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Biomolecules Jun 2024Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of...
Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4 T cells, CD8 T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1β and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1β and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease.
Topics: Animals; Angiotensin II; Aortic Aneurysm, Abdominal; Mice; Male; Sulfonamides; Apolipoproteins E; Phosphate-Binding Proteins; Disease Models, Animal; Mice, Inbred C57BL; Macrophages; Indoles; Mice, Knockout, ApoE; Gasdermins
PubMed: 38927129
DOI: 10.3390/biom14060726 -
BMC Pediatrics Jun 2024Despite the highest (88%) Prevention of Mother-To-Child Transmission (PMTCT) of HIV coverage in Eastern Africa, 50% of new HIV infections in children aged 0-14 years...
Feeding modalities, HIV transmission and its predictors among HIV-exposed infants visited Gamo and Gofa zones public health facilities, Southern Ethiopia: a retrospective follow up study.
BACKGROUND
Despite the highest (88%) Prevention of Mother-To-Child Transmission (PMTCT) of HIV coverage in Eastern Africa, 50% of new HIV infections in children aged 0-14 years occur in the region.
OBJECTIVE
The aim of this study was to assess the feeding modalities, the rate of HIV transmission and its predictors among HIV exposed infants (HIV-EIs) visited Gamo and Gofa Zones public health facilities, Southern Ethiopia from January 2013 to February 2019.
METHOD AND MATERIALS
Institution-based retrospective follow up study was employed among 450 HIV-EIs having DNA/PCR test results. All infant-mother pair records in selected health facilities were reviewed using a standard data extraction tool from March to July 2019. HIV transmission probabilities were assessed by Kaplan-Meier time-to-event analysis method and log-rank tests were used to compare the risk among different groups. The Cox-proportional hazards model, adjusted on infant feeding modalities and other co-variants was used to identify predictors of HIV transmission, and statistical significance was declared at a p-value of < 0.05.
RESULTS
In total, 383 complete records were analyzed. In the study, 85.6% (95%CI: 81.6%, 89.1%) of HIV-EIs were exclusively breastfed in the first six months. The 18 months probability of infant HIV transmission was 64 (16.7%) (95%CI: 13.1%-20.8%). The risk of HIV-transmission was higher among infants who were delivered at the hospital than health centers/health posts (AHR = 3.07; 95%CI: 1.19, 7.95); discontinued Cotrimoxazole prophylaxis in at least one visit (AHR = 6.32; 95%CI: 3.35, 11.94); did not exclusively breastfeed (AHR = 3.07; 95%CI: 1.72, 5.47) and came from urban areas (AHR = 5.90; 95%CI: 1.40, 24.85).
CONCLUSIONS
The study showed that HIV-EIs had a greater rate of 18 months HIV transmission than the national pooled prevalence. The risk of transmission is higher among infants who do not breastfeed exclusively for the first 6 months, and the risk increases with the number of months spent by breastfeeding. Therefore, strengthening counselling on safer feeding options and Cotrimoxazole prophylaxis use; provision of quality PMTCT service with special focus in hospitals and urban residents were recommended.
Topics: Humans; Ethiopia; HIV Infections; Infectious Disease Transmission, Vertical; Retrospective Studies; Infant; Female; Breast Feeding; Male; Infant, Newborn; Follow-Up Studies; Bottle Feeding; Trimethoprim, Sulfamethoxazole Drug Combination; Adult; Risk Factors; Infant Formula
PubMed: 38926639
DOI: 10.1186/s12887-024-04894-w -
Journal of Clinical and Experimental... 2024
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Sulfonamides; Rituximab; Bridged Bicyclo Compounds, Heterocyclic; Retrospective Studies; Male; Aged; Female; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Japan; Treatment Outcome; Aged, 80 and over; East Asian People
PubMed: 38925975
DOI: 10.3960/jslrt.24014 -
Antiviral Research Jun 2024SARS-CoV-2 is a betacoronavirus that causes COVID-19, a global pandemic that has resulted in many infections, deaths, and socio-economic challenges. The virus has a...
SARS-CoV-2 is a betacoronavirus that causes COVID-19, a global pandemic that has resulted in many infections, deaths, and socio-economic challenges. The virus has a large positive-sense, single-stranded RNA genome of ∼30 kb, which produces subgenomic RNAs (sgRNAs) through discontinuous transcription. The most abundant sgRNA is sgRNA N, which encodes the nucleocapsid (N) protein. In this study, we probed the secondary structure of sgRNA N and a shorter model without a 3' UTR in vitro, using the SHAPE (selective 2'-hydroxyl acylation analyzed by a primer extension) method and chemical mapping with dimethyl sulfate and 1-cyclohexyl-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate. We revealed the secondary structure of sgRNA N and its shorter variant for the first time and compared them with the genomic RNA N structure. Based on the structural information, we designed gapmers, siRNAs and antisense oligonucleotides (ASOs) to target the N protein coding region of sgRNA N. We also generated eukaryotic expression vectors containing the complete sequence of sgRNA N and used them to screen for new SARS-CoV-2 gene N expression inhibitors. Our study provides novel insights into the structure and function of sgRNA N and potential therapeutic tools against SARS-CoV-2.
