 mm at the lateral wall. A mesiodistally extended intentional perforation was made in the upper part of the exposed membrane to enhance the access for instrumentation. The antral pseudocyst was removed in its entirety without being deformed to prevent rupture or leakage of the cystic contents. Subsequent detachment and elevation of the Schneiderian membrane at the sinus floor significantly reduced the perforation site, and bone grafting with implant placement was performed simultaneously. This alleviated the need to surgically repair the perforation. The lateral opening was either uncovered or repositioned using bony window lids. Healing abutments were connected after six months, and the final prosthesis was placed after two months. At the 1-year follow-up, the antral pseudocysts had resolved with no specific recurrence, and the stability of the augmented sinus was maintained with excellent implant survival. Within the limitations of our findings, the "one-bony-window" technique can be suggested for the simultaneous removal of large antral pseudocysts and maxillary sinus floor augmentation with favorable clinical outcomes.
Topics: Humans; Sinus Floor Augmentation; Maxillary Sinus; Female; Male; Middle Aged; Cysts; Adult; Treatment Outcome; Aged
PubMed: 38793021
DOI: 10.3390/medicina60050838 -
Molecules (Basel, Switzerland) May 2024Poly(2-hydroxyethylmethacrylate-co-2-(dimethylamino)ethyl methacrylate), P(HEMA-co-DMAEMAx), copolymers were quaternized through the reaction of a part of...
Poly(2-hydroxyethylmethacrylate-co-2-(dimethylamino)ethyl methacrylate), P(HEMA-co-DMAEMAx), copolymers were quaternized through the reaction of a part of (dimethylamino)ethyl moieties of DMAEMA units with 1-bromohexadecane. Antimicrobial coatings were further prepared through the cross-linking reaction between the remaining DMAEMA units of these copolymers and the epoxide ring of poly(,-dimethylacrylamide-co-glycidyl methacrylate), P(DMAm-co-GMAx), copolymers. The combination of P(HEMA-co-DMAEMAx)/P(DMAm-co-GMAx) copolymers not only enabled control over quaternization and cross-linking for coating stabilization but also allowed the optimization of the processing routes towards a more facile cost-effective methodology and the use of environmentally friendly solvents like ethanol. Careful consideration was given to achieve the right content of quaternized units, qDMAEMA, to ensure antimicrobial efficacy through an appropriate amphiphilic balance and sufficient free DMAEMA groups to react with GMA for coating stabilization. Optimal synthesis conditions were achieved by membranes consisting of cross-linked P(HEMA78-co-DMAEMA9-co-qDMAEMA13)/P(DMAm-co-GMA42) membranes. The obtained membranes were multifunctional as they were self-standing and antimicrobial, while they demonstrated a distinct fast response to changes in humidity levels, widening the opportunities for the construction of "smart" antimicrobial actuators, such as non-contact antimicrobial switches.
Topics: Humidity; Methacrylates; Anti-Infective Agents; Cross-Linking Reagents; Microbial Sensitivity Tests; Polymers
PubMed: 38792232
DOI: 10.3390/molecules29102372 -
International Journal of Molecular... May 2024In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems,... (Review)
Review
Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin-Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions.
In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both renin-angiotensin and dopaminergic systems influence intestinal Na/K-ATPase activity, thus maintaining electrolyte and nutritional homeostasis. The colocalization of BAT1 and ACE2 indicates the direct role of the renin-angiotensin system in amino acid absorption. Yet, more studies are needed to thoroughly define the structural and functional interaction between TJ-associated proteins and GI renin-angiotensin and dopaminergic systems.
Topics: Humans; Renin-Angiotensin System; Dopamine; Animals; Tight Junctions; Intestinal Mucosa; Permeability; Gastrointestinal Tract; Intestinal Barrier Function
PubMed: 38791603
DOI: 10.3390/ijms25105566 -
International Journal of Molecular... May 2024Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease characterized by pathologic vascular remodeling of small pulmonary arteries. Endothelial...
Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease characterized by pathologic vascular remodeling of small pulmonary arteries. Endothelial dysfunction in advanced PAH is associated with proliferation, apoptosis resistance, and endothelial to mesenchymal transition (EndoMT) due to aberrant signaling. DLL4, a cell membrane associated NOTCH ligand, plays a pivotal role maintaining vascular integrity. Inhibition of DLL4 has been associated with the development of pulmonary hypertension, but the mechanism is incompletely understood. Here we report that silencing in pulmonary artery endothelial cells (PAECs) activated AKT and suppressed the expression of DLL4. Consistent with these in vitro findings, increased AKT activation and reduced DLL4 expression was found in the small pulmonary arteries of patients with PAH. Increased NOTCH1 activation through exogenous DLL4 blocked AKT activation, decreased proliferation and reversed EndoMT. Exogenous and overexpression of DLL4 induced and PPRE promoter activity, and and mRNA in idiopathic PAH (IPAH) ECs. PPARγ, a nuclear receptor associated with EC homeostasis, suppressed by BMPR2 loss was induced and activated by DLL4/NOTCH1 signaling in both -silenced and IPAH ECs, reversing aberrant phenotypic changes, in part through AKT inhibition. Directly blocking AKT or restoring DLL4/NOTCH1/PPARγ signaling may be beneficial in preventing or reversing the pathologic vascular remodeling of PAH.
Topics: Humans; Proto-Oncogene Proteins c-akt; Signal Transduction; Bone Morphogenetic Protein Receptors, Type II; PPAR gamma; Receptor, Notch1; Pulmonary Artery; Endothelial Cells; Adaptor Proteins, Signal Transducing; Calcium-Binding Proteins; Pulmonary Arterial Hypertension; Male; Cell Proliferation; Hypertension, Pulmonary; Female; Cells, Cultured
PubMed: 38791441
DOI: 10.3390/ijms25105403 -
International Journal of Molecular... May 2024The pathogenicity of many bacteria, including and , depends on pore-forming toxins (PFTs), which cause the lysis of host cells by forming pores in the membranes of...
The pathogenicity of many bacteria, including and , depends on pore-forming toxins (PFTs), which cause the lysis of host cells by forming pores in the membranes of eukaryotic cells. Bioinformatic analysis revealed a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from in over 600 PFTs, which we designated as a "homologous peptide". Three β-barrel PFTs were used for a detailed comparative analysis. Two of them-HlyII and cytotoxin K2 (CytK2)-are synthesized in ; the third, α-toxin (Hla), is the most investigated representative of the family. Protein modeling showed certain amino acids of the homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide, DSFNTFYGNQLFMK, as part of the homologous peptide. The HlyII, CytK2, and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of this work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.
Topics: Bacterial Toxins; Bacillus cereus; Hemolysin Proteins; Staphylococcus aureus; Amino Acid Sequence; Hemolysis; Pore Forming Cytotoxic Proteins; Models, Molecular; Animals; Antibodies, Monoclonal; Humans; Bacterial Proteins
PubMed: 38791367
DOI: 10.3390/ijms25105327 -
International Journal of Molecular... May 2024Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated... (Review)
Review
Drug-Induced Fatty Liver Disease (DIFLD): A Comprehensive Analysis of Clinical, Biochemical, and Histopathological Data for Mechanisms Identification and Consistency with Current Adverse Outcome Pathways.
Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated steatotic liver disease (MASLD), which specifically refers to the accumulation of fat in the liver unrelated to alcohol intake. A bi-directional relationship between DILI and MASLD is likely to exist: while certain drugs can cause MASLD by acting as pro-steatogenic factors, MASLD may make hepatocytes more vulnerable to drugs. Having a pre-existing MASLD significantly heightens the likelihood of experiencing DILI from certain medications. Thus, the prevalence of steatosis within DILI may be biased by pre-existing MASLD, and it can be concluded that the genuine true incidence of DIFLD in the general population remains unknown. In certain individuals, drug-induced steatosis is often accompanied by concomitant injury mechanisms such as oxidative stress, cell death, and inflammation, which leads to the development of drug-induced steatohepatitis (DISH). DISH is much more severe from the clinical point of view, has worse prognosis and outcome, and resembles MASH (metabolic-associated steatohepatitis), as it is associated with inflammation and sometimes with fibrosis. A literature review of clinical case reports allowed us to examine and evaluate the clinical features of DIFLD and their association with specific drugs, enabling us to propose a classification of DIFLD drugs based on clinical outcomes and pathological severity: Group 1, drugs with low intrinsic toxicity (e.g., ibuprofen, naproxen, acetaminophen, irinotecan, methotrexate, and tamoxifen), but expected to promote/aggravate steatosis in patients with pre-existing MASLD; Group 2, drugs associated with steatosis and only occasionally with steatohepatitis (e.g., amiodarone, valproic acid, and tetracycline); and Group 3, drugs with a great tendency to transit to steatohepatitis and further to fibrosis. Different mechanisms may be in play when identifying drug mode of action: (1) inhibition of mitochondrial fatty acid β-oxidation; (2) inhibition of fatty acid transport across mitochondrial membranes; (3) increased de novo lipid synthesis; (4) reduction in lipid export by the inhibition of microsomal triglyceride transfer protein; (5) induction of mitochondrial permeability transition pore opening; (6) dissipation of the mitochondrial transmembrane potential; (7) impairment of the mitochondrial respiratory chain/oxidative phosphorylation; (8) mitochondrial DNA damage, degradation and depletion; and (9) nuclear receptors (NRs)/transcriptomic alterations. Currently, the majority of, if not all, adverse outcome pathways (AOPs) for steatosis in AOP-Wiki highlight the interaction with NRs or transcription factors as the key molecular initiating event (MIE). This perspective suggests that chemical-induced steatosis typically results from the interplay between a chemical and a NR or transcription factors, implying that this interaction represents the primary and pivotal MIE. However, upon conducting this exhaustive literature review, it became evident that the current AOPs tend to overly emphasize this interaction as the sole MIE. Some studies indeed support the involvement of NRs in steatosis, but others demonstrate that such NR interactions alone do not necessarily lead to steatosis. This view, ignoring other mitochondrial-related injury mechanisms, falls short in encapsulating the intricate biological mechanisms involved in chemically induced liver steatosis, necessitating their consideration as part of the AOP's map road as well.
Topics: Humans; Fatty Liver; Chemical and Drug Induced Liver Injury; Adverse Outcome Pathways; Liver; Oxidative Stress
PubMed: 38791241
DOI: 10.3390/ijms25105203 -
International Journal of Molecular... May 2024The membrane F factor of ATP synthase is highly sensitive to mutations in the proton half-channel leading to the functional blocking of the entire protein. To identify...
The membrane F factor of ATP synthase is highly sensitive to mutations in the proton half-channel leading to the functional blocking of the entire protein. To identify functionally important amino acids for the proton transport, we performed molecular dynamic simulations on the selected mutants of the membrane part of the bacterial FF-ATP synthase embedded in a native lipid bilayer: there were nine different mutations of -subunit residues (E219, H245, N214, Q252) in the inlet half-channel. The structure proved to be stable to these mutations, although some of them (H245Y and Q252L) resulted in minor conformational changes. H245 and N214 were crucial for proton transport as they directly facilitated H transfer. The substitutions with nonpolar amino acids disrupted the transfer chain and water molecules or neighboring polar side chains could not replace them effectively. E219 and Q252 appeared not to be determinative for proton translocation, since an alternative pathway involving a chain of water molecules could compensate the ability of H transmembrane movement when they were substituted. Thus, mutations of conserved polar residues significantly affected hydration levels, leading to drastic changes in the occupancy and capacity of the structural water molecule clusters (W1-W3), up to their complete disappearance and consequently to the proton transfer chain disruption.
