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Redox Biology Jul 2024Inflammation and subsequent mitochondrial dysfunction and cell death worsen outcomes after revascularization in ischemic stroke. Receptor-interacting protein kinase 1...
Modulation of NLRP3 inflammasome-related-inflammation via RIPK1/RIPK3-DRP1 or HIF-1α signaling by phenothiazine in hypothermic and normothermic neuroprotection after acute ischemic stroke.
BACKGROUND
Inflammation and subsequent mitochondrial dysfunction and cell death worsen outcomes after revascularization in ischemic stroke. Receptor-interacting protein kinase 1 (RIPK1) activated dynamin-related protein 1 (DRP1) in a NLRPyrin domain containing 3 (NLRP3) inflammasome-dependent fashion and Hypoxia-Inducible Factor (HIF)-1α play key roles in the process. This study determined how phenothiazine drugs (chlorpromazine and promethazine (C + P)) with the hypothermic and normothermic modality impacts the RIPK1/RIPK3-DRP1 and HIF-1α pathways in providing neuroprotection.
METHODS
A total of 150 adult male Sprague-Dawley rats were subjected to 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. 8 mg/kg of C + P was administered at onset of reperfusion. Infarct volumes, mRNA and protein expressions of HIF-1α, RIPK1, RIPK3, DRP-1, NLRP3-inflammation and cytochrome c-apoptosis were assessed. Apoptotic cell death, infiltration of neutrophils and macrophages, and mitochondrial function were evaluated. Interaction between RIPK1/RIPK3 and HIF-1α/NLRP3 were determined. In SH-SY5Y cells subjected to oxygen/glucose deprivation (OGD), the normothermic effect of C + P on inflammation and apoptosis were examined.
RESULTS
C + P significantly reduced infarct volumes, mitochondrial dysfunction (ATP and ROS concentration, citrate synthase and ATPase activity), inflammation and apoptosis with and without induced hypothermia. Overexpression of RIPK1, RIPK3, DRP-1, NLRP3-inflammasome and cytochrome c-apoptosis were all significantly reduced by C + P at 33 °C and the RIPK1 inhibitor (Nec1s), suggesting hypothermic effect of C + P via RIPK1/RIPK3-DRP1pathway. When body temperature was maintained at 37 °C, C + P and HIF-1α inhibitor (YC-1) reduced HIF-1α expression, leading to reduction in mitochondrial dysfunction, NLRP3 inflammasome and cytochrome c-apoptosis, as well as the interaction of HIF-1α and NLRP3. These were also evidenced in vitro, indicating a normothermic effect of C + P via HIF-1α.
CONCLUSION
Hypothermic and normothermic neuroprotection of C + P involve different pathways. The normothermic effect was mediated by HIF-1α, while hypothermic effect was via RIPK1/RIPK3-DRP1 signaling. This provides a theoretical basis for future precise exploration of hypothermic and normothermic neuroprotection.
Topics: Animals; Receptor-Interacting Protein Serine-Threonine Kinases; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Ischemic Stroke; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Signal Transduction; Inflammasomes; Dynamins; Rats, Sprague-Dawley; Phenothiazines; Inflammation; Neuroprotection; Humans; Disease Models, Animal; Hypothermia, Induced
PubMed: 38692093
DOI: 10.1016/j.redox.2024.103169 -
Organic Letters May 2024A new method to synthesize -bromobenzenethiol equivalents through aryne intermediates is disclosed. Various -bromobenzenethiol equivalents are prepared by the...
A new method to synthesize -bromobenzenethiol equivalents through aryne intermediates is disclosed. Various -bromobenzenethiol equivalents are prepared by the bromothiolation of aryne intermediates with potassium xanthates. Aryl xanthates serve in the synthesis of diverse organosulfurs involving phenothiazines and thianthrenes by further transformations.
PubMed: 38688840
DOI: 10.1021/acs.orglett.4c00944 -
Scientific Reports Apr 2024Our study focused on the optical behavior, methylene blue (MB) dye degradation potential, antibacterial performance, and silver and trioxide mineral interaction with...