PubMed: 38925369
DOI: 10.1016/j.antiviral.2024.105946 -
CPT: Pharmacometrics & Systems... Jun 2024This study employed physiologically-based pharmacokinetic-pharmacodynamics (PBPK/PD) modeling to predict the effect of obesity and gastric bypass surgery on the...
This study employed physiologically-based pharmacokinetic-pharmacodynamics (PBPK/PD) modeling to predict the effect of obesity and gastric bypass surgery on the pharmacokinetics and intragastric pH following omeprazole treatment. The simulated plasma concentrations closely matched the observed data from non-obese, morbidly obese, and post-gastric bypass populations. Obesity significantly reduces CYP3A4 and CYP2C19 activities, as reflected by the metabolic ratio [omeprazole sulphone]/[omeprazole] and [5-hydroxy-omeprazole]/[omeprazole]. The morbidly obese model accounted for the down-regulation of CYP2C19 and CYP3A4 to recapitulate the observed data. Sensitivity analysis showed that intestinal CYP3A4, gastric pH, small intestine bypass, and the delay in bile release do not have a major influence on omeprazole exposure. Hepatic CYP3A4 had a significant impact on the AUC of (S)-omeprazole, while hepatic CYP2C19 affected both (R)- and (S)-omeprazole AUC. After gastric bypass surgery, the activity of CYP3A4 and CYP2C19 is restored. The PBPK model was linked to a mechanism-based PD model to assess the effect of omeprazole on intragastric pH. Following 40 mg omeprazole, the mean intragastric pH was 4.3, 4.6, and 6.6 in non-obese, obese, and post-gastric bypass populations, and the daily time with pH >4 was 14.7, 16.4, and 24 h. Our PBPK/PD approach provides a comprehensive understating of the impact of obesity and weight loss on CYP3A4 and CYP2C19 activity and omeprazole pharmacokinetics. Given that simulated intragastric pH is relatively high in post-RYGB patients, irrespective of the dose of omeprazole, additional clinical outcomes are imperative to assess the effect of proton pump inhibitor in preventing marginal ulcers in this population.
PubMed: 38923321
DOI: 10.1002/psp4.13189 -
Nanomaterials (Basel, Switzerland) Jun 2024This study aims to enhance the optical and thermal properties of cesium-based perovskite nanocrystals (NCs) through surface passivation with organic sulfonate (or...
This study aims to enhance the optical and thermal properties of cesium-based perovskite nanocrystals (NCs) through surface passivation with organic sulfonate (or sulfonic acid) ligands. Four different phenylated ligands, including sodium β-styrenesulfonate (SbSS), sodium benzenesulfonate (SBS), sodium -toluenesulfonate (SPTS), and 4-dodecylbenzenesulfonic acid (DBSA), were employed to modify blue-emitting CsPbBrCl perovskite NCs, resulting in improved size uniformity and surface functionalization. Transmission electron microscopy and X-ray photoelectron spectroscopy confirmed the successful anchoring of sulfonate or sulfonic acid ligands on the surface of perovskite NCs. Moreover, the photoluminescence quantum yield increased from 32% of the original perovskite NCs to 63% of the SPTS-modified ones due to effective surface passivation. Time-resolved photoluminescence decay measurements revealed extended PL lifetimes for ligand-modified NCs, indicative of reduced nonradiative recombination. Thermal stability studies demonstrated that the SPTS-modified NCs retained nearly 80% of the initial PL intensity when heated at 60 °C for 10 min, surpassing the performance of the original NCs. These findings emphasize the optical and thermal stability enhancement of cesium-based perovskite NCs through surface passivation with suitable sulfonate ligands.
PubMed: 38921925
DOI: 10.3390/nano14121049 -
Marine Drugs May 2024Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence...
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.
