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1.
Nat Biotechnol ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090305

RESUMO

Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside. exNA incorporation is compatible with common oligonucleotide synthetic protocols and the PS backbone, provides stabilization against 3' and 5' exonucleases and is tolerated at multiple oligonucleotide positions. A combined exNA-PS backbone enhances resistance to 3' exonuclease by ~32-fold over the conventional PS backbone and by >1,000-fold over the natural phosphodiester backbone, improving tissue exposure, tissue accumulation and efficacy in mice, both systemically and in the brain. The improved efficacy and durability imparted by exNA may enable therapeutic interventions in extrahepatic tissues, both with siRNA and with other oligonucleotides such as CRISPR guide RNA, antisense oligonucleotides, mRNA and tRNA.

2.
Am J Otolaryngol ; 45(5): 104423, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39059166

RESUMO

OBJECTIVE: To evaluate the impact of obstructive sleep apnea (OSA) on the quality-of-life (QoL) of patients with chronic rhinosinusitis (CRS). METHODS: Retrospective cohort study of all adult patients with CRS presenting to our rhinology clinic between August 2020 and February 2023 was performed. OSA was established based on positive polysomnography. Patients' characteristics, apnea-hypopnea index, comorbidities, endoscopy scores, and SNOT-22 scores were collected. RESULTS: A total of 513 patients with CRS were included, 127 patients with OSA and 386 without OSA. CRS patients with OSA were older (p < 0.001), had higher BMI (p < 0.001), more likely to be males (p = 0.07), more likely to have asthma (p < 0.001), and more likely to have COPD (p = 0.001). Presence of nasal polyps did not differ between the two groups. Baseline SNOT-22 scores were worse in the OSA cohort (44.4 vs 40.5, p = 0.064) secondary to worse sleep (13.4 vs 11.1; p = 0.002) and psychological (14.2 vs 11.5; p = 0.002) domains. Worse SNOT scores were strongly associated with presence of OSA after adjusting for confounding variables, including age, gender, asthma, allergic rhinitis, nasal septal deviation, and smoking status. CONCLUSION: OSA is an independent negative contributor to the disease specific QoL in patients with CRS. CPAP use does not seem to affect the QoL in CRS patients with OSA. Further research is warranted to explore the impact of OSA in the outcome of medical and surgical treatment of CRS patients.

3.
Sci Rep ; 14(1): 16713, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030264

RESUMO

Developing stable and highly efficient metal oxide photocatalysts remains a significant challenge in managing organic pollutants. In this study, zinc oxide nanoparticles (ZnO NPs) were successfully synthesized using various plant extracts, pomegranate (P.M), beetroot roots (B.S), and seder, along with a chemical process. The produced ZnO NPs were characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), Field Emission Scanning Electron Microscope (FESEM), High-Resolution Transmission Electron Microscopy (HRTEM), and Surface Area. For all prepared samples, the results indicated that the composition of the plant extract affects several characteristics of the produced particles, such as their photocatalytic properties, energy bandgap (Eg), particle size, and the ratio of the two intensity (0 0 2) and (1 0 0) crystalline planes. The particle size of the produced NPs varies between 20 and 30 nm. To examine NPs' photocatalytic activity in the presence of UV light, Methyl Orange (MO) was utilized. The Eg of  ZnO synthesized by the chemical method was 3.16 e. V, whereas it was 2.84, 2.63, and 2.59 for P.M, Seder, and B.S extracts, respectively. The most effective ZnO NPs, synthesized using Beetroots, exhibited a degradation efficiency of 87 ± 0.5% with a kinetic rate constant of 0.007 min-1. The ratio of the two intensity (0 0 2) and (1 0 0) crystalline planes was also examined to determine a specific orientation in (0 0 2) that is linked to the production of oxygen vacancies in ZnO, which enhances their photocatalytic efficiency. Furthermore, the increase in photocatalytic effectiveness can be attributed to the improved light absorption by the inter-band gap states and effective charge transfer.