Our study focused on the optical behavior, methylene blue (MB) dye degradation potential, antibacterial performance, and silver and trioxide mineral interaction with different bacterial species. We found that the addition of silver nanoparticles (Ag NPs) to neodymium oxide (NdO) resulted in a significant response, with an enlargement of the inhibition zone for bacterial species such as Staphylococcus aureus and Escherichia coli. Specifically, the inhibition zone for S. aureus increased from 9.3 ± 0.5 mm for pure NdO to 16.7 ± 0.4 mm for the Ag/NdO nano-composite, while for E. coli, it increased from 8.8 ± 0.4 mm for NdO to 15.9 ± 0.3 mm for Ag/NdO. Furthermore, the optical behavior of the composites showed a clear band-gap narrowing with the addition of Ag NPs, resulting in enhanced electronic localization. The direct and indirect transitions reduced from 6.7 to 6.1 eV and from 5.2 to 2.9 eV, respectively. Overall, these results suggest that the Ag/NdO nano-composite has potential applications in sensor industries and water treatment, thanks to its enhanced optical behavior, antibacterial performance, and efficient MB degradation capabilities. In terms of MB degradation, the Ag/NdO mixed system exhibited more efficient degradation compared to pure NdO. After 150 min, the MB concentration in the mixed system decreased to almost half of its starting point, while pure NdO only reached 33%.
Topics: Methylene Blue; Metal Nanoparticles; Silver; Escherichia coli; Staphylococcus aureus; Anti-Bacterial Agents; Neodymium; Oxides; Adsorption
PubMed: 38684756
DOI: 10.1038/s41598-024-57226-4 -
Journal of Clinical Anesthesia Sep 2024The objective of this anatomical study was to investigate the distribution of a solution administered using the Clavipectoral Fascia Plane Block (CPB) technique in a... (Observational Study)
Observational Study
STUDY OBJECTIVE
The objective of this anatomical study was to investigate the distribution of a solution administered using the Clavipectoral Fascia Plane Block (CPB) technique in a series of cadaveric models with midshaft clavicular fractures. The study aimed to address the knowledge gap regarding the impact of clavicular fractures on the distribution pattern of the CPB-administered solution.
DESIGN
Observational cadaveric study.
SETTING
The research was conducted in the laboratory setting of the University of Barcelona, adhering to the institution's ethical guidelines and standards.
PATIENTS
Five unembalmed human cadavers were used, generating ten clavicle samples.
INTERVENTIONS
A postmortem fracture was induced in the middle third of the clavicle using a blunt-edged hammer, simulating a midshaft clavicular fracture.
MEASUREMENTS
Anatomical dissection was performed in three layers: the superficial muscle plane, deep muscle plane, and clavicular periosteum plane. Dye staining with methylene blue was utilized to assess the distribution pattern.
MAIN RESULTS
In the superficial muscular plane, methylene blue was observed in the deltoid (100%), pectoralis major (100%), sternocleidomastoid (SCM) (70%), and trapezius muscles (100%). Conversely, the deep muscular plane, including the subclavius muscle, pectoralis minor, and Clavipectoral Fascia (CPF), exhibited no staining. At the clavicular periosteum plane, methylene blue distributed predominantly to the antero-superior region (57.3%), with a minimal impact on the postero-inferior area (6.5%).
CONCLUSIONS
The study reveals that the presence of a midshaft clavicular fracture does not significantly alter the diffusion pattern of the CPB-administered solution, maintaining a consistent distribution in both intact and fractured clavicle models.
Topics: Humans; Clavicle; Cadaver; Fractures, Bone; Nerve Block; Fascia; Male; Aged; Anesthetics, Local; Female; Methylene Blue; Aged, 80 and over; Muscle, Skeletal; Dissection
PubMed: 38678917
DOI: 10.1016/j.jclinane.2024.111469 -
Brain Research Bulletin Jun 2024In clinical trials for Alzheimer's disease (AD), hydromethylthionine mesylate (HMTM) showed reduced efficacy when administered as an add-on to symptomatic treatments,...