Topics: Humans; Sulfonamides; Leukemia, Myeloid, Acute; Histone Deacetylase Inhibitors; Drug Synergism; Bridged Bicyclo Compounds, Heterocyclic; Apoptosis; Cell Line, Tumor; Antineoplastic Agents; Histone Deacetylase 1; Histone Deacetylases; Animals; Caspase 3; Myeloid Cell Leukemia Sequence 1 Protein
PubMed: 38921561
DOI: 10.3390/md22060250 -
Membranes Jun 2024The combination of ion exchange membranes with carbon quantum dots (CQDs) is a promising field that could lead to significant advances in water treatment. Composite...
The combination of ion exchange membranes with carbon quantum dots (CQDs) is a promising field that could lead to significant advances in water treatment. Composite membranes formed by sulfonated poly(ether ether ketone) (SPEEK) with embedded CQDs were used for the detection and removal of heavy metal ions, such as lead and cadmium, from water. SPEEK is responsible for the capture of heavy metals based on the cation exchange mechanism, while CQDs detect their contamination by exhibiting changes in fluorescence. Water-insoluble "red" carbon quantum dots (rCQDs) were synthesized from p-phenylenediamine so that their photoluminescence was shifted from that of the polymer matrix. CQDs and the composites were characterized by several techniques: FTIR, Raman, UV/VIS, photoluminescence, XPS spectroscopies, and AFM microscopy. The heavy metal ion concentration was analyzed by inductively coupled plasma-optical emission spectroscopy (ICP-OES). The concentration ranges were 10.8-0.1 mM for Pb and 10.0-0.27 mM for Cd. SPEEK/rCQDs showed a more pronounced turn-off effect for lead. The composite achieved 100% removal efficiency for lead and cadmium when the concentration was below a half of the ion exchange capacity of SPEEK. The regeneration of membranes in 1 M NaCl was also studied. A second order law was effective to describe the kinetics of the process.
PubMed: 38921501
DOI: 10.3390/membranes14060134 -
Membranes May 2024This study introduces an innovative approach to enhancing membrane distillation (MD) performance by developing bead-containing superhydrophobic sulfonated...
This study introduces an innovative approach to enhancing membrane distillation (MD) performance by developing bead-containing superhydrophobic sulfonated polyethersulfone (SPES) nanofibers with S-MWCNTs. By leveraging SPES's inherent hydrophobicity and thermal stability, combined with a nanostructured fibrous configuration, we engineered beads designed to optimize the MD process for water purification applications. Here, oxidized hydrophobic S-MWCNTs were dispersed in a SPES solution at concentrations of 0.5% and 1.0% by weight. These bead membranes are fabricated using a novel electrospinning technique, followed by a post-treatment with the hydrophobic polyfluorinated grafting agent to augment nanofiber membrane surface properties, thereby achieving superhydrophobicity with a water contact angle (WCA) of 145 ± 2° and a higher surface roughness of 512 nm. The enhanced membrane demonstrated a water flux of 87.3 Lm h and achieved nearly 99% salt rejection efficiency at room temperature, using a 3 wt% sodium chloride (NaCl) solution as the feed. The results highlight the potential of superhydrophobic SPES nanofiber beads in revolutionizing MD technology, offering a scalable, efficient, and robust membrane for salt rejection.
PubMed: 38921487
DOI: 10.3390/membranes14060120 -
Gels (Basel, Switzerland) Jun 2024The aim of this work was to synthesize and study the functional properties of polymer-clay nanocomposite (PCNCs) based on poly(sodium 4-styrene sulfonate) (NaPSS) and...
Synthesis and Characterization of Nanocomposite Hydrogels Based on Poly(Sodium 4-Styrene Sulfonate) under Very-High Concentration Regimen of Clays (Bentonite and Kaolinite).
The aim of this work was to synthesize and study the functional properties of polymer-clay nanocomposite (PCNCs) based on poly(sodium 4-styrene sulfonate) (NaPSS) and two types of clay in the dispersed phase: bentonite and kaolinite, in order to advance in the development of new geomimetic materials for agricultural and environmental applications. In this study, the effect of adding high concentrations of clay (10-20 wt. %) on the structural and functional properties of a polymer-clay nanocomposite was evaluated. The characterization by infrared spectroscopy made it possible to show that the PCNCs had a hybrid nature structure through the identification of typical vibration bands of the clay matrix and NaPSS. In addition, scanning electron microscopy allowed us to verify its hybrid composition and an amorphous particle-like morphology. The thermal characterization showed degradation temperatures higher than ~300 °C with Tg values higher than 100 °C and variables depending on the clay contents. In addition, the PCNCs showed a high water-retention capacity (>2900%) and cation exchange capacity (>112 meq/100 g). Finally, the results demonstrated the ability of geomimetic conditioners to mimic the structure and functional properties of soils, suggesting their potential application in improving soil quality for plant growth.
PubMed: 38920951
DOI: 10.3390/gels10060405