4.
ACS Omega ; 9(29): 31714-31731, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39072084

RESUMO

The corrosion inhibition of C-steel by two s-triazine/morpholino-anilino-pyrazole derivatives, namely, 4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-N-phenyl-1,3,5-triazin-2-amine (1) and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-1,3,5-triazin-2-amine (2) was investigated by impedimetric and potentiometric studies. It was found that (1) and (2) acted as cathodic-type corrosion inhibitors that retard the hydrogen evolution reaction. The percent corrosion inhibition, 98.5% for compound (2) (with bromo substituent) at 80 ppm, was slightly higher than 97.8% for (1) at 100 ppm. Thus, the replacement of a -H with -Br substituent increased the corrosion inhibition properties. Compound (2) exhibited Temkin isotherm adsorption, whereas compound (1) exhibited Langmuir adsorption. Scanning electron microscopy (SEM) analysis of the steel surface indicated that the inhibitors caused protection of the surface. The weight loss experiment also proved the decrease in the corrosion rate when inhibitors were added. The difference in inhibitory efficiency between compounds (1) and (2) was investigated by density functional theory (DFT) to study neutral and protonated species in gaseous and aqueous phases. The theoretical analysis demonstrated that compound (2) exhibited higher inhibitory activity on a metal surface compared to compound (1), aligning with the experimental results. The energy associated with the metal/adsorbate arrangement, represented by dE ads/dNi , was higher for (2) (-380.91 kcal mol-1) compared to (1) (-371.64 kcal mol-1). This indicated better adsorption of (2) over (1).

5.
Front Pharmacol ; 15: 1370344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38898922

RESUMO

Background: This study examined the time to sputum smear and culture conversion and determinants of conversion, as well as variables associated with treatment outcomes among drug-resistant pulmonary tuberculosis (DR-PTB) cases. Methods: The electronic database and written medical records of patients were utilized to assess the sociodemographic, clinical, microbiological, and treatment characteristics and outcomes of study participants. Results: Among 736 patients with pulmonary tuberculosis (PTB), the mean age was 36.5 ± 16.5 years, with males comprising 53.4% and a mean weight of 47.76 ± 11.97 kg. The median time period for sputum smear conversion and sputum culture conversion was a month. The first-month culture conversion (p < 0.001, aOR = 5.817, and 95% CI = 3.703-9.138) was the determinant of sputum smear conversion and receiver operating curve analysis with AUC = 0.881, 95% CI = 0.855-0.907, and p < 0.001, which showed a high level of predictive ability for the regression model for the initial sputum smear conversion. However, the first-month sputum conversion (p < 0.001, aOR = 7.446, and 95% CI = 4.869-11.388) was attributed to sputum culture conversion, and the model has shown excellent predictive ability for regression with ROC curve analysis demonstrating AUC = 0.862, 95% CI = 0.835-0.889, and p < 0.001. A total of 63.2% of patients showed favorable treatment outcomes, with 63.1% of cases achieving treatment-cured status. The previous use of SLD, history of smoking, duration of illness ≤ 1 year, extensively drug-resistant tuberculosis, and first-month sputum conversion were the variables attributed to favorable treatment outcomes observed in drug-resistant pulmonary tuberculosis cases. ROC curve analysis with AUC = 0.902, 95% CI = 0.877-0.927, and p < 0.001) has shown outstanding ability for regression model prediction for the variables influencing treatment outcomes. Conclusions: Within 2 months of treatment, most patients had converted their sputum cultures and sputum smears. The determinants of early sputum smear and sputum culture conversion, as well as favorable treatment outcomes, were identified. These factors should be considered during the design and implementation of effective strategies for drug-resistant tuberculosis control programs.

6.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38931404

RESUMO

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with ß-cyclodextrin (ßCD) and hydroxy propyl ß-cyclodextrin (HPßCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with ßCD and HPßCD. This study identified the most soluble complex (ALB-HPßCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPßCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPßCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration.