Topics: Lipid Bilayers; Molecular Dynamics Simulation; Mutation; Protein Conformation; Protein Subunits; Bacterial Proton-Translocating ATPases
PubMed: 38791189
DOI: 10.3390/ijms25105143 -
International Journal of Molecular... May 2024Identifying alterations caused by aging could be an important tool for improving the diagnosis of cardiovascular diseases. Changes in vascular tone regulation involve... (Review)
Review
Identifying alterations caused by aging could be an important tool for improving the diagnosis of cardiovascular diseases. Changes in vascular tone regulation involve various mechanisms, like NO synthase activity, activity of the sympathetic nervous system, production of prostaglandin, endothelium-dependent relaxing, and contracting factors, etc. Surprisingly, Ca-dependent Cl channels (CaCCs) are involved in all alterations of the vascular tone regulation mentioned above. Furthermore, we discuss these mechanisms in the context of ontogenetic development and aging. The molecular and electrophysiological mechanisms of CaCCs activation on the cell membrane of the vascular smooth muscle cells (VSMC) and endothelium are explained, as well as the age-dependent changes that imply the activation or inhibition of CaCCs. In conclusion, due to the diverse intracellular concentration of chloride in VSMC and endothelial cells, the activation of CaCCs depends, in part, on intracellular Ca concentration, and, in part, on voltage, leading to fine adjustments of vascular tone. The activation of CaCCs declines during ontogenetic development and aging. This decline in the activation of CaCCs involves a decrease in protein level, the impairment of Ca influx, and probably other alterations in vascular tone regulation.
Topics: Humans; Aging; Animals; Calcium; Muscle, Smooth, Vascular; Chloride Channels; Endothelium, Vascular; Myocytes, Smooth Muscle
PubMed: 38791133
DOI: 10.3390/ijms25105093 -
Antioxidants (Basel, Switzerland) May 2024Dimethyl sulfoxide (DMSO), an organosulfur compound, is widely used as the gold standard solvent in biological research. It is used in cell culture experiments and as a...
Dimethyl sulfoxide (DMSO), an organosulfur compound, is widely used as the gold standard solvent in biological research. It is used in cell culture experiments and as a component of formulations in in vivo studies. Unfortunately, parameters related to sulfur metabolism are often not taken into account when using DMSO. Therefore, in this work we aim to show that the addition of DMSO to the culture medium (even in amounts commonly considered acceptable) alters some parameters of sulfur metabolism. For this study, we used three cell lines: a commercially available Caco-2 line (HTB-37, ATCC) and two lines created as part of our early studies (likewise previously described in the literature) to investigate the anomalies of sulfur metabolism in mucopolysaccharidosis. As the negative effects of DMSO on the cell membrane are well known, additional experiments with the partial loading of DMSO into polymerosomes (poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide), PEG-PLGA) were performed to eliminate these potentially disruptive effects. The results show that DMSO is a source of interference in studies related to sulfur metabolism and that there are not just simple effects that can be corrected in the final result by subtracting control values, since complex synergisms are also observed.
PubMed: 38790687
DOI: 10.3390/antiox13050582 -
Current Opinion in Cell Biology Jun 2024Caveolae are atypical plasma membrane invaginations that take part in lipid sorting and regulation of oxidative and mechanical plasma membrane stress. Caveola formation... (Review)
Review
Caveolae are atypical plasma membrane invaginations that take part in lipid sorting and regulation of oxidative and mechanical plasma membrane stress. Caveola formation requires caveolin, cavin, and specific lipid types. The recent advances in understanding the structure and assembly of caveolin and cavin complexes within the membrane context have clarified the fundamental processes underlying caveola biogenesis. In addition, the curvature of the caveola membrane is controlled by the regulatory proteins EHD2, pacsin2, and dynamin2, which also function to restrain the scission of caveolae from the plasma membrane (PM). Here, this is integrated with novel insights on caveolae as lipid and mechanosensing complexes that can dynamically flatten or disassemble to counteract mechanical, and oxidative stress.
Topics: Humans; Caveolae; Cell Membrane; Animals; Caveolins
PubMed: 38788266
DOI: 10.1016/j.ceb.2024.102371