In clinical trials for Alzheimer's disease (AD), hydromethylthionine mesylate (HMTM) showed reduced efficacy when administered as an add-on to symptomatic treatments, while it produced a significant improvement of cognitive function when taken as monotherapy. Interference of cholinesterase inhibition with HMTM was observed also in a tau transgenic mouse model, where rivastigmine reduced the pharmacological activity of HMTM at multiple brain levels including hippocampal acetylcholine release, synaptosomal glutamate release and mitochondrial activity. Here, we examined the effect of HMTM, given alone or in combination with the acetylcholinesterase inhibitor, rivastigmine, at the level of expression of selected pre-synaptic proteins (syntaxin-1; SNAP-25, VAMP-2, synaptophysin-1, synapsin-1, α-synuclein) in brain tissue harvested from tau-transgenic Line 1 (L1) and wild-type mice using immunohistochemistry. L1 mice overexpress the tau-core unit that induces tau aggregation and results in an AD-like phenotype. Synaptic proteins were lower in hippocampus and cortex but greater in basal forebrain regions in L1 compared to wild-type mice. HMTM partially normalised the expression pattern of several of these proteins in basal forebrain. This effect was diminished when HMTM was administered in combination with rivastigmine, where mean protein expression seemed supressed. This was further confirmed by group-based correlation network analyses where important levels of co-expression correlations in basal forebrain regions were lost in L1 mice and partially re-established when HMTM was given alone but not in combination with rivastigmine. These data indicate a reduction in pharmacological activity of HMTM when given as an add-on therapy, a result that is consistent with the responses observed in the clinic. Attenuation of the therapeutic effects of HMTM by cholinergic treatments may have important implications for other potential AD therapies.
Topics: Animals; Tauopathies; Mice, Transgenic; Disease Models, Animal; Cholinesterase Inhibitors; Rivastigmine; Mice; tau Proteins; Synapses; Brain; Alzheimer Disease; Male; Methylene Blue
PubMed: 38677558
DOI: 10.1016/j.brainresbull.2024.110955 -
Molecules (Basel, Switzerland) Apr 2024In this study, we prepared high-nitrogen self-doped porous carbons (NPC1 and NPC2) derived from the pruned branches and seeds of using a simple one-step method. NPC1...
In this study, we prepared high-nitrogen self-doped porous carbons (NPC1 and NPC2) derived from the pruned branches and seeds of using a simple one-step method. NPC1 and NPC2 exhibited elevated nitrogen contents of 3.56% and 4.22%, respectively, along with rich porous structures, high specific surface areas of 1492.9 and 1712.7 m g and abundant surface groups. Notably, both NPC1 and NPC2 demonstrated remarkable adsorption abilities for the pollutant methylene blue (MB), with maximum monolayer adsorption capacities of 568.18 and 581.40 mg g, respectively. The adsorption kinetics followed the pseudo-second-order kinetics and the adsorption isotherms conformed to the Langmuir isotherm model. The adsorption mechanism primarily relied on the hierarchical pore structures of NPC1 and NPC2 and their diverse strong interactions with MB molecules. This study offers a new approach for the cost-effective design of nitrogen self-doped porous carbons, facilitating the efficient removal of MB from wastewater.
Topics: Zanthoxylum; Adsorption; Nitrogen; Methylene Blue; Porosity; Carbon; Kinetics; Water Pollutants, Chemical; Water Purification; Wastewater
PubMed: 38675629
DOI: 10.3390/molecules29081809 -
International Journal of Molecular... Apr 2024This study focuses on synthesizing and characterizing a graphene oxide/ZnTiO/TiO (GO/ZTO/TO) composite to efficiently remove methylene blue (MB) from water, presenting a...
This study focuses on synthesizing and characterizing a graphene oxide/ZnTiO/TiO (GO/ZTO/TO) composite to efficiently remove methylene blue (MB) from water, presenting a novel solution to address industrial dye pollution. GO and ZTO/TO were synthesized by the modified Hummers and sol-gel methods, respectively, while GO/ZTO/TO was prepared using a hydrothermal process. The structural and surface properties of the composite were characterized using various analytical techniques confirming the integration of the constituent materials and suitability for dye adsorption. The study revealed that GO/ZTO/TO exhibits an adsorption capacity of 78 mg g for MB, with only a 15% reduction in adsorption efficiency until the fifth reuse cycle. Furthermore, the study suggests optimal adsorption near neutral pH and enhanced performance at elevated temperatures, indicating an endothermic reaction. The adsorption behavior fits the Langmuir isotherm, implying monolayer adsorption on homogeneous surfaces, and follows pseudo-second-order kinetics, highlighting chemical interactions at the surface as the rate-limiting step. The photocatalytic degradation of MB by GO/ZTO/TO follows pseudo-first-order kinetics, with a higher rate constant than that of GO alone, demonstrating the enhanced photocatalytic activity of the composite. In conclusion, GO/ZTO/TO emerges as a promising and sustainable approach for water purification, through an adsorption process and subsequent photocatalytic degradation.
Topics: Methylene Blue; Titanium; Adsorption; Graphite; Catalysis; Water Pollutants, Chemical; Water Purification; Kinetics; Photochemical Processes; Hydrogen-Ion Concentration; Zinc
PubMed: 38673952
DOI: 10.3390/ijms25084367 -
International Journal of Molecular... Apr 2024Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first...
Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first compound used successfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from its activity in neurons, chlorpromazine has also been reported to display anticancer and antibacterial properties. In this study, we present the synthesis and research on the activity of A549, MDA, MiaPaCa, PC3, and HCT116 cancer cell lines and of , , , and bacterial strains against a series of new tetracyclic chlorpromazine analogues containing a quinoline scaffold in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been determined by H NMR, C NMR, and HRMS spectral techniques. The seven most active of the twenty-four new chlorpromazine analogues tested were selected to study the mechanism of cytotoxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected compounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, MiaPaCa-2, and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis.
Topics: Humans; Chlorpromazine; Anti-Bacterial Agents; Antineoplastic Agents; Phenothiazines; Cell Line, Tumor; Apoptosis; Quinolines; Microbial Sensitivity Tests; Cell Proliferation; Structure-Activity Relationship; HCT116 Cells
PubMed: 38673734
DOI: 10.3390/ijms25084148 -
Scientific Reports Apr 2024A simple and rapid electrochemical sensing method with high sensitivity and specificity of aptamers was developed for the detection of methylamphetamine (MAMP). A short...
A simple and rapid electrochemical sensing method with high sensitivity and specificity of aptamers was developed for the detection of methylamphetamine (MAMP). A short anti-MAMP thiolated aptamer (Apt) with a methylene blue (MB) probe at 3'-end was immobilized on the surface of a gold electrode (MB-Apt-S/GE). The electrochemical signal appeared when MAMP presenting in the sample solution competed with cDNA for binding with MB-Apt-S. Under optimized conditions, the liner range of this signal-on electrochemical aptasensor for the detection of MAMP achieved from 1.0 to 10.0 nmol/L and 10.0-400 nmol/L. LOD 0.88 nmol/L were obtained. Satisfactory spiked recoveries of saliva and urine were also obtained. In this method, only 5 min were needed to incubate before the square wave voltammetry (SWV) analysis, which was much more rapid than other electrochemical sensors, leading to a bright and broad prospect for the detection of MAMP in biological sample. This method can be used for on-site rapid detection on special occasions, such as drug driving scenes, entertainment venues suspected of drug use, etc.
Topics: Electrochemical Techniques; Biosensing Techniques; Aptamers, Nucleotide; Humans; Methamphetamine; DNA, Complementary; Saliva; Electrodes; Limit of Detection; Gold; Methylene Blue
PubMed: 38654039
DOI: 10.1038/s41598-024-59505-6 -
Medical Science Monitor : International... Apr 2024BACKGROUND This retrospective study of 42 patients with popliteal cysts (or Baker cysts) aimed to compare the effects on duration and outcomes of arthroscopic surgical... (Comparative Study)
Comparative Study
BACKGROUND This retrospective study of 42 patients with popliteal cysts (or Baker cysts) aimed to compare the effects on duration and outcomes of arthroscopic surgical debridement with and without the use of cyst injection with methylene blue (MB). MATERIAL AND METHODS Medical records of patients who underwent conventional arthroscopic surgery (n=20) or arthroscopic surgery after MB injection (n=22) for popliteal cysts between 2018 and 2021 were reviewed. The MB group underwent arthroscopic popliteal cystectomy with MB as the marker, and the control group underwent conventional arthroscopic popliteal cystectomy. Surgical time of cyst resection, postoperative bruising extent, complication rate, and cyst recurrence rate of the 2 groups were compared. RESULTS The MB group had a faster surgical cyst removal time (16.5±1.5 min) than the control group (24.5±1.6 min; P<0.05). The MB group had less postoperative bruising (1 case, 4.5%) than the control group (5 cases, 25%; P<0.05). The surgical results were similar in both groups, with a Lysholm score of 87.23±1.80 in the MB group and 87.23±1.62 (P>0.05) in the control group. CONCLUSIONS This study showed that preoperative injection of MB for popliteal cysts before arthroscopic debridement improved cyst localization and ease and accuracy of surgery and reduced operative time, adjacent tissue damage, postoperative complications, and recurrence rate.
Topics: Humans; Arthroscopy; Popliteal Cyst; Male; Debridement; Retrospective Studies; Female; Middle Aged; Methylene Blue; Treatment Outcome; Adult; Postoperative Complications; Aged
PubMed: 38650310
DOI: 10.12659/MSM.941102