7.
Am J Otolaryngol ; 45(4): 104325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696896

RESUMO

OBJECTIVES: To evaluate the impact of allergic rhinitis (AR) on the quality of life (QoL) in patients with chronic rhinosinusitis (CRS). METHODS: Retrospective cross-sectional study of adult patients with CRS presenting to our clinic between August 2020 and February 2023 was performed. AR was diagnosed based on a positive skin or blood allergy test. Patients' characteristics, AR status, comorbidities, endoscopy scores, and SNOT-22 scores were collected. RESULTS: A total of 514 CRS patients were included, with 265 (51.6 %) patients with AR. CRS patients with AR were younger (p = 0.004), more likely to be female (p < 0.001), and more likely to have asthma (p < 0.001). Polyp status and endoscopy scores did not differ between patients with and without AR. Baseline SNOT-22 scores were slightly worse in the AR cohort (43.6 vs 38.7, p = 0.007), which was mainly secondary to rhinologic (p = 0.002), extrarhinologic (p = 0.007), and ear/facial (p = 0.007) subdomains. Worse rhinologic and extrarhinologic scores were associated with the presence of AR after adjusting for confounding variables (Coef = 1.55, p = 0.011; and Coef = 0.83, p = 0.021 respectively). CONCLUSION: The impact of allergic rhinitis on QoL is mainly on the nasal symptoms. Further studies should look at the role of AR on the QoL of different CRS endotypes; and at the role of AR-specific treatment, such as immunotherapy, on the QoL of patients with CRS.


Assuntos
Qualidade de Vida , Rinite Alérgica , Rinite , Sinusite , Humanos , Feminino , Sinusite/psicologia , Masculino , Doença Crônica , Rinite Alérgica/psicologia , Rinite Alérgica/complicações , Estudos Transversais , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Rinite/psicologia , Idoso , Rinossinusite
8.
Cureus ; 16(4): e58095, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38737997

RESUMO

Infective endocarditis (IE) is defined as an infection in the cardiac endothelium. It is triggered by both bacteremia and endothelial dysfunction and poses many risks to the health of the patient. Many organisms can cause IE with Staphylococcus aureus being the major cause. Signs and symptoms may vary according to age and agent but almost all cases are presented with fever, fatigue, and a maculopapular rash. Although pediatric IE is very rare, risk factors such as congenital heart defects have been identified, with some of the cases remaining a mystery. We present a case of a 19-year-old patient, previously healthy and developing subacute IE with sepsis and septic embolic showers in multiple organs. IE cannot be taken for granted as mortality is high, hence a multidisciplinary approach is prompt and necessary for the survival of the patient.

9.
Artif Cells Nanomed Biotechnol ; 52(1): 238-249, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38696111

RESUMO

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between -9.93 and -11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.


Assuntos
Antimaláricos , Química Verde , Nanopartículas Metálicas , Extratos Vegetais , Folhas de Planta , Plasmodium falciparum , Prata , Terminalia , Prata/química , Prata/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Antimaláricos/síntese química , Nanopartículas Metálicas/química , Terminalia/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Simulação de Acoplamento Molecular , Humanos
10.
R Soc Open Sci ; 11(5): 231229, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38721132

RESUMO

4,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-1,3,5-triazin-2-amine (PTA-1), N-(4-bromophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine (PTA-2) and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine (PTA-3) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H2SO4 was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that s-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor PTA-2 and PTA-3 bearing -Br and -OCH3 groups on aniline, respectively. While PTA-1 without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant K°ads and free energy change ΔG°ads revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement dE ads/dN i, for both forms of PTA-2 and PTA-3 with electron donating groups (-439.73 and -436.62 kcal mol-1) is higher than that of PTA-1 molecule (-428.73 kcal mol-1). This aligned with experimental inhibition efficiency results.

11.
Nucleic Acids Res ; 52(9): 4799-4817, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38613388

RESUMO

Glioblastoma multiforme is a universally lethal brain tumor that largely resists current surgical and drug interventions. Despite important advancements in understanding GBM biology, the invasiveness and heterogeneity of these tumors has made it challenging to develop effective therapies. Therapeutic oligonucleotides-antisense oligonucleotides and small-interfering RNAs-are chemically modified nucleic acids that can silence gene expression in the brain. However, activity of these oligonucleotides in brain tumors remains inadequately characterized. In this study, we developed a quantitative method to differentiate oligonucleotide-induced gene silencing in orthotopic GBM xenografts from gene silencing in normal brain tissue, and used this method to test the differential silencing activity of a chemically diverse panel of oligonucleotides. We show that oligonucleotides chemically optimized for pharmacological activity in normal brain tissue do not show consistent activity in GBM xenografts. We then survey multiple advanced oligonucleotide chemistries for their activity in GBM xenografts. Attaching lipid conjugates to oligonucleotides improves silencing in GBM cells across several different lipid classes. Highly hydrophobic lipid conjugates cholesterol and docosanoic acid enhance silencing but at the cost of higher neurotoxicity. Moderately hydrophobic, unsaturated fatty acid and amphiphilic lipid conjugates still improve activity without compromising safety. These oligonucleotide conjugates show promise for treating glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Oligonucleotídeos Antissenso , RNA Interferente Pequeno , Ensaios Antitumorais Modelo de Xenoenxerto , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Animais , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Humanos , Camundongos , Linhagem Celular Tumoral , Neoplasias Encefálicas/genética , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/uso terapêutico , Inativação Gênica , Camundongos Nus
12.
Environ Sci Pollut Res Int ; 31(19): 28719-28733, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38558346

RESUMO

Green hydrogen generation technologies are currently the most pressing worldwide issues, offering promising alternatives to existing fossil fuels that endanger the globe with growing global warming. The current research focuses on the creation of green hydrogen in alkaline electrolytes utilizing a Ni-Co-nano-graphene thin film cathode with a low overvoltage. The recommended conditions for creating the target cathode were studied by electrodepositing a thin Ni-Co-nano-graphene film in a glycinate bath over an iron surface coated with a thin copper interlayer. Using a scanning electron microscope (SEM) and energy-dispersive X-ray (EDX) mapping analysis, the obtained electrode is physically and chemically characterized. These tests confirm that Ni, Co, and nano-graphene are homogeneously dispersed, resulting in a lower electrolysis voltage in green hydrogen generation. Tafel plots obtained to analyze electrode stability revealed that the Ni-Co-nano-graphene cathode was directed to the noble direction, with the lowest corrosion rate. The Ni-Co-nano-graphene generated was used to generate green hydrogen in a 25% KOH solution. For the production of 1 kg of green hydrogen utilizing Ni-Co-nano-graphene electrode, the electrolysis efficiency was 95.6% with a power consumption of 52 kwt h-1, whereas it was 56.212. kwt h-1 for pure nickel thin film cathode and 54. kwt h-1 for nickel cobalt thin film cathode, respectively.


Assuntos
Cobalto , Eletrodos , Grafite , Hidrogênio , Níquel , Grafite/química , Hidrogênio/química , Níquel/química , Cobalto/química , Eletrólise
13.
Int J Pediatr Otorhinolaryngol ; 179: 111936, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583371

RESUMO

BACKGROUND: Studies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS. METHODS: Cross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size. RESULTS: 124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma. CONCLUSION: There is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.


Assuntos
Asma , Rinite Alérgica , Rinite , Rinossinusite , Sinusite , Adulto , Humanos , Feminino , Criança , Pré-Escolar , Adolescente , Masculino , Estudos Transversais , Qualidade de Vida , Rinite/complicações , Rinite/diagnóstico , Sinusite/complicações , Sinusite/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Endoscopia , Doença Crônica
14.
Med Oncol ; 41(5): 101, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546811

RESUMO

Lung cancer is a disease in which lung cells grow abnormally and uncontrollably, and the cause of it is direct smoking, secondhand smoke, radon, asbestos, and certain chemicals. The worldwide leading cause of death is lung cancer, which is responsible for more than 1.8 million deaths yearly and is expected to rise to 2.2 million by 2030. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which accounts for about 80% and small cell lung cancer (SCLC), which is more aggressive than NSCLC and is often diagnosed later and accounts for 20% of cases. The global concern for lung cancer demands efficient drugs with the slightest chance of developing resistance, and the idea of multitargeted drug designing came up with the solution. In this study, we have performed multitargeted molecular docking studies of Drug Bank compounds with HTVS, SP and XP algorithms followed by MM\GBSA against the four proteins of lung cancer cellular survival and stress responses, which revealed Mitoglitazone as a multitargeted inhibitor with a docking and MM\GBSA score ranging from - 5.784 to - 7.739 kcal/mol and - 25.81 to - 47.65kcal/mol, respectively. Moreover, we performed pharmacokinetics studies and QM-based DFT analysis, showing suitable candidate and interaction pattern analysis revealed the most count of interacting residues was 4GLY, 5PHE, 6ASP, 6GLU, 6LYS, and 6THR. Further, the results were validated with SPC water model-based MD simulation for 100ns in neutralised condition, showing the cumulative deviation and fluctuation < 2Å with many intermolecular interactions. The whole analysis has suggested that Mitoglitazone can be used as a multitargeted inhibitor against lung cancer-however, experimental studies are needed before human use.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Sítios de Ligação , Neoplasias Pulmonares/tratamento farmacológico , Simulação de Acoplamento Molecular , Ligação Proteica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Simulação de Dinâmica Molecular , Proteínas de Choque Térmico , Detecção Precoce de Câncer , Ligação de Hidrogênio
15.
Laryngoscope ; 134(8): 3489-3492, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38451036

RESUMO

OBJECTIVES: Prior studies evaluating the role of sinonasal anatomic variants with recurrent acute rhinosinusitis (RARS) are limited by inconsistent results. The goal of this study is to evaluate the association between sinonasal anatomic variants and RARS. METHODS: A 1:2 retrospective case-control study was conducted using patients presenting to the rhinology clinic from August 2020 to January 2023. A total of 60 patients with RARS were compared to 120 control patients. RARS was diagnosed based on the International Consensus Statement on Allergy and Rhinology criteria of four or more independent episodes of acute rhinosinusitis per year with at least one episode documented by objective findings, with complete resolution of the infection in-between episodes. Sinonasal anatomic variants included nasal septal deviation (NSD), concha bullosa (CB), infraorbital (Haller) cells, nasal septal spur in the middle meatus, and frontal sinus cells (supra-agger, supra-agger frontal, and suprabullar frontal cells). RESULTS: Age was similar in RARS and control patients (47.4 ± 16.5 vs. 49.3 ± 14.5, p = 0.432). Both the RARS group and control group were more likely to be female (78.3% vs. 77.5%, p = 0.899). There was no significant association between NSD and RARS compared to the control group (OR = 0.97, p = 0.916), and no significant association between any of the anatomic variants and RARS [infraorbital cells (OR = 0.64, p = 0.167), CB (OR = 0.84, p = 0.596), spur in the middle meatus (OR = 1.28, p = 0.514), supra-agger (OR = 0.88, p = 0.708), supra-agger frontal cells (OR = 0.97, p = 0.939), or suprabullar frontal cells (OR = 1.13, p = 0.766)]. CONCLUSION: Our findings suggest no association between nasal septal deviation or any of the anatomic variants studied and RARS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3489-3492, 2024.


Assuntos
Recidiva , Rinite , Sinusite , Humanos , Feminino , Rinite/patologia , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Doença Aguda , Adulto , Variação Anatômica , Septo Nasal/anormalidades , Seios Paranasais/anormalidades , Rinossinusite
16.
Nucleic Acid Ther ; 34(2): 52-72, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38507678

RESUMO

Nucleic acid-based therapies have become the third major drug class after small molecules and antibodies. The role of nucleic acid-based therapies has been strengthened by recent regulatory approvals and tremendous clinical success. In this review, we look at the major obstacles that have hindered the field, the historical milestones that have been achieved, and what is yet to be resolved and anticipated soon. This review provides a view of the key innovations that are expanding nucleic acid capabilities, setting the stage for the future of nucleic acid therapeutics.


Assuntos
Ácidos Nucleicos , Ácidos Nucleicos/genética , Ácidos Nucleicos/uso terapêutico , Sistemas de Liberação de Medicamentos
17.
Appl Radiat Isot ; 208: 111281, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38554688

RESUMO

In the present study, a facile nano-sized gamma alumina was synthesized and then examined for immobilization of cobalt and cesium ions individually from aqueous solutions. The comprehensive analysis of functional groups, phase composition, surface morphology and sorption characteristics of the synthesized nano-sized ϒ alumina was executed. It was deduced that acquired material was low-crystalline with a high elimination efficacy towards the concerned cations under slightly alkali and acidic conditions. Time-transient elimination scrutiny was executed and cobalt elimination rate was found relatively faster than cesium cations. Equilibrium sorption examinations confirmed that the sorption is proceeding via two diverse sites on the scavenger surface. Cobalt and cesium elimination is a spontaneous endothermic reaction of increased chaos. The attained results proved the high proficiency of the synthesized scavenger in the cations immobilization.

18.
Pathol Res Pract ; 256: 155223, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452587

RESUMO

Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética
19.
Int J Biol Macromol ; 264(Pt 1): 130544, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428778

RESUMO

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive and severe muscle weakening and degeneration. Among the various forms of muscular dystrophy, it stands out as one of the most common and impactful, predominantly affecting boys. The condition arises due to mutations in the dystrophin gene, a key player in maintaining the structure and function of muscle fibers. The manuscript explores the structural features of dystrophin protein and their pivotal roles in DMD. We present an in-depth analysis of promising therapeutic approaches targeting dystrophin and their implications for the therapeutic management of DMD. Several therapies aiming to restore dystrophin protein or address secondary pathology have obtained regulatory approval, and many others are ongoing clinical development. Notably, recent advancements in genetic approaches have demonstrated the potential to restore partially functional dystrophin forms. The review also provides a comprehensive overview of the status of clinical trials for major therapeutic genetic approaches for DMD. In addition, we have summarized the ongoing therapeutic approaches and advanced mechanisms of action for dystrophin restoration and the challenges associated with DMD therapeutics.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Distrofia Muscular de Duchenne , Masculino , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Distrofia Muscular de Duchenne/patologia , Distrofina/genética , Distrofina/metabolismo , Distrofina/uso terapêutico , Fibras Musculares Esqueléticas/metabolismo
20.
Braz J Biol ; 84: e281415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511782

RESUMO

Diseases in fish due to helminth parasites, especially Philometra species, are the primary worry in aquaculture. Philometra are responsible for health problem in fishes they directly affect fish growth and population parameters. A comprehensive survey was conducted involving the examination of the marine fish species Terapon jarbua, gathered from the coastal waters of Sindh, Pakistan In this research different Philometra species from marine fish Terapon jarbua during 2021 and 2022. Philometra nematodes, belonging to the family Philometridae, are common parasitic organisms inhabiting both marine and freshwater environments. Their prevalence, particularly when existing in high numbers within host organisms, can lead to severe and potentially lethal consequences. Employing light microscopy techniques, diverse species of Philometra were identified, including Philometra teraponi, P. jarbuai, P. arabiai, P. karachii, and P. awarii, localized primarily within the ovaries of the host fish. A total of 140 fish samples were examined and 76 were infected. The intensity of infected fish was 54.28%. The identification process encompassed meticulous analysis of crucial parameters, such as body size, esophagus length, positioning of the nerve ring, dimensions of the ventriculus, and ligament size. Intriguingly, the parasites were found in varying contexts; while some were free within the ovaries, others were embedded within tissues, inducing severe muscular dystrophy. This research presents novel findings of Philometra nematodes in the marine waters of Pakistan, extending their host and geographical distribution records. Future studies are needed to better evaluate and describe the dynamics and the epidemiology of Philometra infection in wild and cultured fish species.


Assuntos
Dracunculoidea , Doenças dos Peixes , Animais , Paquistão , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/parasitologia , Peixes/parasitologia , Dracunculoidea/fisiologia , Tamanho Corporal
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